Methods for Predictor Analysis of Repeated Measurements: Application to Psychiatric Data

2004 ◽  
Vol 43 (02) ◽  
pp. 184-191 ◽  
Author(s):  
M. Eisenacher ◽  
M. Riesbeck ◽  
W. Gaebel ◽  
W. Köpcke ◽  
S. A. Seuchter ◽  
...  
Keyword(s):  
Term Treatment ◽  
Repeated Measurements ◽  
Research Network ◽  
First Episode ◽  
Correlated Response ◽  
Data Set ◽  
Data Presentation ◽  
Long Term Treatment ◽  
Presentation Methods ◽  
Artificial Neural Network Ann

Summary Objectives: In schizophrenia research, little attention yet has been directed on methods for analyzing data from studies with repeated measurements over time. Motivation for this research stems from a project within the German Research Network on Schizophrenia, in which an algorithm is developed to guide prodrome-based early intervention strategies in stable first episode patients. Methods: We present two different approaches for the analysis of correlated response data, the Generalized Estimating Equations (GEE) method and the Artificial Neural Network (ANN) approach. We illustrate the methods using the data of the A.N.I. study, which is one of the largest German multicenter treatment studies in regard to the long-term treatment of schizophrenia conducted between 1983 and 1989. Results: The results of statistical model selection prior to GEE analysis and various data presentation methods for ANNs are presented. The primary goal of our evaluation is to investigate if the defined prodromes are valid predictors for relapse. Additionally, it is shown that both methods are applicable on a realistic data set. Conclusions: It is concluded that both methods are suitable for predictor analysis especially since all variable time points of the patients are included instead of only selected, so that it can be assumed that results are not biased. With the GEE method a test of association for each predictor can be performed whereas with ANNs a general proposition can be made for pro-dromes depending on the type of data presentation. Using the A.N.I. data the prodrome ‘trouble sleeping’ seems to be the most informative predictor. Finally, the important differences of the two methods are discussed.

scholarly journals Do antipsychotic drugs lose their efficacy for relapse prevention over time?

2017 ◽  
Vol 211 (3) ◽  
pp. 127-129 ◽  
Author(s):  
Stefan Leucht ◽  
John M. Davis
Keyword(s):  
Relapse Prevention ◽  
Antipsychotic Drugs ◽  
Meta Analysis ◽  
Term Treatment ◽  
First Episode ◽  
Brain Volume Loss ◽  
New Findings ◽  
Long Term Treatment ◽  
Long Term Follow Up

SummaryThere is a debate about long-term treatment of schizophrenia with antipsychotic drugs, with some experts suggesting that these drugs should be discontinued. In this issue, Takeuchi et al demonstrated by a meta-analysis of 11 trials that antipsychotic drugs maintained their efficacy for relapse prevention for 1 year, whereas patients on placebo kept getting worse. We consider these findings in the light of the current discussion about possible dose-related brain volume loss, supersensitivity psychosis, the high variability of results in long-term follow-up studies and recent approaches to discontinue antipsychotics in patients with a first-episode. The new findings speak in favour of continuing antipsychotics at the same dose, at least in patients whose condition is chronic, but the topic is complex.

scholarly journals Clinical guideline recommendations for antipsychotic long-acting injections

2009 ◽  
Vol 195 (S52) ◽  
pp. s63-s67 ◽  
Author(s):  
John M. Kane ◽  
Carlos Garcia-Ribera
Keyword(s):  
First Generation ◽  
Term Treatment ◽  
First Episode ◽  
Patterns Of Use ◽  
Episode Psychosis ◽  
Long Term Treatment ◽  
Long Acting ◽  
Over 40 Years ◽  
Subsequent Relapse

BackgroundLong-acting injections (LAIs) of antipsychotic drugs were developed over 40 years ago in an attempt to improve the long-term treatment of schizophrenia.AimsTo review existing guidelines concerning antipsychotic use generally, and LAIs in particular, and how patients might be identified as potential candidates for LAI treatment.MethodLiterature review.ResultsCurrently several first-generation and one second-generation antipsychotic LAIs are available, with others under development. Although the use of LAIs is widespread around the world, patterns of use vary widely. Important considerations regarding the use of LAIs include the indications for long-term pharmacotherapy in schizophrenia in general, the indications for LAIs, the risks associated with LAIs, the need to update guidelines and the issue of cost.ConclusionsThe use of these injections in first-episode psychosis and treatment-refractory schizophrenia is not currently a focus of recommendations, but should be considered. Long-acting injections remain an underutilised option in many countries despite frequent non-adherence with oral medication and subsequent relapse.

scholarly journals Evaluation of NDEL1 oligopeptidase activity in blood and brain in an animal model of schizophrenia: effects of psychostimulants and antipsychotics

