Effects of cognitive behavior therapy on patients with chronic whiplash-associated disorders: a systematic review and meta-analysis

Effects of cognitive behavior therapy on patients with chronic whiplash-associated disorders: a systematic review and meta-analysis | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Effects of cognitive behavior therapy on patients with chronic whiplash-associated disorders: a systematic review and meta-analysis Yu Kondo, Takahiro Miki, Hiroshi Kurakata, Tsuneo Takebayashi, and 1 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-1360019/v2 This work is licensed under a CC BY 4.0 License Status: Posted Version 2 posted You are reading this latest preprint version Show more versions Abstract Background: To determine the effectiveness of cognitive behavioral therapy (CBT) alone and a combination of physical interventions and CBT on pain, disability, quality of life, and psychological parameters in patients with chronic whiplash-associated disorders (WADs). Methods: Several databases were systematically searched for randomized controlled trials (RCTs). Pooled effects were analyzed as standardized mean differences (SMD) and 95% confidence intervals (CI). We assessed the quality of the evidence using the Grading of Recommendations, Assessment, Development, and Evaluation approach. Results: In total, 2,287 RCTs were found; among them, eight were included. Two RCTs, we found low evidence that CBT was better than the wait-and-see control group in improving disability (SMD, −0.61; 95% CI, −1.21 to −0.01) and psychological status, such as fear of physical activity (SMD, −1.04; 95% CI, −1.67 to −0.41), in the short-term. In addition, two RCTs, we found moderate evidence that CBT combined with physical interventions was better than what was advised in improving disability (SMD, −0.29; 95% CI, −0.53 to −0.06) in the long-term. Conclusion: The study found moderately favorable evidence of the combined effect of physical interventions and CBT against advice alone in long-term disability. whiplash-associated disorders cognitive behavior therapy systematic review Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 Figure 8 Figure 9 Figure 10 Figure 11 Introduction Chronic whiplash-associated disorders (WADs) often include not only physical but also diverse psychological and cognitive impairments (M. Sterling, 2014), whose characteristics are different from those of chronic idiopathic neck pain (Coppieters et al., 2017 ; Ris et al., 2017 ). Therefore, clinical practice guidelines suggest providing a Bio-Psycho-Social model of care to individuals with chronic WADs by including psychological interventions (Scholten-Peeters et al., 2002 ). One intervention commonly suggested by clinical practice guidelines is cognitive behavior therapy (CBT). CBT helps in cognitive reconditioning and behavioral modifications of specific activities (Butler, Chapman, Forman, & Beck, 2006 ; Flor & Turk, 1984 ; Morley, 2011 ). In 2015, Monticone et al. (Monticone et al., 2015 ) have conducted a meta-analysis to investigate the effects of CBT alone on chronic neck pain. In their meta-analysis, patients with nonspecific neck pain and those with WADs were combined, limiting the clinical implications due to different characteristics of chronic WADs and idiopathic neck pain. Therefore, performing a new analysis by limiting participants to those with chronic WADs is necessary. Investigating the effects of CBT alone on chronic WADs by performing a meta-analysis is an important step in considering the advantages of including CBT in the Bio-Psycho-Social model of care. However, note that CBT is a psychological intervention, not a Bio-Psycho-Social intervention (Urits et al., 2019 ). Therefore, understanding the effects of combining physical interventions and CBT on chronic WADs is clinically useful. In 2016, Shearer et al. (Shearer et al., 2016 ) have investigated the effects of a combination of physical interventions and CBT on chronic WADs in a systematic review involving the literature from 1990 to 2015. However, data synthesis was not undertaken due to the absence of multiple studies. We found multiple randomized controlled trials (RCTs) to be included in a meta-analysis (Michaleff et al., 2014 ; M. J. Stewart et al., 2007), and we found another eligible RCT in 2020 (Andersen et al., 2020 ). Therefore, an updated systematic review was necessary to understand the effects of the combination of physical interventions and CBT on chronic WADs. This systematic review with meta-analysis has two purposes. First is to investigate the effects of CBT alone on pain, disability, quality of life (QoL), and psychological parameters in patients with chronic WADs. Second is to investigate the effects of the combination of physical interventions and CBT compared with those of CBT alone on pain, disability, QoL, and psychological parameters on patients with chronic WADs. Methods Protocol Registration and Search Strategy This review was preregistered in PROSPERO (CRD42020193904) and conducted according to the updated Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines (Moher, Liberati, Tetzlaff, Altman, & Group, 2009 ). The following items were modified after the initial registration in PROSPERO: 1) Review questions were added to investigate the effects of the combination of physical interventions and CBT; 2) the definition of chronic WADs were defined as symptoms lasting for ≥ 3 months, which was revised from symptoms lasting for ≥ 6 months; 3) studies with one author were also included; and 4) the PsycINFO database was excluded due to limited access to the database. An author (HK) systematically searched the following databases from inception to January 2021: CINAHL, Web of Science, MEDLINE, Embase, EMCare, and Physiotherapy Evidence Database (PEDro). The search strategies are presented in Appendix 1. Study Selection Screening and full-text inspection were performed by two authors (YK and TM) independently. Any disagreements on eligibility were resolved by discussion. Cross-referencing was performed with hand searches of the reference lists of studies included in the full-text screening. Eligibility Criteria All RCTs published as full-text articles were eligible for inclusion in this systematic review. No restrictions on language were employed. Eligible participants were as follows: 1) adult individuals (≥ 18 years of age) with WADs with a whiplash injury grade of I, II, or III in the Quebec Task Force Classification (Spitzer et al., 1995 ), 2) patients from primary, secondary, or tertiary care institutions, and 3) patients with any persistent symptoms, such as musculoskeletal pain, sensorimotor control disturbances, and psychological problems, for more than 3 months after the accident. Studies with the following participants were excluded from this systematic review: 1) patients with a cervical fracture or dislocation, 2) patients with injuries in other body areas other than the neck during the accident causing WAD, and 3) patients with previous WADs, preexisting neck pain, or previous neck surgery. Eligible interventions were CBT with and without physical interventions. No consensus was made for a specific definition of CBT (Lamb et al., 2010 ); thus, CBT was identified in this study when the following criteria reported by Richmond et al. (Richmond et al., 2015 ) were satisfied: 1) treatments based on cognitive–behavioral principles that were explicitly or implicitly stated (Fisher et al., 2018 ; Gatchel, Peng, Peters, Fuchs, & Turk, 2007 ; Turk & Flor, 1984 ); 2) interventions using both cognitive and behavioral strategies were used in the same treatment package; 3) CBT was provided by an experienced healthcare professional; and 4) when multimodal treatments were provided, the intervention was assumed to be based on a CBT principle. Any disagreements in selecting CBT techniques were resolved through a discussion between the authors by contacting the corresponding authors of the study for additional information or by finding a process paper associated with the study that provided further information. Eligible comparisons included any type of a single intervention or a wait-and-see control. Eligible primary outcomes included pain intensity, disability, QoL, and eligible secondary outcomes included psychological status. In addition, adverse events were recorded where mentioned. For pain intensity, when more than one patient-reported outcome measure (PROM) was reported, a numerical rating scale was used in the analysis, followed by a visual analog scale. For disability, when more than one PROM was reported, the Neck Disability Index (NDI) was used in the analysis. For QoL, when more than one PROM was reported, the 36-Item Short Form Health Survey (SF-36) was used in the analysis, followed by the 12-Item Short Form Health Survey (SF-12) and the EuroQol-5 Dimensions. For the SF-36 and SF-12, physical and mental component scores were used in the analysis. Risk of Bias Assessment The risk of bias was assessed using the PEDro scores (Maher, Sherrington, Herbert, Moseley, & Elkins, 2003 ). We used the scores reported in the PEDro ( www.pedro.org.au ). When no scores were available in the database, two authors (YK and TM) independently assessed the PEDro scores. Disagreements were resolved by a third author (HK). Moderate to high quality studies were defined as studies with a PEDro score of ≥ 6 (Maher et al., 2003 ). Data Extraction Two authors (YK and TM) independently extracted data, and disagreements were resolved by discussion, moderated by a third author (HK). Extracted data were 1) country where data collection was performed, study design, setting and duration of the intervention, profession providing the intervention, and number of sessions of the intervention; 2) participants’ diagnosis, age, and gender, number of participants, and pain duration; 3) intervention type and comparison; 4) adverse events and dropouts, including reasons, and the means and standard deviations of the PROM scores for pain, disability, QoL, and psychological status at short-, intermediate-, and long-term follow-ups. The definitions of short, intermediate, and long terms were according to previous studies.(Gross et al., 2015 ; Monticone et al., 2015 ) Short term was defined as less than 3 months after the start of the intervention. The time point closest to 4 weeks was used when multiple eligible follow-up points were available. Intermediate term was defined as ≥ 3 months and less than 12 months after the start of the intervention. The time point closest to 6 months was chosen when multiple eligible follow-up points were available. Long term was defined as ≥ 12 months after the start of the intervention. The time point closest to 1 year was chosen if multiple eligible time points were available. When such data were lacking in the published study, we contacted the corresponding author via email to request for the missing data. A reminder email was sent 2 weeks after the first contact. When no response was received after the second reminder, we considered it uncontactable. Data Synthesis and Analysis When multiple datasets of similar outcomes were available, a meta-analysis was performed using Review Manager 5 (The Nordic Cochrane Centre, København Ø, Denmark). First, the meta-analysis was attempted using change values from the baseline to each follow-up point. When the change values were unavailable, the values at each follow-up point were used for the meta-analysis. The standardized mean difference (SMD) with 95% confidence intervals (CI) was calculated using the random-effects model. If necessary, the scores were reversed to show that high scores indicate a healthy status. The I² statistic was assessed for heterogeneity among trials, whose interpretations were as follows: 0%−40%, insignificant heterogeneity; 30%−60%, moderate heterogeneity; 50%−90%, substantial heterogeneity; and 75%−100%, considerable heterogeneity (Deeks JJ HJ, 2019 ). The overall quality of evidence was evaluated in each meta-analysis using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach (Furlan et al., 2015 ; Pollock et al., 2016 ). The GRADE approach has five domains. Our review included RCTs only; thus, the starting GRADE score was high in each domain. The scores were downgraded by one or two levels in each domain as follows: 1) the risk of bias was downgraded one level when more than 25% of the participants are from studies conducted in low-quality methods (e.g. PEDro score of less than 6); 2) the inconsistency was downgraded one level when the I 2 value was more than 75%; 3) the indirectness was downgraded one level when the available evidence for population, interventions, comparisons, and outcomes differs from what was defined in the inclusion criteria of the review; 4) the imprecision was downgraded two levels when the number of participants within the pooled analysis was less than 100 and one level when the number of participants within the pooled analysis was less than 200 (Pollock et al., 2016 ); and 5) the publication bias was downgraded one level when a funnel plot comparing at least 10 studies suggested publication bias. Two authors (YK and TM) independently rated the GRADE scores and disagreements were resolved by discussion. Results Study S election Figure 1 presents the flow of the study selection. Two studies by Söderlund and Lindberg (Söderlund & Lindberg, 2001, 2007) and two studies by Wicksell et al. (Wicksell, Ahlqvist, Bring, Melin, & Olsson, 2008; Wicksell, Olsson, & Hayes, 2010) were from the same study project and, therefore, were treated as one, respectively. The risk of bias was assessed in eight studies (Andersen et al., 2020; Dunne, Kenardy, & Sterling, 2012; Ehrenborg & Archenholtz, 2010; Michaleff et al., 2014; Pato et al., 2010; Söderlund & Lindberg, 2001, 2007; M. J. Stewart et al., 2007; Wicksell et al., 2008; Wicksell et al., 2010). Table 1 demonstrates the results of the risk of bias assessment. One study (Andersen et al., 2020) did not have PEDro scores in the database, and the PEDro scores were determined by the two authors, where there was no disagreement. Six studies (Andersen et al., 2020; Dunne et al., 2012; Michaleff et al., 2014; Söderlund & Lindberg, 2001, 2007; M. J. Stewart et al., 2007; Wicksell et al., 2008; Wicksell et al., 2010) had a low risk of bias, and two studies (Ehrenborg & Archenholtz, 2010; Pato et al., 2010) had a high risk of bias. Study C haracteristics The summary of the eight studies is presented in Table 2. Two studies have compared CBT with the wait-and-see control group (Dunne et al., 2012; Wicksell et al., 2008; Wicksell et al., 2010), where pain, disability, fear of physical activity, anxiety, depression, and posttraumatic stress in the short term were considered eligible for inclusion in the meta-analysis to investigate the effects of CBT alone. Two studies have compared CBT in addition to a comprehensive exercise program with advice alone (Michaleff et al., 2014; M. J. Stewart et al., 2007), where pain, disability, and QoL with SF-36’s physical and mental component summary scores in the long term were considered eligible for inclusion in the meta-analysis to investigate the combined effects of CBT and physical interventions. Other studies were deemed ineligible for the meta-analysis due to the lack of multiple studies with similar interventions. Andersen et al. (Andersen et al., 2020) have compared trauma-focused CBT in addition to exercise with exercise only. Söderlund and Lindberg (Söderlund & Lindberg, 2001, 2007) have compared CBT in addition to physical therapy with physical therapy alone. Pato et al. (Pato et al., 2010) have compared CBT in addition to other treatments (physical therapy, infiltration, or medication) with other treatments alone. Ehrenborg and Archenholtz (Ehrenborg & Archenholtz, 2010) have compared CBT in addition to surface electromyography biofeedback training with CBT alone. In the eight studies, CBT was provided by psychologists in four studies (Andersen et al., 2020; Dunne et al., 2012; Pato et al., 2010; Wicksell et al., 2008; Wicksell et al., 2010) and by physical therapists in four studies (Ehrenborg & Archenholtz, 2010; Michaleff et al., 2014; Söderlund & Lindberg, 2001, 2007; M. J. Stewart et al., 2007). The corresponding authors were never contacted to resolve doubts about the types and treatment characteristics of CBT. Three studies (Andersen et al., 2020; Michaleff et al., 2014; M. J. Stewart et al., 2007) have evaluated the adverse events of CBT, where no serious adverse events were observed. Minor adverse events, including muscle soreness, stiffness, headaches, and/or exacerbation of existing symptoms, were reported in the CBT group (Table 2). Meta-analysis Only one study has reported changes in values from baseline to each follow-up point (Wicksell et al., 2010). In the other studies, no additional data were available, and the values at each follow-up point were used for the meta-analysis. No disagreement was found in any rating of the GRADE scores between the two authors. CBT versus wait-and-see control For short-term pain, 46 patients with chronic WADs from two studies (Dunne et al., 2012; Wicksell et al., 2008; Wicksell et al., 2010) were included in the meta-analysis, whose forest plot is presented in Figure 2. No statistically significant overall effect was observed ( p = 0.11), indicating that CBT was not more effective than the wait-and-see control in reducing pain at the short-term follow-up. The I 2 value was 0%, indicating insignificant heterogeneity. Due to a serious impression with two levels downgraded from the GRADE score, the quality evidence was considered low (Table 3). For short-term disability, 46 patients with chronic WADs from two studies (Dunne et al., 2012; Wicksell et al., 2008; Wicksell et al., 2010) were included in the meta-analysis, whose plot is presented in Figure 3. CBT had a statistically significant overall effect ( p = 0.05), indicating that CBT was more effective than the wait-and-see control in terms of disability reduction at the short-term follow-up. The I 2 value was 0%, indicating insignificant heterogeneity. Due to a serious impression with two levels downgraded from the GRADE score, the quality evidence was considered low (Table 3). For fear of physical activity in the short term, 46 patients with chronic WADs from two studies (Dunne et al., 2012; Wicksell et al., 2008; Wicksell et al., 2010) were included in the meta-analysis, whose forest plot is presented in Figure 4. CBT had a statistically significant overall effect ( p = 0.001), indicating that CBT was more effective than the wait-and-see control in reducing the fear of physical activity at the short-term follow-up. The I 2 value was 0%, indicating insignificant heterogeneity. Due to a serious impression with two levels downgraded from the GRADE score, the quality evidence was considered low (Table 3). For short-term anxiety, 46 patients with chronic WADs from two studies (Dunne et al., 2012; Wicksell et al., 2008; Wicksell et al., 2010) were included in the meta-analysis, whose forest plot is presented in Figure 5. CBT had a statistically significant overall effect ( p = 0.002), indicating that CBT was more effective than the wait-and-see control in reducing anxiety at the short-term follow-up. The I 2 value was 0%, indicating insignificant heterogeneity. Due to a serious impression with two levels being downgraded from the GRADE score, the quality evidence was considered low (Table 3). For short-term depression, 46 patients with chronic WADs from two studies (Dunne et al., 2012; Wicksell et al., 2008; Wicksell et al., 2010) were included in the meta-analysis, whose forest plot is presented in Figure 6. CBT had a statistically significant overall effect ( p = 0.001), indicating that CBT was more effective than the wait-and-see control in reducing depression at the short-term follow-up. The I 2 value was 0%, indicating insignificant heterogeneity. Due to a serious impression with two levels downgraded from the GRADE score, the quality evidence was deemed low (Table 3). For posttraumatic stress in the short term, 46 patients with chronic WADs from two studies (Dunne et al., 2012; Wicksell et al., 2008; Wicksell et al., 2010) were included in the meta-analysis, whose forest plot is presented in Figure 7. CBT had no statistically significant overall effect ( p = 0.34), indicating that CBT was not more effective than the wait-and-see control in reducing posttraumatic stress at the short-term follow-up. The I 2 value was 0%, indicating insignificant heterogeneity. Due to a serious impression with two levels downgraded from the GRADE score, the quality evidence was deemed low (Table 3). CBT in addition to physical interventions versus advice only For long-term pain, 282 patients with chronic WADs from two studies (Michaleff et al., 2014; M. J. Stewart et al., 2007) were included in the meta-analysis, whose forest plot is presented in Figure 8. CBT in addition to physical interventions had no statistically significant overall effect ( p = 0.09), indicating that CBT in addition to physical interventions was not more effective than