Therapies for Children With Autism Spectrum Disorders

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strength of evidence (confidence in the estimate) is low pending replication of the available studies. Not all children receiving such interventions demonstrate rapid gains, with some data suggesting that many children continue to display prominent areas of impairment 114 and that subgroups may account for a majority of change within certain samples. It seems likely based on preliminary evidence that subgroups of children are more amenable to many of the interventions available. These could potentially include groups defined by initial IQ, language and verbal skills as well as severity of ASDs, but there may also be underlying skill differences that may better account for variability. Current evidence is insufficient, however, to adequately identify and target children most likely to benefit from specific interventions. No studies directly compare effects of different treatment approaches (for example, there are no direct comparisons of UCLA/Lovaas and ESDM) and there is little evidence of practical effectiveness or feasibility beyond research studies, so questions remain about whether reported findings would be observed on a larger scale within communities. Furthermore, the studies conducted have used small samples, drastically different treatment approaches and duration and different outcome measurements. Nonetheless, improvements occur in some aspects of language, cognitive ability, adaptive behavior, challenging behaviors and potentially improved educational attainment for some children. While some previous reports 13,296,297 have suggested that it may be unethical to conduct randomized studies of early intensive interventions in the presence of evidence of benefit, the low strength of this evidence suggests that more rigorous trials or well conducted prospective cohort studies are needed. Strength of evidence is insufficient for the effects of social skills training for older children and for play and interaction based approaches for younger children. Cognitive behavioral therapy for associated conditions such as anxiety also has insufficient strength of evidence supporting positive outcomes. There is insufficient strength of evidence for improvements in cognitive outcomes with educational interventions, including the TEACCH intervention, and insufficient strength of evidence for broad-based approaches often based on ABA principles. A few medications show benefit for repetitive behaviors or associated symptoms, with the clearest evidence favoring risperidone and aripiprazole, both studied in RCTs and showing evidence of improvement in problem and repetitive behavior. Significant side effects, however, make it clear that although these drugs are efficacious, caution is warranted regarding their use in patients without severe impairments or risk of injury. A few other medical interventions show some promise for future research, including SRIs, 222- 224 methylphenidate, 228-231,233 omega 3 fatty acids, 246 and melatonin. 244 Others are clearly not efficacious and warrant no further study, including secretin. Evidence was insufficient at this time to support the use of sensory or auditory integration, insufficient for speech and language interventions, and insufficient for complementary and alternative medicine approaches. Importantly, the literature lacks comparisons of medical interventions with behavioral interventions and combinations of the two, despite the fact that most children are undergoing multiple concurrent treatments. This approach has proven crucial in studies of obsessive compulsive disorder, depression, and anxiety, 306-308 but few studies of adequate size have considered combination treatment with risperidone and behavioral treatment, 172,177 and these 126
studies lacked an arm that considered behavioral treatment alone, in addition to lacking a placebo control. In sum, some therapies for ASD do hold promise and warrant further study. Continuing improvements in methodologic rigor are needed, as are larger, potentially multisite, studies of existing interventions in which children are well characterized, both phenotypically and genotypically. 127
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Comparative Effectiveness Review Nu
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This report is based on research co
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Acknowledgments We are indebted to
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Therapies for Children With Autism
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Dietary and Other Medical Intervent
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Figures Figure A. Analytic framewor
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Table A. Description of interventio
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Analytic Framework Figure A. Analyt
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Strength of evidence. The degree of
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epetitive behavior showed improveme
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subgroups of children, although the
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We encourage investigators to provi
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9. Remington B, Hastings RP, Kovsho
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46. Green J, Charman T, McConachie
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82. Reaven JA, Blakeley-Smith A, Ni
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120. Masi G, Cosenza A, Mucci M, et
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157. Evangeliou A, Vlachonikolis I,
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Introduction Need for Evidence for
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Interventions intended primarily to
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Table 1. Description of behavioral
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Serotonin reuptake inhibitors. Sero
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Table 3. Description of medical and
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Table 4. Description of allied heal
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Key Questions and Analytic Framewor
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Chapter 4 discusses the results in
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Methods This chapter documents proc
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• Did not present aggregated resu
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Additional behavioral interventions
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1. Did the study employ a group des
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Scoring: Studies minimally had to h
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These ratings of applicability do n
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Figure 2. Disposition of articles a
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• ABA-based approaches including
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education, children in the intensiv
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abilities. This finding is further
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Table 10. Outcomes of early intensi
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forecast behavior; perspective taki
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interaction with peers; outcome mea
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hyperactivity, inattention, challen
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Table 12. Outcomes of RCTs assessin
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Schedule for Affective Disorders an
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SCAS-P=Spence Child Anxiety Scale-P
