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1

Kong, Robert S., John Butterworth, Wynne Aveling, David A. Stump, Michael J. G. Harrison, John Hammon, Jan Stygall, Kashemi D. Rorie, and Stanton P. Newman. "Clinical Trial of the Neuroprotectant Clomethiazole in Coronary Artery Bypass Graft Surgery." Anesthesiology 97, no. 3 (September 1, 2002): 585–91. http://dx.doi.org/10.1097/00000542-200209000-00011.

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Background The neuroprotective property of clomethiazole has been demonstrated in several animal models of global and focal brain ischemia. In this study the authors investigated the effect of clomethiazole on cerebral outcome in patients undergoing coronary artery bypass surgery. Methods Two hundred forty-five patients scheduled for coronary artery bypass surgery were recruited at two centers and prospectively randomized to clomethiazole edisilate (0.8%), 225 ml (1.8 mg) loading dose followed by a maintenance dose of 100 ml/h (0.8 mg/h) during surgery, or 0.9% NaCl (placebo) in a double-blind trial. Coronary artery grafting was completed during moderate hypothermic (28-32 degrees C) cardiopulmonary bypass. Plasma clomethiazole was measured at several intervals during and up to 24 h after the end of infusion. A battery of eight neuropsychological tests was administered preoperatively and repeated 4-7 weeks after surgery. Analysis of the change in neuropsychological test scores from baseline was used to determine the effect of treatment. Results Neuropsychological assessments were completed in 219 patients (110 clomethiazole; 109 placebo). The mean plasma concentration of clomethiazole during surgery was 66.2 microm. There was no difference between the clomethiazole and placebo group in the postoperative change in neuropsychological test scores. Conclusion Clomethiazole did not improve cerebral outcome following coronary artery bypass surgery.
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2

&NA;. "Clomethiazole." Reactions Weekly &NA;, no. 1014 (August 2004): 8. http://dx.doi.org/10.2165/00128415-200410140-00020.

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3

&NA;. "Clomethiazole." Drugs in R & D 1, no. 1 (January 1999): 20–21. http://dx.doi.org/10.2165/00126839-199901010-00006.

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4

&NA;. "Clomethiazole." Reactions Weekly &NA;, no. 533 (January 1995): 7. http://dx.doi.org/10.2165/00128415-199505330-00019.

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5

Vaishnav, Anand, and Helmi L. Lutsep. "GABA Agonist: Clomethiazole." Current Medical Research and Opinion 18, sup2 (January 2002): s5—s8. http://dx.doi.org/10.1185/030079902125000651.

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6

Wahlgren, N. G., K. W. Ranasinha, T. Rosolacci, C. L. Franke, P. M. M. van Erven, T. Ashwood, and L. Claesson. "Clomethiazole Acute Stroke Study (CLASS)." Stroke 30, no. 1 (January 1999): 21–28. http://dx.doi.org/10.1161/01.str.30.1.21.

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7

Heinemann, F., and H. J. Assion. "Hepatotoxic Side-Effect of Clomethiazole." Pharmacopsychiatry 29, no. 05 (September 1996): 196–97. http://dx.doi.org/10.1055/s-2007-979571.

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8

Jostell, K. G., S. Agurell, L. G. Allgén, B. Kuylenstierna, J. E. Lindgren, G. Åberg, and G. Österlöf. "Pharmacokinetics of Clomethiazole in Healthy Adults." Acta Pharmacologica et Toxicologica 43, no. 3 (March 13, 2009): 180–89. http://dx.doi.org/10.1111/j.1600-0773.1978.tb02253.x.

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9

Petersson, Tomas, and Sven Engström. "Surface and interfacial properties of clomethiazole." International Journal of Pharmaceutics 132, no. 1-2 (April 1996): 231–42. http://dx.doi.org/10.1016/0378-5173(95)04375-6.

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10

Norene, M. F., P. A. Christensen, P. Thiessen, and P. Glenting. "Clomethiazole Treatment in a Child with Status Epilepticus." Acta Paediatrica 76, no. 5 (September 1987): 839–40. http://dx.doi.org/10.1111/j.1651-2227.1987.tb10575.x.

