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A review of treatment interventions in whiplash-associated disorders

A review of treatment interventions in whiplash-associated disorders
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  Introduction From 1989 to 1994, whiplash-associated disorders (WAD)went from the third most common road traffic injury inSweden to the most common [17]. Incidence in Swedenhas been found to be one per 1,000 inhabitants [4]. More-over, rear-end collisions resulting in reported WAD seemto have a substantial impact on health complaints in Swe-den, even long after collision [3, 8]. There has been much confusion with the term whiplash. It has been used to describe the injury mechanism, the in- jury itself, and symptoms following injury. The QuebecTask Force (QTF) redefined WAD in 1995. According tothe QTF, whiplash is an acceleration-deceleration mecha-nism of energy transfer to the neck, which may result fromrear-end or side-impact motor vehicle collisions but canalso occur during diving or other mishaps. The impactmay result in bony or soft-tissue injuries (whiplash in- jury), which in turn may lead to a variety of clinical man-ifestations (WAD) [47].Neck pain, headache, and reduction of cervical mobil-ity are cardinal symptoms in the acute phase. WAD can beclassified by five grades of initial severity on the modifiedQuebec classification [15, 47] (Table1). Exposure with-out initial symptoms is referred to as grade 0. Hartling etal. have shown that the higher the grade initially, thegreater the risk for WAD at 6, 12, 18, and 24 months [15]. Abstract In recent years, there hasbeen much debate on the treatmentof whiplash-associated disorders(WAD). It is not clear if the treat-ments commonly employed are ef-fective, and concerns have beenraised on the available scientific evi-dence of many of these treatments.The aim of this study was to reviewthe literature systematically to ana-lyze the evidence basis of manycommonly used treatments for pa-tients suffering from WAD, both in the acute and the chronic state. A com-puter- assisted search of the databasesMedline (from 1962 to May 2003),CINAHL (1960–2003), Embase(1976–2003), and Psychinfo (1960– 2003) was conducted as well as acheck of the reference lists of rele-vant studies. All randomized con-trolled trials (RCTs) were retrievedand systematically analyzed withthree common instruments of mea-surement of methodological quality.A qualitative analysis (“best-evi-dence synthesis”) was performed.The methodological quality of 26 RCTs was analyzed. The medianquality scores for all three instru-ments were poor. Based on the de-grees of evidence and the practicalobstacles, the following treatmentscan be recommended: Early physicalactivity in acute WAD, radiofre-quency neurotomy, combination of cognitive behavioral therapy withphysical therapy interventions, andcoordination exercise therapy inchronic WAD. High-quality RCTsare not common in the field of WAD.More research is needed, particularlyon the treatment of chronic WAD. Keywords Whiplash · Treatment ·ReviewREVIEW Eur Spine J (2004) 13:387–397DOI 10.1007/s00586-004-0709-1 Aris Seferiadis Mark Rosenfeld Ronny Gunnarsson  A review of treatment interventions in whiplash-associated disorders Received: 24 December 2003 Accepted: 4 March 2004 Published online: 5 May 2004©Springer-Verlag 2004A. Seferiadis ( ✉ )Psychiatric Physiotherapy Unit, Björkängen, Southern Elfsborg Hospital,Klinikvägen 40, 501 82 Borås, Swedene-mail: aris.seferiadis@vgregion.seM. RosenfeldInstitute of Occupational Therapy and Physiotherapy, Faculty of Health and Caring Sciences,The Sahlgrenska Academy at Göteborg University, Göteborg, SwedenA. SeferiadisDepartment of Primary Health Care, The Sahlgrenska Academy at Göteborg University, Göteborg, SwedenR. GunnarssonResearch and Development Unit in Primary Health Care, Southern Elfsborg County, Sweden  Symptoms cover a wide range, particularly in late whiplashsyndrome defined as persisting symptoms or residual dis-ability 6 months after the injury [47].Although