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Summary of the literature. Jarusiew
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Table 14. Overview of educational s
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on the Ankara Developmental Screeni
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Checklist scores decreased by 8.4 f
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Table 15. Outcomes of studies asses
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evaluated the effects of risperidon
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that this somnolence improved over
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Table 17. Outcomes of RCTs of antip
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Serotonin Reuptake Inhibitors SRIs
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One prospective case series of esci
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Most participants were recruited fr
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Dietary and Other Medical Intervent
Page 109 and 110: Summary of the literature-other int
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Page 113 and 114: therefore described separately belo
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Page 121 and 122: Teacher and Parent Scales, behavior
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Page 125 and 126: Educational Interventions Child cha
Page 127 and 128: showed diminished response to escit
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Page 131 and 132: contrast group (n=18) on three meas
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Page 135 and 136: Few studies directly comparing the
Page 137 and 138: Strength of evidence. The strength
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Page 145 and 146: strength of this reviewed literatur
Page 147 and 148: Table 36. Intervention, strength of
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Page 153 and 154: percent of behavioral studies repor
Page 155 and 156: limited followup, lack of comparati
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Page 159: selecting participants for their st
Page 163 and 164: 23. Kanner L. Autistic Disturbances
Page 165 and 166: 62. Dosman CF, Drmic IE, Brian JA,
Page 167 and 168: 104. Ben-Itzchak E and Zachor DA. T
Page 169 and 170: 142. Tyminski RF and Moore PJ. The
Page 171 and 172: 177. Aman MG, McDougle CJ, Scahill
Page 173 and 174: 214. Correia CT, Almeida JP, Santos
Page 175 and 176: 252. Akhondzadeh S, Tajdar H, Moham
Page 177 and 178: 290. Dawson G, Rogers S, Munson J,
Page 179 and 180: Acronyms/Abbreviations ABA Applied
Page 181 and 182: Appendix A. Exact Search Strings an
Page 183 and 184: Table A2. PsycINFO search strategie
Page 185 and 186: Therapies for Children with Autism
Page 187 and 188: Therapies for Children with ASD Sys
Page 189 and 190: Appendix C. Evidence Tables Tables
Page 191 and 192: Evidence Table. Therapies for child
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Evidence Table. Therapies for child
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Country: US Practice setting: Clini
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Dunn-Geier et al., 2000 (continued)
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Evidence Table: Therapies for Child
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Appendix D. List of Excluded Studie
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31. Aarsland D, Cummings JL and Lar
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59. Ahearn WH, Clark KM, Gardenier
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89. Allison DB, Basile VC and MacDo
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118. Ando H, Yoshimura I and Wakaba
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146. Atkinson RP, Jenson WR, Rovner
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177. Bakare MO, Agomoh AO, Ebigbo P
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204. Baron-Cohen S, Scott FJ, Allis
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233. Bebko JM, Perry A and Bryson S
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262. Bergmann F, Stepp H, Metzger R
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291. Birkan B, McClannahan LE and K
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319. Boddy F, Rowan EN, Lett D, et
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348. Bouma R and Schweitzer R. The
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376. Broadstock M, Doughty C and Eg
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404. Brudnak MA. Application of gen
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432. Buitelaar JK. Why have drug tr
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460. Butler DE, Nordin IC, L’Ital
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489. Campbell M, Locascio JJ, Choro
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517. Caronna EB, Augustyn M and Zuc
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546. Case-Smith J and Miller H. Occ
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574. Charlop MH, Burgio LD, Iwata B
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602. Cheng CW, Cho SH, Taylor M, et
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631. Cicero FR and Pfadt A. Investi
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662. Collier D and Reid G. A compar
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691. Coskun M, Karakoc S, Kircelli
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718. Cullen LA, Barlow JH and Cushw
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748. Davidovitch M, Holtzman G and
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777. DeLeon IG, Fisher WW and Marhe
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805. Devlin SD, Harber MM. Collabor
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834. Doherty K, Fitzgerald M and Ma
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863. Dudley LL, Johnson C and Barne
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893. Dybvik AC. Autism and the Incl
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924. Elder JH. In-home communicatio
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953. Erickson CA, Posey DJ, Stigler
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979. Faja S, Aylward E, Bernier R,
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1008. Ferri R, Elia M, Agarwal N, e
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1037. Fisher W, Kerbeshian J and Bu
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1066. Fragala-Pinkham M, Haley SM a
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1095. Furneaux B. Keeping the balan
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1124. Garcaa-Villamisar D, Wehman P
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1152. Ghezzi PM. Discrete Trials Te
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1180. Goin-Kochel RP, Myers BJ and
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1210. Gordon R, Handleman JS and Ha
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1239. Grimaldi BL. The central role
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1268. Guptill JT, Booker AB, Gibbs
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1296. Hamdan-Allen G. Brief report:
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1324. Hare DJ, Jones JPR and Paine
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1356. Harrison S and Berry L. Valui
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1386. Heilbrun AB, Jr., Blum N and
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1414. Hetzroni OE and Shalem U. Fro
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1443. Holburn CS. Counter the mistr
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1473. Horner RH, Carr EG, Strain PS
