...

EBM Journal Club Effectiveness of acupuncture for autism spectrum disorder R2 / 2011/10/24

... &*&o*^%^%$%x#$#@&

5A step 1--Asking

P Problem Autism I Intervention Acupuncture C Comparison Placebo or Sham acupuncture O Outcome Symtom improvement

Autism Spectrum Disorder Autistic disorder Asperger disorder Rett disorder Childhood disintegrative disorder DSM-IV ICD-10 ABC CARS Pervasive developmental disorder-not otherwise specified

Autistic Disorder 0.05% 3-4:1

(if with hyperactivity, inattention, anxiety,sleep disturbance, depressive symptoms, obsessive compulsive disorder,)

5A step 2--Assessing search strategy

Medline

autism and acupuncture Pubmed(Clinical Queries)

EBM reviews(all)

Clinical trials 8

Total Clinical trials 14

+ Autism + Acupuncture + Medline Pubmed EBM Review Expert opinion Clinical trial 14 Case-series R.C.T 6 Individual Case-Control Study R.C.T 2 SR of case-control studies RCT of cohort study Systemic Review 1 SR of cohort studies Individual RCT SR of RCTs Systemic Review 0

Final Result... Acupuncture for autism spectrum disorder(asd) Daniel KL Cheuk, Virginia Wong, Wen Xiong Chen Cochrane Database Systemic Review. 2011 Sep. Systemic Review Level 1a

5A step 3--Appraising

Acupuncture for autism spectrum disorder(asd) Daniel KL Cheuk, Virginia Wong, Wen Xiong Chen Cochrane Database Systemic Review. 2011 Sep 7;9. 15 database 10 RCT articles N= 390 3-18 years olds 1-9 Wong 2002 Wang 2007 Wong 2007 Yan 2007 Allam 2008 Wong 2008 Zhou 2008 Chan 2009 Wong 2010a Wong 2010b

Outcome Measurement Primary outcome (Core features) Aberrant Behavior Checklist(ABC) Ritvo-Freeman Real Life Rating Scale(RFRLRS) Autism Treatment Evaluation Checklist(ATEC) Autism Diagnostic Observation Scale(ADOS) Secondary Outcome Commuication and linguistic ability Cognitive Function Global Functioning Side effects Reynell Language Developmental scale(rlds) Symbolic Play Test(SPT) Griffiths Mental Developmental Scale(GMDS) Leiter International Performance Scale-Revised (Leiter-R) Pediatric Evaluation Disability Inventory(PEDI) Functional Independence Measure for Children (WeeFIM) needle pain, bleeding, faintness, pneumothorax

Acupuncture+Conventional V.S Sham acupuncture+conventional Wong 2010a Wong 2010b 10 RCT trials Acupuncture+Conventional V.S Conventional Wong 2002 Wang 2007 Yan 2007 Allam 2008 Wong 2008 Acupressure+Conventional V.S Conventional Zhou 2008 Chan 2009

Acupuncture(A)+Conventional(C) V.S Sham acupuncture(s)+conventional A S C Primary outcome Secondary outcome Wong 2010a RFRLRS X Wong 2010b 3-5mm RFRLRS ABC RLDS WeeFIM SPT GMDS Leiter-R CGIS PEDI

