Manual therapy with exercise for neck pain

  • Protocol
  • Intervention

Authors


Abstract

This is the protocol for a review and there is no abstract. The objectives are as follows:

This systematic review will assess the efficacy of manual therapy and exercise in the treatment of neck pain. We will assess the influence of manual therapy and exercise on pain, function, disability, patient satisfaction, quality of life and global perceived effect in adults experiencing neck pain with or without radicular symptoms and cervicogenic headache.

Background

Description of the condition

Neck pain is a common condition that is often disabling (Côté 2004; Strine 2007; Carroll 2008a; Hogg-Johnson 2008). Although many people with neck pain experience resolution of symptoms, a substantial portion of people experience neck pain that persists (Hogg-Johnson 2008; Kamper 2008; Hush 2011). Most of the financial burden associated with neck pain involves increased healthcare utilization and societal costs (e.g. time lost from employment, long-term care) associated with this subset of people, who experience persistent neck pain and disability (Côté 1998; Linton 1998; Borghouts 1999; Hansson 2005; Hogg-Johnson 2008; Martin 2008; Davis 2012; Jennum 2013).

Description of the intervention

The intervention under investigation in this review is the combination of manual therapy and exercise. In clinical practice, these interventions are often used in combination.

Manual therapy could include joint manipulation or mobilisation. Manipulation is a localised force of high velocity and low amplitude directed at specific spinal segments or regions. Mobilisations use low-velocity, small- or large-amplitude passive movement techniques or neuromuscular techniques within the patient's physiological range of motion. These techniques could be delivered to different body regions; however, the manual therapy approach had to be implemented with the intention to treat neck pain for the study to be included.

Exercise interventions could include stretching, range of motion, strengthening, motor control, proprioception and cognitive/affective and aerobic exercises.

How the intervention might work

We have previously discussed how exercise may work as an intervention (Kay 2012). Exercise provides both physical and mental benefits through its effects on numerous systems such as the cardiovascular system, immune system and nervous system, sleep, mood and the musculoskeletal system. Similarly, we have previously described the effects of mobilisation and manipulation (Gross 2010). Spinal manipulation or mobilisation has demonstrated neurophysiological effects that can influence pain, motor control and sympathetic nervous system activity (Souvlis 2004). Most studies suggest short-term effects, although scarce evidence of long-term effects is also present in the literature (Souvlis 2004; Martinez-Segura 2006; Bialosky 2009; Fritz 2011). Proposed neurophysiological effects include pain reduction through inhibition of nociceptors, changes in the dorsal horn and descending pathways of the spinal cord (Pickar 2002; Bialosky 2009; Haavik 2012). Neurophysiological changes are expected in the peripheral nervous system, spinal cord and brain (Bialosky 2009).

The effects of the combination of manual therapy and exercise could represent the effects of exercise, the effects of manual therapy or an interaction between manual therapy and exercise. A potential mechanism for an interaction between the two treatments occurs through learning and neuroplastic changes associated with both manual therapy and exercise. Exercise can influence neck pain through learning and neuroplastic changes in the spinal cord and brain; however, it has been suggested that hundreds of repetitions of movements in multiple contexts are needed to create cortical changes (van Vliet 2012). When manual therapy is performed alongside exercises, the short-term analgesic effects of manual therapy (Bialosky 2009) may allow a person with neck pain to perform the movement and exercise associated with lasting changes in pain and function (Kay 2012).

Why it is important to do this review

Recent systematic reviews published by The Cochrane Collaboration suggest that manipulation and exercise may be effective as single modal treatments for neck pain (Gross 2010; Kay 2012). In our previous review (Miller 2010), results supported the use of combined mobilisation or manipulation and exercise for short-term pain reduction over exercise alone. Also, this treatment combination provided greater short- and long-term improvements across multiple outcomes in comparison with manual therapy alone for people with chronic neck pain. The results of our previous review were inconclusive for (1) neck pain with radiculopathy and (2) manual therapy and exercise in comparison with various other treatments at short- and long-term follow-up. The previous systematic review was updated to July 2009. Several new randomised controlled trials have been published since that time; therefore, an update is warranted.

Objectives

This systematic review will assess the efficacy of manual therapy and exercise in the treatment of neck pain. We will assess the influence of manual therapy and exercise on pain, function, disability, patient satisfaction, quality of life and global perceived effect in adults experiencing neck pain with or without radicular symptoms and cervicogenic headache.

Methods

Criteria for considering studies for this review

Types of studies

Any published or unpublished randomised controlled trials (RCTs) in any language will be included.

Types of participants

Participants in the studies that will be included in this review are adults, 18 years of age or older, who are experiencing neck pain with or without cervicogenic headache (Olesen 1988) or radicular findings (Rubinstein 2007).

We will define symptom duration as acute (less than six weeks), subacute (six to 12 weeks) or chronic (12 weeks or longer).

Types of interventions

Studies to be included in the review will use a multimodal treatment approach that includes both manual therapy and exercise.

Manual therapy will include joint manipulation or mobilisation. Both manipulation and mobilisation involve a healthcare provider who is applying passive movements to the joints of the neck or back. Manipulation consists of high velocity and low amplitude of movement, and mobilisation consists of low velocity and small to large amplitude.

Any type of exercise will be included.

Types of outcome measures

This review will focus on outcomes that include pain relief, function, disability, quality of life (QOL), participant satisfaction and global perceived effect (GPE). Because of the lack of Gold Standard tools to measure these outcomes in this population, we will not restrict the search to any specific tools; however, in our past reviews, we have found a number of studies that did use validated tools. Function and disability could be measured by using either self-report measures or observer-based physical performance tests (Beattie 2001; Finch 2002).

The duration of follow-up will be defined as:

  • immediately post treatment (within one day);

  • short-term follow-up (one day to four weeks);

  • intermediate-term follow-up (closest to six months); and

  • long-term follow-up (closest to 12 months).

Primary outcomes  
Primary outcomes

The primary outcomes of interest will be changes in pain, disability and function.

Secondary outcomes

We will consider participant satisfaction, global perceived effect and quality of life to be secondary outcomes of interest.

Search methods for identification of studies

Electronic searches

A research librarian from the Cervical Overview Group will develop the search strategies and search computerized bibliographic databases, without language restrictions, for medical, chiropractic and allied health literature. Controlled vocabulary and keywords will be used to describe the condition of interest, the interventions, and a study design filter to identify randomized controlled trials. Search methods will be consistent with Furlan 2009 and Chapter 6 "Searching for Studies" of the Cochrane Handbook (Higgins 2011).

The following databases will be searched from inception to current: Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, AMED, and Cumulative Index to Nursing and Allied Health Literature (CINAHL).The strategies for these databases can be found in Appendix 1. In addition, the World Health Organization International Clinical Trials Registry Platform (WHO ICTRP http://apps.who.int/trialsearch/) and ClinicalTrials.gov will be searched for ongoing registered trials.

Searching other resources

We will screen reference sections of all retrieved full-text articles, identified content experts and conference proceedings from the World Confederation of Physical Therapists 2007–2011 and the International Federation of Orthopaedic and Manipulative Therapists 2008–2012 and will search personal files for grey literature.

Data collection and analysis

References of retrieved articles will be independently screened by two review authors, as recommended by the Cochrane Back Review Group (CBRG).

Selection of studies

Two review authors from a team of authors with expertise in medicine, physiotherapy, chiropractic, massage therapy, statistics or clinical epidemiology will independently conduct citation identification and study selection using pre-piloted forms. Agreement between raters will be assessed using the quadratic weighted kappa statistic (Kw) and Cicchetti weights (Cicchetti 1976). Disagreements will be resolved through consensus and consultation with a third review author when required.

Data extraction and management

At least two review authors will independently conduct data abstraction using pre-piloted forms. Disagreements will be resolved through consensus. A neutral third party will be consulted if consensus cannot be reached. Study authors will be contacted to obtain missing information and data clarification. We will extract data on design (RCT, numbers analysed/numbers randomly assigned, intention-to-treat analysis, power analysis), participants (disorder subtype, duration of disorder), interventions (treatment characteristics for treatment and comparison groups, dosage/treatment parameters, co-interventions, treatment schedules, duration of follow-up) and outcomes (baseline mean, end of study mean, absolute benefit, reported results, point estimate with 95% confidence interval (CI), power, adverse effects, cost of care and adverse events).

Assessment of risk of bias in included studies

At least two review authors will independently assess risk of bias for included studies using the 12-item CBRG risk of bias assessment (van Tulder 2003; Furlan 2009; Appendix 2). Disagreements will be resolved through consensus (Graham 2011). The Cervical Overview Group uses a calibrated team of assessors, and risk of bias tables will be presented and discussed by the broader validity assessment team to maximise inter-rater reliability (Graham 2011). We will not exclude studies from this review on the basis of risk of bias assessment results.

