127 results on '"Rubio, Jose M"'
Search Results
102. Fluoroscopic Cardiac Anatomy for Catheter Ablation of Tachycardia
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FARRE, JERONIMO, primary, ANDERSON, ROBERT H., additional, CABRERA, JOSE A., additional, SANCHEZ-QUINTANA, DAMIAN, additional, RUBIO, JOSE M., additional, ROMERO, JOSE, additional, and CABESTRERO, FERNANDO, additional
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- 2002
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103. Genotypic Characterization of Toxoplasma gondii Strains Associated with Human Toxoplasmosis in Spain: Direct Analysis from Clinical Samples
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Fuentes, Isabel, primary, Rubio, Jose M., additional, Ramı́rez, Carmen, additional, and Alvar, Jorge, additional
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- 2001
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104. Presence of highly repetitive DNA sequences in Tribolium flour-beetles
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Juan, Carlos, primary, Vazquez, Patricia, additional, Rubio, Jose M, additional, Petitpierre, Eduard, additional, and Hewitt, Godfrey M, additional
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- 1993
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105. Current role and future perspectives for radiofrequency catheter ablation of postmyocardial...
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Farre, Jeronimo and Rubio, Jose M.
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CATHETER ablation , *MYOCARDIAL infarction , *VENTRICULAR tachycardia - Abstract
Examines the current role and future perspectives for radiofrequency catheter ablation (RFCA) of postmyocardial infarction (post-MI) ventricular tachycardia (VT). Difficulties faced by RFCA in post-MI VT; Pathophysiologic considerations in post-MI VT; Theoretical considerations to improve RFCA of VT; Advances predictable in the field of RFCA of VT.
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- 1996
106. Genotypic Characterization of Toxoplasma gondiiStrains Associated with Human Toxoplasmosis in Spain: Direct Analysis from Clinical Samples
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Fuentes, Isabel, Rubio, Jose M., Rami´rez, Carmen, and Alvar, Jorge
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ABSTRACTGenetic analysis of the SAG2locus was performed to determine the prevalence of the different genotypes of Toxoplasma gondii(strain types I, II, and III) associated with human toxoplasmosis in Spain. This determination was made directly from primary clinical samples, obviating the previous process of isolation in mice or cell culture. A total of 34 isolates of T. gondii, collected from immunocompromised patients and congenital infection cases, were analyzed. Restriction fragment length polymorphism in PCR-amplified SAG2products was used to group strains into one of the three genotypes of T. gondii. Complete characterization of the SAG2gene was successful in 76.5% of the cases, demonstrating the feasibility of direct genotype analysis from clinical samples of different origins. Strains of T. gondiitype II were the most prevalent in immunocompromised patients, with 52% of cases, while strains of type I were present in 75% of the congenital infection cases. These data differ from previous reports that show type II strains to be mostly associated with all kinds of human toxoplasmosis. These differences might be an effect of selection in the process of culture and isolation of the samples performed by other researchers prior to strain characterization.
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- 2001
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107. Hyperreactive Malarial Splenomegaly in Europeans: Report of Five Cases.
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Puente, Sabino, Subirats, Mercedes, Benito, Agustin, Rubio, Jose M., and Gonzalez-Lahoz, Juan M.
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COMMUNICABLE diseases ,EUROPEANS ,MALARIA ,PATHOLOGY ,DISEASES - Abstract
Presents a case study which investigated the pathogenesis of the tropical splenomegaly syndrome (TSS) among Europeans. Association of TSS to malaria; Criteria for the diagnosis of TSS; Clinical procedures for TSS.
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- 2001
108. P5-28: Proteomic analysis of patients with arrythmogenic right ventricular cardiomyopathy/dysplasia in comparison with normal subjects
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Rubio, Jose M., Pérez, Pedro P., Melero, Laura, Jiménez-Mateos, Petra, Cabrera, José A., Sanmillan, Federico, Santos-Gallego, Carlos Garcia, Piñero, Antonio, Lopez-Farre, Antonio, Farré, Jerónimo, and Macaya, Carlos
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- 2006
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109. Enalapril prevents electrical and structural remodeling in a canine model of atrial fibrillation: Molecular mechanisms
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Sanmillán, Federico, Cabrera, José A., Santos-Gallego, Carlos G., Pindado, Javier, Rubio, José M., Sánchez-Quintana, Damián, López-Farré, Antonio, Pérez, Pedro P., and Farré, Jerónimo
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- 2005
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110. 1090-213 The sinus nodal tissue arrangement into the musculature of the terminal crest: Implications in ablation of inappropriate sinus node tachycardia?
