Cost-effectiveness of Transforaminal epidural steroid injections for patients with ACUTE sciatica: a randomized controlled trial.

BACKGROUND: Transforaminal epidural injections with steroids (TESI) are increasingly being used in patients sciatica. The STAR (steroids against radiculopathy)-trial aimed to evaluate the (cost-) effectiveness of TESI in patients with acute sciatica (< 8 weeks). This article contains the economic evaluation of the STAR-trial. METHODS: Participants were randomized to one of three study arms: Usual Care (UC), that is oral pain medication with or without physiotherapy, n = 45); intervention group 1: UC and transforaminal epidural steroid injection (TESI) 1 ml of 0.5% Levobupivacaine and 1 ml of 40 mg/ml Methylprednisolone and intervention group 2: UC and transforaminal epidural injection (TEI) with 1 ml of 0,5% Levobupivacaine and 1 ml of 0.9% NaCl (n = 50). The primary effect measure was health-related quality of life. Secondary outcomes were pain, functioning, and recovery. Costs were measured from a societal perspective, meaning that all costs were included, irrespective of who paid or benefited. Missing data were imputed using multiple imputation, and bootstrapping was used to estimate statistical uncertainty. RESULTS: None of the between-group differences in effects were statistically significant for any of the outcomes (QALY, back pain, leg pain, functioning, and global perceived effect) at the 26-weeks follow-up. The adjusted mean difference in total societal costs was €1718 (95% confidence interval [CI]: - 3020 to 6052) for comparison 1 (intervention group 1 versus usual care), €1640 (95%CI: - 3354 to 6106) for comparison 2 (intervention group 1 versus intervention group 2), and €770 (95%CI: - 3758 to 5702) for comparison 3 (intervention group 2 versus usual care). Except for the intervention costs, none of the aggregate and disaggregate cost differences were statistically significant. The maximum probability of all interventions being cost-effective compared to the control was low (< 0.7) for all effect measures. CONCLUSION: These results suggest that adding TESI (or TEI) to usual care is not cost-effective compared to usual care in patients with acute sciatica (< 8 weeks) from a societal perspective in a Dutch healthcare setting. TRIAL REGISTRATION: Dutch National trial register: NTR4457 (March, 6th, 2014).

STeroids Against Radiculopathy (STAR) trial: a statistical analysis plan.

BACKGROUND: Transforaminal epidural injections with steroids (TESI) are used increasingly for patients with sciatica. However, their safety, effectiveness, and cost-effectiveness are still a matter of debate. This a priori statistical analysis plan describes the methodology of the analysis for the STAR trial that assesses the (cost-)effectiveness of TESI during the acute stage of sciatica (< 8 weeks). METHODS: The STAR trial is a multicentre, randomized controlled, prospective trial (RCT) investigating the (cost-)effectiveness of TESI by making a three-group comparison among patients with acute sciatica due to a herniated lumbar disc (< 8 weeks): (1) TESI combined with levobupivacaine added to oral pain medication (intervention group 1) versus oral pain medication alone (control group), (2) intervention group 1 versus transforaminal epidural injection with levobupivacaine and saline solution added to oral pain medication (intervention group 2), and (3) intervention group 2 versus control group. Co-primary outcomes were physical functioning (Roland Morris Disability Questionnaire), pain intensity (10-point numerical rating scale), and global perceived recovery (7-point Likert scale, dichotomized into 'recovered' and 'not recovered'). For all three comparisons, we defined the following minimal clinically relevant between-group differences: two points for pain intensity (range 0-10), four points for physical functioning (range 0-24) and a 20% difference in recovery rate. Secondary outcomes are health-related quality of life (EQ-5D-5L) and patient satisfaction (7-point Likert scale) and surgery rate. We also collected resource use data to perform an economic evaluation. Analyses will be conducted by intention-to-treat with p < 0.05 (two-tailed) for all three comparisons. Effects will be estimated using mixed models by maximum likelihood. For each comparison, mean differences, or difference in proportions, between groups will be tested per time point and an overall mean difference, or difference in proportions, between groups during the complete duration of follow-up (6 months) will be estimated. In the economic evaluation, Multivariate Imputation by Chained Equations will be used to handle missing data. Cost and effect differences will be estimated using seemingly unrelated regression, and uncertainty will be estimated using bootstrapping techniques. DISCUSSION: This statistical analysis plan provides detailed information on the intended analysis of the STAR trial, which aims to deliver evidence about the (cost-)effectiveness of TESI during the acute phase of sciatica (< 8 weeks). TRIAL REGISTRATION: Dutch National trial register NTR4457 (6 March 2014).

