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Sample records for second-generation antipsychotic drugs

  1. A bibliometric study of scientific research conducted on second-generation antipsychotic drugs in Singapore.

    Science.gov (United States)

    López-Muñoz, Francisco; Sim, Kang; Shen, Winston Wu; Huelves, Lorena; Moreno, Raquel; Molina, Juan de Dios; Rubio, Gabriel; Noriega, Concha; Pérez-Nieto, Miguel Ángel; Alamo, Cecilio

    2014-01-01

    A bibliometric study was carried out to ascertain the volume and impact of scientific literature published on second-generation antipsychotic drugs (SGAs) in Singapore from 1997 to 2011. A search of the EMBASE and MEDLINE databases was performed to identify articles originating from Singapore that included the descriptors 'atypic* antipsychotic*', 'second-generation antipsychotic*', 'clozapine', 'risperidone', 'olanzapine', 'ziprasidone', 'quetiapine', 'sertindole', 'aripiprazole', 'paliperidone', 'amisulpride', 'zotepine', 'asenapine', 'iloperidone', 'lurasidone', 'perospirone' and 'blonanserin' in the article titles. Certain bibliometric indicators of production and dispersion (e.g. Price's Law on the increase of scientific literature, and Bradford's Law) were applied, and the participation index of various countries was calculated. The bibliometric data was also correlated with some social and health data from Singapore, such as the total per capita expenditure on health and gross domestic expenditure on research and development. From 1997 to 2011, a total of 51 articles on SGAs in Singapore were published. Our results suggested non-fulfilment of Price's Law (r = 0.0648 after exponential adjustment vs. r = 0.2140 after linear adjustment). The most widely studied drugs were clozapine (21 articles), risperidone (16 articles) and olanzapine (8 articles). Division into Bradford zones yielded a nucleus occupied by the Journal of Clinical Psychopharmacology (6 articles) and the Singapore Medical Journal(4 articles). The analysed material was published in a total of 30 journals, with the majority from six journals. Four of these six journals have an impact factor greater than 2. Publications on SGAs in Singapore are still too few to confirm an exponential growth of scientific literature.

  2. Dropout Rates in Randomized Clinical Trials of Antipsychotics: A Meta-analysis Comparing First- and Second-Generation Drugs and an Examination of the Role of Trial Design Features

    OpenAIRE

    Rabinowitz, Jonathan; Levine, Stephen Z.; Barkai, Orna; Davidov, Ori

    2008-01-01

    Dropout is often used as an outcome measure in clinical trials of antipsychotic medication. Previous research is inconclusive regarding (a) differences in dropout rates between first- and second-generation antipsychotic medications and (b) how trial design features reduce dropout. Meta-analysis of randomized controlled trials (RCTs) of antipsychotic medication was conducted to compare dropout rates for first- and second-generation antipsychotic drugs and to examine how a broad range of design...

  3. Development of Metabolic Syndrome in Drug-Naive Adolescents After 12 Months of Second-Generation Antipsychotic Treatment

    DEFF Research Database (Denmark)

    Sjo, Christina Power; Stenstrøm, Anne Dorte; Bojesen, Anders Bo

    2017-01-01

    if obesity or metabolic aberration starts in childhood or adolescence. METHODS: Drug-naive adolescents were recruited after contact with an outpatient Psychosis Team. Changes relative to baseline in body mass index (BMI), waist circumference (WC), blood pressure (BP), fasting blood glucose (FBG......), triglycerides (TG), and high-density lipoprotein (HDL) cholesterol were determined through regular follow-ups. RESULTS: The sample included 35 SGA-naive patients aged 7-19 (mean: 15.5) with a diagnosis of psychosis. Over 12 months, the overall rate of MetS changed significantly (from 0% to 20% [p 

  4. The Safety of Second-Generation Antipsychotics During Pregnancy

    DEFF Research Database (Denmark)

    Damkier, Per; Videbech, Poul

    2018-01-01

    The issue of antipsychotic treatment during pregnancy is subject to substantial uncertainty and some controversy among healthcare providers, specifically pertaining to second-generation antipsychotics (SGAs) that are subject to a large gap in safety data during pregnancy compared...... with antidepressants. The amount of safety data for the use of SGAs during pregnancy is rapidly increasing, thus constantly changing the level of evidence. We performed a clinically focused review on the safety of SGA during pregnancy. Twenty-three studies provided various pregnancy outcomes for 14,382 pregnant women...... exposed to an SGA during pregnancy. In utero exposure to aripiprazole, olanzapine, and quetiapine is not associated with increased risks of major congenital malformations, whereas risperidone and paliperidone may be associated with a very minor increased risk of congenital malformations. Safety data...

  5. Second-generation antipsychotics for major depressive disorder and dysthymia.

    Science.gov (United States)

    Komossa, Katja; Depping, Anna M; Gaudchau, Andrea; Kissling, Werner; Leucht, Stefan

    2010-12-08

    Major depressive disorder (MDD) is a common condition with a lifetime prevalence of 15% to 18%, which leads to considerable suffering and disability. Some antipsychotics have been reported to induce remission in major depression, when added to an antidepressant. To evaluate the effects of second-generation antipsychotic (SGA) drugs (alone or augmentation) compared with placebo or antidepressants for people with MDD or dysthymia. The Cochrane Depression, Anxiety and Neurosis Group's controlled trial registers (CCDANCTR-Studies and CCDANCTR-References) were searched up to 21 July 2010. The author team ran complementary searches on clinicaltrials.gov and contacted key authors and drug companies. We included all randomised, double-blind trials comparing oral SGA treatment (alone or augmentation) with other forms of pharmaceutical treatment or placebo in people with MDD or dysthymia. We extracted data independently. For dichotomous data we calculated the odds ratio (OR) and 95% confidence interval (CI) on an intention-to-treat basis, and for continuous data the mean difference (MD), based on a random-effects model. We presented each comparison separately; we did not perform a pooled data analysis. We included 28 trials with 8487 participants on five SGAs: amisulpride, aripiprazole, olanzapine, quetiapine and risperidone.Three studies (1092 participants) provided data on aripiprazole augmentation in MDD. All efficacy data (response n = 1092, three RCTs, OR 0.48; 95% CI 0.37 to 0.63), (MADRS n = 1077, three RCTs, MD -3.04; 95% CI -4.09 to -2) indicated a benefit for aripiprazole but  more side effects (weight gain, EPS) .Seven trials (1754 participants) reported data on olanzapine. Compared to placebo fewer people discontinued treatment due to inefficacy; compared to antidepressants there were no efficacy differences, olanzapine augmentation showed symptom reduction (MADRS n = 808, five RCTs, MD -2.84; 95% CI -5.48 to -0.20), but also more weight or prolactin increase

  6. Second-generation antipsychotic use in children and adolescents: a six-month prospective cohort study in drug-naïve patients.

    Science.gov (United States)

    Arango, Celso; Giráldez, Miriam; Merchán-Naranjo, Jessica; Baeza, Inmaculada; Castro-Fornieles, Josefina; Alda, Jose-Angel; Martínez-Cantarero, Carmen; Moreno, Carmen; de Andrés, Pilar; Cuerda, Cristina; de la Serna, Elena; Correll, Christoph U; Fraguas, David; Parellada, Mara

    2014-11-01

    To assess weight and metabolic effects of 6 months of treatment with second-generation antipsychotics in naïve/quasi-naïve youths. This study looked at a nonrandomized, naturalistic, multicenter, inception cohort study of 279 patients aged 4 to 17 years (mean = 14.6 ± 2.9 years). Of those, 248 (88.8%) received a single antipsychotic (risperidone, olanzapine, or quetiapine) and completed 2 visits, and 178 (63.8%) completed the 6-month follow-up. Patients had schizophrenia-spectrum disorders (44.5%), mood-spectrum disorders (23.2%), disruptive behavioral disorders (17.3%), or other disorders (15.1%). Fifteen age- and gender-matched, healthy, nonmedicated individuals served as a comparison group. From baseline to 1 month, 3 months, and 6 months, all anthropometric measures increased significantly with each antipsychotic, that is, 6-month changes with risperidone (n = 157; 7.1 kg and 0.66 body mass index [BMI] z score), olanzapine (n = 44; 11.5 kg and 1.08 BMI z score), and quetiapine (n = 47; 6.3 kg and 0.54 BMI z score), but not in healthy control participants (-0.11 kg and 0.006 BMI z score). Fasting metabolic parameters increased significantly with risperidone (glucose [3.8] mg/dL, insulin [4.9] mU/L, homeostasis model assessment of insulin resistance [HOMA-IR: 1.2], triglycerides [15.6] mg/dL), and olanzapine (glucose [5.0] mg/dL, total cholesterol [21.2] mg/dL, and low-density lipoprotein cholesterol [44.6] mg/dL), but not with quetiapine or in healthy control participants. The percentage of research participants considered to be "at risk of adverse health outcome" increased during the 6 months from 8.9% to 29.2% for risperidone (p < .0001), 6.8% to 38.1% for olanzapine (p < .0001), and 6.3% to 4.0% for quetiapine (p = .91). Olanzapine, quetiapine, and risperidone increase body weight but have different cardiometabolic side effect profiles and different temporal side effect patterns. Copyright © 2014 American Academy of Child and Adolescent

  7. Use of second-generation antipsychotic agents for sleep and sedation: a provider survey.

    Science.gov (United States)

    Hermes, Eric D A; Sernyak, Michael; Rosenheck, Robert

    2013-04-01

    Anecdotal evidence suggests that second-generation antipsychotic agents are increasingly used to treat sleep problems. This study sought to quantify the proportion of new prescriptions for second-generation antipsychotic agents started for sleep/sedation and the correlates of such use. A cross-sectional survey of provider decision making at the time second-generation antipsychotic agents were prescribed, documenting the reasons for the medication, patient demographics, psychiatric and medical diagnoses, patient health characteristics, and provider background. A single Veterans Affairs Medical Center over a 20-month period. Prescribers of second-generation antipsychotic agents. N/A. Seven hundred seven (32.2%) of 2,613 surveys indicated sleep/sedation was at least one reason for using a second-generation anti-psychotic agent, whereas for 266 (12.1%) it was the only reason. Quetiapine was most frequently prescribed overall as well as for sleep/sedation (47.0% and 73.6% respectively). Second-generation antipsychotic agent use for sleep/sedation was unrelated to sociodemographic characteristics, least likely in patients with schizophrenia or bipolar disorder, and most likely as a newly started second-generation antipsychotic agent. Sleep/sedation is a common reason given for new prescriptions of second-generation antipsychotic agents. Quetiapine is most frequently used for this purpose. A greater understanding of why providers use second-generation antipsychotic agents rather than safer and less costly alternatives for sleep problems may advance the development of interventions to reduce adverse effects.

  8. [Eating disorders in psychiatric patients during treatment with second generation antipsychotics].

    Science.gov (United States)

    Vasilenko, L M; Gorobets, L N; Bulanov, V S; Litvinov, A V; Ivanova, G P; Tsarenko, M A; Polyakovskaya, T P

    2015-01-01

    To identify the frequency and characteristics of eating disorders in patients with schizophrenia treated with second generation antipsychotics. A sample included 56 patients (48 women and 8 men, mean age 28 ± 4.5 years) with schizophrenia and schizoaffective disorder. Patients received risperidone, quetiapine and olanzapine. The study employed clinical-anamnestic, endocrinological methods and assessment of eating behavior with DEBQ (The Dutch Eating Behavior Questionnaire). All of the patients had extra Body mass or obesity: extra Body mass of the 1st grade was found in 18 patients (BMIobesity grade 2-3 in 38 patients (BMI>30 kg/m²). Authors identified different types of eating disorders: external, restrictive and emotiogenic as well as the relationship of their prevalence and severity with sex, drug, presence and grade of obesity. Based on these we developed recommendations for management of patients treated with second generation antipsychotics.

  9. Psychiatrists' Attitude and Use of Second-generation Antipsychotics for the Treatment of Schizophrenia in Taiwan.

    Science.gov (United States)

    Chen, C K; Su, H H; Sun, I W

    2017-09-01

    This survey aimed to understand the attitude of psychiatrists and their use of commonly prescribed second-generation antipsychotics (SGAs) for the treatment of schizophrenia in Taiwan. It also attempted to identify the factors that might influence their preference for selecting SGAs. Psychiatrists were interviewed face-to-face using a structured questionnaire. The questionnaire addressed various issues involved in the treatment of patients with schizophrenia, including the reasons for selecting SGAs, psychiatrists' level of satisfaction with commonly prescribed SGAs, and their current use of SGAs in clinical practice. Gender and age of the psychiatrists, and practice setting were not related to SGA selection. The selection of a SGA might be influenced by characteristics of the psychiatrist, properties of the drugs, and the healthcare insurance system. Most psychiatrists agreed that the performance of brand-name drugs was superior to that of generic drugs. Better symptom control, improvement in cognition, and higher tolerability were among the major factors considered by psychiatrists in Taiwan when prescribing antipsychotics. Selection of a SGA in Taiwan is potentially influenced by the characteristics of the psychiatrist, properties of the drug, and the healthcare insurance system. Efficacy and tolerability were among the major determining factors when prescribing antipsychotics for the treatment of patients with schizophrenia.

  10. The Pharmacokinetics of Second-Generation Long-Acting Injectable Antipsychotics: Limitations of Monograph Values.

    Science.gov (United States)

    Lee, Lik Hang N; Choi, Charles; Collier, Abby C; Barr, Alasdair M; Honer, William G; Procyshyn, Ric M

    2015-12-01

    Product monographs (also known by terms such as Summary of Product Characteristics and Highlights of Prescribing Information, depending on the jurisdiction) provide essential information to ensure the safe and effective use of a drug. Medical practitioners often rely on these monographs for guidance on matters related to pharmacokinetics as well as indications, contraindications, clinical pharmacology, and adverse reactions. The clinical and scientific information found within these documents, forming the basis for decision making, are presumed to be derived from well-designed studies. The objective of this review is to examine the source and validity of the pharmacokinetic data used in establishing the half-lives and times to steady-state reported in the product monographs of second-generation long-acting injectable antipsychotics. Thus, we have critically evaluated the clinical trials from which the pharmacokinetic parameters listed in the product monographs were determined. In many cases, the pharmacokinetic information presented in product monographs is of limited use to clinicians wishing to optimize the effectiveness and tolerability of second-generation long-acting injectable antipsychotics. Under such circumstances, off-label prescribing practices may actually produce better clinical outcomes than if decisions were made based on the product monographs alone.

  11. Second-generation antipsychotic and diabetes mellitus in children and adolescents

    Directory of Open Access Journals (Sweden)

    Carlo Ripoli

    2017-12-01

    Full Text Available Second generation antipsychotics (SGA are used in children for the treatment of various psychiatric diseases, including pervasive developmental disorders. These drugs can cause metabolic effects as hyperglycemia and diabetes. A 16-year-old young-boy, diagnosed with autism, developed diabetes mellitus type 1 whilst he was on treatment with olanzapine (started 4 months before, clomipramine, valproic acid and lithium. The hypothesis of druginduced diabetes imposed olanzapine interruption and clozapine initiation. Insulin therapy was practiced, with progressive dosage reduction, until complete cessation of treatment after 13 months. Blood sugar and HbA1c levels remained stable for about a year and then increased again, requiring the introduction of metformin that improved glycemia. In children and adolescents assuming SGA serum glucose and lipid profile should always be assessed before therapy and then frequently monitored. Drug selection must consider family history and the individual risk. Molecule final choice remains equilibrium between efficacy and safety.

  12. Second Generation Antipsychotics in the Treatment of Major Depressive Disorder: An Update

    Science.gov (United States)

    Wang, Sheng-Min; Han, Changsu; Lee, Soo-Jung; Jun, Tae-Youn; Patkar, Ashwin A; Masand, Prakash S

    2016-01-01

    Less than one third of patients who suffer from major depressive disorder (MDD) report remission following antidepressant treatments requiring more diverse treatment approaches. Augmentation of second generation antipsychotics (SGAs) has been increasingly recognized as an important treatment option. The authors have previously provided a comprehensive review of SGAs for the treatment of MDD in 2013. Since then, numerous additional clinical trials have been conducted to investigate diverse issues regarding the utility of SGAs in MDD. Moreover, a new SGA, brexpiprazole, was recently approved by the Food and Drug Administration in July 2015 for the treatment of MDD as an augmentation agent to antidepressants. Thus, the aim of this study was to provide a concise update of all the available SGAs for the treatment of MDD, in particular on the additional clinical trials which have been published since 2013. PMID:27689026

  13. Biases in medication prescribing: the case of second-generation antipsychotics.

    Science.gov (United States)

    Makhinson, Michael

    2010-01-01

    The shift from first-generation antipsychotic medications to second-generation antipsychotic medications initially caused a wave of excitement about the potential for improved and broader efficacy of these medications concurrent with an improved side-effect profile. Recent data from high-quality research analyses have subsequently raised significant questions about these claims. This research evidence has, however, not altered prescribing behavior in a way that would be expected from fully rational evaluation of the evidence. Prescribing decisions represent poorly understood, complex behaviors influenced by a number of external and internal forces, some of which may be elucidated by advances in social and cognitive psychology. In this article, the decision to prescribe first- versus second-generation antipsychotic medications is examined, and specific social psychological biases and individual cognitive biases are hypothesized to be significant influences on clinicians. These biases may perpetuate disparity between research evidence and clinical practice.

  14. Comparative study of treatment continuation using second-generation antipsychotics in patients with schizophrenia or schizoaffective disorder

    Directory of Open Access Journals (Sweden)

    Azekawa T

    2011-11-01

    Full Text Available Takaharu Azekawa, Shizuko Ohashi, Akira ItamiShioiri Mental Clinic, Yokosuka-shi, Kanagawa-ken, JapanBackground: Effectiveness of a drug is a key concept dependent on efficacy, safety, and tolerability. Time to discontinuation of treatment is also representative of effectiveness. We investigated differences in treatment discontinuation among newly started second-generation antipsychotics in the clinical setting.Methods: Using a retrospective cohort study design, we screened all outpatients (n = 7936 who visited the Shioiri Mental Clinic between July 1, 2008 and June 30, 2010. We identified a cohort of patients (n = 703 diagnosed with schizophrenia or schizoaffective disorder and calculated the time to discontinuation of each second-generation antipsychotic.Results: Of the 703 patients, 149 were newly treated with aripiprazole, 67 with blonanserin, 95 with olanzapine, 36 with quetiapine, 74 with perospirone, and 120 with risperidone. The time to discontinuation for all causes was significantly longer for aripiprazole than for blonanserin, olanzapine, and risperidone. In addition, aripiprazole tended to be continued for longer than quetiapine and perospirone, but these differences were not significant.Conclusion: Aripiprazole may be considered the best available option for long-term treatment of patients with schizophrenia or schizoaffective disorder.Keywords: retrospective study, second-generation antipsychotics, effectiveness, treatment continuation, schizophrenia, aripiprazole

  15. Second-generation long-acting injectable antipsychotics in schizophrenia: patient functioning and quality of life

    Directory of Open Access Journals (Sweden)

    Montemagni C

    2016-04-01

    Full Text Available Cristiana Montemagni,1,2 Tiziana Frieri,1,2 Paola Rocca1,2 1Department of Neuroscience, Unit of Psychiatry, University of Turin, 2Department of Mental Health, Azienda Sanitaria Locale (ASL Torino 1 (TO1, Azienda Ospedaliero-Universitaria (AOU Città della Salute e della Scienza di Torino, Turin, Italy Abstract: Long-acting injectable antipsychotics (LAIs were developed to make treatment easier, improve adherence, and/or signal the clinician when nonadherence occurs. Second-generation antipsychotic LAIs (SGA-LAIs combine the advantages of SGA with a long-acting formulation. The purpose of this review is to evaluate the available literature concerning the impact of SGA-LAIs on patient functioning and quality of life (QOL. Although several studies regarding schizophrenia patients’ functioning and QOL have been performed, the quantity of available data still varies greatly depending on the SGA-LAI under investigation. After reviewing the literature, it seems that SGA-LAIs are effective in ameliorating patient functioning and/or QOL of patients with schizophrenia, as compared with placebo. However, while methodological design controversy exists regarding the superiority of risperidone LAI versus oral antipsychotics, the significant amount of evidence in recently published research demonstrates the beneficial influence of risperidone LAI on patient functioning and QOL in stable patients and no benefit over oral treatment in unstable patients. However, the status of the research on SGA-LAIs is lacking in several aspects that may help physicians in choosing the correct drug therapy. Meaningful differences have been observed between SGA-LAIs in the onset of their clinical efficacy and in the relationships between symptoms and functioning scores. Moreover, head-to-head studies comparing the effects of SGA-LAIs on classical measures of psychopathology and functioning are available mainly on risperidone LAI, while those comparing olanzapine LAI with other

  16. Propensity score estimation to address calendar time-specific channeling in comparative effectiveness research of second generation antipsychotics.

    Directory of Open Access Journals (Sweden)

    Stacie B Dusetzina

    Full Text Available Channeling occurs when a medication and its potential comparators are selectively prescribed based on differences in underlying patient characteristics. Drug safety advisories can provide new information regarding the relative safety or effectiveness of a drug product which might increase selective prescribing. In particular, when reported adverse effects vary among drugs within a therapeutic class, clinicians may channel patients toward or away from a drug based on the patient's underlying risk for an adverse outcome. If channeling is not identified and appropriately managed it might lead to confounding in observational comparative effectiveness studies.To demonstrate channeling among new users of second generation antipsychotics following a Food and Drug Administration safety advisory and to evaluate the impact of channeling on cardiovascular risk estimates over time.Florida Medicaid data from 2001-2006.Retrospective cohort of adults initiating second generation antipsychotics. We used propensity scores to match olanzapine initiators with other second generation antipsychotic initiators. To evaluate channeling away from olanzapine following an FDA safety advisory, we estimated calendar time-specific propensity scores. We compare the performance of these calendar time-specific propensity scores with conventionally-estimated propensity scores on estimates of cardiovascular risk.Increased channeling away from olanzapine was evident for some, but not all, cardiovascular risk factors and corresponded with the timing of the FDA advisory. Covariate balance was optimized within period and across all periods when using the calendar time-specific propensity score. Hazard ratio estimates for cardiovascular outcomes did not differ across models (Conventional PS: 0.97, 95%CI: 0.81-3.18 versus calendar time-specific PS: 0.93, 95%CI: 0.77-3.04.Changes in channeling over time was evident for several covariates but had limited impact on cardiovascular risk

  17. Second-generation antipsychotics and risk of cerebrovascular accidents in the elderly.

    Science.gov (United States)

    Percudani, Mauro; Barbui, Corrado; Fortino, Ida; Tansella, Michele; Petrovich, Lorenzo

    2005-10-01

    Concern has been recently raised for risperidone and olanzapine, possibly associated with cerebrovascular events in placebo-controlled trials conducted in elderly subjects with dementia. We investigated the relationship between exposure to second-generation antipsychotics (SGAs) and occurrence of cerebrovascular accidents in the elderly. From the regional database of hospital admissions of Lombardy, Italy, we extracted all patients aged 65 or older with cerebrovascular-related outcomes for the year 2002. From the regional database of prescriptions reimbursed by the National Health Service, we extracted all patients aged 65 or older who received antipsychotic prescriptions during 2001. The 2 databases were linked anonymously using the individual patient code. The proportions of cerebrovascular accidents were 3.31% (95% confidence interval, 2.95-3.69) in elderly subjects exclusively exposed to SGAs and 2.37% (95% confidence interval, 2.19-2.57) in elderly subjects exclusively exposed to first-generation antipsychotics. After background group differences were controlled for, exposure to SGAs significantly increased the risk of accidents. The analysis of cerebrovascular events in elderly subjects exposed to each individual SGA, in comparison with exposure to haloperidol, showed a significantly increased risk for risperidone only (adjusted odds ratio, 1.43; 95% confidence interval, 1.12-1.93). These data provide preliminary epidemiological evidence that exposure to SGAs, in comparison with exposure to first-generation antipsychotics, significantly increased the risk of cerebrovascular accidents in the elderly.

  18. Weight gain with add-on second-generation antipsychotics in bipolar disorder: a naturalistic study.

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    Najar, H; Joas, E; Kardell, M; Pålsson, E; Landén, M

    2017-06-01

    Our aim was to investigate the prevalence and magnitude of weight gain in-patients with bipolar disorder when treated with a second-generation antipsychotic as an add-on treatment to a mood stabilizer in routine clinical practice. Data were derived from the quality register for bipolar disorder in Sweden (BipoläR). Patients with bipolar disorder who started add-on treatment with a SGA (n = 575) were compared at next yearly follow-up with age and sex matched patients who were only treated with a mood stabilizer (n = 566). The primary outcome measure was change in body weight and body mass index (BMI). We also assessed the prevalence of clinically significant weight gain defined as ≥7% gain in body weight. The group that received add-on treatment with antipsychotics neither gained more weight nor were at higher risk for a clinically significant weight gain than the reference group. Instead, factors associated with clinically significant weight gain were female sex, young age, low-baseline BMI, and occurrence of manic/hypomanic episodes. We found no evidence of an overall increased risk of weight gain for patients with bipolar disorder after receiving add-on SGA to a mood stabilizer in a routine clinical setting. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  19. Maintenance therapy with second generation antipsychotics for bipolar disorder - A systematic review and meta-analysis.

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    Lindström, Leif; Lindström, Eva; Nilsson, Mikael; Höistad, Malin

    2017-04-15

    Second generations antipsychotics (SGA) are frequently used for maintenance treatment in bipolar disorder. We systematically reviewed the efficacy and long-term effects of treatment with SGA, regardless of treatment strategy (SGA administered either as monotherapy or as adjunctive therapy), in comparison to placebo, lithium or valproate. Primary outcomes were relapses (mood episode recurrence) and discontinuation. Clinical studies were identified through database searching in PubMed, Embase, PsychInfo and Cochrane Library and critically appraised based on the Cochrane Handbook. Full data extraction of raw data was performed and analyzed with meta-analyses, and level of evidence graded using GRADE. Only randomized controlled studies (RCT) and observational studies were included, with a minimum follow-up of 6 months. Comparators used were restricted to placebo, lithium, valproate or other anti-epileptic drugs. We identified 15 RCTs on SGA in bipolar disorder with follow-up-time of 6 months up to 2 years, and one observational study reporting long-term effects of up to 4 years. A total of 6142 patients were included in the randomized trials. No long-term RCTs beyond 2 years follow-up was identified. All RCTs except for one included patients with bipolar disorder type I only. All RCTs except for two included patients pre-stabilized on the drug under investigation prior to randomization (enrichment design). For SGA as adjunctive therapy to lithium or valproate, meta-analyses showed that treatment with either aripiprazole (RR: 0.65, 95% CI 0.50-0.85), quetiapine (RR: 0.38, 95% CI 0.32-0.46) or ziprasidone (RR: 0.62, 95% CI 0.40-0.96) reduced the overall risk of relapses in patients that had responded during the stabilization phase. Adjunctive therapy with quetiapine was the only drug that reduced both manic and depressive episodes. For SGA as monotherapy, only quetiapine was shown to be better than lithium/ valproate for both manic and depressive relapses, but only for

  20. Safety, tolerability, and risks associated with first- and second-generation antipsychotics: a state-of-the-art clinical review

    Science.gov (United States)

    Solmi, Marco; Murru, Andrea; Pacchiarotti, Isabella; Undurraga, Juan; Veronese, Nicola; Fornaro, Michele; Stubbs, Brendon; Monaco, Francesco; Vieta, Eduard; Seeman, Mary V; Correll, Christoph U; Carvalho, André F

    2017-01-01

    Since the discovery of chlorpromazine (CPZ) in 1952, first-generation antipsychotics (FGAs) have revolutionized psychiatric care in terms of facilitating discharge from hospital and enabling large numbers of patients with severe mental illness (SMI) to be treated in the community. Second-generation antipsychotics (SGAs) ushered in a progressive shift from the paternalistic management of SMI symptoms to a patient-centered approach, which emphasized targets important to patients – psychosocial functioning, quality of life, and recovery. These drugs are no longer limited to specific Diagnostic and Statistical Manual of Mental Disorders (DSM) categories. Evidence indicates that SGAs show an improved safety and tolerability profile compared with FGAs. The incidence of treatment-emergent extrapyramidal side effects is lower, and there is less impairment of cognitive function and treatment-related negative symptoms. However, treatment with SGAs has been associated with a wide range of untoward effects, among which treatment-emergent weight gain and metabolic abnormalities are of notable concern. The present clinical review aims to summarize the safety and tolerability profile of selected FGAs and SGAs and to link treatment-related adverse effects to the pharmacodynamic profile of each drug. Evidence, predominantly derived from systematic reviews, meta-analyses, and clinical trials of the drugs amisulpride, aripiprazole, asenapine, brexpiprazole, cariprazine, clozapine, iloperidone, lurasidone, olanzapine, paliperidone, quetiapine, risperidone, sertindole, ziprasidone, CPZ, haloperidol, loxapine, and perphenazine, is summarized. In addition, the safety and tolerability profiles of antipsychotics are discussed in the context of the “behavioral toxicity” conceptual framework, which considers the longitudinal course and the clinical and therapeutic consequences of treatment-emergent side effects. In SMI, SGAs with safer metabolic profiles should ideally be prescribed

  1. Effect of second-generation antipsychotics on employment and productivity in individuals with schizophrenia: an economic perspective.

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    Percudani, Mauro; Barbui, Corrado; Tansella, Michele

    2004-01-01

    Schizophrenia is a serious mental illness that imposes a considerable burden not only on those who are ill, but also on their families, neighbours and the wider society. Costs associated with treating people with schizophrenia are those derived from the use of a wide range of services provided by public psychiatric facilities and/or by voluntary and private agencies. In addition, a large part of the economic impact of schizophrenia is related to the difficulties that patients encounter in finding and keeping paid employment. The introduction of second-generation antipsychotics (SGAs), also defined as atypicals, has increased the therapeutic options available for individuals with schizophrenia. Potential benefits of these agents include a more favourable profile in terms of positive and negative symptoms, less adverse effects and better cognitive functioning than first-generation antipsychotics (FGAs). As a consequence, SGAs might favourably affect the capacity, seriously impaired in schizophrenia, of finding and keeping paid employment. To date, only 13 published studies have investigated the effect of SGA agents on employment and work productivity. Clozapine was studied in eight studies, while both olanzapine and risperidone were studied in three. Clozapine emerged as the SGA with at least some effect on work status. However, all but one clozapine study enrolled only a few individuals and did not adopt an experimental design, making it very difficult to judge the validity and generalisability of findings. Taken together, studies found little benefit, in terms of employment and work productivity, for the use of SGAs compared with FGAs. The evidence available suggests that until data demonstrate a robust effect of newer agents on employment, it remains mandatory for mental health professionals to use the most effective drug treatment together with non-pharmacological interventions, such as vocational rehabilitative programmes nested into models of community

  2. Safety, tolerability, and risks associated with first- and second-generation antipsychotics: a state-of-the-art clinical review

    Directory of Open Access Journals (Sweden)

    Solmi M

    2017-06-01

    Full Text Available Marco Solmi,1,2 Andrea Murru,3 Isabella Pacchiarotti,3 Juan Undurraga,4,5 Nicola Veronese,2,6 Michele Fornaro,7,8 Brendon Stubbs,2,9–11 Francesco Monaco,2 Eduard Vieta,3 Mary V Seeman,12 Christoph U Correll,13,14 André F Carvalho2,15 1Neuroscience Department, University of Padua, 2Institute for Clinical Research and Education in Medicine, Padua, Italy; 3Bipolar Disorders Unit, Institute of Neuroscience, Hospital Clínic, University of Barcelona, IDIBAPS, CIBERSAM, Barcelona, Catalonia, Spain; 4Department of Psychiatry, Faculty of Medicine, Clínica Alemana Universidad del Desarrollo, 5Early Intervention Program, J. Horwitz Psychiatric Institute, Santiago, Chile; 6National Research Council, Ageing Section, Padua, 7Laboratory of Molecular and Translational Psychiatry, Department of Neuroscience, School of Medicine, University “Federico II”, Naples, Italy; 8New York State Psychiatric Institute, Columbia University, New York, NY, USA; 9Health Service and Population Research Department, Institute of Psychiatry, Psychology and Neuroscience, King’s College London, 10Physiotherapy Department, South London and Maudsley NHS Foundation Trust, London, 11Faculty of Health, Social Care and Education, Anglia Ruskin University, Chelmsford, UK; 12Institute of Medical Science, Toronto, ON, Canada; 13Department of Psychiatry Research, Zucker Hillside Hospital, Northwell Health, Glen Oaks, 14Department of Psychiatry and Molecular Medicine Hempstead, Hofstra Northwell School of Medicine, Hempstead, NY, USA; 15Translational Psychiatry Research Group and Department of Clinical Medicine, Faculty of Medicine, Federal University of Ceará, Fortaleza, Ceará, Brazil Abstract: Since the discovery of chlorpromazine (CPZ in 1952, first-generation antipsychotics (FGAs have revolutionized psychiatric care in terms of facilitating discharge from hospital and enabling large numbers of patients with severe mental illness (SMI to be treated in the community. Second-generation

  3. Lurasidone for schizophrenia: a review of the efficacy and safety profile for this newly approved second-generation antipsychotic.

    Science.gov (United States)

    Citrome, L

    2011-02-01

    To describe the efficacy and safety of lurasidone for the treatment of schizophrenia. The pivotal registration trials were accessed by querying the literature databases PubMed, EMBASE, ISI Web of Knowledge, as well as http://www.fda.gov and http://www.clinicaltrials.gov for the search term 'lurasidone'. Product labelling provided additional information. All available clinical reports of studies were identified. Descriptions of the principal results and calculation of number needed to treat (NNT) and number needed to harm (NNH) for relevant dichotomous outcomes were extracted from the available study reports, abstracts and posters. Additional safety outcomes subject to NNH analysis were obtained from product labelling. Lurasidone is a second-generation antipsychotic approved for the treatment of schizophrenia at a recommended starting dose of 40 mg/day administered once daily with food (≥350 calories). The maximum recommended dose is 80 mg/day. Regulatory approval was based primarily on a clinical trial programme that included four 6-week randomised clinical trials demonstrating efficacy vs. placebo in acute patients with schizophrenia. One additional Phase II clinical trial was considered a failed study because neither lurasidone nor the active control, haloperidol, separated from placebo on the primary outcome measure. One additional Phase III study was completed after the new drug application was submitted to the US Food and Drug Administration. Efficacy outcomes appear consistently in favour of lurasidone 80 mg/day vs. placebo on multiple measures of psychopathology, however, at least two studies also demonstrated efficacy for the doses of 40 and 120 mg/day. NNT vs. placebo was 3-6 for response as defined by ≥20% reduction in psychopathological rating scale total scores from baseline, depending on the study and the dose. Response as defined by a ≥30% improvement yielded NNTs ranging from 7 to 13. The most common adverse events in the clinical trials were

  4. Haloperidol versus second-generation antipsychotics in the long-term treatment of schizophrenia.

    Science.gov (United States)

    Buoli, Massimiliano; Kahn, René S; Serati, Marta; Altamura, A Carlo; Cahn, Wiepke

    2016-07-01

    The purpose of the study was to compare antipsychotic monotherapies in terms of time to discontinuation in a sample of schizophrenia patients followed-up for 36 months. Two hundred and twenty schizophrenia patients, treated with antipsychotic monotherapy and followed-up in psychiatric outpatient clinics of Universities of Milan and Utrecht were included in the study. A survival analysis (Kaplan-Meier) of the 36-month follow-up period was performed to compare the single treatment groups. End-point was considered as discontinuation of treatment for recurrence, side effects or non-compliance. Patients treated with haloperidol discontinued more than the other groups (Breslow: risperidone p haloperidol group than in the olanzapine group (p haloperidol group than with olanzapine (p haloperidol. In addition, atypical antipsychotics seem to be more protective against recurrences than haloperidol. However, these results should be cautiously interpreted in the light of potential confounder factors such as duration of illness. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

  5. Hyperprolactinemia with Antipsychotic Drugs in Children and Adolescents

    Directory of Open Access Journals (Sweden)

    Arlan L. Rosenbloom

    2010-01-01

    Full Text Available There is increasing use of antipsychotic drugs in pediatric and psychiatry practice for a wide range of behavioral and affective disorders. These drugs have prominent side effects of interest to pediatric endocrinologists, including weight gain and associated metabolic risk factors and hyperprolactinemia. The drugs block dopamine action, thus disinhibiting prolactin secretion. Hyperprolactinemia is especially prominent with first-generation antipsychotics such as haloperidol and the second-generation drugs, most commonly risperidone, with some patients developing gynecomastia or galactorrhea or, as a result of prolactin inhibition of gonadotropin releasing hormone from the hypothalamus, amenorrhea. With concern about the long-term effects of antipsychotics on bone mass and pituitary tumor formation, it is prudent to monitor serum prolactin levels in antipsychotic drug-treated pediatric patients and consider treatment with an agent less likely to induce hyperprolactinemia.

  6. Therapeutic drug monitoring of atypical antipsychotic drugs

    Directory of Open Access Journals (Sweden)

    Grundmann Milan

    2014-12-01

    Full Text Available Schizophrenia is a severe psychiatric disorder often associated with cognitive impairment and affective, mainly depressive, symptoms. Antipsychotic medication is the primary intervention for stabilization of acute psychotic episodes and prevention of recurrences and relapses in patients with schizophrenia. Typical antipsychotics, the older class of antipsychotic agents, are currently used much less frequently than newer atypical antipsychotics. Therapeutic drug monitoring (TDM of antipsychotic drugs is the specific method of clinical pharmacology, which involves measurement of drug serum concentrations followed by interpretation and good cooperation with the clinician. TDM is a powerful tool that allows tailor-made treatment for the specific needs of individual patients. It can help in monitoring adherence, dose adjustment, minimizing the risk of toxicity and in cost-effectiveness in the treatment of psychiatric disorders. The review provides complex knowledge indispensable to clinical pharmacologists, pharmacists and clinicians for interpretation of TDM results.

  7. Use of second-generation antipsychotics in the acute inpatient management of schizophrenia in the Middle East

    Directory of Open Access Journals (Sweden)

    Alkhadhari S

    2015-04-01

    Full Text Available Sulaiman Alkhadhari,1 Nasser Al Zain,2 Tarek Darwish,3 Suhail Khan,4 Tarek Okasha,5 Hisham Ramy,5 Talaat Matar Tadros6 1Kuwait Center for Mental Health, Safat, Kuwait; 2Al Amal Complex for Mental Health Hospital, Dammam, Saudi Arabia; 3Behavioural Science Pavilion, Sheikh Khalifa Medical City, Abu Dhabi, United Arab Emirates; 4Jeddah Psychiatric Hospital, Jeddah, Saudi Arabia; 5Institute of Psychiatry, Ain Shams University, Cairo, Egypt; 6Ibrahim Bin Hamad Obaidallah and Seif Bin Ghubash Hospitals, Ras Alkhaimah, United Arab Emirates Background: Management of acute psychotic episodes in schizophrenic patients remains a significant challenge for clinicians. Despite treatment guidelines recommending that second-generation antipsychotics (SGAs should be used as monotherapy, first-generation antipsychotics, polypharmacy, and lower than recommended doses are frequently administered in clinical practice. Minimal data exist regarding the use of SGAs in the Middle East. The objective of this study was to examine the discrepancies between current clinical practice and guideline recommendations in the region. Methods: RECONNECT-S Beta was a multicenter, noninterventional study conducted in Egypt, Kuwait, Saudi Arabia, and the United Arab Emirates to observe the management of schizophrenic patients who were hospitalized due to an acute psychotic episode. Patients underwent one visit on the day of discharge. Demographic and medical history, together with data on antipsychotic treatment and concomitant medication during the hospitalization period and medication recommendations at discharge were recorded. Results: Of the 1,057 patients, 180 (17.0% and 692 (65.5% received SGAs as monotherapy and in combination therapy, respectively. Overall, the most frequently administered medications were given orally, and included risperidone (40.3%, olanzapine (32.5%, and quetiapine (24.6%; the doses administered varied between countries and deviated from the recommended

  8. Hypothermia following antipsychotic drug use

    NARCIS (Netherlands)

    Marum, R.J. van; Wegewijs, M.A.; Loonen, A.J.M.; Beers, E.

    2007-01-01

    Objective: Hypothermia is an adverse drug reaction (ADR) of antipsychotic drug (APD) use. Risk factors for hypothermia in ADP users are unknown. We studied which risk factors for hypothermia can be identified based on case reports. Method: Case reports of hypothermia in APD-users found

  9. Hypothermia following antipsychotic drug use

    NARCIS (Netherlands)

    van Marum, Rob J.; Wegewijs, Michelle A.; Loonen, Anton J. M.; Beers, Erna

    Objective Hypothermia is an adverse drug reaction (ADR) of antipsychotic drug (APD) use. Risk factors for hypothermia in ADP users are unknown. We studied which risk factors for hypothermia can be identified based on case reports. Methods Case reports of hypothermia in APD-users found in PUBMED or

  10. Metabolic effects of second-generation antipsychotics in bipolar youth: comparison with other psychotic and nonpsychotic diagnoses.

    Science.gov (United States)

    Moreno, Carmen; Merchán-Naranjo, Jessica; Alvarez, Mar; Baeza, Inmaculada; Alda, Jose A; Martínez-Cantarero, Carmen; Parellada, Mara; Sánchez, Bernardo; de la Serna, Elena; Giráldez, Marisa; Arango, Celso

    2010-03-01

    Despite known metabolic effects of second-generation antipsychotics (SGAs) on children and adolescents, comparative effects in youth with different diagnoses remain underreported. We compared differences in metabolic changes three months after starting treatment with SGAs in youth with bipolar disorder and with other psychotic and nonpsychotic disorders. Weight and metabolic differences among diagnostic groups before and three months after starting treatment with SGAs were compared in a naturalistic cohort of children and adolescents (14.9 +/- 3.0 years) diagnosed with bipolar disorder (n = 31), other psychotic disorders (n = 29), and other nonpsychotic disorders (n = 30), with no (35.6%) or very little (6.6 +/- 9.0 days) previous exposure to antipsychotics. Composite measurements of significant weight gain [weight increase > or = 5% at three months or increase > or = 0.5 in body mass index (BMI) z-score] and 'risk for adverse health outcome' (> or = 95(th) BMI percentile, or > or = 85(th) BMI percentile plus presence of one other obesity-related complication) were included. SGAs (risperidone, olanzapine, and quetiapine) were prescribed in comparable proportion among groups. Baseline weight and metabolic indices were not significantly different among diagnoses. Three months after starting treatment with SGAs, more than 70% patients had significant weight gain, BMI z-score increased in all diagnostic groups (p or = 1 obesity-related complication at follow-up. There are early weight gain and metabolic changes across diagnoses in youth treated with SGAs.

  11. Novel versus conventional antipsychotic drugs.

    Science.gov (United States)

    Love, R C

    1996-01-01

    Novel antipsychotic agents differ from conventional ones in several key characteristics, including effectiveness, adverse reactions, and receptor-binding profile. Most of the newer agents have an affinity for the serotonin 5HT2 receptor that is at least 10 times greater than that for the dopamine D2 receptor. This increased affinity for the serotonin receptor may be responsible for another distinguishing characteristic of novel antipsychotic agents--decreased frequency of extrapyramidal side effects. These side effects, which include pseudoparkinsonism, acute dystonias, and akathisia, frequently are the reason for noncompliance with conventional drug therapy. The newer drugs are often effective in patients resistant to treatment with conventional agents. They also appear to reduce the negative symptoms of schizophrenia in many patients.

  12. A randomized controlled trial undertaken to test a nurse-led weight management and exercise intervention designed for people with serious mental illness who take second generation antipsychotics.

    Science.gov (United States)

    Usher, Kim; Park, Tanya; Foster, Kim; Buettner, Petra

    2013-07-01

    To test the effect of a nurse-led intervention on weight gain in people with serious mental illness prescribed and taking second generation antipsychotic medication. Weight gain and obesity has reached epidemic proportions in the general population with the prevalence of Metabolic Syndrome reaching 20-25% of the global population. People with serious mental illness are at even higher risk, particularly those taking second generation antipsychotic medication. An experimental randomized controlled trial was undertaken. The control group received a 12-week healthy lifestyle booklet. In addition to the booklet, the intervention group received weekly nutrition and exercise education, exercise sessions, and nurse support. Participants (n = 101) were assessed at baseline and 12 weeks. Data were collected between March 2008-December 2010. Seven outcome measures were used: body measurements included girth (cm), weight (kg), height (cm), and body mass index (kg/m(2) ); questionnaires included the medication compliance questionnaire, the Drug Attitude Inventory, the Liverpool University Neuroleptic Side Effect Rating Scale, and the Medical Outcomes Study Short Form 36. Differences in primary outcome measures between baseline and 12 weeks follow-up were compared between intervention and control groups using standard bi-variate statistical tests. The study was conducted between 2008-2010. The analysis of outcome measures for the control group (n = 50) and intervention group (n = 51) was not statistically significant. There was a mean weight change of -0·74 kg at 12 weeks for the intervention group (n = 51), while the control group (n = 50) had a mean weight change of -0·17 kg at 12 weeks. The results were not statistically significant. © 2012 Blackwell Publishing Ltd.

  13. Metabolic and endocrine adverse effects of second-generation antipsychotics in children and adolescents : A systematic review of randomized, placebo controlled trials and guidelines for clinical practice

    NARCIS (Netherlands)

    De Hert, M.; Dobbelaere, M.; Sheridan, E. M.; Cohen, D.; Correll, C. U.

    Second-generation antipsychotics (SGA) are being used more often than ever before in children and adolescents with psychotic and a wide range of non-psychotic disorders. Several SGA have received regulatory approval for some paediatric indications in various countries, but off-label use is still

  14. Monitoring of Recommended Metabolic Laboratory Parameters Among Medicaid Recipients on Second-Generation Antipsychotics in Federally Qualified Health Centers.

    Science.gov (United States)

    Uzal, Natalia E; Chavez, Benjamin; Kosirog, Emily R; Billups, Sarah J; Saseen, Joseph J

    2018-02-01

    In 2004, a consensus statement outlining recommended metabolic monitoring for patients prescribed second-generation antipsychotics (SGAs) was published. More than a decade later, suboptimal adherence rates to these recommendations continue to be reported, which could lead to long-term and costly complications. To define the prevalence of appropriately monitored Medicaid patients receiving care at federally qualified health centers (FQHCs) prescribed SGAs. This was a retrospective study examining electronic health record and Medicaid claims data to assess the rates of glucose and lipid monitoring for patients prescribed SGAs from January 2014 to August 2016 in a FQHC. Prescription and laboratory claims for patients receiving care at 4 FQHCs were reviewed. Descriptive statistics were used to evaluate the primary outcome. A total of 235 patients were included in the analysis. Patients initiated on SGA therapy (n = 92) had baseline glucose and lipid monitoring rates of 50% and 23%, respectively. The 3-month monitoring rates were 37% for glucose and 26% for lipids, whereas annual rates were 71% and 40%, respectively. Patients continuing SGA therapy (n = 143) had annual glucose and lipid monitoring rates of 67% and 44%. Medicaid patients at FQHCs initially prescribed SGAs have low baseline and 3-month metabolic monitoring, whereas annual monitoring was comparable to previously published studies. Adults receiving chronic care at a FQHC were more likely to receive glucose monitoring. Those with type 2 diabetes mellitus and/or hyperlipidemia were more likely to receive glucose and lipid monitoring.

  15. Some side effects and effcts on physical activity of second-generation antipsychotics: A study in children and adolescents

    Directory of Open Access Journals (Sweden)

    Soroor Arman

    2014-01-01

    Full Text Available Background: This study was designed to investigate the metabolic adverse effects (AEs of second-generation antipsychotics (SGAs and their relationship with physical activity and non-metabolic AE in children and adolescents. Materials and Methods: After exclusion of patients with metabolic syndrome, 62 patients (34 children, 28 adolescents of both genders who were candidates for SGA therapy were selected. Metabolic parameters included fasting blood glucose (FBG, triglyceride (TG, blood pressure (BP, and waist circumference (WC; non-metabolic AEs and physical activity were evaluated at baseline, 1 month, and 3 months after starting the treatment. Results: Mean of post-treatment FBG and TG were significantly higher than the baseline values (P 0.05. The frequency of patients with AbH-TG at the end point was not significantly higher than those with baseline AbH-TG (P = 0.10. Although no patient was obese at baseline, 11 (18% patients developed abdominal obesity at the end point (P 0.05. There was no significant correlation between metabolic and non-metabolic AE (P > 0.05. Frequency of inactive patients was significantly more than the baseline value (P-0.008, and abdominal obesity was significantly more prevalent in less active participants (P = 0.03. Conclusion: The present study showed the AE of SGA on FBG and TG, but no effect on BP and WC. We also found that children are more prone to develop abnormally high FBG.

  16. Persistence of metabolic monitoring for psychiatry inpatients treated with second-generation antipsychotics utilizing a computer-based intervention.

    Science.gov (United States)

    Lee, J; Dalack, G W; Casher, M I; Eappen, S A; Bostwick, J R

    2016-04-01

    Monitoring and intervention for metabolic abnormalities secondary to second-generation antipsychotics (SGAs) remain weak areas of performance in mental health care. This study evaluated the sustained impact of a computerized physician order entry (CPOE) pop-up alert designed to improve rates of laboratory metabolic monitoring of patients treated with SGAs in an inpatient psychiatry unit. Interventions carried out by the psychiatry team to manage metabolic abnormalities found on screening were also identified. A retrospective chart review of patients treated with scheduled SGAs at a large Midwestern academic medical centre's inpatient adult psychiatry unit was conducted nearly 4 years after the initial implementation of a pop-up alert. Rates of laboratory monitoring (blood glucose level, haemoglobin A1C [HbA1c], lipid panel) were compared to those following the initial implementation. Medical charts of patients with abnormal laboratory results were also reviewed to summarize interventions made by the psychiatry team to manage identified abnormalities. Patient demographics in the current study population (n = 129) were similar to those in the initial test cohort (n = 157). There was no significant decrease in monitoring of glucose levels and lipid panels (fasting or random). Nine patients with abnormally elevated laboratories were identified. Interventions by the psychiatry team included referrals to appropriate healthcare professionals and initiation of medication. The rate of metabolic monitoring for inpatients on SGA therapy did not significantly change over time with the continued use of the CPOE pop-up alert. Optimal monitoring utilizing a CPOE pop-up alert may allow the psychiatry team, including psychiatric pharmacists, to better manage metabolic conditions. © 2016 John Wiley & Sons Ltd.

  17. Off-Label Prescribing of Second-Generation Antipsychotics to Elderly Veterans with Posttraumatic Stress Disorder and Dementia.

    Science.gov (United States)

    Semla, Todd P; Lee, Austin; Gurrera, Ronald; Bajor, Laura; Li, Mingfei; Miller, Donald R; Smith, Eric G; Wang, Chao; Wan, Yun; Kazis, Lewis E; Bauer, Mark S

    2017-08-01

    To determine whether elderly veterans with posttraumatic stress disorder (PTSD) and dementia are more likely to be prescribed second-generation antipsychotics (SGAs) than those with PTSD alone. National serial cross-sectional study. Veterans Health Affairs inpatient and outpatient settings. Veterans aged 65 and older with PTSD (excluding schizophrenia or bipolar disorder) with or without concomitant dementia who received care from the Veterans Health Administration between 2003 and 2010 were identified using International Classification of Diseases, Ninth Revision, codes (N = 93,068; 11.1% with dementia). Trends in SGA prescribing and odds of being prescribed an SGA were determined using a multivariable logistic regression model adjusted for clinical, sociodemographic, and geographic covariates. Between 2004 and 2009, SGA prescribing declined annually from 7.0% to 5.1% of elderly veterans with PTSD without dementia and 13.2% to 8.9% in those with dementia; findings over time consistently indicated that veterans with PTSD and dementia had at least twice the odds of being prescribed an SGA as those without PTSD (odds ratios 2.03 (95% confidence interval (CI) = 1.82-2.26) to 2.33 (95% CI = 2.10-2.58). Although the prescribing of SGAs to elderly veterans with PTSD has decreased, prescribing an SGA to those with dementia remained consistently higher than for those with PTSD alone and is problematic given the high prevalence of medical comorbidities in this aging population coupled with the lack of compelling evidence for effectiveness of SGAs in individuals with dementia. © 2017, Copyright the Authors Journal compilation © 2017, The American Geriatrics Society.

  18. A critical assessment of antipsychotic drug monitoring.

    Science.gov (United States)

    Waraska, J; Nagle, J D

    1987-06-01

    Analytic problems associated with monitoring antipsychotic drug levels have largely been resolved. Despite the establishment of target values for some drugs, the clinical utility of such levels remains to be determined.

  19. Metabolic and Endocrine Side Effects of Atypical Antipsychotic Drugs in Children and Adolescents

    Directory of Open Access Journals (Sweden)

    Aysegul Tahiroglu

    2011-03-01

    Full Text Available omorbid psychiatric disorders, frequent hospitalization, multiple outpatient treatment, prior history of hypertension, obesity and lipid dysregulation are associated with higher risk of metabolic syndrome in children. Side effects of antipsychotic drugs and their management have recently become a major subject of research due to enhanced antipsychotic drug usage in child and adolescents. Prevention strategies are usually preferred to secondary or tertiary strategies in the management of metabolic syndrome associated with antipsychotic drugs. Clinicians should present multidisciplinary approach to endocrine and metabolic side effects due to antipsychotic use in pediatric patient groups and avoid multiple drug use in such patients. In this paper, we briefly reviewed metabolic side effects of second generation antipsychotic drugs in child and adolescent population, possible mechanisms of susceptibility to metabolic syndrome and pharmacological and non pharmacological treatment approach to prevention of weight gain.

  20. Second generation antipsychotics in Asperger's Disorder and high functioning autism: a systematic review of the literature and effectiveness of meta-analysis.

    Science.gov (United States)

    Sochocky, Natalie; Milin, Robert

    2013-11-01

    Second generation antipsychotics (SGA) have gained increased evidence for the treatment of irritability and aggression in children and adolescents with lower functioning autistic disorder. Individuals with Asperger's Disorder (AD) and High Functioning Autism (HFA) experience significant emotional and behavioral problems and psychiatric comorbidity. There is a need to review the published literature on SGA treatment efficacy in the AD and HFA populations to provide more effective treatment choices for these subgroups. We conducted a systematic review and meta-analysis of the recent English literature on SGA use in children and adolescents (ages 0-24 years) with AD and HFA using the Medline/PubMed and PsychINFO computerized databases. Key search words were 'Asperger', 'high functioning autism', 'autism spectrum disorders (ASD)', and 'pervasive developmental disorder (PDD)' in combination with 'second generation antipsychotics', 'aripiprazole; 'olanzapine', 'quetiapine', 'risperidone', or 'ziprasidone'. Our search yielded 214 citations, however only open-label or randomized-controlled trials (RCT) with ≥25% of their subjects having an IQ≥71 were included in our review. Eleven original studies met our inclusion parameters for review; eight studies for the meta-analysis. These studies, although limited in methodological rigor, and the meta-analytic results suggest that SGAs provide improvement in behavioral symptoms associated with AD and HFA. The majority of the studies reported weight gain as a potentially concerning adverse effect. There is a lack of robustly conducted trials on the use of SGAs in the management of AD and HFA. More research in pharmacological and psychosocial treatments is warranted. Clinicians are cautioned to approach pharmacological treatment prudently balancing benefit with potential cardiometabolic risk.

  1. Second-generation antipsychotic use in schizophrenia and associated weight gain: a critical review and meta-analysis of behavioral and pharmacologic treatments.

    Science.gov (United States)

    Das, Chandan; Mendez, Guillermo; Jagasia, Sonal; Labbate, Lawrence A

    2012-08-01

    Weight gain in schizophrenia, particularly secondary to second-generation antipsychotic (SGA) use, is a common adverse effect and often is associated with significant physical and psychological morbidity. We performed a critical literature review of all controlled clinical trials for pharmacologic and/or behavioral management of SGA-induced weight gain in schizophrenia patients by searching PubMed and Google Scholar. A meta-analysis was performed to estimate and compare weight changes for various medications and behavioral interventions. Sample sizes generally were small. Clinical trials were 6 weeks to 1 year, and weight loss was modest with any treatment. Although several adjunctive pharmacologic treatments showed no weight loss, sibutramine, metformin, and topiramate showed some benefit. Amantadine and orlistat were somewhat less effective and had lower rates of tolerability. Among the behavioral therapies, nutritional counseling combined with exercise showed the most benefit. Behavioral therapies, although modest, showed the most consistent benefits compared with controls. Scheduled pharmacologic treatment to prevent weight gain or promote weight loss in schizophrenia patients on SGA therapy is limited based on current studies. Switching antipsychotic agents has not been established as a long-term solution. Additional long-term studies are required to influence clinical practice.

  2. Treatment patterns in Medicaid patients with schizophrenia initiated on a first- or second-generation long-acting injectable versus oral antipsychotic

    Directory of Open Access Journals (Sweden)

    Pilon D

    2017-03-01

    Full Text Available Dominic Pilon,1 Kruti Joshi,2 Neeta Tandon,2 Marie-Hélène Lafeuille,1 Rhiannon L Kamstra,1 Bruno Emond,1 Patrick Lefebvre2 1Groupe d’analyse, Ltée, Montréal, QC, Canada; 2Janssen Scientific Affairs, LLC, Titusville, NJ, USA Background: Poor antipsychotic (AP adherence is a key issue in patients with schizophrenia. First-generation antipsychotic (FGA and second-generation antipsychotic (SGA long-acting injectable therapies (LAI may improve adherence compared to oral antipsychotics (OAP. The objective of the study was to compare treatment adherence and persistence in Medicaid patients with schizophrenia initiated on first-generation long-acting injectable therapies (FGA-LAI or second-generation long-acting injectable therapies (SGA-LAI versus OAP.Methods: Adults with schizophrenia initiated on FGA-LAI, SGA-LAI, or OAP on or after January 2010 were identified using a six-state Medicaid database (January 2009– March 2015. Outcomes were assessed during the 12 months following treatment initiation. Index medication adherence was assessed using the proportion of days covered ≥80%, while persistence was assessed as no gap of ≥30, ≥60, or ≥90 days between days of supply. Outcomes were compared between FGA/SGA-LAI and OAP cohorts using chi-squared tests and adjusted odds ratios (OR.Results: During follow-up, AP polypharmacy was more common in FGA-LAI patients (N=1,089; 36%; P=0.029 and less common in SGA-LAI patients (N=2,209; 27%; P<0.001 versus OAP patients (N=20,478; 33%. After adjustment, SGA-LAI patients had 24% higher odds of adherence at 12 months (OR: 1.24; P<0.001, in contrast to FGA-LAI patients who had 48% lower odds of adherence (OR: 0.52; P<0.001 relative to OAP patients. SGA-LAI patients were more likely to be persistent (no gap ≥60 days at 12 months than OAP patients (37% vs 30%; P<0.001, but not FGA-LAI patients (31% vs 30%; P=0.776. In comparison to OAP patients, SGA-LAI patients had 46% higher adjusted odds of

  3. Incidence of periprocedural myocardial infarction following stent implantation: Comparison between first- and second-generation drug-eluting stents

    NARCIS (Netherlands)

    Tandjung, Kenneth; Basalus, Mounir W.Z.; Muurman, Esther; Louwerenburg, Hans W.; van Houwelingen, Gert K.; Stoel, Martin G.; de Man, Frits H.A.F.; Jansen, Hanneke; Huisman, Jennifer; Linssen, Gerard C.M.; Droste, Herman T.; Nienhuis, Mark B.; von Birgelen, Clemens

    2012-01-01

    Background: First- and second-generation drug-eluting stents (DES) differ in coating materials, which may influence the incidence of periprocedural myocardial infarction (PMI). Objective: To compare the incidence of PMI between first- and second-generation DES, using the current Academic Research

  4. Pharmacogenetics and outcome with antipsychotic drugs.

    Science.gov (United States)

    Pouget, Jennie G; Shams, Tahireh A; Tiwari, Arun K; Müller, Daniel J

    2014-12-01

    Antipsychotic medications are the gold-standard treatment for schizophrenia, and are often prescribed for other mental conditions. However, the efficacy and side-effect profiles of these drugs are heterogeneous, with large interindividual variability. As a result, treatment selection remains a largely trial-and-error process, with many failed treatment regimens endured before finding a tolerable balance between symptom management and side effects. Much of the interindividual variability in response and side effects is due to genetic factors (heritability, h(2)~ 0.60-0.80). Pharmacogenetics is an emerging field that holds the potential to facilitate the selection of the best medication for a particular patient, based on his or her genetic information. In this review we discuss the most promising genetic markers of antipsychotic treatment outcomes, and present current translational research efforts that aim to bring these pharmacogenetic findings to the clinic in the near future.

  5. Antipsychotic drugs a last resort for these 5 conditions (ADHD, Anxiety, Depression, Insomnia and PTSD)

    Science.gov (United States)

    ... more about antipsychotic drugs, see these additional Best Buy Drugs reports. ■ Use of Antipsychotic Drugs in Children ■ Antipsychotic ... depression with antidepressant medication, see our FREE Best Buy Drugs report here . For more about augmentation therapy with ...

  6. Adiposity-independent hypoadiponectinemia as a potential marker of insulin resistance and inflammation in schizophrenia patients treated with second generation antipsychotics.

    Science.gov (United States)

    Sapra, Mamta; Lawson, Donna; Iranmanesh, Ali; Varma, Anjali

    2016-07-01

    The purpose of this study was to explore body fat independent effect of second generation antipsychotics (SGAs) on measures of glucose and adipokine homeostasis, and markers of inflammation. Eight non-diabetic men with schizophrenia (age: 55±3years, BMI: 29.7±1.2kg/m(2)) on SGAs were studied after an overnight fast. DXA and single-cut CT of abdomen were respectively used for the assessment of total body and abdominal fat. Blood samples were collected for measurements of glucose, insulin, leptin, adiponectin, C-reactive protein (CRP), and TNF-α. Data in schizophrenic subjects were compared to eight age (55±2.8years) and BMI (29.6±1.1kg/m(2)) matched healthy men. The results were significant for markedly decreased serum adiponectin in schizophrenia patients (4.6±0.9 vs 11.1±1.5ng/mL, p=0.001). Lower levels of adiponectin in schizophrenia men were associated with significant increases in insulin resistance (4.2±0.7 vs 1.7±0.4, p=0.004), CRP (3.5±1.2 vs 1.2±0.3, p=0.037), and leptin (12±1.4 vs 8.5±1.4ng/mL, p=0.05). Various measures of adiposity, including fat mass index (FMI) and abdominal fat were not different in the two study groups. These findings in the context of comparable age and total body/abdominal fat mass are assumed to be either disease specific, and/or treatment inflicted. The definitive invoking etiology and a presumptive role of hypoadiponectinemia in the development of insulin resistance and increased risk of inflammation warrant future investigation. Published by Elsevier B.V.

  7. Effect of Clozapine vs Other Second-Generation Antipsychotics on Hospitalization and Seclusion: A Retrospective Mirror-Image Study in a Japanese Public Psychiatric Hospital.

    Science.gov (United States)

    Misawa, Fuminari; Suzuki, Takefumi; Fujii, Yasuo

    2017-12-01

    Clozapine has been regarded as the gold standard for patients with treatment-resistant schizophrenia, but a recent network meta-analysis has questioned its relative superiority over other second-generation antipsychotics (SGAs) such as olanzapine and risperidone. We conducted a retrospective mirror-image study of clozapine vs other SGAs to evaluate real-world effectiveness of clozapine in terms of the duration of hospitalization and seclusion, both of which represent a critical outcome. We included all patients who initiated clozapine at the Yamanashi Prefectural KITA Hospital and had continued to take any SGA(s) other than clozapine for at least 1 year before the initiation of clozapine. We obtained data on hospitalization and seclusion during 1 year of SGA treatment (SGA phase) and 1 year after the treatment was switched to clozapine (clozapine phase). The study included 35 patients (21 men, 31 with schizophrenia, 4 with schizoaffective disorder) with the average ± SD age of 37.3 ± 11.1 years. The results indicated that total hospitalization days did not differ significantly between SGA and clozapine treatment. However, total duration of seclusion was significantly shorter in the clozapine phase than in the SGA phase. Furthermore, the number of patients who were secluded at least once was significantly smaller in the clozapine phase than in the SGA phase. The results were essentially unchanged when outlier patients were excluded and only when patients taking olanzapine and/or risperidone during the SGA phase were considered. Although the findings from this retrospective analysis need to be further tested in prospective trials, they endorse the relative effectiveness of clozapine over other SGAs in the real world.

  8. Differences in body mass index z-scores and weight status in a Dutch pediatric psychiatric population with and without use of second-generation antipsychotics.

    Science.gov (United States)

    de Hoogd, Sjoerd; Overbeek, Wieske A; Heerdink, Eibert R; Correll, Christoph U; de Graeff, Elisabeth R; Staal, Wouter G

    2012-04-01

    Weight gain and metabolic adverse effects of second-generation antipsychotics (SGAs) have become a major concern, particularly in youth. However, the specific contribution of SGAs versus other medications or the underlying illness is unclear. In a chart review study of psychiatric outpatients aged ≤ 18 years treated with SGAs and psychiatric controls without lifetime SGA, use body mass index (BMI) z-scores between patients and controls were compared in the entire sample, patients without co-medications, diagnostic subgroups, and age subgroups. In patients with follow-up data, weight z-score change was calculated. Altogether, 592 Caucasian patients aged 4-18 (mean: 10.0) years with a psychiatric diagnosis were included. BMI z-scores in 96 youth treated with SGAs for 9.0 ± 6.1 months were significantly higher than in 496 patients without lifetime SGA use (0.81 ± 1.1 vs. 0.05 ± 1.2; pz-score differences remained significant in all age groups z-score increased significantly from -0.17 ± 1.5 to 0.25 ± 1.4 (p<0.0001) with 12.5% transitioning to overweight or obese status. These data show robust and significant differences in sex- and age-adjusted body weight and weight status in young pediatric Caucasian samples with and without use of SGAs independent of Diagnostic and Statistical Manual of Mental Disorders, 4th edition, Text Revision (DSM-IV-TR) (American Psychiatric Association 2000 ) diagnosis and nonantipsychotic medications. Weight status and metabolic effects of SGAs require careful attention, especially in youth.

  9. Determination of antipsychotic drug in human serum by radioreceptor assay

    International Nuclear Information System (INIS)

    Wu Jinchang; Jiang Yimin

    1989-01-01

    Serum antipsychotic drug in 50 psychosis cases were measured by radioreceptor assay (RRA) and the values were compared in parallel with that by radioimmunoassay (RIA). The results showed that the RRA values were lower than the RIA values, but both assays gave significant correlation between the serum drug level and antipsychotic dose

  10. Pharmacokinetic-pharmacodynamic modelling of antipsychotic drugs in patients with schizophrenia : Part II: The use of subscales of the PANSS score

    NARCIS (Netherlands)

    Reddy, Venkatesh Pilla; Kozielska, Magdalena; Suleiman, Ahmed Abbas; Johnson, Martin; Vermeulen, An; Liu, Jing; de Greef, Rik; Groothuis, Geny M. M.; Danhof, Meindert; Proost, Johannes H.

    Background and objectives: The superiority of atypical antipsychotics (also known as second-generation antipsychotics (SGAs)) over typical antipsychotics (first generation antipsychotics (FGAs)) for negative symptom control in schizophrenic patients is widely debated. The objective of this study was

  11. Sex differences in the subjective tolerability of antipsychotic drugs

    NARCIS (Netherlands)

    Barbui, Corrado; Nosè, Michela; Bindman, Jonathan; Schene, Aart; Becker, Thomas; Mazzi, Maria A.; Kikkert, Martijn; Camara, Jayne; Born, Anja; Tansella, Michele

    2005-01-01

    In recent years, research efforts have been directed to better characterize the Subjective experience of taking psychotropic drugs. This Study investigated the sex difference in the subjective tolerability of antipsychotic drugs. Participants were recruited from patients under the care of

  12. Easy and low-cost identification of metabolic syndrome in patients treated with second-generation antipsychotics: artificial neural network and logistic regression models.

    Science.gov (United States)

    Lin, Chao-Cheng; Bai, Ya-Mei; Chen, Jen-Yeu; Hwang, Tzung-Jeng; Chen, Tzu-Ting; Chiu, Hung-Wen; Li, Yu-Chuan

    2010-03-01

    Metabolic syndrome (MetS) is an important side effect of second-generation antipsychotics (SGAs). However, many SGA-treated patients with MetS remain undetected. In this study, we trained and validated artificial neural network (ANN) and multiple logistic regression models without biochemical parameters to rapidly identify MetS in patients with SGA treatment. A total of 383 patients with a diagnosis of schizophrenia or schizoaffective disorder (DSM-IV criteria) with SGA treatment for more than 6 months were investigated to determine whether they met the MetS criteria according to the International Diabetes Federation. The data for these patients were collected between March 2005 and September 2005. The input variables of ANN and logistic regression were limited to demographic and anthropometric data only. All models were trained by randomly selecting two-thirds of the patient data and were internally validated with the remaining one-third of the data. The models were then externally validated with data from 69 patients from another hospital, collected between March 2008 and June 2008. The area under the receiver operating characteristic curve (AUC) was used to measure the performance of all models. Both the final ANN and logistic regression models had high accuracy (88.3% vs 83.6%), sensitivity (93.1% vs 86.2%), and specificity (86.9% vs 83.8%) to identify MetS in the internal validation set. The mean +/- SD AUC was high for both the ANN and logistic regression models (0.934 +/- 0.033 vs 0.922 +/- 0.035, P = .63). During external validation, high AUC was still obtained for both models. Waist circumference and diastolic blood pressure were the common variables that were left in the final ANN and logistic regression models. Our study developed accurate ANN and logistic regression models to detect MetS in patients with SGA treatment. The models are likely to provide a noninvasive tool for large-scale screening of MetS in this group of patients. (c) 2010 Physicians

  13. Prediabetes in patients treated with antipsychotic drugs.

    Science.gov (United States)

    Manu, Peter; Correll, Christoph U; van Winkel, Ruud; Wampers, Martien; De Hert, Marc

    2012-04-01

    In 2010, the American Diabetes Association (ADA) proposed that individuals with fasting glucose level of 100-125 mg/dL (5.6-6.9 mmol/L) or glucose level of 140-199 mg/dL (7.8-11.0 mmol/L) 2 hours after a 75-g oral glucose tolerance test or hemoglobin A(1c) 5.7%-6.4% be classified as prediabetic, indicating increased risk for the emergence of diabetes mellitus. At the same time, the ADA formulated guidelines for the use of metformin for the treatment of prediabetes. To determine the prevalence of prediabetes in a cohort of psychiatrically ill adults receiving antipsychotics and to compare the clinical and metabolic features of prediabetic patients with those of patients with normal glucose tolerance and those with diabetes mellitus. The 2010 ADA criteria were applied to a large, consecutive, single-site European cohort of 783 adult psychiatric inpatients (mean age: 37.6 years) without a history of diabetes who were receiving antipsychotics. All patients in this cross-sectional study underwent measurement of body mass index (BMI), waist circumference, oral glucose tolerance test, and fasting insulin and lipids from November 2003 through July 2007. 413 patients (52.8%) had normal glucose tolerance, 290 (37.0%) had prediabetes, and 80 (10.2%) had diabetes mellitus. The fasting glucose and/or hemoglobin A(1c) criteria were met by 89.7% of prediabetic patients. A statistically significant intergroup gradient from normal glucose tolerance to prediabetes and from prediabetes to diabetes mellitus was observed for waist circumference, triglycerides, fasting insulin levels, and frequency of metabolic syndrome (P = .02 to P prediabetic patients (6.6%) met the 2010 ADA criteria for treatment with metformin. Prediabetes is highly prevalent in adults treated with antipsychotic drugs and correlates with markers of increased intraabdominal adiposity, enhanced lipolysis, and insulin resistance. Criteria for using metformin to prevent the emergence of diabetes mellitus may need to be

  14. Interaction between anti-Alzheimer and antipsychotic drugs in modulating extrapyramidal motor disorders in mice

    Directory of Open Access Journals (Sweden)

    Saki Shimizu

    2015-04-01

    Full Text Available Antipsychotics are often used in conjunction with anti-Alzheimer drugs to treat the behavioral and psychological symptoms of dementia (BPSD. Here, we examined the effects of cholinesterase inhibitors (ChEIs, donepezil and galantamine, on antipsychotic-induced extrapyramidal side effects (EPS in mice. The effects of serotonergic agents on the EPS drug interaction were also evaluated. Donepezil (0.3–3 mg/kg did not induce EPS signs by itself; however, it significantly potentiated bradykinesia induction with a low dose of haloperidol (0.5 mg/kg in dose-dependent and synergistic manners. Galantamine (0.3–3 mg/kg elicited mild bradykinesia at a high dose and dose-dependently augmented haloperidol-induced bradykinesia. The EPS potentiation by galantamine was blocked by trihexyphenidyl (a muscarinic antagonist, but not by mecamylamine (a nicotinic antagonist. In addition, the bradykinesia potentiation by galantamine was significantly reduced by (±-8-hydroxy-2-(di-n-propylamino-tetralin (a 5-HT1A agonist, ritanserin (a 5-HT2 antagonist, and SB-258585 (a 5-HT6 antagonist. The present results give us a caution for the antipsychotics and ChEIs interaction in inducing EPS in the treatment of BPSD. In addition, second generation antipsychotics, which can stimulate 5-HT1A receptors or antagonize 5-HT2 and 5-HT6 receptors, seem to be favorable as an adjunctive therapy for BPSD.

  15. Early Nonresponse Determined by the Clinical Global Impressions Scale Predicts Poorer Outcomes in Youth with Schizophrenia Spectrum Disorders Naturalistically Treated with Second-Generation Antipsychotics

    DEFF Research Database (Denmark)

    Stentebjerg-Olesen, Marie; Jeppesen, Pia; Pagsberg, Anne K

    2013-01-01

    Abstract Objective: The use of early response/nonresponse (ER/ENR) to antipsychotics as a predictor for ultimate response/nonresponse (UR/UNR) may help decrease inefficacious treatment continuation. However, data have been limited to adults, and ER/ENR has only been determined using time-consuming...

  16. Prevalence of concurrent use of antipsychotic drugs and herbal ...

    African Journals Online (AJOL)

    The use of herbal medicines with conventional medicines is on the rise. Therefore, drug-herb interactions have become an important issue in drug safety and efficacy in clinical practice. A cross-sectional prospective study using a structured questionnaire was carried out on patients using antipsychotic drugs attending the ...

  17. Time Trends in Antipsychotic Drug Use in Patients with Dementia

    DEFF Research Database (Denmark)

    Nørgaard, Ane; Jensen-Dahm, Christina; Gasse, Christiane

    2015-01-01

    : To investigate time trends in use of antipsychotics and other psychotropic drugs in dementia care. METHODS: The study included longitudinal data on all Danish residents ≥65 years. The study population was defined on January 1 of each year from 2000-2012. Data included prescriptions, discharge diagnoses......, and somatic and psychiatric comorbidities. Multivariate time trend analyses of psychotropic drug use in patients with dementia within 4-year age bands were performed. RESULTS: Overall, among patients with dementia the prevalence of antipsychotic drug use decreased from 31.3% in 2000 to 20.4% in 2012...

