Antibiotic Treatment Trial for the PANDAS/PANS Phenotype

Summary

The purpose of this research study is to know if the antibiotic azithromycin, an antibiotic approved by the U.S. Food and Drug Administration (FDA) for treating infections, improves symptom severity in children with sudden and severe onset obsessive compulsive symptoms known as PANS, Pediatric Acute Onset Neuropsychiatric Syndrome, and PANDAS, Pediatric Autoimmune Neuropsychiatric Disorder Associated with Streptococcus. This study seeks to compare the effects of placebo vs. azithromycin on Obsessive Compulsive Disorder (OCD) symptom severity as well as to assess immune risk factors in children with PANDAS/PANS. Obsessions are repetitive, unwanted thoughts or worries that may be unpleasant, silly, or embarrassing. Compulsions are repetitive or ritualistic actions that are performed to ease anxiety or worries. Doctors think these symptoms may be caused or exacerbated by certain infections such as Streptococcus pyogenes, Mycoplasma pneumonia, Borrelia burgordfi, etc. These infections commonly cause strep throat, walking pneumonia, and Lyme Disease, among others. This study will involve a 4 week double-blind, placebo-controlled randomized trial of azithromycin (Double Blind Phase). At the end of this 4 week trial, the child will be assigned to azithromycin for 8 weeks (Open Label Phase). At the end of these 12 weeks, a Naturalistic Observation phase will assess the child's symptom characteristics for up to 40 weeks. The study hypothesizes that children receiving antibiotic will show significantly greater overall improvement in severity compared with placebo, and that children with sudden onset of OCD and whose subsequent course shows dramatic fluctuations will have evidence of immune risk factors that predisposes to this presentation.

Timeline

Start

2012-05

Primary completion

2014-12

Completion

2014-12

Publications

• Background Allen AJ, Leonard HL, Swedo SE. Case study: a new infection-triggered, autoimmune subtype of pediatric OCD and Tourette's syndrome. J Am Acad Child Adolesc Psychiatry. 1995 Mar;34(3):307-11. doi: 10.1097/00004583-199503000-00015.
• Background Chia KS. Multivariate statistical analysis: a brief introduction. Ann Acad Med Singap. 1999 Nov;28(6):879-80. No abstract available.
• Background Birmaher B, Khetarpal S, Brent D, Cully M, Balach L, Kaufman J, Neer SM. The Screen for Child Anxiety Related Emotional Disorders (SCARED): scale construction and psychometric characteristics. J Am Acad Child Adolesc Psychiatry. 1997 Apr;36(4):545-53. doi: 10.1097/00004583-199704000-00018.
• Background Bronze MS, Dale JB. Epitopes of streptococcal M proteins that evoke antibodies that cross-react with human brain. J Immunol. 1993 Sep 1;151(5):2820-8.
• Background Brook I. The role of beta-lactamase-producing bacteria in the persistence of streptococcal tonsillar infection. Rev Infect Dis. 1984 Sep-Oct;6(5):601-7. doi: 10.1093/clinids/6.5.601.
• Background Brook I. Failure of penicillin to eradicate group A beta-hemolytic streptococci tonsillitis: causes and management. J Otolaryngol. 2001 Dec;30(6):324-9. doi: 10.2310/7070.2001.19359.
• Background Brook I. The role of beta-lactamase producing bacteria and bacterial interference in streptococcal tonsillitis. Int J Antimicrob Agents. 2001 Jun;17(6):439-42. doi: 10.1016/s0924-8579(01)00321-1.
• Background Brook I. A pooled comparison of cefdinir and penicillin in the treatment of group a beta-hemolytic streptococcal pharyngotonsillitis. Clin Ther. 2005 Aug;27(8):1266-73. doi: 10.1016/j.clinthera.2005.08.003.
• Background Brook I, Dohar JE. Management of group A beta-hemolytic streptococcal pharyngotonsillitis in children. J Fam Pract. 2006 Dec;55(12):S1-11; quiz S12.