advice in reducing pain at the long-term follow-up. The I 2 value was 0%, indicating insignificant heterogeneity. Due to a serious impression with one level downgraded from the GRADE score, the quality evidence was deemed moderate (Table 3). For long-term disability, 282 patients with chronic WADs from two studies (Michaleff et al., 2014; M. J. Stewart et al., 2007) were included in the meta-analysis, whose forest plot is presented in Figure 9. CBT in addition to physical interventions had a statistically significant overall effect ( p = 0.01), indicating that CBT in addition to physical interventions was more effective than advice only in reducing disability at the long-term follow-up. The I 2 value was 0%, indicating insignificant heterogeneity. Due to a serious impression with one level downgraded from the GRADE score, the quality evidence was considered moderate (Table 3). For QoL in the long term, 282 patients with chronic WADs from two studies (Michaleff et al., 2014; M. J. Stewart et al., 2007) were included in the meta-analysis with the SF-36 scores. The forest plot of the physical component summary score in the SF-36 is presented in Figure 10, and that of the mental component summary score is presented in Figure 11. CBT in addition to physical interventions had no statistically significant overall effect ( p = 0.09 for the physical component summary score; p = 0.32 for the mental component summary score), indicating that CBT in addition to physical interventions was not more effective than advice only in improving the QoL at the long-term follow-up. The I 2 value was 0%, indicating insignificant heterogeneity. Due to a serious impression with one level downgraded from the GRADE score, the quality evidence was considered moderate (Table 3). Discussion As far as the authors know, this is the first meta-analysis investigating the effects of CBT alone and those of the combination of CBT and physical interventions on patients with chronic WADs. Regarding the effects of CBT alone, data synthesis was possible only for the short term with two RCTs (Dunne et al., 2012 ; Wicksell et al., 2008 ; Wicksell et al., 2010 ), resulting in the low quality of evidence of all findings. Regarding the effects of the combination of CBT and physical interventions, data synthesis was possible in the comparison between CBT with exercises and advice only for the long term with two RCTs (Michaleff et al., 2014 ; M. J. Stewart et al., 2007), resulting in the moderate quality of evidence of all findings. The meta-analysis for the effects of CBT alone compared with those of the wait-and-see control At the short-term follow-up, statistically significant reductions in disability, fear of physical activity, anxiety, and depression were found in favor of CBT, although no difference in pain and posttraumatic stress was observed. Relatively, the effect size of the fear of physical activity, anxiety, and depression seems to be larger than that of disability, indicating the characteristics of CBT as a psychological intervention. In addition, no additional RCTs were included in the meta-analysis after the previous meta-analysis in 2016 (Anstey, Kongsted, Kamper, & Hancock, 2016 ). The lack of additional RCTs may indicate that interest in recent research has shifted to the investigation of the combined effects of CBT and other treatments, such as exercise (Andersen et al., 2020 ; Michaleff et al., 2014 ; Pato et al., 2010 ; Söderlund & Lindberg, 2001 , 2007 ; M. J. Stewart et al., 2007). The meta-analysis of the combined effects of physical interventions and CBT compared with those of advice only A statistically significant reduction in disability was found in favor of CBT. The moderate quality of evidence of the long-term effects of CBT with physical interventions on disability would be an important finding to better guide management strategies for chronic WADs from a Bio-Psycho-Social perspective. However, further investigations are needed to implement this finding in clinical practice. First, the effect size of 0.29 is small; thus, further investigations are required to determine the most effective form of CBT, dose, optimal combination with other therapeutic modalities, and ways to deliver these approaches. Second, the usefulness of the inclusion of CBT components in physical interventions is recognized and provided as a management strategy for patients with chronic low-back pain, such as cognitive functional therapy (O'Sullivan et al., 2018 ). However, Beissner et al. (Beissner et al., 2009 ) have reported that physical therapists lack CBT implementation in clinical practice primarily due to limited knowledge about CBT techniques. Evidence has been increasing that educational/training level, not work experience, can be associated with the implementation of the Bio-Psycho-Social model of care with the identification of patients’ psychological status (Miki, Kondo, Takebayashi, & Takasaki, 2020 ; Suzuki & Takasaki, 2020 ; Takasaki, Saiki, & Iwasada, 2014 ). Establishing a global educational/training system will be a challenge for physical therapists to be able to implement the Bio-Psycho-Social model of care not only using CBT techniques but also other behavioral techniques, such as communication to increase patient’s autonomy (Murray et al., 2019 ) and motivational interviews (Alperstein & Sharpe, 2016 ). Evidence on the long-term effects of the combination of CBT and physical interventions compared with those of advice only is lacking, which is not surprising because the reduction of pain intensity is no longer the primary focus in patients with chronic WADs (Scholten-Peeters et al., 2002 ). However, evidence is lacking on the long-term effects of the combination of CBT and physical interventions compared with those of advice only on QoL measures, which were subscales of the SF-36, although a statistically significant effect on disability was observed measured by the NDI. The discrepancy may reflect the lower responsiveness of the SF-36 than that of the NDI in patients with chronic WADs (Stewart, Maher, Refshauge, Bogduk, & Nicholas, 2007). In this systematic review, all PROMs had the structure of pre-determined items. Such a structured PROM reduces responsiveness from individuals with neck pain (Cleland, Fritz, Whitman, & Palmer, 2006 ; M. Stewart et al., 2007) because each item has the same weight of importance among all participants, resulting in the lack of validity for measuring the intended health construct (Walton, Macdermid, & Nielson, 2010 ). The recently developed Satisfaction and Recovery Index is an importance-weighted health-related satisfaction tool that captures both the process and status of recovery following musculoskeletal trauma and is shown to be more responsive than SF-12 and region-specific disability measures (Modarresi & Walton, 2020 ; Walton, MacDermid, Pulickal, Rollack, & Veitch, 2014 ). Therefore, further studies are required to include such an importance-weighted PROM for outcome measures to clarify the effects of an intervention for those with musculoskeletal trauma. In the two RCTs included in the meta-analysis, CBT was provided by physical therapists. Psychologically informed physical therapy would be recommended for managing patients with acute WADs who have a higher risk of a shift to chronic WADs (Ritchie, Hendrikz, Kenardy, & Sterling, 2013 ; Michele Sterling, 2014) to minimize the number of chronic WADs. However, it has been unknown which is better in terms of treatment effect and cost-effectiveness between multidisciplinary approach with separate roles of CBT for psychologists and physical interventions for physical therapists and physical therapist’s delivering CBT with physical interventions. A solo approach performed by a physical therapist may not be sufficient in terms of the Bio-Psycho-Social model of care (Michele Sterling, 2014), but further investigations are required. Limitations Our meta-analysis had some limitations. The analysis was performed with a limited number of participants. Therefore, studies with a larger sample size should be performed in the future. Furthermore, we were unable to compare the advantages of combination of physical interventions and CBT with other treatments other than advice because of an insufficient number of RCTs pertaining to this topic. Finally, we did not actively seek unpublished studies. However, we believe it is unlikely to have had an important impact on the overall results. Conclusion This systematic review with meta-analysis involving patients with chronic WADs found a low level of evidence on the favorable effects of CBT alone compared with those of the wait-and-see control on disability, the fear of physical activity, anxiety, and depression in the short term. In addition, this study found a moderate favorable evidence on the effects of the combination of physical interventions and CBT compared with those of advice only on disability in the long term. Declarations Acknowledgments: None. Sources of funding: No funding. Conflict of Interest: The authors declare that they have no conflict of interest. Author contributions: Conceptualization: Yu Kondo, Takahiro Miki, Hiroshi Takasaki. Data curation: Yu Kondo, Takahiro Miki, Hiroshi Kurakata. Formal analysis: Yu Kondo, Takahiro Miki, Hiroshi Kurakata. Investigation: Yu Kondo, Takahiro Miki, Hiroshi Kurakata. Methodology: Yu Kondo, Takahiro Miki, Hiroshi Kurakata, Hiroshi Takasaki. Project administration: Miki Takahiro, Tsuneo Takebayashi, Hiroshi Takasaki. Supervision: Tsuneo Takebayashi, Hiroshi Takasaki. Visualization: Tsuneo Takebayashi. Writing – original draft: Yu Kondo, Takahiro Miki, Hiroshi Takasaki. References Alperstein, D., & Sharpe, L. (2016). The Efficacy of Motivational Interviewing in Adults With Chronic Pain: A Meta-Analysis and Systematic Review. J Pain, 17 , 393-403. Andersen, T. E., Ravn, S. L., Armfield, N., Maujean, A., Requena, S. S., & Sterling, M. (2020). Trauma-focused cognitive behavioural therapy and exercise for chronic whiplash with comorbid posttraumatic stress disorder: a randomised controlled trial. Pain, 162 , 1221-1232. Anstey, R., Kongsted, A., Kamper, S., & Hancock, M. J. (2016). Are People With Whiplash-Associated Neck Pain Different From People With Nonspecific Neck Pain? J Orthop Sports Phys Ther, 46 , 894-901. Beissner, K., Henderson, C. 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Psychological models and interventions. Pain, 19 , 209-233. Urits, I., Hubble, A., Peterson, E., Orhurhu, V., Ernst, C. A., Kaye, A. D., & Viswanath, O. (2019). An Update on Cognitive Therapy for the Management of Chronic Pain: a Comprehensive Review. Curr Pain Headache Rep, 23 , 57. Walton, D. M., Macdermid, J. C., & Nielson, W. (2010). Recovery from acute injury: clinical, methodological and philosophical considerations. Disabil Rehabil, 32 , 864-874. Walton, D. M., MacDermid, J. C., Pulickal, M., Rollack, A., & Veitch, J. (2014). Development and Initial Validation of the Satisfaction and Recovery Index (SRI) for Measurement of Recovery from Musculoskeletal Trauma. Open Orthop J, 8 , 316-325. Wicksell, R. K., Ahlqvist, J., Bring, A., Melin, L., & Olsson, G. L. (2008). Can exposure and acceptance strategies improve functioning and life satisfaction in people with chronic pain and whiplash-associated disorders (WAD)? A randomized controlled trial. Cogn Behav Ther, 37 , 169-182. Wicksell, R. K., Olsson, G. L., & Hayes, S. C. (2010). Psychological flexibility as a mediator of improvement in Acceptance and Commitment Therapy for patients with chronic pain following whiplash. Eur J Pain, 14 , 1059.e1051-1059.e1011. Tables Table 1. PEDro scores of the studies included in this systematic review Study Random allocation Concealed allocation Groups similar at baseline Participant blinding Therapist blinding Assessor blinding < 15% dropouts Intention-to-treat analysis Between-group difference reported Point estimate and variability reported Total Andersen 2020 Y Y Y N N Y N Y Y Y 7 Dunne 2012 Y N Y N N N Y Y Y Y 6 Ehrenborg 2010 N N Y N N N Y Y Y Y 5 Michaleff 2014 Y Y Y N N Y Y Y Y Y 8 Pato 2010 Y N Y N N N N N Y Y 4 Soderlund 2001, 2007 Y N Y N N Y Y N Y Y 6 Stewart 2007 Y Y Y N N Y Y Y Y Y 8 Wicksell 2008, 2010 Y Y Y N N N Y Y Y Y 7 Table 2. Summary of the eight studies included in this systematic review Study, data collection country, the source of funding, and study design Participants Interventions Comparisons Outcome measures Results Andersen et al., 2020; Australia and Denmark, NHMRC Project Grant and Danish Victims Fund Project, RCTs Total n (completing) = 103 (79) (from recruited advertisements and clinical practices in Southeast Queensland in Australia and the region of Zealand in Denmark between). Participants were aged between 18 and 70 years and diagnosed with chronic WADs grade II and PTSD. CBT group: Age: 39.7 ± 13.3 years. Gender: 14 males, 39 females. Mean duration of symptoms: 2.49 ± 1.9 years. Control group: Age: 44.5 ± 11.6 years. Gender 14 males, 36 females. Mean duration of symptoms: 3.33 ± 4.2 years. 10 weekly 60–90-minute sessions of individually delivered trauma-focused CBT (PTSD-related psychoeducation, teaching anxiety management strategies, such as progressive muscle relaxation, initiating cognitive restructuring of unhelpful thoughts and assumptions, and applying prolonged imaginal and in vivo exposure relapse prevention) by psychologists who were trained in appropriate protocols and had training in the trial interventions. After receiving the aforementioned psychological interventions, the exercise program was delivered by physical therapists who were trained in appropriate protocols and had training in the trial interventions and comprised 10 sessions for over 6 weeks (specific exercises to improve mobility, strength, and endurance of the neck and shoulder girdle muscles and exercises to improve eye/head coordination). Supportive therapy was given in 10 weekly 60-minute individual sessions including psychoeducation about PTSD symptomatology and the rationale for ST and discussion of current issues and general problem-solving skills. Supportive intervention would specifically avoid exposure, cognitive restructuring, and anxiety management techniques. After receiving the aforementioned psychological interventions, the exercise program was delivered by physical therapists who were trained in appropriate protocols and had training in the trial interventions and comprised 10 sessions for over 6 weeks (specific exercises to improve mobility, strength, and endurance of the neck and shoulder girdle muscles and exercises to improve eye/head coordination). Other objective measures that were not included in this meta-analysis. Pain: Week average, NRS Disability: NDI Functional ability: PSFS Quality of life: SF-12 Depression and anxiety: DASS Fear physical activity: TSK Pain catastrophizing: PCS Self-efficacy: PSEQ PTSD: CAPS-5 and PTSD checklist Global perceived effect: 11-point scale Adverse events Follow-up: 10 weeks, 16 weeks, 6 months, 12 months Statistically significant improvement in the PCS at 16 weeks and TSK at 12 months for the CBT group compared with the control group. No statistically significant improvement in the NRS, NDI, PSFS, SF-12, DASS, and PSEQ in the CBT group compared with the control group at any time point. No serious adverse events. Dunne et al., 2012; Australia, no funding, RCTs Total n (completing) = 26 (22) (recruited through newspaper, poster, and email advertisements in Southeast Queensland, Australia). Participants were aged between 20 and 49 years and diagnosed with chronic WADs grade II or III and motor vehicle crash-related PTSD. Gender: 13 males, 13 females. Duration of symptoms ranged from 3 months to 5years with a mean of 28.5 months. 10 weekly 1-hour sessions of individually delivered CBT based on the Australian guidelines for the treatment of adults with acute stress disorder and PTSD (cognitive strategies, coping self-talk, and cognitive restructuring) administered by a graduate psychologist with post- graduate clinical training and 12 months of prior experience delivering CBT interventions. Wait-and-see control. Pain: current pain on NRS Disability/functional status: NDI Depression and anxiety: DASS Posttraumatic stress: IES-R Fear physical activity: TSK Other objective measures that were excluded from this meta-analysis. Quality of life: SF-36 Psychological distress: PDS Pressure pain thresholds: Digital pressure algometer Follow-up: Post-intervention, 6 months Statistically significant improvement in the NDI, SF36, PDS, IES-R, and TSK in the CBT group compared with the control group after intervention. The improvements in the CBT group were maintained at 6 months. No statistically significant improvement in the NRS in the CBT group compared with the control group after the intervention. Ehrenborg and Lindberg., 2010; Sweden, no funding, RCTs Total n (completing) = 65 (59) (from the pain unit of the Department of Rehabilitation Medicine, Boras Hospital). Participants were aged 39.4 ± 11.1 years and diagnosed with chronic WADs. Gender: 31 males, 34 females. Duration of symptoms ranged from 4 to 177 mouths with a mean of 25.0 ± 30.2 months. Interdisciplinary rehabilitation based on cognitive behavioral perspectives of pain provided 5 hours/day, 5 days/week for 4–6 weeks by occupational therapists, physical therapists, physicians, nurses, nurse assistants, psychologists, and social workers. In addition, eight sessions of biofeedback training (55-minute sessions/week for 4 weeks) conducted during engagement in occupational therapy handicraft with surface electromyography. Interdisciplinary rehabilitation based on cognitive behavioral perspectives of pain provided 5 hours/day, 5 days/week for 4–6 week by occupational therapists, physical therapists, physicians, nurses, nurse assistants, psychologists, and social workers. The control group was active in handicraft on the same terms as the treatment group but without surface electromyography biofeedback. Other objective measures that were excluded from this meta-analysis. Occupational performance and satisfaction with the performance: Canadian Occupational Performance Measure Psychosocial functioning: Multidimensional Pain Inventory Follow-up: 4–6weeks and 6 months No statistically significant improvement in the Canadian Occupational Performance Measure and Multidimensional Pain Inventory in the CBT (with surface electromyography) group compared with the control group at any time point. Michaleff et al., 2014; Australia, no funding, RCTs Total n (completing) = 172 (150) (from sites in Sydney and Brisbane, Australia). Participants were aged between 18 and 65 years and diagnosed with chronic WADs grade I or II. CBT group: Age: 42.6 ± 12.3 years. Gender: 38 males, 48 females. Mean duration of symptoms: 20.9 ± 15.1 months. Control group: Age: 43.1 ± 12.7 years. Gender: 26 males, 60 females. Mean duration of symptoms: 22.0 ± 18.2 months. Individually tailored and supervised comprehensive exercise program provided by physical therapists who were trained at a 1-day workshop. Twenty sessions lasting 1 h for 12 weeks (two sessions per week for 8 weeks; one session per week for 4 weeks). CBT strategies were used for a comprehensive exercise program (encouraging skill acquisition by modeling, setting progressive goals, and self-monitoring, and positively reinforcing progress). The comprehensive exercise program included specific cervical spine exercises, neck extensor endurance exercises, specific neck motor relearning exercises, aerobic exercises, and manual therapy techniques provided with the patient educational booklet. The participants received a 30-min consultation with a physical therapist during which they read the educational booklet, practiced the exercises with minimum guidance (verbal or physical) from the physical therapist. The participants were then required to implement the advice provided and practice the exercises independently at their own discretion. No additional supervision was provided. The participants had the opportunity to contact the physical therapist by telephone on two occasions if they needed further verbal clarification of the information covered in the consultation. Pain: Week average, NRS Disability/functional status: NDI Quality of life: SF-36 Other objective measures that were excluded from this meta-analysis. Global perceived effect: Global perceived effect scale Disability/functional status: Whiplash Disability Questionnaire Functional ability: PSFS Cervical range of motion: Inclinometer Adverse events Follow-up: 14 weeks, 6 months, and 12 months Statistically significant improvement in the Global perceived effect scale at any time point and PSFS at 14 weeks in the CBT group compared with the control group. No statistically significant improvement in the NRS, NDI, Whiplash Disability Questionnaire score, and SF-36 in the CBT group compared with the control group at any time point. No serious adverse events. Minor adverse events included headache, musculoskeletal symptoms, exacerbation of existing symptoms, and stiffness. No patient withdrew from the trial because of adverse effects. Pato et al., 