  18. Cannabidiol, a Cannabis sativa constituent, as an antipsychotic drug

    Directory of Open Access Journals (Sweden)

    Zuardi A.W.

    2006-01-01

    Full Text Available A high dose of delta9-tetrahydrocannabinol, the main Cannabis sativa (cannabis component, induces anxiety and psychotic-like symptoms in healthy volunteers. These effects of delta9-tetrahydrocannabinol are significantly reduced by cannabidiol (CBD, a cannabis constituent which is devoid of the typical effects of the plant. This observation led us to suspect that CBD could have anxiolytic and/or antipsychotic actions. Studies in animal models and in healthy volunteers clearly suggest an anxiolytic-like effect of CBD. The antipsychotic-like properties of CBD have been investigated in animal models using behavioral and neurochemical techniques which suggested that CBD has a pharmacological profile similar to that of atypical antipsychotic drugs. The results of two studies on healthy volunteers using perception of binocular depth inversion and ketamine-induced psychotic symptoms supported the proposal of the antipsychotic-like properties of CBD. In addition, open case reports of schizophrenic patients treated with CBD and a preliminary report of a controlled clinical trial comparing CBD with an atypical antipsychotic drug have confirmed that this cannabinoid can be a safe and well-tolerated alternative treatment for schizophrenia. Future studies of CBD in other psychotic conditions such as bipolar disorder and comparative studies of its antipsychotic effects with those produced by clozapine in schizophrenic patients are clearly indicated.

  19. XIENCE V everolimus-eluting coronary stent system: a novel second generation drug-eluting stent

    NARCIS (Netherlands)

    Beijk, Marcel A. M.; Piek, Jon J.

    2007-01-01

    Drug-eluting stents (DES) have been shown to be safe and significantly reduce clinical events and angiographic restenosis in the percutaneous treatment of coronary artery disease. Currently, three DES have been approved in Europe and Northern America: the sirolimus-eluting stent (SES), the

  20. [Paroxysmal perceptual alteration in comparison with hallucination--a review of its clinical reports and discussion of its pathophysiological mechanism in the present day, when second generation antipsychotics are widely used].

    Science.gov (United States)

    Watanabe, Ken

    2009-01-01

    The syndrome of paroxysmal perceptual alteration (PPA) was first described by Yamaguchi in 1985. Since then, many PPA cases have been reported, and its pathophysiological mechanism has been proposed: a suppressed (blocked) mesolimbic and mesocortical dopaminergic system and sequential compensatory increase of noradrenergic neuronal activity are crucial for the occurrence of PPA. PPA is characterized by hypersensitivity of perception, psychedelic experience (brightening of colors, sharpening of contrast, visual distortion, etc.), and somatic schema disorder (one feels that one is floating, one's extremities are being pulled and elongated, etc.). PPA in chronic schizophrenic patients occurs abruptly like an attack mainly in the evening, often precipitated by fatigue. During the attack, patients also suffer from mood and thought alteration (anxiety, agitation, depressive mood, and inability to distract their thoughts from one thing), but they are aware that symptoms of PPA are not real and apprehensive about them. The attack ceases gradually and spontaneously while the patient rests or sleeps. These clinical features are clearly different from those of schizophrenic hallucinations. It is believed that PPA is closely related to neuroleptic treatment by conventional antipsychotics. I reported the prevalence of PPA as 4.0% in 1991 when high potential D2 blocking agents were prevailing. The occurrence of PPA has been significantly reduced to the present, when second generation (atypical) antipsychotics are prevailing. However, in my inquiry in 2004, the prevalence of PPA was 3.6% in cases treated with risperidone (RIS), while the rates were 0 in cases treated with olanzapine (OLZ), quetiapine (QTP), and perospirone (PRS). Several cases of PPA have been reported in patients who were treated with OLZ and PRS. Until now, no cases of PPA have been reported who were treated with QTP and aripiprazole (APZ). The prevalence of PPA among cases treated with these second generation

  1. Movement side effects of antipsychotic drugs in adults with and without intellectual disability: UK population-based cohort study.

    Science.gov (United States)

    Sheehan, Rory; Horsfall, Laura; Strydom, André; Osborn, David; Walters, Kate; Hassiotis, Angela

    2017-08-03

    To measure the incidence of movement side effects of antipsychotic drugs in adults with intellectual disability and compare rates with adults without intellectual disability. Cohort study using data from The Health Improvement Network. UK primary care. Adults with intellectual disability prescribed antipsychotic drugs matched to a control group of adults without intellectual disability prescribed antipsychotic drugs. New records of movement side effect including acute dystonias, akathisia, parkinsonism, tardive dyskinaesia and neuroleptic malignant syndrome. 9013 adults with intellectual disability and a control cohort of 34 242 adults without intellectual disability together contributed 148 709 person-years data. The overall incidence of recorded movement side effects was 275 per 10 000 person-years (95% CI 256 to 296) in the intellectual disability group and 248 per 10 000 person-years (95% CI 237 to 260) in the control group. The incidence of any recorded movement side effect was significantly greater in people with intellectual disability compared with those without (incidence rate ratio 1.30, 95% CI 1.18 to 1.42, pmovement side effects between the groups were not due to differences in the proportions prescribed first and second-generation antipsychotic drugs. This study provides evidence to substantiate the long-held assumption that people with intellectual disability are more susceptible to movement side effects of antipsychotic drugs. Assessment for movement side effects should be integral to antipsychotic drug monitoring in people with intellectual disability. Regular medication review is essential to ensure optimal prescribing in this group. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  2. Association between P-glycoprotein polymorphisms and antipsychotic drug-induced hyperprolactinemia

    NARCIS (Netherlands)

    Geers, Lisanne; Pozhidaev, Ivan V; Ivanova, Svetlana A.; Freidin, Maxim B.; Cohen, Dan; Boiko, Anastasia S; Osmanova, Diana Z; Fedorenko, Olga Yu; Touw, Daniël; Semke, Arkadiy V.; Wilffert, Berend; Bokhan, Nikolay A.; Loonen, Antonius

    2017-01-01

    Background: Regular therapy for schizophrenia includes maintenance antipsychotic treatment. Unfortunately, antipsychotics also have a spectrum of side effects, including metabolic, endocrine, cardiovascular, and movement disorders. One of the common side effects of these drugs is hyperprolactinemia

  3. The influence of atypical antipsychotic drugs on sexual function

    Directory of Open Access Journals (Sweden)

    Just MJ

    2015-07-01

    Full Text Available Marek J Just Department of General and Endocrine Surgery, Piekary Medical Centre, Piekary Slaskie, Poland Abstract: Human sexuality is contingent upon many biological and psychological factors. Such factors include sexual drive (libido, physiological arousal (lubrication/erection, orgasm, and ejaculation, as well as maintaining normal menstrual cycle. The assessment of sexual dysfunction can be difficult due to the intimate nature of the problem and patients’ unwillingness to discuss it. Also, the problem of dysfunction is often overlooked by doctors. Atypical antipsychotic treatment is a key component of mental disorders’ treatment algorithms recommended by the National Institute of Health and Clinical Excellence, the American Psychiatric Association, and the British Society for Psychopharmacology. The relationship between atypical antipsychotic drugs and sexual dysfunction is mediated in part by antipsychotic blockade of pituitary dopamine D2 receptors increasing prolactin secretion, although direct correlations have not been established between raised prolactin levels and clinical symptoms. Variety of mechanisms are likely to contribute to antipsychotic-related sexual dysfunction, including hyperprolactinemia, sedation, and antagonism of a number of neurotransmitter receptors (α-adrenergic, dopaminergic, histaminic, and muscarinic. Maintaining normal sexual function in people treated for mental disorders can affect their quality of life, mood, self-esteem, attitude toward taking medication, and compliance during therapy. Keywords: schizophrenia, galactorrhea, hyperprolactinemia, mood disorders, anorgasmia

  4. Antipsychotic drug treatment for patients with schizophrenia: theoretical background, clinical considerations and patients preferences

    DEFF Research Database (Denmark)

    Nielsen, René Ernst; Nielsen, Jimmi

    2009-01-01

      The cornerstone in treatment of psychosis is antipsychotic drugs. Treatment options have increased over the years; newer antipsychotic drugs with a proposed efficacy regarding negative and cognitive symptoms, but also a shift in side-effects from neurological side-effects to metabolic side......-effects have arisen as the new challenge. The basis of successful pharmacological treatment is a fundamental understanding of the mechanisms of action, the desired effects and side-effects of antipsychotic drugs, a good relationship with the patient and a thorough monitoring of the patient before and during...... treatment. The clinically relevant aspects of antipsychotic drug treatment are reviewed; mechanism of antipsychotic drug action, clinical considerations in treatment, switching antipsychotic drugs, polypharmacy, safety and patient preference.  ...

  5. Chronic Kidney Disease in the Second-Generation Drug-Eluting Stent Era: Pooled Analysis of the Korean Multicenter Drug-Eluting Stent Registry.

    Science.gov (United States)

    Lee, Joo Myung; Kang, Jeehoon; Lee, Euijae; Hwang, Doyeon; Rhee, Tae-Min; Park, Jonghanne; Kim, Hack-Lyoung; Lee, Sang Eun; Han, Jung-Kyu; Yang, Han-Mo; Park, Kyung Woo; Na, Sang-Hoon; Kang, Hyun-Jae; Koo, Bon-Kwon; Kim, Hyo-Soo

    2016-10-24

    The purpose of this study was to evaluate the clinical impact of chronic kidney disease (CKD) on clinical outcomes in contemporary practice of percutaneous coronary intervention (PCI) using second-generation drug-eluting stents (DES). Although second-generation DES have improved the safety and efficacy issues in PCI, data regarding the performance of second-generation DES in patients with CKD are still limited. We performed a patient-level pooled analysis on 12,426 patients undergoing PCI using second-generation DES from the Korean Multicenter Drug-Eluting Stent Registry. Endpoints were stent-oriented outcomes (target lesion failure [TLF]) and patient-oriented composite outcomes (POCO) during a median follow-up of 35 months. CKD patients were stratified by the estimated glomerular filtration rate (eGFR) from mild CKD to end-stage renal disease patients, and by the coexistence of diabetes mellitus (DM). A total of 2,927 patients had CKD (23.6%), who showed a significantly higher risk of TLF (adjusted hazard ratio [HR adjust ]: 1.50; 95% confidence interval [CI]: 1.21 to 1.86) and POCO (HR adjust 1.34; 95% CI: 1.17 to 1.55) compared to patients with preserved renal function. Stratified analysis by eGFR showed that TLF was not increased in the mild to moderate CKD, whereas severe CKD and dialysis-dependent patients showed significantly higher risk of TLF (HR adjust 2.44; 95% CI: 1.54 to 3.86; HR adjust 3.58; 95% CI: 2.52 to 5.08, respectively). The eGFR threshold of increased clinical events was 40 to 45 ml/min/1.73 m 2 . Among CKD patients, DM CKD patients showed a higher incidence of TLF compared to non-DM CKD patients (HR adjust : 1.82; 95% CI: 1.32 to 2.52), driven by the increase in target vessel-related events. In the era of second-generation DES, CKD patients were at a significantly higher risk of clinical outcomes only in severe CKD and end-stage renal disease patients. Copyright © 2016 American College of Cardiology Foundation. Published by Elsevier Inc. All

  6. Meta-Analysis of Randomized Clinical Trials Comparing Biodegradable Polymer Drug-Eluting Stent to Second-Generation Durable Polymer Drug-Eluting Stents.

    Science.gov (United States)

    El-Hayek, Georges; Bangalore, Sripal; Casso Dominguez, Abel; Devireddy, Chandan; Jaber, Wissam; Kumar, Gautam; Mavromatis, Kreton; Tamis-Holland, Jacqueline; Samady, Habib

    2017-03-13

    The authors sought to perform a meta-analysis of randomized clinical trials (RCTs) comparing the safety and efficacy of biodegradable polymer drug-eluting stents (BP-DES) to second-generation durable polymer drug-eluting stents (DP-DES). Prior meta-analyses have established the superiority of BP-DES over bare-metal stents and first-generation DP-DES; however, their advantage compared with second-generation DP-DES remains controversial. The authors searched PubMed and Scopus databases for RCTs comparing BP-DES to the second-generation DP-DES. Outcomes included target vessel revascularization (TVR) as efficacy outcome and cardiac death, myocardial infarction (MI), and definite or probable stent thrombosis (ST) as safety outcomes. In addition, we performed landmark analysis for endpoints beyond 1 year of follow-up and a subgroup analysis based on the stent characteristics. The authors included 16 RCTs comprising 19,886 patients in the meta-analysis. At the longest available follow-up (mean duration 26 months), we observed no significant differences in TVR (p = 0.62), cardiac death (p = 0.46), MI (p = 0.98), or ST (risk ratio: 0.83, 95% confidence interval: 0.64 to 1.09; p = 0.19). Our landmark analysis showed that BP-DES were not associated with a reduction in the risk of very late ST (risk ratio: 0.87, 95% confidence interval: 0.49 to 1.53; p = 0.62). Similar outcomes were seen regardless of the eluting drug (biolimus vs. sirolimus), the stent platform (stainless steel vs. alloy), the kinetics of polymer degradation or drug release (6 months), the strut thickness of the BP-DES (thin 100 μm), or the DAPT duration (≥6 months vs. ≥12 months). BP-DES have similar safety and efficacy profiles to second-generation DP-DES. Published by Elsevier Inc.

  7. Second generation drug-eluting stents versus bare-metal stents for percutaneous coronary intervention of the proximal left anterior descending artery

    DEFF Research Database (Denmark)

    Mangione, Fernanda Marinho; Biering-Sørensen, Tor; Nochioka, Kotaro

    2017-01-01

    OBJECTIVES: To compare mid-term outcomes between patients undergoing proximal left anterior descending artery (LAD) percutaneous coronary intervention (PCI) with second generation drug-eluting stent (DES) or bare-metal stent (BMS). BACKGROUND: PCI with BMS and first-generation DES have shown to b...

  8. Toward an understanding of antipsychotic drug induced weight gain - use of a rodent model

    OpenAIRE

    Stefanidis, Aneta

    2017-01-01

    Antipsychotic drug therapy is a fundamental tool in the treatment of schizophrenia and other psychoses. Recent years have seen the development of new antipsychotic compounds with an improved acute adverse effect profile; however these are often associated with weight gain and increased risk of metabolic disturbances. Olanzapine, despite its considerable adverse impact on weight gain and associated pathologies, has been recognized as the most efficacious antipsychotic drug in the treatment of ...

  9. Challenges and opportunities for the development of new antipsychotic drugs.

    Science.gov (United States)

    Forray, Carlos; Buller, Raimund

    2017-11-01

    In spite of the significant impact that the serendipitous discovery of drugs with antipsychotic properties had on the care of patients with psychotic disorders, there are significant challenges when aiming at therapeutic goals such as remission, recovery, improved health-related quality of life and functioning. The efficacy and effectiveness of existing antipsychotic drugs fail to address the full spectrum of symptoms and functional deficits that currently prevent patients with psychotic disorders from achieving fulfilling lives. The study of the pharmacological mechanism of action has increased our knowledge on molecular targets and brain circuits related to the antipsychotic properties of this drug class. However, our understanding of how these molecular targets and brain circuits relate to other aspects of disease pathophysiology like cognitive impairment and negative symptoms is incomplete although these are significant clinical unmet needs. Currently, there is still an important knowledge gap between psychopathology and pathophysiology in schizophrenia research. This may have contributed to some recent costly failures of large clinical development programs for drugs targeted at glutamatergic function and nicotinic receptors. The lack of success of these pharmacological approaches to achieve clinical validation raises important questions concerning the underlying hypothesis that guided the choice of molecular targets, and about the predictive validity of translational models that supported the rationale for testing these drugs in clinical studies. From a clinical perspective there is a need to more strongly consider the disease heterogeneity linked to the use of the current diagnostic classification of subjects and to the validity of the psychopathological constructs and assessments that are used to assess clinical outcomes. A paradigm shift in the development of drugs for schizophrenia is needed. This will require among other addressing: the shortcomings of a

  10. Use of antipsychotic drugs in individuals with intellectual disability (ID) in the Netherlands : prevalence and reasons for prescription

    NARCIS (Netherlands)

    de Kuijper, G.; Hoekstra, P.; Visser, F.; Scholte, F. A.; Penning, C.; Evenhuis, H.

    Background We investigated antipsychotic drug prescription practice of Dutch ID physicians, studying prevalence of antipsychotic drug use, reasons for prescription and the relationship between these reasons and patient characteristics. Methods A cross-sectional study of medical and pharmaceutical

  11. Very late stent thrombosis with second generation drug eluting stents compared to bare metal stents: Network meta-analysis of randomized primary percutaneous coronary intervention trials.

    Science.gov (United States)

    Philip, Femi; Stewart, Susan; Southard, Jeffrey A

    2016-07-01

    The relative safety of drug-eluting stents (DES) and bare-metal stents (BMS) in primary percutaneous coronary intervention (PPCI) in ST elevation myocardial infarction (STEMI) continues to be debated. The long-term clinical outcomes between second generation DES and BMS for primary percutaneous coronary intervention (PCI) using network meta-analysis were compared. Randomized controlled trials comparing stent types (first generation DES, second generation DES, or BMS) were considered for inclusion. A search strategy used Medline, Embase, Cochrane databases, and proceedings of international meetings. Information about study design, inclusion criteria, and sample characteristics were extracted. Network meta-analysis was used to pool direct (comparison of second generation DES to BMS) and indirect evidence (first generation DES with BMS and second generation DES) from the randomized trials. Twelve trials comparing all stents types including 9,673 patients randomly assigned to treatment groups were analyzed. Second generation DES was associated with significantly lower incidence of definite or probable ST (OR 0.59, 95% CI 0.39-0.89), MI (OR 0.59, 95% CI 0.39-0.89), and TVR at 3 years (OR 0.50: 95% CI 0.31-0.81) compared with BMS. In addition, there was a significantly lower incidence of MACE with second generation DES versus BMS (OR 0.54, 95% CI 0.34-0.74) at 3 years. These were driven by a higher rate of TVR, MI and stent thrombosis in the BMS group at 3 years. There was a non-significant reduction in the overall and cardiac mortality [OR 0.83, 95% CI (0.60-1.14), OR 0.88, 95% CI (0.6-1.28)] with the use of second generation DES versus BMS at 3 years. Network meta-analysis of randomized trials of primary PCI demonstrated lower incidence of MACE, MI, TVR, and stent thrombosis with second generation DES compared with BMS. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  12. First-Generation Versus Second-Generation Drug-Eluting Stents in Coronary Chronic Total Occlusions: Two-Year Results of a Multicenter Registry.

    Directory of Open Access Journals (Sweden)

    Jong-Hwa Ahn

    Full Text Available Limited data are available regarding the long-term clinical outcomes of second-generation drug-eluting stents (DES versus first-generation DES in patients with coronary chronic total occlusion (CTO who undergo percutaneous coronary intervention (PCI. The aim of this study was to compare the clinical outcomes of second-generation DES with those of first-generation DES for the treatment of CTO.Between March 2003 and February 2012, 1,006 consecutive patients with CTO who underwent successful PCI using either first-generation DES (n = 557 or second-generation DES (n = 449 were enrolled in a multicenter, observational registry. Propensity-score matching was also performed. The primary outcome was cardiac death over a 2-year follow-up period. No significant differences were observed between the two groups regarding the incidence of cardiac death (first-generation DES versus second-generation DES; 2.5% vs 2.0%; hazard ratio [HR]: 0.86; 95% confidence interval [CI]: 0.37 to 1.98; p = 0.72 or major adverse cardiac events (MACE, 11.8% vs 11.4%; HR: 1.00; 95% CI: 0.67 to 1.50; p = 0.99. After propensity score matching, the incidences of cardiac death (HR: 0.86; 95% CI: 0.35 to 2.06; p = 0.86 and MACE (HR: 0.93; 95% CI: 0.63 to 1.37; p = 0.71 were still similar in both groups. Furthermore, no significant differences were observed between sirolimus-eluting, paclitaxel-eluting, zotarolimus-eluting, and everolimus-eluting stents regarding the incidence of cardiac death or MACE.This study shows that the efficacy of second-generation DES is comparable to that of first-generation DES for treatment of CTO over 2 years of follow-up.

  13. Mechanisms and Patterns of Intravascular Ultrasound In-Stent Restenosis Among Bare Metal Stents and First- and Second-Generation Drug-Eluting Stents.

    Science.gov (United States)

    Goto, Kosaku; Zhao, Zhijing; Matsumura, Mitsuaki; Dohi, Tomotaka; Kobayashi, Nobuaki; Kirtane, Ajay J; Rabbani, LeRoy E; Collins, Michael B; Parikh, Manish A; Kodali, Susheel K; Leon, Martin B; Moses, Jeffrey W; Mintz, Gary S; Maehara, Akiko

    2015-11-01

    The most common causes of in-stent restenosis (ISR) are intimal hyperplasia and stent under expansion. The purpose of this study was to use intravascular ultrasound (IVUS) to compare the ISR mechanisms of bare metal stents (BMS), first-generation drug-eluting stents (DES), and second-generation DES. There were 298 ISR lesions including 52 BMS, 73 sirolimus-eluting stents, 52 paclitaxel-eluting stents, 16 zotarolimus-eluting stents, and 105 everolimus-eluting stent. Mean patient age was 66.6 ± 1.1 years, 74.2% were men, and 48.3% had diabetes mellitus. BMS restenosis presented later (70.0 ± 66.7 months) with more intimal hyperplasia compared with DES (BMS 58.6 ± 15.5%, first-generation DES 52.6 ± 20.9%, second-generation DES 48.2 ± 22.2%, p = 0.02). Although reference lumen areas were similar in BMS and first- and second-generation DES, restenotic DES were longer (BMS 21.8 ± 13.5 mm, first-generation DES 29.4 ± 16.1 mm, second-generation DES 32.1 ± 18.7 mm, p = 0.003), and stent areas were smaller (BMS 7.2 ± 2.4 mm(2), first-generation DES 6.1 ± 2.1 mm(2), second-generation DES 5.7 ± 2.0 mm(2), p Stent fracture was seen only in DES (first-generation DES 7 [5.0%], second-generation DES 8 [7.4%], p = 0.13). In conclusion, restenotic first- and second-generation DES were characterized by less neointimal hyperplasia, smaller stent areas, longer stent lengths, and more stent fractures than restenotic BMS. Copyright © 2015 Elsevier Inc. All rights reserved.

  14. Influence of the drug exposure definition on the assessment of the antipsychotic metabolic impact in patients initially treated with mood-stabilizers.

    Science.gov (United States)

    Tournier, Marie; Bégaud, Bernard; Cougnard, Audrey; Auleley, Guy-Robert; Deligne, Jean; Blum-Boisgard, Claudine; Thiébaut, Anne C M; Verdoux, Hélène

    2012-07-01

    • Metabolic disturbances represent a well-known side effect of second generation antipsychotics. However, studies comparing second generation antipsychotic drugs (SGAPs) and first generation antipsychotic drugs (FGAPs) through administrative databases have shown contrasting findings, which may be attributable to methodological differences. • The definition of antipsychotic exposure impacts on the association between antipsychotics and metabolic risk in studies carried out through administrative databases. • Considering cumulative exposure to antipsychotics or including patients exposed to an antipsychotic drug for months or years is likely to over-represent patients who tolerate the drug well with a depletion of susceptible effects. • Antipsychotic drug exposure is a time-varying determinant and episodes of no use, past use and current use should be distinguished over the study period to avoid any misclassification bias that might lead to misleading findings. To assess the influence of three definitions of antipsychotic exposure on the comparison between first generation (FGAP) and second generation (SGAP) antipsychotic drugs and 'conventional' mood stabilizers towards the risk of metabolic events using (i) a dichotomous measure (exposed/non-exposed over the follow-up), (ii) a categorical measure taking into account the chronology of exposure at the time of the metabolic event (current, recent and no use) and (iii) a continuous measure (cumulative duration). A historical fixed cohort was identified from the 2004-2006 claims database of the French health insurance programme for self-employed workers, including 3172 patients aged 18 years and over who used conventional mood stabilizers over a 3 month period. A metabolic event was defined as an incident dispensing of an anti-diabetic or lipid-lowering drug. A metabolic event occurred in 367 patients (11.6%). At least one FGAP had been prescribed in 29% of patients who did not develop a metabolic event and in

  15. Intrinsic and Antipsychotic Drug-Induced Metabolic Dysfunction in Schizophrenia

    Directory of Open Access Journals (Sweden)

    Zachary Freyberg

    2017-07-01

    Full Text Available For decades, there have been observations demonstrating significant metabolic disturbances in people with schizophrenia including clinically relevant weight gain, hypertension, and disturbances in glucose and lipid homeostasis. Many of these findings pre-date the use of antipsychotic drugs (APDs which on their own are also strongly associated with metabolic side effects. The combination of APD-induced metabolic changes and common adverse environmental factors associated with schizophrenia have made it difficult to determine the specific contributions of each to the overall metabolic picture. Data from drug-naïve patients, both from the pre-APD era and more recently, suggest that there may be an intrinsic metabolic risk associated with schizophrenia. Nevertheless, these findings remain controversial due to significant clinical variability in both psychiatric and metabolic symptoms throughout patients' disease courses. Here, we provide an extensive review of classic and more recent literature describing the metabolic phenotype associated with schizophrenia. We also suggest potential mechanistic links between signaling pathways associated with schizophrenia and metabolic dysfunction. We propose that, beyond its symptomatology in the central nervous system, schizophrenia is also characterized by pathophysiology in other organ systems directly related to metabolic control.

  16. The effects of antipsychotic drugs on depression level in patients with schizophrenia: clozapine vs. other atypical antipsychotics

    Directory of Open Access Journals (Sweden)

    Hülya Ertekin

    2016-08-01

    Full Text Available Introduction: Depressive symptoms may occur in all stages of schizophrenia disorder. Clozapine is the only antipsychotic that has been demonstrated superior efficacy in schizophrenia and suicidal ideation. The aim of this study is to evaluate depressive symptoms in patients with schizophrenia treated with clozapine and to compare with treated with other atypical antipsychotics.Methods: A cross-sectional descriptive study was carried out on patients with schizophrenia according to DSM-IV-TR between December 2012 and May 2013. All participants were evaluated for demographic characteristics and points of Brief Psychiatric Rating Scale, Positive, Negative Syndrome Scale, and Calgary Depression Scale for Schizophrenia.Results: A total 23.6% (n = 13 patients treated with clozapine, while 76.4% (n = 42 patients were treated with other antipsychotic drugs. 23.1% (n = 3 of patients taking clozapine were women, 76.9% (n = 10 were male. The mean age of patients treated with clozapine was 43.0 ± 11.2. The level of depression of patients treated with clozapine was 15.4% (n = 2. No statistically significant difference was found between patients between treated with clozapine and other antipsychotics regarding age, sex, marital status, education years, work history, age at onset of disease, depression and history of suicide attemptConclusion: As a result of this study it is found that clozapine did not effect on the level of depression in patients with schizophrenia, and depression level of patients with schizophrenia treated with clozapine had no difference from  patients treated  with other antipsychotics.

  17. Safety and performance of the second generation EnligHTN™ Renal Denervation System in patients with drug-resistant, uncontrolled hypertension.

    Science.gov (United States)

    Worthley, Stephen G; Wilkins, Gerard T; Webster, Mark W; Montarello, Joseph K; Delacroix, Sinny; Whitbourn, Robert J; Warren, Roderic J

    2017-07-01

    Catheter-based renal denervation for the treatment of drug-resistant hypertension has been intensively investigated in recent years. To date, only limited data have been published using multi-electrode radiofrequency ablation systems that can deliver lesions with a pre-determined pattern. This study was designed to evaluate the safety and performance of the second generation EnligHTN™ Renal Denervation System. This first-in-human, prospective, multi-center, non-randomized study included 39 patients (62% male, mean age 63 years, and mean baseline office blood pressure 174/93 mmHg) with drug-resistant hypertension. The primary safety and performance objectives were to characterize, from baseline to 6 months post procedure, the rate of serious procedural and device related adverse events, as adjudicated by an independent Clinical Events Committee, and the reduction of office systolic blood pressure. Renal artery denervation, using the second generation EnligHTN multi-electrode system significantly reduced office blood pressure from baseline to 1, 3, 6, 12, 18 and 24 months by 19/7, 26/9, 25/7, 23/7, 25/8 and 27/9 mmHg, respectively (p ≤ 0.0005). No serious device or procedure related adverse events affecting the renal arteries or renal function occurred through 24 months of follow-up. Renal sympathetic denervation using the second generation EnligHTN Renal Denervation System resulted in safe, rapid, and significant mean office blood pressure reduction that was sustained through 24 months. Future studies will need to address the utility of this system against an appropriate sham based comparator. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

  18. Antipsychotic dose equivalents and dose-years: a standardized method for comparing exposure to different drugs.

    Science.gov (United States)

    Andreasen, Nancy C; Pressler, Marcus; Nopoulos, Peg; Miller, Del; Ho, Beng-Choon

    2010-02-01

    A standardized quantitative method for comparing dosages of different drugs is a useful tool for designing clinical trials and for examining the effects of long-term medication side effects such as tardive dyskinesia. Such a method requires establishing dose equivalents. An expert consensus group has published charts of equivalent doses for various antipsychotic medications for first- and second-generation medications. These charts were used in this study. Regression was used to compare each drug in the experts' charts to chlorpromazine and haloperidol and to create formulas for each relationship. The formulas were solved for chlorpromazine 100 mg and haloperidol 2 mg to derive new chlorpromazine and haloperidol equivalents. The formulas were incorporated into our definition of dose-years such that 100 mg/day of chlorpromazine equivalent or 2 mg/day of haloperidol equivalent taken for 1 year is equal to one dose-year. All comparisons to chlorpromazine and haloperidol were highly linear with R(2) values greater than .9. A power transformation further improved linearity. By deriving a unique formula that converts doses to chlorpromazine or haloperidol equivalents, we can compare otherwise dissimilar drugs. These equivalents can be multiplied by the time an individual has been on a given dose to derive a cumulative value measured in dose-years in the form of (chlorpromazine equivalent in mg) x (time on dose measured in years). After each dose has been converted to dose-years, the results can be summed to provide a cumulative quantitative measure of lifetime exposure. Copyright 2010 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

  19. Geographical Variation in Antipsychotic Drug Use in Elderly Patients with Dementia

    DEFF Research Database (Denmark)

    Zakarias, Johanne Købstrup; Jensen-Dahm, Christina; Nørgaard, Ane

    2016-01-01

    BACKGROUND: Use of antipsychotics in elderly patients with dementia has decreased in the past decade due to safety regulations; however use is still high. Geographical variation may indicate discrepancies in clinical practice and lack of adherence to evidence-based guidelines for the management...... of behavioral symptoms. OBJECTIVE: To investigate potential geographical variances in use of antipsychotic drugs in dementia care. METHODS: A registry-based cross-sectional study in the entire elderly population of Denmark (≥65 years) conducted in 2012. Data included place of residence, prescriptions filled......, and hospital discharge diagnoses. Antipsychotic drug use among elderly with (n = 34,536) and without (n = 931,203) a dementia diagnosis was compared across the five regions and 98 municipalities in Denmark, adjusted for age and sex. RESULTS: In 2012, the national prevalence of antipsychotic drug use was 20...

  20. Second generation registry framework.

    Science.gov (United States)

    Bellgard, Matthew I; Render, Lee; Radochonski, Maciej; Hunter, Adam

    2014-01-01

    Information management systems are essential to capture data be it for public health and human disease, sustainable agriculture, or plant and animal biosecurity. In public health, the term patient registry is often used to describe information management systems that are used to record and track phenotypic data of patients. Appropriate design, implementation and deployment of patient registries enables rapid decision making and ongoing data mining ultimately leading to improved patient outcomes. A major bottleneck encountered is the static nature of these registries. That is, software developers are required to work with stakeholders to determine requirements, design the system, implement the required data fields and functionality for each patient registry. Additionally, software developer time is required for ongoing maintenance and customisation. It is desirable to deploy a sophisticated registry framework that can allow scientists and registry curators possessing standard computing skills to dynamically construct a complete patient registry from scratch and customise it for their specific needs with little or no need to engage a software developer at any stage. This paper introduces our second generation open source registry framework which builds on our previous rare disease registry framework (RDRF). This second generation RDRF is a new approach as it empowers registry administrators to construct one or more patient registries without software developer effort. New data elements for a diverse range of phenotypic and genotypic measurements can be defined at any time. Defined data elements can then be utilised in any of the created registries. Fine grained, multi-level user and workgroup access can be applied to each data element to ensure appropriate access and data privacy. We introduce the concept of derived data elements to assist the data element standards communities on how they might be best categorised. We introduce the second generation RDRF that

  1. Molecular Mechanisms of Antipsychotic Drug-Induced Diabetes

    Directory of Open Access Journals (Sweden)

    Jiezhong Chen

    2017-11-01

    Full Text Available Antipsychotic drugs (APDs are widely prescribed to control various mental disorders. As mental disorders are chronic diseases, these drugs are often used over a life-time. However, APDs can cause serious glucometabolic side-effects including type 2 diabetes and hyperglycaemic emergency, leading to medication non-compliance. At present, there is no effective approach to overcome these side-effects. Understanding the mechanisms for APD-induced diabetes should be helpful in prevention and treatment of these side-effects of APDs and thus improve the clinical outcomes of APDs. In this review, the potential mechanisms for APD-induced diabetes are summarized so that novel approaches can be considered to relieve APD-induced diabetes. APD-induced diabetes could be mediated by multiple mechanisms: (1 APDs can inhibit the insulin signaling pathway in the target cells such as muscle cells, hepatocytes and adipocytes to cause insulin resistance; (2 APD-induced obesity can result in high levels of free fatty acids (FFA and inflammation, which can also cause insulin resistance. (3 APDs can cause direct damage to β-cells, leading to dysfunction and apoptosis of β-cells. A recent theory considers that both β-cell damage and insulin resistance are necessary factors for the development of diabetes. In high-fat diet-induced diabetes, the compensatory ability of β-cells is gradually damaged, while APDs cause direct β-cell damage, accounting for the severe form of APD-induced diabetes. Based on these mechanisms, effective prevention of APD-induced diabetes may need an integrated approach to combat various effects of APDs on multiple pathways.

  2. Cumulative dosages of antipsychotic drugs are associated with increased mortality rate in patients with Alzheimer's dementia

    DEFF Research Database (Denmark)

    Nielsen, R E; Lolk, A; Valentin, J B

    2016-01-01

    OBJECTIVE: We wished to investigate the effects of cumulative dosages of antipsychotic drug in Alzheimer's dementia, when controlling for known risk factors, including current antipsychotic exposure, on all-cause mortality. METHOD: We utilized a nationwide, population-based, retrospective cohort...... study design with mortality as outcome in individual patients diagnosed with Alzheimer's dementia. RESULTS: We included a total of 45 894 patients and followed them for 3 803 996 person-years in total, presenting 27 894 deaths in the study population. Cumulative antipsychotic exposure increased...... or equal to 730 DDDs: HR 1.06, 95% CI (0.95-1.18), P = 0.322, when controlling for proxy markers of severity, somatic and mental comorbid disorders. CONCLUSION: In this nationwide cohort study of 45 894 patients diagnosed with Alzheimer's dementia, we found that cumulative dosages of antipsychotic drugs...

  3. Use-Dependent Inhibition of Synaptic Transmission by the Secretion of Intravesicularly Accumulated Antipsychotic Drugs

    DEFF Research Database (Denmark)

    Tischbirek, Carsten H.; Wenzel, Eva M.; Zheng, Fang

    2012-01-01

    Tischbirek et al. find that weak-base antipsychotic drugs are accumulated in synaptic vesicles and are secreted upon exocytosis, leading to increased extracellular drug concentrations following neuronal activity. The secretion of the drugs in turn inhibits synaptic transmission in a use-dependent...

  4. Development of a Web-Based Clinical Decision Support System for Drug Prescription: Non-Interventional Naturalistic Description of the Antipsychotic Prescription Patterns in 4345 Outpatients and Future Applications.

    Science.gov (United States)

    Berrouiguet, Sofian; Barrigón, Maria Luisa; Brandt, Sara A; Ovejero-García, Santiago; Álvarez-García, Raquel; Carballo, Juan Jose; Lenca, Philippe; Courtet, Philippe; Baca-García, Enrique

    2016-01-01

    The emergence of electronic prescribing devices with clinical decision support systems (CDSS) is able to significantly improve management pharmacological treatments. We developed a web application available on smartphones in order to help clinicians monitor prescription and further propose CDSS. A web application (www.MEmind.net) was developed to assess patients and collect data regarding gender, age, diagnosis and treatment. We analyzed antipsychotic prescriptions in 4345 patients attended in five Psychiatric Community Mental Health Centers from June 2014 to October 2014. The web-application reported average daily dose prescribed for antipsychotics, prescribed daily dose (PDD), and the PDD to defined daily dose (DDD) ratio. The MEmind web-application reported that antipsychotics were used in 1116 patients out of the total sample, mostly in 486 (44%) patients with schizophrenia related disorders but also in other diagnoses. Second generation antipsychotics (quetiapine, aripiprazole and long-acting paliperidone) were preferably employed. Low doses were more frequently used than high doses. Long acting paliperidone and ziprasidone however, were the only two antipsychotics used at excessive dosing. Antipsychotic polypharmacy was used in 287 (26%) patients with classic depot drugs, clotiapine, amisulpride and clozapine. In this study we describe the first step of the development of a web application that is able to make polypharmacy, high dose usage and off label usage of antipsychotics visible to clinicians. Current development of the MEmind web application may help to improve prescription security via momentary feedback of prescription and clinical decision support system.

  5. Adverse drug reactions due to antipsychotics and sedative-hypnotics in the elderly

    Directory of Open Access Journals (Sweden)

    Natasha S Kate

    2015-01-01

    Full Text Available Psychotropic drugs are commonly used to manage mental and behavioral problems in geriatric patients. This is, however, accompanied by the risk of developing adverse drug reactions (ADRs, impacting the safety with which the drug can be used. In this article, we provide an overview of the factors associated with the ADRs due to psychotropic medication in the elderly, and the ADRs associated with the use of antipsychotics and sedative-hypnotics in the geriatric population. For this, literature searches were conducted through MEDLINE, PubMed, and Google Scholar using keyword terms: Geriatric, elderly, safety, adverse events, ADRs, antipsychotic, names of individual antipsychotics, benzodiazepine, sedative, hypnotic, zolpidem, zaleplon, zopiclone. Research data indicate that antipsychotics are associated with an increased risk of metabolic syndrome, thromboembolism, cerebrovascular and cardiac events, pneumonia, fractures, and increased mortality. Among antipsychotics, aripiprazole seems to have fewer ADRs while other antipsychotics (typical and atypicals have reports of troublesome side effect profiles. Sedative-hypnotics are associated with a risk of falls, fractures, cognitive impairment, and may increase the risk of developing dementia with long-term use. The risk of these complications is present with both benzodiazepines and medications such as zolpidem and zopiclone.

  6. Temporal and spatial transcriptional fingerprints by antipsychotic or propsychotic drugs in mouse brain.

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    Kensuke Sakuma

    Full Text Available Various types of antipsychotics have been developed for the treatment of schizophrenia since the accidental discovery of the antipsychotic activity of chlorpromazine. Although all clinically effective antipsychotic agents have common properties to interact with the dopamine D2 receptor (D2R activation, their precise mechanisms of action remain elusive. Antipsychotics are well known to induce transcriptional changes of immediate early genes (IEGs, raising the possibility that gene expressions play an essential role to improve psychiatric symptoms. Here, we report that while different classes of antipsychotics have complex pharmacological profiles against D2R, they share common transcriptome fingerprint (TFP profile of IEGs in the murine brain in vivo by quantitative real-time PCR (qPCR. Our data showed that various types of antipsychotics with a profound interaction of D2R including haloperidol (antagonist, olanzapine (antagonist, and aripiprazole (partial agonist all share common spatial TFPs closely homologous to those of D2R antagonist sulpiride, and elicited greater transcriptional responses in the striatum than in the nucleus accumbens. Meanwhile, D2R agonist quinpirole and propsychotic NMDA antagonists such as MK-801 and phencyclidine (PCP exhibited the contrasting TFP profiles. Clozapine and propsychotic drug methamphetamine (MAP displayed peculiar TFPs that reflect their unique pharmacological property. Our results suggest that transcriptional responses are conserved across various types of antipsychotics clinically effective in positive symptoms of schizophrenia and also show that temporal and spatial TFPs may reflect the pharmacological features of the drugs. Thus, we propose that a TFP approach is beneficial to evaluate novel drug candidates for antipsychotic development.

  7. Central nervous system effects of the second-generation antihistamines marketed in Japan--review of inter-drug differences using the proportional impairment ratio (PIR-.

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    Tatsuya Isomura

    Full Text Available BACKGROUND: Second-generation antihistamines (AHs have, in general, fewer sedative effects than the first-generation. However, important inter-drug differences remain in the degree of cognitive and/or psychomotor impairment. The extent to which a particular compound causes disruption can be conveniently compared, to all other AHs, using the Proportional Impairment Ratio (PIR. Although the PIR can differentiate the relative impairment caused by individual drugs, there is no indication of the reliability of the ratios obtained. OBJECTIVE: To calculate the PIRs -together with 95% confidence intervals (CIs, as an index of reliability- and compare AHs currently, or soon to be, available in Japan, with respect to their intrinsic capacity to cause impairment. METHODS: Results from studies of cetirizine, desloratadine, ebastine, fexofenadine, levocetirizine, loratadine, mequitazine, and olopatadine were included in the PIR calculations. All data utilised came from crossover studies in healthy volunteers which were randomised and placebo and positive-internal controlled. Existing databases from studies reporting the sedative effects of AHs on objective (speed, accuracy, memory and subjective (feeling psychometrics were augmented, via results from suitable studies published after the previous reviews. The null value for a PIR was one. RESULTS: A total of 45 studies were finally included for this review. Of the AHs assessed, fexofenadine, ebastine, and levocetirizine showed a PIR for objective tests of 0. However, only fexofenadine (PIR = 0.49 had an upper limit of the 95% CI of less than 1. Fexofenadine, levocetirizine, desloratadine, olopatadine, loratadine, and mequitazine all had a PIR for subjective ratings of 0, but the upper limits of the 95% CIs were all in excess of 1, although fexofenadine (PIR = 2.57 was the lowest. CONCLUSIONS: The results show that there are differences between second-generation AHs in the extent of sedation produced

  8. Mental disorder diagnoses among children and adolescents who use antipsychotic drugs.

    Science.gov (United States)

    Nesvåg, Ragnar; Hartz, Ingeborg; Bramness, Jørgen G; Hjellvik, Vidar; Handal, Marte; Skurtveit, Svetlana

    2016-09-01

    Antipsychotic drugs are used increasingly by children and adolescents and there is concern about off-label use. We aimed to study which substances, and for which mental disorder diagnoses, antipsychotic drugs were prescribed to 0-18-year-old boys and girls in Norway. Linked data from the national health registry for prescription drugs in 2010 and mental disorder diagnoses in 2008-2012 were used to study the prevalence of antipsychotic drug use, the type of antipsychotic drug substances used, mental disorder diagnoses in users and distribution of drugs per diagnostic category across gender. In total, 0.18% of Norwegian children and adolescents were prescribed antipsychotic drugs during 2010, of which there were more boys (0.23%) than girls (0.13%). Risperidone was the most frequently used substance among boys (57.4%) and girls (32.3%), followed by aripiprazole (19.4%) in boys and quetiapine (27.4%) in girls. The most common mental disorder diagnoses among male users were hyperkinetic (49.9%) and autism spectrum disorder (27.1%), while anxiety disorders (41.5%) and depressive illness (33.6%) were most common among female users. A schizophrenia-like psychosis diagnosis was given to 11.1% of the male and 18.2% of the female users. A hyperkinetic disorder was diagnosed among 56.9% and 52.4% of the male risperidone and aripiprazole users, respectively. Among female quetiapine users, 57.1% were diagnosed with anxiety disorders and 52.4% with depressive illness. These results demonstrate that children and adolescents who use antipsychotic drugs are predominantly diagnosed with non-psychotic mental disorders such as hyperkinetic disorder among boys and anxiety disorder or depressive illness among girls. Copyright © 2016 Elsevier B.V. and ECNP. All rights reserved.

  9. Effects of the Antipsychotic Drug, Haloperidol, on Reproduction in the Fathead Minnow

    Science.gov (United States)

    Haloperidol is a butyrophenone antipsychotic drug used for the treatment of human hyperactive and manic disorders, agitation, and schizophrenia. The drug is thought to act through antagonism of dopaminergic receptors. We have studied a variety of endocrine-disrupting chemicals wi...

  10. In-stent neoatherosclerosis and tissue characteristics of restenotic lesions following implantation of second generation drug-eluting stents in unrestricted coronary lesions: Optical frequency domain imaging study.

    Science.gov (United States)

    Sabbah, Mahmoud; Kadota, Kazushige; El-Eraky, Azza; Kamal, Hanan M; Abdellah, Ahmed-Tageldien; El Hawary, Ahmed

    2017-06-01

    Differences in stent platform, polymer coatings, and antirestenotic drugs among the current in use second-generation drug-eluting stents (G2-DESs) may induce significant variations in neointimal response and vascular healing, which may impact the prevalence of neoatherosclerosis (NA) and morphological appearance of the restenotic tissue. Utilizing Optical frequency domain imaging, two independent reviewers, retrospectively compared the prevalence of neoatherosclerosis (NA), and the morphological differences, and tissue characteristics of 50 G2-DESs in-stent restenosis (ISR) lesions (35 everolimus-eluting stent [22 cobalt-chromium (CoCr), 13 platinum-chromium (PtCr)], and 15 biolimus-eluting stent [BES]) implanted liberally in unrestricted coronary lesions. More than half of the stents were implanted in type C lesions, while 40% of the stents were implanted primarily in lesions with recanalized chronic total occlusion. NA, defined as a neointima formation with the presence of lipids or calcification, was observed in fewer than half (24/50) of all ISR lesions with no significant in-between group differences (41%, 69%, and 40% in CoCr, PtCr, and BES respectively, P = 0.22), nor were there any significant differences in the morphological appearance or tissue characteristics between all G2-DESs subtypes. Acknowledging some limitations, our results may suggest that the prevalence of NA and the morphological appearance of restenotic lesions might not differ when G2-DESs are implanted in unrestricted, rather complex, coronary lesions. © 2017, Wiley Periodicals, Inc.

  11. Prototypical antipsychotic drugs protect hippocampal neuronal cultures against cell death induced by growth medium deprivation

    Directory of Open Access Journals (Sweden)

    Williams Sylvain

    2006-03-01

    Full Text Available Abstract Background Several clinical studies suggested that antipsychotic-based medications could ameliorate cognitive functions impaired in certain schizophrenic patients. Accordingly, we investigated the effects of various dopaminergic receptor antagonists – including atypical antipsychotics that are prescribed for the treatment of schizophrenia – in a model of toxicity using cultured hippocampal neurons, the hippocampus being a region of particular relevance to cognition. Results Hippocampal cell death induced by deprivation of growth medium constituents was strongly blocked by drugs including antipsychotics (10-10-10-6 M that display nM affinities for D2 and/or D4 receptors (clozapine, haloperidol, (±-sulpiride, domperidone, clozapine, risperidone, chlorpromazine, (+-butaclamol and L-741,742. These effects were shared by some caspases inhibitors and were not accompanied by inhibition of reactive oxygen species. In contrast, (--raclopride and remoxipride, two drugs that preferentially bind D2 over D4 receptors were ineffective, as well as the selective D3 receptor antagonist U 99194. Interestingly, (--raclopride (10-6 M was able to block the neuroprotective effect of the atypical antipsychotic clozapine (10-6 M. Conclusion Taken together, these data suggest that D2-like receptors, particularly the D4 subtype, mediate the neuroprotective effects of antipsychotic drugs possibly through a ROS-independent, caspase-dependent mechanism.

  12. Assessment of anti-arrhythmic activity of antipsychotic drugs in an animal model

    DEFF Research Database (Denmark)

    Mow, Tomas; Frederiksen, Kristen; Thomsen, Morten B.

    2015-01-01

    limited experimental information exists about the effects of α1-adrenergic receptor activity of antipsychotic drugs in pro-arrhythmic models, we have decided to investigate this. In this study we show that four antipsychotic drugs all have high affinity for α1-adrenergic receptor (sertindole>risperidone>haloperidol......>olanzapine) and all block IKr (sertindole>haloperidol>risperidone>olanzapine). In canine Purkinje fibres, α1-adrenergic stimulation prolonged action potential duration; however, the stimulation does not cause afterdepolarizations, even in the presence of dofetilide-induced delayed repolarization. We showed...

  13. Antipsychotic drug prescription rates among Dutch nursing homes : the influence of patient characteristics and the dementia special care unit

    NARCIS (Netherlands)

    van der Putten, M. J. G.; Wetzels, R. B.; Bor, H.; Zuidema, S. U.; Koopmans, R. T. C. M.

    2014-01-01

    Objectives: To assess the differences in antipsychotic drug prescription rates in residents with dementia in dementia special care units (SCUs) of Dutch nursing homes, considering the differences in patient characteristics. Method: As part of the Waalbed-II study, the data on antipsychotic drug use

  14. Use of Antipsychotic Drugs in Individuals with Intellectual Disability (ID) in the Netherlands: Prevalence and Reasons for Prescription

    Science.gov (United States)

    de Kuijper, G.; Hoekstra, P.; Visser, F.; Scholte, F. A.; Penning, C.; Evenhuis, H.

    2010-01-01

    Background: We investigated antipsychotic drug prescription practice of Dutch ID physicians, studying prevalence of antipsychotic drug use, reasons for prescription and the relationship between these reasons and patient characteristics. Methods: A cross-sectional study of medical and pharmaceutical records in a population living in residential…

  15. Ultra-hydrophilic stent platforms promote early vascular healing and minimise late tissue response: a potential alternative to second-generation drug-eluting stents.

    Science.gov (United States)

    Kolandaivelu, Kumaran; Bailey, Lynn; Buzzi, Stefano; Zucker, Arik; Milleret, Vincent; Ziogas, Algirdas; Ehrbar, Martin; Khattab, Ahmed A; Stanley, James R L; Wong, Gee K; Zani, Brett; Markham, Peter M; Tzafriri, Abraham R; Bhatt, Deepak L; Edelman, Elazer R

    2017-04-20

    Simple surface modifications can enhance coronary stent performance. Ultra-hydrophilic surface (UHS) treatment of contemporary bare metal stents (BMS) was assessed in vivo to verify whether such stents can provide long-term efficacy comparable to second-generation drug-eluting stents (DES) while promoting healing comparably to BMS. UHS-treated BMS, untreated BMS and corresponding DES were tested for three commercial platforms. A thirty-day and a 90-day porcine coronary model were used to characterise late tissue response. Three-day porcine coronary and seven-day rabbit iliac models were used for early healing assessment. In porcine coronary arteries, hydrophilic treatment reduced intimal hyperplasia relative to the BMS and corresponding DES platforms (1.5-fold to threefold reduction in 30-day angiographic and histological stenosis; p<0.04). Endothelialisation was similar on UHS-treated BMS and untreated BMS, both in swine and rabbit models, and lower on DES. Elevation in thrombotic indices was infrequent (never observed with UHS, rare with BMS, most often with DES), but, when present, correlated with reduced endothelialisation (p<0.01). Ultra-hydrophilic surface treatment of contemporary stents conferred good healing while moderating neointimal and thrombotic responses. Such surfaces may offer safe alternatives to DES, particularly when rapid healing and short dual antiplatelet therapy (DAPT) are crucial.

  16. A comparison of cardiovascular risk factors for ten antipsychotic drugs in clinical practice

    Directory of Open Access Journals (Sweden)

    Bodén R

    2013-03-01

    Full Text Available Robert Bodén,1,2 Gunnar Edman,3,4 Johan Reutfors,2 Claes-Göran Östenson,3 Urban Ösby3,4 1Department of Neuroscience, Psychiatry, Uppsala University, Uppsala, Sweden; 2Department of Medicine Solna, Centre for Pharmacoepidemiology, Karolinska Institutet, Stockholm, Sweden; 3Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden; 4Department of Psychiatry, Tiohundra AB, Norrtälje, Sweden Abstract: It is well known that abdominal obesity, dyslipidemia, and insulin resistance are highly prevalent in patients receiving maintenance treatment with antipsychotics, but there is limited knowledge about the association between cardiovascular risk factors and treatment with antipsychotic drugs. In this naturalistic study we investigated a sample of 809 antipsychotic-treated patients from Swedish psychosis outpatient teams. Cardiovascular risk factors (eg, metabolic syndrome, homeostasis model assessment of insulin resistance, and low-density lipoprotein values were measured, and their associations to current antipsychotic pharmacotherapy were studied. Ten antipsychotic drugs were compared in a stepwise logistic regression model. For the patients, the presence of the components of metabolic syndrome ranged from 35% for hyperglycemia to 64% for elevated waist circumference. Hypertriglyceridemia was associated with clozapine (odds ratio [OR] = 1.81, 95% confidence interval [CI] 1.08–3.04, reduced high-density lipoprotein with both clozapine and olanzapine (OR = 1.73, 95% CI 1.01–2.97; and OR = 2.03, 95% CI 1.32–3.13, hypertension with perphenazine (OR = 2.00, 95% CI 1.21–3.59, and hyperglycemia inversely with ziprasidone (OR = 0.21, 95% CI 0.05–0.89 and positively with haloperidol (OR = 2.02, 95% CI 1.18–3.48. There were no significant relationships between any of the antipsychotic drugs and increased waist circumference, homeostasis model assessment of insulin resistance, or low-density lipoprotein levels. In

  17. Antipsychotic drugs may worsen metabolic control in type 2 diabetes mellitus

    NARCIS (Netherlands)

    Spoelstra, JA; Stolk, RP; Cohen, D; Klungel, OH; Erkens, JA; Leufkens, HGM; Grobbee, DE

    (B)ackground: Several studies have indicated that type 2 diabetes mellitus is more common among schizophrenic patients than in the general population. In this study, we investigated whether the use of antipsychotic drugs in patients with diabetes leads to worsening of glycemic control. Method: In

  18. Central D2-dopamine receptor occupancy in schizophrenic patients treated with antipsychotic drugs

    International Nuclear Information System (INIS)

    Farde, L.; Wiesel, F.A.; Halldin, C.; Sedvall, G.

    1988-01-01

    Using positron emission tomography and the carbon 11-labeled ligand raclopride, central D2-dopamine receptor occupancy in the putamen was determined in psychiatric patients treated with clinical doses of psychoactive drugs. Receptor occupancy in drug-treated patients was defined as the percent reduction of specific carbon 11-raclopride binding in relation to the expected binding in the absence of drug treatment. Clinical treatment of schizophrenic patients with 11 chemically distinct antipsychotic drugs (including both classic and atypical neuroleptics such as clozapine) resulted in a 65% to 85% occupancy of D2-dopamine receptors. In a depressed patient treated with the tricyclic antidepressant nortriptyline, no occupancy was found. The time course for receptor occupancy and drug levels was followed after withdrawal of sulpiride or haloperidol. D2-dopamine receptor occupancy remained above 65% for many hours despite a substantial reduction of serum drug concentrations. In a sulpiride-treated patient, the dosage was reduced in four steps over a nine-week period and a curvilinear relationship was demonstrated between central D2-dopamine receptor occupancy and serum drug concentrations. The results demonstrate that clinical doses of all the currently used classes of antipsychotic drugs cause a substantial blockade of central D2-dopamine receptors in humans. This effect appears to be selective for the antipsychotics, since it was not induced by the antidepressant nortriptyline

  19. Occupancy of dopamine D-2 receptors by antipsychotic drugs is related to nicotine addiction in young patients with schizophrenia

    NARCIS (Netherlands)

    de Haan, Lieuwe; Booij, Jan; Lavalaye, Jules; van Amelsvoort, Therese; Linszen, Don

    2006-01-01

    Rationale: Occupancy of dopamine D-2 receptors by antipsychotic drugs depends on the individual availability of D-2 receptors and on the dose and type of antipsychotic medication. It has been suggested that a low availability of these receptors may increase the risk for addictive behavior.

  20. Cerebrovascular accidents in elderly people treated with antipsychotic drugs: a systematic review.

    Science.gov (United States)

    Sacchetti, Emilio; Turrina, Cesare; Valsecchi, Paolo

    2010-04-01

    After 2002, an association between stroke and antipsychotic use was reported in clinical trials and large database studies. This review considers previous quantitative reviews, newly published clinical trials, and recent observational cohort and case-control studies, and focuses on the clinical significance of the risk for stroke, the difference between typical and atypical antipsychotics, the possible at-risk patient profile and the timing of stroke after exposure. A search of MEDLINE covering the period from 1966 to June 2009 was carried out using selected keywords. Inclusion criteria were (i) quantitative reviews on stroke and antipsychotics; (ii) double-blind, placebo-controlled clinical trials involving patients with dementia treated with antipsychotics; and (iii) observational database cohort studies and observational case-control studies investigating the association between stroke and antipsychotics. Clinical trials were excluded if they were single-blind or if patients were affected by dementia and/or other neurological illnesses. Four reviews with aggregate data, 2 meta-analyses, 13 randomized, double-blind, controlled trials, 7 observational cohort studies and 4 observational case-control studies were selected and analysed. The incidence of cerebrovascular accidents (CVAs) was found to be very low in aggregate reviews and meta-analyses (2-4%). When the number collected was sufficiently high, or different drug treatments were grouped together, the higher rate in subjects exposed to antipsychotics was statistically significant. Inspection of other randomized controlled clinical trials, not included in aggregate reviews and meta-analyses, reported similar rates of CVAs. The majority of observational cohort studies compared typical and atypical antipsychotics and no significant class differences were found. A comparison with non-users was carried out in some cohort studies. In case-control studies, the probability of CVAs in users compared with non-users was

  1. Opposite Effects of Stimulant and Antipsychotic Drugs on Striatal Fast-Spiking Interneurons

    OpenAIRE

    Wiltschko, Alexander B; Pettibone, Jeffrey R; Berke, Joshua D

    2010-01-01

    Psychomotor stimulants and typical antipsychotic drugs have powerful but opposite effects on mood and behavior, largely through alterations in striatal dopamine signaling. Exactly how these drug actions lead to behavioral change is not well understood, as previous electrophysiological studies have found highly heterogeneous changes in striatal neuron firing. In this study, we examined whether part of this heterogeneity reflects the mixture of distinct cell types present in the striatum, by di...

  2. Web Tools: The Second Generation

    Science.gov (United States)

    Pascopella, Angela

    2008-01-01

    Web 2.0 tools and technologies, or second generation tools, help districts to save time and money, and eliminate the need to transfer or move files back and forth across computers. Many Web 2.0 tools help students think critically and solve problems, which falls under the 21st-century skills. The second-generation tools are growing in popularity…

  3. Percutaneous coronary intervention with second-generation drug-eluting stent versus bare-metal stent: Systematic review and cost-benefit analysis.

    Science.gov (United States)

    Poder, Thomas G; Erraji, Jihane; Coulibaly, Lucien P; Koffi, Kouamé

    2017-01-01

    Drug-eluting stents (DESs) were considered as ground-breaking technology promising to eradicate restenosis and the necessity to perform multiple revascularization procedures subsequent to percutaneous coronary intervention. Soon after DESs were released on the market, however, there were reports of a potential increase in mortality and of early or late thrombosis. In addition, DESs are far more expensive than bare-metal stents (BMSs), which has led to their limited use in many countries. The technology has improved over the last few years with the second generation of DESs (DES-2). Moreover, costs have come down and an improved safety profile with decreased thrombosis has been reported. Perform a cost-benefit analysis of DES-2s versus BMSs in the context of a publicly funded university hospital in Quebec, Canada. A systematic review of meta-analyses was conducted between 2012 and 2016 to extract data on clinical effectiveness. The clinical outcome of interest for the cost-benefit analysis was target-vessel revascularization (TVR). Cost units are those used in the Quebec health-care system. The cost-benefit analysis was based on a 2-year perspective. Deterministic and stochastic models (discrete-event simulation) were used, and various risk factors of reintervention were considered. DES-2s are much more effective than BMSs with respect to TVR rate ratio (i.e., 0.29 to 0.62 in more recent meta-analyses). DES-2s seem to cause fewer deaths and in-stent thrombosis than BMSs, but results are rarely significant, with the exception of the cobalt-chromium everolimus DES. The rate ratio of myocardial infraction is systematically in favor of DES-2s and very often significant. Despite the higher cost of DES-2s, fewer reinterventions can lead to huge savings (i.e., -$479 to -$769 per patient). Moreover, the higher a patient's risk of reintervention, the higher the savings associated with the use of DES-2s. Despite the higher purchase cost of DES-2s compared to BMSs

  4. First-generation versus second-generation drug-eluting stents in current clinical practice: updated evidence from a comprehensive meta-analysis of randomised clinical trials comprising 31 379 patients

    NARCIS (Netherlands)

    Navarese, E.P.; Kowalewski, M.; Kandzari, D.; Lansky, A.; Gorny, B.; Koltowski, L.; Waksman, R.; Berti, S.; Musumeci, G.; Limbruno, U.; Schaaf, R.J. van der; Kelm, M.; Kubica, J.; Suryapranata, H.

    2014-01-01

    BACKGROUND: First-generation drug-eluting stents (DES) have become the most widely used devices worldwide for management of coronary artery disease. As remote follow-up data were becoming available, concerns emerged in regard to their long-term safety. Second-generation DES were designed to overcome

  5. Continuous, but not intermittent, antipsychotic drug delivery intensifies the pursuit of reward cues.

    Science.gov (United States)

    Bédard, Anne-Marie; Maheux, Jérôme; Lévesque, Daniel; Samaha, Anne-Noël

    2011-05-01

    Chronic exposure to antipsychotic medications can persistently change brain dopamine systems. Most studies on the functional significance of these neural changes have focused on motor behavior and few have addressed how long-term antipsychotic treatment might influence dopamine-mediated reward function. We asked, therefore, whether a clinically relevant antipsychotic treatment regimen would alter the incentive motivational properties of a reward cue. We assessed the ability of a Pavlovian-conditioned stimulus to function as a conditioned reward, as well as to elicit approach behavior in rats treated with haloperidol, either continuously (achieved via subcutaneous osmotic minipump) or intermittently (achieved via daily subcutaneous injections). Continuous, but not intermittent, treatment enhanced the ability of amphetamine to potentiate the conditioned reinforcing effects of a cue associated with water. This effect was not related to differences in the ability to attribute predictive value to a conditioned stimulus (as measured by conditioned approach behavior), but was potentially linked to the development of behavioral supersensitivity to amphetamine and to augmented amphetamine-induced immediate early-gene expression (c-fos and Nur77) in dorsal striatopallidal and striatonigral cells. By enhancing the ability of reward cues to control behavior and by intensifying dopamine-mediated striatopallidal and striatonigral cell activity, standard (ie, continuous) antipsychotic treatment regimens might exacerbate drug-seeking and drug-taking behavior in schizophrenia. Achieving regular but transiently high antipsychotic levels in the brain (as modeled in the intermittent condition) might be a viable option to prevent these changes. This possibility should be explored in the clinic.

  6. Diabetic ketoacidosis associated with atypical antipsychotic drug, clozapine treatment: Report of a case and review of literature

    OpenAIRE

    Pillai L; Husainy SMK; Ramchandani K

    2006-01-01

    Atypical antipsychotic drugs are associated with metabolic disturbances like weight gain, type 2 diabetes hyperglycaemia and dyslipedemia, which can result in serious health risk in patients. Diabetic ketoacidosis resulting in serious metabolic acidosis, occurring in a schizophrenic patient on treatment with clozapine is being reported to draw attention this association. Frequent monitoring of the blood sugar and lipids is advised before and during therapy with atypical antipsychotic drugs.

  7. Successful treatment of a prolactinoma with the antipsychotic drug aripiprazole

    Directory of Open Access Journals (Sweden)

    Ilse C A Bakker

    2016-06-01

    Full Text Available In this report, we describe a female patient with both prolactinoma and psychotic disorder who was successfully treated with aripiprazole, a partial dopamine 2 receptor agonist. During the follow-up of more than 10 years, her psychotic symptoms improved considerably, prolactin levels normalised and the size of the prolactinoma decreased. This observation may be of clinical relevance in similar patients who often are difficult to treat with the regular dopaminergic drugs.

  8. Antipsychotic medications and stroke in schizophrenia: A case-crossover study.

    Directory of Open Access Journals (Sweden)

    Wen-Yin Chen

    Full Text Available The association between antipsychotic use and the risk of stroke in schizophrenic patients is controversial. We sought to study the association in a nationwide cohort with schizophrenia.Using a retrospective cohort of patients with schizophrenia (N = 31,976 derived from the Taiwan National Health Insurance Research Database, 802 new-onset cases of stroke were identified within 10 years of follow-up (from 2000 through 2010. We designed a case-crossover study using 14-day windows to explore the risk factors of stroke and the association between antipsychotic drugs and the risk of stroke. We analyzed the risks of individual antipsychotics on various subgroups of stroke including ischemic, hemorrhagic, and other strokes, and the risks based on the antipsychotic receptor-binding profile of each drug.Use of any second-generation antipsychotic was associated with an increased risk of stroke (adjusted risk ratio = 1.45, P = .009 within 14 days while the use of any first-generation antipsychotic was not. Intriguingly, the use of any second-generation antipsychotic was associated with ischemic stroke but not hemorrhagic stroke. The antipsychotic receptor-binding profile analysis showed that the antihistamine 1 receptor was significantly associated with ischemic stroke (adjusted risk ratio = 1.72, P = .037, and the sensitivity analysis based on the 7-day window of exposure validated the association (adjusted risk ratio = 1.87, P = .015.Use of second-generation antipsychotic drugs appeared to be associated with an increased risk of ischemic stroke in the patients studied, possibly mediated by high affinity for histamine-1 receptor blockade. Further research regarding the underlying biological mechanism and drug safety is suggested.

  9. Prescribing pattern of antipsychotic drugs in the outpatient department of psychiatry in Silchar Medical College and Hospital, Assam

    Directory of Open Access Journals (Sweden)

    Pinaki Chakravarty

    2016-01-01

    Full Text Available Objective: To study the prescribing pattern of antipsychotic drugs in the outpatient department of psychiatry in Silchar Medical College and Hospital (SMCH of Assam. Methods: It is a prospective cross-sectional study which was carried out for three months from August to November 2015 in the outpatient department of psychiatry. All patients irrespective of their ages and sexes were included in this study. Inpatients, referred patients, patients not willing to give consent, patients of epilepsy as well as those cases where diagnoses were not certain were excluded from the study. The prescription patterns of antipsychotic drugs and the occurrences of various psychiatric diseases on both the sexes were studied after taking permission from the Institutional Ethical Committee (SMCH. Results: A total of 112 prescriptions were analysed. The most common disease was found to be schizophrenia. Total drugs prescribed were 265 and average number of drugs per prescription was 2.36. It was seen that out of the 112 prescriptions, monotherapy was practiced in 19.64% (22 compared to polytherapy in 80.35% (90. Out of 265 prescribed drugs atypical antipsychotics were 112 (42.26%, typical antipsychotics 12 (4.52%, antiepileptics 57 (21.50%, antidepressants 29 (10.94%, antiparkinsonian 29 (10.94%, and others 26 (9.81%. Antipsychotics given orally were 122 of which olanzapine was 54 (44.26%, risperidone 40 (32.78%, chlorpromazine ten (8.19%, quetiapine eight (6.55%, aripiprazole five (4.09%, amisulpiride five (4.09% were seen. Injectable antipsychotics were two, of which only haloperidol two (100%. Antipsychotics in combination prescription with same groups were 14 (12.5%, with antidepressants, antipileptics, antiparkinsonian were 88 (78.57% and other agents were ten (8.92%, which included pantoprazole, multivitamins, and benfotiamine. Conclusion: This study shows that atypical antipsychotics are the most common drugs prescribed in patients with psychotic illness and

  10. Drug information update. Atypical antipsychotics and neuroleptic malignant syndrome: nuances and pragmatics of the association.

    Science.gov (United States)

    Sarkar, Siddharth; Gupta, Nitin

    2017-08-01

    Neuroleptic malignant syndrome (NMS) is a rare but potentially fatal adverse event associated with the use of antipsychotics. Although atypical antipsychotics were initially considered to carry no risk of NMS, reports have accumulated over time implicating them in NMS causation. Almost all atypical antipsychotics have been reported to be associated with NMS. The clinical profile of NMS caused by certain atypical antipsychotics such as clozapine has been reported to be considerably different from the NMS produced by typical antipsychotics, with diaphoresis encountered more commonly, and rigidity and tremor encountered less frequently. This article briefly discusses the evidence relating to the occurrence, presentation and management of NMS induced by atypical antipsychotics.

  11. Self-reported motivation to smoke in schizophrenia is related to antipsychotic drug treatment.

    Science.gov (United States)

    Barr, Alasdair M; Procyshyn, Ric M; Hui, Philip; Johnson, Joy L; Honer, William G

    2008-03-01

    The prevalence of smoking in schizophrenia has reliably been reported as being higher than for any other psychiatric disorder. While a number of theories have been proposed to account for such high rates of smoking, little is known about the subjective motivation for why schizophrenia patients smoke in comparison with those without the disease. The aim of the present study was to evaluate and compare smoking motivation in control subjects and schizophrenia patients, and determine if factors such as type of medication or access to cigarettes could contribute to self-reported motivation for smoking. We assessed motivation to smoke in 61 schizophrenia inpatients and 33 non-psychiatric health worker controls at a tertiary care psychiatric facility in a cross-sectional study. Nicotine dependency and smoking behavior were evaluated using the Fagerstrom Test for Nicotine Dependence and a validated questionnaire that assesses motivation for smoking along seven different dimensions. Schizophrenia patients reported a stronger motivation to smoke than controls for reasons related to pleasure from the act of smoking, as well as a need for psychomotor stimulation. Scores on both these factors were significantly associated with daily antipsychotic drug dose. The sedative and anxiolytic effects of smoking were related to anticholinergic load of psychiatric medications. The findings highlight important differences in self-reported motivation to smoke between schizophrenia patients and normals. Antipsychotic drugs may also influence aspects of motivation to smoke.

  12. Direct and Indirect Drug Design Approaches for the Development of Novel Tricyclic Antipsychotics: Potential 5-HT2A Antagonist

    Directory of Open Access Journals (Sweden)

    Mahantesh Namdev Jadhav

    2013-01-01

    Full Text Available Schizophrenia is a mental disorder manifested largely by disintegration of thought processes and emotional responsiveness. Given the therapeutic and toxic limitations of clinically available drugs, it is clear that there is still a need for the development of new generation antipsychotic agents with an improved clinical profile. Development of novel hybrid atypical tricyclic antipsychotic pharmacophore was achieved using direct (by measuring docking score of designed molecules on modelled 5- receptor and indirect (current, clinically available therapeutic agents’ data drug design approaches.

  13. Successful treatment of dopamine dysregulation syndrome with dopamine D2 partial agonist antipsychotic drug

    Directory of Open Access Journals (Sweden)

    Mizushima Jin

    2012-07-01

    Full Text Available Abstract Dopamine dysregulation syndrome (DDS consists of a series of complications such as compulsive use of dopaminergic medications, aggressive or hypomanic behaviors during excessive use, and withdrawal states characterized by dysphoria and anxiety, caused by long-term dopaminergic treatment in patients with Parkinson’s disease (PD. Although several ways to manage DDS have been suggested, there has been no established treatment that can manage DDS without deterioration of motor symptoms. In this article, we present a case of PD in whom the administration of the dopamine D2 partial agonistic antipsychotic drug aripiprazole improved DDS symptoms such as craving and compulsive behavior without worsening of motor symptoms. Considering the profile of this drug as a partial agonist at D2 receptors, it is possible that it exerts its therapeutic effect on DDS by modulating the dysfunctional dopamine system.

  14. A Survey of the Tardive Dyskinesia Induced by Antipsychotic Drugs in Patients with Schizophrenia

    Directory of Open Access Journals (Sweden)

    Naser tabibi

    2010-11-01

    Full Text Available "nObjective: Tardive Dyskinesia (TD, is one of the important problems of the patients with schizophrenia. The emergence of these side effects depends on so many factors such as the patients' age and the duration of antipsychotic treatment. By discovering new drugs (Atypical, there has been an outstanding decrease in the emergence of these side effects. The present study investigates the symptoms of TD in the Patients with schizophrenia who were under  treatments for more than 6 months. "nMethod: The sample of this study was 200 Patients with schizophrenia of four wards in Razi hospital (two acute and two chronic wards who were hospitalized in the winter of 2006 and were qualified for this study. The subjects were 101 males and 99 females who were younger than 60 and had received antipsychotic drugs for at least 6 months. After psychiatric interview and filling the demographic questionnaire by the patients, the required information about the drugs and the intensity of the symptoms was acquired. Then clinical and physical examinations of tardive dyskinesia were done. Next, the tardive dyskinesia disorders' check list (AIMS was used. Findings of this cross-sectional, descriptive study were analyzed by SPSS. "nResults: There was a high ratio of 95% between TD and the age factor (P=0.05. There was no relationship between symptoms frequency and duration of treatment (P=0.68. Facial muscles and oral zones were mostly involved in T.D disorder (72%. "nConclusion: No significant difference was observed between nine fold symptoms of T.D in patients who were using traditional drugs and those who were using the new ones (typical and atypical. Findings showed that in the intensity of the symptoms, gender does not play a major role.

  15. Antipsychotic treatments for the elderly: efficacy and safety of aripiprazole

    Directory of Open Access Journals (Sweden)

    Izchak Kohen

    2010-03-01

    Full Text Available Izchak Kohen1, Paula E Lester2, Sum Lam31Division of Geriatric Psychiatry, Zucker-Hillside Hospital, Glen Oaks, NY, USA; 2Division of Geriatric Medicine, Winthrop University Hospital, Mineola, NY, USA; 3Division of Pharmacy and Geriatrics, St. John’s University College of Pharmacy and Allied Health Professions, Queens, NY, USAAbstract: Delusions, hallucinations and other psychotic symptoms can accompany a number of conditions in late life. As such, elderly patients are commonly prescribed antipsychotic medications for the treatment of psychosis in both acute and chronic conditions. Those conditions include schizophrenia, bipolar disorder, depression and dementia. Elderly patients are at an increased risk of adverse events from antipsychotic medications because of age-related pharmacodynamic and pharmacokinetic changes as well as polypharmacy. Drug selection should be individualized to the patient’s previous history of antipsychotic use, current medical conditions, potential drug interactions, and potential side effects of the antipsychotic. Specifically, metabolic side effects should be closely monitored in this population. This paper provides a review of aripiprazole, a newer second generation antipsychotic agent, for its use in a variety of psychiatric disorders in the elderly including schizophrenia, bipolar disorder, dementia, Parkinson’s disease and depression. We will review the pharmacokinetics and pharmacodynamics of aripiprazole as well as dosing, diagnostic indications, efficacy studies, and tolerability including its metabolic profile. We will also detail patient focused perspectives including quality of life, patient satisfaction and adherence.Keywords: aripiprazole, antipsychotics, elderly, adverse drug reaction

  16. Second-generation HTS conductors

    CERN Document Server

    2010-01-01

    The discovery of high temperature superconductors (HTS) in 1986 by two IBM scientists led to an unprecedented explosion of research and development efforts world-wide because of the significant potential for practical applications offered by these materials. However, the early euphoria created by the exciting prospects was dampened by the daunting task of fabricating these materials into useful forms with acceptable superconducting properties. Progress towards this goal has been hindered by many intrinsic materials problems, such as weak-links, flux-creep, and poor mechanical properties. The above problems led to the development of the Second-Generation of HTS wires. Three methods were invented to produce flexible metallic substrates, which were also crystallographically biaxially textured, and resembled a long, mosaic single crystal. The first method invented is the Ion-Beam-Assisted-Deposition (IBAD). The second method developed was the Inclined-Substrate-Deposition (ISD). The third method invented is calle...