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
João V. Nani ◽  
Richard S. Lee ◽  
Camila M. Yonamine ◽  
Osvaldo A. Sant’Anna ◽  
Maria A. Juliano ◽  
...  
Keyword(s):  
Animal Model ◽  
Enzyme Activity ◽  
Chronic Schizophrenia ◽  
Brain Regions ◽  
Term Treatment ◽  
First Episode ◽  
Acute Administration ◽  
Long Term Treatment ◽  
Healthy Control ◽  
Normal Rat

Abstract Nuclear distribution element-like 1 (NDEL1) enzyme activity is important for neuritogenesis, neuronal migration, and neurodevelopment. We reported previously lower NDEL1 enzyme activity in blood of treated first episode psychosis and chronic schizophrenia (SCZ) compared to healthy control subjects, with even lower activity in treatment resistant chronic SCZ patients, implicating NDEL1 activity in SCZ. Herein, higher NDEL1 activity was observed in the blood and several brain regions of a validated animal model for SCZ at baseline. In addition, long-term treatment with typical or atypical antipsychotics, under conditions in which SCZ-like phenotypes were reported to be reversed in this animal model for SCZ, showed a significant NDEL1 activity reduction in blood and brain regions which is in line with clinical data. Importantly, these results support measuring NDEL1 enzyme activity in the peripheral blood to predict changes in NDEL1 activity in the CNS. Also, acute administration of psychostimulants, at levels reported to induce SCZ-like phenotype in normal rat strains, increased NDEL1 enzyme activity in blood. Therefore, alterations in NDEL1 activity after treatment with antipsychotics or psychostimulants may suggest a possible modulation of NDEL1 activity secondary to neurotransmission homeostasis and provide new insights into the role of NDEL1 in SCZ pathophysiology.

scholarly journals Effects of Psychostimulants and Antipsychotics on Serum Lipids in an Animal Model for Schizophrenia

Biomedicines ◽  
2021 ◽  
Vol 9 (3) ◽  
pp. 235
Author(s):  
Banny Silva Barbosa Correia ◽  
João Victor Nani ◽  
Raniery Waladares Ricardo ◽  
Danijela Stanisic ◽  
Tássia Brena Barroso Carneiro Costa ◽  
...  
Keyword(s):  
Animal Model ◽  
Lipid Metabolism ◽  
Atypical Antipsychotic ◽  
Serum Lipids ◽  
Spontaneously Hypertensive Rat ◽  
Term Treatment ◽  
First Episode ◽  
Omega 3 ◽  
Long Term Treatment

Schizophrenia (SCZ) treatment is essentially limited to the use of typical or atypical antipsychotic drugs, which suppress the main symptoms of this mental disorder. Metabolic syndrome is often reported in patients with SCZ under long-term drug treatment, but little is known about the alteration of lipid metabolism induced by antipsychotic use. In this study, we evaluated the blood serum lipids of a validated animal model for SCZ (Spontaneously Hypertensive Rat, SHR), and a normal control rat strain (Normotensive Wistar Rat, NWR), after long-term treatment (30 days) with typical haloperidol (HAL) or atypical clozapine (CLZ) antipsychotics. Moreover, psychostimulants, amphetamine (AMPH) or lisdexamfetamine (LSDX), were administered to NWR animals aiming to mimic the human first episode of psychosis, and the effects on serum lipids were also evaluated. Discrepancies in lipids between SHR and NWR animals, which included increased total lipids and decreased phospholipids in SHR compared with NWR, were similar to the differences previously reported for SCZ patients relative to healthy controls. Administration of psychostimulants in NWR decreased omega-3, which was also decreased in the first episode of psychosis of SCZ. Moreover, choline glycerophospholipids allowed us to distinguish the effects of CLZ in SHR. Thus, changes in the lipid metabolism in SHR seem to be reversed by the long-term treatment with the atypical antipsychotic CLZ, which was under the same condition described to reverse the SCZ-like endophenotypes of this validated animal model for SCZ. These data open new insights for understanding the potential influence of the treatment with typical or atypical antipsychotics on circulating lipids. This may represent an outcome effect from metabolic pathways that regulate lipids synthesis and breakdown, which may be reflecting a cell lipids dysfunction in SCZ.

scholarly journals The Effects of Antipsychotic Treatment on the Brain of Patients With First-Episode Schizophrenia: A Selective Review of Longitudinal MRI Studies