2010; Switzerland, no funding, RCTs Total n (completing) = 87 (73) (from Swiss Accident Insurance Fund (SUVA) and the Swiss Insurance Association registers). Participants were aged 41.61 ± 12.0 years and diagnosed with chronic WADs grade I or II. CBT group: Age: 42.6 ± 12.3 years. Gender: 38 males, 48 females. Mean duration of symptoms: 20.9 ± 15.1 months. Control group: Age: 43.1 ± 12.7 years. Gender: 26 males, 60 females. Mean duration of symptoms: 22.0 ± 18.2 months. All patients received two weekly sessions for 8 weeks (16 sessions) of CBT by the same (male) psychologist and were randomly assigned to one of following additional treatments: infiltration, physical therapy, medication for 8 weeks prescribed by the physician or physical therapist, or CBT focused on pain aspects, teaching control of pain, stress reduction, and chronic pain management techniques. Specific skills taught during the sessions were imagery, cognitive therapy for stressful situations, progressive muscle relaxation training, and application of guided mastery for stress/pain management. The infiltration group had 16 sessions, the physical therapy group had 16 sessions, and the medication group were medicated once a day for 8 weeks by the physician or physical therapist. Other objective measures that were excluded from this meta-analysis. Pain: VAS and McGill pain questionnaire Disability/functional status: HAQ Well-being: Well-Being Scale Cognitive ability: Cognitive Failures Questionnaire Follow-up: 8weeks, 3 months, and 6 months Statistically significant improvement in the Well-Being Scale at 8weeks in the CBT group compared with the control group. No statistically significant improvement in the VAS, McGill pain questionnaire, HAQ, and Cognitive Failures Questionnaire in the CBT group compared with the control group at any time point. Soderlund and Lindberg, 2001; 2007; Sweden, Swedish Foundation, RCTs Total n (completing) = 33 (32) (from an orthopedic clinic). Participants were aged between 18 and 60 years and diagnosed with chronic WADs grade I, II, or III. Duration of symptoms: 3 months or more. CBT group: Age: 37.7 years. Gender: seven males, nine females. Control group: Age: 43.5 years. Gender: seven males, 10 females. Patients underwent 12 individual sessions, which included learning of basic physical and psychological skills, application and generalization of these basic skills in everyday activities, and a phase for maintenance of these skills by a physical therapist. The basic skill phase included coping strategies, relaxation training, re-education of a balanced cervicothoracic posture, and exercises aimed to increase neck range of motion, coordination, and endurance. Patients underwent 12 individual sessions of exercises designed to enhance muscular stabilization of the neck, mobility of the neck and shoulders with stretching, and coordination of head movements and exercises to maintain the body posture and arm muscle strength provided by physical therapist. The treatment could also include pain-relieving methods including relaxation, transcutaneous electric nerve stimulation, acupuncture, and heat. Other objective measures that were excluded from this meta-analysis. Pain: Week average, NRS Disability/functional status: PDI Cervicothoracic posture: universal goniometer Cervical range of motion: Lic Rehab Care Svetsary goniometer Follow-up: Post intervention, 3 months, and 6 months No statistically significant improvement in the NRS, PDI, cervicothoracic posture, and cervical range of motion in the CBT group compared with the control group at any time point. Stewart et al., 2007; Australia, NSW Motor Accidents Authority, RCTs Total n (completing) = 132 (125) (from two physical therapy clinics in Sydney). Participants were aged 20 years or more and diagnosed with chronic WADs grade I, II, or III. CBT group: Age: 42.7 ± 14.4 years. Gender: 27 males, 41 females. Mean duration of symptoms: 8.6 ± 2.5 months. Control group: Age: 43.9 ± 15.1 years. Gender: 18 males, 48 females. Mean duration of symptoms: 9.5 ± 2.1 months. The 6-week exercise program (three sessions in the first and second weeks; two sessions in the third and fourth weeks each; and one session in the fifth and sixth weeks each) after advice was an individualized, progressive program designed by a physical therapist. A treatment manual was developed, and each physical therapist was trained in the study protocol and interventions and were educated by an experienced clinical psychologist about the principles of CBT. The therapist used principles of CBT including setting goals of progressively increasing difficulty, shaping, encouraging self-monitoring of progress, and self-reinforcing. Each participant performed aerobic exercises; stretches; functional activities; activities to enhance speed, endurance, and coordination; and trunk- and limb-strengthening exercises. Patients received standardized education, reassurance, and encouragement to resume light activity alone assisted by a physical therapist. The advice was given in one consultation and two follow-up phone contacts. Two and 4 weeks later, patients were contacted via telephone, and the standardized advice was reinforced. Pain: Average over the last 24 hours, NRS Disability/functional status: NDI Quality of life: SF-36 Other objective measures that were excluded from this meta-analysis. Functional ability: PSFS Global perceived effect: Global perceived effect scale Adverse events Follow-up: 6 weeks and 12 months Statistically significant improvement in the NRS, NDI SF36, PSFS, and Global perceived effect scale at 6weeks in the CBT group compared with control group. No significant improvement in the NRS, NDI SF36, PSFS, and Global perceived effect scale at 12 months in the CBT group compared with the control group. No serious adverse events. Minor adverse events included muscle pain, headaches, knee pain, and lumbar pain. Wicksell et al., 2008; 2010; Sweden, Swedish Research Council, RCTs Total n (completing) = 22 (19) (from Swedish Association of Survivors of Traffic Accidents and Polio). Participants were diagnosed with chronic WADs grade I, II, or III. CBT group: Age 48.2 ± 7.8 years. Gender: two males, nine females. Mean duration of symptoms: 79.7 ± 42.2 months. Control group: Age: 55.1 ± 11.2 years. Gender: three males, seven females. Mean duration of symptoms: 76.0 ± 40.9 months. The 10 individual sessions (60 minutes each) for 8 weeks. Eight sessions were conducted by psychologists and two sessions by a physician specializing in pain. Both the psychologists and physician had experience and formal training in CBT. The basic skill phase included pain education, values assessment, shifting perspective, exposure, acceptance, and diffusion. Wait-and-see control. Pain: Week average, VAS Disability/functional status: PDI Depression and anxiety: HADS. Posttraumatic stress: IES-R Fear physical activity: TSK Other objective measures that were excluded from this meta-analysis. Global life satisfaction: SWLS Psychological inflexibility: PIPS Follow-up: Post-intervention, 4 months and 7 months Statistically significant improvement in the PDI, SWLS, HADS, IES-R, TSK, and PIPS at 4 months in the CBT group compared with the control group. Improvement in the CBT group were maintained at the 7-month follow-up. No significant improvement in the VAS in the CBT group compared with the control group at any time point. RCTs, randomized controlled trials; WADs, whiplash-associated disorders; PTSD, posttraumatic stress disorder; CBT, cognitive behavioral therapy; NRS, numerical rating scale; NDI, Neck Disability Index; PSFS, Patient-Specific Functional Scale; SF-36, 36-Item Short Form Health Survey; SF-12, 12-Item Short Form Health Survey, DASS, Depression Anxiety and Stress Scale; CAPS-5, Clinician-Administered PTSD Scale; IES-R, Impact of Events Scale-Revised; TSK, Tampa Scale of Kinesiophobia; PDS, Posttraumatic Stress Diagnostic Scale; PCS, Pain Catastrophizing Scale; VAS, visual analog scale; HAQ, Health Assessment Questionnaire; HADS, Hospital Anxiety and Depression Scale; PDI, Pain Disability Index; PSEQ, Pain Self-Efficacy Questionnaire; SWLS, Satisfaction with Life Scale; PIPS, Psychological Inflexibility in Pain Scale. Table 3 A summary of the quality of the evidence using the GRADE approach Quality assessment Summary of findings No of studies Risk of bias Imprecision Inconsistency Indirectness Publication bias No of participants Pooled standardized mean difference (95% confidence intervals) Quality of evidence CBT versus wait-and-see control on pain in the short term 2 Not serious Very serious 1 Not serious Not serious Undetected 46 −0.48 (−1.07 to 0.11) ⨁⨁◯◯ LOW CBT versus wait-and-see control on disability in the short term 2 Not serious Very serious 1 Not serious Not serious Undetected 46 −0.61 (−1.21 to −0.01) ⨁⨁◯◯ LOW CBT versus wait-and-see control on fear of physical activity in the short term 2 Not serious Very serious 1 Not serious Not serious Undetected 46 −1.04 (−1.67 to −0.41) ⨁⨁◯◯ LOW CBT versus wait-and-see control on anxiety in the short term 2 Not serious Very serious 1 Not serious Not serious Undetected 46 −0.97 (−1.59 to −0.35) ⨁⨁◯◯ LOW CBT versus wait-and-see control on depression in the short term 2 Not serious Very serious 1 Not serious Not serious Undetected 46 −1.04 (−1.66 to −0.41) ⨁⨁◯◯ LOW CBT versus wait-and-see control on posttraumatic stress in the short term 2 Not serious Very serious 1 Not serious Not serious Undetected 46 −0.28 (−0.87 to 0.30) ⨁⨁◯◯ LOW CBT in addition to physical interventions versus advice only on pain in the long term 2 Not serious Serious 2 Not serious Not serious Undetected 282 −0.20 (−0.43 to 0.03) ⨁⨁⨁◯ MODERATE CBT in addition to physical interventions versus advice only on disability in the long term 2 Not serious Serious 2 Not serious Not serious Undetected 282 −0.29 (−0.53 to −0.06) ⨁⨁⨁◯ MODERATE CBT in addition to physical interventions versus advice only on quality of life in the long term (physical component summary) 2 Not serious Serious 2 Not serious Not serious Undetected 282 −0.20 (−0.44 to 0.03) ⨁⨁⨁◯ MODERATE CBT in addition to physical interventions versus advice only on quality of life in the long term (mental component summary) 2 Not serious Serious 2 Not serious Not serious Undetected 282 −0.12 (−0.35 to 0.11) ⨁⨁⨁◯ MODERATE CBT, cognitive behavioral therapy. 1 Due to the limited sample sizes (fewer than 100 participants), significance was rated down two levels. 2 Due to the limited sample sizes (fewer than 200 participants), significance was rated down one level. 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Miki","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAu0lEQVRIiWNgGAWjYDACHh4QmSAHIg88IE4HRIsxWEsCKVoSG8AUMVrsec4e+8CYk5Y+P+zwQ6AtdnK6DYRs4e1LnsG4LSd34+00A6CWZGOzA4S08PMYMzBuq8jdODsBpOVA4jZitaQbzk7/QKQW3h6QlpwEeekcYm05c8aYIXFbmuEG6ZyCAwkGRPiFvSfHmOHjtmR5+dnpmz98qLCTI6gFDBKA2ACs0oAY5TAg30CK6lEwCkbBKBhRAABqFz/YHA7/4gAAAABJRU5ErkJggg==","orcid":"https://orcid.org/0000-0002-0648-2675","institution":"Sapporo Maruyama Orthopedic Hospital","correspondingAuthor":true,"submittingAuthor":false,"prefix":"","firstName":"Takahiro","middleName":"","lastName":"Miki","suffix":""},{"id":84888203,"identity":"610811c1-102d-4bde-9878-c5921d37aa01","order_by":2,"name":"Hiroshi Kurakata","email":"","orcid":"","institution":"Yumenomachi Home Nursing care and rehabilitation service","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Hiroshi","middleName":"","lastName":"Kurakata","suffix":""},{"id":84888204,"identity":"b8403144-9b19-4364-94b8-3f0b5edb88e0","order_by":3,"name":"Tsuneo Takebayashi","email":"","orcid":"","institution":"Sapporo Maruayama Orthopedic Hospital","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Tsuneo","middleName":"","lastName":"Takebayashi","suffix":""},{"id":84888205,"identity":"a16b9537-f70d-4c03-905d-25e4182d7848","order_by":4,"name":"Hiroshi Takasaki","email":"","orcid":"","institution":"Saitama prefectural University","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Hiroshi","middleName":"","lastName":"Takasaki","suffix":""}],"badges":[],"createdAt":"2022-02-15 01:23:11","currentVersionCode":2,"declarations":"","doi":"10.21203/rs.3.rs-1360019/v2","doiUrl":"https://doi.org/10.21203/rs.3.rs-1360019/v2","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":18444395,"identity":"7011be54-e4d4-4923-9817-7bf098ee8ef9","added_by":"auto","created_at":"2022-02-21 15:56:47","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":298070,"visible":true,"origin":"","legend":"\u003cp\u003ePRISMA flow chart demonstrating the study search results.\u003c/p\u003e","description":"","filename":"1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-1360019/v2/b96658c31aebe9a33e370e46.jpg"},{"id":18444300,"identity":"f998a026-3b4d-4bd5-b395-73ddad00db86","added_by":"auto","created_at":"2022-02-21 15:53:47","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":44931,"visible":true,"origin":"","legend":"\u003cp\u003eForest plot of CBT versus wait-and-see control on pain in the short term.\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-1360019/v2/5c9833a6b07bea5eaef4d40e.png"},{"id":18444398,"identity":"8d576f17-e5b3-4588-b58c-098c82de3716","added_by":"auto","created_at":"2022-02-21 15:56:47","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":52406,"visible":true,"origin":"","legend":"\u003cp\u003eForest plot of CBT versus wait-and-see control on fear of physical activity in the short term.\u003c/p\u003e","description":"","filename":"3.png","url":"https://assets-eu.researchsquare.com/files/rs-1360019/v2/e71f7d3b869b90cf86297fb8.png"},{"id":18444310,"identity":"ff0206e2-7984-4ec4-b267-1125bfc9a895","added_by":"auto","created_at":"2022-02-21 15:53:47","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":66930,"visible":true,"origin":"","legend":"\u003cp\u003eForest plot of CBT versus wait-and-see control on fear of physical activity in the short term.\u003c/p\u003e","description":"","filename":"4.png","url":"https://assets-eu.researchsquare.com/files/rs-1360019/v2/88aa2f8f1fa8409e79317cf4.png"},{"id":18444311,"identity":"8bc28c39-c375-4f3b-ab64-29eb887b9637","added_by":"auto","created_at":"2022-02-21 15:53:47","extension":"png","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":51231,"visible":true,"origin":"","legend":"\u003cp\u003eForest plot of CBT versus wait-and-see control on anxiety in the short term.\u003c/p\u003e","description":"","filename":"5.png","url":"https://assets-eu.researchsquare.com/files/rs-1360019/v2/5a41b4e5c2bc10b68293c410.png"},{"id":18444302,"identity":"5805ac4d-1d75-42ab-a6d7-4a7ab185bdb3","added_by":"auto","created_at":"2022-02-21 15:53:47","extension":"png","order_by":6,"title":"Figure 6","display":"","copyAsset":false,"role":"figure","size":55988,"visible":true,"origin":"","legend":"\u003cp\u003eForest plot of CBT versus wait-and-see control on depression in the short term.\u003c/p\u003e","description":"","filename":"6.png","url":"https://assets-eu.researchsquare.com/files/rs-1360019/v2/eb6efa7f7324c9c9f60756dd.png"},{"id":18444397,"identity":"f3ed7f54-2a57-4a19-bb55-1e36a969839a","added_by":"auto","created_at":"2022-02-21 15:56:47","extension":"png","order_by":7,"title":"Figure 7","display":"","copyAsset":false,"role":"figure","size":50404,"visible":true,"origin":"","legend":"\u003cp\u003eForest plot of CBT versus wait-and-see control on posttraumatic stress in the short term.\u003c/p\u003e","description":"","filename":"7.png","url":"https://assets-eu.researchsquare.com/files/rs-1360019/v2/fa8ee9ad71ee6254e19fd4b0.png"},{"id":18444306,"identity":"11f2aaed-bded-4682-8b3a-aa5df48c1eac","added_by":"auto","created_at":"2022-02-21 15:53:47","extension":"png","order_by":8,"title":"Figure 8","display":"","copyAsset":false,"role":"figure","size":48719,"visible":true,"origin":"","legend":"\u003cp\u003eForest plot of CBT in addition to physical interventions versus advice only on pain in the long term.\u003c/p\u003e","description":"","filename":"8.png","url":"https://assets-eu.researchsquare.com/files/rs-1360019/v2/3dc46a838a3a14ca5708b765.png"},{"id":18444396,"identity":"bc5fd012-d69b-4832-9e96-40fd4dc89b5f","added_by":"auto","created_at":"2022-02-21 15:56:47","extension":"png","order_by":9,"title":"Figure 9","display":"","copyAsset":false,"role":"figure","size":48306,"visible":true,"origin":"","legend":"\u003cp\u003eForest plot of CBT in addition to physical interventions versus advice only on disability in the long term.\u003c/p\u003e","description":"","filename":"9.png","url":"https://assets-eu.researchsquare.com/files/rs-1360019/v2/79d0bf5d0b0ca012b86e2dd4.png"},{"id":18444308,"identity":"06609a73-361c-49ce-a8d9-30dc1cc44e05","added_by":"auto","created_at":"2022-02-21 15:53:47","extension":"png","order_by":10,"title":"Figure 10","display":"","copyAsset":false,"role":"figure","size":48786,"visible":true,"origin":"","legend":"\u003cp\u003eForest plot of CBT in addition to physical interventions versus advice only on quality of life in the long term (physical component summary).\u003c/p\u003e","description":"","filename":"10.png","url":"https://assets-eu.researchsquare.com/files/rs-1360019/v2/c75b11f2b8ee07d72077985d.png"},{"id":18444399,"identity":"ded870f3-4693-43de-b5cb-385600e1c143","added_by":"auto","created_at":"2022-02-21 15:56:47","extension":"png","order_by":11,"title":"Figure 11","display":"","copyAsset":false,"role":"figure","size":51084,"visible":true,"origin":"","legend":"\u003cp\u003eForest plot of CBT in addition to physical interventions versus advice only on quality of life in the long term (mental component summary).\u003c/p\u003e","description":"","filename":"11.png","url":"https://assets-eu.researchsquare.com/files/rs-1360019/v2/96c8800efa203d83c9023a56.png"},{"id":18444400,"identity":"efbff5a9-f798-4a99-aec5-9122955d4cf4","added_by":"auto","created_at":"2022-02-21 15:56:51","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":842070,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-1360019/v2/ad902f0f-60ae-4f14-9f0d-ef3f2b9a441f.pdf"},{"id":18444304,"identity":"ba0f9fd2-20ad-4ccd-b0fa-25f74795b2eb","added_by":"auto","created_at":"2022-02-21 15:53:47","extension":"docx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":19238,"visible":true,"origin":"","legend":"\u003cp\u003eAppendix 1. Search strategy.\u003c/p\u003e","description":"","filename":"Appendix1.Searchstrategy.docx","url":"https://assets-eu.researchsquare.com/files/rs-1360019/v2/d3a123f68dc0a0b59ce2625c.docx"}],"financialInterests":"","formattedTitle":"Effects of cognitive behavior therapy on patients with chronic whiplash-associated disorders: a systematic review and meta-analysis","fulltext":[{"header":"Introduction","content":"\u003cp\u003eChronic whiplash-associated disorders (WADs) often include not only physical but also diverse psychological and cognitive impairments (M. Sterling, 2014), whose characteristics are different from those of chronic idiopathic neck pain (Coppieters et al., \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e2017\u003c/span\u003e; Ris et al., \u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e2017\u003c/span\u003e). Therefore, clinical practice guidelines suggest providing a Bio-Psycho-Social model of care to individuals with chronic WADs by including psychological interventions (Scholten-Peeters et al., \u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e2002\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e One intervention commonly suggested by clinical practice guidelines is cognitive behavior therapy (CBT). CBT helps in cognitive reconditioning and behavioral modifications of specific activities (Butler, Chapman, Forman, \u0026amp; Beck, \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e2006\u003c/span\u003e; Flor \u0026amp; Turk, \u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e1984\u003c/span\u003e; Morley, \u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e2011\u003c/span\u003e). In 2015, Monticone et al. (Monticone et al., \u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e2015\u003c/span\u003e) have conducted a meta-analysis to investigate the effects of CBT alone on chronic neck pain. In their meta-analysis, patients with nonspecific neck pain and those with WADs were combined, limiting the clinical implications due to different characteristics of chronic WADs and idiopathic neck pain. Therefore, performing a new analysis by limiting participants to those with chronic WADs is necessary.\u003c/p\u003e \u003cp\u003eInvestigating the effects of CBT alone on chronic WADs by performing a meta-analysis is an important step in considering the advantages of including CBT in the Bio-Psycho-Social model of care. However, note that CBT is a psychological intervention, not a Bio-Psycho-Social intervention (Urits et al., \u003cspan citationid=\"CR43\" class=\"CitationRef\"\u003e2019\u003c/span\u003e). Therefore, understanding the effects of combining physical interventions and CBT on chronic WADs is clinically useful. In 2016, Shearer et al. (Shearer et al., \u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e2016\u003c/span\u003e) have investigated the effects of a combination of physical interventions and CBT on chronic WADs in a systematic review involving the literature from 1990 to 2015. However, data synthesis was not undertaken due to the absence of multiple studies. We found multiple randomized controlled trials (RCTs) to be included in a meta-analysis (Michaleff et al., \u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e2014\u003c/span\u003e; M. J. Stewart et al., 2007), and we found another eligible RCT in 2020 (Andersen et al., \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2020\u003c/span\u003e). Therefore, an updated systematic review was necessary to understand the effects of the combination of physical interventions and CBT on chronic WADs.