  17. Risk of stent thrombosis among bare-metal stents, first-generation drug-eluting stents, and second-generation drug-eluting stents: results from a registry of 18,334 patients.

    Science.gov (United States)

    Tada, Tomohisa; Byrne, Robert A; Simunovic, Iva; King, Lamin A; Cassese, Salvatore; Joner, Michael; Fusaro, Massimiliano; Schneider, Simon; Schulz, Stefanie; Ibrahim, Tareq; Ott, Ilka; Massberg, Steffen; Laugwitz, Karl-Ludwig; Kastrati, Adnan

    2013-12-01

    This study sought to compare the risk of stent thrombosis among patients treated with bare-metal stents (BMS), first-generation drug-eluting stents (G1-DES), and second-generation drug-eluting stents (G2-DES) for a period of 3 years. In patients undergoing coronary stenting, there is a scarcity of long-term follow-up data on cohorts large enough to compare rates of stent thrombosis across the stent generations. A total of 18,334 patients undergoing successful coronary stent implantation from 1998 to 2011 at 2 centers in Munich, Germany, were included in this study. Patients were stratified into 3 groups according to treatment with BMS, G1-DES, and G2-DES. The cumulative incidence of definite stent thrombosis at 3 years was 1.5% with BMS, 2.2% with G1-DES, and 1.0% with G2-DES. On multivariate analysis, G1-DES compared with BMS showed a significantly higher risk of stent thrombosis (odds ratio [OR]: 2.05; 95% confidence interval [CI]: 1.47 to 2.86; p stent thrombosis compared with BMS (OR: 0.82; 95% CI: 0.56 to 1.19; p = 0.30). Beyond 1 year, the risk of stent thrombosis was significantly increased with G1-DES compared with BMS (OR: 4.72; 95% CI: 2.01 to 11.1; p stenting, compared with BMS, there was a significant excess risk of stent thrombosis at 3 years with G1-DES, driven by an increased risk of stent thrombosis events beyond 1 year. G2-DES were associated with a similar risk of stent thrombosis compared with BMS. Copyright © 2013 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

  18. Neural basis for the ability of atypical antipsychotic drugs to improve cognition in schizophrenia

    Directory of Open Access Journals (Sweden)

    Tomiki eSumiyoshi

    2013-10-01

    Full Text Available Cognitive impairments are considered to largely affect functional outcome in patients with schizophrenia, other psychotic illnesses, or mood disorders. Specifically, there is much attention to the role of psychotropic compounds acting on serotonin (5-HT receptors in ameliorating cognitive deficits of schizophrenia.It is noteworthy that atypical antipsychotic drugs, e.g. clozapine, melperone, risperidone, olanzapine, quetiapine, aripiprazole, perospirone, blonanserin, and lurasidone, have variable affinities for these receptors. Among the 5-HT receptor subtypes, the 5-HT1A receptor is attracting particular interests as a potential target for enhancing cognition, based on preclinical and clinical evidence.The neural network underlying the ability of 5-HT1A agonists to treat cognitive impairments of schizophrenia likely includes dopamine, glutamate, and GABA neurons. A novel strategy for cognitive enhancement in psychosis may be benefitted by focusing on energy metabolism in the brain. In this context, lactate plays a major role, and has been shown to protect neurons against oxidative and other stressors. In particular, our data indicate chronic treatment with tandospirone, a partial 5-HT1A agonist, recover stress-induced lactate production in the prefrontal cortex of a rat model of schizophrenia. Recent advances of electrophysiological measures, e.g. event-related potentials, and their imaging have provided insights into facilitative effects on cognition of some atypical antipsychotic drugs acting directly or indirectly on 5-HT1A receptors.These findings are expected to promote the development of novel therapeutics for the improvement of functional outcome in people with schizophrenia.

  19. Association of metabolic syndrome with atypical antipsychotic drug (olanzapine) short term versus long term use

    International Nuclear Information System (INIS)

    Ikram, H.; Ahmed, T.M.; Hayat, A.; Ullah, Q.I.; Nawaz, A.

    2017-01-01

    Objective: To determine the association of metabolic syndrome with atypical antipsychotic drug (olanzapine) short term versus long term use. Study Design: Case control study. Place and Duration of Study: Chemical pathology department Army Medical College Rawalpindi, from Nov 2014 to Oct 2015. Material and Methods: The study was carried out on 240 subjects, 120 cases and 120 controls. For the purpose of the study cases were divided into four groups A, B, C and D according to the duration of drug use. Group A patients included those who the last the drug olanzapine for the last three months. Group B patients included those who were using the drug olanzapine for the last six months. Group C and D included those who were using the drug for last 1 year and more than one year (2-5 years) respectively. By employing non probability convenience sampling technique the data was collected from patients having the diagnosis of psychosis as per DSM IV modified criteria through a proforma and fasting blood samples were drawn. These samples were tested for fasting serum lipid profile and fasting plasma glucose. The data obtained were analyzed using SPSS version 21. For quantitative data Mean and SD were calculated. For qualitative data frequency and percentages were calculated. Qualitative data was compared using chi square test whereas quantitative data was compared using independent sample t-test. Results: There was statistically no significant difference in fasting plasma glucose between group A and B and their controls whereas in group C and D these levels were significantly high as compared to controls. Triglyceride levels were significantly higher and HDL cholesterol levels were significantly lower in all four groups as compared to controls. Comparison of qualitative data which included waist circumference and blood pressure showed statistically no significant rise for group A whereas waist circumference showed insignificant rise and blood pressure showed statistically

  20. Aripiprazole versus other atypical antipsychotics for schizophrenia

    Science.gov (United States)

    Komossa, Katja; Rummel-Kluge, Christine; Schmid, Franziska; Hunger, Heike; Schwarz, Sandra; El-Sayeh, Hany George G; Kissling, Werner; Leucht, Stefan

    2014-01-01

    Background In many countries of the industrialised world second generation (atypical) antipsychotics have become first line drug treatments for people with schizophrenia. The question as to whether, and if so how much, the effects of the various second generation antipsychotics differ is a matter of debate. In this review we examine how the efficacy and tolerability of aripiprazole differs from that of other second generation antipsychotics. Objectives To evaluate the effects of aripiprazole compared with other atypical antipsychotics for people with schizophrenia and schizophrenia-like psychoses. Search methods We searched the Cochrane Schizophrenia Group Trials Register (March 2007) which is based on regular searches of BIOSIS, CENTRAL, CINAHL, EMBASE, MEDLINE and PsycINFO. Selection criteria We included all randomised trials comparing oral aripiprazole with oral forms of amisulpride, clozapine, olanzapine, quetiapine, risperidone, sertindole, ziprasidone or zotepine in people with schizophrenia or schizophrenia-like psychoses. Data collection and analysis We extracted data independently. For dichotomous data we calculated relative risks (RR) and their 95% confidence intervals (CI) on an intention-to-treat basis based on a random-effects model. We calculated numbers needed to treat/harm (NNT/NNH) where appropriate. For continuous data, we calculated weighted mean differences (MD) again based on a random-effects model. Main results The review currently includes four trials with 1404 participants on two out of eight possible comparisons - aripiprazole versus olanzapine and aripiprazole versus risperidone. The overall number of participants leaving the studies early was considerable (38.5%), limiting the validity of the findings, but with no significant differences between groups. Aripiprazole was less efficacious than olanzapine in terms of the general mental state (PANSS total score: n=794, 2 RCTs, MD 4.96 CI 1.85 to 8.06), but it was associated with fewer side

  1. Spanish consensus on the risks and detection of antipsychotic drug-related hyperprolactinaemia.

    Science.gov (United States)

    Montejo, Ángel L; Arango, Celso; Bernardo, Miguel; Carrasco, José L; Crespo-Facorro, Benedicto; Cruz, Juan J; Del Pino, Javier; García Escudero, Miguel A; García Rizo, Clemente; González-Pinto, Ana; Hernández, Ana I; Martín Carrasco, Manuel; Mayoral Cleries, Fermin; Mayoral van Son, Jaqueline; Mories, M Teresa; Pachiarotti, Isabella; Ros, Salvador; Vieta, Eduard

    2016-01-01

    Iatrogenic hyperprolactinaemia (IHPRL) has been more frequently related to some antipsychotic drugs that provoke an intense blockade of dopamine D2 receptors. There is a wide variation in clinical practice, and perhaps some more awareness between clinicians is needed. Due to the high frequency of chronic treatment in severe mental patients, careful attention is recommended on the physical risk. IHPRL symptoms could be underestimated without routine examination. An intense scientific literature search was performed in order to draw up a multidisciplinary consensus, including different specialists of psychiatry, endocrinology, oncology and internal medicine, and looking for a consensus about clinical risk and detection of IHPRL following evidence-based medicine criteria levels (EBM I- IV). Short-term symptoms include amenorrhea, galactorrhoea, and sexual dysfunction with decrease of libido and erectile difficulties related to hypogonadism. Medium and long-term symptoms related to oestrogens are observed, including a decrease bone mass density, hypogonadism, early menopause, some types of cancer risk increase (breast and endometrial), cardiovascular risk increase, immune system disorders, lipids, and cognitive dysfunction. Prolactin level, gonadal hormones and vitamin D should be checked in all patients receiving antipsychotics at baseline although early symptoms (amenorrhea-galactorrhoea) may not be observed due to the risk of underestimating other delayed symptoms that may appear in the medium term. Routine examination of sexual dysfunction is recommended due to possible poor patient tolerance and low compliance. Special care is required in children and adolescents, as well as patients with PRL levels >50ng/ml (moderate hyperprolactinaemia). A possible prolactinoma should be investigated in patients with PRL levels >150ng/ml, with special attention to patients with breast/endometrial cancer history. Densitometry should be prescribed for males >50 years old

  2. Trends in the Outpatient Utilization of Antipsychotic Drugs in the City of Zagreb in the Ten-Year Period as a Tool to Assess Drug Prescribing Rationality.

    Science.gov (United States)

    Polić-Vižintin, Marina; Tripković, Ingrid; Štimac, Danijela; Šostar, Zvonimir; Orban, Mirjana

    2016-12-01

    The aim was to determine distribution and trends in the outpatient utilization of antipsychotics to evaluate the rationality of antipsychotic drug prescribing during the ten year period. The epidemiological method of descriptive and analytical observation was used. Data on drug utilization from Zagreb Municipal Pharmacy were used to calculate the number of defined daily doses (DDD) and DDD per 1000 inhabitants per day (DDD/TID) using the World Health Organization Anatomical-Therapeutic-Chemical methodology. The ratio of typical versus atypical antipsychotics served as an indicator on assessing the rationality of the utilization. Data on the use of anticholinergics in the treatment of neuroleptic side effects were also included. Outpatient utilization of antipsychotics showed a declining pattern from 14.17 in 2001 to 8.42 DDD/TID in 2010. The utilization of atypical antipsychotics increased by 60% (from 3.68 to 5.89 DDD/TID), while the utilization of typical antipsychotics decreased by 76% (from 10.49 to 2.53 DDD/TID). The drugs showing the largest increase were olanzapine (from 1.21 to 2.78 DDD/TID) and quetiapine (from 0 to 0.68 DDD/TID). The typical/atypical antipsychotic ratio changed from 1:0.4 in 2001 to 1:2.3 in 2010. A 2.3-fold decrease was recorded in the utilization of anticholinergics (from 2.05 to 0.91 DDD/TID). Total consumption of neuroleptics significantly decreased. A decrease was also recorded in the utilization of anticholinergics. Study results pointed to two favorable features, i.e. low use of typical antipsychotics and the ratio of typical and atypical antipsychotics. Implementation of the new clinical guidelines for nervous system disorders and updating of the list of reimbursable drugs with the addition of new ones contributed to the observed improvement in the prescribing patterns during the study period. Using the WHO ATC/DDD methodology and rationality indicators in the assessment of trends in the outpatient utilization of

  3. Antipsychotic interventions in prodromal psychosis: safety issues.

    Science.gov (United States)

    Liu, Chen-Chung; Demjaha, Arsime

    2013-03-01

    In recent years, psychopharmacological intervention in prodromal psychosis, also known as the ultra-high risk (UHR) mental state for psychosis, has attracted much attention. Whilst it has been shown that antipsychotic use in UHR individuals may be effective in potentially delaying or even averting progression to frank psychosis, their use in subjects that do not necessarily convert to psychosis has raised considerable ethical concerns because of their adverse effects. Recent treatment guidelines for patients at UHR for psychosis recommend the use of antipsychotics only in exceptional conditions and with great precautions. To date only a few studies have investigated the use of antipsychotic medications in UHR patients and the potential benefits and risks related to their use in prodromal psychosis remain unclear. We review here all published studies that included UHR patients treated with antipsychotics, regardless of study design. These studies were all of second-generation antipsychotics, given that first-generation antipsychotics cannot be recommended because of their adverse drug reactions. We specifically examine the available descriptions of adverse reactions of the individual antipsychotic medication in each study and discuss the potential effects of various demographic and clinical factors that may impact on safety issues of pharmacological interventions in UHR patients. Clinical trials to date investigating potential benefits of antipsychotic treatments in preventing transition to psychosis were of relatively short duration and have involved a small number of patients. Whilst it appears that pharmacological intervention at this stage may be effective in both reducing the psychopathology and decreasing transition rates, and is potentially safe, in the absence of sufficient evidence-based knowledge to guide treatment, definitive clinical recommendations and guidelines cannot be derived. Certain adverse events take time to develop, such as metabolic syndrome

  4. Trends in Antipsychotic Drug Use by Very Young, Privately Insured Children

    Science.gov (United States)

    Olfson, Mark; Crystal, Stephen; Huang, Cecilia; Gerhard, Tobias

    2010-01-01

    Objective: This study describes recent trends and patterns in antipsychotic treatment of privately insured children aged 2 through 5 years. Method: A trend analysis is presented of antipsychotic medication use (1999-2001 versus 2007) stratified by patient characteristics. Data are analyzed from a large administrative database of privately insured…

  5. A bibliometric analysis of scientific production on atypical antipsychotic drugs from Italy

    Science.gov (United States)

    López-Muñoz, Francisco; De Berardis, Domenico; Fornaro, Michele; Vellante, Federica; di Giannantonio, Massimo; Povedano-Montero, Francisco J; Póveda Fernández-Martín, Maria; Rubio, Gabriel; Álamo, Cecilio

    2017-01-01

    A bibliometric study of peer-reviewed scientific publications on atypical antipsychotic drugs (AADs) from Italy is herein presented. We selected the documents from Scopus database. We applied several bibliometric indicators of production and dispersion, including Price’s Law about the increase of scientific literature, and Bradford’s Law. We also calculated the participation index across different countries. The bibliometric data have also been correlated with some social and health data sourcing in Italy, such as total per capita expenditure on health and gross domestic expenditure. A total of 2949 original documents were published within the period 1972-2015. Our results state fulfilment of Price’s Law, with scientific production showing exponential growth (r=0.901, as against an r=0.838 after linear adjustment). The drugs most widely studied were clozapine (257 documents), risperidone (179), and olanzapine (172). Stratification into Bradford zones yielded a nucleus represented by the Journal of Clinical Psychopharmacology and Rivista di Psichiatria (58 articles, each one). A total of 1091 different journals were evaluated. The publications on AADs in Italy have undergone exponential growth over the studied period, which is in line with the progressively burgeoning on novel AAD releases. No evidence of saturation point was observed.

  6. SEXUAL DYSFUNCTION INDUCED BY ANTI-PSYCHOTICS AND ANTI-DEPRESSANTS IN DRUG NAIVE PATIENTS – A COMPARATIVE STUDY

    Directory of Open Access Journals (Sweden)

    M. Mohanalakshmi

    2017-03-01

    Full Text Available BACKGROUND The aim of this study was to determine and compare sexual dysfunction caused by anti-psychotics and anti-depressants in drug naïve patients. MATERIALS AND METHODS Patients diagnosed as drug naïve schizophrenic and depression as per DSM-5 criteria & age between 18-45 years were recruited and allocated into group A (n=30–receiving anti-psychotics & group B (n=30 receiving anti-depressants after informed consent by the patients. Sexual dysfunction was assessed by Arizona Sexual Experiences Scale (ASEX during the initial 2 months of therapy. RESULTS ASEX mean for patients receiving antipsychotics increased from the baseline of 7.97 to 17.23 and the ASEX mean for patients receiving antidepressants increased from baseline of 7.80 to 18.67 with p value of 0.249 which is not statistically significant. Among the antipsychotics haloperidol ASEX mean increased from 7.87 to 18.00 and risperidone mean increased from 8.07 to 16.47 with the p value of 0.335 which is not significant. More patients on haloperidol showed evidence of sexual dysfunction as assessed by ASEX scoring than risperidone though p value was not significant. Among the two antidepressants ASEX score mean for amitriptyline patients increased from 8.07 to 16.47, and that of fluoxetine from 7.53 to 16.47 with the p value of 0.018* statistically significant at α of 0.05 level. CONCLUSION This study shows presence of sexual dysfunction in patients receiving antipsychotics & antidepressants by 2 nd month of therapy though statistically not significant. Fluoxetine group patients developed statistically significant sexual dysfunction. Implications for future research about sexual dysfunction in all new treatments should be strongly taken into account because this side effect adds to the emotional stress and worsening of mental dysfunction.

  7. Relationship of symptomatology, gender, and antipsychotic drug treatment with plasma homovanillic acid in schizophrenia.

    Science.gov (United States)

    Zhang, Z J; Reynolds, G P; Ramchand, C; Peet, M; Shah, S

    2001-01-01

    To study the role of dopamine neurotransmission in schizophrenia and its drug treatment by assessing the relationship of plasma homovanillic acid (pHVA), a major central dopamine metabolite to various clinical parameters in schizophrenic patients. pHVA was measured by high-performance liquid chromatography with electrochemical detection in a large cohort of both medicated and unmedicated DSM-IV schizophrenic patients. Prior to the measurement of pHVA, the patients were rated on the schedule for the assessment of positive and negative symptoms (PANSS). (1) pHVA in 46 patients receiving antipsychotic drugs was decreased, and in 58 drug-free patients increased, (7.4+/-2.7) microg/L and (10+/-4) microg/L compared with a matched control group (9 microg/L+/-3 microg/L, n=62) (ANOVA F=8.57, df=2, P pHVA was higher in the patients with a more negative symptom profile. (2) No significant correlation of pHVA with overall SAPS or SANS scores was apparent in the drug-free patients, although within the SANS subscales, a significant relationships to anhedonia-asociality (r=0.32, P pHVA with negative symptoms (r=0.42, P < 0.05) while females showed no significant relationship with any PANSS subscales. The results suggest that an increased dopaminergic metabolism is apparent in (male) schizophrenic patients with predominantly negative symptoms, supporting reports that this change in neuronal activity may be related to the neuropathological abnormalities seen in the disease, which may differ between males and females. Such neuronal deficits of developmental origin may thus result in an elevation/disinhibition of central dopamine metabolism in schizophrenia.

  8. Simultaneous Determination of Antipsychotic Drugs and Their Active Metabolites by LC-MS-MS and its Application to Therapeutic Drug Monitoring.

    Science.gov (United States)

    Miroshnichenko, Igor I; Baymeeva, Natalia V

    2018-04-07

    A quantitative method was developed to support therapeutic drug monitoring of eight antipsychotic drugs: chlorpromazine, haloperidol, zuclopenthixol, clozapine, risperidone, quetiapine, aripiprazole or olanzapine and some active metabolites (dehydroaripiprazole, N-desmethylclozapine and 9-hydroxyrisperidone) in human serum. Separation of the compounds was achieved using a Zorbax SB-C18 (150 mm × 4.6 mm, 5 μm) column and mass-spectrometric detection in multiple reaction monitoring mode. Human blood samples were collected in vacutainer tubes and the analytes were extracted with methyl-tert-butyl ether. The lower limits of quantitation were equal 0.5-1 ng/mL for all analytes. The method was applied with success to serum samples from schizophrenic patients undergoing polypharmacy with two or more different antipsychotic drugs. Precision data, accuracy results were satisfactory, and no interference from other psychotropic drugs was found. Hence, the method is suitable for the TDM of the analytes in psychotic patients' serum.

  9. An epidemiological study of concomitant use of Chinese medicine and antipsychotics in schizophrenic patients: implication for herb-drug interaction.

    Directory of Open Access Journals (Sweden)

    Zhang-Jin Zhang

    Full Text Available BACKGROUND: Herb-drug interactions are an important issue in drug safety and clinical practice. The aim of this epidemiological study was to characterize associations of clinical outcomes with concomitant herbal and antipsychotic use in patients with schizophrenia. METHODS AND FINDINGS: In this retrospective, cross-sectional study, 1795 patients with schizophrenia who were randomly selected from 17 psychiatric hospitals in China were interviewed face-to-face using a structured questionnaire. Association analyses were conducted to examine correlates between Chinese medicine (CM use and demographic, clinical variables, antipsychotic medication mode, and clinical outcomes. The prevalence of concomitant CM and antipsychotic treatment was 36.4% [95% confidence interval (95% CI 34.2%-38.6%]. Patients using concomitant CM had a significantly greater chance of improved outcomes than non-CM use (61.1% vs. 34.3%, OR = 3.44, 95% CI 2.80-4.24. However, a small but significant number of patients treated concomitantly with CM had a greater risk of developing worse outcomes (7.2% vs. 4.4%, OR = 2.06, 95% CI 2.06-4.83. Significant predictors for concomitant CM treatment-associated outcomes were residence in urban areas, paranoid psychosis, and exceeding 3 months of CM use. Herbal medicine regimens containing Radix Bupleuri, Fructus Gardenia, Fructus Schisandrae, Radix Rehmanniae, Akebia Caulis, and Semen Plantaginis in concomitant use with quetiapine, clozapine, and olanzepine were associated with nearly 60% of the risk of adverse outcomes. CONCLUSIONS: Concomitant herbal and antipsychotic treatment could produce either beneficial or adverse clinical effects in schizophrenic population. Potential herb-drug pharmacokinetic interactions need to be further evaluated.

  10. Drug-induced activation of SREBP-controlled lipogenic gene expression in CNS-related cell lines: Marked differences between various antipsychotic drugs

    Directory of Open Access Journals (Sweden)

    Vik-Mo Audun O

    2006-10-01

    Full Text Available Abstract Background The etiology of schizophrenia is unknown, but neurodevelopmental disturbances, myelin- and oligodendrocyte abnormalities and synaptic dysfunction have been suggested as pathophysiological factors in this severe psychiatric disorder. Cholesterol is an essential component of myelin and has proved important for synapse formation. Recently, we demonstrated that the antipsychotic drugs clozapine and haloperidol stimulate lipogenic gene expression in cultured glioma cells through activation of the sterol regulatory element-binding protein (SREBP transcription factors. We here compare the action of chlorpromazine, haloperidol, clozapine, olanzapine, risperidone and ziprasidone on SREBP activation and SREBP-controlled gene expression (ACAT2, HMGCR, HMGCS1, FDPS, SC5DL, DHCR7, LDLR, FASN and SCD1 in four CNS-relevant human cell lines. Results There were marked differences in the ability of the antipsychotic drugs to activate the expression of SREBP target genes, with clozapine and chlorpromazine as the most potent stimulators in a context of therapeutically relevant concentrations. Glial-like cells (GaMg glioma and CCF-STTG1 astrocytoma cell lines displayed more pronounced drug-induced SREBP activation compared to the response in HCN2 human cortical neurons and SH-SY5Y neuroblastoma cells, indicating that antipsychotic-induced activation of lipogenesis is most prominent in glial cells. Conclusion Our present data show a marked variation in the ability of different antipsychotics to induce SREBP-controlled transcriptional activation of lipogenesis in cultured human CNS-relevant cells. We propose that this effect could be relevant for the therapeutic efficacy of some antipsychotic drugs.

  11. Comparison of the effectiveness of brand-name and generic antipsychotic drugs for treating patients with schizophrenia in Taiwan.

    Science.gov (United States)

    Hsu, Chih-Wei; Lee, Sheng-Yu; Wang, Liang-Jen

    2018-03-01

    The purpose of this nationwide population-based study is to compare the long-term effectiveness of brand-name antipsychotics with generic antipsychotics for treating schizophrenia. We identified patients with schizophrenia who were prescribed antipsychotics from a random sample of one million records from Taiwan's National Health Insurance database, observed between January 1, 2000 and December 31, 2012. Only those with no prior use of antipsychotics for at least 180days were included. We selected patients who were prescribed brand-name risperidone (N=404), generic risperidone (N=145), brand-name sulpiride (N=334), or generic sulpiride (N=991). The effectiveness of the treatments researched in this study consisted of average daily doses, rates of treatment discontinuation, augmentation therapy, and psychiatric hospitalization. We found that compared to patients treated with generic risperidone, those treated with brand-name risperidone required lower daily doses (2.14mg vs. 2.61mg). However, the two groups demonstrated similar rates of treatment discontinuation, augmentation, and psychiatric hospitalization. On the other hand, in comparison with patients prescribed generic sulpiride, those treated with brand-name sulpiride not only required lower daily doses (302.72mg vs. 340.71mg) but also had lower psychiatric admission rates (adjusted hazard ratio: 0.24, 95% confidence interval: 0.10-0.56). In conclusion, for both risperidone and sulpiride, higher daily doses of the respective generic drugs were prescribed than with brand-name drugs in clinical settings. Furthermore, the brand-name sulpiride is more effective at preventing patients from hospitalization than generic sulpiride. These findings can serve as an important reference for clinical practices and healthcare economics for treating schizophrenic patients. Copyright © 2017 Elsevier B.V. All rights reserved.

  12. Differential effects of antipsychotic and propsychotic drugs on prepulse inhibition and locomotor activity in Roman high- (RHA) and low-avoidance (RLA) rats

    DEFF Research Database (Denmark)

    Oliveras, Ignasi; Sánchez-González, Ana; Sampedro-Viana, Daniel

    2017-01-01

    acutely administered propsychotic (DOI, MK-801) and antipsychotic drugs (haloperidol, clozapine), as well as apomorphine, on prepulse inhibition (PPI) of startle and locomotor activity (activity cages). RESULTS: RHA-I rats display a consistent deficit of PPI compared with RLA-I rats. The typical...... antipsychotic haloperidol (dopamine D2 receptor antagonist) reversed the PPI deficit characteristic of RHA-I rats (in particular at 65 and 70 dB prepulse intensities) and reduced locomotion in both strains. The atypical antipsychotic clozapine (serotonin/dopamine receptor antagonist) did not affect PPI...

  13. Antipsychotics and amotivation.

    Science.gov (United States)

    Fervaha, Gagan; Takeuchi, Hiroyoshi; Lee, Jimmy; Foussias, George; Fletcher, Paul J; Agid, Ofer; Remington, Gary

    2015-05-01

    Antipsychotic drugs are thought to produce secondary negative symptoms, which can also exacerbate primary negative symptoms. In the present study, we examined whether motivational deficits in particular were related to antipsychotic treatment in patients with schizophrenia in a dose-dependent manner. Five hundred and twenty individuals with schizophrenia who were receiving antipsychotic monotherapy for at least 6 months and followed prospectively were included in the present study. Participants were receiving one of five antipsychotic medications (olanzapine, perphenazine, quetiapine, risperidone, or ziprasidone), and analyses were conducted for patients receiving each drug separately. Analysis of covariance models were constructed to examine the effect of antipsychotic dose on level of motivational impairment, controlling for selected demographic and clinical variables (eg, positive symptoms). Level of motivation, or deficits therein, were evaluated using a derived measure from the Quality of Life Scale, and in addition with scores derived from the Positive and Negative Syndrome Scale. Antipsychotic dose was not related to the level of amotivation for any of the medications examined. Moreover, severity of sedation was not significantly related to the degree of amotivation. One hundred and twenty-one individuals were identified as antipsychotic-free at baseline, and after 6 months of antipsychotic treatment, no change in motivation was found. Chronic treatment with antipsychotics does not necessarily impede or enhance goal-directed motivation in patients with schizophrenia. It is possible that the negative impact of antipsychotics in this regard is overstated; conversely, the present results also indicate that we must look beyond antipsychotics in our efforts to improve motivation.

  14. Sertindole versus other atypical antipsychotics for schizophrenia

    Science.gov (United States)

    Komossa, Katja; Rummel-Kluge, Christine; Hunger, Heike; Schwarz, Sandra; Schmid, Franziska; Lewis, Ruth; Kissling, Werner; Leucht, Stefan

    2014-01-01

    Background In many countries of the industrialised world second generation (atypical) antipsychotics have become the first line drug treatment for people with schizophrenia. The question as to whether and, if so, how much the effects of the various second generation antipsychotics differ is a matter of debate. Objectives To evaluate the effects of sertindole compared with other second generation antipsychotics for people with schizophrenia and schizophrenia-like psychosis. Search methods We searched the Cochrane Schizophrenia Group Trials Register (April 2007) and ClinicalTrials.gov (February 2009). Selection criteria We included all randomised trials comparing oral sertindole with oral forms of amisulpride, aripiprazole, clozapine, olanzapine, quetiapine, risperidone, ziprasidone or zotepine for people with schizophrenia or schizophrenia-like psychosis. Data collection and analysis We extracted data independently. For dichotomous data we calculated relative risks (RR) and their 95% confidence intervals (CI) on an intention-to-treat basis based on a random-effects model. For continuous data, we calculated weighted mean differences (WMD) again based on a random-effects model. Main results The review currently includes two short-term low-quality randomised trials (total n=508) both comparing sertindole with risperidone. One third of participants left the studies early (2 RCTs, n=504, RR 1.23 CI 0.94 to 1.60). There was no difference in efficacy (2 RCTs, n=493, WMD PANSS total change from baseline 1.98 CI −8.24 to 12.20). Compared with relatively high doses of risperidone (between 4 and 12 mg/day), sertindole produced significantly less akathisia and parkinsonism (1 RCT, n=321, RR 0.24 CI 0.09 to 0.69, NNT 14, CI 8 to 100). Sertindole produced more cardiac effects (2 RCTs, n=508, RR QTc prolongation 4.86 CI 1.94 to 12.18), weight change (2 RCTs, n=328, WMD 0.99 CI 0.12 to 1.86) and male sexual dysfunction (2 RCTs, n=437, RR 2.90 CI 1.32 to 6.35, NNH 13 CI 8 to 33

  15. Atypicality of Atypical Antipsychotics

    OpenAIRE

    Farah, Andrew

    2005-01-01

    Objective: To review the current definition of atypicality, discuss the unique features of each atypical antipsychotic, and determine whether the available drugs in this class really meet the classical definition of atypicality.

  16. Differential regulation of dopamine receptors after chronic typical and atypical antipsychotic drug treatment

    International Nuclear Information System (INIS)

    Creese, I.; Florijn, W.J.; Tarazi, F.I.

    1997-01-01

    Changes in dopamine receptor subtype binding in different brain regions were examined after 28 days treatment of rats with haloperidol, raclopride, clozapine or SCH23390 using in vitro receptor autoradiography. [ 3 H]7-hydroxy-N,N-di-n-propyl-2-aminotetralin binding to dopamine D 3 receptors was not changed in any brain region by any of the drug treatments. [ 3 H]SCH23390 was only increased by chronic SCH23390 treatment. Haloperidol significantly increased [ 3 H]nemonapride and [ 3 H]spiperone binding to dopamine D 2 -like receptors in the caudate-putamen. In contrast, haloperidol caused a small, significant increase in [ 3 H]raclopride binding in the lateral caudate-putamen only. Raclopride also elevated, but to a lesser extent [ 3 H]nemonapride and [ 3 H]spiperone binding in caudate-putamen, whereas it did not affect [ 3 H]raclopride binding. Clozapine did not significantly change D 2 -like striatal binding of [ 3 H]nemonapride, [ 3 H]spiperone or [ 3 H]raclopride. The differences in radioligand binding suggest that [ 3 H]nemonapride and [ 3 H]spiperone may be binding to additional subsets of dopamine D 2 -like receptors (including D 4 -like receptors) that are not recognized by [ 3 H]raclopride, which has high affinity for D 2 and D 3 receptors only.Quantification of [ 3 H]nemonapride or [ 3 H]spiperone binding in the presence of 300 nM raclopride (to block D 2 and D 3 receptors) revealed that haloperidol, raclopride and clozapine up-regulated D 4 -like receptors in the caudate-putamen using either radioligand. These results suggest that D 4 -like receptors may be a common site of action of both typical and atypical antipsychotics. (Copyright (c) 1997 Elsevier Science B.V., Amsterdam. All rights reserved.)

  17. Thrombosis of second-generation drug-eluting stents in real practice results from the multicenter Spanish registry ESTROFA-2 (Estudio Español Sobre Trombosis de Stents Farmacoactivos de Segunda Generacion-2).

    Science.gov (United States)

    de la Torre Hernández, José M; Alfonso, Fernando; Gimeno, Federico; Diarte, Jose A; Lopez-Palop, Ramón; Pérez de Prado, Armando; Rivero, Fernando; Sanchis, Juan; Larman, Mariano; Diaz, Jose F; Elizaga, Jaime; Moreiras, Javier Martín; Gomez Jaume, Alfredo; Hernández, José M; Mauri, Josepa; Recalde, Angel Sánchez; Bullones, Juan A; Rumoroso, Jose R; Del Blanco, Bruno García; Baz, Jose A; Bosa, Francisco; Botas, Javier; Hernández, Felipe

    2010-09-01

    This study sought to evaluate second-generation drug-eluting stent (DES) thrombosis in clinical practice. First-generation DES are associated with a significant incidence of late thrombosis. There is paucity of data regarding real practice late thrombosis incidence and predictors with second-generation DES, zotarolimus-eluting stent (ZES), and everolimus-eluting stents (EES). A prospective, large-scale, non-industry-linked multicenter registry was designed. Complete clinical-procedural data and systematic follow-up of all patients treated with these stents was reported in a dedicated registry supported by the Spanish Working Group on Interventional Cardiology. From 2005 to 2008, 4,768 patients were included in 34 centers: 2,549 treated with ZES, and 2,219 with EES. The cumulative incidence of definite/probable thrombosis for ZES was 1.3% at 1 year and 1.7% at 2 years and for EES 1.4% at 1 year and 1.7% at 2 years (p = 0.8). The increment of definite thrombosis between the first and second year was 0.2% and 0.25%, respectively. In a propensity score analysis, the incidence remained very similar. Ejection fraction (adjusted hazard ratio [HR]: 0.97; 95% confidence interval [CI]: 0.95 to -0.99; p = 0.008), stent diameter (adjusted HR: 0.37; 95% CI: 0.17to 0.81; p = 0.01) and bifurcations (adjusted HR: 2.1; 95% CI: 1.14 to 3.7; p = 0.02) emerged as independent predictors of thrombosis. In the subgroup of patients with bifurcations, the use of ZES was independently associated with a higher thrombosis rate (adjusted HR: 4; 95% CI: 1.1 to 13; p = 0.03). In a real practice setting, the incidence of thrombosis at 2 years with ZES and EES was low and quite similar. The incidence of very late thrombosis resulted lower than was reported in registries of first-generation DES. In the subset of bifurcations, the use of ZES significantly increased the risk of thrombosis. Copyright © 2010 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

  18. The natural hallucinogen 5-MeO-DMT, component of Ayahuasca, disrupts cortical function in rats: reversal by antipsychotic drugs.

    Science.gov (United States)

    Riga, Maurizio S; Soria, Guadalupe; Tudela, Raúl; Artigas, Francesc; Celada, Pau

    2014-08-01

    5-Methoxy-N,N-dimethyltryptamine (5-MeO-DMT) is a natural hallucinogen component of Ayahuasca, an Amazonian beverage traditionally used for ritual, religious and healing purposes that is being increasingly used for recreational purposes in US and Europe. 5MeO-DMT is of potential interest for schizophrenia research owing to its hallucinogenic properties. Two other psychotomimetic agents, phencyclidine and 2,5-dimethoxy-4-iodo-phenylisopropylamine (DOI), markedly disrupt neuronal activity and reduce the power of low frequency cortical oscillations (<4 Hz, LFCO) in rodent medial prefrontal cortex (mPFC). Here we examined the effect of 5-MeO-DMT on cortical function and its potential reversal by antipsychotic drugs. Moreover, regional brain activity was assessed by blood-oxygen level dependent (BOLD) functional magnetic resonance imaging (fMRI). 5-MeO-DMT disrupted mPFC activity, increasing and decreasing the discharge of 51 and 35% of the recorded pyramidal neurons, and reducing (-31%) the power of LFCO. The latter effect depended on 5-HT1A and 5-HT2A receptor activation and was reversed by haloperidol, clozapine, risperidone, and the mGlu2/3 agonist LY379268. Likewise, 5-MeO-DMT decreased BOLD responses in visual cortex (V1) and mPFC. The disruption of cortical activity induced by 5-MeO-DMT resembles that produced by phencyclidine and DOI. This, together with the reversal by antipsychotic drugs, suggests that the observed cortical alterations are related to the psychotomimetic action of 5-MeO-DMT. Overall, the present model may help to understand the neurobiological basis of hallucinations and to identify new targets in antipsychotic drug development.

  19. Reporting sexual function disorders caused by antipsychotic drugs : is there a role for the community pharmacy?

    NARCIS (Netherlands)

    Rijcken, CAW; Dekens-Konter, JAM; Knegtering, H; de Jong-van den Berg, LTW

    2001-01-01

    Sexual function disorders are frequent adverse effects of antipsychotic use. These effects can lead to non-compliance to medication, which dramatically worsen the outcome of the psychotic disease. Detecting sexual dysfunction by the carers may be difficult, since feelings of embarrassment may occur

  20. The second generation biofuels from the biomass

    International Nuclear Information System (INIS)

    2007-01-01

    The author takes stock on the second generation biofuels in the world, the recent technologies, their advantages, the research programs and the economical and environmental impacts of the biofuels development. (A.L.B.)

  1. The effect of antipsychotic drugs on nonspecific inflammation markers in the first episode of schizophrenia

    Directory of Open Access Journals (Sweden)

    Stefanović Vesna

    2015-01-01

    Full Text Available Background/Aim. Immune system disorder, including inflammation, takes a significant place when considering still unclear etiology of schizophrenia. The aim of this study was to determine the blood levels of nonspecific inflammation markers in the first episode of schizophrenia and their relation to the therapy response. Methods. In this study we determined the blood levels of nonspecific inflammation markers: white blood cells count (WBC, C-reactive protein (CRP, erythrocytes sedimentation rate (ESR and the elements of differential white blood cell counts (or the leukocyte formula: granulocytes (Gra, lymphocytes (Lym and monocytes (Mon, in the first episode of schizofrenia, in 78 patients hospitalized at the Clinic for Psychiatric Disorders “Dr Laza Lazarević” in Belgrade. The levels were measured at admission to the clinic, as well as after 4 weeks of antipsychotic treatment. The Positive and negative syndrome scale for schizophrenia (PANSS was applied to measure the severity of psychopathology and response to the treatment. Results. During the first episode of schizophrenia, before initiation of antipsychotic treatment, the frequency of abnormal values was high (≥ 25% of the patients for the following non-specific inflammation markers: WBC, CRP, ESR and Gra, in the leukocyte formula, but dropped after 4 weeks of antipsychotic treatment at the level of high statistical significance for WBC and Gra (p < 0.001. The ESR remained unchanged in as many as 50% of the patients even after 4-week antipsychotic treatment, at the level of statistical significance in the non-responders compared to the responders (p = 0.045. Conclusion. The obtained results indicate that in the first episode of schizophrenia the blood levels of non-specific inflammation markers (WBS, CRP, ESR and Gra from the leukocyte formula were high in the subpopulation of patients with the tendency towards normalization of inflammation parameters after a 4-week antipsychotic

  2. Differential regulation of dopamine receptors after chronic typical and atypical antipsychotic drug treatment

    Energy Technology Data Exchange (ETDEWEB)

    Creese, I; Florijn, W J; Tarazi, F I [Center for Molecular and Behavioral Neuroscience, Rutgers University, 197 University Avenue, Newark, NJ (United States)

    1997-04-14

    Changes in dopamine receptor subtype binding in different brain regions were examined after 28 days treatment of rats with haloperidol, raclopride, clozapine or SCH23390 using in vitro receptor autoradiography. [{sup 3}H]7-hydroxy-N,N-di-n-propyl-2-aminotetralin binding to dopamine D{sub 3} receptors was not changed in any brain region by any of the drug treatments. [{sup 3}H]SCH23390 was only increased by chronic SCH23390 treatment. Haloperidol significantly increased [{sup 3}H]nemonapride and [{sup 3}H]spiperone binding to dopamine D{sub 2}-like receptors in the caudate-putamen. In contrast, haloperidol caused a small, significant increase in [{sup 3}H]raclopride binding in the lateral caudate-putamen only. Raclopride also elevated, but to a lesser extent [{sup 3}H]nemonapride and [{sup 3}H]spiperone binding in caudate-putamen, whereas it did not affect [{sup 3}H]raclopride binding. Clozapine did not significantly change D{sub 2}-like striatal binding of [{sup 3}H]nemonapride, [{sup 3}H]spiperone or [{sup 3}H]raclopride. The differences in radioligand binding suggest that [{sup 3}H]nemonapride and [{sup 3}H]spiperone may be binding to additional subsets of dopamine D{sub 2}-like receptors (including D{sub 4}-like receptors) that are not recognized by [{sup 3}H]raclopride, which has high affinity for D{sub 2} and D{sub 3} receptors only.Quantification of [{sup 3}H]nemonapride or [{sup 3}H]spiperone binding in the presence of 300 nM raclopride (to block D{sub 2} and D{sub 3} receptors) revealed that haloperidol, raclopride and clozapine up-regulated D{sub 4}-like receptors in the caudate-putamen using either radioligand. These results suggest that D{sub 4}-like receptors may be a common site of action of both typical and atypical antipsychotics. (Copyright (c) 1997 Elsevier Science B.V., Amsterdam. All rights reserved.)

  3. The ticking of the epigenetic clock: antipsychotic drugs in old age

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    Adonis Sfera

    2016-08-01

    Full Text Available AbstractBackground: Exposed to antipsychotic drugs (APDs, older individuals with dementing illness are at risk of cerebrovascular adverse effects (CVAE, including sudden death. Transient microvascular dysfunctions are known to occur in younger persons exposed to APDs, however they seldom progresses to CVAE, suggesting that APDs alone are insufficient for engendering this untoward effect. It is, therefore believed that a preexistent microvascular damage is necessary for CVAE to take place, but the exact nature of this lesion remains unclear.CNS small vessel disease (SVD is a well-known age-related risk factor for strokes, dementia and sudden death, which may constitute the initial CVAE-predisposing pathology. We therefore propose a two strike CVAE paradigm in which SVD represents the first strike, while exposure to APDs, the second. In this model, both strikes must be present for CVAE to take place, and the neuroimaging load of white matter hyperintensities (WMH may be directly proportional with the CVAE risk.To investigate this hypothesis at the molecular level, we focused on a seemingly unrelated phenomenon: both APDs and SVD were found protective against a similar repertoire of cancers and their spread to the brain (1-4. Since microRNA-29 has shown efficacy against the same malignancies, and has been associated with small vessels pathology, we narrowed our search down to this miR, hypothesizing that the APDs mechanism of action includes miR-29 up-regulation, which in turn facilitates the development of SVD. Aim: to assess whether miR-29 can be utilized as a peripheral blood biomarker for SVD and CVAE risk.Method: we conducted a search of experimentally verified miR-29 target genes utilizing the public domain tools miRanda, RNA22 and Weizemann Institute of Science miRNA Analysis. We identified in total 67 experimentally verified target genes for miR-29 family, 18 of which correlate with microvascular integrity, and may be relevant for CVAE

  4. The use of random-effects models to identify health care center-related characteristics modifying the effect of antipsychotic drugs.

    Science.gov (United States)

    Nordon, Clementine; Battin, Constance; Verdoux, Helene; Haro, Josef Maria; Belger, Mark; Abenhaim, Lucien; van Staa, Tjeerd Pieter

    2017-01-01

    A case study was conducted, exploring methods to identify drugs effects modifiers, at a health care center level. Data were drawn from the Schizophrenia Outpatient Health Outcome cohort, including hierarchical information on 6641 patients, recruited from 899 health care centers from across ten European countries. Center-level characteristics included the following: psychiatrist's gender, age, length of practice experience, practice setting and type, countries' Healthcare System Efficiency score, and psychiatrist density in the country. Mixed multivariable linear regression models were used: 1) to estimate antipsychotic drugs' effectiveness (defined as the association between patients' outcome at 3 months - dependent variable, continuous - and antipsychotic drug initiation at baseline - drug A vs other antipsychotic drug); 2) to estimate the similarity between clustered data (using the intra-cluster correlation coefficient); and 3) to explore antipsychotic drug effects modification by center-related characteristics (using the addition of an interaction term). About 23% of the variance found for patients' outcome was explained by unmeasured confounding at a center level. Psychiatrists' practice experience was found to be associated with patient outcomes ( p =0.04) and modified the relative effect of "drug A" ( p <0.001), independent of center- or patient-related characteristics. Mixed models may be useful to explore how center-related characteristics modify drugs' effect estimates, but require numerous assumptions.

  5. No alterations of brain GABA after 6 months of treatment with atypical antipsychotic drugs in early-stage first-episode schizophrenia.

    Science.gov (United States)

    Goto, Naoki; Yoshimura, Reiji; Kakeda, Shingo; Moriya, Junji; Hori, Hikaru; Hayashi, Kenji; Ikenouchi-Sugita, Atsuko; Nakano-Umene, Wakako; Katsuki, Asuka; Nishimura, Joji; Korogi, Yukunori; Nakamura, Jun

    2010-12-01

    We investigated the effects of atypical antipsychotic drugs on GABA concentrations in early-stage, first-episode schizophrenia patients. Sixteen (8 males, 8 females; age, 30±11 years old) patients were followed up for six months. We also included 18 sex- and age-matched healthy control subjects. All patients were treated with atypical antipsychotic drugs (5 patients with risperidone, 5 patients with olanzapine, 4 patients with aripiprazole, and 2 patients with quetiapine). In all three regions measured (frontal lobe, left basal ganglia, and parieto-occipital lobe), no differences in GABA concentrations were observed in a comparison of pre-treatment levels and those six months after treatment. These results suggest that relatively short-term treatment with atypical antipsychotic drugs may not affect GABAergic neurotransmission; however, it is also possible that such treatment prevents further reductions in brain GABA levels in people with early-stage, first-episode schizophrenia. Copyright © 2010 Elsevier Inc. All rights reserved.

  6. Atypical antipsychotic drugs and diabetes mellitus in the US Food and Drug Administration Adverse Event database: a systematic Bayesian signal detection analysis.

    Science.gov (United States)

    Baker, Ross A; Pikalov, Andrei; Tran, Quynh-Van; Kremenets, Tatyana; Arani, Ramin B; Doraiswamy, P Murali

    2009-01-01

    Prior literature suggests that the risk of diabetes-related adverse events (DRAEs) differs between atypical antipsychotics. The present study evaluated the potential association between atypical antipsychotics or haloperidol and diabetes using data from the FDA AERS database. Analysis of AERS data was conducted for clozapine, risperidone, olanzapine, quetiapine, ziprasidone, aripiprazole or haloperidol with 24 DRAEs from the Medical Dictionary for Regulatory Activities using a Multi-item Gamma Poisson Shrinker (MGPS) data-mining algorithm. Using MGPS, adjusted reporting ratios (Empiric Bayes Geometric Mean or EBGM) and 90% confidence intervals (CIs; EB05-EB95) were calculated to estimate the degree of drug-event association relative to all drugs and events. Logistic regression odds ratios and 90% CIs (LR05-LR95) were calculated for diabetes mellitus events. All six atypicals had an EB05 >/= 2 for at least one DRAE. The most common event was diabetes mellitus (2,784 cases). Adjusted reporting ratios (CIs) for diabetes mellitus were: olanzapine 9.6 (9.2-10.0; 1306 cases); risperidone 3.8 (3.5-4.1; 447 cases); quetiapine 3.5 (3.2-3.9; 283 cases); clozapine 3.1 (2.9-3.3; 464 cases); ziprasidone 2.4 (2.0-2.9; 74 cases); aripiprazole 2.4 (1.9-2.9; 71 cases); haloperidol 2.0 (1.7-2.3; 139 cases). Logistic regression odds ratios agreed with adjusted reporting ratios. In the AERS database, lower associations with DRAEs were seen for haloperidol, aripiprazole and ziprasidone, and higher associations were seen for olanzapine, risperidone, clozapine and quetiapine. Our findings support differential risk of diabetes across atypical antipsychotics, reinforcing the need for metabolic monitoring of patients taking antipsychotics.

  7. Crosstalk between insulin and dopamine signaling: A basis for the metabolic effects of antipsychotic drugs.

    Science.gov (United States)

    Nash, Abigail I

    2017-10-01

    In the setting of rising rates of obesity and metabolic syndrome, characterized in part by hyperinsulinemia, it is increasingly important to understand the mechanisms that contribute to insulin dysregulation. The higher risk for metabolic syndrome imparted by antipsychotic medication use highlights one such mechanism. Though there is great variation in the number and types of signaling pathways targeted by these medications, the one common mechanism of action is through dopamine. Dopamine's effects on insulin signaling begin at the level of insulin secretion from the pancreas and continue through the central nervous system. In a reciprocal fashion, insulin also affects dopamine signaling, with specific effects on dopamine reuptake from the synapse. This review probes the dopamine-insulin connection to provide a comprehensive examination of how antipsychotics may contribute towards insulin resistance. Published by Elsevier B.V.

  8. A pilot randomised controlled trial of community-led ANtipsychotic Drug REduction for Adults with Learning Disabilities.

    Science.gov (United States)

    McNamara, Rachel; Randell, Elizabeth; Gillespie, David; Wood, Fiona; Felce, David; Romeo, Renee; Angel, Lianna; Espinasse, Aude; Hood, Kerry; Davies, Amy; Meek, Andrea; Addison, Katy; Jones, Glyn; Deslandes, Paul; Allen, David; Knapp, Martin; Thapar, Ajay; Kerr, Michael

    2017-08-01

    Data suggest that approximately 50,000 adults with learning disabilities (LDs) in England and Wales are currently prescribed antipsychotic medication. Illness in this population is common, including significant rates of challenging behaviour and mental illness, but there is particular concern over the use of antipsychotics prescribed for reasons other than the treatment of psychosis. Control of challenging behaviour is the primary reason why such medications are prescribed despite the absence of good evidence for any therapeutic effect for this purpose. To assess the feasibility of recruitment and retention and to explore non-efficacy-based barriers to a blinded antipsychotic medication withdrawal programme for adults with LDs without psychosis compared with treatment as usual. A secondary objective was to compare trial arms regarding clinical outcomes. A two-arm individually randomised double-blind placebo-controlled drug reduction trial. Recruitment was through community learning disability teams (CLDTs) in south Wales and south-west England. Adults with LDs who are prescribed risperidone for treatment of challenging behaviour with no known current psychosis or previous recurrence of psychosis following prior drug reduction. A double-blind drug reduction programme leading to full withdrawal within 6 months. Treatment in the intervention group was gradually reduced over a 6-month period and then maintained at the same level for a further 3 months, still under blind conditions. In the control group, the baseline level of medication was maintained throughout the 9-month period. The blind was broken at 9 months, following final data collection. Feasibility outcomes were (1) the number and proportion of general practices/CLDTs that progressed from initial approach to recruitment of participants and (2) the number and proportion of recruited participants who progressed through the various stages of the study. Trial arms were also compared regarding clinical outcomes

  9. Second generation biofuels: Economics and policies

    International Nuclear Information System (INIS)

    Carriquiry, Miguel A.; Du Xiaodong; Timilsina, Govinda R.

    2011-01-01

    This study reviews economics of production of second generation biofuels from various feedstocks, including crop and wood/forestry residues, lignocellulosic energy crops, jatropha, and algae. The study indicates that while second generation biofuels could significantly contribute to the future energy supply mix, cost is a major barrier to its commercial production in the near to medium term. Depending upon type of biofuels, feedstock prices and conversion costs, the cost of cellulosic ethanol is found to be two to three times higher than the current price of gasoline on an energy equivalent basis. The median cost (across the studies reviewed) of biodiesel produced from microalgae, a prospective feedstock, is seven times higher than the current price of diesel, although much higher cost estimates have been reported. As compared with the case of first generation biofuels, in which feedstock can account for over two-thirds of the total costs, the share of feedstock in the total costs is relatively lower (30-50%) in the case of second generation biofuels. While significant cost reductions are needed for both types of second generation biofuels, the critical barriers are at different steps of the production process. For cellulosic ethanol, the biomass conversion costs needs to be reduced. On the other hand, feedstock cost is the main issue for biodiesel. At present, policy instruments, such as fiscal incentives and consumption mandates have in general not differentiated between the first and second generation biofuels except in the cases of the US and EU. The policy regime should be revised to account for the relative merits of different types of biofuels. - Highlights: → Second generation biofuels could significantly contribute to the future energy supply mix. → Cost is a major barrier to its the commercial production in the near to medium term. → The policy regime should be revised to account for the relative merits of different biofuels.

  10. Second generation biofuels: Economics and policies

    Energy Technology Data Exchange (ETDEWEB)

    Carriquiry, Miguel A., E-mail: miguelc@iastate.edu [Center for Agricultural and Rural Development, Iowa State University (United States); Du Xiaodong, E-mail: xdu23@wisc.edu [Department of Agricultural and Applied Economics, University of Wisconsin-Madison (United States); Timilsina, Govinda R., E-mail: gtimilsina@worldbank.org [Development Research Group, The World Bank (United States)

    2011-07-15

    This study reviews economics of production of second generation biofuels from various feedstocks, including crop and wood/forestry residues, lignocellulosic energy crops, jatropha, and algae. The study indicates that while second generation biofuels could significantly contribute to the future energy supply mix, cost is a major barrier to its commercial production in the near to medium term. Depending upon type of biofuels, feedstock prices and conversion costs, the cost of cellulosic ethanol is found to be two to three times higher than the current price of gasoline on an energy equivalent basis. The median cost (across the studies reviewed) of biodiesel produced from microalgae, a prospective feedstock, is seven times higher than the current price of diesel, although much higher cost estimates have been reported. As compared with the case of first generation biofuels, in which feedstock can account for over two-thirds of the total costs, the share of feedstock in the total costs is relatively lower (30-50%) in the case of second generation biofuels. While significant cost reductions are needed for both types of second generation biofuels, the critical barriers are at different steps of the production process. For cellulosic ethanol, the biomass conversion costs needs to be reduced. On the other hand, feedstock cost is the main issue for biodiesel. At present, policy instruments, such as fiscal incentives and consumption mandates have in general not differentiated between the first and second generation biofuels except in the cases of the US and EU. The policy regime should be revised to account for the relative merits of different types of biofuels. - Highlights: > Second generation biofuels could significantly contribute to the future energy supply mix. > Cost is a major barrier to its the commercial production in the near to medium term. > The policy regime should be revised to account for the relative merits of different biofuels.

  11. Typical and Atypical Antipsychotic Drugs Increase Extracellular Histamine Levels in the Rat Medial Prefrontal Cortex: Contribution of Histamine H1 Receptor Blockade

    Directory of Open Access Journals (Sweden)

    Kjell A Svensson

    2012-05-01

    Full Text Available Atypical antipsychotics such as clozapine and olanzapine have been shown to enhance histamine turnover and this effect has been hypothesized to contribute to their improved therapeutic profile compared to typical antipsychotics. In the present study, we examined the effects of antipsychotic drugs on histamine (HA efflux in the mPFC of the rat by means of in vivo microdialysis and sought to differentiate the receptor mechanisms which underlie such effects. Olanzapine and clozapine increased mPFC HA efflux in a dose related manner. Increased HA efflux was also observed after quetiapine, chlorpromazine and perphenazine treatment. We found no effect of the selective 5-HT2A antagonist MDL100907, 5-HT2c antagonist SB242084 or the 5-HT6 antagonist Ro 04-6790 on mPFC HA efflux. HA efflux was increased following treatment with selective H1 receptor antagonists pyrilamine, diphenhydramine and triprolidine, the H3 receptor antagonist ciproxifan and the mixed 5HT2A/H1 receptor antagonist ketanserin. The potential novel antipsychotic drug FMPD, which has a lower affinity at H1 receptors than olanzapine, did not affect HA efflux. Similarly, other antipsychotics with lower H1 receptor affinity (risperidone, aripiprazole and haloperidol were also without effect on HA efflux. Perfusion of clozapine and pyrilamine into the TMN, but not the mPFC, increased local HA efflux. Finally, HA efflux after antipsychotic treatment was significantly correlated with affinity at H1 receptors whereas 9 other receptors, including 5-HT2A, were not. These results demonstrate that both typical and atypical antipsychotics increase mPFC histamine efflux and this effect may be mediated via antagonism of histamine H1 receptors.

  12. State of the art of drug treatment of schizophrenia and the future position of the novel/atypical antipsychotics.

    Science.gov (United States)

    Möller, H J

    2000-10-01

    Neuroleptic medication is the most important part of the treatment regimen for schizophrenic patients. The efficacy of neuroleptics in the acute and long-term treatment of schizophrenia is very well proven and the effect size is comparatively high. After more than 40 years of clinical practice with the classical neuroleptics, several more or less generally accepted rules for the management of drug treatment in schizophrenia have been established. The paper aims to describe these standards, discussing, among other things, developments which have appeared in the last 10 to 20 years, e.g. the tendency to a lower daily dose during acute treatment and the tendency to alternative strategies during long-term treatment. The paper especially also takes into consideration the benefits of the novel/atypical antipsychotics as compared to the classical neuroleptics, which will change the current treatment standards under several aspects--a change which is already ongoing. The novel/atypical antipsychotics will be much better accepted by patients, thus leading to increased compliance, will be associated with a better quality of life and will possibly change the long-term outcome of schizophrenic patients in a very important manner. It should be considered that the so-called novel/atypical neuroleptics do not constitute a homogeneous group but are a group of individual drugs, each with their own advantages and disadvantages. As was the situation with the classical neuroleptics, the physician also has to choose the most adequate drug under consideration of the risk/benefit profile of each drug in relation to the disposition of the individual patient.

  13. Recovery of behavioral changes and compromised white matter in C57BL/6 mice exposed to cuprizone: Effects of antipsychotic drugs

    Directory of Open Access Journals (Sweden)

    Haiyun eXu

    2011-07-01

    Full Text Available Recent animal and human studies have suggested that the cuprizone (CPZ, a copper chelator-feeding C57BL/6 mouse may be used as an animal model of schizophrenia. The goals of this study were to see the recovery processes of CPZ-induced behavioral changes and damaged white matter and to examine possible effects of antipsychotic drugs on the recovery processes. Mice were fed a CPZ-containing diet for five weeks then returned to normal food for three weeks, during which period mice were treated with different antipsychotic drugs. Various behaviors were measured at the end of CPZ-feeding phase as well as on the 14th and 21st days after CPZ-withdrawal. The damage to and recovery status of white matter in the brains of mice were examined. Dietary CPZ resulted in white matter damage and behavioral abnormalities in the elevated plus-maze, social interaction and Y-maze test. Elevated plus-maze performance recovered to normal range within two weeks after CPZ withdrawal. But, alterations in social interaction showed no recovery. Antipsychotics did not alter animals’ behavior in either of these tests during the recovery period. Altered performance in the Y-maze showed some recovery in the vehicle group; atypical antipsychotics, but not haloperidol, significantly promoted this recovery process. The recovery of damaged white matter was incomplete during the recovery period. None of the drugs significantly promoted the recovery of damaged white matter. These results suggest that CPZ-induced white matter damage and social interaction deficit may be resistant to the antipsychotic treatment employed in this study. They are in good accordance with the clinical observations that positive symptoms in schizophrenic patients respond well to antipsychotic drugs while social dysfunction is usually intractable.

  14. Atypical antipsychotics induce both proinflammatory and adipogenic gene expression in human adipocytes in vitro

    International Nuclear Information System (INIS)

    Sárvári, Anitta K.; Veréb, Zoltán; Uray, Iván P.; Fésüs, László; Balajthy, Zoltán

    2014-01-01

    Highlights: • Antipsychotics modulate the expression of adipogenic genes in human adipocytes. • Secretion of proinflammatory cytokine IL8 and MCP-1 is induced by antipsychotics. • Adipocyte-dependent inflammatory abnormality could develop during chronic treatment. • Infiltrated macrophages would further enhance proinflammatory cytokine production. - Abstract: Schizophrenia requires lifelong treatment, potentially causing systemic changes in metabolic homeostasis. In the clinical setting, antipsychotic treatment may differentially lead to weight gain among individual patients, although the molecular determinants of such adverse effects are currently unknown. In this study, we investigated changes in the expression levels of critical regulatory genes of adipogenesis, lipid metabolism and proinflammatory genes during the differentiation of primary human adipose-derived stem cells (ADSCs). These cells were isolated from patients with body mass indices <25 and treated with the second-generation antipsychotics olanzapine, ziprasidone, clozapine, quetiapine, aripiprazole and risperidone and the first-generation antipsychotic haloperidol. We found that antipsychotics exhibited a marked effect on key genes involved in the regulation of cell cycle, signal transduction, transcription factors, nuclear receptors, differentiation markers and metabolic enzymes. In particular, we observed an induction of the transcription factor NF-KB1 and NF-KB1 target genes in adipocytes in response to these drugs, including the proinflammatory cytokines TNF-α, IL-1β, IL-8 and MCP-1. In addition, enhanced secretion of both IL8 and MCP-1 was observed in the supernatant of these cell cultures. In addition to their remarkable stimulatory effects on proinflammatory gene transcription, three of the most frequently prescribed antipsychotic drugs, clozapine, quetiapine and aripiprazole, also induced the expression of essential adipocyte differentiation genes and the adipocyte hormones leptin

  15. Atypical antipsychotics induce both proinflammatory and adipogenic gene expression in human adipocytes in vitro

    Energy Technology Data Exchange (ETDEWEB)

    Sárvári, Anitta K., E-mail: anittasarvari@med.unideb.hu [Department of Biochemistry and Molecular Biology, Medical and Health Science Center, University of Debrecen, Debrecen (Hungary); Veréb, Zoltán, E-mail: jzvereb@gmail.com [Department of Biochemistry and Molecular Biology, Medical and Health Science Center, University of Debrecen, Debrecen (Hungary); Uray, Iván P., E-mail: ipuray@mdanderson.org [Clinical Cancer Prevention Department, The University of Texas, MD Anderson Cancer Center, Houston, TX (United States); Fésüs, László, E-mail: fesus@med.unideb.hu [Department of Biochemistry and Molecular Biology, Medical and Health Science Center, University of Debrecen, Debrecen (Hungary); MTA DE Apoptosis, Genomics and Stem Cell Research Group of the Hungarian Academy of Sciences (Hungary); Balajthy, Zoltán, E-mail: balajthy@med.unideb.hu [Department of Biochemistry and Molecular Biology, Medical and Health Science Center, University of Debrecen, Debrecen (Hungary)

    2014-08-08

    Highlights: • Antipsychotics modulate the expression of adipogenic genes in human adipocytes. • Secretion of proinflammatory cytokine IL8 and MCP-1 is induced by antipsychotics. • Adipocyte-dependent inflammatory abnormality could develop during chronic treatment. • Infiltrated macrophages would further enhance proinflammatory cytokine production. - Abstract: Schizophrenia requires lifelong treatment, potentially causing systemic changes in metabolic homeostasis. In the clinical setting, antipsychotic treatment may differentially lead to weight gain among individual patients, although the molecular determinants of such adverse effects are currently unknown. In this study, we investigated changes in the expression levels of critical regulatory genes of adipogenesis, lipid metabolism and proinflammatory genes during the differentiation of primary human adipose-derived stem cells (ADSCs). These cells were isolated from patients with body mass indices <25 and treated with the second-generation antipsychotics olanzapine, ziprasidone, clozapine, quetiapine, aripiprazole and risperidone and the first-generation antipsychotic haloperidol. We found that antipsychotics exhibited a marked effect on key genes involved in the regulation of cell cycle, signal transduction, transcription factors, nuclear receptors, differentiation markers and metabolic enzymes. In particular, we observed an induction of the transcription factor NF-KB1 and NF-KB1 target genes in adipocytes in response to these drugs, including the proinflammatory cytokines TNF-α, IL-1β, IL-8 and MCP-1. In addition, enhanced secretion of both IL8 and MCP-1 was observed in the supernatant of these cell cultures. In addition to their remarkable stimulatory effects on proinflammatory gene transcription, three of the most frequently prescribed antipsychotic drugs, clozapine, quetiapine and aripiprazole, also induced the expression of essential adipocyte differentiation genes and the adipocyte hormones leptin

  16. Antipsychotic-induced Hyperprolactinemia

    Directory of Open Access Journals (Sweden)

    Suheyla Dogan Bulut

    2015-06-01

    Full Text Available Prolactin provides the growth of the mammary gland during pregnancy and synthesis and preparation of breast milk for lactation. Antipsychotics and antidepressants that are frequently used in psychiatry, cause hyperprolactinemia. The prevalent opinion is that especially typical antipsychotics increase prolactin levels primarily by blocking D2 receptors in the anterior pituitary. The effects of atypical antipsychotics on hyperprolactinemia vary. Hyperprolactinemia causes galactorrhea, gynecomastia, sexual dysfunction, infertility, acne, hirsutism in women, weight gain, obesity and mood changes in addition to menstrual irregularities such as oligomenorrhea, polymenorrhea and amenorrhea. In the long term, hyperprolactinemia may cause reduction in bone density and osteoporosis. Hyperprolactinemia as a side effect of antipsychotics drugs and its treatment will be reviewed in this article. [Psikiyatride Guncel Yaklasimlar - Current Approaches in Psychiatry 2015; 7(2: 109-124

  17. Revisiting Antipsychotic-induced Akathisia: Current Issues and Prospective Challenges

    Science.gov (United States)

    Salem, Haitham; Nagpal, Caesa; Pigott, Teresa; Teixeira, Antonio Lucio

    2017-01-01

    Background: Akathisia continues to be a significant challenge in current neurological and psychiatric practice. Prompt and accurate detection is often difficult and there is a lack of consensus concerning the neurobiological basis of akathisia. No definitive treatment has been established for akathisia despite numerous preclinical and clinical studies. Method: We reviewed antipsychotic-induced akathisia including its clinical presentation, proposed underlying pathophysiology, current and under investigation therapeutic strategies. Conclusion: Despite the initial promise that second generation antipsychotics would be devoid of akathisia effects, this has not been confirmed. Currently, there are limited therapeutic options for the clinical practice and the evidence supporting the most widely used treatments (beta blockers, anticholinergic drugs) is still absent or inconsistent. PMID:27928948

  18. Second Generation Waste Package Design Study

    International Nuclear Information System (INIS)

    Armijo, J.S.; Misra, M.; Kar, Piyush

    2007-01-01

    The following describes the objectives of Project Activity 023 ''Second Generation Waste Package Design Study'' under DOE Cooperative Agreement DE-FC28-04RW12232. The objectives of this activity are: to review the current YMP baseline environment and establish corrosion test environments representative of the range of dry to intermittently wet conditions expected in the drifts as a function of time; to demonstrate the oxidation and corrosion resistance of A588 weathering steel and reference Alloy 22 samples in the representative dry to intermittently dry conditions; and to evaluate backfill and design features to improve the thermal performance analyses of the proposed second-generation waste packages using existing models developed at the University of Nevada, Reno(UNR). The work plan for this project activity consists of three major tasks: Task 1. Definition of expected worst-case environments (humidity, liquid composition and temperature) at waste package outer surfaces as a function of time, and comparison with environments defined in the YMP baseline; Task 2. Oxidation and corrosion tests of proposed second-generation outer container material; and Task 3. Second Generation waste package thermal analyses. Full funding was not provided for this project activity

  19. Amisulpride versus other atypical antipsychotics for schizophrenia

    Science.gov (United States)

    Komossa, Katja; Rummel-Kluge, Christine; Hunger, Heike; Schmid, Franziska; Schwarz, Sandra; da Mota Neto, Joaquim I Silveira; Kissling, Werner; Leucht, Stefan

    2014-01-01

    Background In many countries of the industrialised world second generation (atypical) antipsychotics have become first line drug treatments for people with schizophrenia. The question as to whether, and if so how much, the effects of the various second generation antipsychotics differ is a matter of debate. In this review we examine how the efficacy and tolerability of amisulpride differs from that of other second generation antipsychotics. Objectives To evaluate the effects of amisulpride compared with other atypical antipsychotics for people with schizophrenia and schizophrenia-like psychoses. Search methods We searched the Cochrane Schizophrenia Group Trials Register (April 2007) which is based on regular searches of BIOSIS, CINAHL, EMBASE, MEDLINE and PsycINFO. We updated this search in July 2012 and added 47 new trials to the awaiting classification section. Selection criteria We included randomised, at least single-blind, trials comparing oral amisulpride with oral forms of aripiprazole, clozapine, olanzapine, quetiapine, risperidone, sertindole, ziprasidone or zotepine in people with schizophrenia or schizophrenia-like psychoses. Data collection and analysis We extracted data independently. For continuous data we calculated weighted mean differences (MD), for dichotomous data we calculated relative risks (RR) and their 95% confidence intervals (CI) on an intention-to-treat basis based on a random effects model. We calculated numbers needed to treat/harm (NNT/NNH) where appropriate. Main results The review currently includes ten short to medium term trials with 1549 participants on three comparisons: amisulpride versus olanzapine, risperidone and ziprasidone. The overall attrition rate was considerable (34.7%) with no significant difference between groups. Amisulpride was similarly effective as olanzapine and risperidone and more effective than ziprasidone (leaving the study early due to inefficacy: n=123, 1 RCT, RR 0.21 CI 0.05 to 0.94, NNT 8 CI 5 to 50

  20. Pharmacokinetic-pharmacodynamic modeling of antipsychotic drugs in patients with schizophrenia Part I : The use of PANSS total score and clinical utility

    NARCIS (Netherlands)

    Reddy, Venkatesh Pilla; Kozielska, Magdalena; Suleiman, Ahmed Abbas; Johnson, Martin; Vermeulen, An; Liu, Jing; de Greef, Rik; Groothuis, Geny M. M.; Danhof, Meindert; Proost, Johannes H.

    Background: To develop a pharmacokinetic-pharmacodynamic (PK-PD) model using individual-level data of Positive and Negative Syndrome Scale (PANSS) total score to characterize the antipsychotic drug effect taking into account the placebo effect and dropout rate. In addition, a clinical utility (CU)

  1. Minimizing Cardiovascular Adverse Effects of Atypical Antipsychotic Drugs in Patients with Schizophrenia

    Directory of Open Access Journals (Sweden)

    Fadi T. Khasawneh

    2014-01-01

    Full Text Available The use of atypical antipsychotic agents has rapidly increased in the United States and worldwide in the last decade. Nonetheless, many health care practitioners do not appreciate the significance of the cardiovascular side effects that may be associated with their use and the means to minimize them. Thus, atypical antipsychotic medications can cause cardiovascular side effects such as arrhythmias and deviations in blood pressure. In rare cases, they may also cause congestive heart failure, myocarditis, and sudden death. Patients with schizophrenia have a higher risk of cardiovascular mortality than healthy individuals, possibly because of excessive smoking, the underlying disorder itself, or a combination of both factors. Increased awareness of these potential complications can allow pharmacists and physicians to better manage and monitor high risk patients. Accurate assessments are very important to avoid medications from being given to patients inappropriately. Additionally, monitoring patients regularly via blood draws and checking blood pressure, heart rate, and electrocardiogram can help catch any clinical problems and prevent further complications. Finally, patient and family-member education, which pharmacists in particular can play key roles in, is central for the management and prevention of side effects, which is known to reflect positively on morbidity and mortality in these patients.

  2. Effect of clinical response to active drugs and placebo on antipsychotics and mood stabilizers relative efficacy for bipolar depression and mania: A meta-regression analysis.

    Science.gov (United States)

    Bartoli, Francesco; Clerici, Massimo; Di Brita, Carmen; Riboldi, Ilaria; Crocamo, Cristina; Carrà, Giuseppe

    2018-04-01

    Randomised placebo-controlled trials investigating treatments for bipolar disorder have been hampered by wide variations of active drugs and placebo clinical response rates. It is important to estimate whether the active drug or placebo response has a greater influence in determining the relative efficacy of drugs for psychosis (antipsychotics) and relapse prevention (mood stabilisers) for bipolar depression and mania. We identified 53 randomised, placebo-controlled trials assessing antipsychotic or mood stabiliser monotherapy ('active drugs') for bipolar depression or mania. We carried out random-effects meta-regressions, estimating the influence of active drugs and placebo response rates on treatment relative efficacy. Meta-regressions showed that treatment relative efficacy for bipolar mania was influenced by the magnitude of clinical response to active drugs ( p=0.002), but not to placebo ( p=0.60). On the other hand, treatment relative efficacy for bipolar depression was influenced by response to placebo ( p=0.047), but not to active drugs ( p=0.98). Despite several limitations, our unexpected findings showed that antipsychotics / mood stabilisers relative efficacy for bipolar depression seems unrelated to active drugs response rates, depending only on clinical response to placebo. Future research should explore strategies to reduce placebo-related issues in randomised, placebo-controlled trials for bipolar depression.

  3. Diabetic control and atypical antipsychotics: a case report

    Directory of Open Access Journals (Sweden)

    Gaston Romina

    2008-05-01

    Full Text Available Abstract Introduction People with schizophrenia are at increased risk of developing metabolic disturbances. This risk may be further exacerbated by the use of antipsychotic agents. Research is still ongoing to determine the metabolic impact of antipsychotics on glucose regulation. In this case report we review some of the possible mechanisms of action of antipsychotic medication on glucose regulation. Case presentation We present the case of a 50-year-old man diagnosed with paranoid schizophrenia who developed type 2 diabetes mellitus whilst on treatment with second generation antipsychotics (SGA. His diabetes was controlled by a combination of antidiabetic drugs that were associated with his psychotropic treatment. Due to deterioration in his mental state, the patient was admitted on two occasions to a psychiatric unit during which his prescribed medication (olanzapine and risperidone was discontinued and changed to aripiprazole. On both occasions, the patient suffered hypoglycaemic episodes and his antidiabetic treatment had to be adjusted accordingly. The patient did not require any antidiabetic treatment whilst on aripiprazole during the follow up period. Conclusion Clinicians face regular dilemmas in trying to find the right balance between achieving control over a patient's mental illness and reducing any adverse effects associated with the prescribed medication. In patients receiving concomitant antidiabetic therapy, caution should be exercised when changing from one SGA to another. Whilst more longitudinal data are required, a trial of alternative SGAs, including aripiprazole in those developing type 2 diabetes and impaired glucose tolerance may be a worthwhile therapeutic option.