RFRLRS

Study or subgroup Treatment Control Mean Difference Weight Mean Difference N Mean(SD) N Mean(SD) IV,Fixed,95% CI IV,Fixed,95% CI 1Improvementincomprehensionage Wong 2010a 25 0.21 (0.19) 25 0.06 (0.28) 77.5 % 0.15 [ 0.02, 0.28 ] Significant difference! Wong 2010b 30 0.12 (0.4) 25 0.03 (0.51) 22.5 % 0.09 [ -0.16, 0.34 ] Subtotal (95% CI) 55 50 100.0 % 0.14 [ 0.02, 0.25 ] Heterogeneity: Chi 2 =0.18,df=1(P=0.67);I 2 =0.0% Test for overall effect: Z = 2.29 (P = 0.022) 2Improvementincomprehensionscore Wong 2010a 25 0.76 (9.73) 25 2.08 (3.67) 100.0 % -1.32 [ -5.40, 2.76 ] Subtotal (95% CI) 25 25 100.0 % -1.32 [ -5.40, 2.76 ] Heterogeneity: not applicable Test for overall effect: Z = 0.63 (P = 0.53) 3Improvementinexpressionage Wong 2010a 25 0.25 (0.3) 25 0.2 (0.26) 91.0 % 0.05 [ -0.11, 0.21 ] Wong 2010b 30 0.09 (0.7) 25 0.05 (1.09) 9.0 % 0.04 [ -0.46, 0.54 ] Subtotal (95% CI) 55 50 100.0 % 0.05 [ -0.10, 0.20 ] Heterogeneity: Chi 2 =0.00,df=1(P=0.97);I 2 =0.0% Test for overall effect: Z = 0.65 (P = 0.52) 4Improvementinexpressionscore Wong 2010a 25 5.44 (4.68) 25 3.48 (4.48) 100.0 % 1.96 [ -0.58, 4.50 ] Subtotal (95% CI) 25 25 100.0 % 1.96 [ -0.58, 4.50 ] Heterogeneity: not applicable Test for overall effect: Z = 1.51 (P = 0.13) Test for subgroup differences: Chi 2 =3.34,df=3(P=0.34),I 2 =10% RLDS -4-2 0 2 4 Favours control Favours treatment

Study or subgroup Treatment Control Mean Difference Weight Mean Difference N Mean(SD) N Mean(SD) IV,Random,95% CI IV,Random,95% CI 1Improvementintotalscore Wong 2010a 25 7.92 (4.96) 25 3.04 (4.02) 52.3 % 4.88 [ 2.38, 7.38 ] WeeFIM Wong 2010b 30 1.03 (3.85) 25-0.08 (6.7) 47.7 % 1.11 [ -1.86, 4.08 ] Subtotal (95% CI) 55 50 100.0 % 3.08 [ -0.61, 6.77 ] Heterogeneity: Tau 2 =5.15;Chi 2 =3.63,df=1(P=0.06);I 2 =72% Test for overall effect: Z = 1.64 (P = 0.10) 2 Improvement in self-care Wong 2010a 25 5 (3.92) 25 1.5 (2.59) 50.6 % 3.50 [ 1.66, 5.34 ] Wong 2010b 30 0.3 (3.29) 25-0.36 (3.93) 49.4 % 0.66 [ -1.28, 2.60 ] Subtotal (95% CI) 55 50 100.0 % 2.10 [ -0.69, 4.88 ] Heterogeneity: Tau 2 =3.10;Chi 2 =4.33,df=1(P=0.04);I 2 =77% Test for overall effect: Z = 1.48 (P = 0.14) 3Improvementinmobility Wong 2010a 25 1.52 (1.73) 25 1.13 (2.05) 47.5 % 0.39 [ -0.66, 1.44 ] Wong 2010b 30-0.17 (0.75) 25 0.4 (2.36) 52.5 % -0.57 [ -1.53, 0.39 ] Subtotal (95% CI) 55 50 100.0 % -0.11 [ -1.05, 0.83 ] Heterogeneity: Tau 2 =0.20;Chi 2 =1.74,df=1(P=0.19);I 2 =43% Test for overall effect: Z = 0.24 (P = 0.81) 4Improvementincognition Wong 2010a 25 1.28 (1.37) 25 0.42 (1.61) 53.2 % 0.86 [ 0.03, 1.69 ] Wong 2010b 30 1.07 (1.29) 25 0.56 (1.92) 46.8 % 0.51 [ -0.37, 1.39 ] Subtotal (95% CI) 55 50 100.0 % 0.70 [ 0.09, 1.30 ] Heterogeneity: Tau 2 =0.0;Chi 2 =0.32,df=1(P=0.57);I 2 =0.0% Test for overall effect: Z = 2.26 (P = 0.024) 5Improvementincomprehension Wong 2010b 30 0.53 (0.57) 25 0.16 (0.85) 100.0 % 0.37 [ -0.02, 0.76 ] Subtotal (95% CI) 30 25 100.0 % 0.37 [ -0.02, 0.76 ] Heterogeneity: not applicable Test for overall effect: Z = 1.86 (P = 0.063) Significant difference! -4-2 0 2 4