• Background Brooks-Gunn J, Warren MP, Rosso J, Gargiulo J. Validity of self-report measures of girls' pubertal status. Child Dev. 1987 Jun;58(3):829-41.
• Background Brooks BM, Hart CA, Coleman JW. Differential effects of beta-lactams on human IFN-gamma activity. J Antimicrob Chemother. 2005 Dec;56(6):1122-5. doi: 10.1093/jac/dki373. Epub 2005 Oct 20.
• Background Brooks BM, Thomas AL, Coleman JW. Benzylpenicillin differentially conjugates to IFN-gamma, TNF-alpha, IL-1beta, IL-4 and IL-13 but selectively reduces IFN-gamma activity. Clin Exp Immunol. 2003 Feb;131(2):268-74. doi: 10.1046/j.1365-2249.2003.02069.x.
• Background Budman CL, Kerjakovic M, Bruun RD. Viral infection and tic exacerbation. J Am Acad Child Adolesc Psychiatry. 1997 Feb;36(2):162. doi: 10.1097/00004583-199702000-00004. No abstract available.
• Background Carapetis JR, Currie BJ. Rheumatic chorea in northern Australia: a clinical and epidemiological study. Arch Dis Child. 1999 Apr;80(4):353-8. doi: 10.1136/adc.80.4.353.
• Background Cardona F, Orefici G. Group A streptococcal infections and tic disorders in an Italian pediatric population. J Pediatr. 2001 Jan;138(1):71-5. doi: 10.1067/mpd.2001.110325.
• Background Faul F, Erdfelder E, Lang AG, Buchner A. G*Power 3: a flexible statistical power analysis program for the social, behavioral, and biomedical sciences. Behav Res Methods. 2007 May;39(2):175-91. doi: 10.3758/bf03193146.
• Background Constantino, J., & CP, G. The Social Responsiveness Scale (SRS) Manual. Los Angeles: Western Psychological Services, 2005.
• Background Cook EH, Wagner KD, March JS, Biederman J, Landau P, Wolkow R, Messig M. Long-term sertraline treatment of children and adolescents with obsessive-compulsive disorder. J Am Acad Child Adolesc Psychiatry. 2001 Oct;40(10):1175-81. doi: 10.1097/00004583-200110000-00011.
• Background Currie BJ. Are the currently recommended doses of benzathine penicillin G adequate for secondary prophylaxis of rheumatic fever? Pediatrics. 1996 Jun;97(6 Pt 2):989-91.
• Background Dajani A, Taubert K, Ferrieri P, Peter G, Shulman S. Treatment of acute streptococcal pharyngitis and prevention of rheumatic fever: a statement for health professionals. Committee on Rheumatic Fever, Endocarditis, and Kawasaki Disease of the Council on Cardiovascular Disease in the Young, the American Heart Association. Pediatrics. 1995 Oct;96(4 Pt 1):758-64.
• Background Diggle, P. Analysis of longitudinal data. Oxford University Press, 2002.
• Background Garvey MA, Perlmutter SJ, Allen AJ, Hamburger S, Lougee L, Leonard HL, Witowski ME, Dubbert B, Swedo SE. A pilot study of penicillin prophylaxis for neuropsychiatric exacerbations triggered by streptococcal infections. Biol Psychiatry. 1999 Jun 15;45(12):1564-71. doi: 10.1016/s0006-3223(99)00020-7.
• Background Garvey MA, Swedo SE. Sydenham's chorea. Clinical and therapeutic update. Adv Exp Med Biol. 1997;418:115-20. doi: 10.1007/978-1-4899-1825-3_28. No abstract available.
• Background Gerson AC, Gerring JP, Freund L, Joshi PT, Capozzoli J, Brady K, Denckla MB. The Children's Affective Lability Scale: a psychometric evaluation of reliability. Psychiatry Res. 1996 Dec 20;65(3):189-98. doi: 10.1016/s0165-1781(96)02851-x.