  4. Serotonin-1A receptor gene polymorphism and the ability of antipsychotic drugs to improve attention in schizophrenia.

    Science.gov (United States)

    Sumiyoshi, Tomiki; Tsunoda, Masahiko; Higuchi, Yuko; Itoh, Toru; Seo, Tomonori; Itoh, Hiroko; Suzuki, Michio; Kurachi, Masayoshi

    2010-05-01

    The purpose of this study was to determine if the functional single nucleotide polymorphisms of rs6259 C(-1019)G in the promoter region, which regulates serotonin 5-HT(1A) receptor transcription, affects the ability of antipsychotic drugs to improve attention in patients with schizophrenia. Subjects were neuroleptic-free and meeting DSM-IV-TR criteria for schizophrenia. Psychopathology and attention were evaluated with the Scale for the Assessment of Positive Symptoms (SAPS) and the Scale for the Assessment of Negative Symptoms (SANS) at baseline and 3 months after treatment with atypical antipsychotic drugs (AAPDs). DNA was extracted from peripheral blood following standard procedures. Genotyping was performed with HS-Taq assay (LaboPass). Data were available from 30 subjects (male/female=19/11), in which 17 had the CC genotype, three had the GG genotype, and 10 were heterozygous. The 3-month treatment with AAPDs was associated with significant improvements in positive and negative symptoms, but not attention as measured by SANS-Attention subscale in the entire subject group. There were no significant differences in the degree of improvements of SAPS and SANS scores between the CC genotype group and the (C/G plus G/G) combined group. On the other hand, improvement of attention was significantly greater for the former group compared to the latter group (P<0.016), suggesting a detrimental influence of the G-allele. These results provide additional support to the role of 5-HT(1A) receptors in some of the cognitive disturbances of schizophrenia. Further studies with a larger number of subjects are warranted.

  5. Herbert: A Second Generation Mobile Robot.

    Science.gov (United States)

    1988-01-01

    PROJECT. TASK S Artificial Inteligence Laboratory AREA A WORK UNIT NUMBERS ’ ~ 545 Technology Square Cambridge, MA 02139 11. CONTROLLING OFFICE NAME...AD-AI93 632 WMRT: A SECOND GENERTION MOBILE ROWT(U) / MASSACHUSETTS IMST OF TECH CAMBRIDGE ARTIFICIAL INTELLIGENCE LAB R BROOKS ET AL .JAN l8 Al-M...MASSACHUSETTS INSTITUTE OF TECHNOLOGY ARTIFICIAL INTELLIGENCE LABORATORY A. I. Memo 1016 January, 1988 HERBERT: A SECOND GENERATION MOBILE ROBOT Rodney A

  6. [Maintenance Treatment With Antipsychotics for Adult Patients Diagnosed With Schizophrenia].

    Science.gov (United States)

    Gómez-Restrepo, Carlos; Bohórquez Peñaranda, Adriana Patricia; de la Hoz Bradford, Ana María; Tamayo Martínez, Nathalie; García Valencia, Jenny; Jaramillo González, Luis Eduardo

    2014-01-01

    To determine the effectiveness and security of the antipsychotics available for the management of adult patients with schizophrenia in the maintenance phase. To develop recommendations of treatment for the maintenance phase of the disease. A clinical practice guideline was elaborated under the parameters of the Methodological Guide of the Ministerio de Salud y Protección Social to identify, synthesize and evaluate the evidence and make recommendations about the treatment and follow-up of adult patients with schizophrenia. The evidence of NICE guide 82 was adopted and updated. The evidence was presented to the Guideline Developing Group and recommendations, employing the GRADE system, were produced. 18 studies were included to evaluate the effectiveness and / or safety of different antipsychotic drugs first and second generation. Overall, antipsychotics (AP) showed superiority over placebo in relapse rate over 12 months (RR 0.59 95% CI 0.42, 0.82) and hospitalization rate over 24 months of follow-up (RR 0.38 95% 0.27, 0.55); its use is associated with increased risk of treatment dropout (RR 0.53 95% CI 0.46, 0.61) and adverse events such as weight gain, dystonia, extrapyramidal symptoms and sedation. There was no difference in the outcome of re hospitalizations, comparisons on quality of life, negative symptoms or weight gain between AP first and second generation. Continuous or standard dose regimens appear to be superior to intermittent or low doses in reducing the risk of abandonment of treatment regimes. Adult patients diagnosed with schizophrenia should receive maintenance treatment with antipsychotics. The medication of choice will depend on the management of the acute phase, the patient's tolerance to it and the presentation of adverse events. Copyright © 2014 Asociación Colombiana de Psiquiatría. Publicado por Elsevier España. All rights reserved.

  7. A "second generation" of ministry leadership.

    Science.gov (United States)

    Giammalvo, Peter J

    2005-01-01

    Catholic health care leaders differ from others in the field in that "they are expected to serve as Jesus served, teach as Jesus taught, and lead as Jesus led, in order to heal as Jesus healed." The Catholic health ministry today is led largely by laypeople-what might be called the "first generation" of lay leaders. This first generation was privileged in that it was tutored by and worked alongside women and men religious. Those religious are now mostly gone from the ministry, and that first generation of lay leaders will also be retiring in the not too distant future. Leadership will then pass to a "second generation," laypeople who have not worked alongside religious. How is this new generation to learn "to heal as Jesus healed"? Catholic Health East (CHE), Newtown Square, PA, has developed a program explicitly directed at the recruitment and development of second-generation leaders. In its efforts to fill a position, the system first assembles a preferred-candidate profile, based on 15 competencies, including seven core competencies. CHE then employs a recruitment process based on behavioral event interviewing. All involved stakeholders participate in the interviews.

  8. Emergency Department Visits Involving Misuse and Abuse of the Antipsychotic Quetiapine: Results from the Drug Abuse Warning Network (DAWN

    Directory of Open Access Journals (Sweden)

    Margaret E. Mattson

    2015-01-01

    Full Text Available Case reports in medical literature suggest that the atypical antipsychotic quetiapine, a medication not previously considered to have abuse potential, is now being subject to misuse and abuse (MUA; ie, taken when not prescribed for them or used in a way other than instructed by their health professional. Here we present systematic, nationally representative data from the 2005 to 2011 Drug Abuse Warning Network (DAWN for prevalence of emergency department (ED visits among the U.S. general population involving quetiapine and related to MUA, suicide attempts, and adverse reactions. Nationally, quetiapine-related ED visits increased 90% between 2005 and 2011, from 35,581 ED visits to 67,497. DAWN data indicate that when used without medical supervision for recreational/self-medication purposes, quetiapine poses health risks for its users, especially among polydrug users and women. These findings suggest that the medical and public health communities should increase vigilance concerning this drug and its potential for MUA.

  9. Effects of Antipsychotic Drugs Haloperidol and Clozapine on Visual Responses of Retinal Ganglion Cells in a Rat Model of Retinitis Pigmentosa.

    Science.gov (United States)

    Jensen, Ralph J

    2016-12-01

    In the P23H rat model of retinitis pigmentosa, the dopamine D2 receptor antagonists sulpiride and eticlopride appear to improve visual responses of retinal ganglion cells (RGCs) by increasing light sensitivity of RGCs and transforming abnormal, long-latency ON-center RGCs into OFF-center cells. Antipsychotic drugs are believed to mediate their therapeutic benefits by blocking D2 receptors. This investigation was conducted to test whether haloperidol (a typical antipsychotic drug) and clozapine (an atypical antipsychotic drug) could similarly alter the light responses of RGCs in the P23H rat retina. Extracellular recordings were made from RGCs in isolated P23H rat retinas. Responses of RGCs to flashes of light were evaluated before and during bath application of a drug. Both haloperidol and clozapine increased light sensitivity of RGCs on average by ∼0.3 log unit. For those ON-center RGCs that exhibit an abnormally long-latency response to the onset of a small spot of light, both haloperidol and clozapine brought out a short-latency OFF response and markedly reduced the long-latency ON response. The selective serotonin 5-HT2A antagonist MDL 100907 had similar effects on RGCs. The effects of haloperidol on light responses of RGCs can be explained by its D2 receptor antagonism. The effects of clozapine on light responses of RGCs on the other hand may largely be due to its 5-HT2A receptor antagonism. Overall, the results suggest that antipsychotic drugs may be useful in improving vision in patients with retinitis pigmentosa.

  10. Sixty Years of Placebo-Controlled Antipsychotic Drug Trials in Acute Schizophrenia: Systematic Review, Bayesian Meta-Analysis, and Meta-Regression of Efficacy Predictors.

    Science.gov (United States)

    Leucht, Stefan; Leucht, Claudia; Huhn, Maximilian; Chaimani, Anna; Mavridis, Dimitris; Helfer, Bartosz; Samara, Myrto; Rabaioli, Matteo; Bächer, Susanne; Cipriani, Andrea; Geddes, John R; Salanti, Georgia; Davis, John M

    2017-10-01

    Antipsychotic drug efficacy may have decreased over recent decades. The authors present a meta-analysis of all placebo-controlled trials in patients with acute exacerbations of schizophrenia, and they investigate which trial characteristics have changed over the years and which are moderators of drug-placebo efficacy differences. The search included multiple electronic databases. The outcomes were overall efficacy (primary outcome); responder and dropout rates; positive, negative, and depressive symptoms; quality of life; functioning; and major side effects. Potential moderators of efficacy were analyzed by meta-regression. The analysis included 167 double-blind randomized controlled trials with 28,102 mainly chronic participants. The standardized mean difference (SMD) for overall efficacy was 0.47 (95% credible interval 0.42, 0.51), but accounting for small-trial effects and publication bias reduced the SMD to 0.38. At least a "minimal" response occurred in 51% of the antipsychotic group versus 30% in the placebo group, and 23% versus 14% had a "good" response. Positive symptoms (SMD 0.45) improved more than negative symptoms (SMD 0.35) and depression (SMD 0.27). Quality of life (SMD 0.35) and functioning (SMD 0.34) improved even in the short term. Antipsychotics differed substantially in side effects. Of the response predictors analyzed, 16 trial characteristics changed over the decades. However, in a multivariable meta-regression, only industry sponsorship and increasing placebo response were significant moderators of effect sizes. Drug response remained stable over time. Approximately twice as many patients improved with antipsychotics as with placebo, but only a minority experienced a good response. Effect sizes were reduced by industry sponsorship and increasing placebo response, not decreasing drug response. Drug development may benefit from smaller samples but better-selected patients.

  11. The antipsychotic drug loxapine is an opener of the sodium-activated potassium channel slack (Slo2.2).

    Science.gov (United States)

    Biton, B; Sethuramanujam, S; Picchione, Kelly E; Bhattacharjee, A; Khessibi, N; Chesney, F; Lanneau, C; Curet, O; Avenet, P

    2012-03-01

    Sodium-activated potassium (K(Na)) channels have been suggested to set the resting potential, to modulate slow after-hyperpolarizations, and to control bursting behavior or spike frequency adaptation (Trends Neurosci 28:422-428, 2005). One of the genes that encodes K(Na) channels is called Slack (Kcnt1, Slo2.2). Studies found that Slack channels were highly expressed in nociceptive dorsal root ganglion neurons and modulated their firing frequency (J Neurosci 30:14165-14172, 2010). Therefore, Slack channel openers are of significant interest as putative analgesic drugs. We screened the library of pharmacologically active compounds with recombinant human Slack channels expressed in Chinese hamster ovary cells, by using rubidium efflux measurements with atomic absorption spectrometry. Riluzole at 500 μM was used as a reference agonist. The antipsychotic drug loxapine and the anthelmintic drug niclosamide were both found to activate Slack channels, which was confirmed by using manual patch-clamp analyses (EC(50) = 4.4 μM and EC(50) = 2.9 μM, respectively). Psychotropic drugs structurally related to loxapine were also evaluated in patch-clamp experiments, but none was found to be as active as loxapine. Loxapine properties were confirmed at the single-channel level with recombinant rat Slack channels. In dorsal root ganglion neurons, loxapine was found to behave as an opener of native K(Na) channels and to increase the rheobase of action potential. This study identifies new K(Na) channel pharmacological tools, which will be useful for further Slack channel investigations.

  12. Second generation PMR polyimide/fiber composites

    Science.gov (United States)

    Cavano, P. J.

    1979-01-01

    A second generation polymerization monomeric reactants (PMR) polyimdes matrix system (PMR 2) was characterized in both neat resin and composite form with two different graphite fiber reinforcements. Three different formulated molecular weight levels of laboratory prepared PMR 2 were examined, in addition to a purchased experimental fully formulated PMR 2 precurser solution. Isothermal aging of graphite fibers, neat resin samples and composite specimens in air at 316 C were investigated. Humidity exposures at 65 C and 97 percent relative humidity were conducted for both neat resin and composites for eight day periods. Anaerobic char of neat resin and fire testing of composites were conducted with PMR 15, PMR 2, and an epoxy system. Composites were fire tested on a burner rig developed for this program. Results indicate that neat PMR 2 resins exhibit excellent isothermal resistance and that PMR 2 composite properties appear to be influenced by the thermo-oxidative stability of the reinforcing fiber.

  13. Progress toward Brazilian cesium fountain second generation

    Science.gov (United States)

    Bueno, Caio; Rodriguez Salas, Andrés; Torres Müller, Stella; Bagnato, Vanderlei Salvador; Varela Magalhães, Daniel

    2018-03-01

    The operation of a Cesium fountain primary frequency standard is strongly influenced by the characteristics of two important subsystems. The first is a stable frequency reference and the second is the frequency-transfer system. A stable standard frequency reference is key factor for experiments that require high accuracy and precision. The frequency stability of this reference has a significant impact on the procedures for evaluating certain systematic biases in frequency standards. This paper presents the second generation of the Brazilian Cesium Fountain (Br-CsF) through the opto-mechanical assembly and vacuum chamber to trap atoms. We used a squared section glass profile to build the region where the atoms are trapped and colled by magneto-optical technique. The opto-mechanical system was reduced to increase stability and robustness. This newest Atomic Fountain is essential to contribute with time and frequency development in metrology systems.

  14. AC application of second generation HTS wire

    Science.gov (United States)

    Thieme, C. L. H.; Gagnon, K.; Voccio, J.; Aized, D.; Claassen, J.

    2008-02-01

    For the production of Second Generation (2G) YBCO High Temperature Superconductor wire American Superconductor uses a wide-strip MOD-YBCO/RABiTSTM process, a low-cost approach for commercial manufacturing. It can be engineered with a high degree of flexibility to manufacture practical 2G conductors with architectures and properties tailored for specific applications and operating conditions. For ac applications conductor and coil design can be geared towards low hysteretic losses. For applications which experience high frequency ac fields, the stabilizer needs to be adjusted for low eddy current losses. For these applications a stainless-steel laminate is used. An example is a Low Pass Filter Inductor which was developed and built in this work.

  15. sigma opiates and certain antipsychotic drugs mutually inhibit (+)-[3H]SKF 10,047 and [3H]haloperidol binding in guinea pig brain membranes

    International Nuclear Information System (INIS)

    Tam, S.W.; Cook, L.

    1984-01-01

    The relationship between binding of antipsychotic drugs and sigma psychotomimetic opiates to binding sites for the sigma agonist (+)-[ 3 H]SKF 10,047 (N-allylnormetazocine) and to dopamine D 2 sites was investigated. In guinea pig brain membranes, (+)-[ 3 H]SKF 10,047 bound to single class of sites with a K/sub d/ of 4 x 10 -8 M and a B/sub max/ of 333 fmol/mg of protein. This binding was different from μ, kappa, or delta opiate receptor binding. It was inhibited by opiates that produce psychotomimetic activities but not by opiates that lack such activities. Some antipsychotic drugs inhibited (+)-[ 3 H]SKF 10,047 binding with high to moderate affinities in the following order of potency: haloperidol > perphenazine > fluphenazine > acetophenazine > trifluoperazine > molindone greater than or equal to pimozide greater than or equal to thioridazine greater than or equal to chlorpromazine greater than or equal to triflupromazine. However, there were other antipsychotic drugs such as spiperone and clozapine that showed low affinity for the (+)-[ 3 H]SKF 10,047 binding sites. Affinities of antipsychotic drugs for (+)-[ 3 H]SKF 10,047 binding sites did not correlate with those for [ 3 H]spiperone (dopamine D 2 ) sites. [ 3 H]-Haloperidol binding in whole brain membranes was also inhibited by the sigma opiates pentazocine, cyclazocine, and (+)-[ 3 H]SKF 10,047. In the striatum, about half of the saturable [ 3 H]haloperidol binding was to [ 3 H]spiperone (D 2 ) sites and the other half was to sites similar to (+)-[ 3 H]SKF 10,047 binding sites. 15 references, 4 figures, 1 table

  16. Screening of cardiovascular risk factors in patients with schizophrenia and patients treated with antipsychotic drugs: are we equally exhaustive as with the general population?

    Science.gov (United States)

    Castillo-Sánchez, Miguel; Fàbregas-Escurriola, Mireia; Bergè-Baquero, Daniel; Fernández-SanMartín, MªIsabel; Goday-Arno, Albert

    2017-01-01

    Many studies have previously shown increased cardiovascular risk factors related to schizophrenia independently from the use of antipsychotic drugs. However, a poorer effort in clinical detection and management of cardiovascular risk in patients with severe mental illness could also explain these results. To test this hypothesis, we analyzed the differences in screening and incidence of cardiovascular risk factors between schizophrenia, non-schizophrenic patients on treatment with antipsychotic drugs (NS-TAD) and the general population. Data from adult subjects assessed by high-quality register general practitioners from 2006 to 2011 were extracted from the Catalonian SIDIAP database. The schizophrenia, NS-TAD, and control groups were compared in terms of measurements and incidence of diabetes, dyslipidemia, obesity, hypertension, and smoking. A total of 4911 patients in the schizophrenia group, 4157 in NS-TAD group, and 98644 in the control group were included. Schizophrenia patients were screened for dyslipidemia and diabetes more frequently than the control group, while for obesity or hypertension, they were screened equal to controls. Also, as compared to the control group, the NS-TAD group was more frequently screened for obesity with no differences in dyslipidemia and diabetes and less frequently for hypertension. Smoking was less frequently screened in both study groups. The incidence of all risk factors studied in both study groups was higher than or equal to the control group, except for hypertension, which had lower incidence. The lack of screening of risk factors does not appear decisive in the increased cardiovascular risk of patients diagnosed with schizophrenia seen in primary care. Studies evaluating the possible under diagnosis of the risk factors are required. Schizophrenia (SZ); Treatment with antipsychotic drugs (TAD); Cardiovascular risk factor/s (CVRF); Without schizophrenia but on therapy with antipsychotic drugs (NS-TAD); Defined Daily Dose

  17. Serum total homocystein, folate and vitamin B12 levels and their correlation with antipsychotic drug doses in adult male patients with chronic schizophrenia.

    Science.gov (United States)

    Eren, Esin; Yeğin, Ayşenur; Yilmaz, Necat; Herken, Hasan

    2010-01-01

    Elevated blood levels of homocysteine (hCY) have been associated with schizophrenic male patients. However, controversy remains regarding the association between lowered plasma folate and vitamin B12, hyperhomocysteinemia, and schizophrenia. Sixty-six (66) male patients with chronic schizophrenia were investigated to test the hypotheses that alterations in Hcy, folate, and vitamin B12 levels might be related to the antipsychotic drug doses used in treatment. Serum total homocysteine, folic acid, and vitamin B12 levels were determined by chemiluminescence methods in both patients and control subjects. The patients were grouped according to the antipsychotic drug doses used in their treatment. Patients had higher homocysteine levels but they did not differ from controls in terms of folate and vitamin B12 levels. On the other hand, only folate levels were negatively correlated in the patient group treated with higher therapeutic doses of chlorpromazine equivalents (> 400 mg/day) compared to the patient group with lower doses (< 400 mg/day). Our findings show that higher typical antipsychotic drugs may play a role as modifiying factor for folate metabolism in chronic schizoprenic male patients.

  18. Some novelties and recommendations by swithing antipsychotics

    Directory of Open Access Journals (Sweden)

    Nika Aleksandra Kravos

    2014-11-01

    Full Text Available Clinical outcome of patients with severe mental disorders treated with antipsychotics depends on individual response to therapy, adverse events, physical health, maintaining of physical health and of the patient’s, interpersonal (patient - therapist, health and environmental features. Replacement of antipsychotics is a common therapeutic measure. The response depends on mostly unknown genetic factors, physiological particularities of the patient and its variations. This article summarizes the most important and the most recent pharmacological properties and consequences of cross-action of antipsychotics. It specifies the basic rules and ways of replacing antipsychotic drugs in different clinical situations, and summarizes alerts, recommendations and suggestions when changing antipsychotics.

  19. Proline-induced changes in acetylcholinesterase activity and gene expression in zebrafish brain: reversal by antipsychotic drugs.

    Science.gov (United States)

    Savio, L E B; Vuaden, F C; Kist, L W; Pereira, T C; Rosemberg, D B; Bogo, M R; Bonan, C D; Wyse, A T S

    2013-10-10

    Hyperprolinemia is an inherited disorder of proline metabolism and hyperprolinemic patients can present neurological manifestations, such as seizures, cognitive dysfunctions, and schizoaffective disorders. However, the mechanisms related to these symptoms are still unclear. In the present study, we evaluated the in vivo and in vitro effects of proline on acetylcholinesterase (AChE) activity and gene expression in the zebrafish brain. For the in vivo studies, animals were exposed at two proline concentrations (1.5 and 3.0mM) during 1h or 7 days (short- or long-term treatments, respectively). For the in vitro assays, different proline concentrations (ranging from 3.0 to 1000 μM) were tested. Long-term proline exposures significantly increased AChE activity for both treated groups when compared to the control (34% and 39%). Moreover, the proline-induced increase on AChE activity was completely reverted by acute administration of antipsychotic drugs (haloperidol and sulpiride), as well as the changes induced in ache expression. When assessed in vitro, proline did not promote significant changes in AChE activity. Altogether, these data indicate that the enzyme responsible for the control of acetylcholine levels might be altered after proline exposure in the adult zebrafish. These findings contribute for better understanding of the pathophysiology of hyperprolinemia and might reinforce the use of the zebrafish as a complementary vertebrate model for studying inborn errors of amino acid metabolism. Copyright © 2013 IBRO. Published by Elsevier Ltd. All rights reserved.

  20. Methodology toward second generation expert systems

    International Nuclear Information System (INIS)

    Dormoy, J.L.

    1989-01-01

    So-called First Generation Expert Systems were aimed at capturing the expert's know-how. Though providing remarkable achievements, this first wave did not give the expected outcome. A new generation is getting out from the laboratories. Instead of remaining at a shallow level of knowledge - that is the unmotivated reasoning processes expressed by an expert when he is forced to tell them - one attempts to re-build this level of knowledge from the first principles which constitute the basis of an expert's knowledge. These systems are called deep knowledge-based, or second generation expert systems. Discussion in the three first parts rests on two examples: A first generation and a half system for process control in nuclear powers plants, than the system EXTRA for alarm processing in nuclear plants, wherein fonctional knowledge is explicitely represented. We show how deep knowledge can be implemented, and the advantages that can be expected from this methodology. Qualitative Physics is discussed in the next part. Future research developments as well as potential payoffs are mentioned [fr

  1. Quetiapine versus other atypical antipsychotics for schizophrenia

    Science.gov (United States)

    Komossa, Katja; Rummel-Kluge, Christine; Schmid, Franziska; Hunger, Heike; Schwarz, Sandra; Srisurapanont, Manit; Kissling, Werner; Leucht, Stefan

    2014-01-01

    Background In many countries of the industrialised world second generation (’atypical’) antipsychotic drugs have become the first line drug treatment for people with schizophrenia. It is not clear how the effects of the various second generation antipsychotic drugs differ. Objectives To evaluate the effects of quetiapine compared with other second generation antipsychotic drugs for people with schizophrenia and schizophrenia-like psychosis. Search methods We searched the Cochrane Schizophrenia Group Trials Register (April 2007), inspected references of all identified studies, and contacted relevant pharmaceutical companies, drug approval agencies and authors of trials for additional information. Selection criteria We included all randomised control trials comparing oral quetiapine with oral forms of amisulpride, aripiprazole, clozapine, olanzapine, risperidone, sertindole, ziprasidone or zotepine in people with schizophrenia or schizophrenia-like psychosis. Data collection and analysis We extracted data independently. For dichotomous data we calculated relative risks (RR) and their 95% confidence intervals (CI) on an intention-to-treat basis based on a random-effects model. We calculated numbers needed to treat/harm (NNT/NNH) where appropriate. For continuous data, we calculated weighted mean differences (WMD) again based on a random-effects model. Main results The review currently includes 21 randomised control trials (RCTs) with 4101 participants. These trials provided data on four comparisons - quetiapine versus clozapine, olanzapine, risperidone or ziprasidone. A major limitation to all findings is the high number of participants leaving studies prematurely (57.6%) and the substantial risk of biases in studies. Efficacy data favoured olanzapine and risperidone compared with quetiapine (PANSS total score versus olanzapine:10 RCTs, n=1449, WMD 3.66 CI 1.93 to 5.39; versus risperidone: 9 RCTs, n=1953, WMD 3.09 CI 1.01 to 5.16), but clinical meaning is unclear

  2. Detection of the antipsychotic drug quetiapine in the blood, urine and hair samples of the victim of a drug-facilitated sexual assault

    DEFF Research Database (Denmark)

    Johansen, Sys Stybe

    2017-01-01

    A drug rape facilitated with the sedative antipsychotic drug quetiapine is presented here. A teenage girl and her girlfriend went to the home of an adult couple they had met at a bar. Here, the teenage girl (victim) felt tired after consuming some alcoholic drinks and fell asleep. While she......-three hours after the suspected drug-facilitated sexual assault (DFSA), blood and urine samples were collected and the initial toxicological screening detected quetiapine. Confirmation and quantification by ultra high performance liquid chromatography coupled to tandem mass spectrometry (UHPLC-MS/MS) revealed...... a concentration of 0.007mg/kg quetiapine in blood and 0.19mg/l in urine. Six months after the DFSA, a hair sample was collected and segmental hair analysis was performed on four washed segments (0-3cm, 3-5cm, 5-7cm, and 7-9cm). The last segment contained 0.011ng/mg of quetiapine, whereas the other segments were...

  3. Pharmacotherapy of schizophrenic patients: preponderance of off-label drug use.

    Directory of Open Access Journals (Sweden)

    David Pickar

    Full Text Available Multiple drug class combinations are often prescribed for the treatment of schizophrenia, although antipsychotic monotherapy reflects FDA labeling and scientific justification for combinations is highly variable. This study was performed to gain current data regarding drug treatment of schizophrenia as practiced in the community and to assess the frequencies of off-label drug class combinations. 200 DSM IV-diagnosed schizophrenic patients recruited from community treatment sources participated in this cross-sectional study of community based schizophrenic patients. Drug class categories include First and Second Generation Antipsychotic drugs (FGA and SGA, respectively, mood stabilizers, antidepressants and anti-anxiety drugs. 25.5% of patients received antipsychotic monotherapy; 70% of patients received an antipsychotic and another drug class. A total of 42.5% of patients received more than one antipsychotic drug. The most common drug class combination was antipsychotic and a mood stabilizer. Stepwise linear discriminant function analysis identified the diagnosis of schizoaffective schizophrenia, history of having physically hurt someone and high scores on the General Portion of the PANSS rating scale predicted the combined use of an antipsychotic drug and a mood stabilizer. "Real world" pharmacotherapy of schizophrenia has developed its own established practice that is predominantly off-label and may have outstripped current data support. The economic implications for public sector payers are substantial as well as for the revenue of the pharmaceutical industry, whose promotion of off-label drug use is an increasingly problematic. These data are consistent with the recognition of the therapeutic limitations of both first and second generation antipsychotic drugs.

  4. Differential effects of antipsychotic drugs on insight in first episode schizophrenia: Data from the European First-Episode Schizophrenia Trial (EUFEST).

    Science.gov (United States)

    Pijnenborg, G H M; Timmerman, M E; Derks, E M; Fleischhacker, W W; Kahn, R S; Aleman, A

    2015-06-01

    Although antipsychotics are widely prescribed, their effect of on improving poor illness insight in schizophrenia has seldom been investigated and therefore remains uncertain. This paper examines the effects of low dose haloperidol, amisulpride, olanzapine, quetiapine, and ziprasidone on insight in first-episode schizophrenia, schizoaffective disorder, or schizophreniform disorder. The effects of five antipsychotic drugs in first episode psychosis on insight were compared in a large scale open randomized controlled trial conducted in 14 European countries: the European First-Episode Schizophrenia Trial (EUFEST). Patients with at least minimal impairments in insight were included in the present study (n=455). Insight was assessed with item G12 of the Positive and Negative Syndrome Scale (PANSS), administered at baseline and at 1, 3, 6, 9, and 12 months after randomization. The use of antipsychotics was associated with clear improvements in insight over and above improvements in other symptoms. This effect was most pronounced in the first three months of treatment, with quetiapine being significantly less effective than other drugs. Effects of spontaneous improvement cannot be ruled out due to the lack of a placebo control group, although such a large spontaneous improvement of insight would seem unlikely. Copyright © 2015 Elsevier B.V. and ECNP. All rights reserved.

  5. Atypical antipsychotics induce both proinflammatory and adipogenic gene expression in human adipocytes in vitro.

    Science.gov (United States)

    Sárvári, Anitta K; Veréb, Zoltán; Uray, Iván P; Fésüs, László; Balajthy, Zoltán

    2014-08-08

    Schizophrenia requires lifelong treatment, potentially causing systemic changes in metabolic homeostasis. In the clinical setting, antipsychotic treatment may differentially lead to weight gain among individual patients, although the molecular determinants of such adverse effects are currently unknown. In this study, we investigated changes in the expression levels of critical regulatory genes of adipogenesis, lipid metabolism and proinflammatory genes during the differentiation of primary human adipose-derived stem cells (ADSCs). These cells were isolated from patients with body mass indices <25 and treated with the second-generation antipsychotics olanzapine, ziprasidone, clozapine, quetiapine, aripiprazole and risperidone and the first-generation antipsychotic haloperidol. We found that antipsychotics exhibited a marked effect on key genes involved in the regulation of cell cycle, signal transduction, transcription factors, nuclear receptors, differentiation markers and metabolic enzymes. In particular, we observed an induction of the transcription factor NF-KB1 and NF-KB1 target genes in adipocytes in response to these drugs, including the proinflammatory cytokines TNF-α, IL-1β, IL-8 and MCP-1. In addition, enhanced secretion of both IL8 and MCP-1 was observed in the supernatant of these cell cultures. In addition to their remarkable stimulatory effects on proinflammatory gene transcription, three of the most frequently prescribed antipsychotic drugs, clozapine, quetiapine and aripiprazole, also induced the expression of essential adipocyte differentiation genes and the adipocyte hormones leptin and adiponectin, suggesting that both glucose and fat metabolism may be affected by these drugs. These data further suggest that antipsychotic treatments in patients alter the gene expression patterns in adipocytes in a coordinated fashion and priming them for a low-level inflammatory state. Copyright © 2014 Elsevier Inc. All rights reserved.

  6. Brain Targeting of a Water Insoluble Antipsychotic Drug Haloperidol via the Intranasal Route Using PAMAM Dendrimer.

    Science.gov (United States)

    Katare, Yogesh K; Daya, Ritesh P; Sookram Gray, Christal; Luckham, Roger E; Bhandari, Jayant; Chauhan, Abhay S; Mishra, Ram K

    2015-09-08

    Delivery of therapeutics to the brain is challenging because many organic molecules have inadequate aqueous solubility and limited bioavailability. We investigated the efficiency of a dendrimer-based formulation of a poorly aqueous soluble drug, haloperidol, in targeting the brain via intranasal and intraperitoneal administration. Aqueous solubility of haloperidol was increased by more than 100-fold in the developed formulation. Formulation was assessed via different routes of administration for behavioral (cataleptic and locomotor) responses, and for haloperidol distribution in plasma and brain tissues. Dendrimer-based formulation showed significantly higher distribution of haloperidol in the brain and plasma compared to a control formulation of haloperidol administered via intraperitoneal injection. Additionally, 6.7 times lower doses of the dendrimer-haloperidol formulation administered via the intranasal route produced behavioral responses that were comparable to those induced by haloperidol formulations administered via intraperitoneal injection. This study demonstrates the potential of dendrimer in improving the delivery of water insoluble drugs to brain.

  7. The sonic window: second generation results

    Science.gov (United States)

    Walker, William F.; Fuller, Michael I.; Brush, Edward V.; Eames, Matthew D. C.; Owen, Kevin; Ranganathan, Karthik; Blalock, Travis N.; Hossack, John A.

    2006-03-01

    Medical Ultrasound Imaging is widely used clinically because of its relatively low cost, portability, lack of ionizing radiation, and real-time nature. However, even with these advantages ultrasound has failed to permeate the broad array of clinical applications where its use could be of value. A prime example of this untapped potential is the routine use of ultrasound to guide intravenous access. In this particular application existing systems lack the required portability, low cost, and ease-of-use required for widespread acceptance. Our team has been working for a number of years to develop an extremely low-cost, pocket-sized, and intuitive ultrasound imaging system that we refer to as the "Sonic Window." We have previously described the first generation Sonic Window prototype that was a bench-top device using a 1024 element, fully populated array operating at a center frequency of 3.3 MHz. Through a high degree of custom front-end integration combined with multiplexing down to a 2 channel PC based digitizer this system acquired a full set of RF data over a course of 512 transmit events. While initial results were encouraging, this system exhibited limitations resulting from low SNR, relatively coarse array sampling, and relatively slow data acquisition. We have recently begun assembling a second-generation Sonic Window system. This system uses a 3600 element fully sampled array operating at 5.0 MHz with a 300 micron element pitch. This system extends the integration of the first generation system to include front-end protection, pre-amplification, a programmable bandpass filter, four sample and holds, and four A/D converters for all 3600 channels in a set of custom integrated circuits with a combined area smaller than the 1.8 x 1.8 cm footprint of the transducer array. We present initial results from this front-end and present benchmark results from a software beamformer implemented on the Analog Devices BF-561 DSP. We discuss our immediate plans for further

  8. A second-generation supersonic transport

    Science.gov (United States)

    Humphrey, W.; Grayson, G.; Gump, J.; Hutko, G.; Kubicko, R.; Obrien, J.; Orndorff, R.; Oscher, R.; Polster, M.; Ulrich, C.

    1989-01-01

    already existing technology. This is of particular importance with respect to support technology such as airport terminals and runways. Based on the above introductory remarks, a possible approach to the design of a second-generation supersonic civil transport is presented here. The design Mach number for this aircraft is 3.5. This value was chosen as it represents the limiting Mach number in the absence of active cooling. The ensuing design attempts to deal with the particular problems that are the most demanding, while relying on proven technology where it is adequate. The report clearly does not solve, or even deal with, every aspect of the aircraft design. Rather, a general direction is suggested and supported with initial, approximate calculations.

  9. Antipsychotics and physical attractiveness.

    Science.gov (United States)

    Seeman, Mary V

    2011-10-01

    Antipsychotics are effective in treating the symptoms of schizophrenia, but they may induce adverse effects, some of which-those that impact negatively on physical appearance-have not been sufficiently discussed in the psychiatric literature. Through a narrative review, to catalog antipsychotic side effects that interfere with physical attractiveness and to suggest ways of addressing them. PubMed databases were searched for information on the association between "antipsychotic side effects" and "attractiveness" using those two search phrases plus the following terms: "weight," "teeth," "skin," "hair," "eyes," "gait," "voice," "odor." Data from relevant qualitative and quantitative articles were considered, contextualized, and summarized. Antipsychotics, as a group, increase weight and may lead to dry mouth and bad breath, cataracts, hirsutism, acne, and voice changes; they may disturb symmetry of gait and heighten the risk for tics and spasms and incontinence, potentially undermining a person's attractiveness. Clinicians need to be aware of the impact of therapeutic drugs on appearance and how important this issue is to patients. Early in treatment, they need to plan preventive and therapeutic strategies.

  10. A preliminary investigation of alpha-lipoic acid treatment of antipsychotic drug-induced weight gain in patients with schizophrenia.

    Science.gov (United States)

    Kim, Eosu; Park, Dong-Wha; Choi, Song-Hee; Kim, Jae-Jin; Cho, Hyun-Sang

    2008-04-01

    Weight gain and other metabolic disturbances have now become discouraging, major side effects of atypical antipsychotic drugs (AAPDs). The novel strategies required to counteract these serious consequences, however, should avoid modulating the activities of the neurotransmitter receptors involved because those receptors are the therapeutic targets of AAPDs. Adenosine monophosphate-activated protein kinase is an enzyme that plays a pivotal role in energy homeostasis. We hypothesized that alpha-lipoic acid (ALA), which is known to modulate adenosine monophosphate-activated protein kinase activity in the hypothalamus and peripheral tissues, would ameliorate AAPD-induced weight gain. We describe the case series of a 12-week ALA trial in schizophrenia patients treated with AAPDs. Two of 7 enrolled subjects were dropped from the study because of noncompliance and demand for new medication to treat depressive symptoms, respectively. The mean (SD) weight loss was 3.16 (3.20) kg (P = 0.043, last observation carried forward; median, 3.03 kg; range, 0-8.85 kg). On average, body mass index showed a significant reduction (P = 0.028) over the 12 weeks. During the same period, a statistically significant reduction was also observed in total cholesterol levels (P = 0.042), and there was a weak trend toward the reduction in insulin resistance (homeostasis model assessment of insulin resistance) (P = 0.080). Three subjects reported increased energy subjectively. The total scores on the Brief Psychiatric Rating Scale and the Montgomery-Asberg Depression Rating Scale did not vary significantly during the study. These preliminary data suggest the possibility that ALA can ameliorate the adverse metabolic effects induced by AAPDs. To confirm the benefits of ALA, more extended study is warranted.

  11. Impact of depression and social support on nonadherence to antipsychotic drugs in persons with schizophrenia in Thailand

    Directory of Open Access Journals (Sweden)

    Sirijit Suttajit

    2010-09-01

    Full Text Available Sirijit Suttajit, Sutrak PilakantaDepartment of Psychiatry, Faculty of Medicine, Chiang Mai University, Chiang Mai, ThailandBackground: Little is known about the effect of social support on nonadherence in persons with schizophrenia, especially in developing Asian countries where social support is considered to be imperative. Additionally, the role of depression as a mediator in the association between social support deficits and nonadherence has not been evaluated.Methods: This was a cross-sectional study conducted in 75 participants at a university hospital in Thailand. Logistic regression was used to determine whether depression and a deficit in social support were associated with nonadherence, and whether depression mediated this association.Results: There were strong relationships between nonadherence and major depressive episodes (odds ratio [OR] 9.5, confidence interval [CI] 2.3–38.9, living alone (OR 21.8, CI 3.5–143.0, and dissatisfaction with support from family (OR 10.0, CI 1.9–53.1. The OR of the association between social support deficits and nonadherence decreased by nearly one half after adjusting for depression.Discussion: Depression and social support deficits were significantly associated with nonadherence in persons with schizophrenia. Depression is important in mediating the association between social support deficits and nonadherence. Enhancing social support, as well as early detection and effective intervention for depression should be emphasized in interventions to improve adherence in persons with schizophrenia.Keywords: nonadherence, schizophrenia, depression, social support, antipsychotic drugs

  12. The use of random-effects models to identify health care center-related characteristics modifying the effect of antipsychotic drugs

    Directory of Open Access Journals (Sweden)

    Nordon C

    2017-12-01

    Full Text Available Clementine Nordon,1 Constance Battin,1 Helene Verdoux,2 Josef Maria Haro,3 Mark Belger,4 Lucien Abenhaim,1 Tjeerd Pieter van Staa5 On behalf of the IMI GetReal WP2 Group 1Epidemiological Research, Analytica LASER, Paris, 2Population Health Research Center, Team Pharmaco-Epidemiology, UMR 1219, Bordeaux-2 University, INSERM, Bordeaux, France; 3Parc Sanitari Sant Joan de Deu, CIBERSAM, University of Barcelona, Barcelona, Spain; 4Eli Lilly and Company Limited, Erl Wood Manor, Windlesham, 5Farr Institute, University of Manchester, Manchester, UK Purpose: A case study was conducted, exploring methods to identify drugs effects modifiers, at a health care center level.Patients and methods: Data were drawn from the Schizophrenia Outpatient Health Outcome cohort, including hierarchical information on 6641 patients, recruited from 899 health care centers from across ten European countries. Center-level characteristics included the following: psychiatrist’s gender, age, length of practice experience, practice setting and type, countries’ Healthcare System Efficiency score, and psychiatrist density in the country. Mixed multivariable linear regression models were used: 1 to estimate antipsychotic drugs’ effectiveness (defined as the association between patients’ outcome at 3 months – dependent variable, continuous – and antipsychotic drug initiation at baseline – drug A vs other antipsychotic drug; 2 to estimate the similarity between clustered data (using the intra-cluster correlation coefficient; and 3 to explore antipsychotic drug effects modification by center-related characteristics (using the addition of an interaction term.Results: About 23% of the variance found for patients’ outcome was explained by unmeasured confounding at a center level. Psychiatrists’ practice experience was found to be associated with patient outcomes (p=0.04 and modified the relative effect of “drug A” (p<0.001, independent of center- or patient

  13. Animal behavior models of the mechanisms underlying antipsychotic atypicality.

    NARCIS (Netherlands)

    Geyer, M.A.; Ellenbroek, B.A.

    2003-01-01

    This review describes the animal behavior models that provide insight into the mechanisms underlying the critical differences between the actions of typical vs. atypical antipsychotic drugs. Although many of these models are capable of differentiating between antipsychotic and other psychotropic

  14. 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

    Directory of Open Access Journals (Sweden)

    Bobo William V

    2011-11-01

    Full Text Available Abstract 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.

  15. Do patients with paranoid and disorganized schizophrenia respond differently to antipsychotic drugs?

    Science.gov (United States)

    Corves, C; Engel, R R; Davis, J; Leucht, S

    2014-07-01

    The aim of this study was to compare the differential response to amisulpride in patients with paranoid versus disorganized schizophrenia. We reanalyzed the original data from five different randomized drug trials comparing Brief Psychiatric Rating Scale (BPRS) scores in a database containing 427 paranoid and 296 disorganized patients with schizophrenia. Both the disorganized and the paranoid group showed a substantial improvement of the BPRS total score within the first 4 weeks. In the paranoid group, mean (±SD) BPRS reduction was 16.9 (±14.6) (t = 24.06, df = 426, P Paranoid patients improved by 4.8 BPRS points more than disorganized patients (adjusted means 18.90 (CI = 17.33-20.37) for the paranoid and 14.1 (CI = 12.04 - 16.11) for the disorganized group. We conclude that amisulpride is effective in disorganized as well as in paranoid schizophrenia, but that symptom reduction in the disorganized subtype is less pronounced. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  16. The second generation of biofuels aims at 2015; La seconde generation de biocarburants vise 2015

    Energy Technology Data Exchange (ETDEWEB)

    Orliac, A

    2008-12-15

    Research work is intensifying on the second generation of biofuels in order to optimize the processes and to reduce the production costs. Poorly valorized vegetable resources are targeted in order to avoid conflicts with other agricultural processes. Two ways are explored since several years: the biological way (bio-ethanol) and the thermochemical way (bio-diesel). So far, no method allows to recover oils with a satisfactory energy efficiency but several pilot-plants are under study or already in operation (Futurol, BTL (biomass-to-liquid)..). Short paper. (J.S.)

  17. Zotepine versus other atypical antipsychotics for schizophrenia

    Science.gov (United States)

    Subramanian, Selvizhi; Rummel-Kluge, Christine; Hunger, Heike; Schmid, Franziska; Schwarz, Sandra; Kissling, Werner; Leucht, Stefan; Komossa, Katja

    2014-01-01

    Background In many parts of the world, particularly in industrialised countries, second generation (atypical) antipsychotic drugs have become first line treatment for people suffering from schizophrenia. The question as to whether the effects of various second generation antipsychotic drugs differ is a matter of debate. Objectives To evaluate the effects of zotepine compared with other second generation antipsychotic drugs for people suffering from schizophrenia and schizophrenia-like psychoses. Search methods We searched the Cochrane Schizophrenia Group Trials Register (November 2009), inspected references of all identified studies for further trials and contacted authors of trials for additional information. Selection criteria We included only randomised clinical controlled trials that compared zotepine with any forms of amisulpride, aripiprazole, clozapine, olanzapine, risperidone, sertindole or ziprasidone in people suffering from only schizophrenia or schizophrenia-like psychoses. Data collection and analysis SS and KK extracted data independently. For dichotomous data we calculated relative risks (RR) and their 95% confidence intervals (CI) on an intention-to-treat basis based on a random-effects model. For continuous data, we calculated weighted mean differences (MD) again based on a random-effects model. Main results We included three studies (total n=289; 2 RCTs zotepine vs clozapine; 1 RCT zotepine vs clozapine vs risperidone (at 4 mg, 8 mg doses) vs remoxipride. All studies were of limited methodological quality. When zotepine was compared with clozapine, it was clozapine that was found to be more effective in terms of global state (n=59, 1 RCT, RR No clinically significant response 8.23 CI 1.14 to 59.17). Mental state scores also favoured clozapine (n=59, 1 RCT, MD average score (BPRS total, high = poor) 6.00 CI 2.17 to 9.83) and there was less use of antiparkinson medication in the clozapine group (n=116, 2 RCTs, RR 20.96 CI 2.89 to 151.90). In the

  18. Changes in antipsychotics and other psychotropic drugs during a 30-month lifestyle intervention among outpatients with schizophrenia

    DEFF Research Database (Denmark)

    Hojlund, Mikkel; Elliott, Anja Friis; Madsen, Nikolaj Juul

    2017-01-01

    BACKGROUND: Patients with schizophrenia have high risk of early death from diabetes and cardiovascular diseases, partly because of poor lifestyle and partly because of long-lasting exposure to antipsychotic treatment. AIMS: To investigate the influence of a lifestyle intervention program on chang...

  19. In vivo serial invasive imaging of the second-generation drug-eluting absorbable metal scaffold (Magmaris - DREAMS 2G) in de novo coronary lesions: Insights from the BIOSOLVE-II First-In-Man Trial.

    Science.gov (United States)

    Garcia-Garcia, Hector M; Haude, Michael; Kuku, Kayode; Hideo-Kajita, Alexandre; Ince, Hüseyin; Abizaid, Alexandre; Tölg, Ralph; Lemos, Pedro Alves; von Birgelen, Clemens; Christiansen, Evald Høj; Wijns, William; Escaned, Javier; Dijkstra, Jouke; Waksman, Ron

    2018-03-15

    Bioresorbable scaffolds may confer clinical benefit in long-term studies; early mechanistic studies using intravascular imaging have provided insightful information about the immediate and mid-term local serial effects of BRS on the coronary vessel wall. We assessed baseline, 6- and 12-month imaging data of the drug-eluting absorbable metal scaffold (DREAMS 2G). The international, first-in-man BIOSOLVE-II trial enrolled 123 patients with up to 2 de novo lesions (in vessels of 2.2 to 3.7mm). Angiographic based vasomotion, curvature and angulation were assessed; intravascular ultrasound (IVUS) derived radiofrequency (RF) data analysis and echogenicity were evaluated; optical coherence tomography (OCT) attenuation and backscattering analysis were also performed. There was hardly any difference in curvature between pre-procedure and 12months (-0.0019; p=0.48). The change in angulation from pre- to 12months was negligible (-3.58°; 95% CI [-5.97, -1.20]), but statistically significant. At 6months, the change in QCA based minimum lumen diameter in response to high dose of acetylcholine and IVUS-RF necrotic core percentage showed an inverse relationship (estimate of -0.489; p=0.055) and with fibrous volume a positive relationship (estimate of 0.53, p=0.035). Bioresorption analysis by OCT showed that the maximum attenuation values decreased significantly from post-procedure at 6months (Δ 6months vs. post-proc. is -13.5 [95% CI -14.6, -12.4]) and at 12months (Δ 12months vs. post-proc. is -14.0 [95% CI -15.4, -12.6]). By radiofrequency data, the percentage of dense calcium decreased significantly from post-procedure at 6months and at 12months. Likewise, by echogenicity, hyperechogenic structures decreased significantly from post-procedure at 6months; thereafter, they remained unchanged. Following implantation of DREAMS 2G, restoration of the vessel geometry, vasomotion and bioresorption signs were observed at up to 12months; importantly, these changes occurred with

  20. Paliperidone extended-release: does it have a place in antipsychotic therapy?

    Directory of Open Access Journals (Sweden)

    Carlos Schönfeldt-Lecuona

    2011-03-01

    Full Text Available Maximilian Gahr1,*, Markus A Kölle1,*, Carlos Schönfeldt-Lecuona1, Peter Lepping2, Roland W Freudenmann11Department of Psychiatry and Psychotherapy, University of Ulm, Ulm, Germany; 2Department of Psychiatry, Glyndwr University, Wales, UK *Both authors contributed equally and their order was determined by coin toss.Abstract: Paliperidone (9-hydroxy-risperidone, the active metabolite of risperidone, was approved for treating schizophrenia worldwide in 2006 as paliperidone extended-release (PER, and became the first second-generation antipsychotic specifically licensed for treating schizoaffective disorder in 2009. However, at the same time, its comparatively high cost gave rise to concerns about the cost-effectiveness of PER as compared with its precursor, risperidone. This paper reviews the existing knowledge of the pharmacology, kinetics, efficacy, tolerability, and fields of application of PER, and compares PER with risperidone in order to determine whether it has a place in antipsychotic therapy. An independent assessment of all relevant publications on PER published until July 2010 was undertaken. PER has a unique pharmacological profile, including single dosing, predominantly renal excretion, low drug–drug interaction risk, and differs from risperidone in terms of mode of action and pharmacokinetics. High-level evidence suggests that PER is efficacious and safe in schizophrenia, schizoaffective disorder, and acute manic episodes. There is a striking lack of published head-to-head comparisons between PER and risperidone, irrespective of indication. Low-level evidence shows a lower risk for hyperprolactinemia and higher patient satisfaction with PER than with risperidone. PER adds to the still limited arsenal of second-generation antipsychotics. In the absence of direct comparisons with risperidone, it remains difficult to come to a final verdict on the potential additional therapeutic benefits of PER which would justify its substantially

  1. Endogenous and Antipsychotic-Related Risks for Diabetes Mellitus in Young People With Schizophrenia: A Danish Population-Based Cohort Study.

    Science.gov (United States)

    Rajkumar, Anto P; Horsdal, Henriette Thisted; Wimberley, Theresa; Cohen, Dan; Mors, Ole; Børglum, Anders D; Gasse, Christiane

    2017-07-01

    Diabetes mellitus contributes to excessive cardiovascular deaths and reduced life expectancy in schizophrenia. This population-based cohort study investigated the endogenous risk for diabetes in antipsychotic-naive schizophrenia and evaluated the risks added by starting antipsychotic treatment in people with schizophrenia. The study followed all people born in Denmark on or after Jan. 1, 1977, until Jan. 1, 2013 (N=2,736,510). The Danish Psychiatric Central Research Register ascertained schizophrenia diagnoses. The Danish National Prescription Registry provided data on prescriptions of antipsychotics. Diabetes was ascertained from the Danish National Patient Register and Danish National Prescription Registry. The authors estimated the endogenous and antipsychotic-related risks for diabetes by using Cox proportional hazards regression models, while accounting for potential confounders. Of the cohort members, 14,118 (0.52%) developed diabetes, and 8,945 (0.33%) developed schizophrenia during follow-up (49,582,279 person-years). The adjusted hazard ratio for diabetes was 3.07 (95% confidence interval [CI], 1.71-5.41) in antipsychotic-naive schizophrenia compared with the general population. The risk for diabetes after starting antipsychotic treatment was significantly higher (adjusted hazard ratio, 3.64; 95% CI, 1.95-6.82) than the risk in antipsychotic-naive schizophrenia, after adjustment for family history of diabetes and other potential confounders. First-line treatment with either first-generation antipsychotics (adjusted hazard ratio, 3.06; 95% CI, 1.32-7.05) or second-generation antipsychotics (adjusted hazard ratio, 3.44; 95% CI, 1.73-6.83) increased the risk for diabetes without a statistically significant difference. Appropriate sensitivity analyses limited to type 2 diabetes corroborated these results. Schizophrenia confers a high endogenous risk for diabetes, and the risk is further increased by both first-generation and second-generation antipsychotics

  2. Understanding Antipsychotic Drug Treatment Effects: A Novel Method to Reduce Pseudospecificity of the Positive and Negative Syndrome Scale (PANSS) Factors.

    Science.gov (United States)

    Hopkins, Seth C; Ogirala, Ajay; Loebel, Antony; Koblan, Kenneth S

    2017-12-01

    The Positive and Negative Syndrome Scale (PANSS) is the most widely used efficacy measure in acute treatment studies of schizophrenia. However, interpretation of the efficacy of antipsychotics in improving specific symptom domains is confounded by moderate-to-high correlations among standard (Marder) PANSS factors. The authors review the results of an uncorrelated PANSS score matrix (UPSM) transform designed to reduce pseudospecificity in assessment of symptom change in patients with schizophrenia. Based on a factor analysis of five pooled, placebo-controlled lurasidone clinical trials (N=1,710 patients), a UPSM transform was identified that generated PANSS factors with high face validity (good correlation with standard Marder PANSS factors), and high specificity/orthogonality (low levels of between-factor correlation measuring change during treatment). Between-factor correlations were low at baseline for both standard (Marder) PANSS factors and transformed PANSS factors. However, when measured change in symptom severity was measured during treatment (in a pooled 5-study analysis), there was a notable difference for standard PANSS factors, where changes across factors were found to be highly correlated (factors exhibited pseudospecificity), compared to transformed PANSS factors, where factor change scores exhibited the same low levels of between-factor correlation observed at baseline. At Week 6-endpoint, correlations among PANSS factor severity scores were moderate-to-high for standard factors (0.34-0.68), but continued to be low for the transformed factors (-0.22-0.20). As an additional validity check, we analyzed data from one of the original five pooled clinical trials that included other well-validated assessment scales (MADRS, Negative Symptom Assessment scale [NSA]). In this baseline analysis, UPSM-transformed PANSS factor severity scores (negative and depression factors) were found to correlate well with the MADRS and NSA. The availability of transformed

  3. A review of the evidence for the use of metformin in the treatment of metabolic syndrome caused by antipsychotics.

    Science.gov (United States)

    Jesus, Cátia; Jesus, Inês; Agius, Mark

    2015-09-01

    Psychiatric patients requiring therapy with antipsychotics have a greater incidence of becoming overweight or obese compared with the general population. Many of these patients are often treated with second-generation (atypical) antipsychotics (SGAs), which are associated with weight gain, dyslipidaemia, and other metabolic derangements. The most important and first line of treatment for the metabolic syndrome is lifestyle changes including diet and exercise. However, other approaches like the use of medication (e.g. Metformin) have been also used, mainly when the lifestyle changes are difficult to achieve. Therefore, the treatment of antipsychotic-induced weight gain with metformin may be an option after the lifestyle and dietary changes fail. The use of metformin is still experimental and off license regarding the treatment of metabolic syndrome in Psychiatric patients, however we wished to assess the evidence for its use. Our study is a literature based research. For our research we reviewed 12 Pubmed published articles from 2006 to 2013. Metformin have been reported to counteract effectively antipsychotic-induced body weight gain and has been demonstrated to improve glycaemic control and promote a moderate weight loss in both diabetic and non-diabetic subjects. Metformin use appears to be a benefit when started early in the course of treatment and mostly in young adults newly exposed to antipsychotic drugs.

  4. Relationships among neurocognition, symptoms and functioning in patients with schizophrenia: a path-analytic approach for associations at baseline and following 24 weeks of antipsychotic drug therapy

    Directory of Open Access Journals (Sweden)

    Keefe Richard SE

    2009-07-01

    Full Text Available Abstract Background Neurocognitive impairment and psychiatric symptoms have been associated with deficits in psychosocial and occupational functioning in patients with schizophrenia. This post-hoc analysis evaluates the relationships among cognition, psychopathology, and psychosocial functioning in patients with schizophrenia at baseline and following sustained treatment with antipsychotic drugs. Methods Data were obtained from a clinical trial assessing the cognitive effects of selected antipsychotic drugs in patients with schizophrenia. Patients were randomly assigned to 24 weeks of treatment with olanzapine (n = 159, risperidone (n = 158, or haloperidol (n = 97. Psychosocial functioning was assessed with the Heinrichs-Carpenter Quality of Life Scale [QLS], cognition with a standard battery of neurocognitive tests; and psychiatric symptoms with the Positive and Negative Syndrome Scale [PANSS]. A path-analytic approach was used to evaluate the effects of changes in cognitive functioning on subdomains of quality of life, and to determine whether such effects were direct or mediated via changes in psychiatric symptoms. Results At baseline, processing speed affected functioning mainly indirectly via negative symptoms. Positive symptoms also affected functioning at baseline although independent of cognition. At 24 weeks, changes in processing speed affected changes in functioning both directly and indirectly via PANSS negative subscale scores. Positive symptoms no longer contributed to the path-analytic models. Although a consistent relationship was observed between processing speed and the 3 functional domains, variation existed as to whether the paths were direct and/or indirect. Working memory and verbal memory did not significantly contribute to any of the path-analytic models studied. Conclusion Processing speed demonstrated direct and indirect effects via negative symptoms on three domains of functioning as measured by the QLS at baseline and

  5. Antipsychotic prescribing in older people.

    Science.gov (United States)

    Neil, Wendy; Curran, Stephen; Wattis, John

    2003-09-01

    Antipsychotic medications have made a significant contribution to the care of the mentally ill people over the past 50 years, with good evidence that both typical and atypical agents are effective in the treatment of schizophrenia and related conditions. In addition they are widely used to good effect in other disorders including psychotic depression, dementia and delirium. Both typical and atypical agents may cause severe side-effects and, in the elderly in particular, there is an increased propensity for drug interactions. If used with care, antipsychotics are usually well tolerated, especially the atypical drugs. Although antipsychotics are effective at reducing psychotic symptoms their limitations should be recognised. They do not 'cure' the underlying illness, and the management of psychotic and behavioural symptoms must take into consideration treatment of physical illness as well as psychosocial interventions. In addition, the antipsychotic effect may take one to two weeks to be evident so doses should not be increased too rapidly. Often small doses are effective in the elderly if they are given sufficient time to work. As our understanding of the mechanisms of psychosis improves it is hoped that new drugs will be developed with novel mechanisms of action with improved efficacy and reduced side-effects. There are several drugs in development, some sharing similarities to currently available agents whilst others have novel mechanisms of actions involving glutamate and nicotinic receptors. Pharmacogenetics is also likely to be increasingly important over the next few years. As the genetic basis of many psychiatric disorders becomes more clearly established it is likely that drugs specifically designed for particular sub-groups of receptors will be developed. Finally, although the pharmacological treatment of psychotic disorders in younger people has been given considerable attention, there is a paucity of good quality research on antipsychotic drug use in

  6. [From cradle to grave? Expectations from atypical antipsychotics].

    Science.gov (United States)

    Frecska, Ede

    2005-03-01

    Clinical expectations are high toward atypical, second generation antipsychotics (SGAs). Controlled clinical trials supporting the superiority of SGAs over traditional agents are scarce. Meta-analysis of existing data may come for the rescue but that kind of method has its limitations. One of the most meticulous approaches (Davis et al. 2003) reached the conclusion that some, but not all, SGAs are more efficacious than traditional ones. Within the group of distinguished drugs, clozapine and amisulpride have the highest efficacy. The present paper critically overviews the study of the Davis group. Based on in vivo D2 receptor binding data of the new SGAs and the usual post marketing changes of clinical dosing, it is expected that some of the currently and most recently marketed SGAs may show similar superiority.

  7. Association between Ghrelin gene (GHRL) polymorphisms and clinical response to atypical antipsychotic drugs in Han Chinese schizophrenia patients

    OpenAIRE

    Yang Yongfeng; Li Wenqiang; Zhao Jingyuan; Zhang Hongxing; Song Xueqin; Xiao Bo; Yang Ge; Jiang Chengdi; Zhang Dai; Yue Weihua; Lv Luxian

    2012-01-01

    Abstract Background Ghrelin (GHRL) is a pivotal peptide regulator of food intake, energy balance, and body mass. Weight gain (WG) is a common side effect of the atypical antipsychotics (AAPs) used to treat schizophrenia (SZ). Ghrelin polymorphisms have been associated with pathogenic variations in plasma lipid concentrations, blood pressure, plasma glucose, and body mass index (BMI). However, it is unclear whether GHRL polymorphisms are associated with WG due to AAPs. Furthermore, there is no...

  8. Chronic treatment with antipsychotics in rats as a model for antipsychotic-induced weight gain in human

    DEFF Research Database (Denmark)

    Pouzet, B; Mow, T; Kreilgaard, Mads

    2003-01-01

    compounds in an animal model of weight gain. With the aim of evaluating whether the rat can be used as a model for antipsychotic-induced weight gain, we have investigated the effect of chronic treatment (3 weeks) with one antipsychotic drug inducing weight gain in clinic (olanzapine) and one antipsychotic...

  9. Second-generation migrants: Europe and the United States

    NARCIS (Netherlands)

    Crul, M.R.J.; Schneider, J.; Ness, I.; Bellwood, P.

    2013-01-01

    The public debate about the second generation in Europe has taken a dramatic shift in the last five years. The riots in the banlieues in France, involving mostly Algerian and Moroccan second-generation youth, pitched the cherished republican model into deep crisis. In the Netherlands, arguments

  10. Improving metabolic parameters of antipsychotic child treatment (IMPACT) study: rationale, design, and methods

    OpenAIRE

    Reeves, Gloria M; Keeton, Courtney; Correll, Christoph U; Johnson, Jacqueline L; Hamer, Robert M; Sikich, Linmarie; Hazzard, Lindsey; Alderman, Cheryl; Scheer, Abigail; Mabe, Micah; Kapoor, Sandeep; Sheridan, Eva; Borner, Irmgard; Bussell, Kristin; Pirmohamed, Sara

    2013-01-01

    Background Youth with serious mental illness may experience improved psychiatric stability with second generation antipsychotic (SGA) medication treatment, but unfortunately may also experience unhealthy weight gain adverse events. Research on weight loss strategies for youth who require ongoing antipsychotic treatment is quite limited. The purpose of this paper is to present the design, methods, and rationale of the Improving Metabolic Parameters in Antipsychotic Child Treatment (IMPACT) stu...

  11. ABC transporters P-gp and Bcrp do not limit the brain uptake of the novel antipsychotic and anticonvulsant drug cannabidiol in mice

    Directory of Open Access Journals (Sweden)

    Natalia Brzozowska

    2016-05-01

    Full Text Available Cannabidiol (CBD is currently being investigated as a novel therapeutic for the treatment of CNS disorders like schizophrenia and epilepsy. ABC transporters such as P-glycoprotein (P-gp and breast cancer resistance protein (Bcrp mediate pharmacoresistance in these disorders. P-gp and Bcrp are expressed at the blood brain barrier (BBB and reduce the brain uptake of substrate drugs including various antipsychotics and anticonvulsants. It is therefore important to assess whether CBD is prone to treatment resistance mediated by P-gp and Bcrp. Moreover, it has become common practice in the drug development of CNS agents to screen against ABC transporters to help isolate lead compounds with optimal pharmacokinetic properties. The current study aimed to assess whether P-gp and Bcrp impacts the brain transport of CBD by comparing CBD tissue concentrations in wild-type (WT mice versus mice devoid of ABC transporter genes. P-gp knockout (Abcb1a/b−∕−, Bcrp knockout (Abcg2−∕−, combined P-gp/Bcrp knockout (Abcb1a/b−∕−Abcg2−∕− and WT mice were injected with CBD, before brain and plasma samples were collected at various time-points. CBD results were compared with the positive control risperidone and 9-hydroxy risperidone, antipsychotic drugs that are established ABC transporter substrates. Brain and plasma concentrations of CBD were not greater in P-gp, Bcrp or P-gp/Bcrp knockout mice than WT mice. In comparison, the brain/plasma concentration ratios of risperidone and 9-hydroxy risperidone were profoundly higher in P-gp knockout mice than WT mice. These results suggest that CBD is not a substrate of P-gp or Bcrp and may be free from the complication of reduced brain uptake by these transporters. Such findings provide favorable evidence for the therapeutic development of CBD in the treatment of various CNS disorders.

  12. TADIR: a second-generation 480 x 4 TDI FLIR

    Science.gov (United States)

    Sarusi, Gabby

    1997-08-01

    'TADIR' is an El-Op's new second generation thermal imager based on 480 by 4 TDI MCT detector operated in the 8 - 10.5 micrometer spectral range. Although the prototype configuration design of TADIR is aimed toward the light weight low volume applications, TADIR is a generic modular technology of which the future El-Op second generation FLIR applications will be derived from. Beside the detector, what put the system in the second generation category are the state of the art features implemented in every component. This paper describes the system concept and design consideration have been taken during the development of its components.

  13. Antipsychotic prescription patterns and treatment costs of ...

    African Journals Online (AJOL)

    Peshawar, Pakistan and to analyze the treatment costs associated with these drugs. Methods: One hundred ..... Kendall T. The rise and fall of the atypical antipsychotics. ... size determination in health studies: a practical manual. 1991. 18.

  14. Comparison of Unlicensed and Off-Label Use of Antipsychotics Prescribed to Child and Adolescent Psychiatric Outpatients for Treatment of Mental and Behavioral Disorders with Different Guidelines: The China Food and Drug Administration Versus the FDA.

    Science.gov (United States)

    Zhu, Xiuqing; Hu, Jinqing; Sun, Bin; Deng, Shuhua; Wen, Yuguan; Chen, Weijia; Qiu, Chang; Shang, Dewei; Zhang, Ming

    2018-04-01

    This study aims to compare the prevalence of unlicensed and off-label use of antipsychotics among child and adolescent psychiatric outpatients with guidelines proposed by the China Food and Drug Administration (CFDA) and the U.S. Food and Drug Administration (FDA), and to identify factors associated with inconsistencies between the two regulations. A retrospective analysis of 29,326 drug prescriptions for child and adolescent outpatients from the Affiliated Brain Hospital of Guangzhou Medical University was conducted. Antipsychotics were classified as "unlicensed" or "off-label use" according to the latest pediatric license information registered by the CFDA and the FDA or the package inserts of antipsychotics authorized by the CFDA or the FDA for the treatment of pediatric mental and behavioral disorders, respectively. Binary logistic regression analysis was performed to assess factors associated with inconsistencies between the two regulations. The total unlicensed use, according to the CFDA analysis, was higher than that found in the FDA analysis (74.14% vs. 22.04%, p according to the FDA analysis, was higher than that found in the CFDA analysis (46.53% vs. 15.77%, p gender, diagnosis of schizophrenia and schizotypal and delusional disorders, diagnosis of mood [affective] disorders, diagnosis of mental retardation, and diagnosis of psychological development disorders were associated with inconsistent off-label use. The difference in prevalence of total unlicensed and off-label use of antipsychotics between the two regulations was statistically significant. This inconsistency could be partly attributed to differences in pediatric license information and package inserts of antipsychotics. The results indicate a need for further clinical pediatric studies and better harmonization between agencies regarding antipsychotic used in pediatrics.

  15. A new generation of antipsychotics: pharmacology and clinical utility of cariprazine in schizophrenia

    Directory of Open Access Journals (Sweden)

    Caccia S

    2013-08-01

    Full Text Available Silvio Caccia, Roberto William Invernizzi, Alessandro Nobili, Luca Pasina IRCCS-Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy Abstract: Cariprazine is a potential antipsychotic awaiting approval from the US Food and Drug Administration. It is a dopamine D2- and D3-receptor partial agonist, with higher affinity for D3 receptors, as opposed to the D2 antagonism of most older antipsychotic agents. Like most lipophilic antipsychotics, it undergoes extensive hepatic metabolism by cytochrome P450 (CYP, mainly the highly variable 3A4, with the formation of active metabolites. However, the parent compound – particularly its active didesmethyl derivative – is cleared very slowly, with elimination half-lives in schizophrenic patients ranging from 2–5 days for cariprazine to 2–3 weeks for didesmethyl-cariprazine. Exposure to the latter was several times that for cariprazine, although didesmethyl-cariprazine did not reach steady state within the 3 weeks of 12.5 mg/day dosing. Preliminary information on its therapeutic role comes from press releases and a few abstracts presented at scientific meetings. In short-term controlled trials, it was more effective than placebo in reducing positive and negative symptoms of schizophrenia, with an effective dose range of 1.5–12 mg/day. Although cariprazine was associated with a higher incidence of akathisia and extrapyramidal side effects than placebo, it did not cause weight gain, metabolic abnormalities, prolactin increase, or corrected QT prolongation. Similarly, cariprazine's efficacy and tolerability for the treatment of bipolar disorder (manic/mixed and depressive episodes was established in the dose range of 3–12 mg/day, although again no long-term data are available. Well-designed clinical trials, mainly direct "head-to-head" comparisons with other second-generation antipsychotic agents, are needed to define the therapeutic role and safety profile of cariprazine in schizophrenia and

  16. Antipsychotics for fibromyalgia in adults.

    Science.gov (United States)

    Walitt, Brian; Klose, Petra; Üçeyler, Nurcan; Phillips, Tudor; Häuser, Winfried

    2016-06-02

    quality of evidence using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach. We included a total of four studies with 296 participants.Three studies with 206 participants compared quetiapine, an atypical (second-generation) antipsychotic, with placebo. One study used a cross-over design and two studies a parallel-group design. Study duration was eight or 12 weeks. Quetiapine was used in all studies with a bedtime dosage between 50 and 300 mg/day. All studies had one or more sources of potential major bias and we judged them to be at moderate risk of bias overall. The primary outcomes in this review were participant-reported pain relief of 50% or greater, Patient Global Impression of Change (PGIC) much or very much improved, withdrawal due to adverse events (tolerability) and serious adverse events (safety).Second tier evidence indicated that quetiapine was not statistically superior to placebo in the number of participants with a 50% or more pain reduction (very low quality evidence). No study reported data on PGIC. A greater proportion of participants on quetiapine reported a 30% or more pain reduction (risk difference (RD) 0.12, 95% confidence interval (CI) 0.00 to 0.23; number needed to treat for an additional benefit (NNTB) 8, 95% CI 5 to 100) (very low quality evidence). A greater proportion of participants on quetiapine reported a clinically relevant improvement of health-related quality of life compared to placebo ( RD 0.18, 95% CI 0.05 to 0.31; NNTB 5, 95% CI 3 to 20) (very low quality evidence). Quetiapine was statistically superior to placebo in reducing sleep problems (standardised mean difference (SMD) -0.67, 95% CI -1.10 to -0.23), depression (SMD -0.39, 95% CI -0.74 to -0.04) and anxiety (SMD -0.40, 95% CI -0.69 to -0.11) (very low quality evidence). Quetiapine was statistically superior to placebo in reducing the risk of withdrawing from the study due to a lack of efficacy (RD -0.14, 95% CI -0.23 to -0.05) (very low

  17. Antipsychotics and Sexual Dysfunction: Sexual Dysfunction - Part III

    Directory of Open Access Journals (Sweden)

    Anil Kumar Mysore Nagaraj

    2009-11-01

    Full Text Available Satisfying sexual experience is an essential part of a healthy and enjoyable life for most people. Antipsychotic drugs are among the various factors that affect optimal sexual functioning. Both conventional and novel antipsychotics are associated with significant sexual side effects. This review has presented various studies comparing different antipsychotic drugs. Dopamine antagonism, increased serum prolactin, serotonergic, adrenergic and cholinergic mechanisms are all proposed to be the mechanisms for sexual dysfunction. Drug treatment for this has not given satisfactory long-term results. Knowledge of the receptor pharmacology of an individual antipsychotic will help to determine whether it is more or less likely to cause sexual side effects and its management.

  18. Second-Generation Prisoners and the Transmission of Domestic Violence.

    Science.gov (United States)

    Will, Joanna L; Loper, Ann B; Jackson, Shelly L

    2016-01-01

    Adult inmates who experienced the incarceration of a parent, known as "second-generation prisoners," experience unique challenges and are at heightened risk for experiencing other adversities throughout the life span. Our study investigated one specific, and previously unexplored, type of adversity--domestic violence--within a sample of 293 incarcerated adults. We examined the relation between generation status (first- or second-generation prisoners), childhood exposure to domestic violence, and participation in adult relationship violence prior to incarceration. Results indicate that prisoners who had been exposed to domestic violence in childhood were more likely to engage in intimate partner violence resulting in inflicted and received injury. Relative to first-generation prisoners, second-generation prisoners reported more childhood domestic violence exposure and were more likely to have been injured by a relationship partner. However, this relation between second-generation status and injury victimization was mediated by domestic violence exposure. These results support an intergenerational pattern of domestic violence and suggest that second-generation prisoners are a unique population worthy of future investigation and mental health intervention. © The Author(s) 2014.

  19. Classification of typical and atypical antipsychotic drugs on the basis of dopamine D-1, D-2 and serotonin2 pKi values.

    Science.gov (United States)

    Meltzer, H Y; Matsubara, S; Lee, J C

    1989-10-01

    The pKi values of 13 reference typical and 7 reference atypical antipsychotic drugs (APDs) for rat striatal dopamine D-1 and D-2 receptor binding sites and cortical serotonin (5-HT2) receptor binding sites were determined. The atypical antipsychotics had significantly lower pKi values for the D-2 but not 5-HT2 binding sites. There was a trend for a lower pKi value for the D-1 binding site for the atypical APD. The 5-HT2 and D-1 pKi values were correlated for the typical APD whereas the 5-HT2 and D-2 pKi values were correlated for the atypical APD. A stepwise discriminant function analysis to determine the independent contribution of each pKi value for a given binding site to the classification as a typical or atypical APD entered the D-2 pKi value first, followed by the 5-HT2 pKi value. The D-1 pKi value was not entered. A discriminant function analysis correctly classified 19 of 20 of these compounds plus 14 of 17 additional test compounds as typical or atypical APD for an overall correct classification rate of 89.2%. The major contributors to the discriminant function were the D-2 and 5-HT2 pKi values. A cluster analysis based only on the 5-HT2/D2 ratio grouped 15 of 17 atypical + one typical APD in one cluster and 19 of 20 typical + two atypical APDs in a second cluster, for an overall correct classification rate of 91.9%. When the stepwise discriminant function was repeated for all 37 compounds, only the D-2 and 5-HT2 pKi values were entered into the discriminant function.(ABSTRACT TRUNCATED AT 250 WORDS)

  20. Atypical antipsychotics and glucose homeostasis.

    Science.gov (United States)

    Bergman, Richard N; Ader, Marilyn

    2005-04-01

    needed. A major problem in assessing drug effects is that psychiatric disease itself can cause many of the manifestations leading to diabetes, including weight gain and sedentary lifestyle. While studies in healthy subjects are limited and inconclusive, studies in animal models are more revealing. In the conscious canine model, some atypical antipsychotics cause adiposity, including visceral obesity, a strong risk factor for the metabolic syndrome. Furthermore, while few studies have examined effects of antipsychotics on pancreatic beta-cell function, canine studies demonstrate that expected beta-cell compensation for insulin resistance may be reduced or even eliminated with these agents. Atypical antipsychotics have been shown to contribute to weight gain, which may well reflect increased body fat deposition. Such increased fat is known to cause resistance to insulin action, although more information regarding effect on insulin action is needed. The effect of these drugs on fat distribution has been clearly shown in animal models. It is known that the normal response to insulin resistance is compensatory hyperinsulinemia, which may prevent diabetes. In animals, there is evidence that the hyperinsulinemic compensation is inadequate in the face of atypical antipsychotic agents. It remains to be examined whether failure of adequate pancreatic beta-cell compensation for insulin resistance plays a central role in the pathogenesis of diabetes associated with this class of drugs.