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Angel Cabrera, José, Sanchez-Quintana, Damian, Ho, Siew Y, Climent, Vicente, Rubio, Jose M, Cabestrero, Fernando, Anderson, Robert H, and Farre, Jeronimo
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- 2004
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111. 1034-214 Effects of candesartan and enalapril on atrial endocardial nitric oxide synthase expression in an animal model of pacing induced atrial remodelling
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Cabestrero, Fernando, Cabrera, Jose A, Courtois, Elise, Rubio, Jose M, Orejas, Miguel, Pérez, Pedro P, Herrera, Ana B, López-Farré, Antonio, and Farré, Jeronimo
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- 2004
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112. Síndrome de twiddler y fallo de sensado auricular
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Rivas, Pablo, Tuñón, José, Rubio, José M., Almeida, Pedro, Artiz, Víctor, and Farré, Jerónimo
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- 2001
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113. 6 - Cardiac Anatomy for Catheter Mapping and Ablation of Arrhythmias
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Farré, Jerónimo, Anderson, Robert H., Cabrera, José A., Sánchez-Quintana, Damián, Rubio, José M., and Benezet-Mazuecos, Juan
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114. Contributors
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Al-Ahmad, Amin, Anderson, Robert H., Arora, Rishi, Badhwar, Nitish, Banchs, Javier E., Benezet-Mazuecos, Juan, Bhakta, Deepak, Buch, Eric, Cabrera, José A., Calkins, Hugh, Callans, David J., Chang, Shih-Lin, Chen, Henry, Chen, Shih-Ann, Crawford, Thomas, Das, Mithilesh K., Dixit, Sanjay, Doshi, Shephal K., Dubuc, Marc, Dukkipati, Srinivas, Ernst, Sabine, Farré, Jerónimo, Feld, Gregory K., Fisher, Westby G., Forclaz, Andrei, Gonzalez, Mario D., Haines, David E., Haïssaguerre, Michel, Haqqani, Haris M., Higa, Satoshi, Hocini, Mélèze, Hoppe, Bobbi, Hsia, Henry H., Hung, Lynne, Jadidi, Amir, Jaïs, Pierre, Kadish, Alan, Kalman, Jonathan M., Keane, David, Khairy, Paul, Klein, George J., Knecht, Sebastien, Krahn, Andrew D., Lai, Ling-Ping, Lee, Byron K., Lerman, Bruce B., Lin, David, Lin, Kuo-Hung, Lin, Yenn-Jiang, Linton, Nick, Lo, Li-Wei, Marchlinski, Francis E., Markowitz, Steven M., Miller, John M., Miyazaki, Shinsuke, Morton, Joseph B., Nault, Isabelle, Nogami, Akihiko, Olgin, Jeffrey E., Oral, Hakan, Petrellis, Basilios, Reddy, Vivek Y., Rivera, Jaime, Ro, Alexander S., Rosso, Raphael, Rubio, José M., Sánchez-Quintana, Damián, Sanders, Prashanthan, Saul, J. Philip, Scanavacca, Mauricio, Shah, Ashok, Shivkumar, Kalyanam, Skanes, Allan C., Soejima, Kyoko, Sosa, Eduardo, Srivatsa, Uma, Tai, Ching-Tai, Taneja, Taresh, Turakhia, Mintu, Van Hare, George F., Walsh, Edward P., Wang, Paul J., Wright, Matthew, Yadav, Anil V., Yee, Raymond, and Zei, Paul C.
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115. Introducing S.C.O.P.E.™ (Schizophrenia Clinical Outcome Scenarios and Patient-Provider Engagement), an Interactive Digital Platform to Educate Healthcare Professionals on Schizophrenia Care.
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Correll CU, Rubio JM, Citrome L, Mychaskiw MA, Thompson S, Franzenburg KR, Suett M, Kotak S, and Kane JM
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Despite evidence of benefits beyond those of oral antipsychotics, long-acting injectable antipsychotics (LAIs) are underused in schizophrenia treatment. Underuse may be partially a result of misconceptions held by some healthcare professionals (HCPs) pertaining to LAIs. A panel of four experts convened between January 2022 and May 2022 to identify these misconceptions, and example cases or scenarios were created to illustrate common clinical situations relevant to these beliefs. Ultimately, an online platform and heuristic tool, Schizophrenia Clinical Outcome Scenarios and Patient-Provider Engagement (S.C.O.P.E.™), was developed to help prescribing clinicians and other HCPs better understand common clinical dilemmas, as well as the place for LAIs in schizophrenia treatment. Three main misconceptions related to the use of LAIs to treat schizophrenia were identified and included "physicians/providers know when patients are nonadherent", "patients do not accept/want LAI treatment", and "LAIs are only appropriate for patients who have demonstrated nonadherence". All misconceptions are refuted by current evidence and were used to develop clinical scenarios with questions to consider when patients present to various sites of care for treatment. These cases are presented on the S.C.O.P.E. educational platform. The platform also includes videos designed to help non-prescribing HCPs and mental health professionals address patient/caregiver concerns and to communicate LAI benefits. In addition, S.C.O.P.E. provides a section with information about each LAI that is currently FDA approved in the United States for the treatment of schizophrenia, to help familiarize HCPs