Correction to: Disc inflammation and Modic changes show an interaction effect on recovery after surgery for lumbar disc herniation.

In Tables 3 and 4: In the first column and row, the text reads "Mixed model test (patients with Modic changes)". This should have been just "Mixed model". The complete correct Tables 3 and 4 are given below.

Cost-effectiveness of combination therapy (Mechanical Diagnosis and Treatment and Transforaminal Epidural Steroid Injections) among patients with an indication for a Lumbar Herniated Disc surgery: Protocol of a randomized controlled trial.

OBJECTIVES: The general consensus is that surgical treatment is advised when conservative methods fail in patients with lumbosacral radicular syndrome (LRS). Preliminary evidence from our pilot study indicates that combination therapy (mechanical diagnosis therapy and transforaminal epidural injections) can prevent surgical treatment in patients on the waiting list for surgery. The pilot study lacked a control group, and therefore, firm conclusions pertaining to effects could not be made. This study aims to determine if combination therapy, performed while being on the waiting list for lumbar herniated disc surgery, is effective and cost-effective compared with usual care (i.e., no intervention while being on the waiting list) among patients with a magnetic resonance imaging (MRI)-confirmed indication for a lumbar herniated disc surgery. METHODS: A randomized controlled trial will be conducted with an economic evaluation. Patients aged 18 and above with incapacitating LRS, with leg pain and an MRI confirmed indication for lumbar disc hernia surgery, will be recruited from seven Dutch hospitals. While being on the waiting list for lumbar herniated disc surgery, patients will be randomized to either the combination therapy or usual care group. The primary outcome measure is the number of patients undergoing lumbar disc surgery during 12-month follow-up. Secondary outcomes include back and leg pain intensity (numeric pain rating scale), physical functioning (Roland Morris Disability Questionnaires-23), self-perceived recovery (global perceived effect), and health-related quality of life (EuroQol Five Dimensions Health Questionnaire (EQ-5D-5L) and 12-Item Short Form Health Survey (SF-12)). For the economic evaluation, societal and health care costs will be measured. Measurements moments are baseline, 1, 2, 4, 6, 9, and 12 months. Data will be analysed according to the intention-to-treat principle. CONCLUSION: No randomized controlled trials have evaluated the effectiveness and cost-effectiveness of combination therapy compared with usual care in patients with an indication for lumbar herniated disc surgery, which emphasizes the importance of this study.

Disc inflammation and Modic changes show an interaction effect on recovery after surgery for lumbar disc herniation.