For each study, we will rate each criterion as 'low risk,' 'high risk' or 'unclear' to identify its performance against the criteria. Studies fulfilling at least six of 12 criteria and not having a fatal flaw will be judged as having ‘low risk of bias.’ Studies with a fatal flaw and those meeting fewer than six criteria will be judged as having ‘high risk of bias.’ Examples of fatal flaws include (1) a high dropout rate (>50% at the first and subsequent follow-up measurements); (2) an unacceptably low adherence rate; and (3) statistically and clinically relevant important baseline differences for one or more primary outcomes (i.e. pain, functional status), indicating unsuccessful randomisation.

Assessment of clinical relevance of included studies

Two review authors will independently assess the clinical relevance of each included study. We will use the five clinical relevance items recommended by the CBRG (Furlan 2009; Appendix 3). Each question will be answered Yes, No or Unclear, and disagreements between raters will be resolved by consensus. If consensus cannot be reached between the two review authors, a third review author will be asked to achieve consensus. Answers to the clinical relevance items will be used to inform the discussion of the clinical relevance of the review conclusions.

Measures of treatment effect

We plan to report standardised mean differences (SMDs) with 95% confidence intervals (CIs) for continuous data. Estimations of minimum clinically important differences (MCIDs) for pain, function and disability will be in accordance with CBRG recommendations (Furlan 2009). For the purposes of this review, the MCID for pain will be 10 on a 100-point pain intensity scale (Goldsmith 1993; Felson 1995; Farrar 2001). To assign some descriptors on the size of the difference between treatment and control groups, we will consider the effect to be small when it is less than 10% of the visual analogue scale (VAS), medium when it is between 10% and 20% of the VAS scale and large when it is 20% to 30% of the VAS scale. For the neck disability index (NDI), we will use an MCID of 7/50 neck disability index units (MacDermid 2009). It is noted that the minimal detectable change varies from 5/50 for non-complicated neck pain to 10/50 for cervical radiculopathy (MacDermid 2009). For other outcomes (i.e. global perceived effect and quality of life scales), when clear guidance on the size of clinically important effect sizes is absent, we will use the common hierarchy of Cohen 1988: small (0.20), medium (0.50) or large (0.80). Risk ratios (RRs) will be calculated for dichotomous outcomes.

Unit of analysis issues

We do not expect that cluster-randomised or cross-over trials have been carried out in manual therapy and exercise for neck pain. However, if we identify cluster-randomised or cross-over trials, we will follow the guidance provided in Chapters 16.3 and 16.4 of the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2011) in assessing their suitability and including them in the analysis, if appropriate.

Dealing with missing data

When data are not extractable, we will contact the primary authors. For continuous outcomes reported as medians, we will calculate effect size (Kendal 1963; p 237).

Assessment of heterogeneity

Before pooled effect measures are calculated, the reasonableness of pooling will be assessed on the basis of clinical judgement (duration of the disorder, intervention used, comparison group, outcomes measured and timing of follow-up). Clinically heterogeneous studies will be described separately, rather than combined. For clinically similar studies, we will test statistical heterogeneity by using the Chi2 test with a level of significance of 0.1. We will pool clinically similar studies with I2 < 80%. Studies with I2 between 40% and 79% will be pooled, but the grade of evidence will be downgraded for inconsistency. We will consider studies statistically homogenous with I2 < 40% and P value < 0.1.

Assessment of reporting biases

First, we will search for a published protocol (if no protocol is available, risk of reporting bias is rated as unclear). When the protocol is available, outcomes in the published report will be compared with those included in the protocol (including both outcome measures and timeline of assessments). Risk of reporting bias is low if the results from all prespecified outcomes have been adequately reported in the published report of the trial. Risk of reporting bias is high if one or more outcomes of interest are not measured or reported as prespecified, are not reported or are reported incompletely, so that data cannot be entered into a meta-analysis. If a group of trials with similar comparisons is identified and a subset of these trials have high risk of reporting bias, we will perform a sensitivity analysis in which we compare the magnitude of effect when all trials are included versus the magnitude of effect when only trials with low risk of reporting bias are included. We will also include a funnel plot, as recommended by the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2011).

Data synthesis

Dichotomous outcomes will be analysed by calculating the risk ratio (RR). Continuous outcomes will be analysed by calculating the mean difference (MD) when the same instrument is used to measure outcomes, or the standardised mean difference (SMD) when different instruments are used to measure outcomes. Uncertainty will be expressed with 95% CIs. Outcome measures from individual trials will be combined through meta-analysis when possible (clinical comparability of population, intervention, comparison and outcomes between trials) using a random-effects model. If a meta-analysis is not possible, the results from clinically comparable trials will be described in the text.

Regardless of whether sufficient data are available for use in quantitative analyses to summarise the data, we will assess the overall quality of the evidence for each outcome. To accomplish this, we will use the GRADE approach, as recommended in the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2011) and adapted in the updated CBRG method guidelines (Furlan 2009). The evidence grading method consists of four major domains.

  1. Risk of bias (described above). This criterion will be downgraded when > 25% of participants are obtained from studies with a high risk of bias (RoB).

  2. Consistency (degree to which results for a given comparison are consistent in terms of direction and significance). When a meta-analysis is performed, this criterion will be downgraded when results suggest statistical heterogeneity (I² > 40%). When a meta-analysis is not performed, this criterion will be downgraded if trials do not show statistically significant or non-significant effects in the same direction.

  3. Directness (the extent to which people, interventions and outcome measures are similar to those of interest). Inclusion of any of our outcomes (pain, function, disability, participant satisfaction, global perceived effect and quality of life) will be considered ‘direct evidence.’ Other measures, such as proportion of participants who improved and pressure or cold pain thresholds, will be considered indirect evidence; therefore this criterion will be downgraded. Comparisons that include only immediate post-treatment outcomes (not short-, intermediate-, or long-term follow-ups) will also be downgraded on the basis of this criterion.

  4. Precision (degree of variability/uncertainty around the pooled effect estimate). We will not downgrade the quality of the evidence in this domain on the basis of inclusion of a single study in a comparison or inability to perform a meta-analysis. The quality of evidence will be downgraded owing to imprecision when fewer than 70 participants are included per study arm in a comparison.

The overall quality of the evidence for a given outcome and comparison will be determined from the four domains above.

  1. High-quality evidence: Findings among at least 75% of RCTs are consistent, with low risk of bias; consistent, direct and precise data; and no known or suspected publication biases. Further research is unlikely to change the estimate or our confidence in the results.

  2. Moderate-quality evidence: One of the domains is not met. Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.

  3. Low-quality evidence: Two of the domains are not met. Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.

  4. Very low-quality evidence: Three of the domains are not met. We are very uncertain about the results.

  5. No evidence: No studies that addressed this outcome were identified.

Summary of findings tables

A summary of findings table will be generated for primary and secondary comparisons. Outcomes included in the summary of findings table will be pain, function, quality of life, participant satisfaction and global perceived effect. Comparisons will include manual therapy and exercise versus exercise alone, manual therapy and exercise versus manual therapy alone, manual therapy and exercise versus a control and manual therapy and exercise versus other treatment. Effect size, treatment advantage and quality of evidence will be presented in the table. A summary of findings will be reported, regardless of statistical heterogeneity, but when present, this will be reported.

Subgroup analysis and investigation of heterogeneity

Given the number of trials included in the previous review and the number of new trials available for review, we do not anticipate a large enough volume of data for performance of subgroup analysis.

Sensitivity analysis

We do not anticipate performing sensitivity analysis because of the small number of studies. When we find comparisons that include six or more trials with mixed risks of bias (low and high), we will conduct a sensitivity analysis by including only trials with low risk of bias to check whether this would change the main conclusions.

Acknowledgements

We would like to acknowledge the work of four students from the School of Rehabilitation Science at McMaster University in helping us prepare for this review: Alex Gurba, Sarah Kolbuc, Gurprit Sahota and Jeff Slemon.

Appendices

Appendix 1. Search strategies

MEDLINE - Ovid

1. Neck Pain/

2. exp Brachial Plexus Neuropathies/

3. exp neck injuries/ or exp whiplash injuries/

4. cervical pain.mp.

5. neckache.mp.

6. whiplash.mp.

7. cervicodynia.mp.

8. cervicalgia.mp.

9. brachialgia.mp.

10. brachial neuritis.mp.

11. brachial neuralgia.mp.

12. neck pain.mp.

13. neck injur*.mp.

14. brachial plexus neuropath*.mp.

15. brachial plexus neuritis.mp.

16. thoracic outlet syndrome/ or cervical rib syndrome/

17. Torticollis/

18. exp brachial plexus neuropathies/ or exp brachial plexus neuritis/

19. cervico brachial neuralgia.ti,ab.

20. cervicobrachial neuralgia.ti,ab.

21. (monoradicul* or monoradicl*).tw.

22. or/1-21

23. exp headache/ and cervic*.tw.

24. exp genital diseases, female/

25. genital disease*.mp.

26. or/24-25

27. 23 not 26

28. 22 or 27

29. neck/

30. neck muscles/

31. exp cervical plexus/

32. exp cervical vertebrae/

33. atlanto-axial joint/

34. atlanto-occipital joint/

35. Cervical Atlas/

36. spinal nerve roots/

37. exp brachial plexus/

38. (odontoid* or cervical or occip* or atlant*).tw.