  1. Search for second generation leptoquarks with ATLAS at the LHC

    International Nuclear Information System (INIS)

    Krobath, Gernot

    2008-01-01

    The Large Hadron Collider will collide protons with protons at a center-of-mass energy of up to 14 TeV. New physics phenomena and new particles are predicted to be detectable with the ATLAS detector at the Large Hadron Collider. One of these predicted new particles beyond the Standard Model are leptoquarks. This thesis deals with the search for scalar second generation leptoquarks produced in pairs. Second generation leptoquarks decay into a muon-type lepton and a quark. In this thesis the decay of both second generation leptoquarks into a muon and a quark is considered. Since pair production is studied the final state consists of two high-energetic muons and two high-energetic jets. This thesis studies second generation leptoquarks with masses of m LQ =300 GeV, m LQ =400 GeV, m LQ =600 GeV and m LQ =800 GeV. The best cut variables for the discrimination between the signal and the main Standard Model backgrounds t anti t and Z/γ * found in this analysis are the p T of the muons, S T (the scalar sum of the transverse momenta of the two selected muons and the transverse energies of the two selected jets), the mass of the selected dimuon system and the reconstructed leptoquark mass. The latter three cut variables have been optimized for a discovery with a 5σ significance including the systematic uncertainties and trigger efficiencies. Second generation leptoquarks have been excluded up to the mass of 300 GeV with a 95% confidence level at present experiments. The expected integrated luminosities needed for a 5σ discovery of the tested second generation leptoquark masses with the ATLAS detector have been calculated. This thesis shows that for a discovery with 5σ significance of a second generation leptoquark with m LQ =300 GeV and m LQ =400 GeV an expected integrated luminosity of 1.51 pb -1 and 7.42 pb -1 is needed respectively; this corresponds to a very early phase, i.e. the first few months, of the Large Hadron Collider run. For the discovery with a 5

  2. Predictive Ability of the SYNergy Between Percutaneous Coronary Intervention with TAXus and Cardiac Surgery Score II for Long-term Mortality in Patients with Three-vessel Coronary Artery Disease Undergoing Percutaneous Coronary Intervention Treated with Second-generation Drug-eluting Stents

    Directory of Open Access Journals (Sweden)

    Ji-Qiang He

    2015-01-01

    Conclusion: The SS-II is an independent predictor of 5-year mortality in patients with three-vessel CAD undergoing PCI treated with second-generation DES, and demonstrates a superior predictive ability over the SS alone.

  3. The use of antipsychotic medication in child and adolescent psychiatric treatment in Denmark. A cross-sectional survey

    DEFF Research Database (Denmark)

    Deurell, Maria; Weischer, Merete; Pagsberg, Anne Katrine

    2008-01-01

    for patients in antipsychotic treatment were: schizophrenia, schizotypal disorder, autism spectrum disorders and personality disorders. Monotherapy was used in 87% of cases. Sixty-four per cent of patients treated with antipsychotics, received a second-generation antipsychotic as the main treatment. All 244......The number of children and adolescents with psychiatric disorders being treated with antipsychotic medication is increasing significantly; however, only a limited evidence-base is available on this topic, especially when children are concerned. This study reports and discusses the use...... patients received one or more additional treatment modalities other than medication. Antipsychotic medication has a definite role in the treatment of children and adolescents with psychiatric disorders. Second-generation antipsychotics used as monotherapy prevail....

  4. Search for Second Generation Leptoquarks with ATLAS at the LHC

    CERN Document Server

    Krobath, Gernot

    The Large Hadron Collider will collide protons with protons at a center-of-mass energy of up to 14 TeV. New physics phenomena and new particles are predicted to be detectable with the ATLAS detector at the Large Hadron Collider. One of these predicted new particles beyond the Standard Model are leptoquarks. This thesis deals with the search for scalar second generation leptoquarks produced in pairs. Second generation leptoquarks decay into a muon-type lepton and a quark. In this thesis the decay of both second generation leptoquarks into a muon and a quark is considered. Since pair production is studied the final state consists of two high-energetic muons and two high-energetic jets. This thesis studies second generation leptoquarks with masses of mLQ = 300 GeV, mLQ = 400 GeV, mLQ = 600 GeV and mLQ = 800 GeV. The best cut variables for the discrimination between the signal and the main Standard Model backgrounds ttbar and Z/gamma* found in this analysis are the pT of the muons, ST (the scalar sum of the trans...

  5. Panorama 2015 - Second generation biofuels: a new milestone reached

    International Nuclear Information System (INIS)

    Sagnes, Charlene; Chabrelie, Marie-Francoise

    2015-01-01

    The commissioning of several commercial lignocellulosic ethanol production units worldwide marks a new stage in the development of second generation biofuels. Certainly many obstacles, both technological and economic, still remain to be overcome, and considerable investment amounts will have to be mobilized to develop and sustain these sectors. Favorable evolution of the regulatory environment in the markets remains the key to their future. (authors)

  6. Second Generation Dutch Pulsar Machine - PuMa-II

    NARCIS (Netherlands)

    Karuppusamy, Ramesh; Stappers, Ben; Slump, Cornelis H.; van der Klis, Michiel

    2004-01-01

    The Second Generation Pulsar Machine (PuMa- II) is under development for the Westerbork Synthesis Radio Telescope. This is a summary of th e system design and architecture. We show that state of the art pulsar research is possible with commercially available hardware components. This approach

  7. Evolution to 3G Mobile Communication - Second Generation ...

    Indian Academy of Sciences (India)

    Home; Journals; Resonance – Journal of Science Education; Volume 8; Issue 9. Evolution to 3G Mobile Communication - Second Generation Cellular Systems. R Ramachandran. General Article Volume 8 Issue 9 September 2003 pp 60-72 ... Keywords. Wireless communication; cellular networks; GSM; CdmaOne; TDMA ...

  8. Policies for second generation biofuels: current status and future challenges

    Energy Technology Data Exchange (ETDEWEB)

    Egger, Haakan; Greaker, Mads; Potter, Emily

    2011-07-01

    Current state-of-the-art knowledge concludes that green house gas (GHG) emissions must be controlled and reduced within the next 30-40 years. The transport sector contributes almost a fifth of the current global emissions, and its share is likely to increase in the future. The US and a number of European countries have therefore introduced various support schemes for research and development (RandD) of low emission fuels that can potentially replace the current fossil fuels. One such alternative is biofuels. The advantage of biofuels are that it is easy to introduce into the transport sector. On the other hand, recent research papers question whether the supply of feedstock is sufficient, and to what extent biofuels lead to GHG emission reductions. This report reviews the current status of second generation biofuels. Second generation biofuels are made from cellulose, which according to our survey of the literature, is in more abundant supply than the first generation biofuels feedstocks. Furthermore, it seems to have the potential to reduce GHG emissions from the transport sector without leading to devastating land use changes, which recent critique has held against first generation biofuels. Given that governments have decided to support RandD of low emission fuels, we ask the following questions: Should second generation biofuels receive RandD support to the same extent as other low emission fuels like hydrogen? How should support schemes for second generation biofuels be designed? Second generation biofuels can be divided according to the production process into thermo-chemical and bio-chemical. With respect to the thermo-chemical process the potential for cost reductions seems to be low. On the other hand, ethanol made from cellulose using the biochemical conversion process is far from a ripe technology. Expert reports point to several potential technological breakthroughs which may reduce costs substantially. Hence, cellulosic ethanol, should receive direct

  9. Antipsychotics and Associated Risk of Out-of-Hospital Cardiac Arrest

    DEFF Research Database (Denmark)

    Weeke, Peter; Jensen, Aksel; Folke, Fredrik

    2014-01-01

    % confidence interval [CI]:1.23-1.89) as was use with typical antipsychotics (OR= 1.66, CI: 1.27-2.17). By contrast, overall atypical antipsychotics drug use was not (OR= 1.29, CI: 0.90-1.85). Two individual typical antipsychotic drugs were associated with OHCA, haloperidol (OR= 2.43, CI: 1...

  10. A novel role for dopamine signaling in the pathogenesis of bone loss from the atypical antipsychotic drug risperidone in female mice.

    Science.gov (United States)

    Motyl, Katherine J; Beauchemin, Megan; Barlow, Deborah; Le, Phuong T; Nagano, Kenichi; Treyball, Annika; Contractor, Anisha; Baron, Roland; Rosen, Clifford J; Houseknecht, Karen L

    2017-10-01

    Atypical antipsychotic (AA) drugs, including risperidone (RIS), are used to treat schizophrenia, bipolar disorder, and autism, and are prescribed off-label for other mental health issues. AA drugs are associated with severe metabolic side effects of obesity and type 2 diabetes. Cross-sectional and longitudinal data also show that risperidone causes bone loss and increases fracture risk in both men and women. There are several potential mechanisms of bone loss from RIS. One is hypogonadism due to hyperprolactinemia from dopamine receptor antagonism. However, many patients have normal prolactin levels; moreover we demonstrated that bone loss from RIS in mice can be blocked by inhibition of β-adrenergic receptor activation with propranolol, suggesting the sympathetic nervous system (SNS) plays a pathological role. Further, when, we treated ovariectomized (OVX) and sham operated mice daily for 8weeks with RIS or vehicle we demonstrated that RIS causes significant trabecular bone loss in both sham operated and OVX mice. RIS directly suppressed osteoblast number in both sham and OVX mice, but increased osteoclast number and surface in OVX mice alone, potentially accounting for the augmented bone loss. Thus, hypogonadism alone cannot explain RIS induced bone loss. In the current study, we show that dopamine and RIS are present in the bone marrow compartment and that RIS can exert its effects directly on bone cells via dopamine receptors. Our findings of both direct and indirect effects of AA drugs on bone are relevant for current and future clinical and translational studies investigating the mechanism of skeletal changes from AA drugs. Copyright © 2017 Elsevier Inc. All rights reserved.

  11. Association between Ghrelin gene (GHRL polymorphisms and clinical response to atypical antipsychotic drugs in Han Chinese schizophrenia patients

    Directory of Open Access Journals (Sweden)

    Yang Yongfeng

    2012-02-01

    Full Text Available Abstract Background Ghrelin (GHRL is a pivotal peptide regulator of food intake, energy balance, and body mass. Weight gain (WG is a common side effect of the atypical antipsychotics (AAPs used to treat schizophrenia (SZ. Ghrelin polymorphisms have been associated with pathogenic variations in plasma lipid concentrations, blood pressure, plasma glucose, and body mass index (BMI. However, it is unclear whether GHRL polymorphisms are associated with WG due to AAPs. Furthermore, there is no evidence of an association between GHRL polymorphisms and SZ or the therapeutic response to AAPs. We explored these potential associations by genotyping GHRL alleles in SZ patients and controls. We also examined the relation between these SNPs and changes in metabolic indices during AAP treatment in SZ subgroups distinguished by high or low therapeutic response. Methods Four SNPs (Leu72Met, -501A/C, -604 G/A, and -1062 G > C were genotyped in 634 schizophrenia patients and 606 control subjects. Results There were no significant differences in allele frequencies, genotype distributions, or the distributions of two SNP haplotypes between SZ patients and healthy controls (P > 0.05. There was also no significant difference in symptom reduction between genotypes after 8 weeks of AAP treatment as measured by positive and negative symptom scale scores (PANSS. However, the -604 G/A polymorphism was associated with a greater BMI increase in response to AAP administration in both APP responders and non-responders as distinguished by PANSS score reduction (P P Conclusions These four GHRL gene SNPs were not associated with SZ in this Chinese Han population. The -604 G/A polymorphism was associated with significant BW and BMI increases during AAP treatment. Patients exhibiting higher WG showed greater improvements in positive and negative symptoms than patients exhibiting lower weight gain or weight loss.

  12. Association between ghrelin gene (GHRL) polymorphisms and clinical response to atypical antipsychotic drugs in Han Chinese schizophrenia patients.

    Science.gov (United States)

    Yang, Yongfeng; Li, Wenqiang; Zhao, Jingyuan; Zhang, Hongxing; Song, Xueqin; Xiao, Bo; Yang, Ge; Jiang, Chengdi; Zhang, Dai; Yue, Weihua; Lv, Luxian

    2012-02-28

    Ghrelin (GHRL) is a pivotal peptide regulator of food intake, energy balance, and body mass. Weight gain (WG) is a common side effect of the atypical antipsychotics (AAPs) used to treat schizophrenia (SZ). Ghrelin polymorphisms have been associated with pathogenic variations in plasma lipid concentrations, blood pressure, plasma glucose, and body mass index (BMI). However, it is unclear whether GHRL polymorphisms are associated with WG due to AAPs. Furthermore, there is no evidence of an association between GHRL polymorphisms and SZ or the therapeutic response to AAPs. We explored these potential associations by genotyping GHRL alleles in SZ patients and controls. We also examined the relation between these SNPs and changes in metabolic indices during AAP treatment in SZ subgroups distinguished by high or low therapeutic response. Four SNPs (Leu72Met, -501A/C, -604 G/A, and -1062 G > C) were genotyped in 634 schizophrenia patients and 606 control subjects. There were no significant differences in allele frequencies, genotype distributions, or the distributions of two SNP haplotypes between SZ patients and healthy controls (P > 0.05). There was also no significant difference in symptom reduction between genotypes after 8 weeks of AAP treatment as measured by positive and negative symptom scale scores (PANSS). However, the -604 G/A polymorphism was associated with a greater BMI increase in response to AAP administration in both APP responders and non-responders as distinguished by PANSS score reduction (P GHRL gene SNPs were not associated with SZ in this Chinese Han population. The -604 G/A polymorphism was associated with significant BW and BMI increases during AAP treatment. Patients exhibiting higher WG showed greater improvements in positive and negative symptoms than patients exhibiting lower weight gain or weight loss.

  13. Antipsychotic-induced somnolence in mothers with schizophrenia.

    Science.gov (United States)

    Seeman, Mary V

    2012-03-01

    Although it is known that many antipsychotic drugs, at the doses prescribed for schizophrenia, are sedative and cause daytime drowsiness, the effect of potentially diminished vigilance on parenting parameters has not been studied. The aim of this paper is to advise clinicians about sedative load in mothers who are prescribed antipsychotic medication. A Medline search was conducted into the sedative effects of antipsychotics, with the following search terms: sleep; sedation; somnolence; wakefulness; antipsychotics; schizophrenia, parenting, maternal behavior, and custody. The results showed that antipsychotic drugs differ in their propensity to induce sedation and do so via their effects on a variety of neurotransmitter systems. It is important to note that mothers with schizophrenia risk losing custody of their infants if they are perceived as potentially neglectful because of excessive daytime sleepiness. Clinicians must choose antipsychotic medications carefully and monitor for sedative effects whenever the patient has important responsibilities that require the maintenance of vigilance.

  14. Search for second generation leptoquarks with ATLAS at the LHC

    Energy Technology Data Exchange (ETDEWEB)

    Krobath, Gernot

    2008-07-18

    The Large Hadron Collider will collide protons with protons at a center-of-mass energy of up to 14 TeV. New physics phenomena and new particles are predicted to be detectable with the ATLAS detector at the Large Hadron Collider. One of these predicted new particles beyond the Standard Model are leptoquarks. This thesis deals with the search for scalar second generation leptoquarks produced in pairs. Second generation leptoquarks decay into a muon-type lepton and a quark. In this thesis the decay of both second generation leptoquarks into a muon and a quark is considered. Since pair production is studied the final state consists of two high-energetic muons and two high-energetic jets. This thesis studies second generation leptoquarks with masses of m{sub LQ}=300 GeV, m{sub LQ}=400 GeV, m{sub LQ}=600 GeV and m{sub LQ}=800 GeV. The best cut variables for the discrimination between the signal and the main Standard Model backgrounds t anti t and Z/{gamma}{sup *} found in this analysis are the p{sub T} of the muons, S{sub T} (the scalar sum of the transverse momenta of the two selected muons and the transverse energies of the two selected jets), the mass of the selected dimuon system and the reconstructed leptoquark mass. The latter three cut variables have been optimized for a discovery with a 5{sigma} significance including the systematic uncertainties and trigger efficiencies. Second generation leptoquarks have been excluded up to the mass of 300 GeV with a 95% confidence level at present experiments. The expected integrated luminosities needed for a 5{sigma} discovery of the tested second generation leptoquark masses with the ATLAS detector have been calculated. This thesis shows that for a discovery with 5{sigma} significance of a second generation leptoquark with m{sub LQ}=300 GeV and m{sub LQ}=400 GeV an expected integrated luminosity of 1.51 pb{sup -1} and 7.42 pb{sup -1} is needed respectively; this corresponds to a very early phase, i.e. the first few months

  15. Dynamics of carbon abatement in the Second Generation Model

    International Nuclear Information System (INIS)

    Sands, Ronald D.

    2004-01-01

    The Second Generation Model (SGM) is a collection of computable-general-equilibrium models developed for analysis of policies to reduce greenhouse gas emissions. Behavior of the Second Generation Model, with respect to changes in carbon prices, can be summarized using marginal abatement cost curves. Marginal abatement costs vary over time, as capital stocks adjust to a new set of prices, and across countries, depending in part on the mix of fuels in the existing energy system. This paper documents the production structure in SGM, marginal abatement cost curves derived from SGM with constant-carbon-price experiments, an application to several Energy Modeling Forum scenarios, and a methodology for including carbon capture and disposal in SGM

  16. In vivo analysis of torsadogenic potential of an antipsychotic drug paliperidone using the acute atrioventricular block rabbit as a proarrhythmia model

    Directory of Open Access Journals (Sweden)

    Mihoko Hagiwara

    2016-09-01

    Full Text Available We assessed electrophysiological effects of an atypical antipsychotic drug paliperidone in acute atrioventricular block rabbits. Intravenous administration of paliperidone at a clinically relevant dose (0.06 mg/kg hardly affected the QT interval or monophasic action potential (MAP duration, and the higher doses (0.6 and 6 mg/kg prolonged the QT interval and MAP duration. Meanwhile, premature ventricular contractions with R on T phenomenon were observed in 3 out of 6 animals at the middle dose, and torsades de pointes (TdP episodes were detected in 2 out of 6 animals at the high dose. Intravenous administration of its chemically related compound risperidone at a clinically relevant dose (0.03 mg/kg hardly affected the electrophysiological parameters, and the higher doses (0.3 and 3 mg/kg prolonged the QT interval and MAP duration. Meanwhile, the premature ventricular contractions with R on T were observed in 2 out of 6 animals at the middle dose, and TdP episodes were detected in 4 out of 6 animals at the high dose. These results suggest that paliperidone showed torsadogenic potential at supra-therapeutic doses, whose potency can be estimated to be equal or slightly subordinate in comparison with that of risperidone.

  17. Decreased left middle temporal gyrus volume in antipsychotic drug-naive, first-episode schizophrenia patients and their healthy unaffected siblings.

    Science.gov (United States)

    Hu, Maorong; Li, Jun; Eyler, Lisa; Guo, Xiaofeng; Wei, Qingling; Tang, Jingsong; Liu, Feng; He, Zhong; Li, Lihua; Jin, Hua; Liu, Zhening; Wang, Juan; Liu, Fang; Chen, Huafu; Zhao, Jingping

    2013-03-01

    The shared neuropathological characteristics of patients with schizophrenia and their siblings might represent intermediate phenotypes that could be used to investigate genetic susceptibility to the illness. We sought to discover gray matter volume differences in patients with schizophrenia and their unaffected siblings with voxel-based morphometry (VBM). We recruited antipsychotic drug-naive, first-episode schizophrenia (FES) patients, their unaffected siblings and age-, sex- and handedness-matched healthy controls. We used VBM to investigate differences in gray matter volume among the 3 groups. There were significant gray matter volumetric differences among the 3 groups in bilateral hippocampal and parahippocampal gyri, bilateral middle temporal gyri, and superior temporal gyri (FDR ptemporal gyrus, and volume of this region was not different between siblings and patients. Our findings confirm and extend previous VBM analyses in schizophrenia and it indicate that schizophrenia may be characterized by an abnormal development of cerebral lateralization. Furthermore, these data argue that patients and their unaffected siblings might share decreases in the gray matter volume of the left middle temporal gyrus, and this regional reduction might be a potential endophenotype for schizophrenia. Copyright © 2013 Elsevier B.V. All rights reserved.

  18. Aberrant functioning of the putamen links delusions, antipsychotic drug dose, and compromised connectivity in first episode psychosis--Preliminary fMRI findings.

    Science.gov (United States)

    Raij, Tuukka T; Mäntylä, Teemu; Kieseppä, Tuula; Suvisaari, Jaana

    2015-08-30

    The dopamine theory proposes the relationship of delusions to aberrant signaling in striatal circuitries that can be normalized with dopamine D2 receptor-blocking drugs. Localization of such circuitries, as well as their upstream and downstream signaling, remains poorly known. We collected functional magnetic resonance images from first-episode psychosis patients and controls during an audiovisual movie. Final analyses included 20 patients and 20 controls; another sample of 10 patients and 10 controls was used to calculate a comparison signal-time course. We identified putamen circuitry in which the signal aberrance (poor correlation with the comparison signal time course) was predicted by the dopamine theory, being greater in patients than controls; correlating positively with delusion scores; and correlating negatively with antipsychotic-equivalent dosage. In Granger causality analysis, patients showed a compromised contribution of the cortical salience network to the putamen and compromised contribution of the putamen to the default mode network. Results were corrected for multiple comparisons at the cluster level with primary voxel-wise threshold p < 0.005 for the salience network contribution, but liberal primary threshold p < 0.05 was used in other group comparisons. If replicated in larger studies, these findings may help unify and extend current hypotheses on dopaminergic dysfunction, salience processing and pathogenesis of delusions. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  19. Development of a second generation rolling contact fatigue tester

    Science.gov (United States)

    Deshmukh, Satyam U.

    Contact fatigue failure has been in research since the early twentieth century. The need for a second generation sliding-rolling contact fatigue tester was proposed by Gregory Dvorak and Dr. Marcellin Zahui. The first generation RCF tester was used for testing super finishing processes for gear surfaces. The second generation RCF tester was funded by the Advanced Engineering Materials lab of University of North Dakota. Verification of the second generation Rolling Contact Fatigue Tester will be discussed in this thesis including the design details, assembly and testing procedure and to discuss its different parameters. The tester will have the capability of testing hollow specimens using a bobbin eddy current testing probe. This tester will allow a wide range of experiments and is not built for one specific purpose. An eddy current device is used for detecting cracks. The loading force is applied using hydraulic cylinders and a hydraulic power unit. Before testing began, the machine was run for some time at full speed. A lot of minor problems were detected and fixed. Three specimens of AISI 8620 were tested in this tester. All tests gave results matching with some of the other well-known RCF testers. These tests were performed to evaluate mechanical limits of the tester and to evaluate the software performance of the tester.

  20. The Impact of Cannabis Use on the Dosage of Antipsychotic Drugs in Patients Admitted on the Psychiatric Ward at the University Hospital of the West Indies

    Directory of Open Access Journals (Sweden)

    P Thomas

    2015-03-01

    Full Text Available Objective: To assess the impact of cannabis use on the efficacy of antipsychotic drugs in male subjects presenting to the University Hospital of the West Indies (UHWI with psychotic episodes. Methods: Male subjects, 18–40 years old, admitted to the psychiatric ward of the UHWI between February 2013 and May 2013, diagnosed with schizophrenia, schizophreniform disorder and who tested positive for ∆9-tetrahydrocannabinol were recruited for the study. On day one, consenting subjects were assessed using the Brief Psychiatric Rating Scale (BPRS. Patients were prescribed seven days of an oral antipsychotic medication (haloperidol, chlorpromazine, risperidone, quetiapine, olanzapine. Medicated subjects were then reassessed using the BPRS on days three and seven. Statistical analysis involved the use of Student’s t-test and repeated measure analysis of variance. Results: In total, 20 subjects were recruited (mean age = 26.00 ± 5.96 years. Subjects were grouped based on the daily chlorpromazine equivalent (CPZE dose given on day one into CPZE1 (CPZE dose of 100–300mg; n = 8 and CPZE2 (CPZE dose of 400–1250 mg; n = 12. There was no significant difference in the total BPRS score between the groups on day one (CPZE1 = 41.38 ± 16.47 versus CPZE2 = 49.42 ± 25.58; p = 0.44; similar findings were obtained for the positive (26.75 ± 9.27 versus 31.83 ± 17.30; p = 0.46 and negative (14.63 ± 7.73 versus 17.58 ± 9.74; p = 0.48 symptom component on the BPRS. For subjects in CPZE1, there was no significant decrease in total BPRS score [F(2,21 = 0.07, p = 0.93] over the study period. For CPZE2, significant reduction in total BPRS scores was achieved [F(2,33 =7.12, p = 0.01], contributed by significant decrease in the positive [F(2,33 = 5.64, p = 0.02 and negative [F(2,33 = 7.53, p = 0.01 symptom components of the BPRS. Conclusion: The findings of this study purport that male cannabis users presenting with psychotic disorders may not achieve optimal

  1. Second generation H1 - antihistamines interaction with food and alcohol-A systematic review.

    Science.gov (United States)

    Paśko, Paweł; Rodacki, Tomasz; Domagała-Rodacka, Renata; Palimonka, Krzysztof; Marcinkowska, Monika; Owczarek, Danuta

    2017-09-01

    Histamine is a mediator of many physiological processes. It plays an important role in modulating allergy reactions and immune system responses. H1 receptor is a therapeutic target for drugs applied in allergic diseases such as allergic rhinoconjunctivitis, urticarial, or atopic dermatitis. H1-antihistamines display different chemical structures, pharmacokinetics and a potential for drug-drug and drug-food interactions. Drug-food interactions are known to reduce therapeutic effects of the medicine, as well as to induce a potent adverse drug reactions. Considering it all, a systematic review was conducted to investigate the importance of drug-food interaction for H1-antihistamine drugs. As non-sedating second generation H1-antihistamines remain to be drugs of choice in treating allergic conditions, the review has been focused on this particular class of medicines. The aim of this paper is to examine the evidence of food-drug and food-alcohol interactions for second generation H1-antihistamine drugs. A systematic literature queries were performed in the following databases: Medline (via PubMed), Cochrane Library, Embase and Web of Science (all from their inception date till October 2016). The queries covered nine specific names of second generation anthistamine drugs, namely bilastine, cetirizine, desloratadine, ebastine, fexofenadine, levocetirizine, loratadine, mizolastine, and rupatadine, in combinations with such terms as "food", "juice", "grapefruit", "fruits", "alcohol", "pharmacokinetics", and "meal". Additional publications were found by checking all the reference lists. Where none data on drug-food interaction could be found within the investigated databases, a specific drug prescribing information was used. 2326 publications were identified with the database queries. Articles were subjected to analysis by reviewing their title, abstract and full text; duplicated papers were removed. Having collected a complete set of data, a critical review was undertaken

  2. Differential effects of antipsychotic drugs on insight in first episode schizophrenia: Data from the European First-Episode Schizophrenia Trial (EUFEST)

    NARCIS (Netherlands)

    Pijnenborg, G. H. M.; Timmerman, M. E.; Derks, E. M.; Fleischhacker, W. W.; Kahn, R. S.; Aleman, A.

    2015-01-01

    Although antipsychotics are widely prescribed, their effect of on improving poor illness insight in schizophrenia has seldom been investigated and therefore remains uncertain. This paper examines the effects of low dose haloperidol, amisulpride, olanzapine, quetiapine, and ziprasidone on insight in

  3. Differential effects of antipsychotic drugs on insight in first episode schizophrenia : Data from the European First-Episode Schizophrenia Trial (EUFEST)

    NARCIS (Netherlands)

    Pijnenborg, G. H. M.; Timmerman, Marieke; Derks, E.M.; Fleischhacker, W. W.; Kahn, R. S.; Aleman, A.

    Although antipsychotics are widely prescribed, their effect of on improving poor illness insight in schizophrenia has seldom been investigated and therefore remains uncertain. This paper examines the effects of low dose haloperidol, amisulpride, olanzapine, quetiapine, and ziprasidone on insight in

  4. Effects of typical antipsychotic, haloperidol on regional cerebral blood flow in drug-naive schizophrenic patients-study with 99mTc-HMPAO SPECT

    International Nuclear Information System (INIS)

    Kamoya, Masatoshi

    2001-01-01

    For the purpose of examining antipsychotic action of haloperidol (HPD), effects of chronic perioral administration of HPD 4.5 mg/day on regional cerebral blood flow (rCBF) with 99mTc-HMPAO SPECT were investigated in 12 drug-naive schizophrenic patients with acute hallucinatory and delusional state. Further, the SPECT examinations were performed on 20 normal adult volunteers to investigate differences in rCBFs between schizophrenics and the normal subjects. Results are itemized as follows. The rCBF values were significantly increased in the bilateral superior and middle frontal, cingulate, middle temporal, pre-and post-central gyri, the left superior temporal gyrus, the bilateral inferior parietal lobule, and the bilateral hippocampal and thalamic cortices in comparison between normal subjects and before the HPD dose in schizophrenics. However, the rCBF values after the HPD dose showed significant increases only in the bilateral pre-and post-central gyri in comparison with the normal subjects. The rCBF values were significantly decreased in the bilateral superior, middle and inferior frontal, superior and middle temporal gyri, and the left insular gyrus after the HPD dose in comparison with before the HPD dose. The psychiatric assessment with PANSS showed an improvement of positive symptoms consisting of auditory hallucination and delusions after the HPD dose. Statistical analyses on relationships between the rCBF values and PANSS scores before and after the HPD dose showed positive correlations between the right inferior frontal gyrus and auditory hallucination or positive symptoms, between the right superior temporal gyrus, left thalamus and delusions, and between the left thalamus, insular gyrus and negative symptoms. These results suggest that acute drug-naive schizophrenic patients have widespread cortico-subcortical energic hypermetabolism and HPD reduces the hypermetabolism, leading to whole normalized brain metabolism, in particular with the larger region

  5. Effects of typical antipsychotic, haloperidol on regional cerebral blood flow in drug-naive schizophrenic patients-study with 99mTc-HMPAO SPECT

    Energy Technology Data Exchange (ETDEWEB)

    Kamoya, Masatoshi [Kanazawa Medical Univ., Ishikawa (Japan)

    2001-03-01

    For the purpose of examining antipsychotic action of haloperidol (HPD), effects of chronic perioral administration of HPD 4.5 mg/day on regional cerebral blood flow (rCBF) with 99mTc-HMPAO SPECT were investigated in 12 drug-naive schizophrenic patients with acute hallucinatory and delusional state. Further, the SPECT examinations were performed on 20 normal adult volunteers to investigate differences in rCBFs between schizophrenics and the normal subjects. Results are itemized as follows. The rCBF values were significantly increased in the bilateral superior and middle frontal, cingulate, middle temporal, pre-and post-central gyri, the left superior temporal gyrus, the bilateral inferior parietal lobule, and the bilateral hippocampal and thalamic cortices in comparison between normal subjects and before the HPD dose in schizophrenics. However, the rCBF values after the HPD dose showed significant increases only in the bilateral pre-and post-central gyri in comparison with the normal subjects. The rCBF values were significantly decreased in the bilateral superior, middle and inferior frontal, superior and middle temporal gyri, and the left insular gyrus after the HPD dose in comparison with before the HPD dose. The psychiatric assessment with PANSS showed an improvement of positive symptoms consisting of auditory hallucination and delusions after the HPD dose. Statistical analyses on relationships between the rCBF values and PANSS scores before and after the HPD dose showed positive correlations between the right inferior frontal gyrus and auditory hallucination or positive symptoms, between the right superior temporal gyrus, left thalamus and delusions, and between the left thalamus, insular gyrus and negative symptoms. These results suggest that acute drug-naive schizophrenic patients have widespread cortico-subcortical energic hypermetabolism and HPD reduces the hypermetabolism, leading to whole normalized brain metabolism, in particular with the larger region

  6. Incident users of antipsychotics

    DEFF Research Database (Denmark)

    Baandrup, Lone; Kruse, Marie

    2016-01-01

    PURPOSE: In Denmark, as well as in many other countries, consumption of antipsychotics is on the rise, partly due to increasing off-label use. The aim of this study was to analyze and quantify the extent of off-label use and polypharmacy in incident users of antipsychotic medication, and to examine...

  7. Acalabrutinib (ACP-196: a selective second-generation BTK inhibitor

    Directory of Open Access Journals (Sweden)

    Jingjing Wu

    2016-03-01

    Full Text Available Abstract More and more targeted agents become available for B cell malignancies with increasing precision and potency. The first-in-class Bruton’s tyrosine kinase (BTK inhibitor, ibrutinib, has been in clinical use for the treatment of chronic lymphocytic leukemia, mantle cell lymphoma, and Waldenstrom’s macroglobulinemia. More selective BTK inhibitors (ACP-196, ONO/GS-4059, BGB-3111, CC-292 are being explored. Acalabrutinib (ACP-196 is a novel irreversible second-generation BTK inhibitor that was shown to be more potent and selective than ibrutinib. This review summarized the preclinical research and clinical data of acalabrutinib.

  8. Second generation wave energy device - the clam concept

    Energy Technology Data Exchange (ETDEWEB)

    Bellamy, N.W.

    1981-01-01

    A device concept is presented which has arisen from a system approach adopted by a research group with considerable experience in the discipline of wave energy. The Clam, which can be classified as a spine-based pneumatic terminator, is deemed to be a second generation wave energy device in that it tries to utilize system components already identified as attractive, while at the same time avoiding known problem areas. A working model of this wave power device at an engineering scale is discussed for trials in real waves. 3 refs.

  9. Comparative study of wavelets of the first and second generation

    International Nuclear Information System (INIS)

    Ososkov, G.A.; Shitov, A.B.; Stadnik, A.V.

    2001-01-01

    In order to compare efficiency a comprehensive set of benchmarking tests is developed, which is used to compare abilities of continuous wavelet transform of the vanishing momenta type as well as the second generation wavelets constructed on the basis of the lifting scheme. It is based on processing of various types of pure and contaminated harmonic signals, delta-function, study of the signal phase dependence and the gain-frequency characteristics. The results of a comparative multiscale analysis allow one to reveal advantages and flaws of the considered types of wavelets

  10. Second generation superconducting super collider dipole magnet cryostat design

    International Nuclear Information System (INIS)

    Niemann, R.C.; Bossert, R.C.; Carson, J.A.; Engler, N.H.; Gonczy, J.D.; Larson, E.T.; Nicol, T.H.; Ohmori, T.

    1988-12-01

    The SSC Magnet Development Program is developing accelerator dipole magnets in successive iterations. The initial iteration is complete with six full length model magnets and a thermal model having been built and tested. This initial experience along with the evolving SSC Magnet System Requirements have resulted in the second generation magnet cryostat design. It is this configuration that will be employed for the near term ongoing magnetic, thermal, string and accelerated life testing and will be the design considered for Phase I; i.e., Technology Orientation, of the SSC Magnet Industrialization Program. 5 refs., 7 figs., 1 tab

  11. Isomerization of Second-Generation Isoprene Peroxy Radicals

    DEFF Research Database (Denmark)

    D'Ambro, Emma L.; Møller, Kristian Holten; Lopez-Hilfiker, Felipe D.

    2017-01-01

    kinetics box model, we find that to explain the behavior of low-volatility products and SOA mass yields relative to input H2O2 concentrations, the second-generation dihydroxy hydroperoxy peroxy radical (C5H11O6·) must undergo an intramolecular H-shift with a net forward rate constant of order 0.1 s-1...... products under atmospheric conditions and, thus, on the importance of nonreactive gas-particle partitioning of isoprene oxidation products as an SOA source....

  12. A second-generation superconducting undulator cryostat for the APS

    Science.gov (United States)

    Fuerst, J.; Hasse, Q.; Ivanyushenkov, Y.; Kasa, M.; Shiroyanagi, Y.

    2017-12-01

    A second-generation cryocooler-based cryostat has been designed and built to support a new helically wound superconducting undulator (SCU) magnet for the Advanced Photon Source (APS) at Argonne National Laboratory (ANL). The design represents an evolution of existing SCU cryostats currently in operation in the APS storage ring. Value engineering and lessons learned have resulted in a smaller, cheaper, and simpler cryostat design compatible with existing planar magnets as well as the new helically wound device. We describe heat load and quench response results, design and operational details, and the “build-to-spec” procurement strategy.

  13. Pharmaco-epidemiological description of the population of the Marche Region (central Italy treated with the antipsychotic drug olanzapine

    Directory of Open Access Journals (Sweden)

    Fiorenzo Mignini

    2013-03-01

    Full Text Available BACKGROUND. In Italy, even though olanzapine has been discouraged for treatment of behaviour disorders in older patients affected by dementia, some physicians chose to prescribe for them. In response to this situation, the Italian Drug Agency (Agenzia Italiana del Farmaco, AIFA promulgated a cautionary note. MATERIALS AND METHODS. This study examined epidemiological indices for olanzapine prescriptions between 2004 and 2007 in the Marche Region of central Italy and in its provinces, to assess physician compliance with the AIFA note, and to determine whether there were differences in drug prescription between populations of the same territory, or differences based on gender or age group. RESULTS. Our analyses revealed high olanzapine use among young men and mature women, suggesting that these groups are most prone to psychotic symptoms. Analysis revealed that olanzapine prescription in elderly patients was reduced in some provinces, in line with the AIFA note. CONCLUSIONS. Prudent use of olanzapine prescription, in compliance with the AIFA note, was noted throughout the Region. Furthermore, this work offers details that may be useful in future studies of adverse drug reactions.

  14. ATYPICAL ANTIPSYCHOTICS USE IN CHILDREN AND ADOLESCENTS

    Directory of Open Access Journals (Sweden)

    Nataša Potočnik-Dajčman

    2002-06-01

    Full Text Available Background. Classical antipsychotics – neuroleptics are one of the most frequently prescribed psychotropic drugs in child psychiatry. Atypical antipsychotics are used for the same indications – psychotic (schizophrenia as well as unpsychotic disorders (pervasive developmental disorders, mood disorders, conduct disorders and tics disorders. It is surprising that the studies on their use with regard to this age group are rather rare. They are carried out on a small number of samples and only exceptionally double blind. This article summarizes published clinical experience with atypical antipsychotics in children and adolescents. A short overview of pharmacodynamics, pharmacokinetics and side effects is given. Schizophrenia and pervasive developmental disorders are major indications for use of atypical antipsychotics in children and adolescents, but they have also been successfully used for other disorders such as aggressive behaviour, tics and anorexia nervosa.Conclusions. With better side-effect profile, some of the atypical antipsychotics are expected to be doctrinally recognised as the first-line treatment for childhood schizophrenia and pervasive developmental disorders. However, more long-term studies carried out on a larger sample are needed. Atypical antipsychotics are already used in everyday practice as first-line treatment of childhood and adolescents schizophrenia.

  15. An explorative study of school performance and antipsychotic medication

    NARCIS (Netherlands)

    van der Schans, J.; Vardar, S; Cicek, R.; Bos, H. J.; Hoekstra, P. J.; de Vries, T. W.; Hak, E.

    2016-01-01

    Background: Antipsychotic therapy can reduce severe symptoms of psychiatric disorders, however, data on school performance among children on such treatment are lacking. The objective was to explore school performance among children using antipsychotic drugs at the end of primary education. Methods:

  16. Promon's participation in the Brasilsat program: first & second generations

    Science.gov (United States)

    Depaiva, Ricardo N.

    This paper presents an overview of the Brasilsat program, space and ground segments, developed by Hughes and Promon. Promon is a Brazilian engineering company that has been actively participating in the Brasilsat Satellite Telecommunications Program since its beginning. During the first generation, as subcontractor of the Spar/Hughes/SED consortium, Promon had a significant participation in the site installation of the Ground Segment, including the antennas. During the second generation, as partner of a consortium with Hughes, Promon participated in the upgrade of Brasilsat's Ground Segment systems: the TT&C (TCR1, TCR2, and SCC) and the COCC (Communications and Operations Control Center). This upgrade consisted of the design and development of hardware and software to support the second generation requirements, followed by integration and tests, factory acceptance tests, transport to site, site installation, site acceptance tests and warranty support. The upgraded systems are distributed over four sites with remote access to the main ground station. The solutions adopted provide a high level of automation, and easy operator interaction. The hardware and software technologies were selected to provide the flexibility to incorporate new technologies and services from the demanding satellite telecommunications market.

  17. Search for first and second generation leptoquarks at D0

    International Nuclear Information System (INIS)

    Abachi, S.; Abbott, B.; Abolins, M.

    1995-07-01

    A search for first and second generation pair produced scalar leptoquarks has been done with the DO detector at Fermilab's p bar p machine with √s = 1.8 TeV. Leptoquarks are assumed to be strictly generational; for example, a first generation leptoquark couples only to the electron, its neutrino, and the u and d quarks. 95% C.L. mass limits of 133 GeV/c 2 and 120 GeV/c 2 for respective 100% and 50% decay branching ratios to electron plus quark for first generation scalar leptoquarks have been published. The preliminary results of a search for second generation scalar leptoquarks in the absence of a signal are mass limits of 111 GeV/c 2 and 89 GeV/c 2 for 100% and 50% decay branching ratios to muon plus quark. A feature of these mass limits is that they are independent of the unknown coupling of the leptoquark to leptons and quarks. The detection for e + e - and e-p machines depends on the strength of this coupling

  18. UrtheCast Second-Generation Earth Observation Sensors

    Science.gov (United States)

    Beckett, K.

    2015-04-01

    UrtheCast's Second-Generation state-of-the-art Earth Observation (EO) remote sensing platform will be hosted on the NASA segment of International Space Station (ISS). This platform comprises a high-resolution dual-mode (pushbroom and video) optical camera and a dual-band (X and L) Synthetic Aperture RADAR (SAR) instrument. These new sensors will complement the firstgeneration medium-resolution pushbroom and high-definition video cameras that were mounted on the Russian segment of the ISS in early 2014. The new cameras are expected to be launched to the ISS in late 2017 via the Space Exploration Technologies Corporation Dragon spacecraft. The Canadarm will then be used to install the remote sensing platform onto a CBM (Common Berthing Mechanism) hatch on Node 3, allowing the sensor electronics to be accessible from the inside of the station, thus limiting their exposure to the space environment and allowing for future capability upgrades. The UrtheCast second-generation system will be able to take full advantage of the strengths that each of the individual sensors offers, such that the data exploitation capabilities of the combined sensors is significantly greater than from either sensor alone. This represents a truly novel platform that will lead to significant advances in many other Earth Observation applications such as environmental monitoring, energy and natural resources management, and humanitarian response, with data availability anticipated to begin after commissioning is completed in early 2018.

  19. A quest for antipsychotic drug actions in the brain: personal experiences from 50 years of neuropsychiatric research at Karolinska Institutet.

    Science.gov (United States)

    Sedvall, Göran

    2007-09-10

    The exploration of physiological and molecular actions of psychoactive drugs in the brain represents a fundamental approach to the understanding of emerging psychological phenomena. The author gives a personal account of his medical training and research career at Karolinska Institutet over the past 50 years. The paper aims at illustrating how a broad medical education and the integration of basic and clinical neuroscience research is a fruitful ground for the development of new methods and knowledge in this complicated field. Important aspects for an optimal research environment are recruitment of well-educated students, a high intellectual identity of teachers and active researchers, international input and collaboration in addition to good physical resources. In depth exploration of specific signaling pathways as well as an integrative analysis of genes, molecules and systems using multivariate modeling, and bioinformatics, brain mechanisms behind mental phenomena may be understood at a basic level and will ultimately be used for the alleviation and treatment of mental disorders.

  20. [Treatment of Adult Schizophrenic Patients With Depot Antipsychotics].

    Science.gov (United States)

    Jaramillo González, Luis Eduardo; Gómez Restrepo, Carlos; García Valencia, Jenny; de la Hoz Bradford, Ana María; Ávila-Guerra, Mauricio; Bohórquez Peñaranda, Adriana

    2014-01-01

    To determine the indications of long-acting antipsychotic injection and what its effectiveness and safety in adult patients with schizophrenia during the treatment maintenance phase. A clinical practice guideline was elaborated under the parameters of the Methodological Guide of the Ministerio de Salud y Protección Social to identify, synthesize and evaluate the evidence and make recommendations about the treatment and follow-up of adult patients with schizophrenia. The evidence of NICE guide 82 was adopted and updated. The evidence was presented to the Guideline Developing Group and recommendations, employing the GRADE system, were produced. The literature review shows that the evidence has moderate to low quality. 8 articles were used. The risk of relapse was lower with depot risperidone and paliperidone palmitate when compared with placebo. For the risk of hospitalizations comparing depot antipsychotics (APD) versus oral AP, the result is inconclusive. Globally the second-generation APD had a lower risk of discontinuation when compared with placebo. The second generation AP had higher risk of extrapyramidal syndromes than placebo, as in the use of antiparkinsonian. The comparison of second-generation AP injections versus placebo showed an increased risk of early weight gain. The use of depot antipsychotics in the maintenance phase of adult patients diagnosed with schizophrenia is recommended if there is no adherence to oral antipsychotics as the patient's preference. It is not recommended depot antipsychotics in the acute phase of schizophrenia in adults. Copyright © 2014 Asociación Colombiana de Psiquiatría. Publicado por Elsevier España. All rights reserved.

  1. [The key role of patient in the antipsychotic therapy: shared decision making, adherence and research].

    Science.gov (United States)

    Gallingani, Francesca; Piccinni, Carlo; Simeoni, Angela; Poluzzi, Elisabetta; Menchetti, Marco; Berardi, Domenico

    2015-11-01

    A large number of currently available antipsychotic drugs are included into two main classes: traditional (or first-generation), and atypical (or second-generation) antipsychotics. This wide availability of medicinal products allows, at least in part, to address the need to identify the most appropriate treatment for the individual patient. A precondition for the effectiveness of antipsychotic treatment is the adherence, a multi-determined phenomenon that depends on factors related to the pharmacological properties of each agent and on factors independent from the therapy: among them, therapeutic alliance between patients and medical team, patient's belief in benefits and risks of medicines, and patient's relationship with the family and social environment are the most clearly recognized. The collection of data from patient helps the management of the individual clinical case, but this information could also become a source of data for research. In both cases, data must be collected in a ordered and well-coded way, therefore numerous instruments (like questionnaires and registers) are developing. This approach permits to make a recognition of patient's perception of his health condition, as well as the positive and negative outcomes of his pharmacological treatment. These tools are known in the literature by the name of PROMs (patient-reported outcome measures). From the clinical point of view, the PROMs can reduce the gap between patient and clinician in different therapeutic areas. They also enables the physician to identify the most suitable treatment to the individual patient, to meet his needs and preferences, and to adapt the therapy over time to the changes of his medical condition. About the research, the effects reported by the patient, in terms of both benefits and adverse reactions, represent important information useful to conduct observational studies that better define the benefit-risk profile of drug therapies, especially in psychiatry.

  2. Second-generation 1024-channel portable gamma-ray spectrometer

    International Nuclear Information System (INIS)

    McGibbon, A.L.

    1976-01-01

    Following the successful design in 1974 of a 256-channel battery-powered pulse-height analyzer system, we have completed a second-generation analyzer with advanced features, lighter weight, and more rugged construction. The 17-kg analyzer includes a NaI detector and is packaged as a small suitcase; it has high stability and accuracy to allow use over the temperature range from --30 to +70 0 C. The waterproof unit has many features not found on any commercial unit to allow sophisticated analysis by non-electronics oriented personnel. Its 36-button keyboard will allow manipulation of multiple spectra, integrations, and expanded energy scale with readout in keV. If its self-contained SX70 display camera is not sufficient for record keeping, the unit will telemeter all data onto analog tape or send to a remote computer via phone coupler

  3. Search for Second Generation Leptoquarks in the dimuon channel

    Energy Technology Data Exchange (ETDEWEB)

    Song, Xiaofei [Northern Illinois Univ., DeKalb, IL (United States)

    2005-08-01

    A search for second generation leptoquarks in p$\\bar{p}$ collision s at the Fermilab Teva- tron is presented using DØ data with an integrated luminosit y of 370 pb -1 collected in Run II between September 2002 and August 2004 at a center of mass energy of √ s =1.96 TeV. Leptoquarks are assumed to be pair produced, and e ach decays into a muon and a quark with a branching ratio of β . The number of events in data after the selection cuts is consistent with the expected Standard Model background. No evidence for leptoquark production is found; a lower limit o f 247 GeV (NN based), 236 GeV (cut based) for β = 1 and 184 GeV (NN based), 174 GeV (cut based) for β = 1 / 2 on the leptoquark mass at the 95% confidence level is obtained.

  4. Use of extremophilic bacteria for second generation bioethanol production

    DEFF Research Database (Denmark)

    Tomás, Ana Faria; Karakashev, Dimitar Borisov; Angelidaki, Irini

    production from food crops, such as corn (starch) or sugar cane (sucrose) is already an established process, with the USA and Brazil supplying 86% of the market. The major challenge remains in the use of different waste sources – agricultural, forestry, animal and household waste - as a feedstock....... The recalcitrance of these materials and their diverse sugar composition make the industrial yeast strains currently used unsuitable for a second generation bioethanol production process. One of the alternative strategies is the use of extreme thermophilic microorganisms. Currently, selected members from the genera...... Clostridium, Thermoanaerobacter, Geobacillus and Thermoanaerobacterium are among the best candidates. A new strain of Thermoanaerobacter, closely related to T. italicus and T. mathranii, has achieved 0.43 gethanol/gxylose, which is 83% of the theoretical yield of ethanol based on xylose and the highest value...

  5. Development of second-generation pressurized fluidized bed combustion process

    Energy Technology Data Exchange (ETDEWEB)

    Wolowodiuk, W.; Robertson, A. [Foster Wheeler Development Corp., Livingston, NJ (United States); Bonk, D. [Dept. of Energy, Morgantown, WV (United States)

    1995-12-01

    Under the sponsorship of the United States Department of Energy, Foster Wheeler Development Corporation, and its team members, Westinghouse, Gilbert/Commonwealth, and the Institute of Gas Technology are developing second-generation pressurized fluidized bed combustion technology capable of achieving net plant efficiency in excess of 45 percent based on the higher heating value of the coal. A three-phase program entails design and costing of a 500 MWe power plant and identification of developments needed to commercialize this technology (Phase 1), testing of individual components (Phase 2), and finally testing these components in an integrated mode (Phase 3). This paper briefly describes the results of the first two phases as well as the progress on the third phase. Since other projects which use the same technology are in construction or in negotiation stages-namely, the Power System Development Facility and the Four Rivers Energy Modernization Projects-brief descriptions of these are also included.

  6. Panorama 2014 - Overview of second-generation biofuel projects

    International Nuclear Information System (INIS)

    Bouter, Anne; Lorne, Daphne

    2013-12-01

    Second-generation biofuels produced from lingo-cellulosic biomass are now one of the main technological options for reducing the climatic impacts imposed by fuels used in transportation. These processes are designed to significantly boost the quantities of biofuels available and to take over from their first-generation counterparts, given the ready availability of raw materials and their excellent environmental performances. They are already the subject of multiple pre-industrial scale projects in many regions of the world as part of R and D programs, and the first industrial installations are already operational or under construction, the majority of them in Europe and the United States. They now require a stable regulatory framework in order to progress to the industrial learning stage required for them to become fully competitive. This is why the current uncertainties surrounding regulations in Europe and to a lesser extent in the United States could delay their development. (authors)

  7. Process Alternatives for Second Generation Ethanol Production from Sugarcane Bagasse

    DEFF Research Database (Denmark)

    F. Furlan, Felipe; Giordano, Roberto C.; Costa, Caliane B. B.

    2015-01-01

    on the economic feasibility of the process. For the economic scenario considered in this study, using bagasse to increase ethanol production yielded higher ethanol production costs compared to using bagasse for electric energy production, showing that further improvements in the process are still necessary.......In ethanol production from sugarcane juice, sugarcane bagasse is used as fuel for the boiler, to meet the steam and electric energy demand of the process. However, a surplus of bagasse is common, which can be used either to increase electric energy or ethanol production. While the first option uses...... already established processes, there are still many uncertainties about the techno-economic feasibility of the second option. In this study, some key parameters of the second generation ethanol production process were analyzed and their influence in the process feasibility assessed. The simulated process...

  8. Second-generation Holocaust survivors: Psychological, theological, and moral challenges.

    Science.gov (United States)

    Juni, Samuel

    2016-01-01

    Drawing from trauma theory, psychodynamic conceptualization, developmental psychology, clinical data, and personal experience, this article portrays a life haunted by tragedy predating its victims. Healthy child development is outlined, with particular attention to socialization and theological perspectives. Key characteristics of trauma are delineated, highlighting the nuances of trauma that are most harmful. As is the case with general trauma, Holocaust survivors are described as evincing survivor's guilt and paranoia in response to their experiences. Divergent disorders resulting from the Holocaust are described for 1st-generation and 2nd-generation survivors, respectively. Primary trauma responses and pervasive attitudes of survivors are shown to have harmful ramifications on their children's personality and worldview as well as on their interpersonal and theistic object relations. These limitations translate into problems in the adult lives of second generation survivors.

  9. Development of second-generation PFB combustion plants

    Energy Technology Data Exchange (ETDEWEB)

    Robertson, A.; Domeracki, W.; Horazak, D. [and others

    1995-12-31

    Research is being conducted under United States Department of Energy (USDOE) Contract DE-AC21-86MC21023 to develop a new type of coal-fueled plant for electric power generation. This new type of plant--called an Advanced or Second-generation Pressurized Fluidized Bed Combustion (APFBC) plant--offers the promise of efficiencies greater than 45 percent (HHV), with both emissions and a cost of electricity that are significantly lower than conventional pulverized-coal-fired plants with scrubbers. This paper summarizes the pilot-plant R&D work being conducted to develop this new type of plant and discusses a proposed design that should reduce demonstration-plant risks and costs.

  10. Second generation spectrograph for the Hubble Space Telescope

    Science.gov (United States)

    Woodgate, B. E.; Boggess, A.; Gull, T. R.; Heap, S. R.; Krueger, V. L.; Maran, S. P.; Melcher, R. W.; Rebar, F. J.; Vitagliano, H. D.; Green, R. F.; Wolff, S. C.; Hutchings, J. B.; Jenkins, E. B.; Linsky, J. L.; Moos, H. W.; Roesler, F.; Shine, R. A.; Timothy, J. G.; Weistrop, D. E.; Bottema, M.; Meyer, W.

    1986-01-01

    The preliminary design for the Space Telescope Imaging Spectrograph (STIS), which has been selected by NASA for definition study for future flight as a second-generation instrument on the Hubble Space Telescope (HST), is presented. STIS is a two-dimensional spectrograph that will operate from 1050 A to 11,000 A at the limiting HST resolution of 0.05 arcsec FWHM, with spectral resolutions of 100, 1200, 20,000, and 100,000 and a maximum field-of-view of 50 x 50 arcsec. Its basic operating modes include echelle model, long slit mode, slitless spectrograph mode, coronographic spectroscopy, photon time-tagging, and direct imaging. Research objectives are active galactic nuclei, the intergalactic medium, global properties of galaxies, the origin of stellar systems, stelalr spectral variability, and spectrographic mapping of solar system processes.

  11. Superconducting super collider second generation dipole magnet cryostat design

    International Nuclear Information System (INIS)

    Niemann, R.C.; Bossert, R.C.; Carson, J.A.; Engler, N.H.; Gonczy, J.D.; Larson, E.T.; Nicol, T.H.; Ohmori, T.

    1988-12-01

    The Superconducting Super Collider, a planned colliding beam particle physics research facility, requires /approximately/10,000 superconducting devices for the control of high energy particle beams. The /approximately/7,500 collider ring superconducting dipole magnets require cryostats that are functional, cryogenically efficient, mass producible and cost effective. A second generation cryostat design has been developed utilizing the experiences gained during the construction, installation and operation of several full length first generation dipole magnet models. The nature of the cryostat improvements is presented. Considered are the connections between the magnet cold mass and its supports, cryogenic supports, cold mass axial anchor, thermal shields, insulation, vacuum vessel and interconnections. The details of the improvements are enumerated and the abstracted results of available component and system evaluations are presented. 8 refs., 11 figs

  12. Evaluation of second-generation central receiver technologies

    International Nuclear Information System (INIS)

    Kolb, G.L.; Chavez, J.M.; Klimas, P.; Meinecke, W.; Becker, M.; Kiera, M.

    1993-01-01

    This paper summarizes the results of a study performed by the US and Germany to assess the technical and economic potential of central receiver power plants and to identify the necessary research and development (R ampersand D) activities required to reach demonstration and commercialization. Second generation power plant designs, employing molten-salt and volumetric-air receivers, were assessed at the size of 30 and 100 MWe. The study developed a common guideline and used data from previous system tests and studies. The levelized-energy costs for the second generation plants were estimated and found to be competitive with costs from fossil-fueled power plants. Potential for further cost reductions exists if technical improvements can be introduced successfully in the long term. Additionally, the study presents results of plant reliability and uncertainty analyses. Mid- and long-term technical potentials are described, as well as recommendations for the R ampersand D activities needed to reach the goal of large-scale commercialization. The results of this study have already helped direct research in the US and Europe. For example, the favorable potential for these technologies has led to the Solar Two molten-salt project in the US and the TSA volumetric receiver test in Spain. In addition, early analysis conducted within this study indicated that an advanced thermal storage medium was necessary to achieve favorable economics for the air plant. This led to the design of the thermal storage system currently being tested in Spain. In summary, each of the investigated receiver technologies has mid- and long-term potential for improving plant performance and reducing capital and energy costs (resulting in less than 10 cts/kWh given excellent insolation conditions) in an environmentally safe way and largely independent of fossil-fuel prices

  13. Second generation sequencing of the mesothelioma tumor genome.

    Directory of Open Access Journals (Sweden)

    Raphael Bueno

    2010-05-01

    Full Text Available The current paradigm for elucidating the molecular etiology of cancers relies on the interrogation of small numbers of genes, which limits the scope of investigation. Emerging second-generation massively parallel DNA sequencing technologies have enabled more precise definition of the cancer genome on a global scale. We examined the genome of a human primary malignant pleural mesothelioma (MPM tumor and matched normal tissue by using a combination of sequencing-by-synthesis and pyrosequencing methodologies to a 9.6X depth of coverage. Read density analysis uncovered significant aneuploidy and numerous rearrangements. Method-dependent informatics rules, which combined the results of different sequencing platforms, were developed to identify and validate candidate mutations of multiple types. Many more tumor-specific rearrangements than point mutations were uncovered at this depth of sequencing, resulting in novel, large-scale, inter- and intra-chromosomal deletions, inversions, and translocations. Nearly all candidate point mutations appeared to be previously unknown SNPs. Thirty tumor-specific fusions/translocations were independently validated with PCR and Sanger sequencing. Of these, 15 represented disrupted gene-encoding regions, including kinases, transcription factors, and growth factors. One large deletion in DPP10 resulted in altered transcription and expression of DPP10 transcripts in a set of 53 additional MPM tumors correlated with survival. Additionally, three point mutations were observed in the coding regions of NKX6-2, a transcription regulator, and NFRKB, a DNA-binding protein involved in modulating NFKB1. Several regions containing genes such as PCBD2 and DHFR, which are involved in growth factor signaling and nucleotide synthesis, respectively, were selectively amplified in the tumor. Second-generation sequencing uncovered all types of mutations in this MPM tumor, with DNA rearrangements representing the dominant type.

  14. A second generation genetic map for rainbow trout (Oncorhynchus mykiss

    Directory of Open Access Journals (Sweden)

    Gahr Scott A

    2008-11-01

    Full Text Available Abstract Background Genetic maps characterizing the inheritance patterns of traits and markers have been developed for a wide range of species and used to study questions in biomedicine, agriculture, ecology and evolutionary biology. The status of rainbow trout genetic maps has progressed significantly over the last decade due to interest in this species in aquaculture and sport fisheries, and as a model research organism for studies related to carcinogenesis, toxicology, comparative immunology, disease ecology, physiology and nutrition. We constructed a second generation genetic map for rainbow trout using microsatellite markers to facilitate the identification of quantitative trait loci for traits affecting aquaculture production efficiency and the extraction of comparative information from the genome sequences of model fish species. Results A genetic map ordering 1124 microsatellite loci spanning a sex-averaged distance of 2927.10 cM (Kosambi and having 2.6 cM resolution was constructed by genotyping 10 parents and 150 offspring from the National Center for Cool and Cold Water Aquaculture (NCCCWA reference family mapping panel. Microsatellite markers, representing pairs of loci resulting from an evolutionarily recent whole genome duplication event, identified 180 duplicated regions within the rainbow trout genome. Microsatellites associated with genes through expressed sequence tags or bacterial artificial chromosomes produced comparative assignments with tetraodon, zebrafish, fugu, and medaka resulting in assignments of homology for 199 loci. Conclusion The second generation NCCCWA genetic map provides an increased microsatellite marker density and quantifies differences in recombination rate between the sexes in outbred populations. It has the potential to integrate with cytogenetic and other physical maps, identifying paralogous regions of the rainbow trout genome arising from the evolutionarily recent genome duplication event, and

  15. Uncertainty, irreversibility, and investment in second-generation biofuels

    Science.gov (United States)

    McCarty, Tanner Joseph

    The present study formalizes and quantifies the importance of uncertainty for investment in a corn-stover based cellulosic biofuel plant. Using a real options model we recover prices of gasoline that would trigger entry into the market and calculate the portion of that entry trigger price required to cover cost and the portion that corresponds to risk premium. We then discuss the effect of managerial flexibility on the entry risk premium and the prices of gasoline that would trigger mothballing, reactivation, and exit. Results show that the risk premium required by plants to enter the second-generation biofuel market is likely to be substantial. The analysis also reveals that a break-even approach (which ignores the portion of entry price composed of risk premium), and the traditional Marshallian approach (which ignores the portion of entry price composed of both the risk premium and the drift rate), would significantly underestimate the gasoline entry trigger price and the magnitude of that underestimation increases as both volatility and mean of gasoline prices increase. Results also uncover a great deal of hysteresis (i.e. a range of gasoline prices for which there is neither entry nor exit in the market) in entry/exit behavior by plants. Hysteresis increases as gasoline prices become more volatile. Hysteresis suggests that, at the industry level, positive (negative) demand shocks will have a significant impact on prices (production) and a limited impact on production (prices). In combination all of these results suggest that policies supporting second generation biofuels may have fallen short of their targets because of their failure to alleviate uncertainty.

  16. A consensus guideline for antipsychotic drug use for dementia in care homes. Bridging the gap between scientific evidence and clinical practice

    NARCIS (Netherlands)

    Zuidema, Sytse U.; Johansson, Alice; Selbaek, Geir; Murray, Matt; Burns, Alistair; Ballard, Clive; Koopmans, Raymond T. C. M.

    Background: To produce a practice guideline that includes a set of detailed consensus principles regarding the prescription of antipsychotics (APs) amongst people with dementia living in care homes. Methods: We used a modified Delphi consensus procedure with three rounds, where we actively specified

  17. Recruitment of beta-arrestin2 to the dopamine D2 receptor: insights into anti-psychotic and anti-parkinsonian drug receptor signaling

    DEFF Research Database (Denmark)

    Klewe, Ib V; Nielsen, Søren M; Tarpø, Louise

    2008-01-01

    , SNPA all acted as partial agonists with decreasing efficacy in the BRET assay. In contrast, a wide selection of typical and atypical anti-psychotics was incapable of stimulating beta-arrestin2 recruitment to the D2 receptor. Moreover, we observed that haloperidol, sertindole, olanzapine, clozapine...

  18. A consensus guideline for antipsychotic drug use for dementia in care homes. Bridging the gap between scientific evidence and clinical practice

    NARCIS (Netherlands)

    Zuidema, S.U.; Johansson, A; Selbaek, G.; Murray, M.; Burns, A.; Ballard, C.; Koopmans, R.T.C.M.

    2015-01-01

    BACKGROUND: To produce a practice guideline that includes a set of detailed consensus principles regarding the prescription of antipsychotics (APs) amongst people with dementia living in care homes. METHODS: We used a modified Delphi consensus procedure with three rounds, where we actively specified

  19. Climate regulation enhances the value of second generation biofuel technology

    Science.gov (United States)

    Hertel, T. W.; Steinbuks, J.; Tyner, W.

    2014-12-01

    Commercial scale implementation of second generation (2G) biofuels has long been 'just over the horizon - perhaps a decade away'. However, with recent innovations, and higher oil prices, we appear to be on the verge of finally seeing commercial scale implementations of cellulosic to liquid fuel conversion technologies. Interest in this technology derives from many quarters. Environmentalists see this as a way of reducing our carbon footprint, however, absent a global market for carbon emissions, private firms will not factor this into their investment decisions. Those interested in poverty and nutrition see this as a channel for lessening the biofuels' impact on food prices. But what is 2G technology worth to society? How valuable are prospective improvements in this technology? And how are these valuations affected by future uncertainties, including climate regulation, climate change impacts, and energy prices? This paper addresses all of these questions. We employ FABLE, a dynamic optimization model for the world's land resources which characterizes the optimal long run path for protected natural lands, managed forests, crop and livestock land use, energy extraction and biofuels over the period 2005-2105. By running this model twice for each future state of the world - once with 2G biofuels technology available and once without - we measure the contribution of the technology to global welfare. Given the uncertainty in how these technologies are likely to evolve, we consider a range cost estimates - from optimistic to pessimistic. In addition to technological uncertainty, there is great uncertainty in the conditions characterizing our baseline for the 21st century. For each of the 2G technology scenarios, we therefore also consider a range of outcomes for key drivers of global land use, including: population, income, oil prices, climate change impacts and climate regulation. We find that the social valuation of 2G technologies depends critically on climate change

  20. Second generation of TELEPERM XS applications successful in operation

    International Nuclear Information System (INIS)

    Weber, P.

    2008-01-01

    Safety I and C plays an important part in safety and availability of nuclear power plants. AREVA NP, the nuclear technology enterprise, recently began delivery of the second generation TELEPERM XS digital safety I and C technology. Qinshan 1, the first Chinese-built reactor, had its reactor protection system replaced. The plant has been back on the grid since January 12, 2008. Moreover, the Swedish Ringhals 1 nuclear generating unit has operated a neutron flux measuring system of the second-generation TELEPERM XS since October 2007. Both systems are running to their users' full satisfaction. TELEPERM XS has meanwhile been employed in 49 plants in twelve countries. This safety I and C system by AREVA NP can be used with nearly all reactor lines, for both new reactor designs and upgrading nuclear power plants in operation. Here are some examples of successful installations of reactor protection, reactor control and limiting, neutron flux measurement and Diesel power control systems with TELEPERM XS: the Tianwan 1 and 2 units in China (VVER plants), Oskarsham 2 in Sweden (boiling water reactor), and Neckarwestheim 1 and 2 in Germany (pressurized water reactors). TELEPERM XS systems are being planned for the new plants of Olkiluoto 3 in Finland (EPR), Flamanville 3 in France (EPR), Taishan 1 and 2 in China (EPR), and Ling Ao 3 and 4 in China (CPR 1000). For quick and unproblematic implementation of TELEPERM XS in a plant, the system with all subassemblies, functions, and input/output signals is fully tested in a testing station. For this purpose, AREVA NP built one of the largest testing stations in the world for I and C cabinets, the 'TELEPERM XS Integration Center', at its German location in Erlangen. More than 200 I and C cabinets can be tested simultaneously in these installations. The 'I and C and Electrical Systems' Forum is attached to the testing station. This is where the company presents to its customers and partner firms realistic solutions, in combination

  1. Study on effects of an atypical antipsychotic, risperidone on regional cerebral blood flow with 99mTc-HMPAO SPECT in drug-naive and unmedicated schizophrenic patients

    International Nuclear Information System (INIS)

    Koiwa, Daisuke

    2003-01-01

    To examine the underlying mechanisms of intracerebral or clinical actions of the atypical antipsychotic, risperidone (RIS), the effects of RIS on absolute regional cerebral blood flows (rCBFs) measured with 99mTc-HMPAO SPECT and correlations between the rCBFs and psychotic symptoms assessed with positive and negative syndrome scale (PANSS) were investigated in 10 drug-naive and unmedicated schizophrenic patients with acute hallucinatory and delusional state. Both the SPECT and PANSS were repeated before and after oral 2-week administration of RIS 3 mg/day in all of the 10 patients and after subsequent 2-week administration of RIS 4-6 mg/day in half of the patients. The rCBF values were significantly decreased in the left precentral gyrus alone after the low dose of RIS 3 mg/day in comparison with before the RIS dose. The rCBF values were significantly decreased in the right cingulate, postcentral, inferior parietal gyri and the left inferior temporal gyrus after the high dose of RIS 4-6 mg/day in comparison with before the low dose of RIS 3 mg/day. The psychiatric assessment with PANSS showed an improvement of positive and negative symptoms after the low RIS dose and still more after the high RIS dose. Statistical analyses on relationships between the rCBF values and PANSS scores before and after the low RIS dose showed a positive correlation between the rCBF values in the right middle temporal gyrus and hallucinations (mainly auditory hallucination). These results suggest that chronic RIS administration dose-dependently produces a decrease of rCBF in the cerebral cortex in the manner that the low dose decreases rCBF in a few restricted cortical regions, while the high dose induces the rCBF reduction in more widespread cortical regions. The RIS-induced rCBF decrease in the cerebral cortex is considered to be attributable to a secondary inactivation in the cerebral cortex due to D 2 dopamine receptor blockade of RIS in the striatum through the cortico

  2. Second-Generation Outcomes of the Great Migration.

    Science.gov (United States)

    Alexander, J Trent; Leibbrand, Christine; Massey, Catherine; Tolnay, Stewart

    2017-12-01

    The mass migration of African Americans out of the South during the first two-thirds of the twentieth century represents one of the most significant internal migration flows in U.S. Those undertaking the Great Migration left the South in search of a better life, and their move transformed the cultural, social, and political dynamics of African American life specifically and U.S. society more generally. Recent research offers conflicting evidence regarding the migrants' success in translating their geographic mobility into economic mobility. Due in part to the lack of a large body of longitudinal data, almost all studies of the Great Migration have focused on the migrants themselves, usually over short periods of their working lives. Using longitudinally linked census data, we take a broader view, investigating the long-term economic and social effects of the Great Migration on the migrants' children. Our results reveal modest but statistically significant advantages in education, income, and poverty status for the African American children of the Great Migration relative to the children of southerners who remained in the South. In contrast, second-generation white migrants experienced few benefits from migrating relative to southern or northern stayers.

  3. The ASAC Air Carrier Investment Model (Second Generation)

    Science.gov (United States)

    Wingrove, Earl R., III; Johnson, Jesse P.; Sickles, Robin C.; Good, David H.

    1997-01-01

    To meet its objective of assisting the U.S. aviation industry with the technological challenges of the future, NASA must identify research areas that have the greatest potential for improving the operation of the air transportation system. To accomplish this, NASA is building an Aviation System Analysis Capability (ASAC). The ASAC differs from previous NASA modeling efforts in that the economic behavior of buyers and sellers in the air transportation and aviation industries is central to its conception. To link the economics of flight with the technology of flight, ASAC requires a parametrically based mode with extensions that link airline operations and investments in aircraft with aircraft characteristics. This model also must provide a mechanism for incorporating air travel demand and profitability factors into the airlines' investment decisions. Finally, the model must be flexible and capable of being incorporated into a wide-ranging suite of economic and technical models that are envisioned for ASAC. We describe a second-generation Air Carrier Investment Model that meets these requirements. The enhanced model incorporates econometric results from the supply and demand curves faced by U.S.-scheduled passenger air carriers. It uses detailed information about their fleets in 1995 to make predictions about future aircraft purchases. It enables analysts with the ability to project revenue passenger-miles flown, airline industry employment, airline operating profit margins, numbers and types of aircraft in the fleet, and changes in aircraft manufacturing employment under various user-defined scenarios.

  4. Decoloring hemoglobin as a feedstock for second-generation bioplastics.

    Science.gov (United States)

    Low, Aaron; Lay, Mark; Verbeek, Johan; Swan, Janis

    2012-01-01

    The color of red blood cell concentrate (RBCC) limits its application in human food, but there is potential to use it for second-generation bioplastics. Several methods have been developed to remove color from RBCC, but they are expensive or may produce difficult-to-remove toxic residues. Hydrogen peroxide treatment is a cheaper alternative. The effects of RBCC concentration, pH, and reaction temperature were the most important factors influencing the decolorizing process. They were investigated with the aim of developing a method that could be scaled to commercial level for producing a bioplastic feedstock. Initial trials showed pH was an important factor for decolorization and foaming. At pH 15 there was a 96% reduction in solution color and 8.4% solids were lost due to foaming. There was a 76% reduction in solution color at pH 2 and only 2.6% solids were lost due to foaming. The optimal reaction conditions were to centrifuge 9% w/w, pH 2 aqueous RBCC solution to remove aggregates. The solution was reacted at 30°C with 7.5 g of 30% (w/w) hydrogen peroxide. These conditions achieved a 93% reduction in solution color after 3 hr and the molecular weight of the decolored protein was not significantly reduced.

  5. ADMAP-2: The second generation Antarctic crustal magnetic anomaly map.

    Science.gov (United States)

    Ferraccioli, F.; Golynsky, A.; Golynsky, D.; Young, D. A.; Eagles, G.; Damaske, D.; Finn, C.; Aitken, A.; von Frese, R. R. B.; Ghidella, M. E.; Kim, H. R.; Hong, J.

    2017-12-01

    ADMAP-2 is the second generation crustal magnetic anomaly compilation for the Antarctic region south of 60°S. It was produced from more than 3.5 million line-km of near-surface terrestrial, airborne and marine magnetic observations collected since the International Geophysical Year 1957/58 through 2013. The data were edited, IGRF corrected, profile levelled and gridded at a 1.5-km interval on a polar stereographic projection using the minimum curvature technique. Given the ubiquitous polar cover of snow, ice and sea water, the magnetic anomaly compilation offers important constraints on the global tectonic processes and crustal properties of the Antarctic. It also links widely separated areas of outcrop to help unify disparate geologic studies, and provides insights on the lithospheric transition between Antarctica and adjacent oceans, as well as the geodynamic evolution of the Antarctic lithosphere in the assembly and break-up of the Gondwana, Rodinia, and Columbia supercontinents and key piercing points for reconstructing linkages between the protocontinents. The magnetic data together with ice-probing radar and gravity information greatly facilitate understanding the evolution of fundamental large-scale geological processes such as continental rifting, intraplate mountain building, subduction and terrane accretion processes, and intraplate basin formation.