PURPOSE: To study the interaction between Modic changes (MC) and inflammation by macrophages in the disc, in relation to clinical symptoms before and after discectomy for lumbar disc herniation. METHODS: Disc tissue was embedded in paraffin and stained with haematoxylin and CD68. Subsequently, tissue samples were categorized for degree of inflammation. Type of MC was scored on MRI at baseline. Roland Disability Questionnaire (RDQ) score and visual analogue scale for back pain and leg pain separately were considered at baseline and 1-year follow-up post-surgery. Main and interaction effects of MC and inflammation were tested against clinical outcome questionnaires. In addition, this analysis was repeated in bulging and extruded discs separately. RESULTS: Disc material and MRI's of 119 patients were retrieved and analysed. Forty-eight patients demonstrated mild inflammation, 45 showed moderate inflammation, and 26 showed considerable inflammation. In total, 49 out of 119 patients demonstrated MC. Grade of disc inflammation did not associate with the presence of MC. At baseline, no main or interaction effects of MC and inflammation were found on the clinical scores. However, during follow-up after discectomy, significant interaction effects were found for RDQ score: Only in patients with MC at baseline, patients remained significantly more disabled (3.2 points p = 0.006) if they showed considerable disc inflammation compared to patients with mild inflammation. The additional analysis showed similar results in extruded discs, but no significant effects in bulging discs. CONCLUSIONS: An interaction effect of MC and disc inflammation by macrophages is present. Only in patients with MC, those with considerable inflammation recover less satisfactory during follow-up after surgery. These slides can be retrieved under Electronic Supplementary Material.

Inflammatory biomarkers in patients with sciatica: a systematic review.

BACKGROUND: This systematic review focusses on inflammation as an underlying pathogenic mechanism in sciatica. We addressed two questions in particular: (1) what inflammatory biomarkers have been identified in patients with sciatica in the literature so far? 2) is there an association between the level of inflammatory activity and clinical symptoms? METHODS: The search was conducted up to December 19th 2018 in MEDLINE, EMBASE, CENTRAL and Web of Science. The study selection criteria: (1) observational cohort studies, cross-sectional studies and randomized clinical trials (RCT), (2) adult population (≥ 18 years) population with sciatica, (3) concentrations of inflammatory biomarkers measured in serum, cerebrospinal fluid (CSF) or biopsies, and (4) evaluation of clinically relevant outcome measures (pain or functional status). Three reviewers independently selected studies and extracted data regarding the study characteristics and the outcomes. Risk of Bias was evaluated using an adjusted version of the Quality in Prognosis Studies (QUIPS) tool. RESULTS: In total 16 articles fulfilled the criteria for inclusion: 7 cross sectional observational studies and 9 prospective cohort studies that included a total of 1212 patients. With regard to question 1) the following markers were identified: interleukin (IL)-1ß, IL-2, IL-4, IL-6, IL-8, IL-10, IL-17, IL-21, tumor necrosis factor-α (TNF-α), phospholipase A2, high sensitivity C-reactive protein (hsCRP), C-X-C motif chemokine 5 (CXCM5), CX3CL1, CCL2, epidermal growth factor (EGF), and monocyte chemotactic protein 4 (MCP-4). With regard to question 2) several positive correlations were found in longitudinal studies: a strong positive correlation between inflammatory mediators or byproducts and pain (measured by visual analogue scale, VAS) was found for IL-21 in two studies (r > 0,8), and moderate positive correlations for TNF-a in both serum (r = 0,629) and biopsy (r = 0.65); severe pain (VAS > 4) is associated with increased hsCRP levels among patients with sciatica (adjusted OR = 3.4 (95% CI, 1.1 to 10). CONCLUSION: In this systematic review there was considerable heterogeneity in the type of biomarkers and in the clinical measurements in the included studies. Taking into account the overall risk of bias of the included studies there is insufficient evidence to draw firm conclusions regarding the relationship between inflammation and clinical symptoms in patients with sciatica.

Gadolinium Enhancement Is Not Associated With Disc Inflammation in Patients With Sciatica.

