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Treatment Success and Psychiatric Stability in Adults With Tardive Dyskinesia: Post Hoc Analyses of Two Long-Term Valbenazine Studies
- Andrew J. Cutler, Rakesh Jain, Alon Bloom, Scott Siegert, Leslie Lundt
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- Journal:
- CNS Spectrums / Volume 28 / Issue 2 / April 2023
- Published online by Cambridge University Press:
- 14 April 2023, pp. 216-217
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Introduction
Tardive dyskinesia (TD) is a persistent and potentially disabling movement disorder associated with exposure to antipsychotics and other dopamine receptor blocking agents. Effective and comprehensive treatment of TD requires reducing patients’ abnormal involuntary movements without disrupting their psychiatric stability. This can be especially challenging when patients have complex psychiatric conditions (e.g., >1 psychiatric diagnosis) and are taking multiple medications. Valbenazine, a highly potent and selective vesicular monoamine transporter 2 (VMAT2) inhibitor, is approved for the once-daily treatment of TD. This post hoc analysis of two long-term studies (KINECT 3, KINECT 4) was conducted to evaluate changes in psychiatric status and clinician- and patient-reported treatment success in study participants who received valbenazine (40 or 80 mg) for 48 weeks.
MethodsData from KINECT 3 and KINECT 4 were pooled and analyzed in participants categorized by their primary psychiatric diagnosis: schizophrenia/schizoaffective disorder (“SCHZ”) or mood disorder (“MD”). Concomitant medications needed for managing these and other psychiatric or medical conditions were allowed. Treatment success was defined as achieving a rating of “much improved” or “very much improved” at Week 48, as assessed using the Clinical Global Impression of Change-Tardive Dyskinesia (CGI-TD) and Patient Global Impression of Change (PGIC). Psychiatric stability was monitored using the following scales: Positive and Negative Syndrome Scale (PANSS) and Calgary Depression Scale for Schizophrenia (CDSS) in the SCHZ subgroup; Young Mania Rating Scale (YMRS) and Montgomery-Åsberg Depression Rating Scale (MADRS) in the MD subgroup. Suicidal ideation/behavior was monitored using the Columbia-Suicide Severity Rating Scale.
ResultsMore than 75% of study participants in the SCHZ subgroup achieved treatment success with valbenazine, based on clinician assessment (CGI-TD, 79.7%) and patient self-report (PGIC, 78.0%). Mean changes from baseline to Week 48 for PANSS scores (positive symptoms [-0.7], negative symptoms [‑0.6], general psychopathology [-1.9], total [-3.2]) and CDSS total score (-0.5) indicated maintenance of psychiatric stability in the SCHZ subgroup. Similar treatment success rates were found in the MD subgroup for both CGI-TD (77.6%) and PGIC (84.5%), with mean changes from baseline in YMRS total score (-1.0) and MADRS total score (+0.3) indicating psychiatric stability was maintained. No emergence of suicidal ideation/behavior was observed during the studies.
ConclusionsPooled analyses from two 48-week studies indicate that long-term treatment of TD with once-daily valbenazine resulted in substantial clinician- and patient-reported global improvements in TD, while psychiatric stability was maintained regardless of primary psychiatric condition.
FundingNeurocrine Biosciences, Inc.
A multi-proxy paleolimnological reconstruction of Holocene climate conditions in the Great Basin, United States
- Scott A. Reinemann, David F. Porinchu, Amy M. Bloom, Bryan G. Mark, Jason E. Box
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- Journal:
- Quaternary Research / Volume 72 / Issue 3 / November 2009
- Published online by Cambridge University Press:
- 20 January 2017, pp. 347-358
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A sediment core spanning ∼ 7000 cal yr BP recovered from Stella Lake, a small sub-alpine lake located in Great Basin National Park, Nevada, was analyzed for subfossil chironomids (non-biting midges), diatoms, and organic content (estimated by loss-on-ignition (LOI)). Subfossil chironomid analysis indicates that Stella Lake was characterized by a warm, middle Holocene, followed by a cool “Neoglacial” period, with the last two millennia characterized by a return to warmer conditions. Throughout the majority of the core the Stella Lake diatom-community composition is dominated by small, periphytic taxa which are suggestive of shallow, cool, alkaline, oligotrophic waters with extensive seasonal ice cover. A reconstruction of mean July air temperature (MJAT) was developed by applying a midge-based inference model for MJAT (two-component WA-PLS) consisting of 79 lakes and 54 midge taxa (rjack2 = 0.55, RMSEP = 0.9°C). Comparison of the chironomid-inferred temperature record to existing regional paleoclimate reconstructions suggests that the midge-inferred temperatures correspond well to regional patterns. This multi-proxy record provides valuable insight into regional Holocene climate and environmental conditions by providing a quantitative reconstruction of peak Holocene warmth and aquatic ecosystem response to these changes in the Great Basin, a region projected to experience increased aridity and higher temperatures.