2021 ◽  
Vol 12 ◽  
Author(s):  
Chengmin Yang ◽  
Jing Tang ◽  
Naici Liu ◽  
Li Yao ◽  
Mengyuan Xu ◽  
...  
Keyword(s):  
Functional Imaging ◽  
Term Treatment ◽  
First Episode ◽  
Antipsychotic Treatment ◽  
Imaging Studies ◽  
Temporal Lobes ◽  
Long Term Treatment ◽  
Before And After ◽  
First Episode Schizophrenia ◽  
The Brain

A large number of neuroimaging studies have detected brain abnormalities in first-episode schizophrenia both before and after treatment, but it remains unclear how these abnormalities reflect the effects of antipsychotic treatment on the brain. To summarize the findings in this regard and provide potential directions for future work, we reviewed longitudinal structural and functional imaging studies in patients with first-episode schizophrenia before and after antipsychotic treatment. A total of 36 neuroimaging studies was included, involving 21 structural imaging studies and 15 functional imaging studies. Both anatomical and functional brain changes in patients after treatment were consistently observed in the frontal and temporal lobes, basal ganglia, limbic system and several key components within the default mode network (DMN). Alterations in these regions were affected by factors such as antipsychotic type, course of treatment, and duration of untreated psychosis (DUP). Over all we showed that: (a) The striatum and DMN were core target regions of treatment in schizophrenia, and their changes were related to different antipsychotics; (b) The gray matter of frontal and temporal lobes tended to reduce after long-term treatment; and (c) Longer DUP was accompanied with faster hippocampal atrophy after initial treatment, which was also associated with poorer outcome. These findings are in accordance with previous notions but should be interpreted with caution. Future studies are needed to clarify the effects of different antipsychotics in multiple conditions and to identify imaging or other biomarkers that may predict antipsychotic treatment response. With such progress, it may help choose effective pharmacological interventional strategies for individuals experiencing recent-onset schizophrenia.

High frequency of HER2-specific immunity observed in patients (pts) with HER2+ cancers treated with margetuximab (M), an Fc-enhanced anti-HER2 monoclonal antibody (mAb).

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 1030-1030 ◽  
Author(s):  
Jeffrey L. Nordstrom ◽  
John Muth ◽  
Courtney L. Erskine ◽  
Catherine Sanders ◽  
Erik C. Yusko ◽  
...  
Keyword(s):  
T Cell ◽  
High Frequency ◽  
Phase 1 ◽  
Term Treatment ◽  
Cell Repertoire ◽  
Post Dose ◽  
Specific Immunity ◽  
Long Term Treatment ◽  
Presentation Methods

1030 Background: Previous studies have shown that 44-71% of trastuzumab (T)-treated pts develop HER2-specific immunity (Clin Cancer Res 2007, 13:5133; Cancer Res 2016, 76:3702; Breast Cancer Res 2018, 20:52). M is an Fc-engineered mAb that shares similar HER2 binding and antiproliferative activity as T. The Fc region of M has been engineered for increased affinity to the activating FcγRIIIA (CD16A) and lower binding to the inhibitory FcγRIIB (CD32B), attributes that may enhance the mAb’s immune function, such as antigen presentation. Methods: HER2+ cancer pts who progressed on prior therapy received M (0.1-6 mg/kg QW for 3 of every 4 weeks [N = 34]; or 10-18 mg/kg Q3W [N = 32]) in phase 1 trial NCT01148849. PBMC and plasma were collected pre-dose and 50 days post-dose for 46 pts and > 4 years for 3 pts on long-term treatment. Response to HER2 or control antigens (Ag) was assessed by IFNγ ELISpot and antibody (Ab) ELISA. In 14 pts, T-cell antigen receptor (TCR) repertoire was assessed by immunosequencing. Results: Following M treatment, mean frequencies of IFNγ-producing T cells specific for intra- or extracellular fragments of HER2 increased by 2.5 to 6-fold (p < 0.0027, paired t test). Most (95%) of subjects responded to ≥2 of 6 (median = 5) HER2 Ag. Mean HER2-specific Ab concentration increased by 19-54% (p < 0.0001), with all subjects responding to ≥2 (median = 5) of the 6 Ag. A small 1.6-fold increase in IFNγ response to control CMV/EBV/Flu (but not tetanus or cyclin D1) peptides was observed; no increase in Ab response to control Ag was noted. Subsets of HER2-specific T-cell and Ab responses persisted during long-term treatment. Median TCR clonality increased by 54% (p = 0.003), with an average of 125 unique clones expanding, while overall TCR diversity remained unchanged (p = 0.19). Conclusions: Treatment of HER2+ cancer with M was associated with enhanced HER2-specific T-cell and Ab responses together with increased TCR clonality, indicative of a more focused T-cell repertoire. The high frequency of HER2-specific immunity in M-treated patients ( > 95%) is consistent with its enhanced Fc region contributing to linkage of innate and adaptive immune responses.

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