STUDY DESIGN: Retrospective observational histological study. OBJECTIVE: To evaluate the reliability of gadolinium enhancement as a marker for inflammation by associating gadolinium enhancement findings with the degree of inflammation as measured by macrophage infiltration in disc material retrieved during disc surgery in patients with sciatica. SUMMARY OF BACKGROUND DATA: Disc inflammation often occurs in sciatica patients, a noninvasive tool that is used to assess disc inflammation is Gadolinium enhanced MR imaging. METHODS: Disc tissue was retrieved from patients in the Sciatica trial (N = 119), a multicenter randomized controlled trial in patients with sciatica. Disc tissue was embedded in paraffin and stained with hematoxylin and CD68. Tissue samples were categorized as mild (0-10 macrophages/cm), moderate (10-100 macrophages/cm), and considerable (>100 macrophages/cm) inflammation. Of the 119 MRIs, 96 were additionally performed with contrast-enhanced gadolinium. RESULTS: Seventy-four patients showed gadolinium enhancement of the disc herniation and 26 of the nerve root. Degree of inflammation by macrophages was not associated with gadolinium enhancement of nerve roots or herniated discs. These results did not change if the patient groups with and without Modic type 2 changes were evaluated separately. Furthermore, no associations were observed between gadolinium enhancement and presence of Modic type 2 changes. CONCLUSION: This study found gadolinium enhanced MRI findings to be unreliable as an indicator for inflammation of disc herniation or nerve root in patients with sciatica. LEVEL OF EVIDENCE: 2.

Can patient-reported profiles avoid unnecessary referral to a spine surgeon? An observational study to further develop the Nijmegen Decision Tool for Chronic Low Back Pain.

INTRODUCTION: Chronic Low Back Pain (CLBP) is a heterogeneous condition with lack of diagnostic clarity. Therapeutic interventions show small effects. To improve outcomes by targeting interventions it is recommended to develop a triage system to surgical and non-surgical treatments based on treatment outcomes. The objective of the current study was to develop and internally validate prognostic models based on pre-treatment patient-reported profiles that identify patients who either respond or do not respond to two frequently performed treatments (lumbar spine surgery and multidisciplinary pain management program). METHODS: A consecutive cohort study in a secondary referral spine center was performed. The study followed the recommendations of the PROGRESS framework and was registered in the Dutch Trial Register (NTR5946). Data of forty-seven potential pre-consultation (baseline) indicators predicting 'response' or 'non-response' at one-year follow-up for the two treatments were obtained to develop and validate four multivariable logistic regression models. The source population consisted of 3,410 referred CLBP-patients. Two treatment cohorts were defined: elective 'spine surgery' (n = 217 [6.4%]) and multidisciplinary bio-psychosocial 'pain management program' (n = 171 [5.0%]). Main inclusion criteria were age ≥18, CLBP (≥6 months), and not responding to primary care treatment. The primary outcome was functional ability: 'response' (Oswestry Disability Index [ODI] ≤22) and 'non-response' (ODI ≥41). RESULTS: Baseline indicators predictive of treatment outcome were: degree of disability (all models), ≥2 previous spine surgeries, psychosocial complaints, age (onset <20 or >50), and patient expectations of treatment outcomes. The explained variances were low for the models predicting response and non-response to pain management program (R2 respectively 23% and 26%) and modest for surgery (R2 30% and 39%). The overall performance was acceptable (c-index; 0.72-0.83), the model predicting non-response to surgery performed best (R2 = 39%; c-index = 0.83). CONCLUSION: This study was the first to identify different patient-reported profiles that predict response to different treatments for CLBP. The model predicting 'non-response' to elective lumbar spine surgery performed remarkably well, suggesting that referrals of these patients to a spine surgeon could be avoided. After external validation, the patient-reported profiles could potentially enhance timely patient triage to the right secondary care specialist and improve decision-making between clinican and patient. This could lead to improved treatment outcomes, which results in a more efficient use of healthcare resources.

Which patient-reported factors predict referral to spinal surgery? A cohort study among 4987 chronic low back pain patients.