with characteristics of LAIs. S.C.O.P.E. is an educational tool designed for HCPs to help improve their understanding of how to manage common clinical dilemmas in the treatment of people with schizophrenia, to clarify the role of LAIs in medication management, and to increase understanding of the characteristics of available LAIs. S.C.O.P.E. also aims to improve care in schizophrenia by facilitating increased awareness to patients and caregivers., Competing Interests: CUC has been a consultant for or has received honoraria from AbbVie, Acadia Pharmaceuticals, Adock Ingram, Alkermes, Allergan, Angelini Pharma, Aristo Pharma, Biogen, Boehringer Ingelheim, Cardio Diagnostics, Cerevel Therapeutics, CNX Therapeutics, COMPASS Pathways, Darnitsa, Denovo Biopharma, Gedeon Richter, Hikma, Holmusk, Intra-Cellular Therapies, Janssen, Johnson & Johnson, Karuna Therapeutics, LB Pharmaceuticals, Laboratorios Farmacéuticos ROVI, Lundbeck, MedAvante-ProPhase, MedinCell, Merck, Mindpax, Mitsubishi Tanabe Pharma, Maplight, Mylan, Neumora Therapeutics, Neurocrine Biosciences, Neurelis, Newron Pharmaceuticals, Noven, Novo Nordisk, Otsuka, Pharmabrain, PPD Biotech, Recordati, Relmada, Reviva, Sunovion, Supernus Pharmaceuticals, Takeda, Teva Pharmaceuticals, and Viatris; has provided expert testimony for Janssen and Otsuka and served on data safety monitoring boards or advisory boards for COMPASS Pathways, Denovo Biopharma, Laboratorios Farmacéuticos ROVI, Lundbeck, Relmada, Reviva, Sage Therapeutics, Supernus Pharmaceuticals, Tolmar, and Teva Pharmaceuticals; has received grant support from Janssen and Takeda and received royalties from UpToDate; serves on the board of directors for the American Society of Clinical Psychopharmacology; and is a stock option shareholder of Cardio Diagnostics, Mindpax, LB Pharmaceuticals, PsiloSterics, and Quantic Group. JMR has been a consultant for and has received support for attending meetings/travel from Teva Pharmaceuticals; has received honoraria from Lundbeck; has received grants from Alkermes, Janssen, Karuna, and the National Institute of Mental Health (NIMH); has received royalties/licensing fees from UpToDate; and owns stock/stock options in Doximity. LC is a consultant for AbbVie/Allergan, Acadia, Adamas, Alkermes, Angelini, Astellas, Avanir, Axsome, BioXcel, Boehringer Ingelheim, Cadent Therapeutics, Cerevel, Clinilabs, COMPASS, Delpor, Eisai, Enteris BioPharma, HLS Therapeutics, Idorsia, INmune Bio, Impel, Intra-Cellular Therapies, Janssen, Karuna, Lundbeck, Lyndra, Medavante-ProPhase, Marvin, Merck, Mitsubishi-Tanabe Pharma, Neurocrine, Neurelis, Noema, Novartis, Noven, Otsuka, Ovid, Praxis, Recordati, Relmada, Reviva, Sage, Sunovion, Supernus, Teva, and University of Arizona, Vanda, Wells Fargo, and provides one-off ad hoc consulting for individuals/entities conducting marketing, commercial, or scientifi c scoping research; is a speaker for AbbVie/Allergan, Acadia, Alkermes, Angelini, Axsome, BioXcel, Eisai, Idorsia, Intra-Cellular Therapies, Janssen, Lundbeck, Neurocrine, Noven, Otsuka, Recordati, Sage, Sunovion, Takeda, Teva, and CME activities organized by medical education companies, such as Medscape, NACCME, NEI, Vindico, and universities and professional organizations/societies; holds stocks (small number of shares of common stock) in Bristol-Myers Squibb, Eli Lilly, Johnson & Johnson, Merck, and Pfizer, purchased over 10 years ago, with stock options in Reviva; receives royalties/publishing income from Taylor & Francis (Editor-in-Chief, Current Medical Research and Opinion, 2022–present), Wiley (Editor-in-Chief, International Journal of Clinical Practice, through the end of 2019), UpToDate (reviewer), Springer Healthcare (book), and Elsevier (Topic Editor, Psychiatry, Clinical Therapeutics). MAM, ST, KRF, and MS are employees or stockholders, or both, of Teva Pharmaceuticals. SK is an employee of Yorker Health, which has received payments from Teva Pharmaceuticals in relation to this study. JMK has been a consultant for or received honoraria from Alkermes, Boehringer Ingelheim, Cerevel, Click Therapeutics, Dainippon Sumitomo, HealthRhythms, HLS Therapeutics, Eli Lilly, EnVivo Pharmaceuticals (Forum), Forest (Allergan), Genentech, Indivior, Intra-Cellular Therapies, Janssen, Johnson & Johnson, Karuna Therapeutics, LB Pharmaceuticals, Lundbeck, Lyndra Therapeutics, Mapi, Maplight, Merck, Neurocrine Biosciences, Minerva, Neurocrine, Newron, Novartis, NW PharmaTech, Otsuka, Pierre Fabre, Reviva Pharmaceuticals, Roche, Saladax Biomedical, Sunovion, Takeda, Terran, and Teva Pharmaceuticals; has received grant support from Otsuka, Lundbeck, and Janssen; and is a shareholder of Cerevel, North Shore Therapeutics, LB Pharmaceuticals and Vanguard Research Group; has received royalties from UpToDate., (© 2024 Correll et al.)
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- 2024
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116. Long-term persistence of the risk of agranulocytosis with clozapine compared with other antipsychotics: a nationwide cohort and case-control study in Finland.