• Background Gioia GA, Isquith PK, Retzlaff PD, Espy KA. Confirmatory factor analysis of the Behavior Rating Inventory of Executive Function (BRIEF) in a clinical sample. Child Neuropsychol. 2002 Dec;8(4):249-57. doi: 10.1076/chin.8.4.249.13513.
• Background Giulino L, Gammon P, Sullivan K, Franklin M, Foa E, Maid R, March JS. Is parental report of upper respiratory infection at the onset of obsessive-compulsive disorder suggestive of pediatric autoimmune neuropsychiatric disorder associated with streptococcal infection? J Child Adolesc Psychopharmacol. 2002 Summer;12(2):157-64. doi: 10.1089/104454602760219199.
• Background Green B, Shirk S, Hanze D, Wanstrath J. The Children's Global Assessment Scale in clinical practice: an empirical evaluation. J Am Acad Child Adolesc Psychiatry. 1994 Oct;33(8):1158-64. doi: 10.1097/00004583-199410000-00011.
• Background Guchev IA, Klochkov OI, Ivanitsa GV, Pervov IuA, Shturmina SM, Rosman SV. [Efficacy and safety of azithromycin prophylaxis of respiratory tract infections in military community]. Antibiot Khimioter. 2004;49(8-9):34-5, 37-42. Russian.
• Background Guilherme L, Kalil J, Cunningham M. Molecular mimicry in the autoimmune pathogenesis of rheumatic heart disease. Autoimmunity. 2006 Feb;39(1):31-9. doi: 10.1080/08916930500484674.
• Background Guy, W. Assessment Manual for Psychopharmacology, rev. edn. Rockville, MD: National Institute of Mental Health, 1976.
• Background Hagelskjaer LH, Hansen NJ. [Neurological complications of Mycoplasma pneumoniae infections]. Ugeskr Laeger. 1993 Apr 26;155(17):1265-9. Danish.
• Background Hamstra-Bletz L, Blote AW. A longitudinal study on dysgraphic handwriting in primary school. J Learn Disabil. 1993 Dec;26(10):689-99. doi: 10.1177/002221949302601007.
• Background Husby G, van de Rijn I, Zabriskie JB, Abdin ZH, Williams RC Jr. Antibodies reacting with cytoplasm of subthalamic and caudate nuclei neurons in chorea and acute rheumatic fever. J Exp Med. 1976 Oct 1;144(4):1094-110. doi: 10.1084/jem.144.4.1094.
• Background Jacobs MR, Johnson CE. Macrolide resistance: an increasing concern for treatment failure in children. Pediatr Infect Dis J. 2003 Aug;22(8 Suppl):S131-8. doi: 10.1097/00006454-200308001-00004.
• Background Kantor L, Hewlett GH, Gnegy ME. Enhanced amphetamine- and K+-mediated dopamine release in rat striatum after repeated amphetamine: differential requirements for Ca2+- and calmodulin-dependent phosphorylation and synaptic vesicles. J Neurosci. 1999 May 15;19(10):3801-8. doi: 10.1523/JNEUROSCI.19-10-03801.1999.
• Background Karno M, Golding JM, Sorenson SB, Burnam MA. The epidemiology of obsessive-compulsive disorder in five US communities. Arch Gen Psychiatry. 1988 Dec;45(12):1094-9. doi: 10.1001/archpsyc.1988.01800360042006.
• Background Kaufman J, Birmaher B, Brent D, Rao U, Flynn C, Moreci P, Williamson D, Ryan N. Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present and Lifetime Version (K-SADS-PL): initial reliability and validity data. J Am Acad Child Adolesc Psychiatry. 1997 Jul;36(7):980-8. doi: 10.1097/00004583-199707000-00021.