PURPOSE: It is unknown which chronic low back pain (CLBP) patients are typically referred to spinal surgery. The present study, therefore, aimed to explore which patient-reported factors are predictive of spinal surgery referral among CLBP patients. METHODS: CLBP patients were consecutively recruited from a Dutch orthopedic hospital specialized in spine care (n = 4987). The outcome of this study was referral to spinal surgery (yes/no), and was assessed using hospital records. Possible predictive factors were assessed using a screening questionnaire. A prediction model was constructed using logistic regression, with backwards selection and p < 0.10 for keeping variables in the model. The model was internally validated and evaluated using discrimination and calibration measures. RESULTS: Female gender, previous back surgery, high intensity leg pain, somatization, and positive treatment expectations increased the odds of being referred to spinal surgery, while being obese, having comorbidities, pain in the thoracic spine, increased walking distance, and consultation location decreased the odds. The model's fit was good (X 2 = 10.5; p = 0.23), its discriminative ability was poor (AUC = 0.671), and its explained variance was low (5.5%). A post hoc analysis indicated that consultation location was significantly associated with spinal surgery referral, even after correcting for case-mix variables. CONCLUSION: Some patient-reported factors could be identified that are predictive of spinal surgery referral. Although the identified factors are known as common predictive factors of surgery outcome, they could only partly predict spinal surgery referral.

Validity and Reproducibility of the STarT Back Tool (Dutch Version) in Patients With Low Back Pain in Primary Care Settings.

OBJECTIVE: The purpose of this study was to translate and to investigate the reliability and validity of the STarT Back screening tool (SBT) in the primary care setting among patients with nonspecific low back pain (LBP). DESIGN: The SBT was formally translated into Dutch following a multistep approach for forward and backward translation. General practitioners and physical therapists included patients with LBP. METHODS: Patients completed a baseline questionnaire and a follow-up at 3 days and 3 months. The construct validity was calculated with Pearson's correlation coefficient. The reproducibility was assessed using the quadratic weighted kappa and the specific agreement. Predictive validity was assessed using relative risk ratios for persisting disability at 3 months. Content validity was analyzed using floor and ceiling effects. RESULTS: In total, 184 patients were included; 52.2% were categorized in the "low-risk" subgroup, 38.0% "medium-risk," and 9.8% "high-risk." For the construct validity we found, as expected, a moderate to high Pearson's correlation for questions 3 to 9 and a low correlation for questions 1 and 2 with their respective reference questionnaires. The reproducibility had a quadratic weighted kappa of 0.65 and the specific agreement of 82.4% for "low-risk," 53.3% for "medium-risk," and 33.3% for "high-risk." For the predictive validity for persisting disability we found a relative risk ratio for "medium-risk" of 1.8 (95% confidence interval [CI]: 1.0-3.1) and 2.7 (95% CI: 1.4-4.9) for "high-risk" compared with "low-risk." For the content validity, we found that no floor and ceiling effects were present. LIMITATIONS: There was a relatively small sample size for the retest reliability study. Patients were not compared between physical therapist and GP, as there were not enough patients in both groups. For practical reasons, the patients filled out the baseline questionnaire after receiving the first treatment/consultation; however, the questionnaire is intended to be filled in before the first consultation/treatment. CONCLUSION: The SBT has been successfully translated into Dutch. The psychometric analysis showed acceptable results and, therefore, the SBT is a valid screening tool for patients with LBP in Dutch primary care.

Determination of the Oswestry Disability Index score equivalent to a "satisfactory symptom state" in patients undergoing surgery for degenerative disorders of the lumbar spine-a Spine Tango registry-based study.