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Rubio JM, Kane JM, Tanskanen A, Tiihonen J, and Taipale H
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- Humans, Finland epidemiology, Male, Female, Case-Control Studies, Adult, Middle Aged, Psychotic Disorders drug therapy, Cohort Studies, Schizophrenia drug therapy, Risk Factors, Time Factors, Young Adult, Clozapine adverse effects, Clozapine therapeutic use, Agranulocytosis chemically induced, Agranulocytosis epidemiology, Antipsychotic Agents adverse effects, Antipsychotic Agents therapeutic use
- Abstract
Background: Agranulocytosis is a life-threatening side-effect of clozapine, the only approved drug for treatment-resistant schizophrenia. The long-term profile of this complication has not yet been well established. Here we aim to describe the risk of clozapine-induced agranulocytosis over the long term., Methods: We used the entire population of Finland to identify people diagnosed with schizophrenia or schizoaffective disorder between 1972 and 2014 and developed a Kaplan-Meier model of time to diagnosis of agranulocytosis during clozapine versus non-clozapine treatment over a 22-year observation period (1996 to 2017). Next, we developed a nested case-control model for agranulocytosis matching by sex, age, time since diagnosis, and being in the incident cohort on a 1 to 5 ratio. Various durations of use for clozapine and non-clozapine antipsychotic treatment were compared to the modal antipsychotic use duration, deriving adjusted odds ratios (aORs) in a multivariable regression model. Recurrence and lethality rates for clozapine-induced agranulocytosis were described. These data reflect on all individuals with lived experience of schizophrenia in Finland during the study time, although individuals with lived experience were not included in the design of the study., Findings: We identified 61 769 people with schizophrenia or schizoaffective disorder (14 037 individuals treated with clozapine and 47 732 individuals treated with non-clozapine antipsychotics), with a mean age of 46·67 years (IQR 34·44-57·61), of whom 30 721 (49·7%) were female and 31 048 (50·3%) were male (data on ethnicity not available). Among those, 398 individuals were diagnosed with agranulocytosis (231 individuals treated with clozapine and 167 individuals treated with non-clozapine antipsychotics), representing a cumulative incidence of agranulocytosis for 1·37% (95% CI 0·58-3·16) on clozapine and 0·13% (0·04-0·23) on non-clozapine antipsychotics. In the case (n=398) versus control (n=1987) model, the risk of clozapine-induced agranulocytosis decreased steeply over time from an aOR of 36·01 (95% CI 16·79-77·22) for less than 6 months on clozapine to 4·38 (1·86-10·34) for clozapine use of 54 months or more. Only one of 3559 individuals starting clozapine died because of clozapine-induced agranulocytosis., Interpretation: The risk of clozapine-induced agranulocytosis decreases steeply over time but might be persistently greater than that of non-clozapine antipsychotics. This long-term risk excess seems small in absolute terms compared with the known magnitude of the advantages of clozapine in relevant outcomes, including life expectancy. Given the widespread underuse of clozapine, relaxing the long-term neutrophil monitoring could favour the advantages of long-term clozapine use, including greater life expectancy, without incurring the intolerable risk of clozapine-induced agranulocytosis., Funding: Northwell Health and Sigrid Jusèlius Foundation., Competing Interests: Declaration of interests JMR has received honoraria from Teva, Karuna, and Janssen; royalties from UpToDate; and grant support from Saladax and Alkermes. JMK has received consulting fees or honoraria for lectures from Alkermes, Allergan, Boehringer Ingelheim, Cerevel, Click Therapeutics, Dainippon Sumitomo, H Lundbeck, Health Rhythms, HLS Therapeutics, Indivior, Intracellular Therapies, Janssen, Johnson and Johnson, Karuna, LB Pharmaceuticals, Merck, Minerva, Newron, Novartis, NW PharmaTech, Otsuka, Roche, Saladax, Sunovion, and Teva; grant support from Click Therapeutics, H Lundbeck, Janssen, Otsuka, Saladax, Sunovion, and Valera; and is a stockholder for Cerevel, Health Rhythms, Karuna, LB Pharmaceuticals, North Shore Therapies, and the Vanguard Research Group. JT, HT, and AT have participated in research projects funded by grants from Janssen-Cilag and Eli Lilly paid to their institution. JT has been a consultant or advisor to or has received honoraria from Eli Lilly, Evidera, Janssen-Cilag, Lundbeck, Orion, Otsuka, Mediuutiset, Sidera, and Sunovion. HT has received personal fees from Janssen-Cilag and Otsuka., (Copyright © 2024 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.)
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- 2024
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117. Sex differences in the functional network underpinnings of psychotic-like experiences in children.
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Dhamala E, Chopra S, Ooi LQR, Rubio JM, Yeo BTT, Malhotra AK, and Holmes AJ
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Psychotic-like experiences (PLEs) include a range of sub-threshold symptoms that resemble aspects of psychosis but do not necessarily indicate the presence of psychiatric illness. These experiences are highly prevalent in youth and are associated with developmental disruptions across social, academic, and emotional domains. While not all youth who report PLEs develop psychosis, many develop other psychiatric illnesses during adolescence and adulthood. As such, PLEs are theorized to represent early markers of poor mental health. Here, we characterized the similarities and differences in the neurobiological underpinnings of childhood PLEs across the sexes using a large sample from the ABCD Study (n=5,260), revealing sex-specific associations between functional networks connectivity and PLEs. We find that although the networks associated with PLEs overlap to some extent across the sexes, there are also crucial differences. In females, PLEs are associated with dispersed cortical and non-cortical connections, whereas in males, they are primarily associated with functional connections within limbic, temporal parietal, somato/motor, and visual networks. These results suggest that early transdiagnostic markers of psychopathology may be distinct across the sexes, further emphasizing the need to consider sex in psychiatric research as well as clinical practice., Competing Interests: Financial Disclosures All authors reported no biomedical financial interests or potential conflicts of interest.
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- 2024
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118. Replication of a neuroimaging biomarker for striatal dysfunction in psychosis.