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11

Clarkson, Andrew N., Hanzhong Liu, Rosanna Rahman, David M. Jackson, Ian Appleton, and D. Steven Kerr. "Clomethiazole: mechanisms underlying lasting neuroprotection after hypoxia‐ischemia." FASEB Journal 19, no. 8 (April 4, 2005): 1036–38. http://dx.doi.org/10.1096/fj.04-3367fje.

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12

Brünen, S., P. D. Vincent, P. Baumann, C. Hiemke, and U. Havemann-Reinecke. "Therapeutic drug monitoring of drugs for treatment of substance-related disorders." European Psychiatry 26, S2 (March 2011): 13. http://dx.doi.org/10.1016/s0924-9338(11)71724-2.

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IntroductionThe effect of pharmacotherapy of substance-related disorders is moderate at best.ObjectivesTherapeutic drug monitoring (TDM) could be an instrument to improve the outcomes. TDM is for most of these drugs not established yet.AimsThe authors built a literature based rating scale to evaluate the necessity of TDM for these pharmacological agents.MethodsA literature research was performed for TDM related properties of acamprosate, bupropion, buprenorphine, clomethiazole, disulfiram, methadone, naltrexone, and varenicline. A rating scale was established for evaluation. It included 28 items related to five categories (efficacy, toxicity, pharmacokinetics, patient characteristics and cost effectiveness). For comparison, three reference substances with established TDM were similarly assessed: clozapine, lithium and nortriptyline.ResultsThe three reference substances, lithium, clozapine and nortriptyline, achieved scores of 15, 18, and 14 points, respectively. Rating of methadone (19 points), bupropion (14 points), buprenorphine (14 points), disulfiram (13) and naltrexone (12 points in the indication opioid-dependency and 10 points in the indication alcohol dependency) achieved more than 30% of the reachable points, whereas acamprosate (9 points), clomethiazole (9 points), and varenicline (5 points) had fewer points especially in the main characteristics in favor of TDM.ConclusionsThese results suggest this rating scale is sensitive to detect the appropriateness of TDM for drug treatment. Literature based rating and clinical experience give evidence that TDM has the potential to optimize the pharmacotherapy of substance related-disorders with different rank orders of the single substances.
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13

Das, Darshan, Sophia Varadkar, and Krishna B. Das. "Oral clomethiazole treatment for paediatric non-convulsive status epilepticus." Epileptic Disorders 18, no. 1 (March 2016): 87–91. http://dx.doi.org/10.1684/epd.2016.0795.

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14

Evenden, J., K. Ensler, D. M. Jackson, and C. Stephan-Dahlin. "The discriminative stimulus effects of clomethiazole in the rat." Behavioural Pharmacology 9, no. 5 (September 1998): 379–88. http://dx.doi.org/10.1097/00008877-199809000-00001.

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15

Engelhardt, W., M. Fischer, H. Pistner, and N. Roewer. "A213 ALCOHOL OR CLOMETHIAZOLE TO PREVENT POSTOPERATIVE ALCOHOL WITHDRAWAL?" Anesthesiology 87, Supplement (September 1997): 213A. http://dx.doi.org/10.1097/00000542-199709001-00213.

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16

Lyden, P., A. Shuaib, K. Ng, K. Levin, R. P. Atkinson, A. Rajput, L. Wechsler, et al. "Clomethiazole Acute Stroke Study in Ischemic Stroke (CLASS-I)." Stroke 33, no. 1 (January 2002): 122–29. http://dx.doi.org/10.1161/hs0102.101478.

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17

Franz, Michael, Hans Dlabal, Susanne Kunz, Jens Ulferts, Harald Gruppe, and Bernd Gallhofer. "Treatment of alcohol withdrawal: tiapride and carbamazepine versus clomethiazole." European Archives of Psychiatry and Clinical Neuroscience 251, no. 4 (August 1, 2001): 185–92. http://dx.doi.org/10.1007/s004060170039.

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18

Marshall, J. W. B., A. J. Cross, D. M. Jackson, A. R. Green, H. F. Baker, and R. M. Ridley. "Clomethiazole protects against hemineglect in a primate model of stroke." Brain Research Bulletin 52, no. 1 (May 2000): 21–29. http://dx.doi.org/10.1016/s0361-9230(99)00275-0.