\u003c/p\u003e \u003cp\u003eThis systematic review with meta-analysis has two purposes. First is to investigate the effects of CBT alone on pain, disability, quality of life (QoL), and psychological parameters in patients with chronic WADs. Second is to investigate the effects of the combination of physical interventions and CBT compared with those of CBT alone on pain, disability, QoL, and psychological parameters on patients with chronic WADs.\u003c/p\u003e"},{"header":"Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eProtocol Registration and Search Strategy\u003c/h2\u003e \u003cp\u003eThis review was preregistered in PROSPERO (CRD42020193904) and conducted according to the updated Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines (Moher, Liberati, Tetzlaff, Altman, \u0026amp; Group, \u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e2009\u003c/span\u003e). The following items were modified after the initial registration in PROSPERO: 1) Review questions were added to investigate the effects of the combination of physical interventions and CBT; 2) the definition of chronic WADs were defined as symptoms lasting for \u0026ge;\u0026thinsp;3 months, which was revised from symptoms lasting for \u0026ge;\u0026thinsp;6 months; 3) studies with one author were also included; and 4) the PsycINFO database was excluded due to limited access to the database.\u003c/p\u003e \u003cp\u003eAn author (HK) systematically searched the following databases from inception to January 2021: CINAHL, Web of Science, MEDLINE, Embase, EMCare, and Physiotherapy Evidence Database (PEDro). The search strategies are presented in Appendix 1.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003eStudy Selection\u003c/h2\u003e \u003cp\u003eScreening and full-text inspection were performed by two authors (YK and TM) independently. Any disagreements on eligibility were resolved by discussion. Cross-referencing was performed with hand searches of the reference lists of studies included in the full-text screening.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003eEligibility Criteria\u003c/h2\u003e \u003cp\u003eAll RCTs published as full-text articles were eligible for inclusion in this systematic review. No restrictions on language were employed.\u003c/p\u003e \u003cp\u003eEligible participants were as follows: 1) adult individuals (\u0026ge;\u0026thinsp;18 years of age) with WADs with a whiplash injury grade of I, II, or III in the Quebec Task Force Classification (Spitzer et al., \u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e1995\u003c/span\u003e), 2) patients from primary, secondary, or tertiary care institutions, and 3) patients with any persistent symptoms, such as musculoskeletal pain, sensorimotor control disturbances, and psychological problems, for more than 3 months after the accident. Studies with the following participants were excluded from this systematic review: 1) patients with a cervical fracture or dislocation, 2) patients with injuries in other body areas other than the neck during the accident causing WAD, and 3) patients with previous WADs, preexisting neck pain, or previous neck surgery.\u003c/p\u003e \u003cp\u003eEligible interventions were CBT with and without physical interventions. No consensus was made for a specific definition of CBT (Lamb et al., \u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e2010\u003c/span\u003e); thus, CBT was identified in this study when the following criteria reported by Richmond et al. (Richmond et al., \u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e2015\u003c/span\u003e) were satisfied: 1) treatments based on cognitive\u0026ndash;behavioral principles that were explicitly or implicitly stated (Fisher et al., \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e2018\u003c/span\u003e; Gatchel, Peng, Peters, Fuchs, \u0026amp; Turk, \u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e2007\u003c/span\u003e; Turk \u0026amp; Flor, \u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e1984\u003c/span\u003e); 2) interventions using both cognitive and behavioral strategies were used in the same treatment package; 3) CBT was provided by an experienced healthcare professional; and 4) when multimodal treatments were provided, the intervention was assumed to be based on a CBT principle. Any disagreements in selecting CBT techniques were resolved through a discussion between the authors by contacting the corresponding authors of the study for additional information or by finding a process paper associated with the study that provided further information.\u003c/p\u003e \u003cp\u003eEligible comparisons included any type of a single intervention or a wait-and-see control.\u003c/p\u003e \u003cp\u003eEligible primary outcomes included pain intensity, disability, QoL, and\u003c/p\u003e \u003cp\u003eeligible secondary outcomes included psychological status. In addition, adverse events were recorded where mentioned. For pain intensity, when more than one patient-reported outcome measure (PROM) was reported, a numerical rating scale was used in the analysis, followed by a visual analog scale. For disability, when more than one PROM was reported, the Neck Disability Index (NDI) was used in the analysis. For QoL, when more than one PROM was reported, the 36-Item Short Form Health Survey (SF-36) was used in the analysis, followed by the 12-Item Short Form Health Survey (SF-12) and the EuroQol-5 Dimensions. For the SF-36 and SF-12, physical and mental component scores were used in the analysis.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003eRisk of Bias Assessment\u003c/h2\u003e \u003cp\u003eThe risk of bias was assessed using the PEDro scores (Maher, Sherrington, Herbert, Moseley, \u0026amp; Elkins, \u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e2003\u003c/span\u003e). We used the scores reported in the PEDro (\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e\u003ca href=\"http://www.pedro.org.au\" target=\"_blank\"\u003ewww.pedro.org.au\u003c/a\u003e\u003c/span\u003e\u003c/span\u003e). When no scores were available in the database, two authors (YK and TM) independently assessed the PEDro scores.\u003c/p\u003e \u003cp\u003eDisagreements were resolved by a third author (HK). Moderate to high quality studies were defined as studies with a PEDro score of \u0026ge;\u0026thinsp;6 (Maher et al., \u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e2003\u003c/span\u003e).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec7\" class=\"Section2\"\u003e \u003ch2\u003eData Extraction\u003c/h2\u003e \u003cp\u003eTwo authors (YK and TM) independently extracted data, and disagreements were resolved by discussion, moderated by a third author (HK). Extracted data were 1) country where data collection was performed, study design, setting and duration of the intervention, profession providing the intervention, and number of sessions of the intervention; 2) participants\u0026rsquo; diagnosis, age, and gender, number of participants, and pain duration; 3) intervention type and comparison; 4) adverse events and dropouts, including reasons, and the means and standard deviations of the PROM scores for pain, disability, QoL, and psychological status at short-, intermediate-, and long-term follow-ups. The definitions of short, intermediate, and long terms were according to previous studies.(Gross et al., \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e2015\u003c/span\u003e; Monticone et al., \u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e2015\u003c/span\u003e) Short term was defined as less than 3 months after the start of the intervention. The time point closest to 4 weeks was used when multiple eligible follow-up points were available. Intermediate term was defined as \u0026ge;\u0026thinsp;3 months and less than 12 months after the start of the intervention. The time point closest to 6 months was chosen when multiple eligible follow-up points were available. Long term was defined as \u0026ge;\u0026thinsp;12 months after the start of the intervention. The time point closest to 1 year was chosen if multiple eligible time points were available. When such data were lacking in the published study, we contacted the corresponding author via email to request for the missing data. A reminder email was sent 2 weeks after the first contact. When no response was received after the second reminder, we considered it uncontactable.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003eData Synthesis and Analysis\u003c/h2\u003e \u003cp\u003eWhen multiple datasets of similar outcomes were available, a meta-analysis was performed using Review Manager 5 (The Nordic Cochrane Centre, K\u0026oslash;benhavn \u0026Oslash;, Denmark). First, the meta-analysis was attempted using change values from the baseline to each follow-up point. When the change values were unavailable, the values at each follow-up point were used for the meta-analysis.\u003c/p\u003e \u003cp\u003eThe standardized mean difference (SMD) with 95% confidence intervals (CI) was calculated using the random-effects model. If necessary, the scores were reversed to show that high scores indicate a healthy status. The I\u0026sup2; statistic was assessed for heterogeneity among trials, whose interpretations were as follows: 0%\u0026minus;40%, insignificant heterogeneity; 30%\u0026minus;60%, moderate heterogeneity; 50%\u0026minus;90%, substantial heterogeneity; and 75%\u0026minus;100%, considerable heterogeneity (Deeks JJ HJ, \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e2019\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eThe overall quality of evidence was evaluated in each meta-analysis using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach (Furlan et al., \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e2015\u003c/span\u003e; Pollock et al., \u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e2016\u003c/span\u003e). The GRADE approach has five domains. Our review included RCTs only; thus, the starting GRADE score was high in each domain. The scores were downgraded by one or two levels in each domain as follows: 1) the risk of bias was downgraded one level when more than 25% of the participants are from studies conducted in low-quality methods (e.g. PEDro score of less than 6); 2) the inconsistency was downgraded one level when the I\u003csup\u003e2\u003c/sup\u003e value was more than 75%; 3) the indirectness was downgraded one level when the available evidence for population, interventions, comparisons, and outcomes differs from what was defined in the inclusion criteria of the review; 4) the imprecision was downgraded two levels when the number of participants within the pooled analysis was less than 100 and one level when the number of participants within the pooled analysis was less than 200 (Pollock et al., \u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e2016\u003c/span\u003e); and 5) the publication bias was downgraded one level when a funnel plot comparing at least 10 studies suggested publication bias. Two authors (YK and TM) independently rated the GRADE scores and disagreements were resolved by discussion.\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003ch2\u003e\u003cem\u003eStudy\u0026nbsp;\u003c/em\u003e\u003cem\u003eS\u003c/em\u003e\u003cem\u003eelection\u0026nbsp;\u003c/em\u003e\u003c/h2\u003e\n\u003cp\u003eFigure 1 presents the flow of the study selection.\u0026nbsp;Two studies by\u0026nbsp;S\u0026ouml;derlund and Lindberg (S\u0026ouml;derlund \u0026amp; Lindberg, 2001, 2007) and two studies by Wicksell et al. (Wicksell, Ahlqvist, Bring, Melin, \u0026amp; Olsson, 2008; Wicksell, Olsson, \u0026amp; Hayes, 2010) were from the same study project and, therefore, were treated as one, respectively.\u0026nbsp;The risk of bias was assessed in eight studies\u0026nbsp;(Andersen et al., 2020; Dunne, Kenardy, \u0026amp; Sterling, 2012; Ehrenborg \u0026amp; Archenholtz, 2010; Michaleff et al., 2014; Pato et al., 2010; S\u0026ouml;derlund \u0026amp; Lindberg, 2001, 2007; M. J. Stewart et al., 2007; Wicksell et al., 2008; Wicksell et al., 2010).\u0026nbsp;Table 1 demonstrates the results of the risk of bias assessment.\u0026nbsp;One study (Andersen et al., 2020)\u0026nbsp;did not have PEDro scores in the\u0026nbsp;database, and the PEDro scores were determined by the two authors, where there was no disagreement. Six\u0026nbsp;studies (Andersen et al., 2020; Dunne et al., 2012; Michaleff et al., 2014; S\u0026ouml;derlund \u0026amp; Lindberg, 2001, 2007; M. J. Stewart et al., 2007; Wicksell et al., 2008; Wicksell et al., 2010)\u0026nbsp;had a low risk of bias, and two studies\u0026nbsp;(Ehrenborg \u0026amp; Archenholtz, 2010; Pato et al., 2010)\u0026nbsp;had a high risk of bias.\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u0026nbsp;\u003c/p\u003e\n\u003ch2\u003e\u003cem\u003eStudy\u0026nbsp;\u003c/em\u003e\u003cem\u003eC\u003c/em\u003e\u003cem\u003eharacteristics\u003c/em\u003e\u003c/h2\u003e\n\u003cp\u003eThe summary of the eight studies is presented in\u0026nbsp;Table 2. Two studies have compared CBT with the wait-and-see control group\u0026nbsp;(Dunne et al., 2012; Wicksell et al., 2008; Wicksell et al., 2010),\u0026nbsp;where\u0026nbsp;pain, disability, fear of physical activity, anxiety, depression, and\u0026nbsp;posttraumatic\u0026nbsp;stress\u0026nbsp;in\u0026nbsp;the short\u0026nbsp;term were\u0026nbsp;considered eligible\u0026nbsp;for\u0026nbsp;inclusion in\u0026nbsp;the meta-analysis to investigate the\u0026nbsp;effects\u0026nbsp;of CBT\u0026nbsp;alone. Two studies have compared CBT in addition to a comprehensive exercise program with advice alone\u0026nbsp;(Michaleff et al., 2014; M. J. Stewart et al., 2007), where pain, disability, and QoL\u0026nbsp;with SF-36\u0026rsquo;s physical and mental component summary scores\u0026nbsp;in the\u0026nbsp;long\u0026nbsp;term were\u0026nbsp;considered eligible\u0026nbsp;for\u0026nbsp;inclusion in\u0026nbsp;the meta-analysis to investigate\u0026nbsp;the\u0026nbsp;combined effects\u0026nbsp;of CBT and physical interventions.\u003c/p\u003e\n\u003cp\u003eOther studies were\u0026nbsp;deemed ineligible\u0026nbsp;for the meta-analysis due to the lack of multiple studies with similar interventions. Andersen et al. (Andersen et al., 2020)\u0026nbsp;have\u0026nbsp;compared\u0026nbsp;trauma-focused CBT in addition to exercise with exercise only. S\u0026ouml;derlund and Lindberg (S\u0026ouml;derlund \u0026amp; Lindberg, 2001, 2007)\u0026nbsp;have\u0026nbsp;compared CBT in addition to physical therapy with physical therapy alone. Pato et al. (Pato et al., 2010)\u0026nbsp;have\u0026nbsp;compared CBT in addition to other treatments (physical therapy, infiltration, or medication) with other treatments alone.\u0026nbsp;Ehrenborg and Archenholtz (Ehrenborg \u0026amp; Archenholtz, 2010)\u0026nbsp;have\u0026nbsp;compared CBT in addition to surface electromyography biofeedback training with CBT alone. In the eight studies, CBT was provided by psychologists in four studies\u0026nbsp;(Andersen et al., 2020; Dunne et al., 2012; Pato et al., 2010; Wicksell et al., 2008; Wicksell et al., 2010)\u0026nbsp;and by physical therapists in four studies\u0026nbsp;(Ehrenborg \u0026amp; Archenholtz, 2010; Michaleff et al., 2014; S\u0026ouml;derlund \u0026amp; Lindberg, 2001, 2007; M. J. Stewart et al., 2007). The\u0026nbsp;corresponding authors\u0026nbsp;were never contacted\u0026nbsp;to resolve doubts about the types and treatment characteristics of CBT.\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003eThree studies (Andersen et al., 2020; Michaleff et al., 2014; M. J. Stewart et al., 2007) have evaluated the adverse events of CBT, where no serious adverse events were observed. Minor adverse events, including muscle soreness, stiffness, headaches, and/or exacerbation of existing symptoms, were reported in the CBT group (Table 2).\u0026nbsp;\u003c/p\u003e\n\u003ch2\u003e\u003cem\u003eMeta-analysis\u003c/em\u003e\u003c/h2\u003e\n\u003cp\u003eOnly one study has reported changes in values from baseline to each follow-up point (Wicksell et al., 2010). In the other studies, no additional data were available, and the values at each follow-up point were used for the meta-analysis. No disagreement was found in any rating of the GRADE scores between the two authors. \u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003ch2\u003e\u003cem\u003eCBT versus wait-and-see control\u003c/em\u003e\u003c/h2\u003e\n\u003cp\u003eFor short-term pain, 46 patients with chronic WADs from two studies\u0026nbsp;(Dunne et al., 2012; Wicksell et al., 2008; Wicksell et al., 2010)\u0026nbsp;were included in the meta-analysis, whose forest plot is presented in Figure 2. No statistically significant overall effect was observed (\u003cem\u003ep\u003c/em\u003e = 0.11), indicating that CBT was not more effective than the wait-and-see control in reducing pain at the short-term follow-up. The I\u003csup\u003e2\u003c/sup\u003e value was 0%, indicating insignificant heterogeneity. Due to a serious impression with two levels downgraded from the GRADE score, the\u0026nbsp;quality evidence was considered low (Table 3).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eFor short-term disability, 46 patients with chronic WADs from two studies\u0026nbsp;(Dunne et al., 2012; Wicksell et al., 2008; Wicksell et al., 2010)\u0026nbsp;were included in the meta-analysis, whose plot is presented in Figure 3. CBT had a statistically significant overall effect (\u003cem\u003ep\u003c/em\u003e = 0.05), indicating that CBT was more effective than the wait-and-see control in terms of disability reduction at the short-term follow-up. The I\u003csup\u003e2\u003c/sup\u003e value was 0%, indicating insignificant heterogeneity. Due to a serious impression with two levels downgraded from the GRADE score, the\u0026nbsp;quality evidence was considered low (Table 3).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eFor fear of physical activity in the short term, 46 patients with chronic WADs from two studies\u0026nbsp;(Dunne et al., 2012; Wicksell et al., 2008; Wicksell et al., 2010)\u0026nbsp;were included in the meta-analysis, whose forest plot is presented in Figure 4. CBT had a statistically significant overall effect (\u003cem\u003ep\u003c/em\u003e = 0.001), indicating that CBT was more effective than the wait-and-see control in reducing the fear of physical activity at the short-term follow-up. The I\u003csup\u003e2\u003c/sup\u003e value was 0%, indicating insignificant heterogeneity. Due to a serious impression with two levels downgraded from the GRADE score, the\u0026nbsp;quality evidence was considered low (Table 3).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eFor short-term anxiety, 46 patients with chronic WADs from two studies\u0026nbsp;(Dunne et al., 2012; Wicksell et al., 2008; Wicksell et al., 2010)\u0026nbsp;were included in the meta-analysis, whose forest plot is presented in Figure 5. CBT had a statistically significant overall effect (\u003cem\u003ep\u003c/em\u003e = 0.002), indicating that CBT was more effective than the wait-and-see control in reducing anxiety at the short-term follow-up. The I\u003csup\u003e2\u003c/sup\u003e value was 0%, indicating insignificant heterogeneity. Due to a serious impression with two levels being downgraded from the GRADE score, the\u0026nbsp;quality evidence was considered low (Table 3).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eFor short-term depression, 46 patients with chronic WADs from two studies\u0026nbsp;(Dunne et al., 2012; Wicksell et al., 2008; Wicksell et al., 2010)\u0026nbsp;were included in the meta-analysis, whose forest plot is presented in Figure 6. CBT had a statistically significant overall effect (\u003cem\u003ep\u003c/em\u003e = 0.001), indicating that CBT was more effective than the wait-and-see control in reducing depression at the short-term follow-up. The I\u003csup\u003e2\u003c/sup\u003e value was 0%, indicating insignificant heterogeneity. Due to a serious impression with two levels downgraded from the GRADE score, the quality evidence was deemed low (Table 3).