• Background Kerbeshian J, Burd L, Pettit R. A possible post-streptococcal movement disorder with chorea and tics. Dev Med Child Neurol. 1990 Jul;32(7):642-4.
• Background Khanna S, Ravi V, Shenoy PK, Chandramuki A, Channabasavanna SM. Cerebrospinal fluid viral antibodies in obsessive-compulsive disorder in an Indian population. Biol Psychiatry. 1997 Apr 15;41(8):883-90. doi: 10.1016/S0006-3223(96)00174-6.
• Background Kiessling LS, Marcotte AC, Culpepper L. Antineuronal antibodies: tics and obsessive-compulsive symptoms. J Dev Behav Pediatr. 1994 Dec;15(6):421-5.
• Background Kirvan CA, Swedo SE, Heuser JS, Cunningham MW. Mimicry and autoantibody-mediated neuronal cell signaling in Sydenham chorea. Nat Med. 2003 Jul;9(7):914-20. doi: 10.1038/nm892.
• Background Kirvan CA, Swedo SE, Kurahara D, Cunningham MW. Streptococcal mimicry and antibody-mediated cell signaling in the pathogenesis of Sydenham's chorea. Autoimmunity. 2006 Feb;39(1):21-9. doi: 10.1080/08916930500484757.
• Background Kirvan CA, Swedo SE, Snider LA, Cunningham MW. Antibody-mediated neuronal cell signaling in behavior and movement disorders. J Neuroimmunol. 2006 Oct;179(1-2):173-9. doi: 10.1016/j.jneuroim.2006.06.017. Epub 2006 Jul 27.
• Background Kurlan R, Kaplan EL. The pediatric autoimmune neuropsychiatric disorders associated with streptococcal infection (PANDAS) etiology for tics and obsessive-compulsive symptoms: hypothesis or entity? Practical considerations for the clinician. Pediatrics. 2004 Apr;113(4):883-6. doi: 10.1542/peds.113.4.883.
• Background Kushner HI, Kiessling LS. The controversy over the classification of Gilles de la Tourette's syndrome, 1800-1995. Perspect Biol Med. 1996 Spring;39(3):409-35. doi: 10.1353/pbm.1996.0010. No abstract available.
• Background Landgraf, J. M., Abetz, L., & Ware, J. E. The CHQ user's manual. Boston: The Health Institute, New England Medical Center, 1996.
• Background Leckman JF, Riddle MA, Hardin MT, Ort SI, Swartz KL, Stevenson J, Cohen DJ. The Yale Global Tic Severity Scale: initial testing of a clinician-rated scale of tic severity. J Am Acad Child Adolesc Psychiatry. 1989 Jul;28(4):566-73. doi: 10.1097/00004583-198907000-00015.
• Background Leckman JF, Sholomskas D, Thompson WD, Belanger A, Weissman MM. Best estimate of lifetime psychiatric diagnosis: a methodological study. Arch Gen Psychiatry. 1982 Aug;39(8):879-83. doi: 10.1001/archpsyc.1982.04290080001001.
• Background Leonard HL, Swedo SE, Rapoport JL, Rickler KC, Topol D, Lee S, Rettew D. Tourette syndrome and obsessive-compulsive disorder. Adv Neurol. 1992;58:83-93. No abstract available.
• Background Lewin AB, Storch EA, Mutch PJ, Murphy TK. Neurocognitive functioning in youth with pediatric autoimmune neuropsychiatric disorders associated with streptococcus. J Neuropsychiatry Clin Neurosci. 2011 Fall;23(4):391-8. doi: 10.1176/jnp.23.4.jnp391.
• Background Lunsing RJ, Hadders-Algra M, Huisjes HJ, Touwen BC. Minor neurological dysfunction from birth to 12 years. I: Increase during late school-age. Dev Med Child Neurol. 1992 May;34(5):399-403. doi: 10.1111/j.1469-8749.1992.tb11451.x.