the whiplash mechanism potentially injuresseveral structures, objective evidence of such injuries hasbeen scarce. Recent studies have shown that 50% of pa-tients with chronic WAD suffer from zygapophysial jointpain [27] and that the brachial plexus is often involved inthe presence of arm symptoms [19, 48]. Instability of thealar ligaments has also been seen in patients with chronicWAD [55].The lack of homogeneity among patients sufferingfrom WAD has led to many treatment options. The Que-bec Task Force [47] highlighted the lack of randomizedcontrolled trials (RCTs) in the field.The RCT is considered the most reliable method to as-sess the efficacy of treatments. Systematic review of RCTsoffers a way to cope with the large number of articles pub-lished. An example of such a review in the field of WADis the investigation of Peeters et al. [34] on the efficacy of conservative treatment.Assessment of the quality of RCTs included in a re-view can give an estimate of the likelihood that results arevalid [49]. Trial quality is difficult to define. It has beendefined as “the confidence that the trial design, conductand analysis has minimized or avoided biases in its treat-ment comparisons.” This definition covers internal valid-ity, although the concept of quality should also encompasscriteria of external validity, statistical analysis and ethics[11, 29, 46].Several scales and checklists have been created to as-sess RCT quality, albeit chiefly in a nonscientific manner [33]. The three most widely accepted criteria lists are: aninstrument to measure the likelihood of bias in pain re-search reports (IMLB) by Jadad et al. [20], the Delphi List(DL) by Verhagen et al. [54], and the criteria list for methodological quality assessment also known as Maas-tricht-Amsterdam List (MAL) by the back review groupof the Cochrane Collaboration [51].The aim of this study was to review the literature sys-tematically using these three instruments to perform aqualitative analysis of the evidence basis of many com-monly used treatment options for patients suffering fromacute and chronic WAD. 388 Table 1  The modified Quebec classification of whiplash-asso-ciated disordersGradeClinical presentation0No complaint about the neckNo physical sign(s)INeck complaint of pain, stiffness or tenderness onlyNo physical sign(s)IIaNeck complaint and musculoskeletal sign(s): These include point tenderness but normal cervical range of motionIIbNeck complaint and musculoskeletal sign(s): These include point tenderness and abnormal cervical range of motionIIINeck complaint and neurological sign(s): These include decreased or absent deep tendon reflexes, weakness and sensory deficitsIVNeck complaint and fracture or dislocationSymptoms and disorders that can appear in all grades includedeafness, dizziness, tinnitus, headache, memory loss, dysphagia,and temporomandibular joint pain Table 2 Domains included inthe three methodological qual-ity lists.  IMLB likelihood of bias in pain research reports,  DL Delphi List,  MAL Maas-tricht-Amsterdam ListDomains of possible interestMethodological quality scoreIMLBDLMAL1 Study question2 Population x x3 Sample size and power calculations a priori4 Treatment allocation x x x5 Study design x6 Ethics7 Intervention x8 Outcome measures x x9 Follow-up/withdrawals x x10 Blinding x x x11 Cointerventions x12 Side-effects x13 Compliance x14 Prognostic comparability15 Analysis x x16 Conclusion17 Presentation  Materials and methods Literature search The Medline database was searched for articles written 1962 through May 2003. The WebSPIRS 5.02 program was used to search thedatabases CINAHL (1960–2003), Embase (1976–2003), and Psych-info (1960–2003). The reference lists of relevant RCTs and con-trolled clinical trials (CCTs) were checked to identify additionalpublished research not found in the computerized, bibliographic databases. The search was conducted using the MESH term whiplash and the word whiplash in the abstract or title of the study. Titlesand abstracts of identified, published articles were initially re-viewed by one