( ) Study or subgroup Treatment Control Mean Difference Weight Mean Difference 6Improvementinexpression N Mean(SD) N Mean(SD) IV,Random,95% CI IV,Random,95% CI Wong 2010b 30 0.3 (0.84) 25 0.16 (0.75) 100.0 % 0.14 [ -0.28, 0.56 ] Subtotal (95% CI) 30 25 100.0 % 0.14 [ -0.28, 0.56 ] Heterogeneity: not applicable Test for overall effect: Z = 0.65 (P = 0.51) 7Improvementinsocialinteraction Wong 2010b 30 0.07 (0.52) 25 0.2 (0.58) 100.0 % -0.13 [ -0.42, 0.16 ] Subtotal (95% CI) 30 25 100.0 % -0.13 [ -0.42, 0.16 ] Heterogeneity: not applicable Test for overall effect: Z = 0.87 (P = 0.39) 8Improvementinproblemsolving Wong 2010b 30-0.13 (0.35) 25 0 (0.71) 100.0 % -0.13 [ -0.44, 0.18 ] Subtotal (95% CI) 30 25 100.0 % -0.13 [ -0.44, 0.18 ] Heterogeneity: not applicable Test for overall effect: Z = 0.83 (P = 0.40) 9Improvementinmemory Wong 2010b 30 0.03 (0.49) 25-0.04 (0.54) 100.0 % 0.07 [ -0.20, 0.34 ] Subtotal (95% CI) 30 25 100.0 % 0.07 [ -0.20, 0.34 ] Heterogeneity: not applicable Test for overall effect: Z = 0.50 (P = 0.62) Significant difference was only shown in cognition domain WeeFIM -4-2 0 2 4 Favours control Favours treatment

Acupuncture(A)+Conventional(C) V.S Conventional A C Primary outcome Secondary outcome Wong 2002 RFRLRS X Wong 2007 ATEC Wong 2008 RFRLRS ABC ATES ADOS WeeFIM CGIS Yan 2007 X CPEP Allam 2008 X ALT RLDS SPT SPT Wang 2007 ABC PPVT

Study or subgroup Treatment Control Mean Difference Weight Mean Difference N Mean(SD) N Mean(SD) IV,Fixed,95% CI IV,Fixed,95% CI 1Improvementintotalscore Wong 2002 15 8 (5.606) 13 1 (1.354) 27.8 % 7.00 [ 4.07, 9.93 ] WeeFIM Wong 2007 12 4.01 (3.008) 9-0.08 (1.434) 63.3 % 4.09 [ 2.15, 6.03 ] Wong 2008 18 1.278 (8.532) 18 3.5 (7.312) 8.9 % -2.22 [ -7.41, 2.97 ] Subtotal (95% CI) 45 40 100.0 % 4.34 [ 2.79, 5.89 ] Heterogeneity: Chi 2 =9.37,df=2(P=0.01);I 2 =79% Test for overall effect: Z = 5.50 (P < 0.00001) 2 Improvement in self-care Wong 2002 15 4.933 (6.147) 13 0.54 (1.854) 38.2 % 4.40 [ 1.13, 7.66 ] Wong 2007 12 1.875 (2.815) 9-2.22 (4.645) 34.8 % 4.10 [ 0.67, 7.52 ] Wong 2008 18 0.5 (6.366) 18 2.75 (5.531) 26.9 % -2.25 [ -6.15, 1.65 ] Subtotal (95% CI) 45 40 100.0 % 2.50 [ 0.48, 4.52 ] Heterogeneity: Chi 2 =7.83,df=2(P=0.02);I 2 =74% Test for overall effect: Z = 2.42 (P = 0.015) 3Improvementinmobility Wong 2002 15 11.867 (8.417) 13 1 (1.78) 10.3 % 10.87 [ 6.50, 15.24 ] Wong 2007 12 1.733 (5.123) 9 0.06 (0.167) 23.3 % 1.68 [ -1.22, 4.58 ] Wong 2008 18 0.306 (2.674) 18 0.61 (2.576) 66.5 % -0.31 [ -2.02, 1.41 ] Subtotal (95% CI) 45 40 100.0 % 1.30 [ -0.10, 2.70 ] Heterogeneity: Chi 2 =21.86,df=2(P=0.00002);I 2 =91% Test for overall effect: Z = 1.82 (P = 0.068) 4Improvementincognition Wong 2002 15 8.533 (6.534) 13 1.46 (2.025) 26.6 % 7.07 [ 3.59, 10.56 ] Wong 2007 12 10.34 (6.488) 9 1.96 (2.316) 20.5 % 8.38 [ 4.41, 12.35 ] Wong 2008 18 0.472 (3.16) 18-0.14 (4.321) 52.9 % 0.61 [ -1.86, 3.08 ] Subtotal (95% CI) 45 40 100.0 % 3.92 [ 2.13, 5.72 ] Heterogeneity: Chi 2 =14.87,df=2(P=0.00059);I 2 =87% Test for overall effect: Z = 4.28 (P = 0.000019) Significant differences were shown in total score, self-care and cognition domains -10-5 0 5 10 Favours control Favours treatment