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Rubio JM, Lencz T, Cao H, Kraguljac N, Dhamala E, Homan P, Horga G, Sarpal DK, Argyelan M, Gallego J, Cholewa J, Barber A, Kane JM, and Malhotra AK
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- Humans, Male, Female, Adult, Reproducibility of Results, Connectome methods, Young Adult, Adolescent, Psychotic Disorders physiopathology, Biomarkers, Corpus Striatum diagnostic imaging, Corpus Striatum physiopathology, Neuroimaging methods, Magnetic Resonance Imaging methods, Schizophrenia physiopathology, Schizophrenia diagnostic imaging
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To bring biomarkers closer to clinical application, they should be generalizable, reliable, and maintain performance within the constraints of routine clinical conditions. The functional striatal abnormalities (FSA), is among the most advanced neuroimaging biomarkers in schizophrenia, trained to discriminate diagnosis, with post-hoc analyses indicating prognostic properties. Here, we attempt to replicate its diagnostic capabilities measured by the area under the curve (AUC) in receiver operator characteristic curves discriminating individuals with psychosis (n = 101) from healthy controls (n = 51) in the Human Connectome Project for Early Psychosis. We also measured the test-retest (run 1 vs 2) and phase encoding direction (i.e., AP vs PA) reliability with intraclass correlation coefficients (ICC). Additionally, we measured effects of scan length on classification accuracy (i.e., AUCs) and reliability (i.e., ICCs). Finally, we tested the prognostic capability of the FSA by the correlation between baseline scores and symptom improvement over 12 weeks of antipsychotic treatment in a separate cohort (n = 97). Similar analyses were conducted for the Yeo networks intrinsic connectivity as a reference. The FSA had good/excellent diagnostic discrimination (AUC = 75.4%, 95% CI = 67.0-83.3%; in non-affective psychosis AUC = 80.5%, 95% CI = 72.1-88.0%, and in affective psychosis AUC = 58.7%, 95% CI = 44.2-72.0%). Test-retest reliability ranged between ICC = 0.48 (95% CI = 0.35-0.59) and ICC = 0.22 (95% CI = 0.06-0.36), which was comparable to that of networks intrinsic connectivity. Phase encoding direction reliability for the FSA was ICC = 0.51 (95% CI = 0.42-0.59), generally lower than for networks intrinsic connectivity. By increasing scan length from 2 to 10 min, diagnostic classification of the FSA increased from AUC = 71.7% (95% CI = 63.1-80.3%) to 75.4% (95% CI = 67.0-83.3%) and phase encoding direction reliability from ICC = 0.29 (95% CI = 0.14-0.43) to ICC = 0.51 (95% CI = 0.42-0.59). FSA scores did not correlate with symptom improvement. These results reassure that the FSA is a generalizable diagnostic - but not prognostic - biomarker. Given the replicable results of the FSA as a diagnostic biomarker trained on case-control datasets, next the development of prognostic biomarkers should be on treatment-response data., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)
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- 2024
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119. Sistema de apoyos para personas con discapacidad . Medidas jurídico-civiles y sociales
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González, M. Begoña Fernández, Directora, González, M. Begoña Fernández, Sánchez, Rosa Medina, Cerezo, Alberto Hidalgo, Gómez, Juan Luis Jarillo, Santiago, Héctor Ayllón, Ramos, Carlos Pérez, Calvo, Ignacio Pérez, Rubio, Jose Mª Abella, Montoya, Juan Pablo Maldonado, Jiménez, Rocío Martín, Colao, Manuela Abeleira, González, M. Begoña Fernández, González, M. Begoña Fernández, Sánchez, Rosa Medina, Cerezo, Alberto Hidalgo, Gómez, Juan Luis Jarillo, Santiago, Héctor Ayllón, Ramos, Carlos Pérez, Calvo, Ignacio Pérez, Rubio, Jose Mª Abella, Montoya, Juan Pablo Maldonado, Jiménez, Rocío Martín, and Colao, Manuela Abeleira
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- 2021
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120. Effects of phase encoding direction on test-retest reliability of human functional connectome.
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Cao H, Barber AD, Rubio JM, Argyelan M, Gallego JA, Lencz T, and Malhotra AK
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- Humans, Reproducibility of Results, Rest, Brain diagnostic imaging, Signal-To-Noise Ratio, Magnetic Resonance Imaging methods, Transforming Growth Factor beta, Connectome methods, Sensorimotor Cortex
- Abstract
The majority of human connectome studies in the literature based on functional magnetic resonance imaging (fMRI) data use either an anterior-to-posterior (AP) or a posterior-to-anterior (PA) phase encoding direction (PED). However, whether and how PED would affect test-retest reliability of functional connectome is unclear. Here, in a sample of healthy subjects with two sessions of fMRI scans separated by 12 weeks (two runs per session, one with AP, the other with PA), we tested the influence of PED on global, nodal, and edge connectivity in the constructed brain networks. All data underwent the state-of-the-art Human Connectome Project (HCP) pipeline to correct for phase-encoding-related distortions before entering analysis. We found that at the global level, the PA scans showed significantly higher intraclass correlation coefficients (ICCs) for global connectivity compared with AP scans, which was particularly prominent when using the Seitzman-300 atlas (versus the CAB-NP-718 atlas). At the nodal level, regions most strongly affected by PED were consistently mapped to the cingulate cortex, temporal lobe, sensorimotor areas, and visual areas, with significantly higher ICCs during PA scans compared with AP scans, regardless of atlas. Better ICCs were also observed during PA scans at the edge level, in particular when global signal regression (GSR) was not performed. Further, we demonstrated that the observed reliability differences between PEDs may relate to a similar effect on the reliability of temporal signal-to-noise ratio (tSNR) in the same regions (that PA scans were associated with higher reliability of tSNR than AP scans). Averaging the connectivity outcome from the AP and PA scans could increase median ICCs, especially at the nodal and edge levels. Similar results at the global and nodal levels were replicated in an independent, public dataset from the HCP-Early Psychosis (HCP-EP) study with a similar design but a much shorter scan session interval. Our findings suggest that PED has significant effects on the reliability of connectomic estimates in fMRI studies. We urge that these effects need to be carefully considered in future neuroimaging designs, especially in longitudinal studies such as those related to neurodevelopment or clinical intervention., Competing Interests: Declaration of Competing Interest Dr. Malhotra is a consultant for Genomind, Inc., InformedDNA, Janssen Pharma, and Acadia Pharma. The other authors report no conflicts of interest., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)
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- 2023
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121. Replication of a neuroimaging biomarker for striatal dysfunction in psychosis.