of the authors (AS). All intervention studies dealingwith acute or chronic WAD were retrieved.Selection for quality assessmentStudies were assessed if they met the following criteria: (1) The in-tended design was a prospective RCT; (2) the study population in-cluded patients with WAD; (3) the publication was in English.Quality assessment of studiesThe methodological quality of the studies was independently as-sessed by two reviewers (AS and MR). The assessment was notperformed under masked conditions. All studies received a scorefor each of the criteria lists IMLB, DL, and MAL. In case of anydisagreement between the two reviewers (AS and MR), a consen-sus method was used. If disagreement persisted, a third reviewer (RG) would make the final decision. A pilot assessment of oneRCT (not included in the study) was conducted to familiarize thereviewers with the quality assessment lists. Prior to scoring, the re-viewers discussed the available guidelines to ensure a common in-terpretation of the lists. After the individual assessment, the re-viewers then agreed on a final score for each article.The IMLB consists of three items directly related to the reduc-tion of bias, treatment allocation, follow-up/withdrawals, andblinding (Tables2 and 3). The items were presented as questions toelicit yes or no answers. One point was awarded for each affirma-tive answer. Additionally, one point was added or deducted if themethods used were appropriate or not. This gives a numerical sumscore of 0–5.The DL consists of nine items concerning study population,treatment allocation, outcome measures, blinding, and analysis(Tables2 and 3). All items have a yes/no/don’t know option. If bias was unlikely, the item was rated with one point. If information389 Table 3 Items included in thethree methodological qualitylists and the frequency of an-swers.  IMLB likelihood of biasin pain research reports,  DL Delphi List,  MAL Maas-tricht-Amsterdam List a Domains described in Table2 b Number of Yes (1)/No (0) answers c Number of Appropriate(1)/Nothing (0)/Inappropriate(–1) answers d Number of Yes (1)/No (0)/ Don’t know (0) answers Domain a ItemsMethodological quality scoreIMLBDL d MAL d  2Were the eligibility criteria specified?20/6/08/17/1 4Was the study described as randomized b 25/1 4Was a method of randomization performed?25/1/010/2/14 4Was the method of randomization describedand appropriate?  c 8/17/1 4Was the treatment allocation concealed?4/5/174/5/17 5Were outcome measures relevant?25/1/0 5Was the timing of the outcome assessment in bothgroups comparable?24/1/1 7Were the experimental and control interventionsexplicitly described?25/1/0 8Were the groups similar at baseline regarding the mostimportant prognostic indicators?17/3/65/4/17 8Were point estimates and measures of variabilitypresented for the primary outcome measures?20/6/020/6/0 8Was the sample size of each group described?20/5/1 9Was there a description of withdrawals and/ dropouts? b 16/10 9Was the withdrawal / drop-out rate described andacceptable?16/9/1 9Was a short-term follow-up measurement performed?22/4/0 9Was a long-term follow-up measurement performed?15/11/010Was the care provider blinded to the intervention?7/18/17/18/110Was the patient blinded to the intervention?8/18/08/18/010Was the outcome assessor blinded to the intervention?16/2/816/2/810Was the study described as double blind? b 8/1810Was the method of blinding described and appropriate? c 6/19/111Were co-interventions avoided or comparable?15/8/312Were adverse effects described?8/18/013Was the compliance acceptable in all groups?10/0/1615Did the analysis include an intention-to-treat analysis?13/7/613/8/5  was unavailable or insufficient or if bias was likely, the item wasrated with zero points for an overall numerical sum score of 0–9.The MAL consists of 19 items related to population, treatmentallocation, study design, intervention, outcome measures, follow-up/withdrawals, blinding, cointerventions, side-effects, compli-ance, and analysis (Tables2 and 3). It includes items similar to theIMLB and DL and