• Background Mahone EM, Cirino PT, Cutting LE, Cerrone PM, Hagelthorn KM, Hiemenz JR, Singer HS, Denckla MB. Validity of the behavior rating inventory of executive function in children with ADHD and/or Tourette syndrome. Arch Clin Neuropsychol. 2002 Oct;17(7):643-62.
• Background Matza LS, Rentz AM, Secnik K, Swensen AR, Revicki DA, Michelson D, Spencer T, Newcorn JH, Kratochvil CJ. The link between health-related quality of life and clinical symptoms among children with attention-deficit hyperactivity disorder. J Dev Behav Pediatr. 2004 Jun;25(3):166-74. doi: 10.1097/00004703-200406000-00005.
• Background Mell LK, Davis RL, Owens D. Association between streptococcal infection and obsessive-compulsive disorder, Tourette's syndrome, and tic disorder. Pediatrics. 2005 Jul;116(1):56-60. doi: 10.1542/peds.2004-2058.
• Background Meyers, J., & Meyers, K. Rey Complex Figure Test and recognition trial: Professional manual. Psychological Assessment Resources, 1995.
• Background Miettinen M, Matikainen S, Vuopio-Varkila J, Pirhonen J, Varkila K, Kurimoto M, Julkunen I. Lactobacilli and streptococci induce interleukin-12 (IL-12), IL-18, and gamma interferon production in human peripheral blood mononuclear cells. Infect Immun. 1998 Dec;66(12):6058-62. doi: 10.1128/IAI.66.12.6058-6062.1998.
• Background MILLER JM, STANCER SL, MASSELL BF. A controlled study of beta hemolytic streptococcal infection in rheumatic families. II. Penicillin prophylaxis among rheumatic fever subjects, comparing different regimens. Am J Med. 1958 Dec;25(6):845-56. doi: 10.1016/0002-9343(58)90057-3. No abstract available.
• Background Mineur YS, Picciotto MR, Sanacora G. Antidepressant-like effects of ceftriaxone in male C57BL/6J mice. Biol Psychiatry. 2007 Jan 15;61(2):250-2. doi: 10.1016/j.biopsych.2006.04.037. Epub 2006 Jul 24.
• Background Morikawa K, Torii I, Morikawa S. Modulation of IgD and CD20 by ligation of CD5 on tonsillar B cells. Scand J Immunol. 2002 Jan;55(1):44-52. doi: 10.1046/j.1365-3083.2002.00987.x.
• Background Muller N, Riedel M, Forderreuther S, Blendinger C, Abele-Horn M. Tourette's syndrome and mycoplasma pneumoniae infection. Am J Psychiatry. 2000 Mar;157(3):481-2. doi: 10.1176/appi.ajp.157.3.481-a. No abstract available.
• Background Muller N, Riedel M, Blendinger C, Oberle K, Jacobs E, Abele-Horn M. Mycoplasma pneumoniae infection and Tourette's syndrome. Psychiatry Res. 2004 Dec 15;129(2):119-25. doi: 10.1016/j.psychres.2004.04.009.
• Background Murphy BS, Sundareshan V, Cory TJ, Hayes D Jr, Anstead MI, Feola DJ. Azithromycin alters macrophage phenotype. J Antimicrob Chemother. 2008 Mar;61(3):554-60. doi: 10.1093/jac/dkn007. Epub 2008 Jan 29.
• Background Murphy ML, Pichichero ME. Prospective identification and treatment of children with pediatric autoimmune neuropsychiatric disorder associated with group A streptococcal infection (PANDAS). Arch Pediatr Adolesc Med. 2002 Apr;156(4):356-61. doi: 10.1001/archpedi.156.4.356.
• Background Murphy TK, Sajid M, Soto O, Shapira N, Edge P, Yang M, Lewis MH, Goodman WK. Detecting pediatric autoimmune neuropsychiatric disorders associated with streptococcus in children with obsessive-compulsive disorder and tics. Biol Psychiatry. 2004 Jan 1;55(1):61-8. doi: 10.1016/s0006-3223(03)00704-2.