39. axis/ or odontoid process/

40. Thoracic Vertebrae/

41. cervical vertebrae.mp.

42. cervical plexus.mp.

43. cervical spine.mp.

44. (neck adj3 muscles).mp.

45. (brachial adj3 plexus).mp.

46. (thoracic adj3 vertebrae).mp.

47. neck.mp.

48. (thoracic adj3 spine).mp.

49. (thoracic adj3 outlet).mp.

50. trapezius.mp.

51. cervical.mp.

52. cervico*.mp.

53. 51 or 52

54. exp genital diseases, female/

55. genital disease*.mp.

56. exp *Uterus/

57. 54 or 55 or 56

58. 53 not 57

59. 29 or 30 or 31 or 32 or 33 or 34 or 35 or 36 or 37 or 38 or 39 or 40 or 41 or 42 or 43 or 44 or 45 or 46 or 47 or 48 or 49 or 50 or 58

60. exp pain/

61. exp injuries/

62. pain.mp.

63. ache.mp.

64. sore.mp.

65. stiff.mp.

66. discomfort.mp.

67. injur*.mp.

68. neuropath*.mp.

69. or/60-68

70. 59 and 69

71. Radiculopathy/

72. exp temporomandibular joint disorders/ or exp temporomandibular joint dysfunction syndrome/

73. myofascial pain syndromes/

74. exp "Sprains and Strains"/

75. exp Spinal Osteophytosis/

76. exp Neuritis/

77. Polyradiculopathy/

78. exp Arthritis/

79. Fibromyalgia/

80. spondylitis/ or discitis/

81. spondylosis/ or spondylolysis/ or spondylolisthesis/

82. radiculopathy.mp.

83. radiculitis.mp.

84. temporomandibular.mp.

85. myofascial pain syndrome*.mp.

86. thoracic outlet syndrome*.mp.

87. spinal osteophytosis.mp.

88. neuritis.mp.

89. spondylosis.mp.

90. spondylitis.mp.

91. spondylolisthesis.mp.

92. or/71-91

93. 59 and 92

94. exp neck/

95. exp cervical vertebrae/

96. Thoracic Vertebrae/

97. neck.mp.

98. (thoracic adj3 vertebrae).mp.

99. cervical.mp.

100. cervico*.mp.

101. 99 or 100

102. exp genital diseases, female/

103. genital disease*.mp.

104. exp *Uterus/

105. or/102-104

106. 101 not 105

107. (thoracic adj3 spine).mp.

108. cervical spine.mp.

109. 94 or 95 or 96 or 97 or 98 or 106 or 107 or 108

110. Intervertebral Disk/

111. (disc or discs).mp.

112. (disk or disks).mp.

113. 110 or 111 or 112

114. 109 and 113

115. herniat*.mp.

116. slipped.mp.

117. prolapse*.mp.

118. displace*.mp.

119. degenerat*.mp.

120. (bulge or bulged or bulging).mp.

121. 115 or 116 or 117 or 118 or 119 or 120

122. 114 and 121

123. intervertebral disk degeneration/ or intervertebral disk displacement/

124. intervertebral disk displacement.mp.

125. intervertebral disc displacement.mp.

126. intervertebral disk degeneration.mp.

127. intervertebral disc degeneration.mp.

128. 123 or 124 or 125 or 126 or 127

129. 109 and 128

130. 28 or 70 or 93 or 122 or 129

131. animals/ not (animals/ and humans/)

132. 130 not 131

133. exp *neoplasms/

134. exp *wounds, penetrating/

135. 133 or 134

136. 132 not 135

137. Neck Pain/rh, th [Rehabilitation, Therapy]

138. exp Brachial Plexus Neuropathies/rh, th

139. exp neck injuries/rh, th or exp whiplash injuries/rh, th

140. thoracic outlet syndrome/rh, th or cervical rib syndrome/rh, th

141. Torticollis/rh, th

142. exp brachial plexus neuropathies/rh, th or exp brachial plexus neuritis/rh, th

143. or/137-142

144. Radiculopathy/rh, th

145. exp temporomandibular joint disorders/rh, th or exp temporomandibular joint dysfunction syndrome/rh, th

146. myofascial pain syndromes/rh, th

147. exp "Sprains and Strains"/rh, th

148. exp Spinal Osteophytosis/rh, th

149. exp Neuritis/rh, th

150. Polyradiculopathy/rh, th

151. exp Arthritis/rh, th

152. Fibromyalgia/rh, th

153. spondylitis/rh, th or discitis/rh, th

154. spondylosis/rh, th or spondylolysis/rh, th or spondylolisthesis/rh, th

155. or/144-154

156. 59 and 155

157. acupuncture/ or chiropractic/

158. exp Musculoskeletal Manipulations/

159. massage.tw.

160. mobili?ation.tw.

161. Acupuncture Therapy/

162. (acupuncture or acu-puncture or needling or acupressure or mox?bustion).tw.

163. ((neck or spine or spinal or cervical or chiropractic* or musculoskeletal* or musculo-skeletal*) adj3 (adjust* or manipulat* or mobiliz* or mobilis*)).tw.

164. (manual adj therap*).tw.

165. (manipulati* adj (therap* or medicine)).tw.

166. (massag* or reflexolog* or rolfing or zone therap*).tw.

167. Nimmo.mp.

168. exp Vibration/tu [Therapeutic Use]

169. (vibration adj5 (therap* or treatment*)).tw.

170. (Chih Ya or Shiatsu or Shiatzu or Zhi Ya).tw.

171. (flexion adj2 distraction*).tw.

172. (myofascial adj3 (release or therap*)).tw.

173. muscle energy technique*.tw.

174. trigger point.tw.

175. proprioceptive Neuromuscular Facilitation*.tw.

176. cyriax friction.tw.

177. (lomilomi or lomi-lomi or trager).tw.

178. aston patterning.tw.

179. (strain adj counterstrain).tw.

180. (craniosacral therap* or cranio-sacral therap*).tw.

181. (amma or ammo or effleuurage or petrissage or hacking or tapotment).tw.

182. Complementary Therapies/

183. ((complement* or alternat* or osteopthic*) adj (therap* or medicine)).tw.

184. (Tui Na or Tuina).tw.

185. or/157-184

186. 136 and 185

187. 143 or 156 or 186

188. animals/ not (animals/ and humans/)

189. 187 not 188

190. exp randomized controlled trials as topic/

191. randomized controlled trial.pt.

192. controlled clinical trial.pt.

193. (random* or sham or placebo*).tw.

194. placebos/

195. random allocation/

196. single blind method/

197. double blind method/

198. ((singl* or doubl* or trebl* or tripl*) adj25 (blind* or dumm* or mask*)).ti,ab.

199. (rct or rcts).tw.

200. (control* adj2 (study or studies or trial*)).tw.

201. or/190-200

202. 189 and 201

203. limit 202 to yr="2006 -Current"

204. limit 202 to yr="1902 -Current"

205. limit 202 to yr="1902 -2005"

206. guidelines as topic/

207. practice guidelines as topic/

208. guideline.pt.

209. practice guideline.pt.

210. (guideline? or guidance or recommendations).ti.

211. consensus.ti.

212. or/206-211

213. 189 and 212

214. limit 213 to yr="2006 -Current"

215. limit 213 to yr="1902 -2005"

216. meta-analysis/

217. exp meta-analysis as topic/

218. (meta analy* or metaanaly* or met analy* or metanaly*).tw.

219. review literature as topic/

220. (collaborative research or collaborative review* or collaborative overview*).tw.

221. (integrative research or integrative review* or intergrative overview*).tw.

222. (quantitative adj3 (research or review* or overview*)).tw.

223. (research integration or research overview*).tw.

224. (systematic* adj3 (review* or overview*)).tw.

225. (methodologic* adj3 (review* or overview*)).tw.

226. exp technology assessment biomedical/

227. (hta or thas or technology assessment*).tw.

228. ((hand adj2 search*) or (manual* adj search*)).tw.

229. ((electronic adj database*) or (bibliographic* adj database*)).tw.

230. ((data adj2 abstract*) or (data adj2 extract*)).tw.

231. (analys* adj3 (pool or pooled or pooling)).tw.

232. mantel haenszel.tw.

233. (cohrane or pubmed or pub med or medline or embase or psycinfo or psyclit or psychinfo or psychlit or cinahl or science citation indes).ab.

234. or/216-233

235. 189 and 234

236. limit 235 to yr="2006 -Current"

237. limit 235 to yr="1902 -2005"

238. (ae or to or po or co).fs.

239. (safe or safety or unsafe).tw.

240. (side effect* or side event*).tw.

241. ((adverse or undesirable or harm* or injurious or serious or toxic) adj3 (effect* or event* or reaction* or incident* or outcome*)).tw.

242. (abnormalit* or toxicit* or complication* or consequence* or noxious or tolerabilit*).tw.