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Rubio JM, Lencz T, Cao H, Kraguljac N, Dhamala E, Homan P, Horga G, Sarpal DK, Argyelan M, Gallego J, Cholewa J, Barber A, Kane J, and Malhotra A
- Abstract
To bring biomarkers closer to clinical application, they should be generalizable, reliable, and maintain performance within the constraints of routine clinical conditions. The functional striatal abnormalities (FSA), is among the most advanced neuroimaging biomarkers in schizophrenia, trained to discriminate diagnosis, with post-hoc analyses indicating prognostic properties. Here, we attempt to replicate its diagnostic capabilities measured by the area under the curve (AUC) in receiver operator characteristic curves discriminating individuals with psychosis (n=101) from healthy controls (n=51) in the Human Connectome Project for Early Psychosis. We also measured the test-retest (run 1 vs 2) and phase encoding direction (i.e., AP vs PA) reliability with intraclass correlation coefficients (ICC). Additionally, we measured effects of scan length on classification accuracy (i.e., AUCs) and reliability (i.e., ICCs). Finally, we tested the prognostic capability of the FSA by the correlation between baseline scores and symptom improvement over 12 weeks of antipsychotic treatment in a separate cohort (n=97). Similar analyses were conducted for the Yeo networks intrinsic connectivity as a reference. The FSA had good/excellent diagnostic discrimination (AUC=75.4%, 95%CI=67.0%-83.3%; in non-affective psychosis AUC=80.5%, 95%CI=72.1-88.0%, and in affective psychosis AUC=58.7%, 95%CI=44.2-72.0%). Test-retest reliability ranged between ICC=0.48 (95%CI=0.35-0.59) and ICC=0.22 (95%CI=0.06-0.36), which was comparable to that of networks intrinsic connectivity. Phase encoding direction reliability for the FSA was ICC=0.51 (95%CI=0.42-0.59), generally lower than for networks intrinsic connectivity. By increasing scan length from 2 to 10 minutes, diagnostic classification of the FSA increased from AUC=71.7% (95%CI=63.1%-80.3%) to 75.4% (95%CI=67.0%-83.3%) and phase encoding direction reliability from ICC=0.29 (95%CI=0.14-0.43) to ICC=0.51 (95%CI=0.42-0.59). FSA scores did not correlate with symptom improvement. These results reassure that the FSA is a generalizable diagnostic - but not prognostic - biomarker. Given the replicable results of the FSA as a diagnostic biomarker trained on case-control datasets, next the development of prognostic biomarkers should be on treatment-response data., Competing Interests: Conflict of interest: JR has received research support from Alkermes, speaker bureau or advisory board compensation from TEVA, Karuna, Janssen, royalties from UpToDate. PH has received grants and honoraria from Novartis, Lundbeck, Mepha, Janssen, Boehringer Ingelheim, Neurolite outside of this work. JK has received funds for research support from H. Lundbeck, Janssen, and Otsuka; has received consulting fees or honoraria for lectures from Alkermes, Biogen, Boehringer Ingelheim, Cerevel, Dainippon Sumitomo, H. Lundbeck, HLS, Indivior, Intra-Cellular Therapies, Janssen, Johnson and Johnson, Karuna, LB Pharmaceuticals, Merck, Minerva, Neurocrine, Neumora, Newron, Novartis, Otsuka, Reviva, Roche, Saladax, Sunovion, Takeda, and Teva; and has ownership interest in HealthRhythms, North Shore Therapies, LB Pharmaceuticals, Medincell, and the Vanguard Research Group. The rest of the authors declare no conflict of interest.
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- 2023
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122. Early versus late administration of long-acting injectable antipsychotic agents among patients with newly diagnosed schizophrenia: an analysis of a commercial claims database.
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Kane JM, Chen A, Lim S, Mychaskiw MA, Tian M, Wang Y, Suett M, and Rubio JM
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- Humans, Injections, Health Care Costs, Outpatients, Delayed-Action Preparations therapeutic use, Retrospective Studies, Antipsychotic Agents, Schizophrenia diagnosis, Schizophrenia drug therapy
- Abstract
This study was designed to assess healthcare resource utilization (HCRU) and costs in patients with newly diagnosed schizophrenia based on timing and context of long-acting injectable antipsychotic agent (LAI) initiation. Using claims data, patients (aged 18-40 years) with first schizophrenia diagnosis January 2013-September 2019 (index date), no LAI or oral antipsychotic agent claims during 12-month preindex period, and continuous benefit enrollment from 12 months before index date to 12 months after first LAI administration were identified. Patients were grouped based on timing [early (≤1 year after index date) vs. late] and circumstances [reactive (after schizophrenia-related event) vs. proactive] of LAI initiation. Of 1290 patients with at least one LAI claim, 306 met criteria for early ( n = 204; reactive, n = 107; proactive, n = 97) and late ( n = 102; n = 75; n = 27) initiation. HCRU and costs were numerically lower in early versus late groups, and significantly lower for proactive initiation in both groups. Comparing worst-case (late-reactive) and best-case (early-proactive) scenarios, the average annual cost difference was $7195.13 ( P = 0.0233), with major drivers being emergency department ($171.28; P < 0.05) and other outpatient ($2845.73; P < 0.00001) visits. In addition to the clinical advantages previously described in the literature, the proactive use of LAIs in early-phase schizophrenia is associated with lower healthcare costs., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)
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- 2023
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123. Early Non-Response to Antipsychotic Treatment in Schizophrenia: A Systematic Review and Meta-Analysis of Evidence-Based Management Options.