  6. SAT's infrared equipment using second-generation detectors

    Science.gov (United States)

    Siriex, Michel B.

    1995-09-01

    In 1982 SAT proposed for the first time a second generation detector in the design of FLIRs for the TRIGAT program, since then different types of IR equipment have been developed on the basis of this technology: (1) An infra-red seeker for the MICA missile. (2) Three types of IRST: VAMPIR MB for naval applications, SIRENE for the Army and OSF for the Rafale aircraft. (3) Three thermal imagers: Condor 1 for the mast mounted sight equipping the long range anti tank system, Tiger installed on the sight of the medium range antitank system, and Condor 2 for the pilot sight of the TRIGAT French-German helicopter. Infra-red detectors are MCT IR-CCD focal plane arrays developed by SOFRADIR with the objective of the best standardization possible in spite of different configurations and specifications for each program. In this paper, we intend to present the main features of this technology for these programs and the advantages obtained by comparison with the first generation in terms of performance. Industrialization of these products is starting now, and a specific effort has been made to standardize the components, especially the driving and read out electronics. A set of ASICs has been developed to make compact detection modules including a detector in his dewar, a cooling machine, and a proximity electronic.

  7. Study on effects of an atypical antipsychotic agent, quetiapine, on regional cerebral blood flow with 99mTc-ECD SPECT in drug-naive or unmedicated schizophrenic patients

    International Nuclear Information System (INIS)

    Monkawa, Akikazu

    2007-01-01

    The objective of this study was to investigate the underlying mechanisms of intracerebral actions or clinical efficacies of quetiapine, an atypical antipsychotic agent and a multi-action receptor targeting agent (MARTA), and the influences of quetiapine on absolute regional cerebral blood flows (rCBFs) of schizophrenic patients. Correlations between rCBFs and psychotic symptoms were also examined. Subjects comprised 12 patients who met the ICD-10 criteria for schizophrenia. All patients were drug-naive or unmedicated. Using single photon emission computed tomography (SPECT) with 99m Tc-ethyl cysteinate dimer (ECD), rCBFs were measured. Psychotic symptoms were evaluated with positive and negative syndrome scale (PANSS). The evaluations of SPECT and PANSS were repeated before and after oral 2-week administration of quetiapine 300 mg/day in all patients and after subsequent 2-week administration of quetiapine 600 mg/day in 6 patients. Administration of quetiapine yielded no significant changes in rCBFs at any dose. And there were no significant correlations between the scores of PANSS and the values of rCBFs in any region, though the scores of PANSS decreased after qutiapine administration. It has been reported that, a typical antipsychotic agent, haloperidol, and an atypical antipsychotic agent, risperidone, decrease rCBFs in the cerebral cortex in dose-dependently in drug-naive or unmedicated schizophrenic patients. This phenomenon is considered to be attributable to a secondary inactivation of the cerebral cortex due to D2 receptor blockade of haloperidol or risperidone in the striatum through the cortico-striatal-thalamic pathway. In the frame of this hypothesis, results of this study may relate to the lower degree of D2 blockade induced by quetiapine than that produced by haloperidol and risperidone. (author)

  8. Antipsychotic agents: efficacy and safety in schizophrenia

    Directory of Open Access Journals (Sweden)

    de Araújo AN

    2012-11-01

    Full Text Available Arão Nogueira de Araújo,1 Eduardo Pondé de Sena,1,2 Irismar Reis de Oliveira,1,3 Mario F Juruena41Postgraduation Program in Interactive Processes of Organs and Systems, 2Department of Pharmacology, Institute of Health Sciences, 3Department of Neurosciences and Mental Health, School of Medicine, Federal University of Bahia, Salvador, Brazil; 4Stress and Affective Disorders Program, Department of Neuroscience and Behavior, Faculty of Medicine of Ribeirao Preto, University of Sao Paulo, Sao Paulo, BrazilAbstract: Antipsychotics have provided a great improvement in the management of people with schizophrenia. The first generation antipsychotics could establish the possibility of managing many psychotic subjects in an outpatient setting. With the advent of the second (SGA and third generation antipsychotics (TGA, other psychiatric disorders such as bipolar depression, bipolar mania, autism, and major depressive disorder have now been approved for the use of these drugs for their treatment. Also, the administration of more specific assessment tools has allowed for better delineation of the repercussions of these drugs on symptoms and the quality of life of patients who use antipsychotic agents. In general, the SGA share similar mechanisms of action to achieve these results: dopamine-2 receptor antagonism plus serotonin-2A receptor antagonism. The TGA (eg, aripiprazole have partial agonist activity at the dopamine-2 receptor site, and are also called dopaminergic stabilizers. The pharmacological profile of SGA and TGA may provide better efficacy against negative symptoms, and are less likely to produce extrapyramidal symptoms; however, the SGA and TGA are associated with many other adverse events. The clinician has to balance the risks and benefits of these medications when choosing an antipsychotic for an individual patient.Keywords: antipsychotic agents, schizophrenia, pharmacology, safety

  9. Use of antipsychotics in the treatment of depressive disorders

    Institute of Scientific and Technical Information of China (English)

    Ping WANG; Tianmei SI

    2013-01-01

    There is a long history of using antipsychotic medications in the treatment of depressive disorders. Atypical antipsychotics, which have fewer side effects than traditional antipsychotics, have been used as monotherapy or adjunctively with antidepressants to treat depressive disorders with or without psychotic symptoms. The antidepressant effect of atypical antipsychotics involves regulation of monoamine, glutamate, gamma-aminobutyric acid (GABA), cortisol, and neurotrophic factors. To date, the United States Food and Drug Administration (USFDA) has approved aripiprazole and quetiapine slow-release tablets as adjunctive treatment for depressive disorders, and the combination of olanzapine and fluoxetine for the treatment of treatment-resistant depression. When using atypical antipsychotics in the treatment of depressed patients, clinicians need to monitor patients for the emergence of adverse effects including extrapyramidal symptoms (EPS), weight gain, and hyperglycemia.

  10. Antipsychotic Selection for Acute Agitation and Time to Repeat Use in a Psychiatric Emergency Department.

    Science.gov (United States)

    Gomez, Seth; Dopheide, Julie

    2016-11-01

    Early recognition and treatment of agitated patients is essential to avoid violence in the psychiatric emergency department (ED). Antipsychotics have established efficacy in managing agitation, yet little is known about how the choice of initial antipsychotic impacts time to repeat use and length of stay (LOS) in the psychiatric ED. To describe the impact of initial antipsychotic selection on time to repeat use and LOS in the psychiatric ED. A chart review identified 388 cases in which patients were administered an antipsychotic for agitation in the psychiatric ED between July 1 and August 31, 2014. Time to repeat use and LOS were compared for intramuscular (IM) haloperidol, other IM antipsychotics, and oral second-generation antipsychotics (SGAs) using the Kruskal-Wallis or Wilcoxon-Mann-Whitney test. Of the 388 cases, 31% (n=122) required repeat medications. Mean time to repeat use for IM haloperidol was 20.1±18.4 hours, which was not significantly different from mean time to repeat use in the groups receiving other IM antipsychotics or oral SGAs (P=0.35). The mean LOS was 29.7±28.7 hours for IM haloperidol, 30.3±36.9 hours for other IM antipsychotics, and 22.6±28.0 hours for oral SGAs. Significant differences in LOS between repeat and nonrepeat users of IM haloperidol and other IM antipsychotics were observed, but not among those who received oral SGAs. Mean time to repeat use ranged from 14 to 20 hours with IM haloperidol, other IM antipsychotics, and oral SGAs without significant differences in time to repeat use in the 3 different groups. Repeat users of IM antipsychotics had a significantly longer LOS in the ED compared with nonrepeat users of IM antipsychotics. However, patients who were initially administered oral SGAs did not have longer LOS in the ED even if a repeat dose was given.

  11. Antipsychotics and associated risk of out-of-hospital cardiac arrest.

    Science.gov (United States)

    Weeke, P; Jensen, A; Folke, F; Gislason, G H; Olesen, J B; Fosbøl, E L; Wissenberg, M; Lippert, F K; Christensen, E F; Nielsen, S L; Holm, E; Kanters, J K; Poulsen, H E; Køber, L; Torp-Pedersen, C

    2014-10-01

    Antipsychotic drugs have been associated with sudden cardiac death, but differences in the risk of out-of-hospital cardiac arrest (OHCA) associated with different antipsychotic drug classes are not clear. We identified all OHCAs in Denmark (2001-2010). The risk of OHCA associated with antipsychotic drug use was evaluated by conditional logistic regression analysis in case-time-control models. In total, 2,205 (7.6%) of 28,947 OHCA patients received treatment with an antipsychotic drug at the time of the event. Overall, treatment with any antipsychotic drug was associated with OHCA (odds ratio (OR) = 1.53, 95% confidence interval (CI): 1.23-1.89), as was use with typical antipsychotics (OR = 1.66, CI: 1.27-2.17). By contrast, overall, atypical antipsychotic drug use was not (OR = 1.29, CI: 0.90-1.85). Two individual typical antipsychotic drugs, haloperidol (OR = 2.43, CI: 1.20-4.93) and levomepromazine (OR = 2.05, CI: 1.18-3.56), were associated with OHCA, as was one atypical antipsychotic drug, quetiapine (OR = 3.64, CI: 1.59-8.30).

  12. Progress in second-generation HTS wire development and manufacturing

    International Nuclear Information System (INIS)

    Selvamanickam, V.; Chen, Y.; Xiong, X.; Xie, Y.; Zhang, X.; Rar, A.; Martchevskii, M.; Schmidt, R.; Lenseth, K.; Herrin, J.

    2008-01-01

    2007 has marked yet another year of continued rapid progress in developing and manufacturing high-performance, long-length second-generation (2G) HTS wires at high speeds. Using ion beam assisted deposition (IBAD) MgO and associated buffer sputtering processes, SuperPower has now exceeded piece lengths of 1000 m of fully buffered tape reproducibly with excellent in-plane texture of 6-7 degrees and uniformity of about 2%. These kilometer lengths are produced at high speeds of about 350 m/h of 4 mm wide tape. In combination with metal organic chemical vapor deposition (MOCVD), 2G wires up to single piece lengths to 790 m with a minimum critical current value of 190 A/cm corresponding to a Critical current x Length performance of 150,100 Am have been achieved. Tape speeds up to 180 m/h have been reached MOCVD while maintaining critical currents above 200 A/cm in 100+ m lengths. Thick film MOCVD technology has been transitioned to Pilot manufacturing system where a minimum critical current of 320 A/cm has been demonstrated over a length of 155 m processed at a speed of 70 m/h in 4 mm width. Finally, nearly 10,000 m of 2G wire has been produced, exhaustively tested, and delivered to the Albany Cable project. The average minimum critical current of the wire delivered in 225 segments of 43-44 m is 70 A in 4 mm widths. A 30 m cable has been fabricated with this wire by Sumitomo Electric and has been installed in the power grid of National Grid in downtown Albany and is the world's first 2G device installed in the grid

  13. Progress in second-generation HTS wire development and manufacturing

    Energy Technology Data Exchange (ETDEWEB)

    Selvamanickam, V. [SuperPower, Inc., 450 Duane Avenue, Schenectady, NY 12304 (United States)], E-mail: vselva@superpower-inc.com; Chen, Y.; Xiong, X.; Xie, Y.; Zhang, X.; Rar, A.; Martchevskii, M.; Schmidt, R.; Lenseth, K.; Herrin, J. [SuperPower, Inc., 450 Duane Avenue, Schenectady, NY 12304 (United States)

    2008-09-15

    2007 has marked yet another year of continued rapid progress in developing and manufacturing high-performance, long-length second-generation (2G) HTS wires at high speeds. Using ion beam assisted deposition (IBAD) MgO and associated buffer sputtering processes, SuperPower has now exceeded piece lengths of 1000 m of fully buffered tape reproducibly with excellent in-plane texture of 6-7 degrees and uniformity of about 2%. These kilometer lengths are produced at high speeds of about 350 m/h of 4 mm wide tape. In combination with metal organic chemical vapor deposition (MOCVD), 2G wires up to single piece lengths to 790 m with a minimum critical current value of 190 A/cm corresponding to a Critical current x Length performance of 150,100 Am have been achieved. Tape speeds up to 180 m/h have been reached MOCVD while maintaining critical currents above 200 A/cm in 100+ m lengths. Thick film MOCVD technology has been transitioned to Pilot manufacturing system where a minimum critical current of 320 A/cm has been demonstrated over a length of 155 m processed at a speed of 70 m/h in 4 mm width. Finally, nearly 10,000 m of 2G wire has been produced, exhaustively tested, and delivered to the Albany Cable project. The average minimum critical current of the wire delivered in 225 segments of 43-44 m is 70 A in 4 mm widths. A 30 m cable has been fabricated with this wire by Sumitomo Electric and has been installed in the power grid of National Grid in downtown Albany and is the world's first 2G device installed in the grid.

  14. Application of human reliability analysis methodology of second generation

    International Nuclear Information System (INIS)

    Ruiz S, T. de J.; Nelson E, P. F.

    2009-10-01

    The human reliability analysis (HRA) is a very important part of probabilistic safety analysis. The main contribution of HRA in nuclear power plants is the identification and characterization of the issues that are brought together for an error occurring in the human tasks that occur under normal operation conditions and those made after abnormal event. Additionally, the analysis of various accidents in history, it was found that the human component has been a contributing factor in the cause. Because of need to understand the forms and probability of human error in the 60 decade begins with the collection of generic data that result in the development of the first generation of HRA methodologies. Subsequently develop methods to include in their models additional performance shaping factors and the interaction between them. So by the 90 mid, comes what is considered the second generation methodologies. Among these is the methodology A Technique for Human Event Analysis (ATHEANA). The application of this method in a generic human failure event, it is interesting because it includes in its modeling commission error, the additional deviations quantification to nominal scenario considered in the accident sequence of probabilistic safety analysis and, for this event the dependency actions evaluation. That is, the generic human failure event was required first independent evaluation of the two related human failure events . So the gathering of the new human error probabilities involves the nominal scenario quantification and cases of significant deviations considered by the potential impact on analyzed human failure events. Like probabilistic safety analysis, with the analysis of the sequences were extracted factors more specific with the highest contribution in the human error probabilities. (Author)

  15. Search for second generation scalar leptoquarks using the ATLAS detector

    Energy Technology Data Exchange (ETDEWEB)

    Tam, Jason

    2014-07-24

    Leptoquarks are hypothetical particles that attempt to explain the coincidental similarities between leptons and quarks included in SM. Their exact properties vary between different theoretical models, and there are no strong theoretical constraints on their possible mass values. They can possibly be produced from particle collisions, and there have already been searching efforts at previous collider experiments. Their presence have not yet been observed, and this fact has been translated into lower bound exclusions on their possible mass values. The Large Hadron Collider (LHC) being the most recently constructed particle collider with the highest collision energies ever achieved experimentally, provides a new platform to continue the search for Leptoquarks at even higher mass ranges. This thesis describes a search for pair-produced second-generation Leptoquarks using 20.3 fb{sup -1} of data recorded by the ATLAS detector of LHC at √(s) = 8 TeV. Events with two oppositely charged muons and two or more jets in the final state were used. Candidate leptoquark events were selected with the help of four observables: the di-muon invariant mass (M{sub μμ}), the sum of the p{sub T} of the two muons (L{sub T}), the sum of the p{sub T} of the two leading jets (H{sub T}) and the average Leptoquark mass (M{sub LQ}). Monte Carlo simulations of SM background processes have shown to be in good agreement with data, both in the region constructed using selection requirements for candidate leptoquark events and in the designated control regions. Since no significant excess of events was observed in data, a exclusion limit was set as a function of the Leptoquark mass.

  16. Universal Authenticated Item Monitoring System (AIMS) second generation equipment

    International Nuclear Information System (INIS)

    Schoeneman, J.L.; Baumann, M.J.; Fox, L.J.; Jenkins, C.D.; Perlinsk, A.W.

    1992-01-01

    Sandia National Laboratories (SNL) is in the final stages of developing a Universal Authenticated Item Monitoring System (AIMS). When completed, AIMS will provide applicable agencies in the US government, and those in the International arena, with a secure and convenient method of monitoring the physical status of selected items. The benefit derived from this development activity will be the commercial availability of an item monitoring system with the capability for ''quick set-up'' monitoring, as well as long-term unattended monitoring. The AIMS includes a variety of sensors, a robust and authenticated radio frequency (RF) communication link, a Receiver Processing Unit (RPU), and an inspector-friendly personal computer (PC) interface for collecting, sorting, viewing and archiving pertinent event histories. The system will provide the capability to monitor selected items in a real-time mode, a remotely interrogated mode, and a stand-alone, unattended data collection mode. The sensor suite under development includes advanced motion sensors, interior volumetric intrusion sensors, Re-usable, In-situ Verifiable Authenticated (RIVA) fiber-optic seal sensors, generic utility sensors (to accommodate contact closure inputs), and radiation and environmental sensors. A new generation authentication algorithm recently has been developed that provides a high degree of system security 121. The AIMS has potential safeguards applications in the areas of arms control and treaty verification military asset control, International Atomic Energy Agency (IAEA) and Euratom safeguards verification activities, as well as domestic nuclear safeguard activities. Commercial applications could include high-value inventory control and security systems. This paper describes the second-generation AIMS along with its recently expanded sensor suite and enhanced data collection capabilities

  17. Current status of the UCSF second-generation PACS

    Science.gov (United States)

    Huang, H. K.; Arenson, Ronald L.; Wong, Albert W. K.; Bazzill, Todd M.; Lou, Shyhliang A.; Andriole, Katherine P.; Wang, Jun; Zhang, Jianguo; Wong, Stephen T. C.

    1996-05-01

    This paper describes the current status of the second generation PACS at UCSF commenced in October 1992. The UCSF PACS is designed in-house as a hospital-integrated PACS based on an open architecture concept using industrial standards including UNIX operating system, C programming language, X-Window user interface, TCP/IP communication protocol, DICOM 3.0 image standard and HL7 health data format. Other manufacturer's PACS components which conform with these standards can be easily integrated into the system. Relevant data from HIS and RIS is automatically incorporated into the PACS using HL7 data format and TCP/IP communication protocol. The UCSF system also takes advantage of state-of-the-art communication, storage, and software technologies in ATM, multiple storage media, automatic programming, multilevel processes for a better cost-performance system. The primary PACS network is the 155 Mbits/sec OC3 ATM with the Ethernet as the back-up. The UCSF PACS also connects Mt. Zion Hospital and San Francisco VA Medical Center in the San Francisco Bay area via an ATM wide area network with a T1 line as the back-up. Currently, five MR and five CT scanners from multiple sites, two computed radiography systems, two film digitizers, one US PACS module, the hospital HIS and the department RIS have been connected to the PACS network. The image data is managed by a mirrored database (Sybase). The PACS controller, with its 1.3 terabyte optical disk library, acquires 2.5 gigabytes digital data daily. Four 2K, five, 1,600-line multiple monitor display workstations are on line in neuroradiology, pediatric radiology and intensive care units for clinical use. In addition, the PACS supports over 100 Macintosh users in the department and selected hospital sites for both images and textual retrieval through a client/server mechanism. We are also developing a computation and visualization node in the PACS network for advancing radiology research.

  18. Second generation γ-secretase modulators exhibit different modulation of Notch β and Aβ production.

    Science.gov (United States)

    Wanngren, Johanna; Ottervald, Jan; Parpal, Santiago; Portelius, Erik; Strömberg, Kia; Borgegård, Tomas; Klintenberg, Rebecka; Juréus, Anders; Blomqvist, Jenny; Blennow, Kaj; Zetterberg, Henrik; Lundkvist, Johan; Rosqvist, Susanne; Karlström, Helena

    2012-09-21

    The γ-secretase complex is an appealing drug target when the therapeutic strategy is to alter amyloid-β peptide (Aβ) aggregation in Alzheimer disease. γ-Secretase is directly involved in Aβ formation and determines the pathogenic potential of Aβ by generating the aggregation-prone Aβ42 peptide. Because γ-secretase mediates cleavage of many substrates involved in cell signaling, such as the Notch receptor, it is crucial to sustain these pathways while altering the Aβ secretion. A way of avoiding interference with the physiological function of γ-secretase is to use γ-secretase modulators (GSMs) instead of inhibitors of the enzyme. GSMs modify the Aβ formation from producing the amyloid-prone Aβ42 variant to shorter and less amyloidogenic Aβ species. The modes of action of GSMs are not fully understood, and even though the pharmacology of GSMs has been thoroughly studied regarding Aβ generation, knowledge is lacking about their effects on other substrates, such as Notch. Here, using immunoprecipitation followed by MALDI-TOF MS analysis, we found that two novel, second generation GSMs modulate both Notch β and Aβ production. Moreover, by correlating S3-specific Val-1744 cleavage of Notch intracellular domain (Notch intracellular domain) to total Notch intracellular domain levels using immunocytochemistry, we also demonstrated that Notch intracellular domain is not modulated by the compounds. Interestingly, two well characterized, nonsteroidal anti-inflammatory drugs (nonsteroidal anti-inflammatory drug), R-flurbiprofen and sulindac sulfide, affect only Aβ and not Notch β formation, indicating that second generation GSMs and nonsteroidal anti-inflammatory drug-based GSMs have different modes of action regarding Notch processing.

  19. The Analgesic Acetaminophen and the Antipsychotic Clozapine Can Each Redox-Cycle with Melanin.

    Science.gov (United States)

    Temoçin, Zülfikar; Kim, Eunkyoung; Li, Jinyang; Panzella, Lucia; Alfieri, Maria Laura; Napolitano, Alessandra; Kelly, Deanna L; Bentley, William E; Payne, Gregory F

    2017-12-20

    Melanins are ubiquitous but their complexity and insolubility has hindered characterization of their structures and functions. We are developing electrochemical reverse engineering methodologies that focus on properties and especially on redox properties. Previous studies have shown that melanins (i) are redox-active and can rapidly and repeatedly exchange electrons with diffusible oxidants and reductants, and (ii) have redox potentials in midregion of the physiological range. These properties suggest the functional activities of melanins will depend on their redox context. The brain has a complex redox context with steep local gradients in O 2 that can promote redox-cycling between melanin and diffusible redox-active chemical species. Here, we performed in vitro reverse engineering studies and report that melanins can redox-cycle with two common redox-active drugs. Experimentally, we used two melanin models: a convenient natural melanin derived from cuttlefish (Sepia melanin) and a synthetic cysteinyldopamine-dopamine core-shell model of neuromelanin. One drug, acetaminophen (APAP), has been used clinically for over a century, and recent studies suggest that low doses of APAP can protect the brain from oxidative-stress-induced toxicity and neurodegeneration, while higher doses can have toxic effects in the brain. The second drug, clozapine (CLZ), is a second generation antipsychotic with polypharmacological activities that remain incompletely understood. These in vitro observations suggest that the redox activities of drugs may be relevant to their modes-of-action, and that melanins may interact with drugs in ways that affect their activities, metabolism, and toxicities.

  20. Superwellness Program: a cognitive-behavioral therapy-based group intervention to reduce weight gain in patients treated with antipsychotic drugs

    Directory of Open Access Journals (Sweden)

    Laura R. Magni

    2017-03-01

    Full Text Available Objective: To assess the effectiveness of a cognitive-behavioral therapy-based intervention (Superwellness Program on weight gain compared with a treatment-as-usual (TAU approach in patients treated with antipsychotics, and to evaluate the relationship between body mass index (BMI variation and clinical variables. Method: Eighty-five patients treated with antipsychotics were allocated across two groups, experimental (n=59 and control (n=26. The Superwellness Program (experimental group consisted of 32 twice-weekly 1-hour sessions, conducted by a psychologist and a nutritionist/nurse, concurrently with moderate food intake and moderate physical activity plans. Sociodemographic, clinical, and biological variables were collected at baseline, at the end of intervention (16 weeks, and after 6 months. Results: BMI change from baseline differed significantly between the experimental and control groups, with a larger decrease in the experimental group (F = 5.5, p = 0.021. Duration of illness moderated the effect of treatment on BMI (p = 0.026. No significant (p = 0.499 effect of intervention during the follow-up period was found. Interestingly, the intervention indirectly induced a significant (p = 0.024 reduction in metabolic risk by reducing BMI. Conclusion: A cognitive-behavioral therapy-based intervention could be useful in reducing weight in a clinical population taking antipsychotics, with consequent benefit to physical and mental health.

  1. The second generation in Europe and the United States : How is the transatlantic debate relevant for further research on the European second generation?

    NARCIS (Netherlands)

    Thomson, Mark; Crul, Maurice

    This introductory paper to the special issue of JEMS on the second generation in Europe reviews some of the key themes underpinning the growing interest in the second generation, and asks what 'integration' actually means in contemporary debates about immigration and settlement. The authors attempt

  2. The second generation in Europe and the United States. How is the transatlantic debate relevant for further research on the European second generation?

    NARCIS (Netherlands)

    Crul, M.R.J.; Thomsen, M.

    2007-01-01

    This introductory paper to the special issue of JEMS on the second generation in Europe reviews some of the key themes underpinning the growing interest in the second generation, and asks what 'integration' actually means in contemporary debates about immigration and settlement. The authors attempt

  3. OSSA. A second generation of severe accident management

    International Nuclear Information System (INIS)

    Sauvage, E.C.; Musoyan, G.; Ducros, V.D.

    2009-01-01

    Nowadays the severe accident and their management are an integrated part of the new generation of power plants. The EPR, as the third generation of nuclear plants, includes both systems and instrumentation to mitigate a severe accident, but also a new generation of severe accident management guidelines: the OSSA. Severe accident management guidelines are highly dependent on human means available: emergency organization actors, training and knowledge shall be taken in consideration in an innovative way. Their impacts on ergonomy and content of the document lead to a new generation of guidelines with several innovative features. This second generation of severe accident management guidelines was developed in parallel with the PSA level 2, the human reliability analyses, the validation and verification process, the severe accident simulator progresses. By taking in consideration this variety of input the OSSA were developed in a user aspect orientation. For example in the OSSA a larger responsibility is given to the operational crew to better support the technical support group evaluation. Their existing knowledge of the plant and of the systems and instrumentation is used. This collaboration work implies a strong communication tool that has been developed to enhance the permanent communication within the emergency organization, but although to ensure the main up-to-date information for evaluation will be available where required. The entry condition is based on a strong and stand alone diagnostic for all plant states, that uses in particular a curve of core exit temperature as a function of primary pressure for a fixed core cladding temperature, or its equivalent in term of containment conditions. It ensures relatively consistent core conditions on entry. A first criterion for ultimate final primary depressurization is provided, ensuring all attempts to reflood the core with the available means have been ensured before the OSSA entry condition is reached. This

  4. Second Generation Advanced Reburning for High Efficiency NOx Control

    International Nuclear Information System (INIS)

    Zamansky, Vladimir M.; Maly, Peter M.; Sheldon, Mark; Seeker, W. Randall; Folsom, Blair A.

    1997-01-01

    Energy and Environmental Research Corporation is developing a family of high efficiency and low cost NO x control technologies for coal fired utility boilers based on Advanced Reburning (AR), a synergistic integration of basic reburning with injection of an N-agent. In conventional AR, injection of the reburn fuel is followed by simultaneous N-agent and overfire air injection. The second generation AR systems incorporate several components which can be used in different combinations. These components include: (1) Reburning Injection of the reburn fuel and overfire air. (2) N-agent Injection The N-agent (ammonia or urea) can be injected at different locations: into the reburning zone, along with the overfire air, and downstream of the overfire air injection. (3) N-agent Promotion Several sodium compounds can considerably enhance the NO x control from N-agent injection. These ''promoters'' can be added to aqueous N-agents. (4) Two Stages of N-agent Injection and Promotion Two N-agents with or without promoters can be injected at different locations for deeper NO x control. AR systems are intended for post-RACT applications in ozone non-attainment areas where NO x control in excess of 80% is required. AR will provide flexible installations that allow NO x levels to be lowered when regulations become more stringent. The total cost of NO x control for AR systems is approximately half of that for SCR. Experimental and kinetic modeling results for development of these novel AR systems are presented. Tests have been conducted in a 1.0 MMBtu/hr Boiler Simulator Facility with coal as the main fuel and natural gas as the reburning fuel. The results show that high efficiency NO x control, in the range 84-95%, can be achieved with various elements of AR. A comparative byproduct emission study was performed to compare the emissions from different variants of AR with commercial technologies (reburning and SNCR). For each technology sampling included: CO, SO 2 , N 2 O, total

  5. Determination of circumsolar radiation from Meteosat Second Generation

    Science.gov (United States)

    Reinhardt, B.; Buras, R.; Bugliaro, L.; Wilbert, S.; Mayer, B.

    2014-03-01

    Reliable data on circumsolar radiation, which is caused by scattering of sunlight by cloud or aerosol particles, is becoming more and more important for the resource assessment and design of concentrating solar technologies (CSTs). However, measuring circumsolar radiation is demanding and only very limited data sets are available. As a step to bridge this gap, a method was developed which allows for determination of circumsolar radiation from cirrus cloud properties retrieved by the geostationary satellites of the Meteosat Second Generation (MSG) family. The method takes output from the COCS algorithm to generate a cirrus mask from MSG data and then uses the retrieval algorithm APICS to obtain the optical thickness and the effective radius of the detected cirrus, which in turn are used to determine the circumsolar radiation from a pre-calculated look-up table. The look-up table was generated from extensive calculations using a specifically adjusted version of the Monte Carlo radiative transfer model MYSTIC and by developing a fast yet precise parameterization. APICS was also improved such that it determines the surface albedo, which is needed for the cloud property retrieval, in a self-consistent way instead of using external data. Furthermore, it was extended to consider new ice particle shapes to allow for an uncertainty analysis concerning this parameter. We found that the nescience of the ice particle shape leads to an uncertainty of up to 50%. A validation with 1 yr of ground-based measurements shows, however, that the frequency distribution of the circumsolar radiation can be well characterized with typical ice particle shape mixtures, which feature either smooth or severely roughened particle surfaces. However, when comparing instantaneous values, timing and amplitude errors become evident. For the circumsolar ratio (CSR) this is reflected in a mean absolute deviation (MAD) of 0.11 for both employed particle shape mixtures, and a bias of 4 and 11%, for the

  6. HVRM: a second generation ACE-FTS instrument concept

    Science.gov (United States)

    Lavigne, Jean-François; Larouche, Martin; Dupont, Fabien; Girard, Guillaume; Veilleux, James; Buijs, Henry; Desbiens, Raphaël.; Perron, Gaétan; Grandmont, Frédéric; Paradis, Simon; Moreau, Louis; Bourque, Hugo

    2017-11-01

    The Atmospheric Chemistry Experiment Fourier Transform Spectrometer (ACE-FTS) is the main instrument on-board the SCISAT-1 satellite, a mission mainly supported by the Canadian Space Agency [1]. It is in Low- Earth Orbit at an altitude of 650 km with an inclination of 74E. Its data has been used to track the vertical profile of more than 30 atmospheric species in the high troposphere and in the stratosphere with the main goal of providing crucial information for the comprehension of chemical and physical processes controlling the ozone life cycle. These atmospheric species are detected using high-resolution (0.02 cm-1) spectra in the 750-4400 cm-1 spectral region. This leads to more than 170 000 spectral channels being acquired in the IR every two seconds. It also measures aerosols and clouds to reduce the uncertainty in their effects on the global energy balance. It is currently the only instrument providing such in-orbit high resolution measurements of the atmospheric chemistry and is often used by international scientists as a unique data set for climate understanding. The satellite is in operation since 2003, exceeding its initially planned lifetime of 2 years by more than a factor of 5. Given its success, its usefulness and the uniqueness of the data it provides, the Canadian Space Agency has founded the development of technologies enabling the second generation of ACE-FTS instruments through the High Vertical Resolution Measurement (HVRM) project but is still waiting for the funding for a mission. This project addresses three major improvements over the ACE-FTS. The first one aims at improving the vertical instantaneous field-of-view (iFoV) from 4.0 km to 1.5 km without affecting the SNR and temporal precision. The second aims at providing precise knowledge on the tangent height of the limb observation from an external method instead of that used in SCISAT-1 where the altitude is typically inferred from the monotonic CO2 concentration seen in the spectra. The

  7. In Silico Identification and In Vitro and In Vivo Validation of Anti-Psychotic Drug Fluspirilene as a Potential CDK2 Inhibitor and a Candidate Anti-Cancer Drug.

    Directory of Open Access Journals (Sweden)

    Xi-Nan Shi

    Full Text Available Hepatocellular carcinoma (HCC is one of the leading causes of cancer-related deaths worldwide. Surgical resection and conventional chemotherapy and radiotherapy ultimately fail due to tumor recurrence and HCC's resistance. The development of novel therapies against HCC is thus urgently required. The cyclin-dependent kinase (CDK pathways are important and well-established targets for cancer treatment. In particular, CDK2 is a key factor regulating the cell cycle G1 to S transition and a hallmark for cancers. In this study, we utilized our free and open-source protein-ligand docking software, idock, prospectively to identify potential CDK2 inhibitors from 4,311 FDA-approved small molecule drugs using a repurposing strategy and an ensemble docking methodology. Sorted by average idock score, nine compounds were purchased and tested in vitro. Among them, the anti-psychotic drug fluspirilene exhibited the highest anti-proliferative effect in human hepatocellular carcinoma HepG2 and Huh7 cells. We demonstrated for the first time that fluspirilene treatment significantly increased the percentage of cells in G1 phase, and decreased the expressions of CDK2, cyclin E and Rb, as well as the phosphorylations of CDK2 on Thr160 and Rb on Ser795. We also examined the anti-cancer effect of fluspirilene in vivo in BALB/C nude mice subcutaneously xenografted with human hepatocellular carcinoma Huh7 cells. Our results showed that oral fluspirilene treatment significantly inhibited tumor growth. Fluspirilene (15 mg/kg exhibited strong anti-tumor activity, comparable to that of the leading cancer drug 5-fluorouracil (10 mg/kg. Moreover, the cocktail treatment with fluspirilene and 5-fluorouracil exhibited the highest therapeutic effect. These results suggested for the first time that fluspirilene is a potential CDK2 inhibitor and a candidate anti-cancer drug for the treatment of human hepatocellular carcinoma. In view of the fact that fluspirilene has a long history

  8. Risperidone versus other atypical antipsychotics for schizophrenia

    Science.gov (United States)

    Komossa, Katja; Rummel-Kluge, Christine; Schwarz, Sandra; Schmid, Franziska; Hunger, Heike; Kissling, Werner; Leucht, Stefan

    2014-01-01

    Background In many countries of the industrialised world second-generation (“atypical”) antipsychotics (SGAs) have become the first line drug treatment for people with schizophrenia. The question as to whether and if so how much the effects of the various SGAs differ is a matter of debate. In this review we examined how the efficacy and tolerability of risperidone differs from that of other SGAs. Objectives To evaluate the effects of risperidone compared with other atypical antipsychotics for people with schizophrenia and schizophrenia-like psychosis. Search methods 1. Electronic searching We searched the Cochrane Schizophrenia Group Trials Register (April 2007) which is based on regular searches of BIOSIS, CENTRAL, CINAHL, EMBASE, MEDLINE and PsycINFO. 2. Reference searching We inspected the references of all identified studies for more trials. 3. Personal contact We contacted the first author of each included study for missing information. 4. Drug companies We contacted the manufacturers of all atypical antipsychotics included for additional data. Selection criteria We included all randomised, blinded trials comparing oral risperidone with oral forms of amisulpride, aripiprazole, clozapine, olanzapine, quetiapine, sertindole, ziprasidone or zotepine in people with schizophrenia or schizophrenia-like psychosis. Data collection and analysis We extracted data independently. For dichotomous data we calculated risk ratio (RR) and their 95% confidence intervals (CI) on an intention-to-treat basis based on a random-effects model. We calculated numbers needed to treat/harm (NNT/NNH) where appropriate. For continuous data, we calculated mean differences (MD), again based on a random-effects model. Main results The review currently includes 45 blinded RCTs with 7760 participants. The number of RCTs available for each comparison varied: four studies compared risperidone with amisulpride, two with aripiprazole, 11 with clozapine, 23 with olanzapine, eleven with

  9. Charge transfer complex of some nervous and brain drugs - Part 1: Synthesis, spectroscopic, analytical and biological studies on the reaction between haloperidol antipsychotic drugs with π-acceptors

    Science.gov (United States)

    El-Habeeb, Abeer A.; Al-Saif, Foziah A.; Refat, Moamen S.

    2013-02-01

    Donor-acceptor interactions between the electron donor haloperidol (HPL) and π-acceptors like 7,7,8,8-tetracyanoquinodimethane (TCNQ) and picric acid (PA) have been studied spectrophotometrically in CH3OH solvent. The donor-acceptor (charge transfer complexes) were discussed in terms of formation constant (KCT), molar extinction coefficient (ɛCT), standard free energy (ΔGo), oscillator strength (ƒ), transition dipole moment (μ), resonance energy (RN) and ionization potential (ID). The stoichiometry of these complexes was found to be 1:1 M ratio and having the formulas [(HPL)(TCNQ)] and [(HPL)(PA)], respectively. The charge transfer interaction was successfully applied to determine of HPL drug using mentioned common π-acceptors also, the results obtained herein are satisfactory for estimation of HPL compound in the pharmaceutical form. The formed solid charge-transfer complexes were also isolated and characterized using elemental analysis, conductivity, (infrared, Raman, and 1H NMR) spectra and X-ray powder diffraction (XRD). The experimental data of elemental analyses are in agreement with calculated data. The infrared spectra of both HPL complexes are confirming the participation of sbnd OH of 4-hydroxy-1-piperidyl moiety in the donor-acceptor chelation. The morphological surface of the resulted charge transfer complexes were investigated using scanning electron microscopy (SEM). The thermogravimetric analysis (TG/DTG) and differential scanning calorimetry (DSC) techniques were performed to give knowledge about the thermal stability behavior of the synthesized charge transfer complexes. Thermodynamic parameters were computed from the thermal decomposition data. These complexes were also tested for their antimicrobial activity against six different microorganisms, and the results were compared with the parent drug.

  10. Balanced discussion of second-generation antihistamines' data

    Directory of Open Access Journals (Sweden)

    Boev R

    2016-11-01

    Full Text Available Rossen Boev,1 Jürgen WG Bentz2 1UCB Pharma, Bulle, Switzerland; 2UCB Pharma, Brussels, Belgium It is with interest that we read the paper “Treatment of allergic rhinitis and urticaria: a review of the newest antihistamine drug bilastine” by Wang et al1, in which the authors provide insights into the burden of allergic diseases in the Asia-Pacific region. Unfortunately, we found that the review provides some unsubstantiated information, incorrect statements, and/or data inconsistencies as listed below.The abstract states that bilastine “has very low potential for drug–drug interactions”; however, the drug label lists interactions with ketoconazole, erythromycin, diltiazem, and other intestinal efflux transporters, leading to 2–3-fold increases in drug maximum serum concentration and area under the curve2. Also, food interactions decrease bilastine’s bioavailability by 30%, and the label recommendation is that it is taken 1 hour before or 2 hours after intake of food or fruit juice2. View the original article by Wang et al.

  11. Antipsychotic-associated psoriatic rash - a case report

    DEFF Research Database (Denmark)

    Bujor, Camelia-Eugenia; Vang, Torkel; Nielsen, Jimmi

    2017-01-01

    BACKGROUND: Antipsychotics are a heterogeneous group of drugs. Although, antipsychotics have been used for years, unexpected side effects may still occur. With this case report we focus on a possible association between psoriasis and antipsychotics. Data on the patient's course of psychiatric...... disease, onset of psoriasis and its evolution were extracted from the patient's medical files. CASE PRESENTATION: We present a case of a 21-year-old female diagnosed with schizophrenia. She was initially treated with quetiapine, and later switched to aripiprazole due to weight gain. After initiation...

  12. Second Generation Advanced Reburning for High Efficiency NOx Control

    Energy Technology Data Exchange (ETDEWEB)

    Vladimir M. Zamansky; Peter M. Maly; Vitali V. Lissianski; Mark S. Sheldon; David Moyeda; Roy Payne

    2001-06-30

    This project develops a family of novel Second Generation Advanced Reburning (SGAR) NO{sub x} control technologies, which can achieve 95% NO{sub x} control in coal fired boilers at a significantly lower cost than Selective Catalytic Reduction (SCR). The conventional Advanced Reburning (AR) process integrates basic reburning and N-agent injection. The SGAR systems include six AR variants: (1) AR-Lean--injection of the N-agent and promoter along with overfire air; (2) AR-Rich--injection of N-agent and promoter into the reburning zone; (3) Multiple Injection Advanced Reburning (MIAR)--injection of N-agents and promoters both into the reburning zone and with overfire air; (4) AR-Lean + Promoted SNCR--injection of N-agents and promoters with overfire air and into the temperature zone at which Selective Non-Catalytic Reduction (SNCR) is effective; (5) AR-Rich + Promoted SNCR--injection of N-agents and promoters into the reburning zone and into the SNCR zone; and (6) Promoted Reburning + Promoted SNCR--basic or promoted reburning followed by basic or promoted SNCR process. The project was conducted in two phases over a five-year period. The work included a combination of analytical and experimental studies to confirm the process mechanisms, identify optimum process configurations, and develop a design methodology for full-scale applications. Phase I was conducted from October, 1995 to September, 1997 and included both analytical studies and tests in bench and pilot-scale test rigs. Phase I moved AR technology to Maturity Level III-Major Subsystems. Phase II is conducted over a 45 month period (October, 1997-June, 2001). Phase II included evaluation of alternative promoters, development of alternative reburning fuel and N-Agent jet mixing systems, and scale up. The goal of Phase II was to move the technology to Maturity Level I-Subscale Integrated System. Tests in combustion facility ranging in firing rate from 0.1 x 10{sup 6} to 10 x 10{sup 6} Btu/hr demonstrated the

  13. TESTING OF THE SECOND GENERATION SPINTEK ROTARY FILTER -11357

    Energy Technology Data Exchange (ETDEWEB)

    Herman, D.; Poirier, M.; Fowley, M.; Keefer, M.; Huff, T.

    2011-02-02

    The SpinTek rotary microfilter has been developed under the Department of Energy (DOE) Office of Environmental Management (EM) for the purpose of deployment in radioactive service in the DOE complex. The unit that was fabricated and tested is the second generation of the filter that incorporates recommended improvements from previous testing. The completion of this test satisfied a key milestone for the EM technology development program and technology readiness for deployment by Savannah River Remediation in the Small Column Ion Exchange and Sludge Washing processes at the Savannah River Site (SRS). The Savannah River National Laboratory (SRNL) contracted SpinTek Filtration to fabricate a full scale 25 disk rotary filter and perform a 1000 hour endurance test with a simulated SRS sludge. Over 1500 hours of operation have been completed with the filter. SpinTek Filtration fabricated a prototypic 25 disk rotary filter including updates to manufacturing tolerances, an updated design to the rotary joint, improved cooling to the bottom journal, decreases in disk and filter shaft hydraulic resistances. The filter disks were fabricated with 0.5 {micro} pore size, sintered-metal filter media manufactured by Pall Corporation (M050). After fabrication was complete, the filter passed acceptance tests demonstrating rejection of solids and clean water flux with a 50% improvement over the previous filters. Once the acceptance test was complete, a 1000 hour endurance test was initiated simulating a sludge washing process. The test used a simulated SRS Sludge Batch 6 recipe. The insoluble solids started at 5 wt% and were raised to 10 and 15 wt% insoluble solids to simulate the concentration of a large volume tank. The filter system was automated and set up for 24 hour unattended operation. To facilitate this, process control logic was written to operate the filter. During the development it was demonstrated that the method of starting and stopping the filter can affect the build

  14. Design of second generation Hanford tank corrosion monitoring system

    International Nuclear Information System (INIS)

    Edgemon, G.L.

    1998-01-01

    small amplitude signals that are spontaneously generated by electrochemical reactions occurring at corroding or other surfaces. Laboratory studies and recent reports on field applications have reported that EN analysis is well suited for monitoring and identifying the onset of localized corrosion, and for measuring uniform corrosion rates. A two year laboratory study was started at Hanford in 1995 to provide a technical basis for using EN in Hanford nuclear waste tanks. Based on this study, a prototype system was constructed and deployed in DST 241-AZ-101 in August, 1996. Based on the successful demonstration of this prototype for more than a year, a first-generation full-scale system was designed and installed into DST 241-AN-107 in September 1997. This document summarizes the design and operational requirements of the second-generation full-scale system scheduled for deployment into 241-AY-102

  15. Second-Generation Non-Covalent NAAA Inhibitors are Protective in a Model of Multiple Sclerosis.

    Science.gov (United States)

    Migliore, Marco; Pontis, Silvia; Fuentes de Arriba, Angel Luis; Realini, Natalia; Torrente, Esther; Armirotti, Andrea; Romeo, Elisa; Di Martino, Simona; Russo, Debora; Pizzirani, Daniela; Summa, Maria; Lanfranco, Massimiliano; Ottonello, Giuliana; Busquet, Perrine; Jung, Kwang-Mook; Garcia-Guzman, Miguel; Heim, Roger; Scarpelli, Rita; Piomelli, Daniele

    2016-09-05

    Palmitoylethanolamide (PEA) and oleoylethanolamide (OEA) are endogenous lipid mediators that suppress inflammation. Their actions are terminated by the intracellular cysteine amidase, N-acylethanolamine acid amidase (NAAA). Even though NAAA may offer a new target for anti-inflammatory therapy, the lipid-like structures and reactive warheads of current NAAA inhibitors limit the use of these agents as oral drugs. A series of novel benzothiazole-piperazine derivatives that inhibit NAAA in a potent and selective manner by a non-covalent mechanism are described. A prototype member of this class (8) displays high oral bioavailability, access to the central nervous system (CNS), and strong activity in a mouse model of multiple sclerosis (MS). This compound exemplifies a second generation of non-covalent NAAA inhibitors that may be useful in the treatment of MS and other chronic CNS disorders. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  16. Development of second generation peptides modulating cellular adiponectin receptor responses

    Directory of Open Access Journals (Sweden)

    Laszlo eOtvos

    2014-10-01

    Full Text Available The adipose tissue participates in the regulation of energy homeostasis as an important endocrine organ that secretes a number of biologically active adipokines, including adiponectin. Recently we developed and characterized a first-in-class peptide-based adiponectin receptor agonist by using in vitro and in vivo models of glioblastoma and breast cancer (BC. In the current study, we further explored the effects of peptide ADP355 in additional cellular models and found that ADP355 inhibited chronic myeloid leukemia (CML cell proliferation and renal myofibroblast differentiation with mid-nanomolar IC50 values. According to molecular modeling calculations, ADP355 was remarkably flexible in the global minimum with a turn present in the middle of the peptide. Considering these structural features of ADP355 and the fact that adiponectin normally circulates as multimeric complexes, we developed and tested the activity of a linear branched dimer (ADP399. The dimer exhibited approximately 20-fold improved cellular activity inhibiting K562 CML and MCF-7 cell growth with high pM - low nM relative IC50 values. Biodistribution studies suggested superior tissue dissemination of both peptides after subcutaneous administration relative to intraperitoneal inoculation. After screening of a 397-member adiponectin active site library, a novel octapeptide (ADP400 was designed that counteracted 10-1000 nM ADP355- and ADP399-mediated effects on CML and BC cell growth at nanomolar concentrations. ADP400 induced mitogenic effects in MCF-7 BC cells perhaps due to antagonizing endogenous adiponectin actions or acting as an inverse agonist. While the linear dimer agonist ADP399 meets pharmacological criteria of a contemporary peptide drug lead, the peptide showing antagonist activity (ADP400 at similar concentrations will be an important target validation tool to study adiponectin functions.

  17. Development of second generation peptides modulating cellular adiponectin receptor responses

    Science.gov (United States)

    Otvos, Laszlo; Knappe, Daniel; Hoffmann, Ralf; Kovalszky, Ilona; Olah, Julia; Hewitson, Tim; Stawikowska, Roma; Stawikowski, Maciej; Cudic, Predrag; Lin, Feng; Wade, John; Surmacz, Eva; Lovas, Sandor

    2014-10-01

    The adipose tissue participates in the regulation of energy homeostasis as an important endocrine organ that secretes a number of biologically active adipokines, including adiponectin. Recently we developed and characterized a first-in-class peptide-based adiponectin receptor agonist by using in vitro and in vivo models of glioblastoma and breast cancer (BC). In the current study, we further explored the effects of peptide ADP355 in additional cellular models and found that ADP355 inhibited chronic myeloid leukemia (CML) cell proliferation and renal myofibroblast differentiation with mid-nanomolar IC50 values. According to molecular modeling calculations, ADP355 was remarkably flexible in the global minimum with a turn present in the middle of the peptide. Considering these structural features of ADP355 and the fact that adiponectin normally circulates as multimeric complexes, we developed and tested the activity of a linear branched dimer (ADP399). The dimer exhibited approximately 20-fold improved cellular activity inhibiting K562 CML and MCF-7 cell growth with high pM - low nM relative IC50 values. Biodistribution studies suggested superior tissue dissemination of both peptides after subcutaneous administration relative to intraperitoneal inoculation. After screening of a 397-member adiponectin active site library, a novel octapeptide (ADP400) was designed that counteracted 10-1000 nM ADP355- and ADP399-mediated effects on CML and BC cell growth at nanomolar concentrations. ADP400 induced mitogenic effects in MCF-7 BC cells perhaps due to antagonizing endogenous adiponectin actions or acting as an inverse agonist. While the linear dimer agonist ADP399 meets pharmacological criteria of a contemporary peptide drug lead, the peptide showing antagonist activity (ADP400) at similar concentrations will be an important target validation tool to study adiponectin functions.

  18. Clinical Decision-Making in the Treatment of Schizophrenia: Focus on Long-Acting Injectable Antipsychotics

    Directory of Open Access Journals (Sweden)

    Ludovic Samalin

    2016-11-01

    Full Text Available The purpose of this study was to identify clinician characteristics associated with higher prescription rates of long-acting injectable (LAI antipsychotics, as well as the sources that influence medical decision-making regarding the treatment of schizophrenia. We surveyed 202 psychiatrists during six regional French conferences (Bordeaux, Lyon, Marseille, Nice, Paris, and Strasbourg. Data on the characteristics of practice, prescription rates of antipsychotic, and information sources about their clinical decisions were collected. Most psychiatrists used second-generation antipsychotics (SGAs, and preferentially an oral formulation, in the treatment of schizophrenia. LAI SGAs were prescribed to 30.4% of schizophrenic patients. The duration and type of practice did not influence the class or formulation of antipsychotics used. The clinicians following the higher percentage of schizophrenic patients were associated with a higher use of LAI antipsychotics and a lower use of oral SGAs. Personal experience, government regulatory approval, and guidelines for the treatment of schizophrenia were the three main contributing factors guiding clinicians’ decision-making regarding the treatment of schizophrenia. The more clinicians follow schizophrenic patients, the more they use LAI antipsychotics. The development of specialized programs with top specialists should lead to better use of LAI antipsychotics in the treatment of schizophrenia.

  19. Antipsychotic Prescriptions for Children Aged 5 Years or Younger

    Directory of Open Access Journals (Sweden)

    Ana Lòpez-De Fede

    2014-10-01

    Full Text Available The use of antipsychotics in very young children is of concern given the lack of empirical evidence in their efficacy and long-term impact on children’s health. This study examined the prescription of antipsychotics among children aged ≤5 years enrolled in a state Medicaid program. Secondary data analysis was conducted using the Medicaid administrative data of a southeastern state. Using SAS 9.3, descriptive statistics were performed to examine socio-demographic characteristics, psychiatric diagnoses, off-label use, receipt of medications from multiple psychotropic drug classes, and receipt of non-pharmacologic psychiatric services among children aged ≤5 years who received antipsychotic prescriptions in calendar year (CY 2011. A total of 112 children in the target age group received antipsychotics in CY 2011, the most common prescription being risperidone. The most common listed psychiatric diagnosis was attention deficit hyperactivity disorder. Two in five children received antipsychotics for off-label use. Three in four children also received medications from at least one other psychotropic drug class. More than half did not receive adjunct psychiatric services. State-level policies offering specific guidance and recommendations for antipsychotic use among very young children are urgently needed. Future research is warranted to examine long-term impact of such practices on children’s growth and development.

  20. Reboxetine Enhances the Olanzapine-Induced Antipsychotic-Like Effect, Cortical Dopamine Outflow and NMDA Receptor-Mediated Transmission

    Science.gov (United States)

    Marcus, Monica M; Jardemark, Kent; Malmerfelt, Anna; Björkholm, Carl; Svensson, Torgny H

    2010-01-01

    Preclinical data have shown that addition of the selective norepinephrine transporter (NET) inhibitor reboxetine increases the antipsychotic-like effect of the D2/3 antagonist raclopride and, in parallel, enhances cortical dopamine output. Subsequent clinical results suggested that adding reboxetine to stable treatments with various antipsychotic drugs (APDs) may improve positive, negative and depressive symptoms in schizophrenia. In this study, we investigated in rats the effects of adding reboxetine to the second-generation APD olanzapine on: (i) antipsychotic efficacy, using the conditioned avoidance response (CAR) test, (ii) extrapyramidal side effect (EPS) liability, using a catalepsy test, (iii) dopamine efflux in the medial prefrontal cortex and the nucleus accumbens, using in vivo microdialysis in freely moving animals and (iv) cortical N-methyl--aspartate (NMDA) receptor-mediated transmission, using intracellular electrophysiological recording in vitro. Reboxetine (6 mg/kg) enhanced the suppression of CAR induced by a suboptimal dose (1.25 mg/kg), but not an optimal (2.5 mg/kg) dose of olanzapine without any concomitant catalepsy. Addition of reboxetine to the low dose of olanzapine also markedly increased cortical dopamine outflow and facilitated prefrontal NMDA receptor-mediated transmission. Our data suggest that adjunctive treatment with a NET inhibitor may enhance the therapeutic effect of low-dose olanzapine in schizophrenia without increasing EPS liability and add an antidepressant action, thus in principle allowing for a dose reduction of olanzapine with a concomitant reduction of dose-related side effects, such as EPS and weight gain. PMID:20463659

  1. Wood Quality of Acacia Hybrid and Second-Generation Acacia mangium

    Directory of Open Access Journals (Sweden)

    Ismail Jusoh

    2013-11-01

    Full Text Available Two new tree variants, namely Acacia hybrid and second-generation Acacia mangium, have been introduced in plantation forests in Sarawak, Malaysia, and their wood qualities were examined. The mean basic density of Acacia hybrid was comparable with Acacia mangium. However basic density and strength properties of second-generation A. mangium were significantly lower compared to Acacia hybrid. The mean fibre length and fibre wall thickness in the hybrid were found to be greater than that of second-generation A. mangium. Fibre diameter and fibre lumen diameter of Acacia hybrid were smaller compared to second-generation A. mangium. Runkel and slenderness ratios of Acacia hybrid and second-generation A. mangium fibres showed that they were suitable for pulp and paper production. Acacia hybrid was more resistant to Coptotermes curvignathus attack than second-generation A. mangium. A laboratory soil block test showed that Acacia hybrid and second-generation A. mangium were moderately durable timbers. In summary, marked differences in wood properties and qualities were observed between Acacia hybrid and second-generation A. mangium.

  2. The interaction between EU biofuel policy and first- and second-generation biodiesel production

    NARCIS (Netherlands)

    Boutesteijn, C.; Drabik, D.; Venus, T.J.

    2017-01-01

    We build a tractable partial equilibrium model to study the interactions between the EU biofuel policies (mandate and double-counting of second-generation biofuels) and first- and second-generation biodiesel production. We find that increasing the biodiesel mandate results in a higher share of

  3. Atypical antipsychotics: trends in analysis and sample preparation of various biological samples.

    Science.gov (United States)

    Fragou, Domniki; Dotsika, Spyridoula; Sarafidou, Parthena; Samanidou, Victoria; Njau, Samuel; Kovatsi, Leda

    2012-05-01

    Atypical antipsychotics are increasingly popular and increasingly prescribed. In some countries, they can even be obtained over-the-counter, without a prescription, making their abuse quite easy. Although atypical antipsychotics are thought to be safer than typical antipsychotics, they still have severe side effects. Intoxications are not rare and some of them have a fatal outcome. Drug interactions involving atypical antipsychotics complicate patient management in clinical settings and the determination of the cause of death in fatalities. In view of the above, analytical strategies that can efficiently isolate atypical antipsychotics from a variety of biological samples and quantify them accurately, sensitively and reliably, are of utmost importance both for the clinical, as well as for the forensic toxicologist. In this review, we will present and discuss novel analytical strategies that have been developed from 2004 to the present day for the determination of atypical antipsychotics in various biological samples.

  4. Sustainable Production of Second-Generation Biofuels. Potential and perspectives in major economies and developing countries

    Energy Technology Data Exchange (ETDEWEB)

    Eisentraut, A

    2010-02-15

    The paper focuses on opportunities and risks presented by second-generation biofuels technologies in eight case study countries: Brazil, Cameroon, China, India, Mexico, South Africa, Tanzania and Thailand. The report begins by exploring the state of the art of second-generation technologies and their production, followed by projections of future demand and a discussion of drivers of that demand. The report then delves into various feedstock options and the global potential for bioenergy production. The final chapter offers a look at the potential for sustainable second-generation biofuel production in developing countries including considerations of economic, social and environmental impacts. Key findings of the report include that: second-generation biofuels produced from agricultural and forestry residues can play a crucial role in the transport sector without competing with food production; the potential for second-generation biofuels should be mobilized in emerging and developing countries where a large share of global residues is produced; less-developed countries will first need to invest in agricultural production and infrastructure in order to improve the framework conditions for the production of second-generation biofuels; financial barriers to production exist in many developing countries; and the suitability of second-generation biofuels against individual developing countries' needs should be evaluated.

  5. Sustainable Production of Second-Generation Biofuels. Potential and perspectives in major economies and developing countries

    International Nuclear Information System (INIS)

    Eisentraut, A.

    2010-02-01

    The paper focuses on opportunities and risks presented by second-generation biofuels technologies in eight case study countries: Brazil, Cameroon, China, India, Mexico, South Africa, Tanzania and Thailand. The report begins by exploring the state of the art of second-generation technologies and their production, followed by projections of future demand and a discussion of drivers of that demand. The report then delves into various feedstock options and the global potential for bioenergy production. The final chapter offers a look at the potential for sustainable second-generation biofuel production in developing countries including considerations of economic, social and environmental impacts. Key findings of the report include that: second-generation biofuels produced from agricultural and forestry residues can play a crucial role in the transport sector without competing with food production; the potential for second-generation biofuels should be mobilized in emerging and developing countries where a large share of global residues is produced; less-developed countries will first need to invest in agricultural production and infrastructure in order to improve the framework conditions for the production of second-generation biofuels; financial barriers to production exist in many developing countries; and the suitability of second-generation biofuels against individual developing countries' needs should be evaluated.

  6. Sustainable Production of Second-Generation Biofuels. Potential and perspectives in major economies and developing countries

    Energy Technology Data Exchange (ETDEWEB)

    Eisentraut, A.

    2010-02-15

    The paper focuses on opportunities and risks presented by second-generation biofuels technologies in eight case study countries: Brazil, Cameroon, China, India, Mexico, South Africa, Tanzania and Thailand. The report begins by exploring the state of the art of second-generation technologies and their production, followed by projections of future demand and a discussion of drivers of that demand. The report then delves into various feedstock options and the global potential for bioenergy production. The final chapter offers a look at the potential for sustainable second-generation biofuel production in developing countries including considerations of economic, social and environmental impacts. Key findings of the report include that: second-generation biofuels produced from agricultural and forestry residues can play a crucial role in the transport sector without competing with food production; the potential for second-generation biofuels should be mobilized in emerging and developing countries where a large share of global residues is produced; less-developed countries will first need to invest in agricultural production and infrastructure in order to improve the framework conditions for the production of second-generation biofuels; financial barriers to production exist in many developing countries; and the suitability of second-generation biofuels against individual developing countries' needs should be evaluated.

  7. Atypical antipsychotics in bipolar disorder: systematic review of randomised trials

    Directory of Open Access Journals (Sweden)

    Moore R Andrew

    2007-08-01

    were associated with lower rates of extrapyramidal symptoms, but higher rates of weight gain and somnolence. Conclusion Atypical antipsychotics are effective in treating both phases of bipolar disorder compared with placebo, and as effective as established drug therapies. Atypical antipsychotics produce fewer extrapyramidal symptoms, but weight gain is more common (with olanzapine. There is insufficient data confidently to distinguish between different atypical antipsychotics.

  8. Models of treatment with antipsychotics of the schizophrenic patients

    Directory of Open Access Journals (Sweden)

    Svjetlana Loga-Zec

    2005-11-01

    Full Text Available The aim of this study were to determine which antipsychotic are currently in use, to establish which doses are administrated to patients, to find out is there a practice of proscribing simultaneously more then one antipsychotic drug, to determine whether antipsychotic are proscribed in divided doses, to establish whether there is, besides antipsychotics, treatment with other medicaments (co-administration, especially with antiparkinsonics. The research (study is epidemiological-clinical prospective, descriptive and analytical and it was conducted at University hospitals in Sarajevo, Tuzla and Mostar. Criteria for inclusion, non-inclusion and exclusion from the study were precisely defined as a mean for formation of sample. Based on this hypothesis were established, zero and alterative. According to zero hypothesis in the treatment of schizophrenia at University hospitals in FBiH new antipsychotic drugs are in use, small doses are proscribed (up to 20 mg, not more then one antipsychotic drug is used simultaneously, antipsychotics are administrated once a day and alongside with antipsychotics other medicaments are not co-administrated, especially antiparkinsons. The results of our study are showing that majority of patients are treated with classical antipsychotics. Minority of patients is treated with atypical neuroleptics like olanzapine, which is proscribed only in Sarajevo. Use of risperidone and ziprasidone is registered also only in Sarajevo, but only small number of patients is treated with these drugs. Most frequent antipsychotics were promazine and haloperidol. The range between minimal and maximal daily dose of promazine was from 50 to 450 mg/daily, and for haloperidol from 1 to 75 mg/daily. Above-mentioned drugs were administrated in an average from two to three times a day. Alongside with antipsychotics, other drugs were used. Most frequent was the use of biperidine in oral and parenteral formulation, as

  9. Impact of antipsychotic medication on transcranial direct current stimulation (tDCS) effects in schizophrenia patients.

    Science.gov (United States)

    Agarwal, Sri Mahavir; Bose, Anushree; Shivakumar, Venkataram; Narayanaswamy, Janardhanan C; Chhabra, Harleen; Kalmady, Sunil V; Varambally, Shivarama; Nitsche, Michael A; Venkatasubramanian, Ganesan; Gangadhar, Bangalore N

    2016-01-30

    Transcranial direct current stimulation (tDCS) has generated interest as a treatment modality for schizophrenia. Dopamine, a critical pathogenetic link in schizophrenia, is also known to influence tDCS effects. We evaluated the influence of antipsychotic drug type (as defined by dopamine D2 receptor affinity) on the impact of tDCS in schizophrenia. DSM-IV-TR-diagnosed schizophrenia patients [N=36] with persistent auditory hallucinations despite adequate antipsychotic treatment were administered add-on tDCS. Patients were divided into three groups based on the antipsychotic's affinity to D2 receptors. An auditory hallucinations score (AHS) was measured using the auditory hallucinations subscale of the Psychotic Symptom Rating Scales (PSYRATS). Add-on tDCS resulted in a significant reduction inAHS. Antipsychotic drug type had a significant effect on AHS reduction. Patients treated with high affinity antipsychotics showed significantly lesser improvement compared to patients on low affinity antipsychotics or a mixture of the two. Furthermore, a significant sex-by-group interaction occurred; type of medication had an impact on tDCS effects only in women. Improvement differences could be due to the larger availability of the dopamine receptor system in patients taking antipsychotics with low D2 affinity. Sex-specific differences suggest potential estrogen-mediated effects. This study reports a first-time observation on the clinical utility of antipsychotic drug type in predicting tDCS effects in schizophrenia. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  10. GPM GROUND VALIDATION AIRBORNE SECOND GENERATION PRECIPITATION RADAR (APR-2) GCPEX V1

    Data.gov (United States)

    National Aeronautics and Space Administration — The GPM Ground Validation Airborne Second Generation Precipitation Radar (APR-2) GCPEx dataset was collected during the GPM Cold-season Precipitation Experiment...

  11. The number needed to treat for second-generation biologics when treating established rheumatoid arthritis

    DEFF Research Database (Denmark)

    Kristensen, L. E.; Jakobsen, A. K.; Bartels, E. M.

    2011-01-01

    To evaluate the number needed to treat (NNT) and the number needed to harm (NNH) of the second-generation biologics abatacept, certolizumab, golimumab, rituximab, and tocilizumab in patients with established rheumatoid arthritis (RA) taking concomitant methotrexate (MTX)....

  12. The second generation biofuels from the biomass; Les biocarburants de deuxieme generation issus de la biomasse

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2007-07-01

    The author takes stock on the second generation biofuels in the world, the recent technologies, their advantages, the research programs and the economical and environmental impacts of the biofuels development. (A.L.B.)

  13. GPM GROUND VALIDATION AIRBORNE SECOND GENERATION PRECIPITATION RADAR (APR-2) GCPEX V1

    Data.gov (United States)

    National Aeronautics and Space Administration — The Second Generation Airborne Precipitation Radar (APR-2) is a dual-frequency (13 GHz and 35 GHz), Doppler, dual-polarization radar system. It has a downward...

  14. Differences in the labour market entry of second-generation immigrants and ethnic Danes

    DEFF Research Database (Denmark)

    Datta Gupta, Nabanita; Kromann, Lene

    2014-01-01

    Our study is one of the first to take search friction and cross-firm differences in factor productivity into account when investigating firm behavior towards second-generation immigrants in Denmark. We ensure sub-sample homogeneity in search models by matching second-generation immigrants to thei...... education, in particular males, face lower arrival rates when unemployed and higher layoff rates than those of their twins....... to their ethnic Danish twins according to parental characteristics and informal network quality. We find that second-generation immigrants with a high-school or primary school education, in particular females, perform as well or better than their ethnic counterparts. Second generation immigrants with vocational...

  15. Gender, Culture, and the Educational Choices of Second Generation Hmong American Girls

    OpenAIRE

    Lo, Bao

    2017-01-01

    Research on the educational achievement of racialized minorities and immigrants have largely discussed culture as either a deficit or an advantage for academic success. This paper explores gender differences in educational achievement and how the educational choices of second-generation Hmong American girls are impacted by racially constructed gender norms. In response to hegemonic and subordinated femininities, second-generation Hmong American girls pursue education to enter mainstream Ameri...

  16. The number needed to treat for second-generation biologics when treating established rheumatoid arthritis

    DEFF Research Database (Denmark)

    Kristensen, L E; Jakobsen, A K; Bartels, E M

    2011-01-01

    To evaluate the number needed to treat (NNT) and the number needed to harm (NNH) of the second-generation biologics abatacept, certolizumab, golimumab, rituximab, and tocilizumab in patients with established rheumatoid arthritis (RA) taking concomitant methotrexate (MTX).......To evaluate the number needed to treat (NNT) and the number needed to harm (NNH) of the second-generation biologics abatacept, certolizumab, golimumab, rituximab, and tocilizumab in patients with established rheumatoid arthritis (RA) taking concomitant methotrexate (MTX)....

  17. Antipsychotic medication for early episode schizophrenia

    Science.gov (United States)

    Bola, John; Kao, Dennis; Soydan, Haluk; Adams, Clive E

    2014-01-01

    Background Long-term treatment with antipsychotic medications in early episode schizophrenia spectrum disorders is common, but both short and long-term effects on the illness are unclear. There have been numerous suggestions that people with early episodes of schizophrenia appear to respond differently than those with multiple prior episodes. The number of episodes may moderate response to drug treatment. Objectives To assess the effects of antipsychotic medication treatment on people with early episode schizophrenia spectrum disorders. Search methods We searched the Cochrane Schizophrenia Group register (July 2007) as well as references of included studies. We contacted authors of studies for further data. Selection criteria Studies with a majority of first and second episode schizophrenia spectrum disorders comparing initial antipsychotic medication treatment with placebo, milieu, or psychosocial treatment. Data collection and analysis Working independently, we critically appraised records from 681 studies, of which five studies met inclusion criteria. We calculated risk ratios (RR) and their 95% confidence intervals (CI) where possible. For continuous data, we calculated mean difference (MD). We calculated numbers needed to treat/harm (NNT/NNH) where appropriate. Main results Five studies (combined total n=998) met inclusion criteria. Four studies (n=724) provided leaving the study early data and results suggested that individuals treated with a typical antipsychotic medication are less likely to leave the study early than those treated with placebo (Chlorpromazine: 3 RCTs n=353, RR 0.4 CI 0.3 to 0.5, NNT 3.2, Fluphenaxine: 1 RCT n=240, RR 0.5 CI 0.3 to 0.8, NNT 5; Thioridazine: 1 RCT n=236, RR 0.44 CI 0.3 to 0.7, NNT 4.3, Trifulperazine: 1 RCT n=94, RR 0.96 CI 0.3 to 3.6). Two studies contributed data to assessment of adverse effects and present a general pattern of more frequent side effects among individuals treated with typical antipsychotic medications

  18. Antipsychotic Polypharmacy among Children and Young Adults in Office-Based or Hospital Outpatient Department Settings

    Directory of Open Access Journals (Sweden)

    Minji Sohn

    2017-11-01

    Full Text Available The purpose of the study was three-fold: (1 to estimate the national trends in antipsychotic (AP polypharmacy among 6- to 24-year-old patients in the U.S.; (2 to identify frequently used AP agents and mental disorder diagnoses related to AP polypharmacy; and (3 to assess the strength of association between AP polypharmacy and patient/provider characteristics. We used publicly available ambulatory health care datasets to evaluate AP polypharmacy in office-based or hospital outpatient department settings to conduct a cross-sectional study. First, national visit rates between 2007 and 2011 were estimated using sampling weights. Second, common diagnoses and drugs used in AP polypharmacy were identified. Third, a multivariate logistic regression model was developed to assess the strength of association between AP polypharmacy and patient and provider characteristics. Between 2007 and 2011, approximately 2% of office-based or hospital outpatient department visits made by 6- to 24-year-old patients included one or more AP prescriptions. Of these visits, 5% were classified as AP polypharmacy. The most common combination of AP polypharmacy was to use two or more second-generation APs. Also, bipolar disorder and schizophrenia were the two most frequent primary mental disorder diagnoses among AP polypharmacy visits. The factors associated with AP polypharmacy were: older age (young adults, black, having one or more non-AP prescriptions, and having schizophrenia or ADHD.

  19. Use of Academic Detailing With Audit and Feedback to Improve Antipsychotic Pharmacotherapy.

    Science.gov (United States)

    Brunette, Mary F; Cotes, Robert O; de Nesnera, Alexander; McHugo, Gregory; Dzebisashvili, Nino; Xie, Haiyi; Bartels, Stephen J

    2018-06-08

    Second-generation antipsychotics vary in their propensity to cause serious cardiometabolic side effects. In addition, use of two or more antipsychotics (polypharmacy) may lead to additive side effects and has not been shown to be consistently more effective than monotherapy. This study examined the use of academic detailing with audit and feedback to improve antipsychotic prescribing practices, including antipsychotic polypharmacy and utilization of medication with high or low risk of cardiometabolic side effects ("high risk" or "low risk," respectively). Four intervention sessions were provided over two years to psychiatric care providers at community mental health centers. Segmented regression within the general estimating equation model framework used Medicaid pharmacy claims to examine prescribing patterns before and after the intervention among all beneficiaries (67,721 person-months) over a five-year period. After the intervention, 10.9% of beneficiaries with antipsychotic claims were on polypharmacy, compared with 13.1% before the invention. Use of high-risk and low-risk antipsychotics did not change. The final adjusted polypharmacy model showed that antipsychotic polypharmacy decreased among young adults and adults ages 40 or older compared with beneficiaries ages 30-39 (β=-.02, p=.04, and β=-.02, p=.007, respectively). The raw proportion of beneficiaries on high- and low-risk agents did not change, although final adjusted models demonstrated changes in use of high- and low-risk agents by diagnosis and risk group. Polypharmacy decreased among young and older adults after academic detailing with audit and feedback. Although further research is needed, this low-intensity intervention may help mental health systems reduce antipsychotic polypharmacy.

  20. Survey on schizophrenia treatment in Mexico: perception and antipsychotic prescription patterns

    Directory of Open Access Journals (Sweden)

    de la Fuente-Sandoval Camilo

    2004-04-01

    Full Text Available Abstract Background Since the introduction of antipsychotics, especially the so called atypicals, the treatment of schizophrenia has shown important improvements. At the present time, it is preferred to label clozapine and other antipsychotics sharing similar profiles as second-generation antipsychotics (SGAs. These medications have been proposed by some experts as a first line treatment for schizophrenia. It is critical to have reliable data about antipsychotic prescription in Mexico and to create management guidelines based on expert meetings and not only on studies carried out by the pharmaceutical industry. Only this approach will help to make the right decisions for the treatment of schizophrenia. Methods A translated version of Rabinowitz's survey was used to evaluate antipsychotic prescription preferences and patterns in Mexican psychiatrists. The survey questionnaire was sent by mail to 200 psychiatrists from public institutions and private practice in Mexico City and Guadalajara, Mexico. Results Recommendations for antipsychotics daily doses at different stages of the treatment of schizophrenia varied widely. Haloperidol was considered as the first choice for the treatment of positive symptoms. On the contrary, risperidone was the first option for negative symptoms. For a patient with a high susceptibility for developing extrapyramidal symptoms (EPS, risperidone was the first choice. It was also considered that SGAs had advantages over typical antipsychotics in the management of negative symptoms, cognitive impairment and fewer EPS. Besides, there was a clear tendency for prescribing typical antipsychotics at higher doses than recommended and inadequate doses for the atypical ones. Conclusions Some of the obstacles for the prescription of SGAs include their high cost, deficient knowledge about their indications and dosage, the perception of their being less efficient for the treatment of positive symptoms and the resistance of some

  1. Preparation, structure and microbial evaluation of metal complexes of the second generation quinolone antibacterial drug lomefloxacin

    Science.gov (United States)

    Sadeek, Sadeek A.; El-Shwiniy, Walaa H.