Contributors
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- By Aakash Agarwala, Linda S. Aglio, Rae M. Allain, Paul D. Allen, Houman Amirfarzan, Yasodananda Kumar Areti, Amit Asopa, Edwin G. Avery, Patricia R. Bachiller, Angela M. Bader, Rana Badr, Sibinka Bajic, David J. Baker, Sheila R. Barnett, Rena Beckerly, Lorenzo Berra, Walter Bethune, Sascha S. Beutler, Tarun Bhalla, Edward A. Bittner, Jonathan D. Bloom, Alina V. Bodas, Lina M. Bolanos-Diaz, Ruma R. Bose, Jan Boublik, John P. Broadnax, Jason C. Brookman, Meredith R. Brooks, Roland Brusseau, Ethan O. Bryson, Linda A. Bulich, Kenji Butterfield, William R. Camann, Denise M. Chan, Theresa S. Chang, Jonathan E. Charnin, Mark Chrostowski, Fred Cobey, Adam B. Collins, Mercedes A. Concepcion, Christopher W. Connor, Bronwyn Cooper, Jeffrey B. Cooper, Martha Cordoba-Amorocho, Stephen B. Corn, Darin J. Correll, Gregory J. Crosby, Lisa J. Crossley, Deborah J. Culley, Tomas Cvrk, Michael N. D'Ambra, Michael Decker, Daniel F. Dedrick, Mark Dershwitz, Francis X. Dillon, Pradeep Dinakar, Alimorad G. Djalali, D. John Doyle, Lambertus Drop, Ian F. Dunn, Theodore E. Dushane, Sunil Eappen, Thomas Edrich, Jesse M. Ehrenfeld, Jason M. Erlich, Lucinda L. Everett, Elliott S. Farber, Khaldoun Faris, Eddy M. Feliz, Massimo Ferrigno, Richard S. Field, Michael G. Fitzsimons, Hugh L. Flanagan Jr., Vladimir Formanek, Amanda A. Fox, John A. Fox, Gyorgy Frendl, Tanja S. Frey, Samuel M. Galvagno Jr., Edward R. Garcia, Jonathan D. Gates, Cosmin Gauran, Brian J. Gelfand, Simon Gelman, Alexander C. Gerhart, Peter Gerner, Omid Ghalambor, Christopher J. Gilligan, Christian D. Gonzalez, Noah E. Gordon, William B. Gormley, Thomas J. Graetz, Wendy L. Gross, Amit Gupta, James P. Hardy, Seetharaman Hariharan, Miriam Harnett, Philip M. Hartigan, Joaquim M. Havens, Bishr Haydar, Stephen O. Heard, James L. Helstrom, David L. Hepner, McCallum R. Hoyt, Robert N. Jamison, Karinne Jervis, Stephanie B. Jones, Swaminathan Karthik, Richard M. Kaufman, Shubjeet Kaur, Lee A. Kearse Jr., John C. Keel, Scott D. Kelley, Albert H. Kim, Amy L. Kim, Grace Y. Kim, Robert J. Klickovich, Robert M. Knapp, Bhavani S. Kodali, Rahul Koka, Alina Lazar, Laura H. Leduc, Stanley Leeson, Lisa R. Leffert, Scott A. LeGrand, Patricio Leyton, J. Lance Lichtor, John Lin, Alvaro A. Macias, Karan Madan, Sohail K. Mahboobi, Devi Mahendran, Christine Mai, Sayeed Malek, S. Rao Mallampati, Thomas J. Mancuso, Ramon Martin, Matthew C. Martinez, J. A. Jeevendra Martyn, Kai Matthes, Tommaso Mauri, Mary Ellen McCann, Shannon S. McKenna, Dennis J. McNicholl, Abdel-Kader Mehio, Thor C. Milland, Tonya L. K. Miller, John D. Mitchell, K. Annette Mizuguchi, Naila Moghul, David R. Moss, Ross J. Musumeci, Naveen Nathan, Ju-Mei Ng, Liem C. Nguyen, Ervant Nishanian, Martina Nowak, Ala Nozari, Michael Nurok, Arti Ori, Rafael A. Ortega, Amy J. Ortman, David Oxman, Arvind Palanisamy, Carlo Pancaro, Lisbeth Lopez Pappas, Benjamin Parish, Samuel Park, Deborah S. Pederson, Beverly K. Philip, James H. Philip, Silvia Pivi, Stephen D. Pratt, Douglas E. Raines, Stephen L. Ratcliff, James P. Rathmell, J. Taylor Reed, Elizabeth M. Rickerson, Selwyn O. Rogers Jr., Thomas M. Romanelli, William H. Rosenblatt, Carl E. Rosow, Edgar L. Ross, J. Victor Ryckman, Mônica M. Sá Rêgo, Nicholas Sadovnikoff, Warren S. Sandberg, Annette Y. Schure, B. Scott Segal, Navil F. Sethna, Swapneel K. Shah, Shaheen F. Shaikh, Fred E. Shapiro, Torin D. Shear, Prem S. Shekar, Stanton K. Shernan, Naomi Shimizu, Douglas C. Shook, Kamal K. Sikka, Pankaj K. Sikka, David A. Silver, Jeffrey H. Silverstein, Emily A. Singer, Ken Solt, Spiro G. Spanakis, Wolfgang Steudel, Matthias Stopfkuchen-Evans, Michael P. Storey, Gary R. Strichartz, Balachundhar Subramaniam, Wariya Sukhupragarn, John Summers, Shine Sun, Eswar Sundar, Sugantha Sundar, Neelakantan Sunder, Faraz Syed, Usha B. Tedrow, Nelson L. Thaemert, George P. Topulos, Lawrence C. Tsen, Richard D. Urman, Charles A. Vacanti, Francis X. Vacanti, Joshua C. Vacanti, Assia Valovska, Ivan T. Valovski, Mary Ann Vann, Susan Vassallo, Anasuya Vasudevan, Kamen V. Vlassakov, Gian Paolo Volpato, Essi M. Vulli, J. Matthias Walz, Jingping Wang, James F. Watkins, Maxwell Weinmann, Sharon L. Wetherall, Mallory Williams, Sarah H. Wiser, Zhiling Xiong, Warren M. Zapol, Jie Zhou
