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Search Results: 1 - 10 of 8304 matches for " Sara Kollack-Walker "
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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
Ilya A Lipkovich, Walter Deberdt, John G Csernansky, Bernard Sabbe, Richard SE Keefe, Sara Kollack-Walker
BMC Psychiatry , 2009, DOI: 10.1186/1471-244x-9-44
Abstract: 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.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.Processing speed demonstrated direct and indirect effects via negative symptoms on three domains of functioning as measured by the QLS at baseline and following 24 weeks of antipsychotic treatment.Neurocognitive impairment has been found to be strongly correlated with deficits in psychosocial and occupational functioning in patients with schizophrenia [1,2]. These earlier reviews of the literature (including a meta-analysis) were focused on identifying specific neurocognitive deficits that restrict the functioning of schizophrenia patients, as opposed to the use of more global measures of n
Impact of race on efficacy and safety during treatment with olanzapine in schizophrenia, schizophreniform or schizoaffective disorder
Virginia L Stauffer, Jennifer L Sniadecki, Kevin W Piezer, Jennifer Gatz, Sara Kollack-Walker, Vicki Hoffmann, Robert Conley, Todd Durell
BMC Psychiatry , 2010, DOI: 10.1186/1471-244x-10-89
Abstract: A post-hoc, pooled analysis of 6 randomized, double-blind trials in the treatment of schizophrenia, schizophreniform disorder, or schizoaffective disorder compared white (N = 605) and black (N = 375) patients treated with olanzapine (5 to 20 mg/day) for 24 to 28 weeks. Efficacy measurements included the Positive and Negative Syndrome Scale (PANSS) total score; and positive, negative, and general psychopathology scores; and the Clinical Global Impression of Severity (CGI-S) scores at 6 months. Safety measures included differences in the frequencies of adverse events along with measures of extrapyramidal symptoms, weight, glucose, and lipid changes over time.51% of black patients and 45% of white patients experienced early study discontinuation (P = .133). Of those who discontinued, significantly more white patients experienced psychiatric worsening (P = .002) while significantly more black patients discontinued for reasons other than efficacy or tolerability (P = .014). Discontinuation for intolerability was not different between groups (P = .320). For the estimated change in PANSS total score over 6 months, there was no significant difference in efficacy between white and black patients (P = .928), nor on the estimated PANSS positive (P = .435), negative (P = .756) or general psychopathology (P = .165) scores. Overall, there was no significant difference in the change in CGI-S score between groups from baseline to endpoint (P = .979). Weight change was not significantly different in white and black patients over 6 months (P = .127). However, mean weight change was significantly greater in black versus white patients at Weeks 12 and 20 only (P = .028 and P = .026, respectively). Additionally, a significantly greater percentage of black patients experienced clinically significant weight gain (≥7%) at anytime compared to white patients (36.1% vs. 30.4%, P = .021). Changes across metabolic parameters (combined fasting and random lipids and glucose) were also not signifi
The relationship, structure and profiles of schizophrenia measurements: a post-hoc analysis of the baseline measures from a randomized clinical trial
Lei Chen, Glenn Phillips, Joseph Johnston, Bruce J Kinon, Haya Ascher-Svanum, Sara Kollack-Walker, Paul Succop, Dieter Naber
BMC Psychiatry , 2011, DOI: 10.1186/1471-244x-11-203
Abstract: We used baseline data from a randomized, multicenter study of patients diagnosed with schizophrenia, schizoaffective disorder, or schizophreniform disorder who were experiencing an acute symptom exacerbation (n = 628) to examine the relationship among several outcome measures. These measures included the Positive and Negative Syndrome Scale (PANSS), Montgomery-Asberg Depression Rating Scale (MADRS), Brief Assessment of Cognition in Schizophrenia Symbol Coding Test, Subjective Well-being Under Neuroleptics Scale Short Form (SWN-K), Schizophrenia Objective Functioning Instrument (SOFI), and Quality of Life Scale (QLS). Three analytic approaches were used: 1) path analysis; 2) factor analysis; and 3) categorical latent variable analysis. In the optimal path model, the SWN-K was selected as the final outcome, while the SOFI mediated the effect of the exogenous variables (PANSS, MADRS) on the QLS.The overall model explained 47% of variance in QLS and 17% of the variance in SOFI, but only 15% in SWN-K. Factor analysis suggested four factors: "Functioning," "Daily Living," "Depression," and "Psychopathology." A strong positive correlation was observed between the SOFI and QLS (r = 0.669), and both the QLS and SOFI loaded on the "Functioning" factor, suggesting redundancy between these scales. The measurement profiles from the categorical latent variable analysis showed significant variation in functioning and quality of life despite similar levels of psychopathology.Researchers should consider collecting PANSS, SOFI, and SWN-K in their trials. This would allow a broad spectrum of assessments that would have the ability to capture a wide range of treatment outcomes and allow for a rich characterization of the subgroups involved. Additional research is needed to identify the critical cognitive measures.Clinical trials registration: Predicting Response to Risperidone Treatment Through Identification of Early-onset of Antipsychotic Drug Action in SchizophreniaClinicalTrials.go