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eFor posttraumatic stress in the short term, 46 patients with chronic WADs from two studies\u0026nbsp;(Dunne et al., 2012; Wicksell et al., 2008; Wicksell et al., 2010)\u0026nbsp;were included in the meta-analysis, whose forest plot is presented in Figure 7. CBT had no statistically significant overall effect (\u003cem\u003ep\u003c/em\u003e = 0.34), indicating that CBT was not more effective than the wait-and-see control in reducing posttraumatic stress at the short-term follow-up. The I\u003csup\u003e2\u003c/sup\u003e value was 0%, indicating insignificant heterogeneity. Due to a serious impression with two levels downgraded from the GRADE score, the quality evidence was deemed low (Table 3). \u0026nbsp;\u003c/p\u003e\n\u003ch2\u003e\u003cem\u003eCBT in addition to physical interventions versus advice only\u003c/em\u003e\u003c/h2\u003e\n\u003cp\u003eFor long-term pain, 282 patients with chronic WADs from two studies\u0026nbsp;(Michaleff et al., 2014; M. J. Stewart et al., 2007)\u0026nbsp;were included in the meta-analysis, whose forest plot is presented in Figure 8. CBT in addition to physical interventions had no statistically significant overall effect (\u003cem\u003ep\u003c/em\u003e = 0.09), indicating that CBT in addition to physical interventions was not more effective than advice in reducing pain at the long-term follow-up. The I\u003csup\u003e2\u003c/sup\u003e value was 0%, indicating insignificant heterogeneity. Due to a serious impression with one level downgraded from the GRADE score, the\u0026nbsp;quality evidence was deemed moderate (Table 3).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eFor long-term disability, 282 patients with chronic WADs from two studies\u0026nbsp;(Michaleff et al., 2014; M. J. Stewart et al., 2007)\u0026nbsp;were included in the meta-analysis, whose forest plot is presented in Figure 9. CBT in addition to physical interventions had a statistically significant overall effect (\u003cem\u003ep\u003c/em\u003e = 0.01), indicating that CBT in addition to physical interventions was more effective than advice only in reducing disability at the long-term follow-up. The I\u003csup\u003e2\u003c/sup\u003e value was 0%, indicating insignificant heterogeneity. Due to a serious impression with one level downgraded from the GRADE score, the\u0026nbsp;quality evidence was considered moderate (Table 3).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eFor QoL in the long term, 282 patients with chronic WADs from two studies\u0026nbsp;(Michaleff et al., 2014; M. J. Stewart et al., 2007)\u0026nbsp;were included in the meta-analysis with the SF-36 scores. The forest plot of the physical component summary score in the SF-36 is presented in Figure 10, and that of the mental component summary score is presented in Figure 11. CBT in addition to physical interventions had no statistically significant overall effect (\u003cem\u003ep\u003c/em\u003e = 0.09 for the physical component summary score; \u003cem\u003ep\u003c/em\u003e = 0.32 for the mental component summary score), indicating that CBT in addition to physical interventions was not more effective than advice only in improving the QoL at the long-term follow-up. The I\u003csup\u003e2\u003c/sup\u003e value was 0%, indicating insignificant heterogeneity. Due to a serious impression with one level downgraded from the GRADE score, the quality evidence was considered moderate (Table 3).\u0026nbsp;\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eAs far as the authors know, this is the first meta-analysis investigating the effects of CBT alone and those of the combination of CBT and physical interventions on patients with chronic WADs. Regarding the effects of CBT alone, data synthesis was possible only for the short term with two RCTs (Dunne et al., \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e2012\u003c/span\u003e; Wicksell et al., \u003cspan citationid=\"CR46\" class=\"CitationRef\"\u003e2008\u003c/span\u003e; Wicksell et al., \u003cspan citationid=\"CR47\" class=\"CitationRef\"\u003e2010\u003c/span\u003e), resulting in the low quality of evidence of all findings. Regarding the effects of the combination of CBT and physical interventions, data synthesis was possible in the comparison between CBT with exercises and advice only for the long term with two RCTs (Michaleff et al., \u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e2014\u003c/span\u003e; M. J. Stewart et al., 2007), resulting in the moderate quality of evidence of all findings.\u003c/p\u003e \u003cdiv id=\"Sec16\" class=\"Section2\"\u003e \u003ch2\u003eThe meta-analysis for the effects of CBT alone compared with those of the wait-and-see control\u003c/h2\u003e \u003cp\u003eAt the short-term follow-up, statistically significant reductions in disability, fear of physical activity, anxiety, and depression were found in favor of CBT, although no difference in pain and posttraumatic stress was observed. Relatively, the effect size of the fear of physical activity, anxiety, and depression seems to be larger than that of disability, indicating the characteristics of CBT as a psychological intervention. In addition, no additional RCTs were included in the meta-analysis after the previous meta-analysis in 2016 (Anstey, Kongsted, Kamper, \u0026amp; Hancock, \u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e2016\u003c/span\u003e). The lack of additional RCTs may indicate that interest in recent research has shifted to the investigation of the combined effects of CBT and other treatments, such as exercise (Andersen et al., \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2020\u003c/span\u003e; Michaleff et al., \u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e2014\u003c/span\u003e; Pato et al., \u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e2010\u003c/span\u003e; S\u0026ouml;derlund \u0026amp; Lindberg, \u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e2001\u003c/span\u003e, \u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e2007\u003c/span\u003e; M. J. Stewart et al., 2007).\u003c/p\u003e \u003cp\u003e \u003cem\u003eThe meta-analysis of the combined effects of physical interventions and CBT compared with those of advice only\u003c/em\u003e \u003c/p\u003e \u003cp\u003eA statistically significant reduction in disability was found in favor of CBT. The moderate quality of evidence of the long-term effects of CBT with physical interventions on disability would be an important finding to better guide management strategies for chronic WADs from a Bio-Psycho-Social perspective. However, further investigations are needed to implement this finding in clinical practice. First, the effect size of 0.29 is small; thus, further investigations are required to determine the most effective form of CBT, dose, optimal combination with other therapeutic modalities, and ways to deliver these approaches. Second, the usefulness of the inclusion of CBT components in physical interventions is recognized and provided as a management strategy for patients with chronic low-back pain, such as cognitive functional therapy (O'Sullivan et al., \u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e2018\u003c/span\u003e). However, Beissner et al. (Beissner et al., \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e2009\u003c/span\u003e) have reported that physical therapists lack CBT implementation in clinical practice primarily due to limited knowledge about CBT techniques. Evidence has been increasing that educational/training level, not work experience, can be associated with the implementation of the Bio-Psycho-Social model of care with the identification of patients\u0026rsquo; psychological status (Miki, Kondo, Takebayashi, \u0026amp; Takasaki, \u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e2020\u003c/span\u003e; Suzuki \u0026amp; Takasaki, \u003cspan citationid=\"CR40\" class=\"CitationRef\"\u003e2020\u003c/span\u003e; Takasaki, Saiki, \u0026amp; Iwasada, \u003cspan citationid=\"CR41\" class=\"CitationRef\"\u003e2014\u003c/span\u003e). Establishing a global educational/training system will be a challenge for physical therapists to be able to implement the Bio-Psycho-Social model of care not only using CBT techniques but also other behavioral techniques, such as communication to increase patient\u0026rsquo;s autonomy (Murray et al., \u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e2019\u003c/span\u003e) and motivational interviews (Alperstein \u0026amp; Sharpe, \u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e2016\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eEvidence on the long-term effects of the combination of CBT and physical interventions compared with those of advice only is lacking, which is not surprising because the reduction of pain intensity is no longer the primary focus in patients with chronic WADs (Scholten-Peeters et al., \u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e2002\u003c/span\u003e). However, evidence is lacking on the long-term effects of the combination of CBT and physical interventions compared with those of advice only on QoL measures, which were subscales of the SF-36, although a statistically significant effect on disability was observed measured by the NDI. The discrepancy may reflect the lower responsiveness of the SF-36 than that of the NDI in patients with chronic WADs (Stewart, Maher, Refshauge, Bogduk, \u0026amp; Nicholas, 2007). In this systematic review, all PROMs had the structure of pre-determined items. Such a structured PROM reduces responsiveness from individuals with neck pain (Cleland, Fritz, Whitman, \u0026amp; Palmer, \u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e2006\u003c/span\u003e; M. Stewart et al., 2007) because each item has the same weight of importance among all participants, resulting in the lack of validity for measuring the intended health construct (Walton, Macdermid, \u0026amp; Nielson, \u003cspan citationid=\"CR44\" class=\"CitationRef\"\u003e2010\u003c/span\u003e). The recently developed Satisfaction and Recovery Index is an importance-weighted health-related satisfaction tool that captures both the process and status of recovery following musculoskeletal trauma and is shown to be more responsive than SF-12 and region-specific disability measures (Modarresi \u0026amp; Walton, \u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e2020\u003c/span\u003e; Walton, MacDermid, Pulickal, Rollack, \u0026amp; Veitch, \u003cspan citationid=\"CR45\" class=\"CitationRef\"\u003e2014\u003c/span\u003e). Therefore, further studies are required to include such an importance-weighted PROM for outcome measures to clarify the effects of an intervention for those with musculoskeletal trauma.\u003c/p\u003e \u003cp\u003eIn the two RCTs included in the meta-analysis, CBT was provided by physical therapists. Psychologically informed physical therapy would be recommended for managing patients with acute WADs who have a higher risk of a shift to chronic WADs (Ritchie, Hendrikz, Kenardy, \u0026amp; Sterling, \u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e2013\u003c/span\u003e; Michele Sterling, 2014) to minimize the number of chronic WADs. However, it has been unknown which is better in terms of treatment effect and cost-effectiveness between multidisciplinary approach with separate roles of CBT for psychologists and physical interventions for physical therapists and physical therapist\u0026rsquo;s delivering CBT with physical interventions. A solo approach performed by a physical therapist may not be sufficient in terms of the Bio-Psycho-Social model of care (Michele Sterling, 2014), but further investigations are required.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec17\" class=\"Section2\"\u003e \u003ch2\u003eLimitations\u003c/h2\u003e \u003cp\u003eOur meta-analysis had some limitations. The analysis was performed with a limited number of participants. Therefore, studies with a larger sample size should be performed in the future. Furthermore, we were unable to compare the advantages of combination of physical interventions and CBT with other treatments other than advice because of an insufficient number of RCTs pertaining to this topic. Finally, we did not actively seek unpublished studies. However, we believe it is unlikely to have had an important impact on the overall results.\u003c/p\u003e \u003c/div\u003e"},{"header":"Conclusion","content":"\u003cp\u003eThis systematic review with meta-analysis involving patients with chronic WADs found a low level of evidence on the favorable effects of CBT alone compared with those of the wait-and-see control on disability, the fear of physical activity, anxiety, and depression in the short term. In addition, this study found a moderate favorable evidence on the effects of the combination of physical interventions and CBT compared with those of advice only on disability in the long term.\u003c/p\u003e"},{"header":"Declarations","content":"\u003ch2\u003eAcknowledgments:\u0026nbsp;\u003c/h2\u003e\n\u003cp\u003eNone.\u003c/p\u003e\n\u003ch2\u003eSources of funding:\u0026nbsp;\u003c/h2\u003e\n\u003cp\u003eNo funding.\u003c/p\u003e\n\u003ch2\u003eConflict of Interest:\u0026nbsp;\u003c/h2\u003e\n\u003cp\u003eThe authors declare that they have no conflict of interest.\u003c/p\u003e\n\u003ch2\u003eAuthor contributions:\u003c/h2\u003e\n\u003cp\u003eConceptualization: Yu Kondo, Takahiro Miki, Hiroshi Takasaki.\u003c/p\u003e\n\u003cp\u003eData curation: Yu Kondo, Takahiro Miki, Hiroshi Kurakata.\u003c/p\u003e\n\u003cp\u003eFormal analysis: Yu Kondo, Takahiro Miki, Hiroshi Kurakata.\u003c/p\u003e\n\u003cp\u003eInvestigation: Yu Kondo, Takahiro Miki, Hiroshi Kurakata.\u003c/p\u003e\n\u003cp\u003eMethodology: Yu Kondo, Takahiro Miki, Hiroshi Kurakata, Hiroshi Takasaki.\u003c/p\u003e\n\u003cp\u003eProject administration: Miki Takahiro, Tsuneo Takebayashi, Hiroshi Takasaki. Supervision: Tsuneo Takebayashi, Hiroshi Takasaki.\u003c/p\u003e\n\u003cp\u003eVisualization: Tsuneo Takebayashi.\u003c/p\u003e\n\u003cp\u003eWriting \u0026ndash; original draft: Yu Kondo, Takahiro Miki, Hiroshi Takasaki.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n \u003cli\u003eAlperstein, D., \u0026amp; Sharpe, L. (2016). The Efficacy of Motivational Interviewing in Adults With Chronic Pain: A Meta-Analysis and Systematic Review. \u003cem\u003eJ Pain, 17\u003c/em\u003e, 393-403.\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eAndersen, T. E., Ravn, S. L., Armfield, N., Maujean, A., Requena, S. S., \u0026amp; Sterling, M. (2020). Trauma-focused cognitive behavioural therapy and exercise for chronic whiplash with comorbid posttraumatic stress disorder: a randomised controlled trial. \u003cem\u003ePain, 162\u003c/em\u003e, 1221-1232.\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eAnstey, R., Kongsted, A., Kamper, S., \u0026amp; Hancock, M. J. (2016). 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A randomized controlled trial of cognitive-behavioral therapy for the treatment of PTSD in the context of chronic whiplash. \u003cem\u003eClin J Pain, 28\u003c/em\u003e, 755-765.\u003c/li\u003e\n \u003cli\u003eEhrenborg, C., \u0026amp; Archenholtz, B. (2010). Is surface EMG biofeedback an effective training method for persons with neck and shoulder complaints after whiplash-associated disorders concerning activities of daily living and pain -- a randomized controlled trial. \u003cem\u003eClin Rehabil, 24\u003c/em\u003e, 715-726.\u003c/li\u003e\n \u003cli\u003eFisher, E., Law, E., Dudeney, J., Palermo, T. M., Stewart, G., \u0026amp; Eccleston, C. (2018). Psychological therapies for the management of chronic and recurrent pain in children and adolescents. \u003cem\u003eCochrane Database Syst Rev, 9\u003c/em\u003e(9), Cd003968.\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eFlor, H., \u0026amp; Turk, D. C. (1984). Etiological theories and treatments for chronic back pain. I. Somatic models and interventions. \u003cem\u003ePain, 19\u003c/em\u003e, 105-121.\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eFurlan, A. D., Malmivaara, A., Chou, R., Maher, C. G., Deyo, R. A., Schoene, M., . . . Editorial Board of the Cochrane Back, N. G. (2015). 2015 Updated Method Guideline for Systematic Reviews in the Cochrane Back and Neck Group. \u003cem\u003eSpine (Phila Pa 1976), 40\u003c/em\u003e, 1660-1673.\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eGatchel, R. J., Peng, Y. B., Peters, M. L., Fuchs, P. N., \u0026amp; Turk, D. C. (2007). The biopsychosocial approach to chronic pain: scientific advances and future directions. \u003cem\u003ePsychol Bull, 133\u003c/em\u003e, 581-624.\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eGross, A., Kay, T. M., Paquin, J. P., Blanchette, S., Lalonde, P., Christie, T., . . . Cervical Overview, G. (2015). Exercises for mechanical neck disorders. \u003cem\u003eCochrane Database Syst Rev, 1\u003c/em\u003e, CD004250.\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eLamb, S. E., Hansen, Z., Lall, R., Castelnuovo, E., Withers, E. J., Nichols, V., . . . Underwood, M. R. (2010). Group cognitive behavioural treatment for low-back pain in primary care: a randomised controlled trial and cost-effectiveness analysis. \u003cem\u003eThe Lancet, 375\u003c/em\u003e, 916-923.\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eMaher, C. G., Sherrington, C., Herbert, R. D., Moseley, A. M., \u0026amp; Elkins, M. (2003). Reliability of the PEDro scale for rating quality of randomized controlled trials. \u003cem\u003ePhys Ther, 83\u003c/em\u003e, 713-721.\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eMichaleff, Z. A., Maher, C. G., Lin, C.-W. C., Rebbeck, T., Jull, G., Latimer, J., . . . Sterling, M. (2014). Comprehensive physiotherapy exercise programme or advice for chronic whiplash (PROMISE): a pragmatic randomised controlled trial. \u003cem\u003eThe Lancet, 384\u003c/em\u003e, 133-141.\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eMiki, T., Kondo, Y., Takebayashi, T., \u0026amp; Takasaki, H. (2020). Difference between physical therapist estimation and psychological patient-reported outcome measures in patients with low back pain. \u003cem\u003ePLoS One, 15\u003c/em\u003e, e0227999.\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eModarresi, S., \u0026amp; Walton, D. M. (2020). Reliability, discriminative accuracy, and an exploration of response shift as measured using the satisfaction and Recovery Index over 12 months from musculoskeletal trauma. \u003cem\u003eMusculoskelet Sci Pract, 51\u003c/em\u003e, 102300.\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eMoher, D., Liberati, A., Tetzlaff, J., Altman, D. G., \u0026amp; Group, P. (2009). Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. \u003cem\u003ePLoS Med, 6\u003c/em\u003e, e1000097.\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eMonticone, M., Cedraschi, C., Ambrosini, E., Rocca, B., Fiorentini, R., Restelli, M., . . . Moja, L. (2015). Cognitive-behavioural treatment for subacute and chronic neck pain. \u003cem\u003eCochrane Database Syst Rev\u003c/em\u003e, CD010664.\u003c/li\u003e\n \u003cli\u003eMorley, S. (2011). Efficacy and effectiveness of cognitive behaviour therapy for chronic pain: Progress and some challenges. \u003cem\u003ePain, 152\u003c/em\u003e, 99-106.\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eMurray, A., Hall, A., Williams, G. C., McDonough, S. M., Ntoumanis, N., Taylor, I., . . . Matthews, J. (2019). Assessing physiotherapists\u0026rsquo; communication skills for promoting patient autonomy for self-management: reliability and validity of the communication evaluation in rehabilitation tool. \u003cem\u003eDisability and Rehabilitation, 41\u003c/em\u003e, 1699-1705.\u003c/li\u003e\n \u003cli\u003eO\u0026apos;Sullivan, P. B., Caneiro, J. P., O\u0026apos;Keeffe, M., Smith, A., Dankaerts, W., Fersum, K., \u0026amp; O\u0026apos;Sullivan, K. (2018). Cognitive Functional Therapy: An Integrated Behavioral Approach for the Targeted Management of Disabling Low Back Pain. \u003cem\u003ePhys Ther, 98\u003c/em\u003e, 408-423.\u0026nbsp;\u003c/li\u003e\n \u003cli\u003ePato, U., Di Stefano, G., Fravi, N., Arnold, M., Curatolo, M., Radanov, B. P., . . . Sturzenegger, M. (2010). Comparison of randomized treatments for late whiplash. \u003cem\u003eNeurology, 74\u003c/em\u003e, 1223-1230.\u0026nbsp;\u003c/li\u003e\n \u003cli\u003ePollock, A., Farmer, S. E., Brady, M. C., Langhorne, P., Mead, G. E., Mehrholz, J., . . . Wiffen, P. J. (2016). An algorithm was developed to assign GRADE levels of evidence to comparisons within systematic reviews. \u003cem\u003eJ Clin Epidemiol, 70\u003c/em\u003e, 106-110.\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eRichmond, H., Hall, A. M., Copsey, B., Hansen, Z., Williamson, E., Hoxey-Thomas, N., . . . Lamb, S. E. (2015). The Effectiveness of Cognitive Behavioural Treatment for Non-Specific Low Back Pain: A Systematic Review and Meta-Analysis. \u003cem\u003ePLoS One, 10\u003c/em\u003e, e0134192.\u003c/li\u003e\n \u003cli\u003eRis, I., Juul-Kristensen, B., Boyle, E., Kongsted, A., Manniche, C., \u0026amp; S\u0026oslash;gaard, K. (2017). Chronic neck pain patients with traumatic or non-traumatic onset: Differences in characteristics. A cross-sectional study. \u003cem\u003eScand J Pain, 14\u003c/em\u003e, 1-8.\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eRitchie, C., Hendrikz, J., Kenardy, J., \u0026amp; Sterling, M. (2013). Derivation of a clinical prediction rule to identify both chronic moderate/severe disability and full recovery following whiplash injury. \u003cem\u003ePain, 154\u003c/em\u003e, 2198-2206.