• Background Murphy TK, Snider LA, Mutch PJ, Harden E, Zaytoun A, Edge PJ, Storch EA, Yang MC, Mann G, Goodman WK, Swedo SE. Relationship of movements and behaviors to Group A Streptococcus infections in elementary school children. Biol Psychiatry. 2007 Feb 1;61(3):279-84. doi: 10.1016/j.biopsych.2006.08.031. Epub 2006 Nov 27.
• Background Murphy TK, Storch EA, Lewin AB, Edge PJ, Goodman WK. Clinical factors associated with pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections. J Pediatr. 2012 Feb;160(2):314-9. doi: 10.1016/j.jpeds.2011.07.012. Epub 2011 Aug 25.
• Background Murphy, T. K., Storch, E. A., & Strawser, M. S. Case Report: Selective Serotonin Reuptake Inhibitor-Induced Behavioral Activation in the PANDAS Subtype. [case report]. Primary Psychiatry, 13(8), 87-89, 2006.
• Background Murr C, Gerlach D, Widner B, Dierich MP, Fuchs D. Neopterin production and tryptophan degradation in humans infected by Streptococcus pyogenes. Med Microbiol Immunol. 2001 Apr;189(3):161-3. doi: 10.1007/s430-001-8023-3.
• Background O'Connell PJ, Wang X, Leon-Ponte M, Griffiths C, Pingle SC, Ahern GP. A novel form of immune signaling revealed by transmission of the inflammatory mediator serotonin between dendritic cells and T cells. Blood. 2006 Feb 1;107(3):1010-7. doi: 10.1182/blood-2005-07-2903. Epub 2005 Oct 13.
• Background Perlmutter SJ, Garvey MA, Castellanos X, Mittleman BB, Giedd J, Rapoport JL, Swedo SE. A case of pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections. Am J Psychiatry. 1998 Nov;155(11):1592-8. doi: 10.1176/ajp.155.11.1592. No abstract available.
• Background Perwien AR, Faries DE, Kratochvil CJ, Sumner CR, Kelsey DK, Allen AJ. Improvement in health-related quality of life in children with ADHD: an analysis of placebo controlled studies of atomoxetine. J Dev Behav Pediatr. 2004 Aug;25(4):264-71. doi: 10.1097/00004703-200408000-00006.
• Background Piacentini J, Bergman RL, Keller M, McCracken J. Functional impairment in children and adolescents with obsessive-compulsive disorder. J Child Adolesc Psychopharmacol. 2003;13 Suppl 1:S61-9. doi: 10.1089/104454603322126359.
• Background Piacentini, J. C., & Jaffer, M. P., J. C., & Jaffer, M. Measuring functional impairment in youngsters with OCD: Manual for the Child OCD Impact Scale (COIS). Los Angeles, UCLA Department of Psychiatry, 1999.
• Background Pichichero ME, Casey JR, Mayes T, Francis AB, Marsocci SM, Murphy AM, Hoeger W. Penicillin failure in streptococcal tonsillopharyngitis: causes and remedies. Pediatr Infect Dis J. 2000 Sep;19(9):917-23. doi: 10.1097/00006454-200009000-00035.
• Background Pichichero ME, Gooch WM 3rd. Comparison of cefdinir and penicillin V in the treatment of pediatric streptococcal tonsillopharyngitis. Pediatr Infect Dis J. 2000 Dec;19(12 Suppl):S171-3. doi: 10.1097/00006454-200012001-00007.
• Background Pittenger C, Krystal JH, Coric V. Glutamate-modulating drugs as novel pharmacotherapeutic agents in the treatment of obsessive-compulsive disorder. NeuroRx. 2006 Jan;3(1):69-81. doi: 10.1016/j.nurx.2005.12.006.