Identification of early changes in specific symptoms that predict longer-term response to atypical antipsychotics in the treatment of patients with schizophrenia
Stephen J Ruberg, Lei Chen, Virginia Stauffer, Haya Ascher-Svanum, Sara Kollack-Walker, Robert R Conley, John Kane, Bruce J Kinon
BMC Psychiatry , 2011, DOI: 10.1186/1471-244x-11-23
Abstract: Data were pooled from moderately to severely ill patients (n = 1494) from 6 randomized, double-blind trials (N = 2543). Response was defined as a ≥30% reduction in Positive and Negative Syndrome Scale (PANSS) Total score by Week 8 of treatment. Analyzed predictors were change in individual PANSS items at Weeks 1 and 2. A decision tree was constructed using classification and regression tree (CART) analysis to identify predictors that most effectively differentiated responders from non-responders.A 2-branch, 6-item decision tree was created, producing 3 distinct groups. First branch criterion was a 2-point score decrease in at least 2 of 5 PANSS positive items (Week 2). Second branch criterion was a 2-point score decrease in the PANSS excitement item (Week 2). "Likely responders" met the first branch criteria; "likely non-responders" did not meet first or second criterion; "not predictable" patients did not meet the first but did meet the second criterion. Using this approach, response to treatment could be predicted in most patients (92%) with high positive predictive value (79%) and high negative predictive value (75%). Predictive findings were confirmed through analysis of data from 2 independent trials.Using a data-driven approach, we identified decision rules using early change in the scores of selected PANSS items to accurately predict longer-term treatment response or non-response to atypical antipsychotic therapy. This could lead to development of a simple quantitative evaluation tool to help guide early treatment decisions.This is a retrospective, non-intervention study in which pooled results from 6 previously published reports were analyzed; thus, clinical trial registration is not required.Over 66% of patients with chronic schizophrenia who are started on atypical antipsychotics for treatment of moderate to severe symptoms will fail to show moderate improvement after 3 months of treatment, and 1 in 3 will fail to show even minimal improvement [1,2]. When
Cost-effectiveness of early responders versus early nonresponders to atypical antipsychotic therapy
Peng X, Ascher-Svanum H, Faries DE, Stauffer VL, Kollack-Walker S, Kinon BJ, Kane JM
ClinicoEconomics and Outcomes Research , 2011, DOI: http://dx.doi.org/10.2147/CEOR.S16859
Abstract: st-effectiveness of early responders versus early nonresponders to atypical antipsychotic therapy Original Research (2804) Total Article Views Authors: Peng X, Ascher-Svanum H, Faries DE, Stauffer VL, Kollack-Walker S, Kinon BJ, Kane JM Published Date April 2011 Volume 2011:3 Pages 79 - 87 DOI: http://dx.doi.org/10.2147/CEOR.S16859 Xiaomei Peng1, Haya Ascher-Svanum1, Douglas E Faries1, Virginia L Stauffer1, Sara Kollack-Walker1, Bruce J Kinon1, John M Kane2 1Eli Lilly and Company, Indianapolis, Indiana; 2Zucker Hillside Hospital, Department of Psychiatry, Glen Oaks, New York, USA Background: To compare the cost-effectiveness of treating early responders versus early nonresponders to an atypical antipsychotic (risperidone) and the cost-effectiveness of treating early nonresponders maintained on risperidone versus those switched to olanzapine. Methods: This post hoc analysis used data from a randomized, double-blind, 12-week schizophrenia study (Study Code: HGMN, n = 628). Participants were initially assigned to risperidone therapy. Early response was defined as a ≥ 20% improvement on the Positive and Negative Syndrome Scale (PANSS) total score from baseline to two weeks. Early responders continued on risperidone, whereas early nonresponders were randomized in a double-blind manner to continue on risperidone or switch to olanzapine for 10 additional weeks. Early responders and early nonresponders maintained on risperidone were compared for health-state utilities (benefits) and total cost over the 12-week study; early nonresponders maintained on risperidone or switched to olanzapine were compared from randomization (10-week period). Utilities were derived from the PANSS and adverse events. Mixed models were used to assess group differences in utilities. Treatment costs were calculated based on health states. Incremental cost-effectiveness ratios were then utilized to compare treatment groups. Results: Early responders to risperidone had significantly greater total utility and lower total treatment costs than early nonresponders to risperidone. Compared with early nonresponders who continued on risperidone, those who were switched to olanzapine had significantly higher total utility scores at endpoint and numerically lower total treatment costs, reflecting significantly lower nonmedication treatment costs, even though medication costs were significantly higher compared with generic risperidone. Conclusion: Treatment of early responders was more cost-effective than treatment of early nonresponders to atypical antipsychotic therapy. Switching early nonresponders to olanzapine resulted in improved treatment effectiveness, met the criteria for some dominance, and appeared modestly more cost-effective than maintaining treatment with generic risperidone.