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19

Lemke, M. R., W. Bauer, U. Badent, and W. Hartmann. "Criteria for carbamazepine and clomethiazole treatment regimen of alcohol withdrawal." European Psychiatry 11 (January 1996): 299s. http://dx.doi.org/10.1016/0924-9338(96)88915-2.

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20

Chaulk, Dana, Jennifer Wells, Suzanne Evans, David Jackson, and Dale Corbett. "Long-term effects of clomethiazole in a model of global ischemia." Experimental Neurology 182, no. 2 (August 2003): 476–82. http://dx.doi.org/10.1016/s0014-4886(03)00121-3.

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21

Green, A. R., and T. Ashwood. "Experimental and clinical experiences with clomethiazole, NXY-059 and AR-R15896." European Neuropsychopharmacology 9 (September 1999): 193. http://dx.doi.org/10.1016/s0924-977x(99)80093-5.

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22

Stone, Trevor W. "Effects of clomethiazole on spreading depression in the rat hippocampal slice." European Journal of Pharmacology 399, no. 1 (June 2000): 29–34. http://dx.doi.org/10.1016/s0014-2999(00)00331-9.

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23

Clarkson, A. N., J. Clarkson, D. M. Jackson, and I. A. Sammut. "Mitochondrial involvement in transhemispheric diaschisis following hypoxia–ischemia: Clomethiazole-mediated amelioration." Neuroscience 144, no. 2 (January 2007): 547–61. http://dx.doi.org/10.1016/j.neuroscience.2006.09.040.

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24

Green, A. R., and A. J. Cross. "S.02.04 The effects of clomethiazole in animal models of stroke." European Neuropsychopharmacology 7 (September 1997): S81. http://dx.doi.org/10.1016/s0924-977x(97)88361-7.

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25

Stresser, D. M., E. S. Perloff, A. K. Mason, A. P. Blanchard, S. S. Dehal, T. P. Creegan, R. Singh, and E. T. Gangl. "Selective Time- and NADPH-Dependent Inhibition of Human CYP2E1 by Clomethiazole." Drug Metabolism and Disposition 44, no. 8 (May 5, 2016): 1424–30. http://dx.doi.org/10.1124/dmd.116.070193.

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26

Wester, Per, Tage Strand, Nils-Gunnar Wahlgren, Tim Ashwood, and Gunilla Osswald. "An Open Study of Clomethiazole in Patients with Acute Cerebral Infarction." Cerebrovascular Diseases 8, no. 3 (1998): 188–90. http://dx.doi.org/10.1159/000015846.

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27

Gann, H., K. Hartig, B. Feige, R. Brueck, F. Hohagen, G. Weske, D. van Calker, and D. Riemann. "The effects of clomethiazole on polysomnographically recorded sleep in healthy subjects." European Archives of Psychiatry and Clinical Neuroscience 255, no. 4 (May 6, 2005): 284–90. http://dx.doi.org/10.1007/s00406-005-0589-3.

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28

Groß, Anke, and M. Soyka. "Clomethiazole Treatment of Alcohol Withdrawal Delirium in a Patient under Methadone Maintenance." Pharmacopsychiatry 29, no. 06 (November 1996): 229–30. http://dx.doi.org/10.1055/s-2007-979578.

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29

Nelson, Rachael M., A. Richard Green, and Atticus H. Hainsworth. "Electrophysiological actions of γ-aminobutyric acid and clomethiazole on recombinant GABAA receptors." European Journal of Pharmacology 452, no. 3 (October 2002): 255–62. http://dx.doi.org/10.1016/s0014-2999(02)02233-1.

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30

Lyden, Patrick D., Ashfaq Shuaib, Ken Ng, Richard Atkinson, Timothy Ashwood, Anders Nordlund, and Tomas Odergren. "The Clomethiazole Acute Stroke Study in hemorrhagic stroke (Class-H): Final results." Journal of Stroke and Cerebrovascular Diseases 9, no. 6 (November 2000): 268–75. http://dx.doi.org/10.1053/jscd.2000.18735.