• Background PRECHTL HF, STEMMER J. The choreiform syndrome in children. Dev Med Child Neurol. 1962 Apr;4:119-27. doi: 10.1111/j.1469-8749.1962.tb03120.x. No abstract available.
• Background Rentz AM, Matza LS, Secnik K, Swensen A, Revicki DA. Psychometric validation of the child health questionnaire (CHQ) in a sample of children and adolescents with attention-deficit/hyperactivity disorder. Qual Life Res. 2005 Apr;14(3):719-34. doi: 10.1007/s11136-004-0832-9.
• Background Richter SS, Heilmann KP, Beekmann SE, Miller NJ, Miller AL, Rice CL, Doern CD, Reid SD, Doern GV. Macrolide-resistant Streptococcus pyogenes in the United States, 2002-2003. Clin Infect Dis. 2005 Sep 1;41(5):599-608. doi: 10.1086/432473.
• Background Rothstein JD, Patel S, Regan MR, Haenggeli C, Huang YH, Bergles DE, Jin L, Dykes Hoberg M, Vidensky S, Chung DS, Toan SV, Bruijn LI, Su ZZ, Gupta P, Fisher PB. Beta-lactam antibiotics offer neuroprotection by increasing glutamate transporter expression. Nature. 2005 Jan 6;433(7021):73-7. doi: 10.1038/nature03180.
• Background Scahill L, Riddle MA, McSwiggin-Hardin M, Ort SI, King RA, Goodman WK, Cicchetti D, Leckman JF. Children's Yale-Brown Obsessive Compulsive Scale: reliability and validity. J Am Acad Child Adolesc Psychiatry. 1997 Jun;36(6):844-52. doi: 10.1097/00004583-199706000-00023.
• Background Schafer JL, Graham JW. Missing data: our view of the state of the art. Psychol Methods. 2002 Jun;7(2):147-77.
• Background Seber, G. A. F. Multivariate Observations. New York: Wiley, 1984.
• Background Shaffer D, Gould MS, Brasic J, Ambrosini P, Fisher P, Bird H, Aluwahlia S. A children's global assessment scale (CGAS). Arch Gen Psychiatry. 1983 Nov;40(11):1228-31. doi: 10.1001/archpsyc.1983.01790100074010.
• Background Shytle RD, Silver AA, Sheehan KH, Wilkinson BJ, Newman M, Sanberg PR, Sheehan D. The Tourette's Disorder Scale (TODS): development, reliability, and validity. Assessment. 2003 Sep;10(3):273-87. doi: 10.1177/1073191103255497.
• Background Singer HS, Giuliano JD, Zimmerman AM, Walkup JT. Infection: a stimulus for tic disorders. Pediatr Neurol. 2000 May;22(5):380-3. doi: 10.1016/s0887-8994(00)00131-4.
• Background Snider LA, Lougee L, Slattery M, Grant P, Swedo SE. Antibiotic prophylaxis with azithromycin or penicillin for childhood-onset neuropsychiatric disorders. Biol Psychiatry. 2005 Apr 1;57(7):788-92. doi: 10.1016/j.biopsych.2004.12.035.
• Background Sorensen JL, Hargreaves WA, Friedlander S. Child global rating scales: selecting a measure of client functioning in a large mental health system. Eval Program Plann. 1982;5(4):337-47. doi: 10.1016/0149-7189(82)90006-4.
• Background Storch EA, Geffken GR, Merlo LJ, Mann G, Duke D, Munson M, Adkins J, Grabill KM, Murphy TK, Goodman WK. Family-based cognitive-behavioral therapy for pediatric obsessive-compulsive disorder: comparison of intensive and weekly approaches. J Am Acad Child Adolesc Psychiatry. 2007 Apr;46(4):469-478. doi: 10.1097/chi.0b013e31803062e7.