243. or/238-242

244. 189 and 243

245. limit 244 to yr="2006 -Current"

246. limit 244 to yr="1902 -2005"

247. limit 202 to ed=20100701-20120321

248. limit 213 to ed=20100701-20120321

249. limit 235 to ed=20100701-20120321

250. limit 245 to ed=20100701-20120321

EMBASE—OVID

1. neck pain/

2. brachial plexus neuropathy/

3. neck injury/ or whiplash injury/

4. cervical pain.mp.

5. neckache.mp.

6. whiplash.mp.

7. cervicodynia.mp.

8. cervicalgia.mp.

9. brachialgia/

10. brachialgia.mp.

11. brachial neuritis.mp.

12. brachial neuralgia.mp.

13. neck pain.mp.

14. neck injur*.mp.

15. brachial plexus neuropath*.mp.

16. brachial plexus neuritis.mp.

17. thorax outlet syndrome/

18. torticollis/

19. cervico brachial neuralgia.ti,ab.

20. cervicobrachial neuralgia.ti,ab.

21. (monoradicul* or monoradicl*).tw.

22. or/1-21

23. exp headache/ and cervic*.tw.

24. exp gynecologic disease/

25. genital disease*.mp.

26. exp *uterine cervix/

27. or/24-26

28. 23 not 27

29. 22 or 28

30. neck/ or neck muscle/

31. cervical plexus/

32. cervical spine/

33. atlantoaxial joint/

34. atlantooccipital joint/

35. atlas/

36. "spinal root"/

37. brachial plexus/

38. (odontoid* or cervical or occip* or atlant*).tw.

39. odontoid process/

40. cervical vertebra.mp.

41. cervical vertebrae.mp.

42. cervical plexus.mp.

43. cervical spine.mp.

44. (neck adj3 muscles).mp.

45. (brachial adj3 plexus).mp.

46. (thoracic adj3 vertebra?).mp.

47. neck.mp.

48. (thoracic adj3 spine).mp.

49. (thoracic adj3 outlet).mp.

50. trapezius.mp.

51. cervical.mp.

52. cervico*.mp.

53. 51 or 52

54. exp gynecologic disease/

55. genital disease*.mp.

56. exp *uterine cervix/

57. 54 or 55 or 56

58. 53 not 57

59. 30 or 31 or 32 or 33 or 34 or 35 or 36 or 37 or 38 or 39 or 40 or 41 or 42 or 43 or 44 or 45 or 46 or 47 or 48 or 49 or 50 or 58

60. exp pain/

61. exp injury/

62. pain.mp.

63. ache.mp.

64. sore.mp.

65. stiff.mp.

66. discomfort.mp.

67. injur*.mp.

68. neuropath*.mp.

69. or/60-68

70. radiculopathy/

71. temporomandibular joint disorder/

72. myofascial pain/

73. spondylosis/ or cervical spondylosis/

74. neuritis/

75. exp arthritis/

76. fibromyalgia/

77. exp spondylitis/

78. diskitis/

79. spondylolisthesis/

80. radiculopathy.mp.

81. radiculitis.mp.

82. temporomandibular.mp.

83. myofascial pain syndrome*.mp.

84. spinal osteophytosis.mp.

85. neuritis.mp.

86. spondylosis.mp.

87. spondylitis.mp.

88. spondylolisthesis.mp.

89. or/70-88

90. 59 and 89

91. neck/

92. cervical spine/

93. neck.mp.

94. (thoracic adj3 vertebra?).mp.

95. cervical.mp.

96. cervico*.mp.

97. exp gynecologic disease/

98. genital disease*.mp.

99. exp *uterine cervix/

100. or/97-99

101. 95 or 96

102. 101 not 100

103. (thoracic adj3 spine).mp.

104. cervical spine.mp.

105. 91 or 92 or 93 or 94 or 102 or 103 or 104

106. intervertebral disk/

107. (disc or discs).mp.

108. (disk or disks).mp.

109. 106 or 107 or 108

110. 105 and 109

111. herniat*.mp.

112. slipped.mp.

113. prolapse*.mp.

114. displace*.mp.

115. degenerat*.mp.

116. (bulge or bulged or bulging).mp.

117. 110 or 111 or 112 or 113 or 114 or 115 or 116

118. 110 and 117

119. intervertebral disk hernia/

120. intervertebral disk degeneration/

121. intervertebral disc degeneration.mp.

122. intervertebral disk degeneration.mp.

123. intervertebral disc displacement.mp.

124. intervertebral disk displacement.mp.

125. 119 or 120 or 121 or 122 or 123 or 124

126. 105 and 125

127. 59 and 69

128. 29 or 90 or 118 or 126 or 127

129. exp *neoplasm/

130. exp *penetrating trauma/

131. 129 or 130

132. 128 not 131

133. neck pain/rh, th

134. brachial plexus neuropathy/rh, th

135. neck injury/ or whiplash injury/rh, th

136. brachialgia/rh, th

137. thorax outlet syndrome/rh, th

138. Torticollis/rh, th

139. Radiculopathy/rh, th

140. temporomandibular joint disorder/rh, th

141. myofascial pain/rh, th

142. spondylosis/rh, th or cervical spondylosis/rh, th

143. neuritis/rh, th

144. exp arthritis/rh, th

145. Fibromyalgia/rh, th

146. exp spondylitis/rh, th

147. diskitis/rh, th

148. spondylolisthesis/rh, th

149. acupuncture/ or acupressure/ or acupuncture analgesia/

150. exp manipulative medicine/

151. massage.tw.

152. mobili?ation.tw.

153. (acupuncture or acu-puncture or needling or acupressure or mox?bustion).tw.

154. ((neck or spine or spinal or cervical or chiropractic* or musculoskeletal* or musculo-skeletal*) adj3 (adjust* or manipulat* or mobiliz* or mobilis*)).tw.

155. (manual adj therap*).tw.

156. (manipulati* adj (therap* or medicine)).tw.

157. (massag* or reflexolog* or rolfing or zone therap*).tw.

158. Nimmo.tw.

159. (vibration adj5 (therap* or treatment*)).tw.

160. (Chih Ya or Shiatsu or Shiatzu or Zhi Ya).tw.

161. (flexion adj2 distraction*).tw.

162. (myofascial adj3 (release or therap*)).tw.

163. muscle energy technique*.tw.

164. trigger point.tw.

165. proprioceptive Neuromuscular Facilitation*.tw.

166. cyriax friction.tw.

167. (lomilomi or lomi-lomi or trager).tw.

168. aston patterning.tw.

169. (strain adj counterstrain).tw.

170. (craniosacral therap* or cranio-sacral therap*).tw.

171. (amma or ammo or effleuurage or petrissage or hacking or tapotment).tw.

172. alternative medicine/

173. ((complement* or alternat* or osteopthic*) adj (therap* or medicine)).tw.

174. (Tui Na or Tuina).tw.

175. (swedish massage or rolfing).tw.

176. therapeutic touch.mp.

177. massotherapy.tw.

178. effleurage.mp.

179. or/149-178

180. 132 and 179

181. 133 or 134 or 135 or 136 or 137 or 138

182. or/139-148

183. 59 and 182

184. 180 or 181 or 183

185. randomized controlled trial/

186. controlled clinical trial/

187. (random* or sham or placebo*).tw.

188. placebo/

189. randomization/

190. single blind procedure/

191. double blind procedure/

192. ((singl* or doubl* or trebl* or tripl*) adj5 (blind* or dumm*or mask*)).ti,ab.

193. (rct or rcts).tw.

194. (control* adj2 (study or studies or tiral*)).tw.

195. or/185-194

196. human/

197. nonhuman/

198. animal/

199. animal experiment/

200. or/197-199

201. 200 not (200 and 196)

202. 195 not 201

203. 184 and 202

204. limit 203 to yr="2006 -Current"

205. limit 203 to yr="1928 - 2005"

206. guidelines as topic/

207. practice guidelines as topic/

208. (guideline? or guidance or recommendations).ti.

209. consensus.ti.

210. or/206-209

211. 184 and 210

212. limit 211 to yr="2006 -Current"

213. limit 211 to yr="1928 - 2005"

214. meta analysis/

215. systematic review/

216. (meta analy* or metaanaly* or met analy* or metanaly*).tw.

217. (collaborative research or collaborative review* or collaborative overview*).tw.

218. (integrative research or integrative review* or intergrative overview*).tw.

219. (quantitative adj3 (research or review* or overview*)).tw.

220. (research integration or research overview*).tw.

221. (systematic* adj3 (review* or overview*)).tw.

222. (methodologic* adj3 (review* or overview*)).tw.

223. biomedical technology assessment/

224. (hta or thas or technology assessment*).tw.

225. ((hand adj2 search*) or (manual* adj search*)).tw.

226. ((electronic adj database*) or (bibliographic* adj database*)).tw.

227. ((data adj2 abstract*) or (data adj2 extract*)).tw.

228. (data adj3 (pooled or pool or pooling)).tw.

229. (analys* adj3 (pool or pooled or pooling)).tw.