\u003c/li\u003e\n \u003cli\u003eScholten-Peeters, G. G., Bekkering, G. E., Verhagen, A. P., van Der Windt, D. A., Lanser, K., Hendriks, E. J., \u0026amp; Oostendorp, R. A. (2002). Clinical practice guideline for the physiotherapy of patients with whiplash-associated disorders. \u003cem\u003eSpine (Phila Pa 1976), 27\u003c/em\u003e, 412-422.\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eShearer, H. M., Carroll, L. J., Wong, J. J., Cote, P., Varatharajan, S., Southerst, D., . . . Taylor-Vaisey, A. L. (2016). Are psychological interventions effective for the management of neck pain and whiplash-associated disorders? A systematic review by the Ontario Protocol for Traffic Injury Management (OPTIMa) Collaboration. \u003cem\u003eSpine J, 16\u003c/em\u003e, 1566-1581.\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eS\u0026ouml;derlund, A., \u0026amp; Lindberg, P. (2001). Cognitive behavioural components in physiotherapy management of chronic whiplash associated disorders (WAD)--a randomised group study. \u003cem\u003ePhysiotherapy Theory and Practice, 17\u003c/em\u003e, 229-238.\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eS\u0026ouml;derlund, A., \u0026amp; Lindberg, P. (2007). Cognitive behavioural components in physiotherapy management of chronic whiplash associated disorders (WAD)--a randomised group study. \u003cem\u003eG Ital Med Lav Ergon, 29\u003c/em\u003e, 5-11.\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eSpitzer, W. O., Skovron, M. L., Salmi, L. R., Cassidy, J. D., Duranceau, J., Suissa, S., \u0026amp; Zeiss, E. (1995). Scientific monograph of the Quebec Task Force on Whiplash-Associated Disorders: redefining \u0026quot;whiplash\u0026quot; and its management. \u003cem\u003eSpine (Phila Pa 1976), 20\u003c/em\u003e, 1-73.\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eSterling, M. (2014a). Physiotherapy management of whiplash-associated disorders (WAD). \u003cem\u003eJournal of physiotherapy, 60\u003c/em\u003e, 5-12.\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eSterling, M. (2014b). Physiotherapy management of whiplash-associated disorders (WAD). \u003cem\u003eJ Physiother, 60\u003c/em\u003e, 5-12.\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eStewart, M., Maher, C. G., Refshauge, K. M., Bogduk, N., \u0026amp; Nicholas, M. (2007a). Responsiveness of pain and disability measures for chronic whiplash. \u003cem\u003eSpine (Phila Pa 1976), 32\u003c/em\u003e, 580-585.\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eStewart, M. J., Maher, C. G., Refshauge, K. M., Herbert, R. D., Bogduk, N., \u0026amp; Nicholas, M. (2007b). Randomized controlled trial of exercise for chronic whiplash-associated disorders. \u003cem\u003ePain, 128\u003c/em\u003e, 59-68.\u003c/li\u003e\n \u003cli\u003e\u0026nbsp;Suzuki, K., \u0026amp; Takasaki, H. (2020). Ability of Therapists Trained in Mechanical Diagnosis and Therapy to Guess Pain Catastrophizing and Kinesiophobia Scores for Patients with Low Back Pain. \u003cem\u003eOpen Journal of Therapy and Rehabilitation, 8\u003c/em\u003e, 119-130.\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eTakasaki, H., Saiki, T., \u0026amp; Iwasada, Y. (2014). McKenzie Therapists Adhere More to Evidence-Based Guidelines and Have a More Biopsychosocial Perspective on the Management of Patients with Low Back Pain than General Physical Therapists in Japan. \u003cem\u003eOpen Journal of Therapy and Rehabilitation, 02\u003c/em\u003e, 173-181.\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eTurk, D. C., \u0026amp; Flor, H. (1984). Etiological theories and treatments for chronic back pain. II. Psychological models and interventions. \u003cem\u003ePain, 19\u003c/em\u003e, 209-233.\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eUrits, I., Hubble, A., Peterson, E., Orhurhu, V., Ernst, C. A., Kaye, A. D., \u0026amp; Viswanath, O. (2019). An Update on Cognitive Therapy for the Management of Chronic Pain: a Comprehensive Review. \u003cem\u003eCurr Pain Headache Rep, 23\u003c/em\u003e, 57.\u003c/li\u003e\n \u003cli\u003eWalton, D. M., Macdermid, J. C., \u0026amp; Nielson, W. (2010). Recovery from acute injury: clinical, methodological and philosophical considerations. \u003cem\u003eDisabil Rehabil, 32\u003c/em\u003e, 864-874.\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eWalton, D. M., MacDermid, J. C., Pulickal, M., Rollack, A., \u0026amp; Veitch, J. (2014). Development and Initial Validation of the Satisfaction and Recovery Index (SRI) for Measurement of Recovery from Musculoskeletal Trauma. \u003cem\u003eOpen Orthop J, 8\u003c/em\u003e, 316-325.\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eWicksell, R. K., Ahlqvist, J., Bring, A., Melin, L., \u0026amp; Olsson, G. L. (2008). Can exposure and acceptance strategies improve functioning and life satisfaction in people with chronic pain and whiplash-associated disorders (WAD)? A randomized controlled trial. \u003cem\u003eCogn Behav Ther, 37\u003c/em\u003e, 169-182.\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eWicksell, R. K., Olsson, G. L., \u0026amp; Hayes, S. C. (2010). Psychological flexibility as a mediator of improvement in Acceptance and Commitment Therapy for patients with chronic pain following whiplash. \u003cem\u003eEur J Pain, 14\u003c/em\u003e, 1059.e1051-1059.e1011.\u003c/li\u003e\n\u003c/ol\u003e"},{"header":"Tables","content":"\u003cp style=\"text-align: center;\"\u003eTable 1.\u0026nbsp;\u003c/p\u003e\n\u003cp style=\"text-align: center;\"\u003ePEDro scores of the studies included in this systematic review\u0026nbsp;\u003c/p\u003e\n\u003cdiv align=\"center\"\u003e\n \u003ctable border=\"1\" cellpadding=\"0\" cellspacing=\"0\" width=\"102%\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"15.625%\"\u003e\n \u003cp\u003eStudy\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"8.333333333333334%\"\u003e\n \u003cp\u003eRandom allocation\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"8.333333333333334%\"\u003e\n \u003cp\u003eConcealed allocation\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.291666666666667%\"\u003e\n \u003cp\u003eGroups similar at baseline\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"8.333333333333334%\"\u003e\n \u003cp\u003eParticipant blinding\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.291666666666667%\"\u003e\n \u003cp\u003eTherapist blinding\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.291666666666667%\"\u003e\n \u003cp\u003eAssessor blinding\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.291666666666667%\"\u003e\n \u003cp\u003e\u0026lt; 15% dropouts\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"8.333333333333334%\"\u003e\n \u003cp\u003eIntention-to-treat analysis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"8.333333333333334%\"\u003e\n \u003cp\u003eBetween-group difference reported\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"8.333333333333334%\"\u003e\n \u003cp\u003ePoint estimate and variability reported\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"5.208333333333333%\"\u003e\n \u003cp\u003eTotal\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"15.625%\"\u003e\n \u003cp\u003eAndersen 2020\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"8.333333333333334%\"\u003e\n \u003cp\u003eY\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"8.333333333333334%\"\u003e\n \u003cp\u003eY\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.291666666666667%\"\u003e\n \u003cp\u003eY\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"8.333333333333334%\"\u003e\n \u003cp\u003eN\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.291666666666667%\"\u003e\n \u003cp\u003eN\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.291666666666667%\"\u003e\n \u003cp\u003eY\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.291666666666667%\"\u003e\n \u003cp\u003eN\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"8.333333333333334%\"\u003e\n \u003cp\u003eY\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"8.333333333333334%\"\u003e\n \u003cp\u003eY\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"8.333333333333334%\"\u003e\n \u003cp\u003eY\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"5.208333333333333%\"\u003e\n \u003cp\u003e7\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"15.625%\"\u003e\n \u003cp\u003eDunne 2012\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"8.333333333333334%\"\u003e\n \u003cp\u003eY\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"8.333333333333334%\"\u003e\n \u003cp\u003eN\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.291666666666667%\"\u003e\n \u003cp\u003eY\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"8.333333333333334%\"\u003e\n \u003cp\u003eN\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.291666666666667%\"\u003e\n \u003cp\u003eN\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.291666666666667%\"\u003e\n \u003cp\u003eN\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.291666666666667%\"\u003e\n \u003cp\u003eY\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"8.333333333333334%\"\u003e\n \u003cp\u003eY\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"8.333333333333334%\"\u003e\n \u003cp\u003eY\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"8.333333333333334%\"\u003e\n \u003cp\u003eY\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"5.208333333333333%\"\u003e\n \u003cp\u003e6\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"15.625%\"\u003e\n \u003cp\u003eEhrenborg 2010\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"8.333333333333334%\"\u003e\n \u003cp\u003eN\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"8.333333333333334%\"\u003e\n \u003cp\u003eN\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.291666666666667%\"\u003e\n \u003cp\u003eY\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"8.333333333333334%\"\u003e\n \u003cp\u003eN\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.291666666666667%\"\u003e\n \u003cp\u003eN\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.291666666666667%\"\u003e\n \u003cp\u003eN\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.291666666666667%\"\u003e\n \u003cp\u003eY\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"8.333333333333334%\"\u003e\n \u003cp\u003eY\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"8.333333333333334%\"\u003e\n \u003cp\u003eY\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"8.333333333333334%\"\u003e\n \u003cp\u003eY\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"5.208333333333333%\"\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"15.625%\"\u003e\n \u003cp\u003eMichaleff 2014\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"8.333333333333334%\"\u003e\n \u003cp\u003eY\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"8.333333333333334%\"\u003e\n \u003cp\u003eY\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.291666666666667%\"\u003e\n \u003cp\u003eY\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"8.333333333333334%\"\u003e\n \u003cp\u003eN\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.291666666666667%\"\u003e\n \u003cp\u003eN\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.291666666666667%\"\u003e\n \u003cp\u003eY\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.291666666666667%\"\u003e\n \u003cp\u003eY\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"8.333333333333334%\"\u003e\n \u003cp\u003eY\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"8.333333333333334%\"\u003e\n \u003cp\u003eY\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"8.333333333333334%\"\u003e\n \u003cp\u003eY\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"5.208333333333333%\"\u003e\n \u003cp\u003e8\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"15.625%\"\u003e\n \u003cp\u003ePato 2010\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"8.333333333333334%\"\u003e\n \u003cp\u003eY\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"8.333333333333334%\"\u003e\n \u003cp\u003eN\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.291666666666667%\"\u003e\n \u003cp\u003eY\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"8.333333333333334%\"\u003e\n \u003cp\u003eN\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.291666666666667%\"\u003e\n \u003cp\u003eN\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.291666666666667%\"\u003e\n \u003cp\u003eN\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.291666666666667%\"\u003e\n \u003cp\u003eN\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"8.333333333333334%\"\u003e\n \u003cp\u003eN\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"8.333333333333334%\"\u003e\n \u003cp\u003eY\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"8.333333333333334%\"\u003e\n \u003cp\u003eY\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"5.208333333333333%\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"15.625%\"\u003e\n \u003cp\u003eSoderlund 2001, 2007\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"8.333333333333334%\"\u003e\n \u003cp\u003eY\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"8.333333333333334%\"\u003e\n \u003cp\u003eN\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.291666666666667%\"\u003e\n \u003cp\u003eY\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"8.333333333333334%\"\u003e\n \u003cp\u003eN\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.291666666666667%\"\u003e\n \u003cp\u003eN\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.291666666666667%\"\u003e\n \u003cp\u003eY\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.291666666666667%\"\u003e\n \u003cp\u003eY\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"8.333333333333334%\"\u003e\n \u003cp\u003eN\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"8.333333333333334%\"\u003e\n \u003cp\u003eY\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"8.333333333333334%\"\u003e\n \u003cp\u003eY\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"5.208333333333333%\"\u003e\n \u003cp\u003e6\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"15.625%\"\u003e\n \u003cp\u003eStewart 2007\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"8.333333333333334%\"\u003e\n \u003cp\u003eY\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"8.333333333333334%\"\u003e\n \u003cp\u003eY\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.291666666666667%\"\u003e\n \u003cp\u003eY\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"8.333333333333334%\"\u003e\n \u003cp\u003eN\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.291666666666667%\"\u003e\n \u003cp\u003eN\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.291666666666667%\"\u003e\n \u003cp\u003eY\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.291666666666667%\"\u003e\n \u003cp\u003eY\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"8.333333333333334%\"\u003e\n \u003cp\u003eY\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"8.333333333333334%\"\u003e\n \u003cp\u003eY\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"8.333333333333334%\"\u003e\n \u003cp\u003eY\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"5.208333333333333%\"\u003e\n \u003cp\u003e8\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"15.625%\"\u003e\n \u003cp\u003eWicksell 2008, 2010\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"8.333333333333334%\"\u003e\n \u003cp\u003eY\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"8.333333333333334%\"\u003e\n \u003cp\u003eY\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.291666666666667%\"\u003e\n \u003cp\u003eY\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"8.333333333333334%\"\u003e\n \u003cp\u003eN\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.291666666666667%\"\u003e\n \u003cp\u003eN\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.291666666666667%\"\u003e\n \u003cp\u003eN\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.291666666666667%\"\u003e\n \u003cp\u003eY\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"8.333333333333334%\"\u003e\n \u003cp\u003eY\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"8.333333333333334%\"\u003e\n \u003cp\u003eY\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"8.333333333333334%\"\u003e\n \u003cp\u003eY\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"5.208333333333333%\"\u003e\n \u003cp\u003e7\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n\u003c/div\u003e\n\u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n\u003cdiv align=\"center\" id=\"isPasted\"\u003e\n \u003ctable border=\"0\" cellpadding=\"0\" cellspacing=\"0\" width=\"100%\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"5\" width=\"81.81818181818181%\"\u003e\n \u003cp style=\"text-align: center;\"\u003eTable 2.\u0026nbsp;\u003c/p\u003e\n \u003cp style=\"text-align: center;\"\u003eSummary of the eight studies included in this systematic review\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"18.181818181818183%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"9.090909090909092%\"\u003e\n \u003cp\u003eStudy, data collection country, the source of funding, and study design\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.181818181818183%\"\u003e\n \u003cp\u003eParticipants\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.181818181818183%\"\u003e\n \u003cp\u003eInterventions\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.181818181818183%\"\u003e\n \u003cp\u003eComparisons\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.181818181818183%\"\u003e\n \u003cp\u003eOutcome measures\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.181818181818183%\"\u003e\n \u003cp\u003eResults\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"9.090909090909092%\"\u003e\n \u003cp\u003eAndersen et al., 2020; Australia and Denmark,\u0026nbsp;NHMRC Project Grant and Danish Victims Fund Project, RCTs\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"18.181818181818183%\"\u003e\n \u003cp\u003eTotal n\u0026nbsp;(completing)\u0026nbsp;= 103 (79) (from recruited advertisements and clinical practices in Southeast Queensland in Australia and the region of Zealand in Denmark between).\u003c/p\u003e\n \u003cp\u003eParticipants were aged between 18 and 70 years\u0026nbsp;and\u0026nbsp;diagnosed with chronic WADs grade II and PTSD.\u003c/p\u003e\n \u003cp\u003eCBT group: Age:\u0026nbsp;39.7\u0026nbsp;\u0026plusmn;\u0026nbsp;13.3 years. Gender:\u0026nbsp;14 males, 39 females. Mean duration of symptoms:\u0026nbsp;2.49\u0026nbsp;\u0026plusmn;\u0026nbsp;1.9 years.\u003c/p\u003e\n \u003cp\u003eControl group: Age: 44.5 \u0026plusmn; 11.6 years. Gender 14 males, 36 females. Mean duration of symptoms: 3.33 \u0026plusmn; 4.2 years.\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"18.181818181818183%\"\u003e\n \u003cp\u003e10 weekly 60\u0026ndash;90-minute sessions of individually delivered trauma-focused CBT (PTSD-related psychoeducation, teaching anxiety management strategies, such as progressive muscle relaxation, initiating cognitive restructuring of unhelpful thoughts and assumptions, and applying prolonged imaginal and \u003cem\u003ein vivo\u003c/em\u003e exposure relapse prevention) by psychologists who were trained in appropriate protocols and had training in the trial interventions. After receiving the aforementioned psychological interventions, the exercise program was delivered by physical therapists who were trained in appropriate protocols and had training in the trial interventions and comprised 10 sessions for over 6 weeks (specific exercises to improve mobility, strength, and endurance of the neck and shoulder girdle muscles and exercises to improve eye/head coordination).\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"18.181818181818183%\"\u003e\n \u003cp\u003eSupportive therapy was given in 10 weekly 60-minute individual sessions including psychoeducation about PTSD symptomatology and the rationale for ST and discussion of current issues and general problem-solving skills. Supportive intervention would specifically avoid exposure, cognitive restructuring, and anxiety management techniques.\u0026nbsp;After receiving the aforementioned psychological interventions, the exercise program was delivered by physical therapists who were trained in appropriate protocols and had training in the trial interventions and comprised 10 sessions for over 6 weeks (specific exercises to improve mobility, strength, and endurance of the neck and shoulder girdle muscles and exercises to improve eye/head coordination).\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"18.181818181818183%\"\u003e\n \u003cp\u003eOther objective measures that were not included in this\u0026nbsp;meta-analysis.