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Rubio JM, Guinart D, Kane JM, and Correll CU
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- Humans, Drug Therapy, Combination, Antipsychotic Agents therapeutic use, Schizophrenia drug therapy, Clozapine therapeutic use, Psychotic Disorders drug therapy
- Abstract
Background: Early non-response is a well-established prognostic marker but evidence-based and consistent recommendations to manage it are limited. The aim of this systematic review and meta-analysis was to generate evidence-based strategies for the management of schizophrenia patients with early non-response to 2 weeks of antipsychotic treatment., Methods: We conducted a systematic review and meta-analysis of randomized trials comparing antipsychotic dose escalation, switch, augmentation and continuation in individuals with study-defined early antipsychotic treatment non-response. Eligibility criteria were (1) clinical trials of primary psychosis treating for at least 2 weeks with antipsychotic monotherapy with study-defined operationalized criteria for early non-response; and (2) randomization to at least two of the following treatment strategies: dose escalation, switch, augmentation, or treatment continuation. Information sources were Pubmed, PsycINFO, and EMBASE, and risk of bias was assessed using Jadad scores. Results were synthesized using random-effects meta-analysis, comparing each intervention with treatment continuation for total symptom change as the primary outcome, generating standardized mean differences (SMDs) and 95% confidence intervals (CIs). Studies meeting the selection criteria but providing insufficient data for a meta-analysis were presented separately., Results: We screened 454 records by 1 August 2022, of which 12 individual datasets met the inclusion criteria, representing 947 research participants. Of those studies, five provided data to include in the meta-analysis (four with early non-response at 2 weeks, one at 3 weeks). Early non-response was defined within a timeline of 2 weeks in eight datasets, with the remaining datasets ranging between 3 and 4 weeks. The rates of early non-response ranged between 72.0 and 24.1%, and the endpoint ranged within 4-24 weeks post randomization. Quality was good (i.e., Jadad score of ≥3) in 8 of the 12 datasets. Overall, three studies compared antipsychotic switch versus continuation and two compared antipsychotic switch versus augmentation, in both cases without significant pooled between-group differences for total symptom severity (n = 149, SMD 0.18, 95% CI -0.14 to 0.5). Individually, two relatively large studies for antipsychotic switch versus continuation found small advantages for switching antipsychotics for total symptom severity (n = 149, SMD -0.49, 95% CI -1.05 to -0.06). One relatively large study found an advantage for dose escalation, although this finding has not been replicated and was not included in the meta-analysis. None of the alternatives included antipsychotic switch to clozapine., Conclusions: Despite robust accuracy of early antipsychotic non-response predicting ultimate response, the evidence for treatment strategies that should be used for early non-response after 2-3 weeks is limited. While meta-analytic findings were non-significant, some individual studies suggest advantages of antipsychotic switch or dose escalation. Therefore, any conclusions should be interpreted carefully, given the insufficient high-quality evidence., (© 2023. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)
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- 2023
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124. Efficacy and acceptability of psychosocial interventions in schizophrenia: systematic overview and quality appraisal of the meta-analytic evidence.
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Solmi M, Croatto G, Piva G, Rosson S, Fusar-Poli P, Rubio JM, Carvalho AF, Vieta E, Arango C, DeTore NR, Eberlin ES, Mueser KT, and Correll CU
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- Humans, Psychosocial Intervention, Recurrence, Cognitive Behavioral Therapy, Schizophrenia therapy
- Abstract
Psychosocial interventions are recommended in schizophrenia and first-episode psychosis/early psychosis (EP). Nevertheless, literature is heterogeneous and often contradictory. We conducted an umbrella review of (network) meta-analyses of randomized controlled trials (RCTs) comparing psychosocial interventions vs treatment as usual (TAU)/active interventions(ACTIVE)/MIXED controls. Primary outcome was total symptoms (TS); secondary outcomes were positive/negative/depressive symptoms (PS/NS/DS), cognition, functioning, relapse, hospitalization, quality of life (QoL), treatment discontinuation. Standardized mean difference (SMD)/odds ratio (OR)/risk ratio (RR) vs TAU/ACTIVE/MIXED were summarized at end-of-treatment (EoT)/follow-up (FU). Quality was rated as high/medium/low (AMSTAR-PLUS). Eighty-three meta-analyses were included (RCTs = 1246; n = 84,925). Against TAU, regarding TS, Early Intervention Services (EIS) were superior EoT/FU in EP (SMD = -0.32/-0.21), cognitive behavioral therapy (CBT) in schizophrenia EoT/FU (SMD = -0.38/-0.19). Regarding secondary outcomes, in EP, EIS were superior for all outcomes EoT except cognition, and at FU for PS/NS/QoL, specific family interventions (FI-s) prevented relapse EoT; in schizophrenia, superiority emerged EoT for CBT for PS/NS/relapse/functioning/QoL; psychoeducation (EDU)/any FI for relapse; cognitive remediation therapy (CRT) for cognition/functioning; and hallucination-focused integrative treatment for PS. Against ACTIVE, in EP, mixed family interventions (FI-m) were superior at FU regarding TS (SMD = -0.61) and for functioning/relapse among secondary outcomes. In schizophrenia, regarding TS, mindfulness and social skills training (SST) were superior EoT, CBT at FU; regarding secondary outcomes superiority emerged at EoT for computerized cognitive drill-and-practice training for PS/DS, CRT for cognition/functioning, EDU for relapse, individual placement and support (IPS) for employment; and at FU CBT for PS/NS. Against MIXED, in schizophrenia, CRT/EDU were superior for TS EoT (d = -0.14/SMD = -0.33), CRT regarding secondary outcomes EoT for DS/social functioning, both EoT/FU for NS/cognition/global functioning; compensatory cognitive interventions for PS/functioning EoT/FU and NS EoT; CBT for PS at FU, and EDU/SST for relapse EoT. In conclusion, mental health services should consider prioritizing EIS/any FI in EP and CBT/CRT/any FI/IPS for schizophrenia, but other interventions may be helpful for specific outcomes., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)
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- 2023
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125. The pharmacological treatment of schizophrenia: How far have we come?