230. mantel haenszel.tw.

231. (cochrane or Pubmed or pub med or medline or embase or psycinfo or psyclit or psychinfo or psychlit or cinahl or science citation index).ab.

232. or/214-231

233. 184 and 232

234. limit 233 to yr="2006 -Current"

235. limit 233 to yr="1928 - 2005"

236. (ae or co or si or to).fs.

237. (safe or safety or unsafe).tw.

238. (side effect* or side event*).tw.

239. ((adverse or undesirable or harm* or injurious or serious or toxic) adj3 (effect* or event* or reaction* or incident* or outcome*)).tw.

240. (abnormalit* or toxicit* or complication* or consequence* or noxious or tolerabilit*).tw.

241. or/236-240

242. 184 and 241

243. limit 242 to yr="2006 -Current"

244. limit 242 to yr="1928 - 2005"

245. limit 203 to em=201027-201216

246. limit 211 to em=201027-201216

247. limit 233 to em=201027-201216

248. limit 242 to em=201027-201216

CENTRAL—Ovid

1 Neck Pain/

2 exp Brachial Plexus Neuropathies/

3 exp neck injuries/ or exp whiplash injuries/

4 cervical pain.mp.

5 neckache.mp.

6 whiplash.mp.

7 cervicodynia.mp.

8 cervicalgia.mp.

9 brachialgia.mp.

10 brachial neuritis.mp.

11 brachial neuralgia.mp.

12 neck pain.mp.

13 neck injur*.mp.

14 brachial plexus neuropath*.mp.

15 brachial plexus neuritis.mp.

16 thoracic outlet syndrome/ or cervical rib syndrome/

17 Torticollis/

18 exp brachial plexus neuropathies/ or exp brachial plexus neuritis/

19 cervico brachial neuralgia.ti,ab.

20 cervicobrachial neuralgia.ti,ab.

21 (monoradicul* or monoradicl*).tw.

22 or/1-21

23 exp headache/ and cervic*.tw.

24 exp genital diseases, female/

25 genital disease*.mp.

26 or/24-25

27 23 not 26

28 22 or 27

29 neck/

30 neck muscles/

31 exp cervical plexus/

32 exp cervical vertebrae/

33 atlanto-axial joint/

34 atlanto-occipital joint/

35 Cervical Atlas/

36 spinal nerve roots/

37 exp brachial plexus/

38 (odontoid* or cervical or occip* or atlant*).tw.

39 axis/ or odontoid process/

40 Thoracic Vertebrae/

41 cervical vertebrae.mp.

42 cervical plexus.mp.

43 cervical spine.mp.

44 (neck adj3 muscles).mp.

45 (brachial adj3 plexus).mp.

46 (thoracic adj3 vertebrae).mp.

47 neck.mp.

48 (thoracic adj3 spine).mp.

49 (thoracic adj3 outlet).mp.

50 trapezius.mp.

51 cervical.mp.

52 cervico*.mp.

53 51 or 52

54 exp genital diseases, female/

55 genital disease*.mp.

56 exp *Uterus/

57 54 or 55 or 56

58 53 not 57

59 29 or 30 or 31 or 32 or 33 or 34 or 35 or 36 or 37 or 38 or 39 or 40 or 41 or 42 or 43 or 44 or 45 or 46 or 47 or 48 or 49 or 50 or 58

60 exp pain/

61 exp injuries/

62 pain.mp.

63 ache.mp.

64 sore.mp.

65 stiff.mp.

66 discomfort.mp.

67 injur*.mp.

68 neuropath*.mp.

69 or/60-68

70 59 and 69

71 Radiculopathy/ (121)

72 exp temporomandibular joint disorders/ or exp temporomandibular joint dysfunction syndrome/ (373)

73 myofascial pain syndromes/ (167)

74 exp "Sprains and Strains"/ (634)

75 exp Spinal Osteophytosis/ (83)

76 exp Neuritis/ (62)

77 Polyradiculopathy/ (9)

78 exp Arthritis/ (6553)

79 Fibromyalgia/ (427)

80 spondylitis/ or discitis/ (22)

81 spondylosis/ or spondylolysis/ or spondylolisthesis/ (96)

82 radiculopathy.mp. (233)

83 radiculitis.mp. (15)

84 temporomandibular.mp. (623)

85 myofascial pain syndrome*.mp. (211)

86 thoracic outlet syndrome*.mp. (14)

87 spinal osteophytosis.mp. (85)

88 neuritis.mp. (318)

89 spondylosis.mp. (158)

90 spondylitis.mp. (520)

91 spondylolisthesis.mp. (129)

92 or/71-91 (9396)

93 59 and 92 (699)

94 exp neck/ (318)

95 exp cervical vertebrae/ (515)

96 Thoracic Vertebrae/ (218)

97 neck.mp. (6889)

98 (thoracic adj3 vertebrae).mp. (233)

99 cervical.mp. (6237)

100 cervico*.mp. (378)

101 99 or 100 (6456)

102 exp genital diseases, female/ (8837)

103 genital disease*.mp. (470)

104 exp *Uterus/ (1262)

105 or/102-104 (9648)

106 101 not 105 (4639)

107 (thoracic adj3 spine).mp. (142)

108 cervical spine.mp. (441)

109 94 or 95 or 96 or 97 or 98 or 106 or 107 or 108 (11072)

110 Intervertebral Disk/ (188)

111 (disc or discs).mp. (1953)

112 (disk or disks).mp. (835)

113 110 or 111 or 112 (2478)

114 109 and 113 (227)

115 herniat*.mp. (507)

116 slipped.mp. (19)

117 prolapse*.mp. (692)

118 displace*.mp. (2183)

119 degenerat*.mp. (2406)

120 (bulge or bulged or bulging).mp. (97)

121 115 or 116 or 117 or 118 or 119 or 120 (5481)

122 114 and 121 (135)

123 intervertebral disk degeneration/ or intervertebral disk displacement/ (20)

124 intervertebral disk displacement.mp. (20)

125 intervertebral disc displacement.mp. (492)

126 intervertebral disk degeneration.mp. (10)

127 intervertebral disc degeneration.mp. (19)

128 123 or 124 or 125 or 126 or 127 (536)

129 109 and 128 (71)

130 28 or 70 or 93 or 122 or 129 (4411)

131 animals/ not (animals/ and humans/) (0)

132 130 not 131 (4411)

133 exp *neoplasms/ (32837)

134 exp *wounds, penetrating/ (188)

135 133 or 134 (33025)

136 132 not 135 (4084)

137 Neck Pain/rh, th [Rehabilitation, Therapy] (0)

138 exp Brachial Plexus Neuropathies/rh, th (15)

139 exp neck injuries/rh, th or exp whiplash injuries/rh, th (50)

140 thoracic outlet syndrome/rh, th or cervical rib syndrome/rh, th (3)

141 Torticollis/rh, th (12)

142 exp brachial plexus neuropathies/rh, th or exp brachial plexus neuritis/rh, th (15)

143 or/137-142 (80)

144 Radiculopathy/rh, th (0)

145 exp temporomandibular joint disorders/rh, th or exp temporomandibular joint dysfunction syndrome/rh, th (111)

146 myofascial pain syndromes/rh, th (0)

147 exp "Sprains and Strains"/rh, th (26)

148 exp Spinal Osteophytosis/rh, th (0)

149 exp Neuritis/rh, th (9)

150 Polyradiculopathy/rh, th (0)

151 exp Arthritis/rh, th (117)

152 Fibromyalgia/rh, th (0)

153 spondylitis/rh, th or discitis/rh, th (2)

154 spondylosis/rh, th or spondylolysis/rh, th or spondylolisthesis/rh, th (23)

155 or/144-154 (287)

156 59 and 155 (52)

157 acupuncture/ or chiropractic/ (224)

158 exp Musculoskeletal Manipulations/ (1318)

159 massage.tw. (979)

160 mobili?ation.tw. (1845)

161 Acupuncture Therapy/ (1375)

162 (acupuncture or acu-puncture or needling or acupressure or mox?bustion).tw. (4954)

163 ((neck or spine or spinal or cervical or chiropractic* or musculoskeletal* or musculo-skeletal*) adj3 (adjust* or manipulat* or mobiliz* or mobilis*)).tw. (525)

164 (manual adj therap*).tw. (201)

165 (manipulati* adj (therap* or medicine)).tw. (136)

166 (massag* or reflexolog* or rolfing or zone therap*).tw. (1062)

167 Nimmo.mp. (1)

168 exp Vibration/tu [Therapeutic Use] (0)

169 (vibration adj5 (therap* or treatment*)).tw. (74)

170 (Chih Ya or Shiatsu or Shiatzu or Zhi Ya).tw. (3)

171 (flexion adj2 distraction*).tw. (14)

172 (myofascial adj3 (release or therap*)).tw. (68)

173 muscle energy technique*.tw. (14)

174 trigger point.tw. (117)

175 proprioceptive Neuromuscular Facilitation*.tw. (56)

176 cyriax friction.tw. (0)

177 (lomilomi or lomi-lomi or trager).tw. (2)

178 aston patterning.tw. (0)

179 (strain adj counterstrain).tw. (10)

180 (craniosacral therap* or cranio-sacral therap*).tw. (4)

181 (amma or ammo or effleuurage or petrissage or hacking or tapotment).tw. (4)

182 Complementary Therapies/ (176)

183 ((complement* or alternat* or osteopthic*) adj (therap* or medicine)).tw. (887)

184 (Tui Na or Tuina).tw. (31)

185 or/157-184 (9965)

186 136 and 185 (600)

187 143 or 156 or 186 (677)

188 animals/ not (animals/ and humans/) (0)

189 187 not 188 (677)

190 limit 189 to yr="2010 - 2012" (97)

AMED—Ovid

1. neck pain/

2. Whiplash injuries/

3. cervical pain.mp.