\u003c/p\u003e\n \u003cp\u003ePain: Week average, NRS\u003c/p\u003e\n \u003cp\u003eDisability:\u0026nbsp;NDI\u003c/p\u003e\n \u003cp\u003eFunctional ability: PSFS\u003c/p\u003e\n \u003cp\u003eQuality of life: SF-12\u003c/p\u003e\n \u003cp\u003eDepression and anxiety: DASS\u003cbr\u003e\u0026nbsp;Fear physical activity: TSK\u003c/p\u003e\n \u003cp\u003ePain catastrophizing: PCS\u003c/p\u003e\n \u003cp\u003eSelf-efficacy: PSEQ\u003c/p\u003e\n \u003cp\u003ePTSD: CAPS-5 and\u0026nbsp;PTSD checklist\u003c/p\u003e\n \u003cp\u003eGlobal perceived effect: 11-point scale\u003c/p\u003e\n \u003cp\u003eAdverse events\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eFollow-up: 10\u0026nbsp;weeks, 16 weeks, 6\u0026nbsp;months, 12 months\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"18.181818181818183%\"\u003e\n \u003cp\u003eStatistically significant improvement in the PCS at 16 weeks and TSK at 12 months for the CBT group compared with the\u0026nbsp;control group.\u0026nbsp;No statistically significant improvement in the NRS, NDI, PSFS, SF-12,\u0026nbsp;DASS, and PSEQ\u0026nbsp;in the\u0026nbsp;CBT group compared\u0026nbsp;with the\u0026nbsp;control group at any time point.\u0026nbsp;No serious adverse events.\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"9.090909090909092%\"\u003e\n \u003cp\u003eDunne et al., 2012;\u003c/p\u003e\n \u003cp\u003eAustralia,\u0026nbsp;no\u0026nbsp;funding, RCTs\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"18.181818181818183%\"\u003e\n \u003cp\u003eTotal n\u0026nbsp;(completing)\u0026nbsp;= 26 (22) (recruited through newspaper, poster, and email advertisements in\u0026nbsp;Southeast Queensland, Australia).\u003c/p\u003e\n \u003cp\u003eParticipants were aged between 20 and 49 years and diagnosed with chronic WADs grade II or III and motor vehicle crash-related PTSD. Gender: 13 males, 13 females. Duration of symptoms ranged from 3 months to 5years with a mean of 28.5 months.\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"18.181818181818183%\"\u003e\n \u003cp\u003e10 weekly 1-hour sessions of individually delivered CBT based on the Australian\u0026nbsp;guidelines for the treatment of\u0026nbsp;adults with\u0026nbsp;acute stress disorder\u0026nbsp;and PTSD (cognitive strategies, coping self-talk,\u0026nbsp;and\u0026nbsp;cognitive restructuring)\u0026nbsp;administered by a graduate psychologist with post- graduate clinical training and 12 months of prior experience delivering CBT interventions.\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"18.181818181818183%\"\u003e\n \u003cp\u003eWait-and-see control.\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"18.181818181818183%\"\u003e\n \u003cp\u003ePain: current pain on NRS\u0026nbsp;\u003cbr\u003e\u0026nbsp;Disability/functional status: NDI\u003c/p\u003e\n \u003cp\u003eDepression and anxiety: DASS\u003c/p\u003e\n \u003cp\u003ePosttraumatic stress: IES-R\u0026nbsp;\u003cbr\u003e\u0026nbsp;Fear physical activity: TSK\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eOther objective measures that were\u0026nbsp;excluded from\u0026nbsp;this\u0026nbsp;meta-analysis.\u003c/p\u003e\n \u003cp\u003eQuality of life: SF-36\u003c/p\u003e\n \u003cp\u003ePsychological distress: PDS\u003c/p\u003e\n \u003cp\u003ePressure pain thresholds: Digital pressure algometer\u003c/p\u003e\n \u003cp\u003e\u003cbr\u003e\u0026nbsp;Follow-up: Post-intervention, 6 months\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"18.181818181818183%\"\u003e\n \u003cp\u003eStatistically\u0026nbsp;significant improvement in the NDI, SF36, PDS, IES-R, and\u003c/p\u003e\n \u003cp\u003eTSK\u0026nbsp;in the\u0026nbsp;CBT group compared\u0026nbsp;with the\u0026nbsp;control group\u0026nbsp;after\u0026nbsp;intervention.\u0026nbsp;The\u0026nbsp;improvements in the CBT group were maintained at 6 months.\u0026nbsp;No statistically\u0026nbsp;significant improvement in the NRS\u0026nbsp;in the\u0026nbsp;CBT group compared\u0026nbsp;with the\u0026nbsp;control group\u0026nbsp;after the\u0026nbsp;intervention.\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"9.090909090909092%\"\u003e\n \u003cp\u003eEhrenborg and Lindberg., 2010;\u003c/p\u003e\n \u003cp\u003eSweden,\u003c/p\u003e\n \u003cp\u003eno\u0026nbsp;funding, RCTs\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"18.181818181818183%\"\u003e\n \u003cp\u003eTotal n\u0026nbsp;(completing)\u0026nbsp;= 65 (59) (from\u0026nbsp;the pain unit of the Department of Rehabilitation Medicine,\u0026nbsp;Boras Hospital).\u003c/p\u003e\n \u003cp\u003eParticipants were aged 39.4 \u0026plusmn; 11.1 years and diagnosed with chronic WADs. Gender: 31 males, 34 females. Duration of symptoms ranged from 4 to 177 mouths with a mean of 25.0 \u0026plusmn; 30.2 months.\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"18.181818181818183%\"\u003e\n \u003cp\u003eInterdisciplinary rehabilitation based on cognitive behavioral perspectives of pain provided 5 hours/day, 5 days/week\u0026nbsp;for\u0026nbsp;4\u0026ndash;6 weeks\u0026nbsp;by occupational therapists, physical therapists,\u0026nbsp;physicians, nurses, nurse\u0026nbsp;assistants, psychologists,\u0026nbsp;and social workers. In addition,\u0026nbsp;eight sessions of\u0026nbsp;biofeedback training (55-minute sessions/week for 4 weeks) conducted during engagement in occupational therapy handicraft with surface electromyography.\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"18.181818181818183%\"\u003e\n \u003cp\u003eInterdisciplinary rehabilitation based on cognitive behavioral perspectives of pain provided 5 hours/day, 5 days/week for 4\u0026ndash;6 week by occupational therapists, physical therapists, physicians, nurses, nurse assistants, psychologists, and social workers. The control group was active in handicraft on the same terms as the treatment group but without surface electromyography biofeedback.\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"18.181818181818183%\"\u003e\n \u003cp\u003eOther objective measures that were\u0026nbsp;excluded from\u0026nbsp;this\u0026nbsp;meta-analysis.\u003c/p\u003e\n \u003cp\u003eOccupational performance and satisfaction with the performance: Canadian Occupational Performance Measure\u003c/p\u003e\n \u003cp\u003ePsychosocial functioning:\u0026nbsp;Multidimensional Pain Inventory\u003c/p\u003e\n \u003cp\u003e\u003cbr\u003e\u0026nbsp;Follow-up: 4\u0026ndash;6weeks and 6 months\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"18.181818181818183%\"\u003e\n \u003cp\u003eNo statistically\u0026nbsp;significant improvement in the Canadian Occupational Performance Measure and Multidimensional Pain Inventory\u0026nbsp;in the\u0026nbsp;CBT (with surface electromyography) group compared\u0026nbsp;with the control\u0026nbsp;group at any time point.\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"9.090909090909092%\"\u003e\n \u003cp\u003eMichaleff et al., 2014;\u003c/p\u003e\n \u003cp\u003eAustralia,\u0026nbsp;no\u0026nbsp;funding, RCTs\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"18.181818181818183%\"\u003e\n \u003cp\u003eTotal n\u0026nbsp;(completing)\u0026nbsp;= 172 (150)\u0026nbsp;(from sites in Sydney and Brisbane, Australia).\u003c/p\u003e\n \u003cp\u003eParticipants were aged between 18 and 65 years\u0026nbsp;and\u0026nbsp;diagnosed with chronic WADs grade\u0026nbsp;I\u0026nbsp;or II.\u003c/p\u003e\n \u003cp\u003eCBT group: Age:\u0026nbsp;42.6\u0026nbsp;\u0026plusmn;\u0026nbsp;12.3 years. Gender:\u0026nbsp;38 males, 48 females. Mean duration of symptoms:\u0026nbsp;20.9\u0026nbsp;\u0026plusmn;\u0026nbsp;15.1 months.\u003c/p\u003e\n \u003cp\u003eControl group: Age:\u0026nbsp;43.1\u0026nbsp;\u0026plusmn;\u0026nbsp;12.7 years. Gender:\u0026nbsp;26 males, 60 females. Mean duration of symptoms:\u0026nbsp;22.0\u0026nbsp;\u0026plusmn;\u0026nbsp;18.2 months.\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"18.181818181818183%\"\u003e\n \u003cp\u003eIndividually tailored and supervised comprehensive exercise program\u0026nbsp;provided by physical therapists who were\u0026nbsp;trained at a 1-day workshop.\u0026nbsp;Twenty\u0026nbsp;sessions lasting 1 h for 12 weeks (two sessions per week for 8 weeks; one session per week for 4 weeks). CBT strategies were used for\u0026nbsp;a\u0026nbsp;comprehensive exercise\u0026nbsp;program (encouraging\u0026nbsp;skill acquisition by modeling, setting progressive goals, and self-monitoring, and positively reinforcing\u0026nbsp;progress). The comprehensive exercise program included specific cervical spine exercises,\u0026nbsp;neck extensor endurance exercises, specific neck motor relearning exercises, aerobic\u0026nbsp;exercises, and manual\u0026nbsp;therapy techniques\u0026nbsp;provided with the patient educational booklet.\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"18.181818181818183%\"\u003e\n \u003cp\u003eThe participants\u0026nbsp;received a 30-min consultation with a\u0026nbsp;physical therapist\u0026nbsp;during which they read the educational booklet, practiced the exercises with minimum guidance (verbal or physical) from the\u0026nbsp;physical therapist. The participants\u0026nbsp;were then required to implement the advice provided and practice the exercises independently at their own discretion. No additional supervision was provided.\u0026nbsp;The participants\u0026nbsp;had the opportunity to contact the\u0026nbsp;physical therapist\u0026nbsp;by telephone on two occasions if they needed further verbal clarification of the information covered in the consultation.\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"18.181818181818183%\"\u003e\n \u003cp\u003ePain: Week average, NRS\u003c/p\u003e\n \u003cp\u003eDisability/functional status: NDI\u003c/p\u003e\n \u003cp\u003eQuality of life: SF-36\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eOther objective measures that were\u0026nbsp;excluded from\u0026nbsp;this\u0026nbsp;meta-analysis.\u003c/p\u003e\n \u003cp\u003eGlobal perceived effect: Global perceived effect scale\u003c/p\u003e\n \u003cp\u003eDisability/functional status:\u0026nbsp;Whiplash Disability Questionnaire\u003c/p\u003e\n \u003cp\u003eFunctional ability: PSFS\u0026nbsp;Cervical range of motion:\u0026nbsp;Inclinometer\u003c/p\u003e\n \u003cp\u003eAdverse events\u003c/p\u003e\n \u003cp\u003eFollow-up:\u0026nbsp;14 weeks, 6\u0026nbsp;months, and\u0026nbsp;12 months\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"18.181818181818183%\"\u003e\n \u003cp\u003eStatistically\u0026nbsp;significant improvement in the\u0026nbsp;Global perceived effect scale\u0026nbsp;at any time point and\u0026nbsp;PSFS at 14 weeks\u0026nbsp;in the\u0026nbsp;CBT group compared\u0026nbsp;with the\u0026nbsp;control group.\u0026nbsp;No statistically\u0026nbsp;significant improvement in the NRS, NDI,\u0026nbsp;Whiplash Disability Questionnaire score,\u0026nbsp;and\u0026nbsp;SF-36\u0026nbsp;in the\u0026nbsp;CBT group compared\u0026nbsp;with the\u0026nbsp;control group at any time point.\u0026nbsp;No serious adverse events.\u0026nbsp;Minor adverse events\u0026nbsp;included\u0026nbsp;headache, musculoskeletal symptoms, exacerbation of existing symptoms, and stiffness.\u0026nbsp;No patient\u0026nbsp;withdrew from the trial because of adverse effects.\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"9.090909090909092%\"\u003e\n \u003cp\u003ePato\u0026nbsp;et al., 2010;\u003c/p\u003e\n \u003cp\u003eSwitzerland,\u0026nbsp;no\u0026nbsp;funding, RCTs\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"18.181818181818183%\"\u003e\n \u003cp\u003eTotal n (completing)\u0026nbsp;= 87 (73)\u0026nbsp;(from\u0026nbsp;Swiss Accident Insurance Fund (SUVA) and the Swiss Insurance Association registers).\u003c/p\u003e\n \u003cp\u003eParticipants were aged 41.61\u0026nbsp;\u0026plusmn;\u0026nbsp;12.0 years\u0026nbsp;and\u0026nbsp;diagnosed with chronic WADs grade\u0026nbsp;I\u0026nbsp;or II.\u003c/p\u003e\n \u003cp\u003eCBT group: Age:\u0026nbsp;42.6\u0026nbsp;\u0026plusmn;\u0026nbsp;12.3 years. Gender:\u0026nbsp;38 males, 48 females. Mean duration of symptoms:\u0026nbsp;20.9\u0026nbsp;\u0026plusmn;\u0026nbsp;15.1 months.\u003c/p\u003e\n \u003cp\u003eControl group: Age:\u0026nbsp;43.1\u0026nbsp;\u0026plusmn;\u0026nbsp;12.7 years. Gender:\u0026nbsp;26 males, 60 females. Mean duration of symptoms:\u0026nbsp;22.0\u0026nbsp;\u0026plusmn;\u0026nbsp;18.2 months.\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"18.181818181818183%\"\u003e\n \u003cp\u003eAll patients received two weekly sessions for 8 weeks (16 sessions) of CBT by the same (male) psychologist and were randomly assigned to one of following additional treatments: infiltration, physical therapy, medication for 8 weeks prescribed by the physician or physical therapist, or CBT focused on pain aspects, teaching control of pain, stress reduction, and chronic pain management techniques. Specific skills taught during the sessions were imagery, cognitive therapy for stressful situations, progressive muscle relaxation training, and application of guided mastery for stress/pain management.\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"18.181818181818183%\"\u003e\n \u003cp\u003eThe\u0026nbsp;infiltration group\u0026nbsp;had\u0026nbsp;16 sessions, the physical therapy\u0026nbsp;group\u0026nbsp;had\u0026nbsp;16 sessions, and the\u0026nbsp;medication group\u0026nbsp;were medicated\u0026nbsp;once a day for 8 weeks by the physician or\u0026nbsp;physical therapist.\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"18.181818181818183%\"\u003e\n \u003cp\u003eOther objective measures that were\u0026nbsp;excluded from\u0026nbsp;this\u0026nbsp;meta-analysis.\u003c/p\u003e\n \u003cp\u003ePain: VAS\u0026nbsp;and\u0026nbsp;McGill pain questionnaire\u003c/p\u003e\n \u003cp\u003eDisability/functional status: HAQ\u003c/p\u003e\n \u003cp\u003eWell-being: Well-Being Scale\u003c/p\u003e\n \u003cp\u003eCognitive ability: Cognitive Failures Questionnaire\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eFollow-up:\u0026nbsp;8weeks, 3\u0026nbsp;months, and\u0026nbsp;6 months\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"18.181818181818183%\"\u003e\n \u003cp\u003eStatistically\u0026nbsp;significant improvement in the Well-Being Scale\u0026nbsp;at 8weeks\u0026nbsp;in the\u0026nbsp;CBT group compared\u0026nbsp;with the\u0026nbsp;control group.\u0026nbsp;No statistically\u0026nbsp;significant improvement in the VAS, McGill pain questionnaire, HAQ, and Cognitive Failures Questionnaire\u0026nbsp;in the\u0026nbsp;CBT group compared\u0026nbsp;with the\u0026nbsp;control group at any time point.\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"9.090909090909092%\"\u003e\n \u003cp\u003eSoderlund\u0026nbsp;and Lindberg, 2001; 2007;\u003c/p\u003e\n \u003cp\u003eSweden,\u003c/p\u003e\n \u003cp\u003eSwedish Foundation, RCTs\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"18.181818181818183%\"\u003e\n \u003cp\u003eTotal n (completing)\u0026nbsp;= 33 (32)\u0026nbsp;(from\u0026nbsp;an orthopedic\u0026nbsp;clinic).\u003c/p\u003e\n \u003cp\u003eParticipants were aged between 18 and 60 years\u0026nbsp;and\u0026nbsp;diagnosed with chronic WADs grade\u0026nbsp;I,\u0026nbsp;II,\u0026nbsp;or III.\u0026nbsp;Duration of symptoms:\u0026nbsp;3 months\u0026nbsp;or more.\u003c/p\u003e\n \u003cp\u003eCBT group: Age:\u0026nbsp;37.7 years. Gender: seven\u0026nbsp;males,\u0026nbsp;nine\u0026nbsp;females.\u003c/p\u003e\n \u003cp\u003eControl group: Age: 43.5 years. Gender: seven males, 10 females.\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"18.181818181818183%\"\u003e\n \u003cp\u003ePatients underwent 12 individual sessions,\u0026nbsp;which included learning of basic physical and psychological skills, application and generalization of these basic skills in everyday activities, and a phase for maintenance of these skills by\u0026nbsp;a physical therapist.\u0026nbsp;The basic skill phase included coping strategies, relaxation training, re-education of a balanced cervicothoracic posture,\u0026nbsp;and exercises aimed to increase neck range of motion,\u0026nbsp;coordination,\u0026nbsp;and endurance.\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"18.181818181818183%\"\u003e\n \u003cp\u003ePatients underwent 12 individual sessions of exercises designed to enhance muscular stabilization of\u0026nbsp;the\u0026nbsp;neck, mobility\u0026nbsp;of the neck and shoulders\u0026nbsp;with stretching,\u0026nbsp;and coordination of head movements\u0026nbsp;and\u0026nbsp;exercises to maintain the body posture and arm muscle strength\u0026nbsp;provided by physical therapist.\u0026nbsp;The treatment could also include pain-relieving methods\u0026nbsp;including\u0026nbsp;relaxation,\u0026nbsp;transcutaneous\u0026nbsp;electric nerve stimulation, acupuncture,\u0026nbsp;and heat.\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"18.181818181818183%\"\u003e\n \u003cp\u003eOther objective measures that were\u0026nbsp;excluded from\u0026nbsp;this\u0026nbsp;meta-analysis.\u003c/p\u003e\n \u003cp\u003ePain: Week average, NRS\u003c/p\u003e\n \u003cp\u003eDisability/functional status: PDI\u003c/p\u003e\n \u003cp\u003eCervicothoracic posture: universal goniometer\u003c/p\u003e\n \u003cp\u003eCervical range of motion: Lic Rehab Care Svetsary goniometer\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eFollow-up: Post\u003c/p\u003e\n \u003cp\u003eintervention, 3\u0026nbsp;months, and\u0026nbsp;6 months\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"18.181818181818183%\"\u003e\n \u003cp\u003eNo\u0026nbsp;statistically\u0026nbsp;significant improvement in the NRS, PDI, cervicothoracic posture, and cervical range of motion\u0026nbsp;in the\u0026nbsp;CBT group compared\u0026nbsp;with the\u0026nbsp;control group at any time point.\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"9.090909090909092%\"\u003e\n \u003cp\u003eStewart\u0026nbsp;et al., 2007;\u003c/p\u003e\n \u003cp\u003eAustralia,\u003c/p\u003e\n \u003cp\u003eNSW Motor Accidents Authority, RCTs\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"18.181818181818183%\"\u003e\n \u003cp\u003eTotal n (completing)\u0026nbsp;= 132 (125) (from\u0026nbsp;two physical therapy clinics in Sydney).\u003c/p\u003e\n \u003cp\u003eParticipants were aged 20 years or more\u0026nbsp;and\u0026nbsp;diagnosed with chronic WADs grade\u0026nbsp;I,\u0026nbsp;II,\u0026nbsp;or III.\u003c/p\u003e\n \u003cp\u003eCBT group: Age:\u0026nbsp;42.7\u0026nbsp;\u0026plusmn;\u0026nbsp;14.4 years. Gender:\u0026nbsp;27 males, 41 females. Mean duration of symptoms:\u0026nbsp;8.6\u0026nbsp;\u0026plusmn;\u0026nbsp;2.5 months.\u003c/p\u003e\n \u003cp\u003eControl group: Age:\u0026nbsp;43.9\u0026nbsp;\u0026plusmn;\u0026nbsp;15.1 years. Gender:\u0026nbsp;18 males, 48 females. Mean duration of symptoms:\u0026nbsp;9.5\u0026nbsp;\u0026plusmn;\u0026nbsp;2.1 months.\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"18.181818181818183%\"\u003e\n \u003cp\u003eThe\u0026nbsp;6-week exercise program (three\u0026nbsp;sessions in the first and second weeks;\u0026nbsp;two\u0026nbsp;sessions in the third and fourth weeks\u0026nbsp;each; and\u0026nbsp;one\u0026nbsp;session in the fifth and sixth weeks\u0026nbsp;each) after advice was an individualized, progressive program designed by\u0026nbsp;a physical therapist.\u0026nbsp;A treatment manual was developed,\u0026nbsp;and each\u0026nbsp;physical therapist\u0026nbsp;was trained in the study protocol and interventions and were educated by an experienced clinical psychologist about the principles of CBT. The therapist used principles of CBT including setting goals of progressively increasing difficulty, shaping, encouraging self-monitoring of progress,\u0026nbsp;and self-reinforcing.\u003c/p\u003e\n \u003cp\u003eEach participant performed aerobic exercises; stretches; functional activities; activities to enhance speed, endurance, and coordination; and trunk- and limb-strengthening exercises.\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"18.181818181818183%\"\u003e\n \u003cp\u003ePatients received standardized education, reassurance,\u0026nbsp;and encouragement to resume light activity alone\u0026nbsp;assisted by a physical therapist.\u0026nbsp;The advice was given in one consultation and two follow-up phone contacts. Two and\u0026nbsp;4\u0026nbsp;weeks later, patients\u0026nbsp;were contacted\u0026nbsp;via\u0026nbsp;telephone,\u0026nbsp;and the standardized advice was reinforced.\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"18.181818181818183%\"\u003e\n \u003cp\u003ePain:\u0026nbsp;Average over the last 24 hours, NRS\u003c/p\u003e\n \u003cp\u003eDisability/functional status:\u0026nbsp;NDI\u003c/p\u003e\n \u003cp\u003eQuality of life: SF-36\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eOther objective measures that were\u0026nbsp;excluded from\u0026nbsp;this\u0026nbsp;meta-analysis.\u003c/p\u003e\n \u003cp\u003eFunctional ability: PSFS\u003c/p\u003e\n \u003cp\u003eGlobal perceived effect: Global perceived effect scale\u003c/p\u003e\n \u003cp\u003eAdverse events\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eFollow-up: 6 weeks\u0026nbsp;and 12 months\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"18.181818181818183%\"\u003e\n \u003cp\u003eStatistically\u0026nbsp;significant improvement in the NRS,\u0026nbsp;NDI SF36, PSFS, and Global perceived effect scale at 6weeks\u0026nbsp;in the\u0026nbsp;CBT group compared\u0026nbsp;with\u0026nbsp;control group. No\u0026nbsp;significant improvement in the NRS,\u0026nbsp;NDI SF36, PSFS, and Global perceived effect scale at 12 months\u0026nbsp;in the\u0026nbsp;CBT group compared\u0026nbsp;with the\u0026nbsp;control group.