• Background Storch EA, Murphy TK, Geffken GR, Mann G, Adkins J, Merlo LJ, Duke D, Munson M, Swaine Z, Goodman WK. Cognitive-behavioral therapy for PANDAS-related obsessive-compulsive disorder: findings from a preliminary waitlist controlled open trial. J Am Acad Child Adolesc Psychiatry. 2006 Oct;45(10):1171-8. doi: 10.1097/01.chi.0000231973.43966.a0.
• Background Storch EA, Murphy TK, Geffken GR, Sajid M, Allen P, Roberti JW, Goodman WK. Reliability and validity of the Yale Global Tic Severity Scale. Psychol Assess. 2005 Dec;17(4):486-91. doi: 10.1037/1040-3590.17.4.486.
• Background Storch EA, Murphy TK, Geffken GR, Soto O, Sajid M, Allen P, Roberti JW, Killiany EM, Goodman WK. Further psychometric properties of the Tourette's Disorder Scale-Parent Rated version (TODS-PR). Child Psychiatry Hum Dev. 2004 Winter;35(2):107-20. doi: 10.1007/s10578-004-1880-7.
• Background Swanson, J. M. School-based assessments and interventions for ADD students. Irvine, CA: K C Publishing, 1992.
• Background Swedo SE, Leonard HL, Garvey M, Mittleman B, Allen AJ, Perlmutter S, Lougee L, Dow S, Zamkoff J, Dubbert BK. Pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections: clinical description of the first 50 cases. Am J Psychiatry. 1998 Feb;155(2):264-71. doi: 10.1176/ajp.155.2.264.
• Background Tanner JM, Whitehouse RH. Clinical longitudinal standards for height, weight, height velocity, weight velocity, and stages of puberty. Arch Dis Child. 1976 Mar;51(3):170-9. doi: 10.1136/adc.51.3.170.
• Background Teixeira AL Jr, Guimaraes MM, Romano-Silva MA, Cardoso F. Serum from Sydenham's chorea patients modifies intracellular calcium levels in PC12 cells by a complement-independent mechanism. Mov Disord. 2005 Jul;20(7):843-5. doi: 10.1002/mds.20418.
• Background Tuck MK, Chan DW, Chia D, Godwin AK, Grizzle WE, Krueger KE, Rom W, Sanda M, Sorbara L, Stass S, Wang W, Brenner DE. Standard operating procedures for serum and plasma collection: early detection research network consensus statement standard operating procedure integration working group. J Proteome Res. 2009 Jan;8(1):113-7. doi: 10.1021/pr800545q.
• Background Tucker DM, Leckman JF, Scahill L, Wilf GE, LaCamera R, Cardona L, Cohen P, Heidmann S, Goldstein J, Judge J, Snyder E, Bult A, Peterson BS, King R, Lombroso P. A putative poststreptococcal case of OCD with chronic tic disorder, not otherwise specified. J Am Acad Child Adolesc Psychiatry. 1996 Dec;35(12):1684-91. doi: 10.1097/00004583-199612000-00022.
• Background Wallwork B, Coman W, Mackay-Sim A, Greiff L, Cervin A. A double-blind, randomized, placebo-controlled trial of macrolide in the treatment of chronic rhinosinusitis. Laryngoscope. 2006 Feb;116(2):189-93. doi: 10.1097/01.mlg.0000191560.53555.08.
• Background Wood, H. F., Feinstein, A. R., Taranta, A., & Simpson, R. Rheumatic fever in children and adolescents III. Comparative effectiveness of three prophylaxis regimens in preventing streptococcal infections and rheumatic fever. Annuals of Internal Medicine, 60(supplement 5), 31-46, 1964.
• Background Yamauchi K, Shibata Y, Kimura T, Abe S, Inoue S, Osaka D, Sato M, Igarashi A, Kubota I. Azithromycin suppresses interleukin-12p40 expression in lipopolysaccharide and interferon-gamma stimulated macrophages. Int J Biol Sci. 2009 Oct 23;5(7):667-78. doi: 10.7150/ijbs.5.667.

Drugs

Indications