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1504. Hughes C, Soares-Boucaud I, H
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1533. Ijichi S and Ijichi N. Beyond
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1562. James SJ, Cutler P, Melnyk S,
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1591. Johnson CR, Butter EM, Handen
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1619. Joyce PR. The medical model-w
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1647. Karmali I, Greer RD, Nuzzolo-
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1673. Kelly AB, Garnett MS, Attwood
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1702. Kielinen M, Linna SL and Moil
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1731. Klin A, Lin DJ, Gorrindo P, e
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1761. Koegel RL and Frea WD. Treatm
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1790. Kolmen BK, Feldman HM, Handen
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1819. Kratochvil CJ, Findling RL, M
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1846. Lam MK and Rao N. Developing
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1874. Lattimore LP, Parsons MB and
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1903. Lee PC. Verification of a sim
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1932. Lerman DC, Vorndran C, Addiso
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1960. Licciardello CC, Harchik AE a
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1989. Liptak GS, Orlando M, Yinglin
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2015. Lorimer PA, Simpson RL, Myles
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2043. Luiselli JK, Kane A, Treml T,
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2071. MacFarlane JR and Kanaya T. W
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2099. Malone RP, Maislin G, Choudhu
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2127. Marin FZ. CAM versus nucleopl
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2157. Martineau J, Roux S, Adrien J
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2185. Matson JL and Lo Vullo SV. A
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2213. McCabe H. The Importance of P
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2240. McDougle CJ, Holmes JP, Carls
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2267. McHale SM, Olley JG, Marcus L
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2296. Merlo LJ, Lehmkuhl HD, Geffke
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2325. Minderaa RB, Anderson GM, Vol
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2354. Montgomery JM, Duncan CR and
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2385. Morrison RS, Sainato DM, Benc
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2413. Munesue T, Ono Y, Mutoh K, et
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2445. Napolitano DA, Tessing JL, Mc
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2474. Niederhofer H and Pittschiele
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2501. Nwora AJ and Gee BM. A case s
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2530. Olive ML, Lang RB and Davis T
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2559. Owens JA, Rosen CL and Mindel
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2589. Pansegrouw I and Alant E. Com
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2618. Paul C, Williams KE, Riegel K
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2646. Perry R, Nobler MS and Campbe
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2675. Piazza CC, Hagopian LP, Hughe
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2704. Poon L, Partika N and Bolman
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2734. Prizant BM. Speech-language p
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2764. Rapp JT, Vollmer TR, St. Pete
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2792. Reed P, Broomfield L, McHugh
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2819. Remington G, Sloman L, Konsta
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2849. Ringdahl JE, Kitsukawa K, And
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2877. Rogers SJ. Interventions that
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2908. Rossignol DA. Novel and emerg
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2939. Rutter M, Kreppner J, Croft C
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2967. Sandt D. Social Stories for S
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2994. Scanlon K. Art therapy with a
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3023. Schneider CK, Melmed RD, Bars
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3054. Schwartz IS, Sandall SR, Garf
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3085. Shafer MS, Egel AL and Neef N
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3115. Shipley-Benamou R, Lutzker JR
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3143. Siller M and Sigman M. The be
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3173. Smith C, Felce D, Jones E, et
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3202. Snyder A, Bossomaier T and Mi
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3230. Spero MH. The emancipation of
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3259. Stephens CE. Spontaneous imit
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3289. Strambi M, Longini M, Hayek J
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3318. Suzumura K. How an autistic b
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3346. Tager-Flusberg H and Calkins
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3376. Taylor I, O’Reilly M and La
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3407. Thunberg G, Ahlsen E and Sand
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3435. Trembath D, Balandin S, Toghe
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3464. Turner-Brown LM, Perry TD, Di
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3492. Van Der Putt R, Dineen C, Jan
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3522. Vitiello B. Recent NIMH clini
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3553. Walenski M, Mostofsky SH, Gid
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3581. Weber RC and Thorpe J. Teachi
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3610. Wheeler JJ, Baggett BA, Fox J
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3637. Williams B. Mental handicap n
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3669. Wimpory D, Chadwick P and Nas
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3698. Worth S and Reynolds S. The A
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3728. Young JM, Krantz PJ, McClanna
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3759. Zuddas A, Di Martino A, Mugli
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Appendix F. Approach to Categorizin
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APPENDIX G. Discussion of Recent Sy
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one a casein free regime. Diets wer
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outcome data as Type 6, defined as
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Yes—no disclosures to make G7 Bai
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Table G1. Characteristics of recent
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Random assignment Appropriate compa
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Study Group design Random assignmen
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APPENDIX I. Applicability Summary T
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Social skills (continued) Domain De
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