4. neckache.mp.

5. neck ache.mp.

6. whiplash.mp.

7. cervicodynia.mp.

8. cervicalgia.mp.

9. brachialgia.mp.

10. brachial neuritis.mp.

11. brachial neuralgia.mp.

12. neck pain.mp.

13. neck injur*.mp.

14. brachial plexus neuropath*.mp.

15. brachial plexus neuritis.mp.

16. thoracic outlet syndrome?.mp.

17. cervical rib syndrome.mp.

18. torticollis/

19. cervico brachial neuralgia.ti,ab.

20. cervicobrachial neuralgia.ti,ab.

21. (monoradicul* or monoradicl*).tw.

22. or/1-21

23. exp headache/ and cervic*.tw.

24. exp genital diseases female/

25. genital disease.mp.

26. exp genitalia female/ or uterus/

27. or/24-26

28. 23 not 27

29. 22 or 28

30. neck/

31. neck muscles/

32. exp cervical plexus/

33. cervical vertebrae/ or atlas/ or axis/ or odontoid process/

34. atlanto axial joint/ or atlanto occipital joint/

35. spinal nerve roots/

36. exp brachial plexus/

37. (odontoid* or cervical or occip* or atlant*).tw.

38. thoracic vertebrae/

39. cervical vertebra?.mp.

40. cervical plexus.mp.

41. cervical spine.mp.

42. (neck adj3 muscles).mp.

43. (brachial adj3 plexus).mp.

44. (thoracic adj3 vertebra?).mp.

45. neck.mp.

46. (thoracic adj3 spine).mp.

47. (thoracic adj3 outlet).mp.

48. trapezius.mp.

49. cervical.mp.

50. cervico*.mp.

51. exp genital diseases female/

52. genital disease.mp.

53. exp genitalia female/ or uterus/

54. or/51-53

55. 49 or 50

56. 54 not 55

57. 30 or 31 or 32 or 33 or 34 or 35 or 36 or 37 or 38 or 39 or 40 or 41 or 42 or 43 or 44 or 45 or 46 or 47 or 48 or 56

58. exp pain/

59. injuries/

60. pain.mp.

61. ache.mp.

62. sore.mp.

63. stiff.mp.

64. discomfort.mp.

65. injur*.mp.

66. neuropath*.mp.

67. neuralgia.mp.

68. or/58-67

69. 57 and 68

70. radiculopathy.mp.

71. temporomandibular joint disease/ or temporomandibular joint syndrome/

72. myofasical pain.mp.

73. exp "sprains and strains"/

74. spinal osteophytosis/

75. exp neuritis/

76. Polyradiculopathy.mp.

77. exp arthritis/

78. fibromyalgia/

79. exp spondylitis/

80. discitis.mp.

81. diskitis.mp.

82. spondylolisthesis/ or spondylolysis/

83. radiculitis.mp.

84. temporomandibular.mp.

85. thoracic outlet syndrome?.mp.

86. spinal osteophytosis.mp.

87. neuritis.mp.

88. spondylosis.mp.

89. spondylitis.mp.

90. spondyloisthesis.mp.

91. or/70-90

92. 57 and 91

93. exp neck/

94. exp cervical vertebrae/

95. thoracic vertebrae/

96. neck.mp.

97. (thoracic adj3 vertebra?).mp.

98. cervical.mp.

99. cervico*.mp.

100. exp genital diseases female/

101. genital disease.mp.

102. exp genitalia female/ or uterus/

103. or/100-102

104. 98 or 99

105. 104 not 103

106. (thoracic adj3 spine).mp.

107. cervical spine.mp.

108. 93 or 94 or 95 or 96 or 97 or 106 or 107

109. intervertebral disk/

110. (disc or discs).mp.

111. (disk or disks).mp.

112. or/109-111

113. 108 and 112

114. herniat*.mp.

115. slipped.mp.

116. prolapse.mp.

117. displace*.mp.

118. degenerat*.mp.

119. (bulge or bulged or bulging).mp.

120. or/114-119

121. 113 and 120

122. intervertebral disk displacement/

123. intervertebral disk displacement.mp.

124. intervertebral disc displacement.mp.

125. intervertebral disk degeneration.mp.

126. intervertebral disc degeneration.mp.

127. or/122-126

128. 108 and 127

129. 29 or 69 or 92 or 121 or 128

130. exp neoplasms/

131. 129 not 130

132. acupuncture/

133. acupuncture therapy/ or exp acupoints/ or acupressure/ or acupuncture analgesia/ or ear acupuncture/ or meridians/ or moxibustion/ or needling/ or scalp acupuncture/

134. (acupuncture or acu-puncture or needling or acupressure or mox?bustion).tw.

135. exp musculoskeletal manipulations/ or exp manipulation chiropractic/ or spinal manipulation/

136. chiropractic/

137. ((neck or spine or spinal or cervical or chiropractic* or musculoskeletal* or musculo-skeletal*) adj3 (adjust* or manipulat* or mobiliz* or mobilis*)).tw.

138. (manual adj therap*).tw.

139. (manipulati* adj (therap* or medicine)).tw.

140. massage/

141. (massag* or reflexolog* or rolfing or zone therap*).tw.

142. (Chih Ya or Shiatsu or Shiatzu or Zhi Ya).tw.

143. (flexion adj2 distraction*).tw.

144. (myofasical adj3 (release or therap*)).tw.

145. muscle energy technique*.tw.

146. trigger point.tw.

147. proprioceptive Neuromuscular Facilitation*.tw.

148. cyriax friction.tw.

149. (lomilomi or lomi-lomi or trager).tw.

150. aston patterning.tw.

151. (strain adj counterstrain).tw.

152. (craniosacral therap* or cranio-sacral therap*).tw.

153. (amma or ammo or effleuurage or petrissage or hacking or tapotment).tw.

154. complementary therapies/

155. ((complement* or alternat* or osteopthic*) adj (therap* or medicine)).tw.

156. (mobili?ation or manipulation or massage).tw.

157. or/132-156

158. 131 and 157

159. randomized controlled trials/

160. randomized controlled trial.pt.

161. controlled clinical trial.pt.

162. (random* or sham or placebo*).tw.

163. placebos/

164. double blind method/ or random allocation/

165. ((singl* or doubl* or trebl* or tripl*) adj5 (blind* or dumm*or mask*)).ti,ab.

166. (rct or rcts).tw.

167. (control* adj2 (study or studies or tiral*)).tw.

168. or/159-167

169. 158 and 168

170. limit 169 to yr="2006 -Current"

171. limit 169 to yr="1887 - 2005"

172. practice guideline.pt.

173. (guideline? or guidance or recommendations).ti.

174. consensus.ti.

175. guidelines/ or practice guidelines/

176. or/172-175

177. 158 and 176

178. limit 177 to yr="2006 -Current"

179. limit 177 to yr="1887 - 2005"

180. meta analysis/

181. meta analysis.pt.

182. (meta analy* or metaanaly* or met analy* or metanaly*).tw.

183. (collaborative research or collaborative review* or collaborative overview*).tw.

184. (integrative research or integrative review* or intergrative overview*).tw.

185. (quantitative adj3 (research or review* or overview*)).tw.

186. (research integration or research overview*).tw.

187. (systematic* adj3 (review* or overview*)).tw.

188. (methodologic* adj3 (review* or overview*)).tw.

189. (hta or thas or technology assessment*).tw.

190. ((hand adj2 search*) or (manual* adj search*)).tw.

191. ((electronic adj database*) or (bibliographic* adj database*)).tw.

192. ((data adj2 abstract*) or (data adj2 extract*)).tw.

193. (data adj3 (pooled or pool or pooling)).tw.

194. (analys* adj3 (pool or pooled or pooling)).tw.

195. mantel haenszel.tw.

196. (cochrane or Pubmed or pub med or medline or embase or psycinfo or psyclit or psychinfo or psychlit or cinahl or science citation index).ab.

197. or/180-196

198. 158 and 197

199. limit 198 to yr="2006 -Current"

200. limit 198 to yr="1887 - 2005"

201. (safe or safety or unsafe).tw.

202. (side effect* or side event*).tw.