unique items. The response options are similar to DL, and the overall numerical score is 0–19.Detailed instructions on using these assessment scales havebeen published previously [20, 34, 54]. Differences exist in the as-sessment guidelines between the DL and MAL in three items.Thus, in these items, the same item on the two lists can have dif-ferent scores: –“Were the eligibility criteria specified?” DL requires inclusionand exclusion criteria while MAL only requires that the radia-tion pattern of back pain and duration of the disorder be de-scribed to score a “Yes” –“Was a method of randomization performed?” DL requires thatwords such as random and randomization are used. MAL alsorequires that the randomization procedure is appropriate. Thismeans that articles receiving a “Yes” on DL could score “Don’tknow” on MAL when a description of the randomization proce-dure was lacking. –“Were the groups similar at baseline regarding the most impor-tant prognostic indicators?” DL requires the reviewer to deter-mine this item, while MAL specifically requests adequate de-scriptions of age, duration of complaints, percentage of patientswith radiating pain, and main outcome measures to evaluatesimilarity. Also this item could elicit differing scores, though itexists on both lists.Best-evidence synthesisA qualitative analysis (“best-evidence synthesis”) was conductedusing a rating system utilized by the Cochrane Collaboration BackGroup [52]. It consists of the following degrees of evidence:1.Strong evidence: generally consistent findings in multiplehigh quality RCTs2.Moderate evidence: generally consistent findings in multiplelow quality RCTs and/or one high quality RCT3a.Limited evidence: only one low quality RCT3b.Conflicting evidence: inconsistent findings in multiple RCTs4.No evidence: no RCTs and no double-blind trials.A study was arbitrarily judged to be of high quality if the sumscore in all three scales (IMLB, DL, and MAL) was at least 50%of the total score.Statistical methodsThe outcome of quality assessment and best-evidence synthesis ispresented. Kappa is calculated to estimate interobserver reliabilityof quality assessment.390 Table 4 Scores received onthe instrument for measurementof likelihood of bias (IMLB)stratified after type of study a In each column studies focus-ing on acute/chronic whiplash-associated disorders (WAD) b Instrument for measuring thelikelihood of bias c Combination of physical ther-apy and psychological supportIMLB b Type of study a scoringChiropractic Drug Orthopedic Physical Multimodal interventiontherapysurgerytherapyintervention c 0–25% 0/2 0/1 0/0 3/2 0/126–50% 0/0 0/1 0/0 5/1 0/151–75% 0/0 0/1 0/0 2/0 0/076–100% 0/0 1/1 0/3 1/0 0/0Total 0/2 1/4 0/3 11/3 0/2 Table 5 Scores received onthe Delphi List (DL) stratifiedafter type of study a In each column studies focus-ing on acute/chronic whiplash-associated disorders (WAD) b Delphi List c Combination of physical ther-apy and psychological supportDL b scoringType of study a Chiropractic Drug Orthopedic Physical Multimodal interventiontherapysurgerytherapyintervention c 0–25% 0/0 0/0 0/0 1/0 0/126–50% 0/1 0/1 0/0 3/2 0/051–75% 0/1 0/2 0/1 5/1 0/176–100% 0/0 1/1 0/2 2/0 0/0Total 0/2 1/4 0/3 11/3 0/2 Table 6 Scores received onthe Maastricht-Amsterdam List(MAL) stratified after type of study a In each column studies focus-ing on acute/chronic whiplash-associated disorders (WAD) b Combination of physical ther-apy and psychological supportMAL b scoringType of study a Chiropractic Drug Orthopedic Physical Multimodal interventiontherapysurgerytherapyintervention b 0–25% 0/0 0/0 0/0 0/0 0/026–50% 0/1 0/1 0/0 6/3 0/251–75% 0/1 0/3 0/1 4/0 0/076–100% 0/0 1/0 0/2 1/0 0/0Total 0/2 1/4 0/3 11/3 0/2  Results In the literature search, 1,726 studies were found. 