The Descent of Math
Sara Imari Walker
Physics , 2015,
Abstract: A perplexing problem in understanding physical reality is why the universe seems comprehensible, and correspondingly why there should exist physical systems capable of comprehending it. In this essay I explore the possibility that rather than being an odd coincidence arising due to our strange position as passive (and even more strangely, conscious) observers in the cosmos, these two problems might be related and could be explainable in terms of fundamental physics. The perspective presented suggests a potential unified framework where, when taken together, comprehenders and comprehensibility are part of causal structure of physical reality, which is considered as a causal graph (network) connecting states that are physically possible. I argue that in some local regions, the most probable states are those that include physical systems which contain information encodings - such as mathematics, language and art - because these are the most highly connected to other possible states in this causal graph. Such physical systems include life and - of particular interest for the discussion of the place of math in physical reality - comprehenders capable of making mathematical sense of the world. Within this framework, the descent of math is an undirected outcome of the evolution of the universe, which will tend toward states that are increasingly connected to other possible states of the universe, a process greatly facilitated if some physical systems know the rules of the game. I therefore conclude that our ability to use mathematics to describe, and more importantly manipulate, the natural world may not be an anomaly or trick, but instead could provide clues to the underlying causal structure of physical reality.
Toward homochiral protocells in noncatalytic peptide systems
Marcelo Gleiser,Sara Imari Walker
Physics , 2008, DOI: 10.1007/s11084-009-9166-5
Abstract: The activation-polymerization-epimerization-depolymerization (APED) model of Plasson et al. has recently been proposed as a mechanism for the evolution of homochirality on prebiotic Earth. The dynamics of the APED model in two-dimensional spatially-extended systems is investigated for various realistic reaction parameters. It is found that the APED system allows for the formation of isolated homochiral proto-domains surrounded by a racemate. A diffusive slowdown of the APED network such as induced through tidal motion or evaporating pools and lagoons leads to the stabilization of homochiral bounded structures as expected in the first self-assembled protocells.
Life's Chirality From Prebiotic Environments
Marcelo Gleiser,Sara Imari Walker
Physics , 2012, DOI: 10.1017/S1473550412000377
Abstract: A key open question in the study of life is the origin of biomolecular homochirality: almost every life-form on Earth has exclusively levorotary amino acids and dextrorotary sugars. Will the same handedness be preferred if life is found elsewhere? We review some of the pertinent literature and discuss recent results suggesting that life's homochirality resulted from sequential chiral symmetry breaking triggered by environmental events. In one scenario, autocatalytic prebiotic reactions undergo stochastic fluctuations due to environmental disturbances. In another, chiral-selective polymerization reaction rates influenced by environmental effects lead to substantial chiral excess even in the absence of autocatalysis. Applying these arguments to other potentially life-bearing platforms has implications to the search for extraterrestrial life: we predict that a statistically representative sampling of extraterrestrial stereochemistry will be racemic (chirally neutral) on average.
The Chirality Of Life: From Phase Transitions To Astrobiology
Marcelo Gleiser,Sara Imari Walker
Quantitative Biology , 2008,
Abstract: The search for life elsewhere in the universe is a pivotal question in modern science. However, to address whether life is common in the universe we must first understand the likelihood of abiogenesis by studying the origin of life on Earth. A key missing piece is the origin of biomolecular homochirality: permeating almost every life-form on Earth is the presence of exclusively levorotary amino acids and dextrorotary sugars. In this work we discuss recent results suggesting that life's homochirality resulted from sequential chiral symmetry breaking triggered by environmental events in a mechanism referred to as punctuated chirality. Applying these arguments to other potentially life-bearing platforms has significant implications for the search for extraterrestrial life: we predict that a statistically representative sampling of extraterrestrial stereochemistry will be racemic on average.
An Extended Model for the Evolution of Prebiotic Homochirality: A Bottom-Up Approach to the Origin of Life
Marcelo Gleiser,Sara Imari Walker
Quantitative Biology , 2008, DOI: 10.1007/s11084-008-9134-5
Abstract: A generalized autocatalytic model for chiral polymerization is investigated in detail. Apart from enantiomeric cross-inhibition, the model allows for the autogenic (non-catalytic) formation of left and right-handed monomers from a substrate with reaction rates $\epsilon_L$ and $\epsilon_R$, respectively. The spatiotemporal evolution of the net chiral asymmetry is studied for models with several values of the maximum polymer length, N. For N=2, we study the validity of the adiabatic approximation often cited in the literature. We show that the approximation obtains the correct equilibrium values of the net chirality, but fails to reproduce the short time behavior. We show also that the autogenic term in the full N=2 model behaves as a control parameter in a chiral symmetry- breaking phase transition leading to full homochirality from racemic initial conditions. We study the dynamics of the N -> infinity model with symmetric ($\epsilon_L = \epsilon_R$) autogenic formation, showing that it only achieves homochirality for $\epsilon < \epsilon_c$, where $\epsilon_c$ is an N-dependent critical value. For $\epsilon \leq \epsilon_c$ we investigate the behavior of models with several values of N, showing that the net chiral asymmetry grows as tanh(N). We show that for a given symmetric autogenic reaction rate, the net chirality and the concentrations of chirally pure polymers increase with the maximum polymer length in the model. We briefly discuss the consequences of our results for the development of homochirality in prebiotic Earth and possible experimental verification of our findings.
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