203. ((adverse or undesirable or harm* or injurious or serious or toxic) adj3 (effect* or event* or reaction* or incident* or outcome*)).tw.

204. (abnormalit* or toxicit* or complication* or consequence* or noxious or tolerabilit*).tw.

205. adverse effects/

206. or/201-205

207. 158 and 206

208. limit 207 to yr="2006 -Current"

209. limit 207 to yr="1887 - 2005"

210. limit 169 to yr="2010 - current"

211. limit 177 to yr="2010 - current"

212. limit 198 to yr="2010 - current"

213. limit 207 to yr="2010 - current"

CINAHL—EBSCO

S139. S115 and S131

S138. S115 and S131

S137. S109 and S131

S136. S109 and S131

S135. S94 and S131

S134. S94 and S131

S133. S91 and S131

S132. S91 and S131

S131. S82 and S130

S130. S116 or S117 or S118 or S119 or S120 or S121 or S122 or S123 or S124 or S125 or S126 or S127 or S128 or S129

S129. TX ( ((complement* or alternat* or osteopthic*) N1 (therap* or medicine)) ) OR TX ( (Tui Na or Tuina) )

S128. TX (strain N1 counterstrain) OR TX ( (craniosacral therap* or cranio-sacral therap*) ) OR TX ( (amma or ammo or effleuurage or petrissage or hacking or tapotment) )

S127. TX cyriax friction OR TX ( (lomilomi or lomi-lomi or trager) ) OR TX aston patterning

S126. TX muscle energy technique* OR TX trigger point OR TX proprioceptive Neuromuscular Facilitation*

S125. TX ( (Chih Ya or Shiatsu or Shiatzu or Zhi Ya) ) OR TX (flexion N2 distraction*) OR TX ( (myofascial N3 (release or therap*)) )

S124. (MH "Vibration/TU")

S123. TX ( (massag* or reflexolog* or rolfing or zone therap*) ) OR TX Nimmo OR TX ( (vibration N5 (therap* or treatment*)) )

S122. TX (manipulati* N1 (therap* or medicine))

S121. TX ((neck or spine or spinal or cervical or chiropractic* or musculoskeletal* or musculo-skeletal*) N3 (adjust* or manipulat* or mobiliz* or mobilis*))

S120. TX mobili?ation OR TX ( (acupuncture or acu-puncture or needling or acupressure or mox?bustion) ) OR TX manual therapy

S119. (MH "Massage+") OR (MH "Deep Tissue Massage") OR (MH "Neuromuscular Massage") OR (MH "Sports Massage") OR (MH "Massage Therapists") OR (MH "Swedish Massage")

S118. (MH "Manipulation, Chiropractic") OR (MH "Manual Therapy+")

S117. (MH "Chiropractic+") OR (MH "Manipulation, Chiropractic") OR (MH "Chiropractic Practice") OR (MH "Chiropractors")

S116. (MH "Acupuncture+") OR (MH "Acupuncture Points") OR (MH "Acupuncturists")

S115. S110 or S111 or S112 or S113 or S114

S114. TX toxic reaction OR TX allergic reaction OR TX complications

S113. TX adverse outcome* OR TX adverse incident*

S112. TX adverse event* OR TX adverse effect* OR TX adverse reaction*

S111. TX ( (safe or safety or unsafe) ) OR TX ( (side effect* or side event*) )

S110. (MH "Adverse Drug Event")

S109. S95 or S96 or S97 or S98 or S99 or S100 or S101 or S102 or S103 or S104 or S105 or S106 or S107 or S108

S108. TX PsycINFO or TX psycLIT or TX PsychINFO or TX psychLIT or TX CINAHL

S107. TX cochrane or TX pubmed or TX pub med or TX medline or TX embase

S106. TX mantel haenszel

S105. TX data N2 pool* or TX analys* N2 pool*

S104. TX data N2 abstract* or TX data N2 extract*

S103. TX electronic N2 database* or TX bibliographic database*

S102. TX hand N2 search* or TX manual N2 search

S101. TX hta or TX htas or TX technology assessment*

S100. TX methodologic* N3 review* or TX methodologic* N3 overview*

S99. TX systematic* N3 review* or TX systematic* N3 overview*

S98. TX quantitative research or TX quantitative review* or TX quantitative overview*

S97. TX meta analy* or TX metaanaly* or TX met analy* or TX metanaly*

S96. (MH "Meta Analysis")

S95. PT systematic review

S94. S92 or S93

S93. TI guideline* or TI guidance or TI recommendations or TI consensus

S92. (MH "Practice Guidelines")

S91. S83 or S84 or S85 or S86 or S87 or S88 or S89 or S90

S90. TX control* N2 study or TX control* N2 studies or TX control N2 trial*

S89. TX RCT or TX RCTs

S88. TX (singl* N1 (blind* OR dumm* OR mask*))

S87. (MH "Random Sample+")

S86. (MH "Placebos")

S85. TX random* or TX sham or TX placebo*

S84. PT clinical trial or PT randomized controlled trial

S83. (MH "Clinical Trials+")

S82. S78 NOT S81

S81. S79 or S80

S80. (MM "Pregnancy+")

S79. (MM "Abortion, Induced+")

S78. S74 NOT S77

S77. S75 or S76

S76. (MM "Wounds, Penetrating+")

S75. (MM "Neoplasms+")

S74. S16 or S41 or S56 or S69 or S73

S73. S63 and S72

S72. S70 or S71

S71. TX intervertebral disk displacement or TX intervertebral disc displacement or TX intervertebral disk degeneration or TX intervertebral disc degeneration

S70. (MH "Intervertebral Disk Displacement")

S69. S67 and S68

S68. TX herniat* or TX slipped or TX prolapse* or TX displace* or TX degenerat* or TX ( bulged OR bulge OR bulging )

S67. S63 and S66

S66. S64 or S65

S65. TX disc or TX discs or TX disk or TX disks

S64. (MH "Intervertebral Disk")

S63. S61 NOT S62

S62. (MM "Genital Diseases, Female+") or ( (MM "Cervix") or (MM "Cervix Diseases") )

S61. S57 or S58 or S59 or S60

S60. TX thoracic N3 spine or TX cervical spine or TX cervico*

S59. TX neck or TX thoracic N3 vertebr*

S58. (MH "Thoracic Vertebrae")

S57. (MH "Neck")

S56. S34 and S55

S55. S42 or S43 or S44 or S45 or S46 or S47 or S48 or S49 or S50 or S51 or S52 or S53 or S54

S54. TX neuritis or TX spondylosis or TX spondylitis or TX spondylolisthesis

S53. TX myofascial pain syndome* or TX thoracic outlet syndrome* or TX spinalosteophytosis

S52. TX radiculopathy or TX radiculitis or TX temporomandibular

S51. (MH "Spondylolysis") or (MH "Spondylolisthesis+")

S50. (MH "Fibromyalgia")

S49. (MH "Arthritis+")

S48. (MH "Polyradiculopathy")

S47. (MH "Neuritis+")

S46. (MH "Spinal Osteophytosis")

S45. (MH "Sprains and Strains+")

S44. (MH "Myofascial Pain Syndromes+")

S43. (MH "Temporomandibular Joint Diseases+") or (MH "Temporomandibular Joint Syndrome")

S42. (MH "Radiculopathy")

S41. S34 and S40

S40. S35 or S36 or S37 or S38 or S39

S39. (MH "Neuralgia")

S38. TX stiff or TX discomfort or TX injur* or TX neuropath*

S37. TX pain or TX ache* or TX sore

S36. (MH "Wounds and Injuries+")

S35. (MH "Pain+")

S34. S33 NOT S32

S33. S17 or S18 or S19 or S20 or S21 or S22 or S23 or S24 or S25 or S26 or S27 or S28 or S29 or S30 or S31

S32. (MM "Genital Diseases, Female+") or ( (MM "Cervix") or (MM "Cervix Diseases") )

S31. TX trapezius or TX cervico*

S30. TX thoracic N3 spine or TX thoracic N3 outlet

S29. TX neck

S28. TX thoracic N3 verteb*

S27. TX brachial N3 plexus

S26. TX neck n3 muscles

S25. (MH "Thoracic Vertebrae")

S24. TX ondontoid* or TX cervical or TX occip* or TX atlant*

S23. (MH "Brachial Plexus+")

S22. (MH "Spinal Nerve Roots+")

S21. (MH "Atlanto-Axial Joint") or (MH "Atlanto-Occipital Joint")

S20. (MH "Cervical Vertebrae+") or (MH "Cervical Atlas")

S19. (MH "Cervical Plexus+")

S18. (MH "Neck")

S17. (MH "Neck Muscles+")

S16. S10 or S15

S15. S11 NOT S14

S14. S12 or S13

S13. (MM "Cervix") or (MM "Cervix Diseases")

S12. (MM "Genital Diseases, Female+")

S11. (MH "Headache+") and TX cervic*

S10. S1 or S2 or S3 or S4 or S5 or S6 or S7 or S8 or S9

S9. (MH "Brachial Plexus Neuritis")

S8. TX cervical brachial neuralgia

S7. TX cervical rib sydrome* or TX cervico brachial neuralgia or TX cervicobrachial neuralgia or TX monoradicul* or TX monoradicl*

S6. (MH "Thoracic Outlet Syndrome") or (MH "Torticollis")

S5. TX brachial neuralgia or TX neck pain or TX neck injur* or TX brachial plexus neuropath* or TX brachial plexus neuralgia or TX brachial plexus neuritis

S4. TX cervicalgia or TX brachialgia or TX brachial neuritis

S3. TX cervical pain or TX neckache or TX neck ache or TX whiplash or TX cervicodynia

S2. (MH "Neck Injuries+")

S1. (MH "Neck Pain") or (MH "Brachial Plexus Neuropathies") or (MH "Brachial Plexus Neuritis")

Appendix 2. Criteria for assessing risk of bias for internal validity

Random sequence generation (selection bias)

Selection bias (biased allocation to interventions) due to inadequate generation of a randomised sequence

Risk of selection bias is low if investigators describe a random component in the sequence generation process, such as referring to a random number table; using a computer random number generator; tossing a coin; shuffling cards or envelopes; throwing dice; drawing lots; and performing minimisation (minimisation may be implemented without a random element, and this is considered to be equivalent to being random).