56 wereintervention studies and 33 were CCTs. Seven CCTs didnot use randomization, while 26 studies were RCTs thatsubsequently were quality assessed. The interobserver re-liability in quality assessment between the two indepen-dent reviewers was very good ( κ  =1) for IMLB and goodfor DL ( κ  =0.76) and MAL ( κ  =0.74). There was no needfor the third reviewer to arbitrate. Median scores (in-terquartile range) were for IMLB 2 (1–3), for DL 5 (4–6),and for MAL 9.5 (8–12). Studies evaluating orthopedicsurgery were often scored higher than studies investigat-ing effects of chiropractic, drug therapy, physical therapy,or multimodal interventions (Tables4, 5, and 6). The threemost prevalent shortcomings were lack of information onpatient and/or care provider blinding, lack of informationon concealment of treatment allocation, and lack of de-scription of adverse effects (Table3).Evaluated therapeutic interventions and their degree of evidence according to the Cochrane Collaboration BackGroup system [52] are presented in Table7. An overviewof all references is presented in Table8. Discussion The main finding of this review was the large number of physical therapy articles on the subject. Apparently, thisprofession is often called upon to treat patients withWAD. The interventions for acute WAD that have thestrongest scientific support are: early physical activity [5,6, 14, 31, 32, 35, 39, 40, 45] (degree 2), electromagnetic-field therapy [13, 50] (degree 2), and high-dose methyl- 391 Table 7  Treatment interventions and the degrees of evidence in their support.  WAD  whiplash-associated disordersDegree of evidence a ClaimReferences b 1Radiofrequency neurotomy reduces pain and psychological distressin patients with chronic WAD and zygapophysial joint pain Lord 1996  [27],  Wallis 1997  [55]2Melatonin therapy advances melatonin onset and sleep-wakerhythm in patients with chronic WAD and delayed melatonin onset van Wieringen 2001  [52]2High-dose methylprednisolone therapy administered within 8hof injury reduces sick leave Pettersson 1998  [36]2Intra-articular corticosteroid therapy lacks effect in patientswith chronic WAD and zygapophysial joint pain Barnsley 1994  [1]2Electromagnetic Field therapy reduces pain and increases cervicalrange of motion in patients with acute WAD Foley-Nolan 1992  [13], Thuile 2002 [50] c 2Early physical activity reduces pain, increases cervical range of motion and reduces sick leave in patients with acute WADBonk 2000 [5], Borchgrevink 1998 [6],Gennis 1996 [14} d , McKinney 1989 [30],Mealy 1986 [32], Pennie 1990 [35], Söderlund2000 [45], Rosenfeld 2000 [39] e ,  Rosenfeld2003  [40] e 2Cognitive behavioural therapy combined with Physical therapyreduce pain and sick leave in patients with chronic WADJohansson 1998 [21}, Provinciali 1996 [37],Söderlund 2001 [44]2Coordination exercise therapy reduces pain in patients with chronicWADFitz-Ritson 1995 [12] f  , Humphreys 2002 [18]3aUltra-reiz current therapy combined with physical therapy reducespain and cervical range of motion in patients with acute WADHendriks 1996 [16]3aSpinal manipulation therapy reduces pain and increases cervicalrange of motion in patients with neck pain with radiation to thetrapezius muscle f  Cassidy 1992 [10]3aFluoxetine therapy provides similar pain reduction to thatof Amitriptyline therapy in patients with chronic WADSchreiber 2001 [43]3bSubcutaneous sterile water injection therapy reduces pain andincreases cervical range of motion in patients with chronic WADByrn 1993 [9], Sand 1992[41] h a Rating system derived from the system utilized by the CochraneCollaboration Back Group [52] (See “Methods”-section) b Studies presented by first author in alphabetical order where ap-propriate.  Bold  references denote studies defined as high quality c It was unclear if patients in this randomized controlled trial(RCT) suffered from acute or chronic whiplash-associated disor-ders (WAD) d The results of this RCT conflict with the claim e The two articles by Rosenfeld are based on the same data andshould therefore be regarded as one RCT f  The groups in this RCT were different at baseline g The claim refers to effects immediate following treatment. Long-term effects have not been studied h This RCT conflicts with the claim, and the study population isheterogeneous
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