- Edited by Charles Vacanti, Scott Segal, Pankaj Sikka, Richard Urman
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- Book:
- Essential Clinical Anesthesia
- Published online:
- 05 January 2012
- Print publication:
- 11 July 2011, pp xv-xxviii
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Nanopatterning and Nanomachining with Table-top Extreme Ultraviolet Lasers
- Mario Marconi, Przemyslaw Wojciech Wachulak, Maria Gabriela Capeluto, Georgyi Vaschenko, Herman Bravo, Carmen S Menoni, Jorge Rocca, Erik H Anderson, Weilun Chao, David Attwood, Oscar Hemberg, Bradley Frazer, Scott Bloom
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- Journal:
- MRS Online Proceedings Library Archive / Volume 961 / 2006
- Published online by Cambridge University Press:
- 01 February 2011, 0961-O06-05
- Print publication:
- 2006
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Nanopatterning and nanomachining of PMMA coated wafers was performed using table top extreme ultraviolet lasers. Features below 100 nm were imprinted with short (50-60 s) exposure times.
X-Ray Nanoplasma Instruments and Tools
- Scott Bloom, Harry Rieger, Jim Alwan
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- Journal:
- MRS Online Proceedings Library Archive / Volume 840 / 2004
- Published online by Cambridge University Press:
- 01 February 2011, Q5.16
- Print publication:
- 2004
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Soft x-rays have wavelengths in the range of 1–15 nm and therefore the diffraction limited spot size of focused x-rays can be as small as 1.22 × the radiation wavelength, or less than 20 nm spot size. Using our pulsed x-ray source and focusing a small collected solid angle of this x-ray radiation to a sample provides enough power to form a very hot plasma that emits a range of radiation from UV through IR that can be collected and analyzed on a conventional optical spectrometer. In addition to diagnostic capabilities the instrument can be also used as a tool to form structures at nanometer scale resolution. Since the plasma is formed by ablating the target material with x-rays the target can be patterned or nanomachined using the plasma itself. It should be possible to pattern nanoscale devices by rastering the material under the nanoplasma. Finally in analogy to plasma assisted CVD processes, organometallic vapors could introduced into the sample chamber such that the nanoplasma locally plates out specific species of metals of other materials on the target at nanoscale sizes for forming devices, circuits, wires, etc. This paper presents a design for a nanoplasma instrument, predicted performance parameters will be presented, and development issues identified and discussed.
Magnetoencephalographic recordings demonstrate attentional modulation of mismatch-related neural activity in human auditory cortex
- MARTY G. WOLDORFF, STEVEN A. HILLYARD, CHRIS C. GALLEN, SCOTT R. HAMPSON, FLOYD E. BLOOM
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- Journal:
- Psychophysiology / Volume 35 / Issue 3 / May 1998
- Published online by Cambridge University Press:
- 01 May 1998, pp. 283-292
- Print publication:
- May 1998
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It is widely agreed that the negative brain potential elicited at 150–200 ms by a deviant, less intense sound in a repetitive series can be modulated by attention. To investigate whether this modulation represents a genuine attention effect on the mismatch negativity (MMN) arising from auditory cortex or attention-related activity from another brain region, we recorded both the MMN and the mismatch magnetic field (MMF) elicited by such deviants in a dichotic listening task. Deviant tones in the attended ear elicited a sizable MMF that was well modeled as a dipolar source in auditory cortex. Both the MMN and MMF to unattended-ear deviants were highly attenuated. These findings support the view that the MMN/MMF elicited in auditory cortex by intensity deviants, and thus the underlying feature-analysis and mismatch-detection processes, are not strongly automatic but rather can be gated or suppressed if attention is strongly focused elsewhere.