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31

Visser, Sandra A. G., Susanna Pozarek, Sofia Martinsson, Tomas Forsberg, Svante B. Ross, and Johan Gabrielsson. "Rapid and long-lasting tolerance to clomethiazole-induced hypothermia in the rat." European Journal of Pharmacology 512, no. 2-3 (April 2005): 139–51. http://dx.doi.org/10.1016/j.ejphar.2005.02.036.

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32

Gilby, K. L., M. E. Kelly, D. C. McIntyre, and H. A. Robertson. "Neuro-overprotection? A functional evaluation of clomethiazole-induced neuroprotection following hypoxic-ischemic injury." Neuroscience 131, no. 4 (January 2005): 785–92. http://dx.doi.org/10.1016/j.neuroscience.2004.11.053.

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33

Ratz, Alexandra E., Raymond G. Schlienger, Lilly Linder, Wolf Langewitz, and Walter E. Haefeli. "Pharmacokinetics and pharmacodynamics of clomethiazole after oral and rectal administration in healthy subjects." Clinical Therapeutics 21, no. 5 (May 1999): 829–40. http://dx.doi.org/10.1016/s0149-2918(99)80005-8.

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34

Green, A. "Clomethiazole (Zendra®) in Acute Ischemic Stroke Basic Pharmacology and Biochemistry and Clinical Efficacy." Pharmacology & Therapeutics 80, no. 2 (November 1998): 123–47. http://dx.doi.org/10.1016/s0163-7258(98)00024-2.

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35

Liang, Shih-Ping, Rani Kanthan, Ashfaq Shuaib, and Tom Wishart. "Effects of clomethiazole on radial-arm maze performance following global forebrain ischemia in gerbils." Brain Research 751, no. 2 (March 1997): 189–95. http://dx.doi.org/10.1016/s0006-8993(96)01292-9.

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36

Dammann, Gerhard, Marc Walter, Daniela Gremaud-Heitz, Manfred Wolfersdorf, Susanne Hartmann, and Friedrich M. Wurst. "Association between Leptin Levels and Doses of Clomethiazole during Alcohol Withdrawal: A Pilot Study." European Addiction Research 18, no. 1 (2012): 12–15. http://dx.doi.org/10.1159/000331017.

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37

Marshall, J. W. B., A. J. Cross, and R. M. Ridley. "Functional Benefit from Clomethiazole Treatment after Focal Cerebral Ischemia in a Nonhuman Primate Species." Experimental Neurology 156, no. 1 (March 1999): 121–29. http://dx.doi.org/10.1006/exnr.1998.6994.

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38

Hillemacher, T., C. Weinland, A. Heberlein, J. Wilhelm, K. Bayerlein, J. Kornhuber, H. Frieling, and S. Bleich. "Treatment with Clomethiazole is Associated with Lower Rates of Premature Discharge during Alcohol Withdrawal." Pharmacopsychiatry 41, no. 04 (July 2008): 134–37. http://dx.doi.org/10.1055/s-2008-1058106.

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39

Ulmer, Albrecht, and Cornelia Meinhold. "S07-2DOCUMENTED EXPERIENCE WITH DIHYDROCODEINE, BUPRENORPHINE, BACLOFEN AND CLOMETHIAZOLE IN THE TREATMENT OF ALCOHOL DEPENDENCE." Alcohol and Alcoholism 52, suppl_1 (October 1, 2017): i4—i30. http://dx.doi.org/10.1093/alcalc/agx075.25.

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40

Nimmerrichter, A. A. "DOUBLE-BLIND CONTROLLED TRIAL OF gamma-HYDROXYBUTYRATE AND CLOMETHIAZOLE IN THE TREATMENT OF ALCOHOL WITHDRAWAL." Alcohol and Alcoholism 37, no. 1 (January 1, 2002): 67–73. http://dx.doi.org/10.1093/alcalc/37.1.67.

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41

Sychla, Hannah, Gerhard Gründer, and Sarah Edith Lammertz. "Comparison of Clomethiazole and Diazepam in the Treatment of Alcohol Withdrawal Syndrome in Clinical Practice." European Addiction Research 23, no. 4 (2017): 211–18. http://dx.doi.org/10.1159/000480380.