\u0026nbsp;No serious adverse events. Minor adverse events\u0026nbsp;included\u0026nbsp;muscle pain, headaches, knee pain, and lumbar pain.\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"9.090909090909092%\"\u003e\n \u003cp\u003eWicksell\u0026nbsp;et al., 2008; 2010;\u003c/p\u003e\n \u003cp\u003eSweden,\u003c/p\u003e\n \u003cp\u003eSwedish Research Council, RCTs\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"18.181818181818183%\"\u003e\n \u003cp\u003eTotal n (completing)\u0026nbsp;= 22 (19) (from Swedish Association of Survivors of Traffic Accidents and Polio).\u003c/p\u003e\n \u003cp\u003eParticipants were diagnosed with chronic WADs grade\u0026nbsp;I,\u0026nbsp;II,\u0026nbsp;or III.\u003c/p\u003e\n \u003cp\u003eCBT group: Age 48.2\u0026nbsp;\u0026plusmn;\u0026nbsp;7.8 years. Gender: two\u0026nbsp;males,\u0026nbsp;nine\u0026nbsp;females. Mean duration of symptoms:\u0026nbsp;79.7\u0026nbsp;\u0026plusmn;\u0026nbsp;42.2 months.\u003c/p\u003e\n \u003cp\u003eControl group: Age:\u0026nbsp;55.1\u0026nbsp;\u0026plusmn;\u0026nbsp;11.2 years. Gender: three\u0026nbsp;males,\u0026nbsp;seven\u0026nbsp;females. Mean duration of symptoms:\u0026nbsp;76.0\u0026nbsp;\u0026plusmn;\u0026nbsp;40.9 months.\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"18.181818181818183%\"\u003e\n \u003cp\u003eThe\u0026nbsp;10 individual sessions (60 minutes each) for 8 weeks. Eight sessions were conducted by psychologists and two sessions by a physician specializing in pain. Both the psychologists and physician had experience and formal training in CBT. The basic skill phase included pain education, values assessment, shifting perspective, exposure, acceptance, and diffusion.\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"18.181818181818183%\"\u003e\n \u003cp\u003eWait-and-see control.\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"18.181818181818183%\"\u003e\n \u003cp\u003ePain: Week average, VAS\u003c/p\u003e\n \u003cp\u003eDisability/functional status: PDI\u003c/p\u003e\n \u003cp\u003eDepression and anxiety: HADS.\u003c/p\u003e\n \u003cp\u003ePosttraumatic stress: IES-R\u0026nbsp;\u003cbr\u003e\u0026nbsp;Fear physical activity: TSK\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eOther objective measures that were\u0026nbsp;excluded from\u0026nbsp;this\u0026nbsp;meta-analysis.\u003c/p\u003e\n \u003cp\u003eGlobal life satisfaction: SWLS\u003c/p\u003e\n \u003cp\u003ePsychological inflexibility: PIPS\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eFollow-up: Post-intervention, 4\u0026nbsp;months and\u0026nbsp;7 months\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"18.181818181818183%\"\u003e\n \u003cp\u003eStatistically\u0026nbsp;significant improvement in the PDI, SWLS, HADS, IES-R, TSK, and PIPS at 4 months\u0026nbsp;in the\u0026nbsp;CBT group compared\u0026nbsp;with the\u0026nbsp;control group.\u0026nbsp;Improvement in the CBT group were maintained at the 7-month follow-up.\u0026nbsp;No significant improvement in the VAS\u0026nbsp;in the\u0026nbsp;CBT group compared\u0026nbsp;with the\u0026nbsp;control group at any time point.\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"6\" valign=\"top\" width=\"100%\"\u003e\n \u003cp\u003eRCTs, randomized controlled trials; WADs, whiplash-associated disorders; PTSD, posttraumatic stress disorder; CBT, cognitive behavioral therapy; NRS, numerical rating scale; NDI, Neck Disability Index; PSFS, Patient-Specific Functional Scale; SF-36, 36-Item Short Form Health Survey; SF-12, 12-Item Short Form Health Survey, DASS, Depression Anxiety and Stress Scale; CAPS-5, Clinician-Administered PTSD Scale; IES-R, Impact of Events Scale-Revised; TSK, Tampa Scale of Kinesiophobia; PDS, Posttraumatic Stress Diagnostic Scale; PCS, \u003cem\u003ePain Catastrophizing\u003c/em\u003e Scale; VAS, visual analog scale; HAQ, Health Assessment Questionnaire; HADS, Hospital Anxiety and Depression Scale; PDI, Pain Disability Index; PSEQ, Pain Self-Efficacy Questionnaire; SWLS, Satisfaction with Life Scale; PIPS, Psychological Inflexibility in Pain Scale.\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n\u003c/div\u003e\n\u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cdiv align=\"center\" id=\"isPasted\"\u003e\n \u003ctable border=\"1\" cellpadding=\"0\" cellspacing=\"0\" width=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"9\" width=\"100%\"\u003e\n \u003cp style=\"text-align: center;\"\u003eTable 3\u003c/p\u003e\n \u003cp style=\"text-align: center;\"\u003e\u0026nbsp;A summary of the quality of the evidence using the GRADE approach\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"6\" width=\"65.23605150214593%\"\u003e\n \u003cp\u003eQuality assessment\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"3\" width=\"34.76394849785408%\"\u003e\n \u003cp\u003eSummary of findings\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"9.72818311874106%\"\u003e\n \u003cp\u003eNo of studies\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.72818311874106%\"\u003e\n \u003cp\u003eRisk of bias\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.872675250357654%\"\u003e\n \u003cp\u003eImprecision\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.446351931330472%\"\u003e\n \u003cp\u003eInconsistency\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.301859799713878%\"\u003e\n \u003cp\u003eIndirectness\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.158798283261802%\"\u003e\n \u003cp\u003ePublication bias\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.872675250357654%\"\u003e\n \u003cp\u003eNo of participants\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.874105865522175%\"\u003e\n \u003cp\u003ePooled standardized mean difference (95% confidence intervals)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.017167381974248%\"\u003e\n \u003cp\u003eQuality of evidence\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"9\" width=\"100%\"\u003e\n \u003cp\u003eCBT versus\u0026nbsp;wait-and-see control\u0026nbsp;on pain in the short term\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"9.72818311874106%\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.72818311874106%\"\u003e\n \u003cp\u003eNot serious\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.872675250357654%\"\u003e\n \u003cp\u003eVery serious\u003csup\u003e1\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.446351931330472%\"\u003e\n \u003cp\u003eNot serious\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.301859799713878%\"\u003e\n \u003cp\u003eNot serious\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.158798283261802%\"\u003e\n \u003cp\u003eUndetected\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.872675250357654%\"\u003e\n \u003cp\u003e46\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.874105865522175%\"\u003e\n \u003cp\u003e\u0026minus;0.48\u003cbr\u003e\u0026nbsp;(\u0026minus;1.07 to 0.11)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.017167381974248%\"\u003e\n \u003cp\u003e⨁⨁◯◯\u003c/p\u003e\n \u003cp\u003eLOW\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"9\" width=\"100%\"\u003e\n \u003cp\u003eCBT versus\u0026nbsp;wait-and-see control\u0026nbsp;on disability in the short term\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"9.72818311874106%\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.72818311874106%\"\u003e\n \u003cp\u003eNot serious\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.872675250357654%\"\u003e\n \u003cp\u003eVery serious\u003csup\u003e1\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.446351931330472%\"\u003e\n \u003cp\u003eNot serious\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.301859799713878%\"\u003e\n \u003cp\u003eNot serious\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.158798283261802%\"\u003e\n \u003cp\u003eUndetected\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.872675250357654%\"\u003e\n \u003cp\u003e46\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.874105865522175%\"\u003e\n \u003cp\u003e\u0026minus;0.61\u003cbr\u003e\u0026nbsp;(\u0026minus;1.21 to \u0026minus;0.01)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.017167381974248%\"\u003e\n \u003cp\u003e⨁⨁◯◯\u003c/p\u003e\n \u003cp\u003eLOW\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"9\" width=\"100%\"\u003e\n \u003cp\u003eCBT versus\u0026nbsp;wait-and-see control\u0026nbsp;on fear of physical activity\u0026nbsp;in the\u0026nbsp;short term\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"9.72818311874106%\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.72818311874106%\"\u003e\n \u003cp\u003eNot serious\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.872675250357654%\"\u003e\n \u003cp\u003eVery serious\u003csup\u003e1\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.446351931330472%\"\u003e\n \u003cp\u003eNot serious\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.301859799713878%\"\u003e\n \u003cp\u003eNot serious\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.158798283261802%\"\u003e\n \u003cp\u003eUndetected\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.872675250357654%\"\u003e\n \u003cp\u003e46\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.874105865522175%\"\u003e\n \u003cp\u003e\u0026minus;1.04\u003cbr\u003e\u0026nbsp;(\u0026minus;1.67 to \u0026minus;0.41)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.017167381974248%\"\u003e\n \u003cp\u003e⨁⨁◯◯\u003c/p\u003e\n \u003cp\u003eLOW\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"9\" width=\"100%\"\u003e\n \u003cp\u003eCBT versus\u0026nbsp;wait-and-see control\u0026nbsp;on anxiety\u0026nbsp;in the\u0026nbsp;short term\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"9.72818311874106%\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.72818311874106%\"\u003e\n \u003cp\u003eNot serious\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.872675250357654%\"\u003e\n \u003cp\u003eVery serious\u003csup\u003e1\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.446351931330472%\"\u003e\n \u003cp\u003eNot serious\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.301859799713878%\"\u003e\n \u003cp\u003eNot serious\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.158798283261802%\"\u003e\n \u003cp\u003eUndetected\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.872675250357654%\"\u003e\n \u003cp\u003e46\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.874105865522175%\"\u003e\n \u003cp\u003e\u0026minus;0.97\u003cbr\u003e\u0026nbsp;(\u0026minus;1.59 to \u0026minus;0.35)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.017167381974248%\"\u003e\n \u003cp\u003e⨁⨁◯◯\u003c/p\u003e\n \u003cp\u003eLOW\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"9\" width=\"100%\"\u003e\n \u003cp\u003eCBT versus\u0026nbsp;wait-and-see control\u0026nbsp;on depression\u0026nbsp;in the\u0026nbsp;short term\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"9.72818311874106%\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.72818311874106%\"\u003e\n \u003cp\u003eNot serious\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.872675250357654%\"\u003e\n \u003cp\u003eVery serious\u003csup\u003e1\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.446351931330472%\"\u003e\n \u003cp\u003eNot serious\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.301859799713878%\"\u003e\n \u003cp\u003eNot serious\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.158798283261802%\"\u003e\n \u003cp\u003eUndetected\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.872675250357654%\"\u003e\n \u003cp\u003e46\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.874105865522175%\"\u003e\n \u003cp\u003e\u0026minus;1.04\u003cbr\u003e\u0026nbsp;(\u0026minus;1.66 to \u0026minus;0.41)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.017167381974248%\"\u003e\n \u003cp\u003e⨁⨁◯◯\u003c/p\u003e\n \u003cp\u003eLOW\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"9\" width=\"100%\"\u003e\n \u003cp\u003eCBT versus\u0026nbsp;wait-and-see control\u0026nbsp;on posttraumatic stress in the short term\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"9.72818311874106%\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.72818311874106%\"\u003e\n \u003cp\u003eNot serious\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.872675250357654%\"\u003e\n \u003cp\u003eVery serious\u003csup\u003e1\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.446351931330472%\"\u003e\n \u003cp\u003eNot serious\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.301859799713878%\"\u003e\n \u003cp\u003eNot serious\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.158798283261802%\"\u003e\n \u003cp\u003eUndetected\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.872675250357654%\"\u003e\n \u003cp\u003e46\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.874105865522175%\"\u003e\n \u003cp\u003e\u0026minus;0.28\u003cbr\u003e\u0026nbsp;(\u0026minus;0.87 to 0.30)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.017167381974248%\"\u003e\n \u003cp\u003e⨁⨁◯◯\u003c/p\u003e\n \u003cp\u003eLOW\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"9\" width=\"100%\"\u003e\n \u003cp\u003eCBT in addition to\u0026nbsp;physical interventions\u0026nbsp;versus advice only on pain in the long term\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"9.72818311874106%\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.72818311874106%\"\u003e\n \u003cp\u003eNot serious\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.872675250357654%\"\u003e\n \u003cp\u003eSerious\u003csup\u003e2\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.446351931330472%\"\u003e\n \u003cp\u003eNot serious\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.301859799713878%\"\u003e\n \u003cp\u003eNot serious\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.158798283261802%\"\u003e\n \u003cp\u003eUndetected\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.872675250357654%\"\u003e\n \u003cp\u003e282\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.874105865522175%\"\u003e\n \u003cp\u003e\u0026minus;0.20\u003cbr\u003e\u0026nbsp;(\u0026minus;0.43 to 0.03)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.017167381974248%\"\u003e\n \u003cp\u003e⨁⨁⨁◯\u003c/p\u003e\n \u003cp\u003eMODERATE\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"9\" width=\"100%\"\u003e\n \u003cp\u003eCBT in addition to\u0026nbsp;physical interventions\u0026nbsp;versus advice only on disability in the long term\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"9.72818311874106%\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.72818311874106%\"\u003e\n \u003cp\u003eNot serious\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.872675250357654%\"\u003e\n \u003cp\u003eSerious\u003csup\u003e2\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.446351931330472%\"\u003e\n \u003cp\u003eNot serious\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.301859799713878%\"\u003e\n \u003cp\u003eNot serious\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.158798283261802%\"\u003e\n \u003cp\u003eUndetected\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.872675250357654%\"\u003e\n \u003cp\u003e282\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.874105865522175%\"\u003e\n \u003cp\u003e\u0026minus;0.29\u003cbr\u003e\u0026nbsp;(\u0026minus;0.53 to \u0026minus;0.06)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.017167381974248%\"\u003e\n \u003cp\u003e⨁⨁⨁◯\u003c/p\u003e\n \u003cp\u003eMODERATE\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"9\" width=\"100%\"\u003e\n \u003cp\u003eCBT in addition to\u0026nbsp;physical interventions\u0026nbsp;versus advice only on quality of life in the long term (physical component summary)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"9.72818311874106%\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.72818311874106%\"\u003e\n \u003cp\u003eNot serious\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.872675250357654%\"\u003e\n \u003cp\u003eSerious\u003csup\u003e2\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.446351931330472%\"\u003e\n \u003cp\u003eNot serious\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.301859799713878%\"\u003e\n \u003cp\u003eNot serious\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.158798283261802%\"\u003e\n \u003cp\u003eUndetected\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.872675250357654%\"\u003e\n \u003cp\u003e282\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.874105865522175%\"\u003e\n \u003cp\u003e\u0026minus;0.20\u003cbr\u003e\u0026nbsp;(\u0026minus;0.44 to 0.03)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.017167381974248%\"\u003e\n \u003cp\u003e⨁⨁⨁◯\u003c/p\u003e\n \u003cp\u003eMODERATE\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"9\" width=\"100%\"\u003e\n \u003cp\u003eCBT in addition to\u0026nbsp;physical interventions\u0026nbsp;versus advice only on quality of life in the long term (mental component summary)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"9.72818311874106%\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.72818311874106%\"\u003e\n \u003cp\u003eNot serious\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.872675250357654%\"\u003e\n \u003cp\u003eSerious\u003csup\u003e2\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.446351931330472%\"\u003e\n \u003cp\u003eNot serious\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.301859799713878%\"\u003e\n \u003cp\u003eNot serious\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.158798283261802%\"\u003e\n \u003cp\u003eUndetected\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.872675250357654%\"\u003e\n \u003cp\u003e282\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.874105865522175%\"\u003e\n \u003cp\u003e\u0026minus;0.12\u003cbr\u003e\u0026nbsp;(\u0026minus;0.35 to 0.11)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.017167381974248%\"\u003e\n \u003cp\u003e⨁⨁⨁◯\u003c/p\u003e\n \u003cp\u003eMODERATE\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"9\" width=\"100%\"\u003e\n \u003cp\u003eCBT, cognitive behavioral therapy.\u003c/p\u003e\n \u003cp\u003e\u003csup\u003e1\u003c/sup\u003eDue to the limited sample sizes (fewer than 100 participants), significance was rated down two levels.\u003c/p\u003e\n \u003cp\u003e\u003csup\u003e2\u003c/sup\u003eDue to the limited sample sizes (fewer than 200 participants), significance was rated down one level.\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n\u003c/div\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"whiplash-associated disorders, cognitive behavior therapy, systematic review","lastPublishedDoi":"10.21203/rs.3.rs-1360019/v2","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-1360019/v2","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground: \u003c/strong\u003eTo determine the effectiveness of cognitive behavioral therapy (CBT) alone and a combination of physical interventions and CBT on pain, disability, quality of life, and psychological parameters in patients with chronic whiplash-associated disorders (WADs). \u003c/p\u003e\u003cp\u003e\u003cstrong\u003eMethods: \u003c/strong\u003eSeveral databases were systematically searched for randomized controlled trials (RCTs). Pooled effects were analyzed as standardized mean differences (SMD) and 95% confidence intervals (CI). We assessed the quality of the evidence using the Grading of Recommendations, Assessment, Development, and Evaluation approach.\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eResults:\u003c/strong\u003e In total, 2,287 RCTs were found; among them, eight were included. Two RCTs, we found low evidence that CBT was better than the wait-and-see control group in improving disability (SMD, −0.61; 95% CI, −1.21 to −0.01) and psychological status, such as fear of physical activity (SMD, −1.04; 95% CI, −1.67 to −0.41), in the short-term. In addition, two RCTs, we found moderate evidence that CBT combined with physical interventions was better than what was advised in improving disability (SMD, −0.29; 95% CI, −0.53 to −0.06) in the long-term. \u003c/p\u003e\u003cp\u003e\u003cstrong\u003eConclusion: \u003c/strong\u003eThe study found moderately favorable evidence of the combined effect of physical interventions and CBT against advice alone in long-term disability.\u003c/p\u003e","manuscriptTitle":"Effects of cognitive behavior therapy on patients with chronic whiplash-associated disorders: a systematic review and meta-analysis","msid":"","msnumber":"","nonDraftVersions":[{"code":2,"date":"2022-02-21 15:53:45","doi":"10.21203/rs.3.rs-1360019/v2","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}},{"code":1,"date":"2022-02-18 14:43:49","doi":"10.21203/rs.3.rs-1360019/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"09a2b6e2-bc20-4353-96dc-c33fd70bb2e4","owner":[],"postedDate":"February 21st, 2022","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2022-02-18T14:55:47+00:00","versionOfRecord":[],"versionCreatedAt":"2022-02-21 15:53:45","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v2","identity":"rs-1360019","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-1360019","identity":"rs-1360019","version":["v2"]},"buildId":"FbvkV6FR0MCFSLy54lSbu","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}