Risk of selection bias is high if investigators describe a non-random component in the sequence generation process, such as sequence generated by odd or even date of birth; date (or day) of admission; hospital or clinic record number; or allocation by judgement of the clinician, preference of the participant, results of a laboratory test or a series of tests or availability of the intervention.

Allocation concealment (selection bias)

Selection bias (biased allocation to interventions) due to inadequate concealment of allocations before assignment

Risk of selection bias is low if participants and investigators enrolling participants could not foresee assignment because one of the following, or an equivalent method, was used to conceal allocation: central allocation (including telephone, web-based and pharmacy-controlled randomisation); sequentially numbered drug containers of identical appearance; or sequentially numbered, opaque, sealed envelopes.

Risk of bias is high if participants or investigators enrolling participants could possibly foresee assignments and thus introduce selection bias, such as allocation based on using an open random allocation schedule (e.g. a list of random numbers); assignment envelopes without appropriate safeguards (e.g. if envelopes were unsealed or non-opaque or were not sequentially numbered); alternation or rotation; date of birth; case record number; or other explicitly unconcealed procedures.

Blinding of participants

Performance bias due to knowledge of allocated interventions by participants during the study

Risk of performance bias is low if blinding of participants was ensured, and it was unlikely that the blinding could have been broken; or if no or incomplete blinding was provided, but the review authors judge that the outcome is not likely to be influenced by lack of blinding.

Blinding of personnel/care providers (performance bias)

Performance bias due to knowledge of allocated interventions by personnel/care providers during the study

Risk of performance bias is low if blinding of personnel was ensured and it was unlikely that the blinding could have been broken; or if no or incomplete blinding was provided, but the review authors judge that the outcome is not likely to be influenced by lack of blinding.

Blinding of outcome assessor (detection bias)

Detection bias due to knowledge of allocated interventions by outcome assessors

Risk of detection bias is low if blinding of the outcome assessment was ensured and it was unlikely that the blinding could have been broken; or if no or incomplete blinding was provided, but the review authors judge that the outcome is not likely to be influenced by lack of blinding, or:

  • for participant-reported outcomes in which the participant was the outcome assessor (e.g. pain, disability): Risk of bias for outcome assessors is low if risk of bias is low for participant blinding (Boutron 2005);

  • for outcome criteria that are clinical or therapeutic events that will be determined by the interaction between participants and care providers (e.g. co-interventions, length of hospitalisation, treatment failure), in which the care provider is the outcome assessor: Risk of bias for outcome assessors is low if risk of bias for care providers is low (Boutron 2005); and

  • for outcome criteria assessed from data from medical forms: Risk of bias is low if treatment or adverse effects of treatment could not be noticed in the extracted data (Boutron 2005).

Incomplete outcome data (attrition bias)

Attrition bias due to quantity, nature or handling of incomplete outcome data

Risk of attrition bias is low if no outcome data were missing; reasons for missing outcome data were unlikely to be related to the true outcome (for survival data, censoring is unlikely to be introducing bias); missing outcome data were balanced in numbers, with similar reasons for missing data across groups; for dichotomous outcome data, the proportion of missing outcomes compared with the observed event risk was not enough to have a clinically relevant impact on the intervention effect estimate; for continuous outcome data, the plausible effect size (difference in means or standardised difference in means) among missing outcomes was not enough to have a clinically relevant impact on observed effect size, or missing data were imputed using appropriate methods (if dropout numbers are very large, imputation using even "acceptable" methods may still suggest a high risk of bias) (van Tulder 2003). Percentages of withdrawals and dropouts should not exceed 20% for short-term follow-up and 30% for long-term follow-up and should not lead to substantial bias (these percentages are commonly used but arbitrary and are not supported by the literature) (van Tulder 2003).

Selective reporting (reporting bias)

Reporting bias due to selective outcome reporting

Risk of reporting bias is low if the study protocol is available and all of the study's prespecified (primary and secondary) outcomes that are of interest in the review have been reported in the prespecified way, or if the study protocol is not available but it is clear that published reports include all expected outcomes, including those that were prespecified (convincing text of this nature may be uncommon).

Risk of reporting bias is high if not all of the study's prespecified primary outcomes have been reported; one or more primary outcomes are reported using measurements, analysis methods or subsets of the data (e.g. subscales) that were not prespecified; one or more reported primary outcomes were not prespecified (unless clear justification for their reporting is provided, such as an unexpected adverse effect); one or more outcomes of interest in the review are reported incompletely so that they cannot be entered into a meta-analysis; or the study report fails to include results for a key outcome that would be expected to have been reported for such a study.

Group similarity at baseline (selection bias)

Bias is due to dissimilarity at baseline for the most important prognostic indicators. 

Risk of bias is low if groups are similar at baseline for demographic factors, value of main outcome measure(s) and important prognostic factors (examples in the field of back and neck pain are duration and severity of complaints, vocational status, percentage of participants with neurological symptoms) (van Tulder 2003).

Co-interventions (performance bias)

Bias because co-interventions were different across groups

Risk of bias is low if no co-interventions were provided, or if they were similar between index and control groups (van Tulder 2003).

Compliance (performance bias)

Bias due to inappropriate compliance with interventions across groups

Risk of bias is low if compliance with interventions was acceptable based on reported intensity/dosage, duration, number and frequency for both index and control intervention(s). For single-session interventions (e.g. surgery), this item is irrelevant (van Tulder 2003).

Intention-to-treat analysis

Risk of bias is low if all randomly assigned participants were reported/analysed in the group to which they were allocated by randomisation.   

Timing of outcome assessments (detection bias)

Bias because important outcomes were not measured at the same time across groups

Risk of bias is low if all important outcome assessments for all intervention groups were measured at the same time (van Tulder 2003).

Other bias

Bias due to problems not covered elsewhere in the table

Risk of bias is low if the study appears to be free of other sources of bias not addressed elsewhere (e.g. study funding).

Appendix 3. Questions for clinical relevance

1. Are the patients described in detail so that you can decide whether they are comparable with those that you see in your practice?

2. Are the interventions and treatment settings described well enough that you can provide the same for your patients?

3. Were all clinically relevant outcomes measured and reported?

4. Is the size of the effect clinically important?

5. Are the likely treatment benefits worth the potential harms?

Contributions of authors

This is one review of a series conducted by the Cervical Overview Group: Gross A, Goldsmith C, Graham N, Santaguida PL, Burnie S, Miller J, Peloso P, Kay T, Kroeling P, Trinh K, Langevin P, Patel K, Haines T, Haraldsson B, Radylovick Z, Forget M, Szeto G, LeBlanc F, Ezzo J, Morien A, Rice M, Perry L, Fraser M, Voth S, Rutherford , Lolwcock J, Dziengo S, Cameron I, Wang Z, Quyun Shi M, Lilge L, White R, Bronfort G, Hoving J.

Primary review authors: Jordan Miller, Anita Gross, Alex Gurba, Sarah Kolbuc, Paul Sahota, Jeff Slemon, Theresa Kay, Nadine Graham, Stephen Burnie, Charles H. Goldsmith, Gert Brønfort, Jan Hoving, Joy MacDermid

Statistician: Charles H. Goldsmith

Methodological quality assessment: Stephen Burnie, Nadine Graham, Charles H. Goldsmith, M. Forget, G. Szeto, F. LeBlanc, J. Ezzo

Study identification and selection: D. Brunarski, T. Haines, Nadine Graham, Anita Gross, O. Boers

Research librarian: M. Rice

Data abstraction and synthesis, manuscript preparation, public responsibility, grants, administration: primary review authors

Final synthesis: primary review authors

Declarations of interest

Gert Brønfort and Jan Hoving are primary authors on trials that will be included in this review. They will not be involved in article selection or quality evaluation for those articles.

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