    2010-09-01

    Lomefloxacinate of Y(III), Zr(IV) and U(VI) were isolated as solids with the general formula; [Y(LFX) 2Cl 2]Cl·12H 2O, [ZrO(LFX) 2Cl]Cl·15H 2O and [UO 2(LFX) 3](NO 3) 2·4H 2O. The new synthesized complexes were characterized with physicochemical and diverse spectroscopic techniques (IR, UV-Vis. and 1H NMR spectroscopies) as well as thermal analyses. In these complexes lomefloxacin act as bidentate ligand bound to the metal ions through the pyridone oxygen and one carboxylate oxygen. The kinetic parameters of thermogravimetric (TGA) and its differential (DTG), such as entropy of activation, activation energy, enthalpy of activation and Gibbs free energy evaluated by using Coats- Redfern and Horowitz- Metzger equations for free lomefloxacin and three complexes were carried out. The bond stretching force constant and length of the U dbnd O bond for the [UO 2(LFX) 3](NO 3) 2·4H 2O complex were calculated. The antimicrobial activity of lomefloxacin and its metal complexes was tested against different bacterial species, such as Staphylococcus aureus ( S. aureus), Escherichia coli ( E. coli) and Pseudomonas aeruginosa ( P. aeruginosa) as Gram-positive and Gram-negative bacterial species and also against two species of antifungal, penicillium ( P. rotatum) and trichoderma ( T. sp.). The three complexes are of a good action against three bacterial species but the Y(III) complex exhibit excellent activity against Pseudomonas aeruginosa ( P. aeruginosa), when compared to the free lomefloxacin.

  2. Second generation waste package design and storage concept for the Yucca Mountain Repository

    International Nuclear Information System (INIS)

    Armijo, Joseph Sam; Kar, Piyush; Misra, Manoranjan

    2006-01-01

    The reference waste package design and operating mode to be used in the Yucca Mountain Repository is reviewed. An alternate (second generation) operating concept and waste package design is proposed to reduce the risk of localized corrosion of waste packages and to reduce repository costs. The second generation waste package design and storage concept is proposed for implementation after the initial licensing and operation of the reference repository design. Implementation of the second generation concept at Yucca Mountain would follow regulatory processes analogous to those used successfully to extend the design life and uprate the power of commercial light water nuclear reactors in the United States. The second generation concept utilizes the benefits of hot dry storage to minimize the potential for localized corrosion of the waste package by liquid electrolytes. The second generation concept permits major reductions in repository costs by increasing the number of fuel assemblies stored in each waste package, by eliminating the need for titanium drip shields and by fabricating the outer container from corrosion resistant low alloy carbon steel

  3. Evaluation of the Use of Second Generation Wavelets in the Coherent Vortex Simulation Approach

    Science.gov (United States)

    Goldstein, D. E.; Vasilyev, O. V.; Wray, A. A.; Rogallo, R. S.

    2000-01-01

    The objective of this study is to investigate the use of the second generation bi-orthogonal wavelet transform for the field decomposition in the Coherent Vortex Simulation of turbulent flows. The performances of the bi-orthogonal second generation wavelet transform and the orthogonal wavelet transform using Daubechies wavelets with the same number of vanishing moments are compared in a priori tests using a spectral direct numerical simulation (DNS) database of isotropic turbulence fields: 256(exp 3) and 512(exp 3) DNS of forced homogeneous turbulence (Re(sub lambda) = 168) and 256(exp 3) and 512(exp 3) DNS of decaying homogeneous turbulence (Re(sub lambda) = 55). It is found that bi-orthogonal second generation wavelets can be used for coherent vortex extraction. The results of a priori tests indicate that second generation wavelets have better compression and the residual field is closer to Gaussian. However, it was found that the use of second generation wavelets results in an integral length scale for the incoherent part that is larger than that derived from orthogonal wavelets. A way of dealing with this difficulty is suggested.

  4. Designing Second Generation Anti-Alzheimer Compounds as Inhibitors of Human Acetylcholinesterase: Computational Screening of Synthetic Molecules and Dietary Phytochemicals.

    Science.gov (United States)

    Amat-Ur-Rasool, Hafsa; Ahmed, Mehboob

    2015-01-01

    Alzheimer's disease (AD), a big cause of memory loss, is a progressive neurodegenerative disorder. The disease leads to irreversible loss of neurons that result in reduced level of acetylcholine neurotransmitter (ACh). The reduction of ACh level impairs brain functioning. One aspect of AD therapy is to maintain ACh level up to a safe limit, by blocking acetylcholinesterase (AChE), an enzyme that is naturally responsible for its degradation. This research presents an in-silico screening and designing of hAChE inhibitors as potential anti-Alzheimer drugs. Molecular docking results of the database retrieved (synthetic chemicals and dietary phytochemicals) and self-drawn ligands were compared with Food and Drug Administration (FDA) approved drugs against AD as controls. Furthermore, computational ADME studies were performed on the hits to assess their safety. Human AChE was found to be most approptiate target site as compared to commonly used Torpedo AChE. Among the tested dietry phytochemicals, berberastine, berberine, yohimbine, sanguinarine, elemol and naringenin are the worth mentioning phytochemicals as potential anti-Alzheimer drugs The synthetic leads were mostly dual binding site inhibitors with two binding subunits linked by a carbon chain i.e. second generation AD drugs. Fifteen new heterodimers were designed that were computationally more efficient inhibitors than previously reported compounds. Using computational methods, compounds present in online chemical databases can be screened to design more efficient and safer drugs against cognitive symptoms of AD.

  5. Designing Second Generation Anti-Alzheimer Compounds as Inhibitors of Human Acetylcholinesterase: Computational Screening of Synthetic Molecules and Dietary Phytochemicals.

    Directory of Open Access Journals (Sweden)

    Hafsa Amat-Ur-Rasool

    Full Text Available Alzheimer's disease (AD, a big cause of memory loss, is a progressive neurodegenerative disorder. The disease leads to irreversible loss of neurons that result in reduced level of acetylcholine neurotransmitter (ACh. The reduction of ACh level impairs brain functioning. One aspect of AD therapy is to maintain ACh level up to a safe limit, by blocking acetylcholinesterase (AChE, an enzyme that is naturally responsible for its degradation. This research presents an in-silico screening and designing of hAChE inhibitors as potential anti-Alzheimer drugs. Molecular docking results of the database retrieved (synthetic chemicals and dietary phytochemicals and self-drawn ligands were compared with Food and Drug Administration (FDA approved drugs against AD as controls. Furthermore, computational ADME studies were performed on the hits to assess their safety. Human AChE was found to be most approptiate target site as compared to commonly used Torpedo AChE. Among the tested dietry phytochemicals, berberastine, berberine, yohimbine, sanguinarine, elemol and naringenin are the worth mentioning phytochemicals as potential anti-Alzheimer drugs The synthetic leads were mostly dual binding site inhibitors with two binding subunits linked by a carbon chain i.e. second generation AD drugs. Fifteen new heterodimers were designed that were computationally more efficient inhibitors than previously reported compounds. Using computational methods, compounds present in online chemical databases can be screened to design more efficient and safer drugs against cognitive symptoms of AD.

  6. Pharmacogenetics of Antipsychotics

    Science.gov (United States)

    Brandl, Eva J; Kennedy, James L; Müller, Daniel J

    2014-01-01

    Objective: During the past decades, increasing efforts have been invested in studies to unravel the influence of genetic factors on antipsychotic (AP) dosage, treatment response, and occurrence of adverse effects. These studies aimed to improve clinical care by predicting outcome of treatment with APs and thus allowing for individualized treatment strategies. We highlight most important findings obtained through both candidate gene and genome-wide association studies, including pharmacokinetic and pharmacodynamic factors. Methods: We reviewed studies on pharmacogenetics of AP response and adverse effects published on PubMed until early 2012. Owing to the high number of published studies, we focused our review on findings that have been replicated in independent studies or are supported by meta-analyses. Results: Most robust findings were reported for associations between polymorphisms of the cytochrome P450 system, the dopamine and the serotonin transmitter systems, and dosage, treatment response, and adverse effects, such as AP-induced weight gain or tardive dyskinesia. These associations were either detected for specific medications or for classes of APs. Conclusion: First promising and robust results show that pharmacogenetics bear promise for a widespread use in future clinical practice. This will likely be achieved by developing algorithms that will include many genetic variants. However, further investigation is warranted to replicate and validate previous findings, as well as to identify new genetic variants involved in AP response and for replication of existing findings. PMID:24881126

  7. Risk of schizophrenia in second-generation immigrants: a Danish population-based cohort study

    DEFF Research Database (Denmark)

    Cantor-Graae, Elizabeth; Pedersen, Carsten Bøcker

    2007-01-01

    Background. Urban birth, a risk factor for schizophrenia, is more frequent among second-generation immigrants. The aim of the current study was to determine whether the increased risk for schizophrenia found in second-generation immigrants is explained by the degree of urbanization of birthplace...... for urbanization of birthplace and parental characteristics reduced these risks slightly. However, urbanization had a lesser effect in second-generation immigrants than in Danes. History of residence abroad was a risk factor for schizophrenia, regardless of whether parents were foreign-born or native Danes...... and/or factors related to parentage, such as geographic origin or history of residence abroad during upbringing.Method. Using data from the Danish Civil Registration System (CRS), we established a population-based cohort of 2.0 million Danes (persons born in Denmark). Schizophrenia in cohort members...

  8. Degradation of the tricyclic antipsychotic drug chlorpromazine under environmental conditions, identification of its main aquatic biotic and abiotic transformation products by LC-MSn and their effects on environmental bacteria.

    Science.gov (United States)

    Trautwein, Christoph; Kümmerer, Klaus

    2012-03-15

    The search for environmental transformation products of organic pollutants (like drugs) is a difficult task and usually only few compounds are detected. This might be due to effective degradation but could also be a result of analytical deficits dealing with complex matrices. Especially transformation products of very low concentrations in sludge were difficult to identify so far. Additionally, the use of standard separation techniques might lead to the loss of isomeric compounds, which possess identical spectroscopic and spectrometric properties. To date no complete study investigating the environmental fate of any tricyclic antipsychotic drug has been reported. Therefore, this study investigated the popular neuroleptic drug chlorpromazine and its potential transformation by all main environmental pathways: aerobic and anaerobic biodegradation as well as abiotic photolytic degradation by sunlight. Analysis of test samples by high performance liquid chromatography coupled to multiple stage mass-spectrometry (HPLC-MS(n)) allowed the detection of numerous compounds. Further, the use of a special software allowed distinguishing between transformation products of small intensities and background "noise" caused by sludge or matrix. Three aerobic tests of different bacterial density (the Closed Bottle test, OECD 301D; the Manometric Respiratory test, OECD 301F; the modified Zahn-Wellens test, 302B; one anaerobic test (a modified anaerobic degradation test according to ISO 11734) as well as a photodegradation test were performed in the present study. According to the individual test guidelines, chlorpromazine had to be classified as not biodegradable in all of the biodegradation tests. However, a special chromatographic column and gradient along with mass spectrometric fragmentation experiments of higher order uncovered the presence of a total of 61 abiotic and biotic transformation products which where formed during the course of the tests. The structures of three

  9. Second generation diffusion model of interacting gravity waves on the surface of deep fluid

    Directory of Open Access Journals (Sweden)

    A. Pushkarev

    2004-01-01

    Full Text Available We propose a second generation phenomenological model for nonlinear interaction of gravity waves on the surface of deep water. This model takes into account the effects of non-locality of the original Hasselmann diffusion equation still preserving important properties of the first generation model: physically consistent scaling, adherence to conservation laws and the existence of Kolmogorov-Zakharov solutions. Numerical comparison of both models with the original Hasselmann equation shows that the second generation models improves the angular distribution in the evolving wave energy spectrum.

  10. Automatic inspection Pads second generation; Inspeccion automatica de pastillas de segunda generacion

    Energy Technology Data Exchange (ETDEWEB)

    Gallardo-Lancho gonzalez, J. F.

    2010-07-01

    In recent years, development has addressed Enusa a second generation robot for automatic inspection of tablets incorporating the following advances: more advanced systems that improve vision quality inspection equipment, conducting the inspection in line with the grinding operation, increased productivity of the inspection process to be unnecessary pills buildup in trays and lay-out of the most rational equipment allowing cleaning it easier and faster. This second generation machine is already part of the automatic inspection equipment developed by Enusa and is an example of the ongoing commitment to the development Enusa and innovation in nuclear technology.

  11. The second generation of Slovene Americans and the youth magazine Mladinski list - Juvenile

    Directory of Open Access Journals (Sweden)

    Irena Milanič

    2000-12-01

    Full Text Available From the start the Slovene benefit societies in the United States had a dual purpose: to provide their members with sickness and death benefits and to unite the immigrants by promoting cultural activities. With the growth of the second generation the Slovene benefit societies were faced with a new challenge: how to preserve their role not only as insurance companies, but also as cultural centers. New ways of involving the immigrants' daughters and sons- the second generation of Slovene-Americans - became a central issue for the future existence of these societies.

  12. Does mental health staffing level affect antipsychotic prescribing? Analysis of Italian national statistics.

    Science.gov (United States)

    Starace, Fabrizio; Mungai, Francesco; Barbui, Corrado

    2018-01-01

    In mental healthcare, one area of major concern identified by health information systems is variability in antipsychotic prescribing. While most studies have investigated patient- and prescriber-related factors as possible reasons for such variability, no studies have investigated facility-level characteristics. The present study ascertained whether staffing level is associated with antipsychotic prescribing in community mental healthcare. A cross-sectional analysis of data extracted from the Italian national mental health information system was carried out. For each Italian region, it collects data on the availability and use of mental health facilities. The rate of individuals exposed to antipsychotic drugs was tested for evidence of association with the rate of mental health staff availability by means of univariate and multivariate analyses. In Italy there were on average nearly 60 mental health professionals per 100,000 inhabitants, with wide regional variations (range 21 to 100). The average rate of individuals prescribed antipsychotic drugs was 2.33%, with wide regional variations (1.04% to 4.01%). Univariate analysis showed that the rate of individuals prescribed antipsychotic drugs was inversely associated with the rate of mental health professionals available in Italian regions (Kendall's tau -0.438, p = 0.006), with lower rates of antipsychotic prescriptions in regions with higher rates of mental health professionals. After adjustment for possible confounders, the total availability of mental health professionals was still inversely associated with the rate of individuals exposed to antipsychotic drugs. The evidence that staffing level was inversely associated with antipsychotic prescribing indicates that any actions aimed at decreasing variability in antipsychotic prescribing need to take into account aspects related to the organization of the mental health system.

  13. Brain Connectivity Studies in Schizophrenia: Unravelling the Effects of Antipsychotics

    DEFF Research Database (Denmark)

    Nejad, A.B.; Ebdrup, Bjørn Hylsebeck; Glenthøj, Birte Yding

    2012-01-01

    Impaired brain connectivity is a hallmark of schizophrenia brain dysfunction. However, the effect of drug treatment and challenges on the dysconnectivity of functional networks in schizophrenia is an understudied area. In this review, we provide an overview of functional magnetic resonance imaging...... studies examining dysconnectivity in schizophrenia and discuss the few studies which have also attempted to probe connectivity changes with antipsychotic drug treatment. We conclude with a discussion of possible avenues for further investigation....

  14. Contextual and behavioral control of antipsychotic sensitization induced by haloperidol and olanzapine

    Science.gov (United States)

    Zhang, Chen; Li, Ming

    2011-01-01

    Repeated administration of haloperidol and olanzapine causes a progressively enhanced disruption of conditioned avoidance response (CAR) and a progressively enhanced inhibition of phencyclidine (PCP)-induced hyperlocomotion in rats (termed antipsychotic sensitization). Both actions are thought to reflect intrinsic antipsychotic activity. The present study examined to the extent to which antipsychotic-induced sensitization in one model (e.g. CAR) can be transferred or maintained in another (e.g. PCP hyperlocomotion) as a means of investigating the contextual and behavioral controls of antipsychotic sensitization. Well-trained male Sprague-Dawley rats were first repeatedly tested in the CAR or PCP (3.2 mg/kg, sc) hyperlocomotion model under haloperidol or olanzapine for five consecutive days. Then they were switched to the other model and tested for the expression of sensitization. Finally, all rats were switched back to the original model and retested for the expression of sensitization. Repeated haloperidol or olanzapine treatment progressively disrupted avoidance responding and decreased PCP-induced hyperlocomotion, indicating a robust sensitization. When tested in a different model, rats previously treated with haloperidol or olanzapine did not show a stronger inhibition of CAR or PCP-induced hyperlocomotion than those treated with these drugs for the first time; however, they did show such an effect when tested in the original model in which they received repeated antipsychotic treatment. These findings suggest that the expression of antipsychotic sensitization is strongly influenced by the testing environment and/or selected behavioral response under certain experimental conditions. Distinct contextual cues and behavioral responses may enter an association with unconditional drug effects via a Pavlovian conditioning process. They may also serve as occasion-setters to modulate the expression of sensitized responses. Because antipsychotic sensitization mimics

  15. Contextual and behavioral control of antipsychotic sensitization induced by haloperidol and olanzapine.

    Science.gov (United States)

    Zhang, Chen; Li, Ming

    2012-02-01

    Repeated administration of haloperidol (HAL) and olanzapine (OLZ) causes a progressively enhanced disruption of the conditioned avoidance response (CAR) and a progressively enhanced inhibition of phencyclidine (PCP)-induced hyperlocomotion in rats (termed antipsychotic sensitization). Both actions are thought to reflect intrinsic antipsychotic activity. The present study examined the extent to which antipsychotic-induced sensitization in one model (e.g. CAR) can be transferred or maintained in another (e.g. PCP hyperlocomotion) as a means of investigating the contextual and behavioral controls of antipsychotic sensitization. Well-trained male Sprague-Dawley rats were first repeatedly tested in the CAR or the PCP (3.2 mg/kg, subcutaneously) hyperlocomotion model under HAL or OLZ for 5 consecutive days. Then they were switched to the other model and tested for the expression of sensitization. Finally, all rats were switched back to the original model and retested for the expression of sensitization. Repeated HAL or OLZ treatment progressively disrupted avoidance responding and decreased PCP-induced hyperlocomotion, indicating a robust sensitization. When tested in a different model, rats previously treated with HAL or OLZ did not show a stronger inhibition of CAR-induced or PCP-induced hyperlocomotion than those treated with these drugs for the first time; however, they did show such an effect when tested in the original model in which they received repeated antipsychotic treatment. These findings suggest that the expression of antipsychotic sensitization is strongly influenced by the testing environment and/or selected behavioral response under certain experimental conditions. Distinct contextual cues and behavioral responses may develop an association with unconditional drug effects through a Pavlovian conditioning process. They may also serve as occasion setters to modulate the expression of sensitized responses. As antipsychotic sensitization mimics the clinical

  16. Do Atypical Antipsychotics Have Antisuicidal Effects? A Hypothesis-Generating Overview

    Science.gov (United States)

    Pompili, Maurizio; Baldessarini, Ross J.; Forte, Alberto; Erbuto, Denise; Serafini, Gianluca; Fiorillo, Andrea; Amore, Mario; Girardi, Paolo

    2016-01-01

    Modern antipsychotic drugs are employed increasingly in the treatment of mood disorders as well as psychoses, stimulating interest in their possible contributions to altering suicidal risk. Clozapine remains the only treatment with an FDA-recognized indication for reducing suicidal risk (in schizophrenia). We carried out a systematic, computerized search for reports of studies involving antipsychotic drug treatment and suicidal behaviors. A total of 19 reports provide data with preliminary support for potential suicide risk-reducing effects of olanzapine, quetiapine, ziprasidone, aripiprazole, and asenapine in addition to clozapine, and provide some support for antipsychotic drug treatment in general. These preliminary findings encourage further testing of antipsychotics for effects on suicidal behavior, making use of explicit, pre-planned assessments of suicidal behavior. PMID:27727180

  17. Do Atypical Antipsychotics Have Antisuicidal Effects? A Hypothesis-Generating Overview

    Directory of Open Access Journals (Sweden)

    Maurizio Pompili

    2016-10-01

    Full Text Available Modern antipsychotic drugs are employed increasingly in the treatment of mood disorders as well as psychoses, stimulating interest in their possible contributions to altering suicidal risk. Clozapine remains the only treatment with an FDA-recognized indication for reducing suicidal risk (in schizophrenia. We carried out a systematic, computerized search for reports of studies involving antipsychotic drug treatment and suicidal behaviors. A total of 19 reports provide data with preliminary support for potential suicide risk-reducing effects of olanzapine, quetiapine, ziprasidone, aripiprazole, and asenapine in addition to clozapine, and provide some support for antipsychotic drug treatment in general. These preliminary findings encourage further testing of antipsychotics for effects on suicidal behavior, making use of explicit, pre-planned assessments of suicidal behavior.

  18. Exploring the potential of second-generation sequencing in diverse biological contexts

    DEFF Research Database (Denmark)

    Fordyce, Sarah Louise

    Second generation sequencing (SGS) has revolutionized the study of DNA, allowing massive parallel sequencing of nucleic acids with unprecedented depths of coverage. The research undertaken in this thesis occurred in parallel with the increased accessibility of SGS platforms for routine genetic...

  19. Current and future economic performance of first and second generation biofuels in developing countries

    NARCIS (Netherlands)

    van Eijck, Janske|info:eu-repo/dai/nl/297954296; Batidzirai, Batidzirai|info:eu-repo/dai/nl/341355909; Faaij, Andre

    2014-01-01

    Net Present Value (NPV) and total production cost calculations aremade for first and second generation biofuels in 74 settings, covering 5 fuel output types, 8 feedstock types, 12 countries and 8 combinations of agricultural management systems between 2010 and 2030. Yields are assumed to increase

  20. Second generation bioethanol production from Saccharum spontaneum L. ssp. aegyptiacum (Willd.) Hack.

    Science.gov (United States)

    Danilo Scordia; Salvatore L. Consentino; Thomas W. Jeffries

    2010-01-01

    Saccharum (Saccharum spontaneum L. ssp. aegyptiacum (Willd.) Hack.), is a rapidly growing, wide ranging high-yield perennial, suitable for second generation bioethanol production. This study evaluated oxalic acid as a pretreatment for bioconversion. Overall sugar yields, sugar degradation products, enzymatic glucan hydrolysis and ethanol production were studied as...

  1. Is the antidepressive effect of second-generation antidepressants a myth?

    DEFF Research Database (Denmark)

    Bech, P

    2010-01-01

    Two recent meta-analyses on second-generation antidepressants versus placebo in mild to moderate forms of major depression, based on data on all randomized clinical trials using the Hamilton Depression Scale (HAMD) submitted to FDA, have shown an effect size of approximately 0.30 in favour...

  2. Using Phenomenology to Understand Experiences of Racism for Second-Generation South Asian Women

    Science.gov (United States)

    Beharry, Pauline; Crozier, Sharon

    2008-01-01

    The purpose of this investigation was to describe the lived experiences of racism for second-generation Canadian women of South Asian descent and how this affected their identity. Six adult co-researchers shared their experiences of what occurred when faced with racism. A phenomenological approach was employed, out of which five categories…

  3. The Performance of a Second Generation Service Discovery Protocol In Response to Message Loss

    NARCIS (Netherlands)

    Sundramoorthy, V.; van de Glind, G.J.; Hartel, Pieter H.; Scholten, Johan

    We analyze the behavior of FRODO, a second generation service discovery protocol, in response to message loss in the network. Earlier protocols, like UPnP and Jini rely on underlying network layers to enhance their failure recovery. A comparison with UPnP and Jini shows that FRODO performs more

  4. The Performance of a Second Generation Service Discovery Protocol In Response to Message Loss

    NARCIS (Netherlands)

    Sundramoorthy, V.; van de Glind, G.J.; Hartel, Pieter H.; Scholten, Johan

    We analyze the behavior of FRODO, a second generation service discovery protocol, in response to message loss in the network. First generation protocols, like UPnP and Jini rely on underlying network layers to enhance their failure recovery. A comparison with UPnP and Jini shows that FRODO performs

  5. Rapid Urbanization and the Aspiration and Challenge of Second-Generation Urban-Rural Migrants

    Science.gov (United States)

    Jialing, Han

    2012-01-01

    This article examines the features of second-generation rural migrants and the challenges facing them in terms of schooling and employment. There is a gap that is hard for them to step over: barriers against social inclusion. The article concludes that poverty tends to pass on to the next generation and fossilize. Therefore, it is vital to…

  6. Home Language Policy of Second-Generation Turkish Families in the Netherlands

    Science.gov (United States)

    Bezcioglu-Goktolga, Irem; Yagmur, Kutlay

    2018-01-01

    This study investigated the family language policy of second-generation Turkish immigrant families in the Netherlands by exploring their language ideologies, practices, and management strategies. Using an ethnographic approach, data were collected through a set of observations and interviews with 20 families. Transcriptions of interviews and memos…

  7. Early antihepatitis C virus response with second-generation C200/C22 ELISA

    NARCIS (Netherlands)

    van der Poel, C. L.; Bresters, D.; Reesink, H. W.; Plaisier, A. A.; Schaasberg, W.; Leentvaar-Kuypers, A.; Choo, Q. L.; Quan, S.; Polito, A.; Houghton, M.

    1992-01-01

    Detection of early antibody to hepatitis C virus (HCV) by a new second-generation C200/C22 anti-HCV enzyme-linked immunosorbent assay (ELISA) and a four-antigen recombinant immunoblot assay (4-RIBA) was compared with the first-generation anti-HCV C100 ELISA using sequential serum samples of 9

  8. Discovering Shared Experiences of Second Generation Community College Employees: A Grounded Theory Study

    Science.gov (United States)

    Studebaker, Eric J.

    2012-01-01

    The second generation community college employee had not been a target population of any previous research in the field of higher education. This study added to a broader understanding of employees, their various characteristics, and the implications of those characteristics. The purpose of this study was to develop a grounded theory defining the…

  9. Body fluid identification of blood, saliva and semen using second generation sequencing of micro-RNA

    DEFF Research Database (Denmark)

    Petersen, Christel H.; Hjort, Benjamin Benn; Tvedebrink, Torben

    2013-01-01

    We report a new second generation sequencing method for identification micro-RNA (miRNA) that can be used to identify body fluids and tissues. Principal component analysis of 10 miRNAs with high expression in 16 samples of blood, saliva and semen showed clear differences in the expression of mi...

  10. The Urban Growth Potential of Second-Generation Migrant Entrepreneurs: A Sectoral Study on Amsterdam

    NARCIS (Netherlands)

    Baycan, T.; Nijkamp, P.; Sahin, M.

    2012-01-01

    A rise in second-generation migrant entrepreneurs and an increasing focus on modern economic sectors have become new trends in migrant entrepreneurship in recent years. Although traditional sectors are still the most popular among the first-generation migrant entrepreneurs, because of the increasing

  11. Is the Holocaust implicated in posttraumatic growth in second-generation Holocaust survivors? A prospective study.

    Science.gov (United States)

    Dekel, Sharon; Mandl, Christine; Solomon, Zahava

    2013-08-01

    With the growing interest in posttraumatic growth (PTG), and the ongoing debate on the implications of transgenerational transmission of trauma, this longitudinal study examined PTG among Holocaust survivor offspring following their own exposure to trauma. Using self-report questionnaires, we assessed PTG over time in middle aged (age: M = 53 years) Israeli male combat veterans of the 1973 Yom Kippur War whose parents were (n = 43) and were not (n = 156) second-generation survivors of the Nazi Holocaust at 2 time points: 30 and 35 years following the war (in 2003 and 2008). Posttraumatic stress disorder symptoms and trauma exposure were also assessed in 1991. We hypothesized that second-generation survivors would report more PTG than controls. However, repeated measures design revealed that the second-generation veterans reported less PTG than veterans who were not second generation, which was evident in the PTG domains of relations to others, personal strength, and appreciation of life. Our findings suggest that transmission of trauma from one generation to the next is possibly implicated in the offspring's propensity for growth following subsequent trauma. Future research is warranted to examine the link between transmission of trauma and positive outcomes following trauma. Copyright © 2013 International Society for Traumatic Stress Studies.

  12. A Second Generation Swirl-Venturi Lean Direct Injection Combustion Concept

    Science.gov (United States)

    Tacina, Kathleen M.; Chang, Clarence T.; He, Zhuohui Joe; Lee, Phil; Dam, Bidhan; Mongia, Hukam

    2014-01-01

    A low-NO (sub x) aircraft gas turbine engine combustion concept was developed and tested. The concept is a second generation swirl-venturi lean direct injection (SV-LDI) concept. LDI is a lean-burn combustion concept in which the fuel is injected directly into the flame zone. Three second generation SV-LDI configurations were developed. All three were based on the baseline 9-point SV-LDI configuration reported previously. These second generation configurations had better low power operability than the baseline 9-point configuration. Two of these second generation configurations were tested in a NASA Glenn Research Center flametube; these two configurations are called the at dome and 5-recess configurations. Results show that the 5-recess configuration generally had lower NO (sub x) emissions than the flat dome configuration. Correlation equations were developed for the flat dome configuration so that the landing-takeoff NO (sub x) emissions could be estimated. The flat dome landing-takeoff NO (sub x) is estimated to be 87-88 percent below the CAEP/6 standards, exceeding the ERA project goal of 75 percent reduction.

  13. Second-Generation Turkish Youth in Europe: Explaining the Academic Disadvantage in Austria, Germany, and Switzerland

    Science.gov (United States)

    Song, Steve

    2011-01-01

    This investigation examines the role of students' home and school variables in producing the achievement gap between second-generation Turkish students and their native peers in Austria, Germany, and Switzerland. Using the data from PISA 2006, this study supports past findings that both home and school resources affect the educational outcomes of…

  14. Writing and Reading Knowledge of Spanish/English Second-Generation Bilinguals

    Science.gov (United States)

    Ardila, Alfredo; Garcia, Krystal; Garcia, Melissa; Mejia, Joselyn; Vado, Grace

    2017-01-01

    Written bilingualism represents a particular type of bilingualism that is not frequently approached. The aim of this study was to investigate the writing and reading abilities of second-generation immigrants, Spanish-English bilinguals in South Florida. 58 participants (36 females, 22 males; 18-39 years of age) were selected. Both parents were…

  15. Second-generation Muslims in European societies: Comparative perspectives on education and religion

    NARCIS (Netherlands)

    Fleischmann, F.

    2011-01-01

    The aim of this dissertation is to describe and explain individual and contextual variation in educational attainment and religiosity of second-generation Turkish and Moroccan Muslims in North-West Europe. The two minority groups are compared across local and national receiving contexts in Belgium,

  16. [French Society for Biological Psychiatry and Neuropsychopharmacology task force: Formal Consensus for the prescription of depot antipsychotics].

    Science.gov (United States)

    Samalin, L; Abbar, M; Courtet, P; Guillaume, S; Lancrenon, S; Llorca, P-M

    2013-12-01

    Compliance is often partial with oral antipsychotics and underestimated for patients with serious mental illness. Despite their demonstrated advantages in terms of relapse prevention, depot formulations are still poorly used in routine. As part of a process to improve the quality of care, French Association for Biological Psychiatry and Neuropsychopharmacology (AFPBN) Task Force elaborated a Formal Consensus for the prescription of depot antipsychotics in clinical practice. The Task Force recommends as first-line choice, the use of long-acting injectable (LAI) second-generation antipsychotics in patients with schizophrenia, schizoaffective disorder and delusional disorder. They can be considered as a second-line option as a monotherapy to prevent manic recurrence or in combination with mood stabilizer to prevent depressive recurrence in the maintenance treatment of bipolar disorder. LAI second-generation antipsychotics can also be used after a first episode of schizophrenia. Depot neuroleptics are not recommended during the early course of schizophrenia and are not appropriate in bipolar disorder. They are considered as a second-line option for maintenance treatment in schizophrenia. LAI formulations should be systematically proposed to any patients for whom maintenance antipsychotic treatment is indicated. LAI antipsychotics can be used preferentially for non-compliant patients with frequent relapses or aggressive behaviors. A specific information concerning the advantages and inconveniences of the LAI formulations, in the framework of shared-decision making must be delivered to each patient. Recommendations for switching from one oral/LAI form to another LAI and for using LAI antipsychotics in specific populations (pregnant women, elderly patients, subjects in a precarious situation, and subjects having to be treated in a prison establishment) are also proposed. Copyright © 2013 L’Encéphale. Published by Elsevier Masson SAS.. All rights reserved.

  17. The antipsychotic drug chlorpromazine enhances the cytotoxic effect of tamoxifen in tamoxifen-sensitive and tamoxifen-resistant human breast cancer cells

    DEFF Research Database (Denmark)

    Yde, Christina Westmose; Clausen, Mathias Porsmose; Bennetzen, Martin

    2009-01-01

    , the compound is now also recognized as a multitargeting drug with diverse potential applications, for example, it has antiproliferative properties and it can reverse resistance toward antibiotics in bacteria. Furthermore, chlorpromazine can reverse multidrug resistance caused by overexpression of P......Tamoxifen resistance is a major clinical problem in the treatment of estrogen receptor a-positive breast tumors. It is, at present, unclear what exactly causes tamoxifen resistance. For decades, chlorpromazine has been used for treating psychotic diseases, such as schizophrenia. However......-sensitive breast cancer cell line, MCF-7, and in a tamoxifen-resistant cell line, established from the MCF-7 cells. Tamoxifen-sensitive and tamoxifen-resistant cells were killed equally well by combined treatment with chlorpromazine and tamoxifen. This synergistic effect could be prevented by addition of estrogen...

  18. Oculomotor and neuropsychological effects of antipsychotic treatment for schizophrenia

    Directory of Open Access Journals (Sweden)

    Kristian S. Hill

    2009-04-01

    Full Text Available Cognitive enhancement has become an important target for drug therapies in schizophrenia. Treatment development in this area requires assessment approaches that are sensitive to procognitive effects of antipsychotic and adjunctive treatments. Ideally, new treatments will have translational characteristics for parallel human and animal research. Previous studies of antipsychotic effects on cognition have relied primarily on paper-and-pencil neuropsychological testing. No study has directly compared neurophysiological biomarkers and neuropsychological testing as strategies for assessing cognitive effects of antipsychotic treatment early in the course of schizophrenia. Anti psychotic-naive patients with schizophrenia were tested before treatment with risperidone and again 6 weeks later. Matched healthy participants were tested over a similar time period. Test-retest reliability, effect sizes of within-subject change, and multivariate/univariate analysis of variance were used to compare 3 neurophysiological tests (visually guided saccade, memory-guided saccade, and antisaccade with neuropsychological tests covering 4 cognitive domains (executive function, attention, memory, and manual motor function. While both measurement approaches showed robust neurocognitive impairments in patients prior to risperidone treatment, oculomotor biomarkers were more sensitive to treatment-related effects on neurocognitive function than traditional neuropsychological measures. Further, unlike the pattern of modest generalized cognitive improvement suggested by neuropsychological measures, the oculomotor findings revealed a mixed pattern of beneficial and adverse treatment related effects. These findings warrant further investigation regarding the utility of neurophysiological biomarkers for assessing cognitive outcomes of antipsychotic treatment in clinical trials and in early-phase drug development.

  19. Study on specificity of leukemia among the second generation of A-bomb survivors

    International Nuclear Information System (INIS)

    Takagi, Nobuhiko

    2012-01-01

    The title specificity was studied and discussed for the leukemia (L) of 5 cases of the second generation who had lived in Osaka (Report 1977) in comparison with published statistic data of the second generation's 15 L cases in a life-span investigation (2003) and of 5,098 L cases in a nationwide report (2003). The A-bomb survivors were exposed in either Hiroshima or Nagasaki. The Osaka cases (4/5 boys) were morbid during 1958-1975, had acute L (myeloid L 3 cases, and unidentified type L 2) and died at ages of 10-19 y. Their parents were exposed to A-bomb directly (2 cases) or due to entrance in the city (3), and 1 father, 3 mothers and 1 couple of parents were exposed. Parent(s) in the life-span investigation were classified in high dose exposure (within 2 km distance from the city) and zero exposure (2.5 km afar from the city and other) groups. Their second generation (13/20 boys) were morbid during 1952-1969 at average age of 9.7 y (high dose group) and 8.3-7.2 y (zero group), and had acute myeloid L (8 cases), acute lymphocytic L (5) and other L. Exposure was to their 12 mothers, 4 fathers and 4 both parents. The nationwide statistics showed L of <18 years old pediatric patients (1986-2000) involving 56.7% boys, of morbid age peak of 3-4 y and of acute lymphocytic L in 68.8%. As above, it seemed that, in the second generation, their mothers were mostly exposed relative to fathers, the morbid sex ratio was higher in boys, morbid age was higher than general, and acute myeloid L was more frequent than general. L of the second generation thus seemed to be somehow specific, particularly in the higher age of morbidity and frequency of acute myeloid L. (T.T.)

  20. New users of antipsychotic medication

    DEFF Research Database (Denmark)

    Baandrup, L; Kruse, M

    2016-01-01

    patterns and labor market affiliation, considering both authority approved and off-label prescriptions and the relation to polypharmacy. METHODS: Register-based cohort study using a dataset of 71,254 new antipsychotic users with a psychiatric diagnosis. Labor market affiliation and duration of welfare...... payments were analyzed using linear regression models and duration analysis. The analyses were adjusted for the following confounding variables: age, gender, diagnosis, marital status, length of education, and utilization of mental health care services. RESULTS: The majority of new antipsychotic users...

  1. An explorative study of school performance and antipsychotic medication.

    Science.gov (United States)

    van der Schans, J; Vardar, S; Çiçek, R; Bos, H J; Hoekstra, P J; de Vries, T W; Hak, E

    2016-09-21

    Antipsychotic therapy can reduce severe symptoms of psychiatric disorders, however, data on school performance among children on such treatment are lacking. The objective was to explore school performance among children using antipsychotic drugs at the end of primary education. A cross-sectional study was conducted using the University Groningen pharmacy database linked to academic achievement scores at the end of primary school (Dutch Cito-test) obtained from Statistics Netherlands. Mean Cito-test scores and standard deviations were obtained for children on antipsychotic therapy and reference children, and statistically compared using analyses of covariance. In addition, differences in subgroups as boys versus girls, ethnicity, household income, and late starters (start date within 12 months of the Cito-test) versus early starters (start date > 12 months before the Cito-test) were tested. In all, data from 7994 children could be linked to Cito-test scores. At the time of the Cito-test, 45 (0.6 %) were on treatment with antipsychotics. Children using antipsychotics scored on average 3.6 points lower than the reference peer group (534.5 ± 9.5). Scores were different across gender and levels of household income (p starters were significantly higher than starters within 12 months (533.7 ± 1.7 vs. 524.1 ± 2.6). This first exploration showed that children on antipsychotic treatment have lower school performance compared to the reference peer group at the end of primary school. This was most noticeable for girls, but early starters were less affected than later starters. Due to the observational cross-sectional nature of this study, no causality can be inferred, but the results indicate that school performance should be closely monitored and causes of underperformance despite treatment warrants more research.

  2. Antipsychotic Medications in Major Depression and the Association with Treatment Satisfaction and Quality of Life: Findings of Three National Surveys on Use of Psychotropics in China Between 2002 and 2012

    Directory of Open Access Journals (Sweden)

    Yu-Xi Wang

    2015-01-01

    Conclusions: Concurrent antipsychotic use was found in about one in four treated depressed patients in China, which has increased over a 10-year period. Considering the association of drug-induced side effects and the lack of patients′ and relatives′ satisfaction with antipsychotic treatment, further examination of the rationale and appropriateness of the use of antipsychotics in depression is needed.

  3. Antipsychotic treatment and the risk of hip fracture in subjects with schizophrenia: a 10-year population-based case-control study.

    Science.gov (United States)

    Wu, Chi-Shin; Chang, Chia-Ming; Tsai, Yu-Ting; Huang, Ya-Wen; Tsai, Hui-Ju

    2015-09-01

    To investigate the association between antipsychotic treatment and risk of hip fracture in subjects with schizophrenia. Among patients with schizophrenia (ICD-9-CM code 295), 605 cases with hip fracture and 2,828 matched controls were identified from 2002 to 2011 using the National Health Insurance Research Database in Taiwan. The authors conducted a nested case-control study to investigate the association between antipsychotic treatment and risk of hip fracture in subjects with schizophrenia. The modifiable effects of age and gender were evaluated by stratified analysis. In addition, the effects of antipsychotic use, antipsychotic classes, and receptor-binding profiles of antipsychotics, individually, on hip fracture were estimated, and potential confounding factors were adjusted in subsequent analysis. Conditional logistic regressions were applied to determine the effect of antipsychotic treatment on hip fracture. Current antipsychotic use was associated with an increased risk for hip fracture (adjusted odds ratio [AOR] = 1.61; 95% CI, 1.24-2.10). Among current users, new users had a higher risk of hip fracture (AOR = 4.28; 95% CI, 1.76-10.36) than past users (AOR = 1.11; 95% CI, 0.79-1.56). In addition, a significant increased risk of hip fracture was noted in schizophrenia subjects with first-generation antipsychotic use (AOR = 1.59; 95%CI, 1.15-2.20) but not in those with second-generation antipsychotic use (AOR = 1.16; 95% CI, 0.91-1.48). These results extend previous findings and demonstrate an increased risk of hip fracture associated with antipsychotic use in schizophrenia subjects. Further investigation is needed to dissect the underlying mechanisms related to the effect of antipsychotic use on hip fracture in subjects at risk. © Copyright 2015 Physicians Postgraduate Press, Inc.

  4. Prenatal exposure to a novel antipsychotic quetiapine: impact on neuro-architecture, apoptotic neurodegeneration in fetal hippocampus and cognitive impairment in young rats.

    Science.gov (United States)

    Singh, K P; Tripathi, Nidhi

    2015-05-01

    Reports on prenatal exposure to some of the first generation antipsychotic drugs like, haloperidol, their effects on fetal neurotoxicity and functional impairments in the offspring, are well documented. But studies on in utero exposure to second generation antipsychotics, especially quetiapine, and its effects on fetal neurotoxicity, apoptotic neurodegeneration, postnatal developmental delay and neurobehavioral consequences are lacking. Therefore, the present study was undertaken to evaluate the effect of prenatal administration to equivalent therapeutic doses of quetiapine on neuro-architectural abnormalities, neurohistopathological changes, apoptotic neurodegeneration in fetal hippocampus, and postnatal development and growth as well as its long-lasting imprint on cognitive impairment in young-adult offspring. Pregnant Wistar rats (n=24) were exposed to selected doses (55 mg, 80 mg and 100mg/kg) of quetiapine, equivalent to human therapeutic doses, from gestation day 6 to 21 orally with control subjects. Half of the pregnant subjects of each group were sacrificed at gestation day 21 for histopathological, confocal and electron microscopic studies and rest of the dams were allowed to deliver naturally. Their pups were reared postnatally up to 10 weeks of age for neurobehavioral observations. In quetiapine treated groups, there was significant alterations in total and differential thickness of three typical layers of hippocampus associated with neuronal cells deficit and enhanced apoptotic neurodegeneration in the CA1 area of fetal hippocampus. Prenatally drug treated rat offspring displayed post-natal developmental delay till postnatal day 70, and these young-adult rats displayed cognitive impairment in Morris water maze and passive avoidance regimes as long-lasting impact of the drug. Therefore, quetiapine should be used with cautions considering its developmental neurotoxicological and neurobehavioral potential in animal model, rat. Copyright © 2015 Elsevier

  5. Safety and effectiveness of drug therapy for the acutely agitated patient (Part 2

    Directory of Open Access Journals (Sweden)

    Gianluca Airoldi

    2013-04-01

    patients with primary psychiatric disease, the second-generation atypical antipsychotics, mainly risperidone and olanzapine, were shown to be at least as effective, and possibly safer, than traditional agents.

  6. Dopamine D2 receptor occupancy in normal humans treated with a novel antipsychotic drug YKP1358 measured by PET and [11c]raclopride

    International Nuclear Information System (INIS)

    Lee, J. S.; Kim, S. J.; Lee, K. J.; Kim, E.; Yu, K. S.; Jang, I. J.; Kwon, J. S.; Kang, W. J.; Jeong, J. M.; Lee, D. S.; Chung, J. K.; Lee, M. C.

    2005-01-01

    YKP1358 is a novel serotonin (5-HT 2A ) and dopamine (D 2 ) antagonist, and fitted the general profile of an atypical neuroleptic agent in preclinical studies. The time course of D 2 receptor occupancy in the brain of living human after a single oral dose of YKP1358 was measured using PET and related to the plasma drug levels. A single oral dose, dose escalation (100 mg, 200 mg, and 250 mg), open-label study was performed in 9 healthy male volunteers (3 per each dose) using the [ 11 C]raclopried PET. After the baseline scan, each subject was studied at 2, 5, and 10 hours after the single administration of YKP1358. Blood samples for evaluation of plasma concentration of YKP1358 were also taken at various time points (0-32 hours post-dose). Binding potential (BP) of [ 11 C]raclopride in the putamen was estimated with simplified reference tissue model and percent reduction of the BP was calculated to obtain the D 2 receptor occupancy. BP parametric image was generated using a pixel-wise Logan noninvasive plot. T max of plasma concentration-time profiles was 0.67 hours, and elimination half-life was 5.71, 7.46, and 8.58 hours in 100 mg, 200 mg, and 250 mg dosing groups, respectively. D 2 receptor occupancy of YKP1358 was 60 to 80% at 2 hours, 40 to 60% at 5 hours, and 20 to 50% at 10 hours. The relationship of plasma concentration and D 2 receptor occupancy of YKP1358 was well predicted by Emax model, and Emax was 100 %, EC50 was 8.9 (=1.1) ng/mI, and Hills coefficient was 0.525. PK profile of YKP1358 showed individual variation, but the D 2 receptor occupancy was less variable and well predicted by an Emax model. Since D 2 antagonists show therapeutic effects at 50 to 80% D 2 occupancy and the EC50 of YKP1358 is less than 10 ng/ml, doses of YKP1358 which maintain plasma concentrations above 10 ng/ml are expected to show therapeutic effects

  7. Treatments for acute bipolar depression: meta-analyses of placebo-controlled, monotherapy trials of anticonvulsants, lithium and antipsychotics.

    Science.gov (United States)

    Selle, V; Schalkwijk, S; Vázquez, G H; Baldessarini, R J

    2014-03-01

    Optimal treatments for bipolar depression, and the relative value of specific drugs for that purpose, remain uncertain, including agents other than antidepressants. We searched for reports of placebo-controlled, monotherapy trials of mood-stabilizing anticonvulsants, second-generation antipsychotics, or lithium for acute major depressive episodes in patients diagnosed with type I or II bipolar disorder and applied random-effects meta-analysis to evaluate their efficacy, comparing outcomes based on standardized mean drug-placebo differences (SMD) in improvement, relative response rates (RR), and number-needed-to-treat (NNT). We identified 24 trials of 10 treatments (lasting 7.5 weeks, with ≥ 50 collaborating sites/trial) that met eligibility criteria: lamotrigine (5 trials), quetiapine (5), valproate (4), 2 each for aripiprazole, olanzapine, ziprasidone, and 1 each for carbamazepine, lithium, lurasidone, and olanzapine-fluoxetine. Overall, pooled drug-over-placebo responder-rate superiority (RR) was moderate (29% [CI: 19-40%]), and NNT was 8.2 (CI: 6.4-11). By SMD, apparent efficacy ranked: olanzapine + fluoxetine ≥ valproate > quetiapine > lurasidone > olanzapine, aripiprazole, and carbamazepine; ziprasidone was ineffective, and lithium remains inadequately studied. Notably, drugs were superior to placebo in only 11/24 trials (5/5 with quetiapine, 2/4 with valproate), and only lamotrigine, quetiapine and valproate had > 2 trials. Treatment-associated mania-like reactions were uncommon (drugs: 3.7%; placebo: 4.7%). Controlled trials of non-antidepressant treatments for bipolar depression remain scarce, but findings with olanzapine-fluoxetine, lurasidone, quetiapine, and perhaps carbamazepine and valproate were encouraging; lithium requires adequate testing. © Georg Thieme Verlag KG Stuttgart · New York.

  8. Fault diagnosis of rolling bearing based on second generation wavelet denoising and morphological filter

    International Nuclear Information System (INIS)

    Meng, Lingjie; Xiang, Jiawei; Zhong, Yongteng; Song, Wenlei

    2015-01-01

    Defective rolling bearing response is often characterized by the presence of periodic impulses. However, the in-situ sampled vibration signal is ordinarily mixed with ambient noises and easy to be interfered even submerged. The hybrid approach combining the second generation wavelet denoising with morphological filter is presented. The raw signal is purified using the second generation wavelet. The difference between the closing and opening operator is employed as the morphology filter to extract the periodicity impulsive features from the purified signal and the defect information is easily to be extracted from the corresponding frequency spectrum. The proposed approach is evaluated by simulations and vibration signals from defective bearings with inner race fault, outer race fault, rolling element fault and compound faults, espectively. Results show that the ambient noises can be fully restrained and the defect information of the above defective bearings is well extracted, which demonstrates that the approach is feasible and effective for the fault detection of rolling bearing.

  9. Alcohol consumption among first- and second-generation immigrant and native adolescents in 23 countries

    DEFF Research Database (Denmark)

    Barsties, Lisa S.; Walsh, Sophie D.; Huijts, Tim

    2017-01-01

    and proportions of heavy episodic drinkers (HED) are associated with immigrant adolescents’ alcohol consumption. Design and Methods: We used cross-sectional survey data from the 2013/2014 Health Behaviour in School-aged Children study. Applying multilevel regression analyses, we investigated the lifetime......Introduction and Aims: This internationally comparative study examines differences in alcohol consumption between first- and second-generation immigrant and native adolescents. We also investigate to what extent origin and receiving country alcohol per capita consumption (APCC) rates...... frequency of alcohol use and drunkenness in 69 842 13- to 15-year-olds in 23 receiving countries, with immigrants from over 130 origin countries (82% natives, 6% first-generation immigrants and 12% second-generation immigrants). Results: The lifetime frequency of alcohol use was higher among natives than...

  10. Microvascular pressure responses of second-generation rats chronically exposed to 2 g centrifugation

    Science.gov (United States)

    Richardson, D. R.; Knapp, C. F.

    1977-01-01

    Preliminary results are presented for a study aimed at a quantitative comparison of microvascular dynamics in second-generation rats reared in a 2-g force field produced by centrifugation with similar data from animals reared in a centrifuge that produced only a 1-g force. It is shown that the pressure distribution in the mesenteric microvasculature of the second generation of rats reared in a 2-g environment, as well as the animals' blood pressure response to epinephrine, are significantly different compared to their 1-g counterparts. In particular, 1-g and 2-g chronic centrifugation enhances the arterial blood pressure, and the 2-g force field attenuates the pressor effects of norepinephrine.

  11. Effect of excess air on second-generation PFB combustion plant performance and economics

    International Nuclear Information System (INIS)

    Robertson, A.; Garland, R.; Newby, R.; Rehmat, A.; Rubow, L.; Bonk, D.

    1990-01-01

    This paper presents a conceptual design of a 1.4-MPa (14-atm) coal-fired second-generation pressurized fluidized bed (PFB) combustion plant and identifies the performance and economic changes that result as the excess air and thus gas turbine-to-steam turbine power ratio, is changed. The performance of these plants, another second- generation PFB combustion plant, and a conventional pulverized-coal (PC)-fired plant with wet limestone flue gas desulfurization is compared. Depending upon the conditions selected, the PFB combustion plant can achieve a 45 percent efficiency (based on the higher heating value of the coal used as fuel) and a cost of electricity at least 20 percent lower than that of the conventional PC-fired plant

  12. Preparing for Life: Gender, Religiosity and Education Amongst Second Generation Hindus in Canada

    Directory of Open Access Journals (Sweden)

    Cathy Holtmann

    2012-01-01

    Full Text Available A hallmark of Hinduism is its respect for religious diversity. Amidst religious pluralism in a multicultural Canadian society this strength poses challenges for the second generation. Drawing on qualitative interview data from 57 ‘1.5’ and second generation university students, this article examines the roles that Hinduism and gender play in the process of identity construction in visible minority groups. These young people were raised in families where traditional Hindu religious and cultural practices were valued by immigrants as they creatively adjusted to Canadian society. Parents tried to actively involve their children in their way of life but were largely unable to assist them in articulating the meaning of Hindu rituals and beliefs. As a result, young men and women are caught between the values of their parent’s generation and those implicit in Canadian educational institutions. The secularism of this educational system, permeated by religious illiteracy, contributes to tensions and ambiguities in identity construction.

  13. Parental styles in second generation effects of genocide stemming from the Khmer Rouge regime in Cambodia.

    Science.gov (United States)

    Field, Nigel P; Om, Chariya; Kim, Thida; Vorn, Sin

    2011-11-01

    This study examined the impact of parental styles on second generation effects of trauma among adolescent offspring of survivors of the Khmer Rouge (KR) genocide in Cambodia. Two hundred high school students completed measures addressing their parents' trauma stemming from the KR regime, parental styles (role reversing, overprotective), depression and anxiety. Parents' role reversing parental style and mothers' overprotective parenting were shown to mediate the impact of their trauma symptoms on the child's depression and anxiety. The implications of the findings are discussed.

  14. The quest for a 'better life': Second-generation Turkish-Germans 'return' to 'paradise'

    Directory of Open Access Journals (Sweden)

    Nilay Kılınç

    2017-05-01

    Full Text Available Background: This paper uses a lifestyle-migration lens to analyse the 'return' of the Turkish-German second generation to their parents' homeland, Turkey. It focuses on a scenically attractive touristic region, Antalya on the south coast, where second-generation 'returnees' find a highly congenial environment to pursue their project of living a 'better life' in the ancestral homeland. Methods: Thirty in-depth interviews with second-generation Turkish-Germans, mostly in their 30s and 40s, were carried out in and around Antalya in 2014. Narratives were coded and prepared for thematic analysis using NVivo. Results: According to thematic analysis of interview narratives, many respondents were seeking to 'escape' from difficult personal, family, and economic situations. They mobilised their human capital of educational qualifications, language skills, and life experience to set up or get jobs in hotels, restaurants, and other tourist services, combining work with a relaxed attitude to life in what they saw as a 'paradise' of natural beauty and social open-mindedness. Alongside these practical considerations of seeking a better work-life balance were more existential themes of rediscovering their 'true selves' and reinventing the meaning of 'home' in this cosmopolitan niche. Contribution: The first contribution relates to the use of the concept of lifestyle migration to explain the experiences of second-generation Turkish-German 'returnees' who resettle in Turkey. Secondly we focus on a particular place in Turkey - Antalya - which offers a particular 'space' for the study population to achieve what they perceive as a 'better life'.

  15. Design for a second-generation proton storage ring at LAMPF

    International Nuclear Information System (INIS)

    Colton, E.P.

    1988-01-01

    A conceptual design is presented for a second-generation proton storage ring complex at LAMPF. The facility would consist of two stacked racetrack-shaped machines. These machines would deliver a 1.2-mA beam of 1.6-GeV protons at 48 Hz. The pulse length would be 1.75 μsec which represents a time compression of 570. 1 ref., 8 figs., 1 tab

  16. An Enhanced Multi-Pager Environment Support for Second Generation Microkernels

    OpenAIRE

    Klimiankou, Yauhen

    2014-01-01

    The main objective of this paper is to present a mechanism of enhanced paging support for the second generation microkernels in the form of explicit support of multi-pager environment for the tasks running in the system. Proposed mechanism is based on the intra-kernel high granularity pagers assignments per virtual address space, which allow efficient and simple dispatching of page faults to the appropriate pagers. The paging is one of the major features of the virtual memory, which is extens...

  17. ECOLOGICAL AND ECONOMIC CONFLICTS: AGRICULTURAL USE OR CULTIVATION BIOMASS SECOND GENERATION

    Directory of Open Access Journals (Sweden)

    T. Trohlyuk

    2014-06-01

    Full Text Available To negotiate the consequences of agricultural modernization as an example of nature Polissya areas in Ukraine. Studies addressing the conceptual foundations of ecological and economic conflict over agricultural use or cultivation of second generation biomass due to the transformation of land use during the economic reforms in the country. Proposed to solve it through socio-ecological-economic assessment of environmental audit procedure in the context of the strategy of "green" economy.

  18. Processing Practice of Second Generation Tempeh Recipein Centre of Tempeh Home Industry in Malang

    Directory of Open Access Journals (Sweden)

    Yohanes Kristianto

    2015-11-01

    Full Text Available Background: Malang still faces nutrition problems that need to be solved with the use of local potential in the form of tempeh. More nutritious and attractive tempeh productsmay be produced by introducing new way of processing known as second generation of tempeh. This study was aimed to explore second generation tempe consumption pattern of in Malang. Methods: This study was descriptive qualitative. Tempeh consumption pattern was obtained from group of mother of 6-59 months child with malnutrition and pregnant with chronic energy deficiency in Kendalkerep health care center in which tempeh industry is localised and Arjowinangun health centers as a comparison. Data collection was conducted through FGD and tempeh cooking contest. Results: In general, respondents consumed tempeh almost every day. Tempe products were prepared traditionally in form of snack or protein source side dish. Tempeh processing is generally done by frying. Respondents have recognized the new way of processing tempeh in form of second generations.Respondents living in the tempeh industry area usedmore various ingredients and more complex methods of cooking. They also indicated the ability to adopt new way of tempeh processing. Conclusion: People in Malang consumes tempeh in two forms, ie. side dishes and snack traditionally processed mainly by frying. They may adopt new way of tempeh processing. Recommendation: Futher research is needed to prove the benefit in reducing the malnutrition.

  19. Incidence of Schizophrenia Among Second-Generation Immigrants in the Jerusalem Perinatal Cohort

    Science.gov (United States)

    Corcoran, Cheryl; Perrin, Mary; Harlap, Susan; Deutsch, Lisa; Fennig, Shmuel; Manor, Orly; Nahon, Daniella; Kimhy, David; Malaspina, Dolores; Susser, Ezra

    2009-01-01

    Objective: Increased incidence of schizophrenia is observed among some immigrant groups in Europe, with the offspring of immigrants, ie “second-generation” immigrants particularly vulnerable. Few contemporary studies have evaluated the risk of schizophrenia among second-generation immigrants in other parts of the world. Methods: We studied the incidence of schizophrenia in relation to parental immigrant status in a population-based cohort of 88 829 offspring born in Jerusalem in 1964–1976. Parental countries of birth were obtained from birth certificates and grouped together as (1) Israel, (2) Other West Asia, (3) North Africa, and (4) Europe and industrialized countries. Cox proportional hazards methods were used in adjusting for sex, parents’ ages, maternal education, social class, and birth order. Results: Linkage with Israel's Psychiatric Registry identified 637 people admitted to psychiatric care facilities with schizophrenia-related diagnoses, before 1998. Incidence of schizophrenia was not increased among second-generation immigrants in this birth cohort, neither overall nor by specific group. Conclusions: The difference in risk of schizophrenia among second-generation immigrants in Europe and in this Israeli birth cohort suggests that the nature of the immigration experience may be relevant to risk, including reasons for migration, the nature of entry, and subsequent position in the host country for immigrants and their offspring. Minority status may be of importance as, in later studies, immigrants to Israel from Ethiopia had increased risk of schizophrenia. PMID:18648022

  20. Quality of Life and Stressful Life Events in First and Second Generation Immigrant Adolescents

    Directory of Open Access Journals (Sweden)

    Ida Lemos

    2013-09-01

    Full Text Available The aim of this study was to examine differences in quality of life and stressful life events, in first and second generation immigrant adolescents living in Algarve. A total of 172 immigrant adolescents participated in the study, completing the kidscreen-52, the stressful and negative life events inventory and a socio-demographic questionnaire. Results suggest that younger immigrant adolescents report more physical well-being and a higher mood level. Concerning gender differences, girls scored higher than boys in physical well-being, mood and self-perception, but no differences were found on the other kidscreen subscales. First generation immigrants scored significantly higher than second generation ones on the general quality of life index, psychological well-being, autonomy, financial resources and school environment. However, the second-generation immigrants did not seem to be more exposed to stressful life events than the first-generation group. When selecting relevant variables for well-being promotion and for intervention, we must consider that immigrants are more exposed to economic vulnerability, may experience difficulties in adapting to a different school context, and are at higher risk of social exclusion.

  1. A Comparison of Three Second-generation Swirl-Venturi Lean Direct Injection Combustor Concepts

    Science.gov (United States)

    Tacina, Kathleen M.; Podboy, Derek P.; He, Zhuohui Joe; Lee, Phil; Dam, Bidhan; Mongia, Hukam

    2016-01-01

    Three variations of a low emissions aircraft gas turbine engine combustion concept were developed and tested. The concept is a second generation swirl-venturi lean direct injection (SV-LDI) concept. LDI is a lean-burn combustion concept in which the fuel is injected directly into the flame zone. All three variations were based on the baseline 9- point SV-LDI configuration reported previously. The three second generation SV-LDI variations are called the 5-recess configuration, the flat dome configuration, and the 9- recess configuration. These three configurations were tested in a NASA Glenn Research Center medium pressure flametube. All three second generation variations had better low power operability than the baseline 9-point configuration. All three configurations had low NO(sub x) emissions, with the 5-recess configuration generally having slightly lower NO(x) than the flat dome or 9-recess configurations. Due to the limitations of the flametube that prevented testing at pressures above 20 atm, correlation equations were developed for the at dome and 9-recess configurations so that the landing-takeoff NO(sub x) emissions could be estimated. The flat dome and 9-recess landing-takeoff NO(x) emissions are estimated to be 81-88% below the CAEP/6 standards, exceeding the project goal of 75% reduction.

  2. Electromyographic monitoring for prevention of phrenic nerve palsy in second-generation cryoballoon procedures.

    Science.gov (United States)

    Franceschi, Frédéric; Koutbi, Linda; Gitenay, Edouard; Hourdain, Jérome; Maille, Baptiste; Trévisan, Lory; Deharo, Jean-Claude

    2015-04-01

    Electromyography-guided phrenic nerve (PN) monitoring using a catheter positioned in a hepatic vein can aid in preventing phrenic nerve palsy (PNP) during cryoballoon ablation for atrial fibrillation. We wanted to evaluate the feasibility and efficacy of PN monitoring during procedures using second-generation cryoballoons. This study included 140 patients (43 women) in whom pulmonary vein isolation was performed using a second-generation cryoballoon. Electromyography-guided PN monitoring was performed by pacing the right PN at 60 per minute and recording diaphragmatic compound motor action potential (CMAP) via a quadripolar catheter positioned in a hepatic vein. If a 30% decrease in CMAP amplitude was observed, cryoapplication was discontinued with forced deflation to avoid a PNP. Monitoring was unfeasible in 8 of 140 patients (5.7%), PNP occurred in 1. Stable CMAP amplitudes were achieved before ablation in 132 of 140 patients (94.3%). In 18 of 132 patients (13.6%), a 30% decrease in CMAP amplitude occurred and cryoablation was discontinued. Each time, recovery of CMAP amplitude took <60 s. In 9 of 18 cases, a second cryoapplication in the same pulmonary vein was safely performed. We observed no PNP or complication related to electromyography-guided PN monitoring. Electromyography-guided PN monitoring using a catheter positioned in a hepatic vein seems feasible and effective to prevent PNP during cryoballoon ablation using second-generation cryoballoon. © 2015 American Heart Association, Inc.

  3. Use of atypical antipsychotics in nursing homes and pharmaceutical marketing.

    Science.gov (United States)

    Pimentel, Camilla B; Donovan, Jennifer L; Field, Terry S; Gurwitz, Jerry H; Harrold, Leslie R; Kanaan, Abir O; Lemay, Celeste A; Mazor, Kathleen M; Tjia, Jennifer; Briesacher, Becky A

    2015-02-01

    To describe the current extent and type of pharmaceutical marketing in nursing homes (NHs) in one state and to provide preliminary evidence for the potential influence of pharmaceutical marketing on the use of atypical antipsychotics in NHs. Nested mixed-methods, cross-sectional study of NHs in a cluster randomized trial. Forty-one NHs in Connecticut. NH administrators, directors of nursing, and medical directors (n = 93, response rate 75.6%). Quantitative data, including prescription drug dispensing data (September 2009-August 2010) linked with Nursing Home Compare data (April 2011), were used to determine facility-level prevalence of atypical antipsychotic use, facility-level characteristics, NH staffing, and NH quality. Qualitative data, including semistructured interviews and surveys of NH leaders conducted in the first quarter of 2011, were used to determine encounters with pharmaceutical marketing. Leadership at 46.3% of NHs (n = 19) reported pharmaceutical marketing encounters, consisting of educational training, written and Internet-based materials, and sponsored training. No association was detected between level of atypical antipsychotic prescribing and reports of any pharmaceutical marketing by at least one NH leader. NH leaders frequently encounter pharmaceutical marketing through a variety of ways, although the impact on atypical antipsychotic prescribing is unclear. © 2015, Copyright the Authors Journal compilation © 2015, The American Geriatrics Society.

  4. Recent Progress on the Second Generation CMORPH: A Prototype Operational Processing System

    Science.gov (United States)

    Xie, Pingping; Joyce, Robert; Wu, Shaorong

    2016-04-01

    As reported at the EGU General Assembly of 2015, a conceptual test system was developed for the second generation CMORPH to produce global analyses of 30-min precipitation on a 0.05deg lat/lon grid over the entire globe from pole to pole through integration of information from satellite observations as well as numerical model simulations. The second generation CMORPH is built upon the Kalman Filter based CMORPH algorithm of Joyce and Xie (2011). Inputs to the system include both rainfall and snowfall rate retrievals from passive microwave (PMW) measurements aboard all available low earth orbit (LEO) satellites, precipitation estimates derived from infrared (IR) observations of geostationary (GEO) as well as LEO platforms, and precipitation simulations from numerical global models. Sub-systems were developed and refined to derive precipitation estimates from the GEO and LEO IR observations and to compute precipitating cloud motion vectors. The results were reported at the EGU of 2014 and the AGU 2015 Fall Meetings. In this presentation, we report our recent work on the construction of a prototype operational processing system for the second generation CMORPH. The second generation CMORPH prototype operational processing system takes in the passive microwave (PMW) retrievals of instantaneous precipitation rates from all available sensors, the full-resolution GEO and LEO IR data, as well as the hourly precipitation fields generated by the NOAA/NCEP Climate Forecast System (CFS) Reanalysis (CFS). First, a combined field of PMW based precipitation retrievals (MWCOMB) is created on a 0.05deg lat/lon grid over the entire globe through inter-calibrating retrievals from various sensors against a common reference. For this experiment, the reference field is the GMI based retrievals with climatological adjustment against the TMI retrievals using data over the overlapping period. Precipitation estimation is then derived from the GEO and LEO IR data through calibration against

  5. Cannabidiol as a potential new type of an antipsychotic. A critical review of the evidence

    Directory of Open Access Journals (Sweden)

    Cathrin Rohleder

    2016-11-01

    Full Text Available There is urgent need for the development of mechanistically different and less side-effect prone antipsychotic compounds. The endocannabinoid system has been suggested to represent a potential new target in this indication. While the chronic use of cannabis itself has been considered a risk factor contributing to the development of schizophrenia, triggered by the phytocannabinoid delta-9-tetrahydrocannabinol (Δ9 THC, cannabidiol, the second most important phytocannabinoid, appears to have no psychotomimetic potential. Although results from animal studies are inconsistent to a certain extent and seem to depend on behavioral paradigms, treatment duration and experimental conditions applied, cannabidiol has shown antipsychotic properties in rodents and rhesus monkeys. After some individual treatment attempts, the first randomized, double-blind controlled clinical trial had been conducted and demonstrated that cannabidiol exerts antipsychotic properties in acute schizophrenia comparable to the antipsychotic drug amisulpride accompanied by a superior, placebo-like side effect profile. As the clinical improvement by cannabidiol was significantly associated with elevated anandamide levels, it appears likely that its antipsychotic action is based on mechanisms associated with increased anandamide concentrations. However, a plethora of mechanisms of action has been suggested, but their potential relevance for the antipsychotic effects of cannabidiol needs still to be investigated. The clarification of these mechanisms as well as the establishment of cannabidiol’s antipsychotic efficacy and its hopefully benign side-effect profile remains the subject of a number of previously started clinical trials.

  6. Treatment patterns and clinical characteristics prior to initiating depot typical antipsychotics for nonadherent schizophrenia patients

    Directory of Open Access Journals (Sweden)

    Montgomery William

    2009-07-01

    Full Text Available Abstract Background Nonadherence with antipsychotic medication is an important clinical and economic problem in the treatment of schizophrenia. This study identified treatment patterns and clinical characteristics that immediately precede the initiation of depot typical antipsychotics in the usual treatment of schizophrenia patients with a recent history of nonadherence with oral antipsychotic regimens. Methods Data were drawn from a large, multisite, 3-year prospective noninterventional observational study of persons treated for schizophrenia in the United States, which was conducted between 7/1997 and 9/2003. The analytical sample included patients who, in the 6 months prior to enrollment, were considered nonadherent with oral antipsychotics and were not treated with depot antipsychotics (N = 314. Patients who were subsequently initiated on typical depots during the 3-year follow-up were compared with patients who continued therapy with only oral antipsychotic agents. Group comparisons were made on patient baseline characteristics and precedent variables that were assessed 1 to 6 months prior to depot initiation. Patient assessments were made at predetermined intervals throughout the 3-year study using standard psychiatric measures, a patient-reported questionnaire, and medical record information. Results A small proportion of patients (12.4% who were recently nonadherent with oral antipsychotics were subsequently initiated on depot therapy during the 3-year study. Compared to patients treated with only oral antipsychotics, those subsequently initiated on a depot were significantly more likely to be hospitalized at depot initiation or the previous 30 days, to have recent involvement with the criminal justice system (arrests, recent illicit drug use, recent switching or augmentation of oral antipsychotics, and recent treatment with oral typical antipsychotics. Conclusion Despite prior nonadherence with oral antipsychotic medication, only a

  7. Association between community pharmacy loyalty and persistence and implementation of antipsychotic treatment among individuals with schizophrenia.

    Science.gov (United States)

    Zongo, Frank E; Moisan, Jocelyne; Grégoire, Jean-Pierre; Lesage, Alain; Dossa, Anara Richi; Lauzier, Sophie

    2018-01-01

    Non-adherence is a major obstacle to optimal treatment of schizophrenia. Community pharmacists are in a key position to detect non-adherence and put in place interventions. Their role is likely to be more efficient when individuals are loyal to a single pharmacy. To assess the association between the level of community pharmacy loyalty and persistence with and implementation of antipsychotic drug treatment among individuals with schizophrenia. A cohort study using databases from the Quebec health insurance board (Canada) was conducted among new antipsychotic users insured by Quebec's public drug plan. Level of community pharmacy loyalty was assessed as the number of pharmacies visited in the year after antipsychotics initiation. Persistence was defined as having an antipsychotic supply in the user's possession on the 730 th day after its initiation and implementation as having antipsychotics in the user's possession for ≥80% of the days in the second year after antipsychotics initiation (among persistent only). Generalized linear models were used to estimate adjusted prevalence ratios (aPR) and 95% confidence intervals (95%CI). 6,251 individuals were included in the cohort and 54.1% had their drug prescriptions filled in >1 pharmacy. When compared to those who had their prescriptions filled in a single pharmacy, those who had their prescriptions filled in ≥4 different pharmacies were 22% more likely to be non-persistent (aPR = 1.22; 95%CI = 1.10-1.37) and 49% more likely to have an antipsychotic for loyalty in the context of severe mental illness indicates that this healthcare organisation factor might be associated with antipsychotics persistence and implementation. Identification of individuals with low community pharmacy loyalty and initiatives to optimize community pharmacy loyalty could contribute to enhanced persistence and implementation. Copyright © 2016 Elsevier Inc. All rights reserved.

  8. Diabetes mellitus and impaired glucose tolerance in patients with schizophrenia, before and after antipsychotic treatment

    Directory of Open Access Journals (Sweden)

    Rayees Ahmad Wani

    2015-01-01

    Full Text Available Background: Treatment with antipsychotics increases the risk of developing diabetes in patients of schizophrenia but this diabetogenic potential of different antipsychotics seems to be different. Moreover, there may be an independent link between schizophrenia and diabetes. So we plan to study the prevalence of glucose dysregulation in patients of schizophrenia before and after treatment with various antipsychotics. Materials and Methods: Fifty patients (32 males and 18 females diagnosed with schizophrenia were evaluated for glucose dysregulation using oral glucose tolerance test, initially (drug naive and after antipsychotic treatment. Age- and sex-matched healthy volunteer group of 50 subjects (35 males and 15 females was taken for comparison. Results were interpreted using American Diabetic Association criteria. Results: Though the glycemic status of the patient group was comparable with healthy controls initially but antipsychotic treatment was associated with glucose dysregulation. For first 6 weeks the antipsychotic (olanzapine, risperidone, haloperidol and aripiprazole-induced glucose dysregulation was comparable, which was seen to be maximum with the olanzapine-treated group at the end of this study, 14 weeks. Conclusion: We conclude that antipsychotic treatment of nondiabetic drug naive schizophrenia patients was associated with adverse effects on glucose regulation. For initial 6 weeks the antipsychotic-induced glucose dysregulation was comparable, which was seen to be maximum with olanzapine at the end of study, i.e. 14 weeks. Keeping this at the back of mind we can stabilize a patient initially with a more effective drug, olanzapine, and later on shift to one with less metabolic side effects.

  9. Second-generation magnesium scaffold Magmaris: device design and preclinical evaluation in a porcine coronary artery model.

    Science.gov (United States)

    Waksman, Ron; Zumstein, Philine; Pritsch, Martin; Wittchow, Eric; Haude, Michael; Lapointe-Corriveau, Capucine; Leclerc, Guy; Joner, Michael

    2017-07-20

    The second-generation drug-eluting absorbable magnesium scaffold Magmaris, recently introduced for the treatment of obstructive coronary atherosclerotic lesions, suggests a good safety profile, but preclinical assessment is important for predicting clinical performance. The aim of the present study was to assess subacute and long-term safety as well as pharmacokinetic properties of the Magmaris compared with a current-generation metallic DES and an approved BRS in porcine and rabbit animal models. Ninety Magmaris scaffolds were implanted into non-diseased porcine and rabbit models. A bioresorbable vascular scaffold (Absorb) and a permanent drug-eluting stent (XIENCE Xpedition) served as controls. Scanning electron microscopy showed increased endothelialisation and decreased thrombus formation at three and 28 days in the Magmaris group compared with the Absorb group. In the XIENCE group, inflammation exceeded the level in the Magmaris group at 365 and 730 days. Neointimal growth was greater in the Magmaris group than in the XIENCE group. Late lumen loss decreased over time in both groups. Optical coherence tomography (OCT) showed stable luminal dimensions in both the Magmaris and XIENCE groups. Pharmacokinetic studies demonstrated a retarded elution profile in the Magmaris group with 69.4% of sirolimus released at 90 days. Preclinical results suggest that the Magmaris has a favourable safety profile with advanced healing relative to benchmark, low acute thrombogenicity, and absence of excessive lumen loss up to two years. These results support clinical application of Magmaris for human use.

  10. Metabolic Syndrome and Antipsychotics: The Role of Mitochondrial Fission/Fusion Imbalance

    Directory of Open Access Journals (Sweden)

    Andrea del Campo

    2018-04-01

    Full Text Available Second-generation antipsychotics (SGAs are known to increase cardiovascular risk through several physiological mechanisms, including insulin resistance, hepatic steatosis, hyperphagia, and accelerated weight gain. There are limited prophylactic interventions to prevent these side effects of SGAs, in part because the molecular mechanisms underlying SGAs toxicity are not yet completely elucidated. In this perspective article, we introduce an innovative approach to study the metabolic side effects of antipsychotics through the alterations of the mitochondrial dynamics, which leads to an imbalance in mitochondrial fusion/fission ratio and to an inefficient mitochondrial phenotype of muscle cells. We believe that this approach may offer a valuable path to explain SGAs-induced alterations in metabolic homeostasis.