Acupressure(A )+Conventional V.S Conventional(C) A C Primary Outcome Secondary Outcome Zhou 2008 X CRRC Chan 2009 X

Article Primary outcome Secondary outcome A+C V.S Sham+C Wong 2010a Wong 2010b RFRLRS X ABC RLDS WeeFIM SPT GMDS Leiter-R CGIS PEDI Wong 2002 RFRLRS X A+C V.S Wong 2007 Wong 2008 ATEC RFRLRS ABC ATES ADOS WeeFIM CGIS RLDS SPT SPT C Yan 2007 X CPEP Allam2008 X ALT A +C V.S C Wang2007 Zhou 2008 Chan 2009 ABC X X PPVT CRRC

WeeFIM domain P-value Wong 2010a 2010b Wong 2002 2007 2008 Cognition Cognition Self-care Total score P=0.024 P=0.000019 P=0.015 P<0.00001

Acupuncture for autism spectrum disorder(asd) Daniel KL Cheuk, Virginia Wong, Wen Xiong Chen, Cochrane Database Systemic Review. 2011 Sep. Acupuncture didn t seem to be effective in improving core features of ASD, but it may improve cognition development.

5A step 4--Applying

Q1: A1: Q2: A2: Q3: A3: Q4: A4:

5A step 5--Auditing

&*&o*^%^%$%x# $#@&

Take Home Message Autism spectrum disorder is not only autistic disorder Boy:Girl = 3-4:1 Complicated etiology, complicated symptom, complicated evaluation, complicated treatment A+C V.S C had a little bit of better effect on cognition development with no bad adverse effect.

age N(M:F) (n) (n) Liu 2008 1 ABC CARS ( x s ) n o x 3-9y/o 67(60:7) ABC (33) Selection Bias Blinding bias Attribution bias (34) Unclear High risk CARS ABC CARS 33 98. (Incomplete 21 8. 41 75. outcome 00 6. 76 3 data) 48. 58 4. 89 29. 45 2. 41 3 34 97. 25 8. 76 84. 89 7. 59 3 47. 30 4. 77 31. 27 2. 96 3 Reporting bias (Selective reporting) Low risk High risk 3 2008 35 2

age N(M:F) (n) (n) 202 (173:29) 45 2009 3 2009 5 2009 6

(CARS>42 ) 1 CARS

12 11 10 9 7 6

Grade of recommendation for nonbiological treatments in ASD Treatment Music therapy Vision therapy Acupuncture Auditory integration training Massage and yoga Neurofeedback Homeopathy Vagus nerve stimulator Grade A B C C C C D D A: Supported by at least 2 prospective randomized controlled trials (RCTs) or 1 systematic review B: Supported by at least 1 prospective RCT or 2 nonrandomized controlled trials C: Supported by at least 1 nonrandomized controlled trial or 2 case series D: Troublingly inconsistent or inconclusive studies or studies reporting no improvements Novel and emerging treatments for autism spectrum disorders: A systematic review, Daniel A. Rossignol, MD, FAAFP, Annals of Clinical Psychiatry 2009;21(4):213-236