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Rubio JM and Kane JM
- Abstract
Schizophrenia is a chronic and often severe mental disorder for which antipsychotic drugs are the cornerstone of treatment. Although the essential mechanism of action of these drugs has not changed much since they were first discovered in the 1950s, there have been numerous advances in the context in which these drugs are prescribed, as well as in the considerations for their optimal use. In this review, we summarize five selected issues in which the psychopharmacological treatment of schizophrenia has most evolved. Namely, these are the shift of outcomes of interest from symptoms to recovery, the development of stratified approaches to select the most appropriate treatment for each individual, the recognition of treatment nonadherence as a critical factor determining outcomes, the recommendations for maintenance treatment, and, finally, the promise of new antipsychotic compounds that innovate in their mechanisms of action, improving efficacy/safety profiles. Finally, we discuss how some of these advances have already delivered to improved outcomes in the real world, whereas others have demonstrated efficacy under optimal circumstances yet have not been translated into better outcomes in the community. Thus, the road ahead includes both identifying novel treatments that engage the psychopathology of the illness and improve the efficacy/tolerability profile of currently available agents, as well as developing interventions that mitigate the barriers for the use of novel interventions, some of them already existing, in the real world., Competing Interests: J.R. has received honoraria from TEVA pharmaceuticals and Janssen, royalties from UpToDate, and grant support from Alkermes. J.K. has received honoraria from Alkermes, Allergan, Dainippon Sumitomo, H. Lundbeck, Indivior, Intracellular Therapies, Janssen Pharmaceutical, Johnson & Johnson, LB Pharmaceuticals, Merck, Minerva, Neurocrine, Novartis Pharmaceuticals, Otsuka, Reviva, Roche, Saladex, Sunovion, Takeda, Teva; grant support from Otsuka, Lundbeck, Sunovion, and Janssen; is a shareholder of the Vanguard Research Group, LB Pharmaceuticals Inc., and North Shore Therapeutics; and receives royalties from UptoDate., (© 2022 The Authors. Psychiatry and Clinical Neurosciences Reports published by John Wiley & Sons Australia, Ltd on behalf of Japanese Society of Psychiatry and Neurology.)
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- 2022
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126. Striatal functional connectivity in psychosis relapse: A hypothesis generating study.
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Rubio JM, Lencz T, Barber A, Moyett A, Ali S, Bassaw F, Ventura G, Germano N, Malhotra AK, and Kane JM
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- Corpus Striatum diagnostic imaging, Humans, Magnetic Resonance Imaging methods, Recurrence, Antipsychotic Agents therapeutic use, Psychotic Disorders diagnostic imaging, Psychotic Disorders drug therapy, Schizophrenia diagnostic imaging, Schizophrenia drug therapy
- Abstract
Most individuals with psychotic disorders relapse over their course of illness, yet the neural processes that may lead to symptom worsening are poorly understood. Importantly, such processes could be potentially affected by antipsychotic adherence status upon relapse (i.e., relapse despite ongoing antipsychotic maintenance vs following antipsychotic discontinuation), reflecting distinct mechanisms. As a first foray into this question, we aim to compare the striatal connectivity index (SCI), a biomarker derived from striatal resting state functional connectivity predictive of treatment response, by adherence status upon relapse. In order to confirm adherence status upon relapse, we compared individuals treated with long-acting injectable antipsychotics upon relapse (i.e., breakthrough psychosis) (n = 23), with individuals who had decided to interrupt antipsychotic treatment and then relapsed (n = 27), as well as healthy controls (n = 26). We acquired for each individual >10 min of resting state fMRI, to generate functional connectivity maps. Region of interest (ROI) analyses were conducted to calculate SCI values for each participant. These values were entered as dependent variable in a linear regression adjusted for sex and age for which adherence status was the independent variable. Individuals in the breakthrough psychosis group had significantly lower SCI values than healthy controls (Cohen's d = 0.99, p < 0.001), and non-adherent individuals upon relapse (Cohen's d = 0.58, p = 0.032), whereas non-adherent individuals had also trend level lower SCI values than healthy controls (Cohen's d = 0.44, p = 0.09). These results suggest the hypothesis that striatal functional connectivity may be aberrant in psychosis relapse, and that this dysfunction may be greater among individuals who developed relapse despite ongoing antipsychotic treatment., (Copyright © 2021 Elsevier B.V. All rights reserved.)
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- 2022
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127. Clozapine and long-acting injectable antipsychotics reduce hospitalisation and treatment failure risk in patients with schizophrenia.
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Rubio JM and Correll CU
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- Hospitalization, Humans, Treatment Failure, Antipsychotic Agents, Clozapine, Schizophrenia
- Abstract
Competing Interests: Competing interests: JMR has been an advisor for Lundbeck. CUC has been a consultant and/or advisor to or has received honoraria from Alkermes, Allergan, Angelini, Gerson Lehrman Group, IntraCellular Therapies, Janssen/J&J, LB Pharma, Lundbeck, Medavante, Medscape, Merck, Neurocrine, Otsuka, Pfizer, ROVI, Servier, Sunovion, Takeda and Teva. He has provided expert testimony for Bristol-Myers Squibb, Janssen and Otsuka. He served on a Data Safety Monitoring Board for Lundbeck, ROVI and Teva. He received royalties from UpToDate and grant support from Janssen and Takeda. He is also a shareholder of LB Pharma.
- Published
- 2018
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