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42

Štuhec, M. "Clomethiazole-induced hepatotoxicity as example of successful treatment with cooperation between clinical pharmacist and physician." Journal of the Neurological Sciences 333 (October 2013): e290. http://dx.doi.org/10.1016/j.jns.2013.07.1096.

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43

Wahlgren, Nils Gunnar, Jordi Matias-Guiu, José Miguel Lainez, Felix Veloso, Kingsley Ranasinha, Eva Grossman, and Timothy Ashwood. "The clomethiazole acute stroke study (CLASS): Safety results in 1,356 patients with acute hemispheric stroke." Journal of Stroke and Cerebrovascular Diseases 9, no. 4 (July 2000): 158–65. http://dx.doi.org/10.1053/jscd.2000.7236.

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44

Green, A. R., T. K. Murray, A. Misra, M. F. Snape, J. A. Jones, and A. J. Cross. "The metabolism of clomethiazole in gerbils and the neuroprotective and sedative activity of the metabolites." British Journal of Pharmacology 129, no. 1 (January 2000): 95–100. http://dx.doi.org/10.1038/sj.bjp.0703042.

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45

Addae, Jonas I., Nakisha Ali, and Trevor W. Stone. "Effects of AMPA and clomethiazole on spreading depression cycles in the rat neocortex in vivo." European Journal of Pharmacology 653, no. 1-3 (February 2011): 41–46. http://dx.doi.org/10.1016/j.ejphar.2010.11.021.

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46

Latifi, Sahar, and Thomas Messer. "The Efficacy of Tiapride and Carbamazepine Combination Therapy in Reducing Alcohol Withdrawal Symptoms: A Systematic Review and Meta-Analysis." Pharmacopsychiatry 52, no. 05 (December 6, 2018): 209–16. http://dx.doi.org/10.1055/a-0795-3689.

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AbstractThe combination of tiapride (TIA) and carbamazepine (CBZ) as an alternative treatment option to benzodiazepines and clomethiazole has been investigated by several investigations. We performed a systematic review and meta-analysis to further explore the efficacy of this combination in order to render more definite answers whether this combination can be recommendable in the clinical practice. We systematically searched electronic databases including PubMed (MEDLINE), EMBASE, OVID, Cochrane, Google Scholar, and Scopus for human studies. Statistical homogeneity was checked by χ2 test and I2 using Cochran heterogeneity statistic. Our analysis showed a significant efficacy of the combination of TIA and CBZ in reducing alcohol withdrawal syndrome (AWS) (p<0.0001, z-value: 4.07). The cumulative analysis illustrated that the favorable efficacy of this combination therapy has been consistent over time. Our study shows that the combination of TIA/CBZ is an effective treatment in management of AWS in patients with alcohol abstinence. However, the safety of this combination could not be proven, so we recommend its prescription after an informed consent.
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47

Robinson, Stephen T. "Clinical Trial of the Neuroprotectant Clomethiazole in Coronary Artery Bypass Graft Surgery: A Randomized Controlled Trial." Survey of Anesthesiology 47, no. 5 (October 2003): 255. http://dx.doi.org/10.1097/00132586-200310000-00008.

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48

Sehnert, W., HM Brecht, and FG Nowak. "High dose intravenous clonidine is superior to intravenous clomethiazole in severe alcohol withdrawal syndrome (delirium tremens)." Critical Care 1, Suppl 1 (1997): P133. http://dx.doi.org/10.1186/cc100.

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49

Bonnet, U., M. Lensing, M. Specka, and N. Scherbaum. "Comparison of Two Oral Symptom-triggered Pharmacological Inpatient Treatments of Acute Alcohol Withdrawal: Clomethiazole vs. Clonazepam." Alcohol and Alcoholism 46, no. 1 (December 1, 2010): 68–73. http://dx.doi.org/10.1093/alcalc/agq081.

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50

Lyden, P., M. Jacoby, J. Schim, G. Albers, P. Mazzeo, T. Ashwood, A. Nordlund, and T. Odergren. "The Clomethiazole Acute Stroke Study in tissue-type plasminogen activator-treated stroke (CLASS-T): Final results." Neurology 57, no. 7 (October 9, 2001): 1199–205. http://dx.doi.org/10.1212/wnl.57.7.1199.

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