  11. Weight Gain, Schizophrenia and Antipsychotics: New Findings from Animal Model and Pharmacogenomic Studies

    Directory of Open Access Journals (Sweden)

    Fabio Panariello

    2011-01-01

    Full Text Available Excess body weight is one of the most common physical health problems among patients with schizophrenia that increases the risk for many medical problems, including type 2 diabetes mellitus, coronary heart disease, osteoarthritis, and hypertension, and accounts in part for 20% shorter life expectancy than in general population. Among patients with severe mental illness, obesity can be attributed to an unhealthy lifestyle, personal genetic profile, as well as the effects of psychotropic medications, above all antipsychotic drugs. Novel “atypical” antipsychotic drugs represent a substantial improvement on older “typical” drugs. However, clinical experience has shown that some, but not all, of these drugs can induce substantial weight gain. Animal models of antipsychotic-related weight gain and animal transgenic models of knockout or overexpressed genes of antipsychotic receptors have been largely evaluated by scientific community for changes in obesity-related gene expression or phenotypes. Moreover, pharmacogenomic approaches have allowed to detect more than 300 possible candidate genes for antipsychotics-induced body weight gain. In this paper, we summarize current thinking on: (1 the role of polymorphisms in several candidate genes, (2 the possible roles of various neurotransmitters and neuropeptides in this adverse drug reaction, and (3 the state of development of animal models in this matter. We also outline major areas for future research.

  12. Glutamatergic neurotransmission modulation and the mechanisms of antipsychotic atypicality.

    Science.gov (United States)

    Heresco-Levy, Uriel

    2003-10-01

    The neurotransmission mediated by the excitatory amino acids (EAA) glutamate (GLU) and aspartate is of interest to the pharmacotherapy of psychosis due to its role in neurodevelopment and neurotoxicity, its complex interactions with dopaminergic and other neurotransmitter systems and its pivotal importance in recent models of schizophrenia. Accumulating evidence indicates that modulation of glutamatergic neurotransmission may play an important role in the mechanisms of action of atypical antipsychotic drugs. The principles of the phencyclidine (PCP) model of schizophrenia suggest that conventional neuroleptics cannot counteract all aspects of schizophrenia symptomatology, while a more favorable outcome, including anti-negative and cognitive symptoms effects, would be expected with the use of treatment modalities targeting glutamatergic neurotransmission. Clozapine and other presently used atypical antipsychotics differ from conventional neuroleptics in the way they affect various aspects of glutamatergic receptors function. In this context, a specific hypothesis suggesting an agonistic role of clozapine at the N-methyl-D-aspartate (NMDA) subtype of GLU receptors has been postulated. Furthermore, the results of the first generation of clinical trials with glycine (GLY) site agonists of the NMDA receptor in schizophrenia suggest that this type of compounds (1) have efficacy and side effects profiles different than those of conventional neuroleptics and (2) differ in their synergic effects when used in addition to conventional neuroleptics versus clozapine and possibly additional atypical antipsychotics. These findings (1) bring further support to the hypothesis that glutamatergic effects may play an important role in the mechanism of action of atypical antipsychotics, (2) help explain the unique clinical profile of clozapine, and (3) suggest that GLY site agonists of the NMDA receptor may represent a new class of atypical antipsychotic medication. Future research in

  13. Bioethanol and power from integrated second generation biomass: A Monte Carlo simulation

    International Nuclear Information System (INIS)

    Osaki, Márcia R.; Seleghim, Paulo

    2017-01-01

    Highlights: • The impacts of integrating new sugarcane conversion using bagasse and straw. • Industrial conversion of sugarcane into energy carriers: ethanol and electricity. • A reference sugarcane industrial was simulated by the Monte Carlo method. • Simultaneously optimal ethanol production and electricity generation occur at low burning bagasse rates. - Abstract: The main objective of this work is to assess the impacts of integrating new biomass conversion technologies into an existing sugarcane industrial processing plant in terms of its multi-objective optimal operating conditions. A typical sugarcane mill is identified and a second generation ethanol production pathway is incorporated to give the operator the possibility of controlling the ratio between the rates of burning bagasse and straw (sugarcane tops and leaves) to their second generation processing to achieve optimal ethanol and electricity outputs. A set of equations describing the associated conversion unit operations and chemical reactions is simulated by the Monte Carlo method and the corresponding operating envelope is constructed and statistically analyzed. These equations permit to calculate ethanol production and electricity generation in terms of a virtually infinite number of scenarios characterized by two controlled variables (burning bagasse and straw mass flow rates) and several uncontrolled variables (biomass composition, cellulose, hemicelluloses and lignin yields, fermentation efficiencies, etc.). Results reveal that the input variables have specific statistical characteristics when the corresponding operating states lay near the maximum energy limit (Pareto frontier). For example, since the objectives being optimized are intrinsically antagonistic, i.e. the increase of one dictates the decrease of the other, it is better to convert bagasse to ethanol via second generation pathway because of the high energy requirements of its dewatering prior to combustion and low heat

  14. Testicular cancer risk in first- and second-generation immigrants to Denmark.

    Science.gov (United States)

    Myrup, Charlotte; Westergaard, Tine; Schnack, Tine; Oudin, Anna; Ritz, Christian; Wohlfahrt, Jan; Melbye, Mads

    2008-01-02

    Immigrant studies offer insights into the relative importance of environment and genes in disease etiology. There is considerable variation in testicular cancer incidence worldwide. We investigated testicular cancer risk in first- and second-generation immigrants to Denmark, a high-incidence country, to evaluate the relative influence of genes and environment and the potential timing of action of environmental factor(s). A cohort of 2.1 million men who were born since 1930 and lived in Denmark between 1968 and 2003 was established based on information in the Danish Civil Registration System, which included their immigration histories. Cancer histories were obtained from the Danish Cancer Registry. Testicular cancer risk was estimated as rate ratios (RRs) with 95% confidence intervals (CIs) based on log-linear Poisson regression. Overall, 4216 testicular cancer cases occurred during 43 million person-years of follow-up in 2.1 million men. These included 166 cases among 344,444 direct immigrants to Denmark and 13 cases among 56,189 men born in Denmark to immigrant parents. These first- and second-generation immigrants had RRs of testicular cancer of 0.37 (95% CI = 0.31 to 0.43) and 0.88 (95% CI = 0.51 to 1.53), respectively, compared with men born in Denmark of parents born in Denmark. The rate in first-generation immigrants was not modified by age at immigration or duration of stay and reflected that in the country of origin. The testicular cancer risk in first-generation immigrants was lower than that in native-born Danes and reflected that in the countries of origin, whereas the risk in second-generation immigrants was similar to that in natives of Denmark. Together these findings argue for a substantial influence of environmental factors limited to the period early in life, most probably to the period in utero.

  15. Choice of antipsychotic treatment by European psychiatry trainees: are decisions based on evidence?

    Directory of Open Access Journals (Sweden)

    Jauhar Sameer

    2012-03-01

    Full Text Available Abstract Background Little is known about the factors influencing treatment choice in psychosis, the majority of this work being conducted with specialists (consultant in psychiatry. We sought to examine trainees' choices of treatment for psychosis if they had to prescribe it for themselves, their patients, and factors influencing decision-making. Methods Cross-sectional, semi-structured questionnaire-based study. Results Of the 726 respondents (response rate = 66%, the majority chose second-generation antipsychotics (SGAs if they had to prescribe it for themselves (n = 530, 93% or for their patients (n = 546, 94%. The main factor influencing choice was perceived efficacy, 84.8% (n = 475 of trainees stating this was the most important factor for the patient, and 77.8% (n = 404 stating this was the most important factor for their own treatment. Trainees with knowledge of trials questioning use of SGAs (CATIE, CUtLASS, TEOSS were more likely to choose second-generation antipsychotics than those without knowledge of these trials (χ2 = 3.943; p = 0.047; O.R. = 2.11; 95% C.I. = 1.0-4.48. Regarding psychotherapy, cognitive behavioural therapy (CBT was the most popular choice for self (33.1%; n = 240 and patient (30.9%; n = 224. Trainees were significantly more likely to prefer some form of psychotherapy for themselves rather than patients (χ2 = 9.98; p Conclusions Trainees are more likely to choose second-generation antipsychotic medication for patients and themselves. Despite being aware of evidence that suggests otherwise, they predominantly base these choices on perceived efficacy.

  16. Statmaster and HEROS - web-based courses first and second generation

    DEFF Research Database (Denmark)

    Larsen, Pia Veldt; Rootzen, Helle

    2008-01-01

    With the increasing focus on life-long learning, and with the convenience and accessibility of the Internet, the market for web-based courses has expanded vastly in recent times–in particular in connection with continuing education. However, teaching web-based courses presents various technical...... as well as pedagogical challenges. Some of these challenges are addressed, and means to dealing with them are suggested. A second generation of web-based courses is comprised of learning objects, which allows for tailoring courses for specialized groups of students, and accommodate individualized learning....... The concept of learning objects and how they are used to form new courses are discussed....

  17. Progress in AMSC scale-up of second generation HTS wire

    International Nuclear Information System (INIS)

    Zhang, W.; Rupich, M.W.; Schoop, U.; Verebelyi, D.T.; Thieme, C.L.H.; Li, X.; Kodenkandath, T.; Huang, Y.; Siegal, E.; Buczek, D.; Carter, W.; Nguyen, N.; Schreiber, J.; Prasova, M.; Lynch, J.; Tucker, D.; Fleshler, S.

    2007-01-01

    American Superconductor has successfully scaled up its low-cost, high volume second generation (2G) HTS wire process into pre-pilot scale production, with performance approaching first generation (1G) HTS wire. AMSC's manufacturing approach is based on RABiTS TM /MOD wide strip technology, with metal organic deposition (MOD) process for the YBCO layer and the Rolling Assisted Biaxially Textured Substrate (RABiTS) process for the template. In this paper, we review the status of the 2G manufacturing scale up at AMSC and describe the properties and architecture of the 2G wire being manufactured and developed for various applications

  18. Progress in AMSC scale-up of second generation HTS wire

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, W. [American Superconductor Corporation, 2 Technology Drive, Westborough, MA 01545 (United States)], E-mail: wzhang@amsuper.com; Rupich, M.W.; Schoop, U.; Verebelyi, D.T.; Thieme, C.L.H.; Li, X.; Kodenkandath, T.; Huang, Y.; Siegal, E.; Buczek, D.; Carter, W.; Nguyen, N.; Schreiber, J.; Prasova, M.; Lynch, J.; Tucker, D.; Fleshler, S. [American Superconductor Corporation, 2 Technology Drive, Westborough, MA 01545 (United States)

    2007-10-01

    American Superconductor has successfully scaled up its low-cost, high volume second generation (2G) HTS wire process into pre-pilot scale production, with performance approaching first generation (1G) HTS wire. AMSC's manufacturing approach is based on RABiTS{sup TM}/MOD wide strip technology, with metal organic deposition (MOD) process for the YBCO layer and the Rolling Assisted Biaxially Textured Substrate (RABiTS) process for the template. In this paper, we review the status of the 2G manufacturing scale up at AMSC and describe the properties and architecture of the 2G wire being manufactured and developed for various applications.

  19. Whole system analysis of second generation bioenergy production and Ecosystem Services in Europe

    Science.gov (United States)

    Henner, Dagmar; Smith, Pete; Davies, Christian; McNamara, Niall

    2017-04-01

    Bioenergy crops are an important source of renewable energy and are a possible mechanism to mitigate global climate warming, by replacing fossil fuel energy that has higher greenhouse gas emissions. There is, however, uncertainty about the impacts of the growth of bioenergy crops on ecosystem services. This uncertainty is further enhanced by current climate change. It is important to establish how second generation bioenergy crops (Miscanthus, SRC willow and poplar) can contribute by closing the gap between reducing fossil fuel use and increasing the use of other renewable sources in a sustainable way. The project builds on models of energy crop production, biodiversity, soil impacts, greenhouse gas emissions and other ecosystem services, and on work undertaken in the UK on the ETI-funded ELUM project (www.elum.ac.uk). We will present estimated yields for the above named crops in Europe using the ECOSSE, DayCent, SalixFor and MiscanFor models. These yields will be brought into context with a whole system analysis, detailing trade-offs and synergies for land use change, food security, GHG emissions and soil and water security. Methods like water footprint tools, tourism value maps and ecosystem valuation tools and models (e.g. InVest, TEEB database, GREET LCA Model, World Business Council for Sustainable Development corporate ecosystem valuation, Millennium Ecosystem Assessment and the Ecosystem Services Framework) will be used to estimate and visualise the impacts of increased use of second generation bioenergy crops on the above named ecosystem services. The results will be linked to potential yields to generate "inclusion or exclusion areas" in Europe in order to establish suitable areas for bioenergy crop production and the extent of use possible. Policy is an important factor for using second generation bioenergy crops in a sustainable way. We will present how whole system analysis can be used to create scenarios for countries or on a continental scale. As an

  20. Development of the Second-Generation Oscillating Surge Wave Energy Converter with Variable Geometry: Preprint

    Energy Technology Data Exchange (ETDEWEB)

    Tom, Nathan M [National Renewable Energy Laboratory (NREL), Golden, CO (United States); Yu, Yi-Hsiang [National Renewable Energy Laboratory (NREL), Golden, CO (United States); Thresher, Robert W [National Renewable Energy Laboratory (NREL), Golden, CO (United States); Kelly, Michael [South Dakota School of Mines

    2017-07-25

    This study investigates the effect of design changes on the hydrodynamics of a novel oscillating surge wave energy converter being developed at the National Renewable Energy Laboratory. The design utilizes controllable geometry features to shed structural loads while maintaining a rated power over a greater number of sea states. The second-generation design will seek to provide a more refined control of performance because the first-generation design demonstrated performance reductions considered too large for smooth power output. Performance is evaluated using frequency domain analysis with consideration of a nonideal power-take-off system, with respect to power absorption, foundation loads, and power-take-off torque.

  1. Platelet-rich fibrin: Evolution of a second-generation platelet concentrate

    Directory of Open Access Journals (Sweden)

    Sunitha Raja V

    2008-01-01

    Full Text Available Platelet-rich plasma (PRP is a platelet concentrate that has been used widely to accelerate soft-tissue and hard-tissue healing. The preparation of PRP has been described by several authors. Platelet-rich fibrin (PRF was first described by Choukroun et al. in France. It has been referred to as a second-generation platelet concentrate, which has been shown to have several advantages over traditionally prepared PRP. Its chief advantages include ease of preparation and lack of biochemical handling of blood, which makes this preparation strictly autologous. This article describes the evolution of this novel platelet concentrate, referred to as PRF.

  2. Aesthetic guidelines for second-generation indirect inlay and onlay composite restorations.

    Science.gov (United States)

    Miara, P

    1998-05-01

    Recent innovations in indirect composite technology and adhesive bonding procedures have resulted in the development of advanced materials particularly suited for inlay and onlay restorations. Microhybrid composite resins are characterized by a filler/matrix ratio that is significantly greater than that of earlier materials. This article reviews the physical properties and clinical application of these "second-generation" composite resins, with emphasis on a system that utilizes a heat-curing process in conjunction with nitrogen pressure to fabricate a material with improved mechanical and aesthetic properties.

  3. Second-Generation System for Three-Dimensional Imaging Using a Single Laser Pulse

    Science.gov (United States)

    1990-01-23

    Welford and t. Winston , The Optics of Nonimaging Concentrators , Academic Press, New York, 1978. 14. N. F. Borelli, D. L. Morse, R. H. Bellman, and W. L...inserting such an optical concentrator , we can use a practical- 9ber layout for the converter with moderate ratio of fiber core to unit cell area and...ABSTRACT (Maximum 200 words)15 199t This paper describes the design of a second-generation version of an optical detector capable of producing a 3-D

  4. Adjunctive Treatment of Acute Mania with Risperidone versus Typical Antipsychotics: A Retrospective Study

    Directory of Open Access Journals (Sweden)

    Jui-Hsiu Tsai

    2005-12-01

    Full Text Available Few studies have directly compared atypical antipsychotics (e.g. risperidone with typical antipsychotics as adjunctive therapy in patients hospitalized for acute mania, especially during a lengthy hospital stay. Our retrospective, case-controlled study is a chart review of 64 patients with Diagnostic and Statistical Manual of Mental Disorders, 4th edition, defined bipolar I disorder (current episode, mania. Patients were divided into two groups according to the adjunctive medications used: the risperidone group (mood stabilizers plus risperidone and the control group (mood stabilizers plus typical antipsychotics. Outcome at discharge, medications, adverse drug effects, and length of hospital stay were compared between groups, controlling for gender, age, number of prior admissions, and duration of illness. Results indicated no statistically significant differences between groups in the controlled factors, Global Assessment of Functioning and Clinical Global Impression-Improvement scores, and adverse drug events. Patients in the risperidone group used significantly lower doses of trihexyphenidyl than those in the control group (p < 0.05. Patients treated with risperidone had a shorter hospital stay than those treated with typical antipsychotics (p < 0.01. In conclusion, antipsychotics are effective as adjunctive agents in the treatment of acute mania. The use of risperidone, in particular, decreases the need for anticholinergics and may lead to a shorter hospital stay compared with typical antipsychotics.

  5. Dopamine and incentive learning: a framework for considering antipsychotic medication effects.

    Science.gov (United States)

    Beninger, Richard J

    2006-12-01

    Hyperfunction of brain dopamine (DA) systems is associated with psychosis in schizophrenia and the medications used to treat schizophrenia are DA receptor blockers. DA also plays a critical role in incentive learning produced by rewarding stimuli. Using DA as the link, these results suggest that psychosis in schizophrenia can be understood from the point of view of excessive incentive learning. Incentive learning is mediated through the non-declarative memory system and may rely on the striatum or medial prefrontal cortex depending on the task. Typical and atypical antipsychotics differentially affect expression of the immediate early gene c-fos, producing greater activity in the striatum and medial prefrontal cortex, respectively. This led to the hypothesis that performance of schizophrenic patients on tasks that depend on the striatum or medial prefrontal cortex will be differentially affected by their antipsychotic medication. Results from a number of published papers supported this dissociation. Furthermore, the effects of two atypical drugs, clozapine and olanzapine, on c-fos expression were different from another atypical, risperidone that resembles the typical antipsychotics. Similarly, in tests of incentive learning, risperidone acted like the typical antipsychotics. Thus, typical and atypical antipsychotic drugs differed in the types of cognitive performance they affected and, furthermore, members of the atypical class differed in their effects on cognition. It remains the task of researchers and clinicians to sort out the symptoms associated with the endogenous illness from possible iatrogenic symptoms resulting from the antipsychotic medications used to treat schizophrenia.

  6. Immobilized High-Level Waste (HLW) Interim Storage Alternative Generation and analysis and Decision Report - second Generation Implementing Architecture

    International Nuclear Information System (INIS)

    CALMUS, R.B.

    2000-01-01

    Two alternative approaches were previously identified to provide second-generation interim storage of Immobilized High-Level Waste (IHLW). One approach was retrofit modification of the Fuel and Materials Examination Facility (FMEF) to accommodate IHLW. The results of the evaluation of the FMEF as the second-generation IHLW interim storage facility and subsequent decision process are provided in this document

  7. DISRUPTION OF CONDITIONED REWARD ASSOCIATION BY TYPICAL AND ATYPICAL ANTIPSYCHOTICS

    Science.gov (United States)

    Danna, C.L.; Elmer, G.I.

    2013-01-01

    Antipsychotic drugs are broadly classified into typical and atypical compounds; they vary in their pharmacological profile however a common component is their antagonist effects at the D2 dopamine receptors (DRD2). Unfortunately, diminished DRD2 activation is generally thought to be associated with the severity of neuroleptic-induced anhedonia. The purpose of this study was to determine the effect of the atypical antipsychotic olanzapine and typical antipsychotic haloperidol in a paradigm that reflects the learned transfer of incentive motivational properties to previously neutral stimuli, namely autoshaping. In order to provide a dosing comparison to a therapeutically relevant endpoint, both drugs were tested against amphetamine-induced disruption of prepulse inhibition as well. In the autoshaping task, rats were exposed to repeated pairings of stimuli that were differentially predictive of reward delivery. Conditioned approach to the reward predictive cue (sign-tracking) and to the reward (goal-tracking) increased during repeated pairings in the vehicle treated rats. Haloperidol and olanzapine completely abolished this behavior at relatively low doses (100 μg/kg). This same dose was the threshold dose for each drug to antagonize the sensorimotor gating deficits produced by amphetamine. At lower doses (3–30 μg/kg) both drugs produced a dose-dependent decrease in conditioned approach to the reward predictive cue. There was no difference between drugs at this dose range which indicates that olanzapine disrupts autoshaping at a significantly lower proposed DRD2 receptor occupancy. Interestingly, neither drug disrupted conditioned approach to the reward at the same dose range that disrupted conditioned approach to the reward predictive cue. Thus, haloperidol and olanzapine, at doses well below what is considered therapeutically relevant, disrupts the attribution of incentive motivational value to previously neutral cues. Drug effects on this dimension of reward

  8. Possibility of material cost reduction toward development of low-cost second-generation superconducting wires

    Science.gov (United States)

    Ichinose, Ataru; Horii, Shigeru; Doi, Toshiya

    2017-10-01

    Two approaches to reducing the material cost of second-generation superconducting wires are proposed in this paper: (1) instead of the electrical stabilizing layers of silver and copper presently used on the superconducting layer, a Nb-doped SrTiO3 conductive buffer layer and cube-textured Cu are proposed as an advanced architecture, and (2) the use of an electromagnetic (EM) steel tape as a metal substrate of coated conductors in a conventional architecture. In structures fabricated without using electrical stabilizing layers on the superconducting layer, the critical current density achieved at 77 K in a self-field was approximately 2.6 MA/cm2. On the other hand, in the case of using EM steel tapes, although the critical current density was far from practical at the current stage, the biaxial alignment of YBa2Cu3O y (YBCO) and buffer layers was realized without oxidation on the metal surface. In this study, the possibility of material cost reduction has been strongly indicated toward the development of low-cost second-generation superconducting wires in the near future.

  9. Modeling and Simulation of the Second-Generation Orion Crew Module Air Bag Landing System

    Science.gov (United States)

    Timmers, Richard B.; Hardy, Robin C.; Willey, Cliff E.; Welch, Joseph V.

    2009-01-01

    Air bags were evaluated as the landing attenuation system for earth landing of the Orion Crew Module (CM). Analysis conducted to date shows that airbags are capable of providing a graceful landing of the CM in nominal and off-nominal conditions such as parachute failure, high horizontal winds, and unfavorable vehicle/ground angle combinations, while meeting crew and vehicle safety requirements. The analyses and associated testing presented here surround a second generation of the airbag design developed by ILC Dover, building off of relevant first-generation design, analysis, and testing efforts. In order to fully evaluate the second generation air bag design and correlate the dynamic simulations, a series of drop tests were carried out at NASA Langley s Landing and Impact Research (LandIR) facility in Hampton, Virginia. The tests consisted of a full-scale set of air bags attached to a full-scale test article representing the Orion Crew Module. The techniques used to collect experimental data, develop the simulations, and make comparisons to experimental data are discussed.

  10. Study on the Tribological Characteristics of Australian Native First Generation and Second Generation Biodiesel Fuel

    Directory of Open Access Journals (Sweden)

    Md Mofijur Rahman

    2017-01-01

    Full Text Available Biodiesels are a renewable energy source, and they have the potential to be used as alternatives to diesel fuel. The aim of this study is to investigate the wear and friction characteristics of Australian native first generation and second generation biodiesels using a four-ball tribo tester. The biodiesel was produced through a two-step transesterification process and characterized according to the American Society for Testing and Materials (ASTM standards. The tribological experiment was carried out at a constant 1800 rpm and different loads and temperatures. In addition, the surface morphology of the ball was tested by scanning electron microscope (SEM/energy dispersive X-ray spectroscopy (EDX analysis. The test results indicated that biodiesel fuels have a lower coefficient of frictions (COF and lower wear scar diameter (WSD up to 83.50% and 41.28%, respectively, compared to conventional diesel fuel. The worn surface area results showed that biodiesel fuel has a minimum percentage of C and O, except Fe, compared to diesel. In addition, the worn surface area for diesel was found (2.20%–27.92% to be higher than biodiesel. The findings of this study indicated that both first and second generation biodiesel fuels have better tribological performance than diesel fuel, and between the biodiesel fuels, macadamia biodiesel showed better lubrication performance.

  11. Transnationalism among Second-Generation Muslim Americans: Being and Belonging in Their Transnational Social Field

    Directory of Open Access Journals (Sweden)

    Michelle Byng

    2017-10-01

    Full Text Available An increase in transnationalism, the ability of individuals and families to travel and maintain relationships across national borders, has led to questions about its impact on identity especially for the children of migrants. When combined with concerns about global and national security such as those that are associated with Muslims and Islam, then questions about the strength national identity are particularly pertinent. This analysis uses the theories of transnational social fields and intersectionality to examine the transnational experiences of second-generation Muslim Americans. It relies on qualitative interview data. The data show the intersection of their national, religious, and gender identities. It demonstrates that they experience transnational being in their parents’ country of origin and belonging in the United States. Nationality, religion, and gender influence what they experience in each location. The analysis demonstrates the stability and centrality of American national identity in what second-generation Muslims experience in both locations. Moreover, their belonging in the United States rests squarely on their perceptions of themselves as Americans and their construction of their Muslim identity as an American religious identity.

  12. Second generation bioethanol potential from selected Malaysia's biodiversity biomasses: A review.

    Science.gov (United States)

    Aditiya, H B; Chong, W T; Mahlia, T M I; Sebayang, A H; Berawi, M A; Nur, Hadi

    2016-01-01

    Rising global temperature, worsening air quality and drastic declining of fossil fuel reserve are the inevitable phenomena from the disorganized energy management. Bioethanol is believed to clear out the effects as being an energy-derivable product sourced from renewable organic sources. Second generation bioethanol interests many researches from its unique source of inedible biomass, and this paper presents the potential of several selected biomasses from Malaysia case. As one of countries with rich biodiversity, Malaysia holds enormous potential in second generation bioethanol production from its various agricultural and forestry biomasses, which are the source of lignocellulosic and starch compounds. This paper reviews potentials of biomasses and potential ethanol yield from oil palm, paddy (rice), pineapple, banana and durian, as the common agricultural waste in the country but uncommon to be served as bioethanol feedstock, by calculating the theoretical conversion of cellulose, hemicellulose and starch components of the biomasses into bioethanol. Moreover, the potential of the biomasses as feedstock are discussed based on several reported works. Copyright © 2015 Elsevier Ltd. All rights reserved.

  13. Post-Dictatorship Documentary in Chile: Conversations with Three Second-Generation Film Directors

    Directory of Open Access Journals (Sweden)

    Antonio Traverso

    2018-01-01

    Full Text Available No other medium has rejected the restorative narrative of Chile’s democratic state’s memory discourse as vigorously as documentary cinema. After the several democratic governments that succeeded the civic-military dictatorial alliance that ruled this nation uninterruptedly between 1973 and 1990, documentary films have resisted monumental versions of historical memory by confronting the ambivalent nuances of the traumatic legacy of the dictatorship. Chilean documentarians have investigated, uncovered, and depicted the dictatorial state’s crimes, while offering testimonial space to survivors, and have also interrogated the perspectives of the dictatorship’s supporters, collaborators, and perpetrators while wrestling with an open dialectic of confrontational and reconciliatory gestures. More recently, this interest has intensified and combined with what is often described as a “boom” in second-generation personal-narration memory films. The present article includes the author’s conversations with the directors of three recent Chilean second-generation documentaries that explore the perspectives of former secret service collaborators: Adrian Goycoolea’s ¡Viva Chile Mierda! [Long Live Chile, Damn It!] (2014, Andrés Lübbert’s El color del camaleón [The Color of the Chameleon] (2017, and Lissette Orozco’s El pacto de Adriana [Adriana’s Pact] (2017.

  14. Design, development, and evaluation of a second generation interactive Simulator for Engineering Ethics Education (SEEE2).

    Science.gov (United States)

    Alfred, Michael; Chung, Christopher A

    2012-12-01

    This paper describes a second generation Simulator for Engineering Ethics Education. Details describing the first generation activities of this overall effort are published in Chung and Alfred (Sci Eng Ethics 15:189-199, 2009). The second generation research effort represents a major development in the interactive simulator educational approach. As with the first generation effort, the simulator places students in first person perspective scenarios involving different types of ethical situations. Students must still gather data, assess the situation, and make decisions. The approach still requires students to develop their own ability to identify and respond to ethical engineering situations. However, were as, the generation one effort involved the use of a dogmatic model based on National Society of Professional Engineers' Code of Ethics, the new generation two model is based on a mathematical model of the actual experiences of engineers involved in ethical situations. This approach also allows the use of feedback in the form of decision effectiveness and professional career impact. Statistical comparisons indicate a 59 percent increase in overall knowledge and a 19 percent improvement in teaching effectiveness over an Internet Engineering Ethics resource based approach.

  15. Anticonvulsant use after formulary status change for brand-name second-generation anticonvulsants.

    Science.gov (United States)

    Patel, Hemal; Toe, Diana C; Burke, Shawn; Rasu, Rafia S

    2010-08-01

    Anticonvulsant medications are commonly used for off-label indications. However, managed care organizations can restrict utilization of medication to indicated uses only. To evaluate the pattern of off-label use of second-generation anticonvulsants after implementing a formulary change. We did a retrospective analysis of an administrative pharmacy claims database for a managed care plan with more than 1 million members continuously enrolled during 2004-2005. The study evaluated off-label use and explored pharmacy utilization patterns (by physician specialty, region, plan type, age, sex, copayment) across the study population following the formulary change. A total of 10,185 patients had at least 1 pharmacy claim (total of 137,638 claims) for a second-generation anticonvulsant during the study period. Most members were female (68%), and 4.9% were anticonvulsants prescribed for off-label use in 2004 and 2005, respectively (P = .162). The off-label usage pattern varied for individual anticonvulsants in 2004 and 2005 (P anticonvulsants for off-label uses, followed by neurologists (9.4%), psychiatrists (2.8%), and other (46.5%). The coverage change resulted in cost savings for the plan of $0.16 per member per month. The off-label usage pattern varied for individual anticonvulsants in 2004 and 2005. Future considerations for controlling off-label use may include requiring prior authorization and provider education.

  16. Saccharomyces cerevisiae strains for second-generation ethanol production: from academic exploration to industrial implementation

    Science.gov (United States)

    Jansen, Mickel L. A.; Bracher, Jasmine M.; Papapetridis, Ioannis; Verhoeven, Maarten D.; de Bruijn, Hans; de Waal, Paul P.; van Maris, Antonius J. A.; Klaassen, Paul

    2017-01-01

    Abstract The recent start-up of several full-scale ‘second generation’ ethanol plants marks a major milestone in the development of Saccharomyces cerevisiae strains for fermentation of lignocellulosic hydrolysates of agricultural residues and energy crops. After a discussion of the challenges that these novel industrial contexts impose on yeast strains, this minireview describes key metabolic engineering strategies that have been developed to address these challenges. Additionally, it outlines how proof-of-concept studies, often developed in academic settings, can be used for the development of robust strain platforms that meet the requirements for industrial application. Fermentation performance of current engineered industrial S. cerevisiae strains is no longer a bottleneck in efforts to achieve the projected outputs of the first large-scale second-generation ethanol plants. Academic and industrial yeast research will continue to strengthen the economic value position of second-generation ethanol production by further improving fermentation kinetics, product yield and cellular robustness under process conditions. PMID:28899031

  17. First- and second-generation total synthesis of ciguatoxin CTX3C.

    Science.gov (United States)

    Inoue, Masayuki; Miyazaki, Keisuke; Uehara, Hisatoshi; Maruyama, Megumi; Hirama, Masahiro

    2004-08-17

    More than 20,000 people suffer annually from ciguatera seafood poisoning in subtropical and tropical regions. The extremely low content of the causative neurotoxins, designated as ciguatoxins, in fish has hampered isolation, detailed biological studies, and preparation of anti-ciguatoxin antibodies for detecting these toxins. Furthermore, the large (3 nm in length) and complex molecular structure of ciguatoxins has impeded chemists from completing their total synthesis. In this article, the full details of studies leading to the total synthesis of ciguatoxin CTX3C are provided. The key elements of the first-generation approach include O,O-acetal formation from the right and left wing fragments, conversion from O,O-acetal to O,S-acetal, a radical reaction to cyclize the G ring, a ring-closing metathesis reaction to close the F ring, and final removal of the 2-naphtylmethyl protective groups. Subsequent studies provided a second-generation total synthesis, which is more concise and results in a higher yield. Second-generation synthesis was accomplished by using a direct method of constructing the key intermediate O,S-acetal from alpha-chlorosulfide and a secondary alcohol. These syntheses ensure a practical supply of ciguatoxin for biological applications.

  18. Mood, anxiety, and personality disorders among first and second-generation immigrants to the United States

    Science.gov (United States)

    Salas-Wright, Christopher P.; Kagotho, Njeri; Vaughn, Michael G.

    2014-01-01

    A careful examination of the multigenerational relationship between immigrant status and mental disorders can provide important information about the robustness and nature of the immigrant-mental health link. We examine immigrant status as a protective factor against mental illness, assess intergenerational effects, examine differences across race/ethnicity, and report the prevalence of mood, anxiety, and personality disorders of immigrants across major world regions. We employ data from the National Epidemiologic Survey on Alcohol and Related Conditions (NESARC) and compare first (n = 5,363) and second-generation (n = 4826) immigrants from Asia, Africa, Europe, and Latin America to native-born Americans (n = 24,461) with respect to mental disorders. First-generation immigrants are significantly less likely than native-born Americans to be diagnosed with a mood, anxiety, or personality disorder, though the prevalence of mental health diagnoses increases among second generation immigrants. Similar results were observed for immigrants from major world regions as the prevalence of psychiatric morbidity was lower among immigrants from Africa, Latin America, Europe, and Asia compared to native-born Americans. Findings provide evidence in support of the notion that the immigrant paradox may be extended to include mood, anxiety, and personality disorders in the United States. PMID:25223256

  19. Enhanced protein loading on a planar Si(111)-H surface with second generation NTA

    Science.gov (United States)

    Liu, Xiang; Han, Huan-Mei; Liu, Hong-Bo; Xiao, Shou-jun

    2010-08-01

    A Si(111)-H surface was modified via a direct reaction between Si-H and 1-undecylenic acid (UA) under microwave irradiation to form molecular monolayers with terminal carboxyl groups. After esterifying carboxylic acid being esterified with N-hydroxysuccinimide (NHS), aminobutyl nitrilotriacetic acid (ANTA) was bound to the silicon surface through amidation (pH = 8.0) between its primary amino group and NHS-ester, producing nitrilotriacetic acid (NTA) anions. Then hexa-histidine tagged thioredoxin-urodilatin (his-tagged protein) and FITC-labeled hexa-histidine tagged thioredoxin-urodilatin (FITC-his-tagged protein) can be anchored after NTA was coordinated with Ni 2+. Furthermore, the NTA-terminated chip was acidified with 0.1 M HCl and subsequently esterified with NHS and then amidated with ANTA again to produce a second generation NTA. Thus the surface density of nitrilotriacetic acid anions was improved and resultantly that of anchored proteins was also enhanced through the iterative reactions. Both multiple transmission-reflection infrared spectroscopy (MTR-IR) and fluorescence scanning measurements demonstrated a proximate 1.63 times of anchored proteins on the second generation NTA/Ni 2+ as that on the first generation NTA/Ni 2+ monolayer.

  20. Role of energy policy in renewable energy accomplishment: The case of second-generation bioethanol

    International Nuclear Information System (INIS)

    Tan, Kok Tat; Lee, Keat Teong; Mohamed, Abdul Rahman

    2008-01-01

    Renewable energy has been in the limelight ever since the price of crude petroleum oil increases to the unprecedented height of US$96 per barrel recently. This is due to the diminishing oil reserves in the world and political instabilities in some oil-exporting countries. The advantages of renewable energy compared to fossil fuels are enormous in terms of environment and availability. Biofuels like bioethanol and biodiesel are currently being produced from agricultural products such as sugarcane and rapeseed oil, respectively. Collectively, these biofuels from food sources are known as first-generation biofuels. Although first-generation biofuels have the potential to replace fossil fuels as the main source of energy supply, its production is surrounded by certain issues like tropical forests' destruction. Instead, second-generation bioethanol, which utilizes non-edible sources such as lignocellulose biomass to produce ethanol, has been shown to be more suitable as the source of renewable energy. However, there are challenges and obstacles such as cost, technology and environmental issues that need to be overcome. Hence, the introduction of energy policy is crucial in promoting and implementing second-generation bioethanol effectively and subsequently become a major source of renewable energy

  1. Ground-based gravitational wave interferometric detectors of the first and second generation: an overview

    International Nuclear Information System (INIS)

    Losurdo, Giovanni

    2012-01-01

    The era of first-generation gravitational wave interferometric detectors is ending. No signals have been detected so far. However, remarkable results have been achieved: the design sensitivity has been approached (and in some cases even exceeded) together with the achievement of robustness and reliability; a world-wide network of detectors has been established; the data collected so far has allowed upper limits to be put on several types of sources; some second-generation technologies have been tested on these detectors. The scenario for the next few years is very exciting. The projects to upgrade LIGO and Virgo to second-generation interferometers, capable of increasing the detection rate by a factor of ∼1000, have been funded. The construction of Advanced LIGO and Advanced Virgo has started. GEO600 has started the upgrade to GEO HF, introducing light squeezing for the first time on a large detector. LCGT has been partly funded and the construction of the vacuum system is underway. There is a possibility that the third Advanced LIGO interferometer will be constructed in India. So, a powerful worldwide network could be in operation by the end of the decade. In this paper, we review the results achieved so far and the perspectives for the advanced detectors. (paper)

  2. Second-generation mobile satellite system. A conceptual design and trade-off study

    Science.gov (United States)

    Sue, M. K.; Park, Y. H.

    1985-01-01

    In recent years, interest has grown in the mobile satellite (MSAT) system, a satellite-based communications system capable of providing integrated voice and data services to a large number of users. To explore the potential of a commercial mobile satellite system (MSS) beyond the horizon of the first generation, using technologies of the 1990's and to assist MSAT-X in directing its efforts, a conceptual design has been performed for a second-generation system to be launched around the mid-1990's. The design goal is to maximize the number of satellite channels and/or minimize the overall life-cycle cost, subject to the constraint of utilizing a commercial satellite bus with minimum modifications. To provide an optimal design, a series of trade-offs are performed, including antenna sizing, feed configurations, and interference analysis. Interference is a serious problem for MSAT and often an overlapping feed design is required to reduce interbeam interference. The trade-off studies will show that a simple non-overlapping feed is sufficient for the second-generation system, thus avoiding the need for the complicated beam-forming network that is associated with the overlapping feed designs. In addition, a system that operates at L-band, an alternative frequency band that is being considered by some for possible MSAT applications, is also presented.

  3. Effects of Antipsychotics on Secular Mortality Trends in Patients With Alzheimer's Disease

    DEFF Research Database (Denmark)

    Nielsen, René Ernst; Valentin, Jan B; Lolk, Annette

    2018-01-01

    OBJECTIVE: To investigate secular changes in mortality rates between patients with Alzheimer's disease (AD) and the general population as well as changes in antipsychotic drug treatment and the association between drug treatment and mortality in patients with AD in Denmark during a 12-year study...

  4. Prevalence of Antipsychotic Polypharmacy and Associated Factors among Outpatients with Schizophrenia Attending Amanuel Mental Specialized Hospital, Addis Ababa, Ethiopia

    Directory of Open Access Journals (Sweden)

    Siranesh Tesfaye

    2016-01-01

    Full Text Available Background. Despite recommendations by guidelines to avoid combinations of antipsychotics unless after multiple trials of antipsychotic monotherapy, it is quite a common practice to use combinations. This practice leads to unnecessary expenses and exposes the patient to severe drug adverse effects. Methods. An institution based cross-sectional study was conducted from April to May 2014. Systematic random sampling technique was used to select 423 study subjects. Logistic regression analysis was conducted to identify associated factors of antipsychotic polypharmacy among schizophrenia outpatients. Result. The overall prevalence of antipsychotic polypharmacy was found to be 28.2%. Extra pyramidal side effects (AOR = 2.80; 95% CI: 1.38, 5.71, repeated psychiatric hospitalization (AOR = 2.83; 95% CI: 1.45, 5.50, history of substance use (AOR = 2.82; 95% CI: 1.36, 5.88, longer duration of treatment (AOR = 2.10; 95% CI: 1.14, 3.87, and drug nonadherence (AOR = 1.84; 95% CI: 1.14, 2.98 were found to be significantly associated with antipsychotic polypharmacy. Conclusion. Prevalence of antipsychotic polypharmacy was found to be high among the current study participants. Individuals who had extra pyramidal side effects, admission, substance use, duration of treatment, and drug nonadherence were associated with antipsychotic polypharmacy.

  5. Summary of the comparative effectiveness review on off-label use of atypical antipsychotics.

    Science.gov (United States)

    Maher, Alicia R; Theodore, George

    2012-06-01

    Conventional and atypical antipsychotic medications are approved by the FDA for treatment of schizophrenia and bipolar disorder. Over many decades, the widespread use of conventional antipsychotics produced various side effects requiring additional medications, such as the atypical antipsychotics. Beginning in 2006, 9 atypical antipsychotic drugs have been approved by the FDA for indications that were previously off-label uses: aripiprazole (as augmentation for major depressive disorder [MDD] and for autism spectrum disorders), asenapine, clozapine, iloperidone, olanzapine (in combination with fluoxetine for MDD and bipolar depression), paliperidone, quetiapine (quetiapine and quetiapine XR [extended release] as monotherapy in bipolar depression and quetiapine XR as augmentation for MDD), risperidone (for autism spectrum disorders), and ziprasidone. In 2006, the Agency for Healthcare Research and Quality (AHRQ) published a systematic review on the comparative effectiveness of off-label uses of atypical antipsychotics. Since that time, numerous studies have been published evaluating these therapies in various new off-label uses; new or increased adverse effects have been observed with off-label uses; new atypical antipsychotics have been approved; and previously off-label uses have been approved for some atypical antipsychotics. Hence, AHRQ published an updated review in September 2011 that summarized the benefits and harms of atypical antipsychotics in the treatment of attention-deficit hyperactivity disorder/attention deficit disorder (ADHD), anxiety, behavioral disturbances of dementia and severe geriatric agitation, depression, eating disorders, insomnia, obsessive-compulsive disorder (OCD), personality disorder, post-traumatic stress disorder (PTSD), substance use and dependence disorders, and Tourette's syndrome. The new report also investigated topics for which data in the previous report were found to be insufficient to make conclusions, including

  6. The switch from conventional to atypical antipsychotic treatment should not be based exclusively on the presence of cognitive deficits. A pilot study in individuals with schizophrenia

    Directory of Open Access Journals (Sweden)

    Sánchez-Moreno José

    2010-06-01

    Full Text Available Abstract Background Atypical antipsychotics provide better control of the negative and affective symptoms of schizophrenia when compared with conventional neuroleptics; nevertheless, their heightened ability to improve cognitive dysfunction remains a matter of debate. This study aimed to examine the changes in cognition associated with long-term antipsychotic treatment and to evaluate the effect of the type of antipsychotic (conventional versus novel antipsychotic drugs on cognitive performance over time. Methods In this naturalistic study, we used a comprehensive neuropsychological battery of tests to assess a sample of schizophrenia patients taking either conventional (n = 13 or novel antipsychotics (n = 26 at baseline and at two years after. Results Continuous antipsychotic treatment regardless of class was associated with improvement on verbal fluency, executive functions, and visual and verbal memory. Patients taking atypical antipsychotics did not show greater cognitive enhancement over two years than patients taking conventional antipsychotics. Conclusions Although long-term antipsychotic treatment slightly improved cognitive function, the switch from conventional to atypical antipsychotic treatment should not be based exclusively on the presence of these cognitive deficits.

  7. Antipsychotic treatment for children and adolescents with schizophrenia spectrum disorders

    DEFF Research Database (Denmark)

    Pagsberg, Anne Katrine; Tarp, Simon; Glintborg, D

    2014-01-01

    INTRODUCTION: Antipsychotic treatment in early-onset schizophrenia (EOS) lacks a rich evidence base, and efforts to rank different drugs concerning their efficacy have not proven any particular drug superior. In contrast to the literature regarding adult-onset schizophrenia (AOS), comparative...... allocate children and adolescents presenting with schizophrenia or a related non-affective psychotic condition to an intervention group or to a control group. Two reviewers will-independently and in duplicate-screen titles and abstracts, complete full text reviews to determine eligibility, and subsequently...

  8. Second Generation Electronic Nicotine Delivery System Vape Pen Exposure Generalizes as a Smoking Cue.

    Science.gov (United States)

    King, Andrea C; Smith, Lia J; McNamara, Patrick J; Cao, Dingcai

    2018-01-05

    Second generation electronic nicotine delivery systems (ENDS; also known as e-cigarettes, vaporizers or vape pens) are designed for a customized nicotine delivery experience and have less resemblance to regular cigarettes than first generation "cigalikes." The present study examined whether they generalize as a conditioned cue and evoke smoking urges or behavior in persons exposed to their use. Data were analyzed in N = 108 young adult smokers (≥5 cigarettes per week) randomized to either a traditional combustible cigarette smoking cue or a second generation ENDS vaping cue in a controlled laboratory setting. Cigarette and e-cigarette urge and desire were assessed pre- and post-cue exposure. Smoking behavior was also explored in a subsample undergoing a smoking latency phase after cue exposure (N = 26). The ENDS vape pen cue evoked both urge and desire for a regular cigarette to a similar extent as that produced by the combustible cigarette cue. Both cues produced similar time to initiate smoking during the smoking latency phase. The ENDS vape pen cue elicited smoking urge and desire regardless of ENDS use history, that is, across ENDS naїve, lifetime or current users. Inclusion of past ENDS or cigarette use as covariates did not significantly alter the results. These findings demonstrate that observation of vape pen ENDS use generalizes as a conditioned cue to produce smoking urge, desire, and behavior in young adult smokers. As the popularity of these devices may eventually overtake those of first generation ENDS cigalikes, exposure effects will be of increasing importance. This study shows that passive exposure to a second generation ENDS vape pen cue evoked smoking urge, desire, and behavior across a range of daily and non-daily young adult smokers. Smoking urge and desire increases after vape pen exposure were similar to those produced by exposure to a first generation ENDS cigalike and a combustible cigarette, a known potent cue. Given the increasing

  9. Harmonic US imaging of vesicoureteric reflux in children: usefulness of a second generation US contrast agent.

    Science.gov (United States)

    Ascenti, Giorgio; Zimbaro, Giovanni; Mazziotti, Silvio; Chimenz, Roberto; Fede, Carmelo; Visalli, Carmela; Scribano, Emanuele

    2004-06-01

    Contrast-enhanced voiding urosonography (VUS) is largely accepted both for the diagnosis and follow-up of vesicoureteric reflux (VUR) in children. To evaluate the usefulness of contrast-enhanced second-harmonic VUS in the diagnosis and grading of VUR, using a second-generation contrast agent. Eighty consecutive children were prospectively studied with contrast-enhanced second-harmonic VUS. All children received a second-generation contrast medium, constituted by phospholipid-stabilized microbubbles of sulphur-hexafluoride (SonoVue, Bracco, Milan, Italy). US monitoring of the bladder, of the retrovesical space and of the kidneys was performed using, alternatively, both tissue-harmonic and contrast-harmonic modes. In those young boys where VUR was depicted at VUS, examination was completed with transperineal, sagittal urethral exploration during micturition. VUR was graded in five steps and diagnoses were compared with voiding cystourethrography (VCUG). VUR was diagnosed in 52 reno-ureteral units with VUS. In 49 of these reno-ureteral units, VCUG confirmed the presence of VUR. In comparison to VUS, sensitivity and negative predictive value of VCUG were inferior. The grade of VUR detected at VUS was higher than that detected at VCUG in three units. In no case was the grade of VUR detected at VCUG higher than the one detected at VUS. The differences between VUS and VCUG in grading VUR were statistically significant (p=0.02). Imaging of the normal posterior urethra was skilfully demonstrated with US in 15 young boys with VUR. No statistically significant differences were found between tissue-harmonic and contrast-harmonic mode (p=0.102). Contrast-enhanced second-harmonic VUS is a sensitive and easy technique for the evaluation of VUR. A second-generation US contrast medium such as SonoVue, if available, should be the first choice as the dose required for one examination is much lower and consequently significant reduction of contrast agent cost is possible. Copyright

  10. Risperidone versus typical antipsychotic medication for schizophrenia.

    Science.gov (United States)

    Hunter, R H; Joy, C B; Kennedy, E; Gilbody, S M; Song, F

    2003-01-01

    Risperidone is one of the 'new generation' antipsychotics. As well as its reputed tendency to cause fewer movement disorders than the older drugs such as chlorpromazine and haloperidol, it is claimed that risperidone may improve negative symptoms. To evaluate the effects of risperidone for schizophrenia in comparison to 'conventional' neuroleptic drugs. The original electronic searches of Biological Abstracts (1980-1997), Cochrane Schizophrenia Group's Register (1997), The Cochrane Library (1997, Issue 1), EMBASE (1980-1997), MEDLINE (1966-1997), PsycLIT (1974-1997), and SCISEARCH (1997) were updated with a new electronic search of the same databases in 2002. The search term used in the update was identical to that used in 1997. Any new studies or relevant references were added to the review. In addition, references of all identified studies were searched for further trial citations. Pharmaceutical companies and authors of trials were also contacted. All randomised trials comparing risperidone to any 'conventional' neuroleptic treatment for people with schizophrenia or other similar serious mental illnesses. Citations and, where possible, abstracts were independently inspected by reviewers, papers ordered, re-inspected and quality assessed. Data were also independently extracted. Where possible, sensitivity analyses on dose of risperidone, haloperidol and duration of illness were undertaken for the primary outcomes of clinical improvement, side effects (movement disorders) and acceptability of treatment. For homogeneous dichotomous data the Relative Risk (RR), 95% confidence interval (CI) and, where appropriate, the number needed to treat/harm (NNT/H) were calculated on an intention-to-treat basis. In the short-term, risperidone was more likely to produce an improvement in the Positive and Negative Syndrome Scale (PANSS) when compared with haloperidol (n=2368, 9 RCTs, RR not 20% improved 0.72 CI 0.59 to 0.88 NNT 8). A similar, favourable outcome for risperidone was

  11. Second Generation Amphiphilic Poly-Lysine Dendrons Inhibit Glioblastoma Cell Proliferation without Toxicity for Neurons or Astrocytes.

    Directory of Open Access Journals (Sweden)

    Jolanta Janiszewska

    Full Text Available Glioblastomas are the most common malignant primary brain tumours in adults and one of the most aggressive and difficult-to-treat cancers. No effective treatment exits actually for this tumour and new therapeutic approaches are needed for this disease. One possible innovative approach involves the nanoparticle-mediated specific delivery of drugs and/or genetic material to glioblastoma cells where they can provide therapeutic benefits. In the present work, we have synthesised and characterised several second generation amphiphilic polylysine dendrons to be used as siRNA carriers. We have found that, in addition to their siRNA binding properties, these new compounds inhibit the proliferation of two glioblastoma cell lines while being nontoxic for non-tumoural central nervous system cells like neurons and glia, cell types that share the anatomical space with glioblastoma cells during the course of the disease. The selective toxicity of these nanoparticles to glioblastoma cells, as compared to neurons and glial cells, involves mitochondrial depolarisation and reactive oxygen species production. This selective toxicity, together with the ability to complex and release siRNA, suggests that these new polylysine dendrons might offer a scaffold in the development of future nanoparticles designed to restrict the proliferation of glioblastoma cells.

  12. Drug-induced parkinsonism: diagnosis and management

    Directory of Open Access Journals (Sweden)

    Blanchet PJ

    2016-09-01

    Full Text Available Pierre J Blanchet,1–3 Veronika Kivenko1–3 1Department of Stomatology, Faculty of Dental Medicine, University of Montreal, 2Andre-Barbeau Movement Disorders Unit, University of Montreal Hospital Center (CHU Montreal, 3Montreal Mental Health University Institute, Montreal, QC, Canada Abstract: Drug-induced parkinsonism (DIP has been known for >60 years. It is the second leading cause of parkinsonism, but still underdiagnosis is likely to influence reported incidence figures. Since DIP is clinically undistinguishable from Lewy-body Parkinson’s disease, any new case of parkinsonism should prompt the search for an offending antipsychotic, hidden neuroleptic, or nonneuroleptic agent that may produce DIP. DIP is reversible upon drug withdrawal in most cases. There is no consensus regarding the duration of the recovery period to allow motor signs to fully remit in order to confirm the diagnosis of DIP following removal of the causative agent, but a drug-free interval of at least 6 months is generally recommended. Interestingly, up to 30% of DIP cases may show persisting or worsening motor signs beyond 6 months following drug withdrawal or adjustment, due to complex postsynaptic and presynaptic factors that may variably interact to negatively influence nigrostriatal dopamine transmission in a so-called “double-hit” hypothesis. The condition significantly impacts on quality of life and increases the risks of morbidity and mortality. Management is challenging in psychiatric patients and requires a team approach to achieve the best outcome. Keywords: neuroleptic drugs, extrapyramidal side effects, second generation antipsychotics, calcium channel blockers, valproic acid, tetrabenazine 

  13. SEVIRI, the imaging radiometer on Meteosat second generation: in-orbit results and first assessment

    Science.gov (United States)

    Coste, P.; Pasternak, F.; Faure, F.; Jacquet, B.; Bianchi, S.; Aminou, Donny M. A.; Luhmann, H. J.; Hanson, C.; Pili, P.; Fowler, G.

    2017-11-01

    Meteosat Second Generation (MSG) is a series of 3 geo-stationary satellites developed and procured by the European Space Agency (ESA) on behalf of the European Organisation for the Exploitation of Meteorological Satellites (EUMETSAT). The first satellite (MSG-1) was launched on August 29, 2002 by an Ariane 5 rocket. SEVIRI is the main MSG payload and produces 12 channels imaging in visible and IR range. The 8 Infrared Channels in the 3.9-13.4 mm band benefit from high radiometric performances thanks to the use of detectors operating at 95K and cooled by specifically designed passive radiator. During the commissioning phase, dedicated tests have been conducted to verify the SEVIRI functionality and performances. This paper presents briefly the SEVIRI design and highlights the correlation of data obtained in-flight by EUMETSAT with the ground predictions. A particular emphasis is put on the in-orbit evolution of the IR channel gains and on the instrument decontamination.

  14. Second-generation PVCC design with a dielectric light injector and polyhedron interior cavity

    Science.gov (United States)

    Ortabasi, Ugur; Winston, Roland; Ellis, Scott

    2006-08-01

    The Photovoltaic Cavity Converter (PVCC) under development is a novel approach to convert highly concentrated solar radiation into electricity via a photon entrapment process and subsequent spectral stripping. Equipped with a multi-bandgap, single junction cell system PVCC circumvents most of the present limitations of the four (or more)-junction cell systems with vertical architecture. Our previous studies have shown that the PVCC concept has the potential to reach a collective conversion efficiency of 50% in the near term. Based on our past experiences regarding the cavity geometry and the light injection method we have developed a second generation design for the PVCC that overcomes the limitations of the first generation prototype.

  15. Self-assembly of the second-generation of nitroaryl-ended dendrons onto carbon

    International Nuclear Information System (INIS)

    Farías, E.D.; Paez, J.I.; Strumia, M.C.; Baruzzi, A.M.; Passeggi Jr, M.C.G.; Brunetti, V.

    2014-01-01

    Graphical abstract: - Abstract: We report the self-assembly of the second-generation of nitroaryl-ended dendrons onto carbon surfaces. The immobilized layer was characterized by cyclic voltammetry (CV), electrochemical impedance spectroscopy and atomic force microscopy (AFM). The response was analyzed in comparison to the first-generation dendron behavior. Reduction of both layers generates the hydroxylamine product. The resulting redox-active layer exhibits a well-behaved redox response for the adsorbed nitroso/hydroxylamine couple. The thermodynamic of the adsorption of both dendrons on glassy carbon electrodes was also studied by CV. The Frumkin adsorption isotherm was the best to describe the specific interactions. The AFM images showed a network film formation with embedded aggregates that completely covered the carbon surface. The average height suggests a tilted preferential adsorption for both molecules

  16. A second generation 50 Mbps VLSI level zero processing system prototype

    Science.gov (United States)

    Harris, Jonathan C.; Shi, Jeff; Speciale, Nick; Bennett, Toby

    1994-01-01

    Level Zero Processing (LZP) generally refers to telemetry data processing functions performed at ground facilities to remove all communication artifacts from instrument data. These functions typically include frame synchronization, error detection and correction, packet reassembly and sorting, playback reversal, merging, time-ordering, overlap deletion, and production of annotated data sets. The Data Systems Technologies Division (DSTD) at Goddard Space Flight Center (GSFC) has been developing high-performance Very Large Scale Integration Level Zero Processing Systems (VLSI LZPS) since 1989. The first VLSI LZPS prototype demonstrated 20 Megabits per second (Mbp's) capability in 1992. With a new generation of high-density Application-specific Integrated Circuits (ASIC) and a Mass Storage System (MSS) based on the High-performance Parallel Peripheral Interface (HiPPI), a second prototype has been built that achieves full 50 Mbp's performance. This paper describes the second generation LZPS prototype based upon VLSI technologies.

  17. TADIR: ElOp's high-resolution second-generation 480 x 4 TDI thermal imager

    Science.gov (United States)

    Sarusi, Gabby; Ziv, Natan; Zioni, O.; Gaber, J.; Shechterman, Mark S.; Wiess, I.; Friedland, Igor V.; Lerner, M.; Friedenberg, Abraham

    1998-10-01

    'TADIR' is a new high-end thermal imager, developed in El-Op under contract with the Israeli MOD during the last three years. This new second generation thermal imager is based on 480 X 4 TDI MCT detector operated in the 8 - 12 micrometer spectral range. Although the prototype configuration of TADIR was design for the highly demanded light weight low volume and low power air applications, TADIR can be considered as a generic modular technology of which the future El-Op's FLIR applications such as ground fire control system and surveillance systems will be derived from. Besides the detector, what puts the system in the high-end category are the state of the art features implemented in each system's components. This paper describes the system concept and design considerations as well as the anticipated performances. TADIRs fist prototype was demonstrated at the beginning of 1998 and is currently under evaluation.

  18. Second Generation Youth in Canada, Their Mobilities and Identifications: Relevance to Citizenship Education

    Directory of Open Access Journals (Sweden)

    Mehrunnisa Ali

    2010-05-01

    Full Text Available Based on narrative data recently collected from youth’s in three Canadian cities, our paper focuses on second generation perceptions of youth’s identifications in a society increasingly influenced by the forces of globalization and how these perceptions may or may not be reflected in programs of study dealing with citizenship education. We utilize a framework consisting of a continuum of mobilities of mind, body, and boundaries to situate their sense of self. The façade of globalisation is examined in terms of its impact on identity formation and these youths’ impressions of diversity and multiculturalism. Finally, we consider the relevance of the findings for citizenship education in Ontario, Manitoba, and Alberta.

  19. Second-Generation High-Temperature Superconductor Wires for the Electric Power Grid

    Science.gov (United States)

    Malozemoff, A. P.

    2012-08-01

    Superconductors offer major advantages for the electric power grid, including high current and power capacity, high efficiency arising from the lossless current flow, and a unique current-limiting functionality arising from a superconductor-to-resistive transition. These advantages can be brought to bear on equipment such as underground power cables, fault current limiters, rotating machinery, transformers, and energy storage. The first round of significant commercial-scale superconductor power-equipment demonstrations, carried out during the past decade, relied on a first-generation high-temperature superconductor (HTS) wire. However, during the past few years, with the recent commercial availability of high-performance second-generation HTS wires, power-equipment demonstrations have increasingly been carried out with these new wires, which bring important advantages. The foundation is being laid for commercial expansion of this important technology into the power grid.

  20. Second-generation nanofiltered plasma-derived mannan-binding lectin product

    DEFF Research Database (Denmark)

    Laursen, I.; Houen, G.; Højrup, P.

    2007-01-01

    infections. Substitution therapy with plasma-derived MBL is a promising treatment of diseases associated with MBL deficiency. A first-generation MBL product has been shown to be safe and well tolerated, and patients have benefited from MBL treatment. Following is a description of the development...... of a nanofiltered second-generation MBL product from Cohn fraction III, with the use of a new affinity matrix for MBL purification and the characteristics of this improved product. MATERIALS AND METHODS: Carbohydrate-based gels were comparatively screened as affinity matrices. MBL was extracted from fraction III......, and affinity purified on a Superdex 200 pg column. The eluted material underwent two virus reduction steps: filtration through Planova 20N and solvent/detergent treatment. It was further purified by anion-exchange and gel-filtration chromatography. The affinity eluate and the final MBL fraction were...

  1. Antipsychotic treatment among youth in foster care.

    Science.gov (United States)

    Dosreis, Susan; Yoon, Yesel; Rubin, David M; Riddle, Mark A; Noll, Elizabeth; Rothbard, Aileen

    2011-12-01

    Despite national concerns over high rates of antipsychotic medication use among youth in foster care, concomitant antipsychotic use has not been examined. In this study, concomitant antipsychotic use among Medicaid-enrolled youth in foster care was compared with disabled or low-income Medicaid-enrolled youth. The sample included 16 969 youths younger than 20 years who were continuously enrolled in a Mid-Atlantic state Medicaid program and had ≥1 claim with a psychiatric diagnosis and ≥1 antipsychotic claim in 2003. Antipsychotic treatment was characterized by days of any use and concomitant use with ≥2 overlapping antipsychotics for >30 days. Medicaid program categories were foster care, disabled (Supplemental Security Income), and Temporary Assistance for Needy Families (TANF). Multicategory involvement for youths in foster care was classified as foster care/Supplemental Security Income, foster care/TANF, and foster care/adoption. We used multivariate analyses, adjusting for demographics, psychiatric comorbidities, and other psychotropic use, to assess associations between Medicaid program category and concomitant antipsychotic use. Average antipsychotic use ranged from 222 ± 110 days in foster care to only 135 ± 101 days in TANF (P foster care only and 24% in foster care/adoption compared with youths in the foster care system.

  2. Meta-analysis: Risk of dry mouth with second generation antidepressants.

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    Cappetta, Kiley; Beyer, Chad; Johnson, Jessica A; Bloch, Michael H

    2018-06-08

    The goal of this meta-analysis was to quantify the risk of dry mouth associated with commonly prescribed antidepressant agents and examine the potential implications of medication class, dose, and pharmacodynamics and dose on risk of treatment-induced dry mouth. A PubMed search was conducted to identify double-blind, randomized, placebo-controlled trials examining the efficacy and tolerability of second generation antidepressant medications for adults with depressive disorders, anxiety disorders, and OCD. A random-effects meta-analysis was used to quantify the pooled risk ratio of treatment-emergent dry mouth with second generation antidepressants compared to placebo. Stratified subgroup analysis and meta-regression was utilized to further examine the effects antidepressant agent, class, dosage, indication, and receptor affinity profile on the measured risk of dry mouth. 99 trials involving 20,868 adults. SNRIs (Relative Risk (RR)=2.24, 95% Confidence Interval (CI): 1.95-2.58, z=11.2, pz=5.8, pz=10.32, pz=5.85, pz=3.26, p=0.001) and Alpha-2 (PE=0.49, 95% CI: 0.22-0.75, z=3.64, pz=2.10, p<0.05) was significantly associated with increased risk of dry mouth. The current meta-analysis suggests that SSRIs, SNRIs, and atypical antidepressants are all associated with varying degrees of increased risk of dry mouth. SNRIs were associated with a significantly greater risk of dry mouth compared to SSRIs. Copyright © 2017 Elsevier Inc. All rights reserved.

  3. Biomechanical evaluation of a second generation headless compression screw for ankle arthrodesis in a cadaver model.

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    Somberg, Andrew Max; Whiteside, William K; Nilssen, Erik; Murawski, Daniel; Liu, Wei

    2016-03-01

    Many types of screws, plates, and strut grafts have been utilized for ankle arthrodesis. Biomechanical testing has shown that these constructs can have variable stiffness. More recently, headless compression screws have emerged as an evolving method of achieving compression in various applications but there is limited literature regarding ankle arthrodesis. The aim of this study was to determine the biomechanical stability provided by a second generation fully threaded headless compression screw compared to a standard headed, partially threaded cancellous screw in a cadaveric ankle arthrodesis model. Twenty fresh frozen human cadaver specimens were subjected to simulated ankle arthrodesis with either three standard cancellous-bone screws (InFix 7.3mm) or with three headless compression screws (Acumed Acutrak 2 7.5mm). The specimens were subjected to cyclic loading and unloading at a rate of 1Hz, compression of 525 Newtons (N) and distraction of 20N for a total of 500 cycles using an electromechanical load frame (Instron). The amount of maximum distraction was recorded as well as the amount of motion that occurred through 1, 10, 50, 100, and 500 cycles. No significant difference (p=0.412) was seen in the amount of distraction that occurred across the fusion site for either screw. The average maximum distraction after 500 cycles was 201.9μm for the Acutrak 2 screw and 235.4μm for the InFix screw. No difference was seen throughout each cycle over time for the Acutrak 2 screw (p-value=0.988) or the InFix screw (p-value=0.991). Both the traditional InFix type screw and the second generation Acumed Acutrak headless compression screws provide adequate fixation during ankle arthrodesis under submaximal loads. There is no demonstrable difference between traditional cannulated partially threaded screws and headless compression screws studied in this model. Copyright © 2015 European Foot and Ankle Society. Published by Elsevier Ltd. All rights reserved.

  4. From molecular clusters to nanoparticles: second-generation ion-mediated nucleation model

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    F. Yu

    2006-01-01

    Full Text Available Ions, which are generated in the atmosphere by galactic cosmic rays and other ionization sources, may play an important role in the formation of atmospheric aerosols. In the paper, a new second-generation ion-mediated nucleation (IMN model is presented. The new model explicitly treats the evaporation of neutral and charged clusters and it describes the evolution of the size spectra and composition of both charged and neutral clusters/particles ranging from small clusters of few molecules to large particles of several micrometers in diameter. Schemes used to calculate the evaporation coefficients for small neutral and charged clusters are consistent with the experimental data within the uncertainty range. The present IMN model, which is size-, composition-, and type-resolved, is a powerful tool for investigating the dominant mechanisms and key parameters controlling the formation and subsequent growth of nanoparticles in the atmosphere. This model can be used to analyze simultaneous measurements of the ion-mobility spectra and particle size distributions, which became available only recently. General features of the spectra for ions smaller than the critical size, size-dependent fractions of charged nanoparticles, and asymmetrical charging of freshly nucleated particles predicted by the new IMN model are consistent with recent measurements. Results obtained using the second generation IMN model, in which the most recent thermodynamic data for neutral and charged H2SO4-H2O clusters were used, suggest that ion-mediated nucleation of H2SO4-H2O can lead to a significant production of new particles in the lower atmosphere (including the boundary layer under favorable conditions. It has been shown that freshly nucleated particles of few nanometers in size can grow by the condensation of low volatile organic compounds to the size of cloud condensation nuclei. In such cases, the chemical composition of nucleated particles larger than ~10 nm is dominated

  5. Curcumin Mitigates the Intracellular Lipid Deposit Induced by Antipsychotics In Vitro.

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    Alberto Canfrán-Duque

    Full Text Available First- and second-generation antipsychotics (FGAs and SGAs, respectively, both inhibit cholesterol biosynthesis and impair the intracellular cholesterol trafficking, leading to lipid accumulation in the late endosome/lysosome compartment. In this study we examined if curcumin, a plant polyphenol that stimulates exosome release, can alleviate antipsychotic-induced intracellular lipid accumulation.HepG2 hepatocarcinoma cells were treated with antipsychotics or placebo and DiI-labelled LDL for 18 h and then exposed to curcumin for the last 2 h. Cells and media were collected separately and used for biochemical analyses, electron microscopy and immunocytochemistry. Exosomes were isolated from the incubation medium by ultracentrifugation.Curcumin treatment reduced the number of heterolysosomes and shifted their subcellular localization to the periphery, as revealed by electron microscopy, and stimulated the release of lysosomal β-hexosaminidase and exosome markers flotillin-2 and CD63 into the media. The presence of DiI in exosomes released by cells preloaded with DiI-LDL demonstrated the endolysosomal origin of the microvesicles. Furthermore, curcumin increased the secretion of cholesterol as well as LDL-derived DiI and [3H]-cholesterol, in association with a decrease of intracellular lipids. Thus, the disruption of lipid trafficking induced by FGAs or SGAs can be relieved by curcumin treatment. This polyphenol, however, did not mitigate the reduction of cholesterol esterification induced by antipsychotics.Curcumin stimulates exosome release to remove cholesterol (and presumably other lipids accumulated within the endolysosomal compartment, thereby normalizing intracellular lipid homeostasis. This action may help minimize the adverse metabolic effects of antipsychotic treatment, which should now be evaluated in clinical trials.

  6. Quantifying risk: the role of absolute and relative measures in interpreting risk of adverse reactions from product labels of antipsychotic medications.

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    Citrome, Leslie

    2009-09-01

    Pharmaceutical product labeling as approved by regulatory agencies include statements of adverse event risk. Product labels include descriptive statements such as whether events are uncommon or rare, as well as percentage occurrence for more common events. In addition tables are provided with the frequencies of the latter events for both product and placebo as observed in clinical trials. Competing products are not mentioned in a specific drug's product labeling but indirect comparisons can be made using the corresponding label information for the alternate product. Two types of tools are easily used for this purpose: absolute measures such as number needed to harm (NNH), and relative measures such as relative risk increase (RRI). The calculations for both of these types of quantitative measures are presented using as examples the oral first-line second-generation antipsychotic medications. Among three sample outcomes selected a priori, akathisia, weight gain, and discontinuation from a clinical trial because of an adverse reaction, there appears to be differences among the different antipsychotics versus placebo. Aripiprazole was associated with the highest risk for akathisia, particularly when used as adjunctive treatment of major depressive disorder (NNH 5, 95% CI 4-7; RRI 525%, 95% CI 267%-964%). Although insufficient information was available in product labeling to calculate the CI, olanzapine was associated with the highest risk for weight gain of at least 7% from baseline (NNH 6, RRI 640% for adults; NNH 4, RRI 314% for adolescents), and quetiapine for the indication of bipolar depression was associated with the highest risk of discontinuation from a clinical trial because of an adverse reaction (NNH 8, RRI 265% for 600 mg/d; NNH 15, RRI 137% for 300 mg/d). In conclusion, with certain limitations, it is possible for the clinician to extract information from medication product labeling regarding the frequency with which certain adverse reactions can be

  7. Atypical Antipsychotic Medications and Hyponatremia in Older Adults: A Population-Based Cohort Study

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    Sonja Gandhi

    2016-04-01

    Full Text Available Background: A number of case reports have suggested a possible association between atypical antipsychotic medications and hyponatremia. Currently, there are no reliable estimates of hyponatremia risk from atypical antipsychotic drugs. Objective: The objective of this study was to examine the 30-day risk of hospitalization with hyponatremia in older adults dispensed an atypical antipsychotic drug relative to no antipsychotic use. Design: The design of this study was a retrospective, population-based cohort study. Setting: The setting of this study was in Ontario, Canada, from 2003 to 2012. Patients: Adults 65 years or older with an identified psychiatric condition who were newly dispensed risperidone, olanzapine, or quetiapine in the community setting compared to adults with similar indicators of baseline health who were not dispensed such a prescription. Measurements: The primary outcome was the 30-day risk of hospitalization with hyponatremia. The tracer outcome (an outcome that is not expected to be influenced by the study drugs was the 30-day risk of hospitalization with bowel obstruction. These outcomes were assessed using hospital diagnosis codes. Methods: Using health administrative data, we applied a propensity score technique to match antipsychotic users 1:1 to non-users of antipsychotic drugs (58,008 patients in each group. We used conditional logistic regression to compare outcomes among the matched users and non-users. Results: A total of 104 baseline characteristics were well-balanced between the two matched groups. Atypical antipsychotic use compared to non-use was associated with an increased risk of hospitalization with hyponatremia within 30 days (86/58,008 (0.15 % versus 53/58,008 (0.09 %; relative risk 1.62 (95 % confidence interval (CI 1.15 to 2.29; absolute risk increase 0.06 % (95 % CI 0.02 to 0.10. The limited number of events precluded some additional analyses to confirm if the association was robust. Atypical

  8. Attitudes toward antipsychotic treatment among patients with bipolar disorders and their clinicians: a systematic review

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    Sajatovic M

    2017-08-01

    may reflect a relative lack of experience using antipsychotics in patients with bipolar disorder. Conclusion: Although data are very limited, perceived tolerability and efficacy concerns shape both patient and clinician attitudes toward use of antipsychotic drugs in bipolar disorder. Additional studies are warranted. Keywords: bipolar disorder, antipsychotics, systematic review, attitudes

  9. Patient, Physician and Organizational Influences on Variation in Antipsychotic Prescribing Behavior.

    Science.gov (United States)

    Tang, Yan; Chang, Chung-Chou H; Lave, Judith R; Gellad, Walid F; Huskamp, Haiden A; Donohue, Julie M

    2016-03-01

    Physicians face the choice of multiple ingredients when prescribing drugs in many therapeutic categories. For conditions with considerable patient heterogeneity in treatment response, customizing treatment to individual patient needs and preferences may improve outcomes. To assess variation in the diversity of antipsychotic prescribing for mental health conditions, a necessary although not sufficient condition for personalizing treatment. To identify patient caseload, physician, and organizational factors associated with the diversity of antipsychotic prescribing. Using 2011 data from Pennsylvania's Medicaid program, IMS Health's HCOSTM database, and the AMA Masterfile, we identified 764 psychiatrists who prescribed antipsychotics to 10 patients. We constructed three physician-level measures of diversity/concentration of antipsychotic prescribing: number of ingredients prescribed, share of prescriptions for most preferred ingredient, and Herfindahl-Hirschman index (HHI). We used multiple membership linear mixed models to examine patient caseload, physician, and healthcare organizational predictors of physician concentration of antipsychotic prescribing. There was substantial variability in antipsychotic prescribing concentration among psychiatrists, with number of ingredients ranging from 2-17, share for most preferred ingredient from 16%-85%, and HHI from 1,088-7,270. On average, psychiatrist prescribing behavior was relatively diversified; however, 11% of psychiatrists wrote an average of 55% of their prescriptions for their most preferred ingredient. Female prescribers and those with smaller shares of disabled or serious mental illness patients had more concentrated prescribing behavior on average. Antipsychotic prescribing by individual psychiatrists in a large state Medicaid program varied substantially across psychiatrists. Our findings illustrate the importance of understanding physicians' prescribing behavior and indicate that even among specialties