BACKGROUND CONTEXT: The achievement of a given change score on a valid outcome instrument is commonly used to indicate whether a clinically relevant change has occurred after spine surgery. However, the achievement of such a change score can be dependent on baseline values and does not necessarily indicate whether the patient is satisfied with the current state. The achievement of an absolute score equivalent to a patient acceptable symptom state (PASS) may be a more stringent measure to indicate treatment success. PURPOSE: This study aimed to estimate the score on the Oswestry Disability Index (ODI, version 2.1a; 0-100) corresponding to a PASS in patients who had undergone surgery for degenerative disorders of the lumbar spine. STUDY DESIGN/SETTING: This is a cross-sectional study of diagnostic accuracy using follow-up data from an international spine surgery registry. PATIENT SAMPLE: The sample includes 1,288 patients with degenerative lumbar spine disorders who had undergone elective spine surgery, registered in the EUROSPINE Spine Tango Spine Surgery Registry. OUTCOME MEASURES: The main outcome measure was the ODI (version 2.1a). METHODS: Surgical data and data from the ODI and Core Outcome Measures Index (COMI) were included to determine the ODI threshold equivalent to PASS at 1 year (±1.5 months; n=780) and 2 years (±2 months; n=508) postoperatively. The symptom-specific well-being item of the COMI was used as the external criterion in the receiver operating characteristic (ROC) analysis to determine the ODI threshold equivalent to PASS. Separate sensitivity analyses were performed based on the different definitions of an "acceptable state" and for subgroups of patients. JF is a copyright holder of the ODI. RESULTS: The ODI threshold for PASS was 22, irrespective of the time of follow-up (area under the curve [AUC]: 0.89 [sensitivity {Se}: 78.3%, specificity {Sp}: 82.1%] and AUC: 0.91 [Se: 80.7%, Sp: 85.6] for the 1- and 2-year follow-ups, respectively). Sensitivity analyses showed that the absolute ODI-22 threshold for the two follow-up time-points were robust. A stricter definition of PASS resulted in lower ODI thresholds, varying from 16 (AUC=0.89; Se: 80.2%, Sp: 82.0%) to 18 (AUC=0.90; Se: 82.4%, Sp: 80.4%) depending on the time of follow-up. CONCLUSIONS: An ODI score ≤22 indicates the achievement of an acceptable symptom state and can hence be used as a criterion of treatment success alongside the commonly used change score measures. At the individual level, the threshold could be used to indicate whether or not a patient with a lumbar spine disorder is a "responder" after elective surgery.

Long-term patterns of chronic complaints of the arms, neck, and shoulders and their determinants--the Doetinchem Cohort Study.

Complaints of the arms, neck, and shoulders (CANS) represent a major public health problem but the long-term course is largely unknown. Our objective was to explore the 15-year course of chronic CANS and its determinants in a population-based cohort. During 1993 to 2012, 3050 men and women aged 26 to 65 years at baseline were measured every 5 years, up to 4 times. Complaints of the arms, neck, and shoulders and sociodemographic, lifestyle, mental health, and physical load determinants were obtained by self-reported questionnaires and physical examinations. Information on chronic CANS was used to create patterns of the 15-year course: persistence, recovery, variable, no CANS, and the development of CANS. Only 47% were free of chronic CANS throughout the total 15-year period. The prevalence of other patterns was development (18.3%), persistence (8.5%), recovery (7.5%), and variable (18.7%). In multivariable logistic regression analyses, female gender, age 46 to 55 years, being not employed, former smoking, physical inactivity, an episode of CANS during the past 12 months, and high physical load in daily life (eg, often adopting awkward postures, frequent lifting, carrying, pushing, or pulling) were associated with the development of chronic CANS. Female gender, age 36 to 45 years, being not employed, and awkward postures in daily life were associated with persistent CANS. We conclude that chronic CANS represent a dynamic condition and affect the majority of the general population at least once in 15 years. Determinants associated with chronic CANS, especially physical load in daily life, can be used to develop preventive interventions and give guidance to treatment.

Radiofrequency denervation for chronic low back pain.

BACKGROUND: Radiofrequency (RF) denervation, an invasive treatment for chronic low back pain (CLBP), is used most often for pain suspected to arise from facet joints, sacroiliac (SI) joints or discs. Many (uncontrolled) studies have shown substantial variation in its use between countries and continued uncertainty regarding its effectiveness. OBJECTIVES: The objective of this review is to assess the effectiveness of RF denervation procedures for the treatment of patients with CLBP. The current review is an update of the review conducted in 2003. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, three other databases, two clinical trials registries and the reference lists of included studies from inception to May 2014 for randomised controlled trials (RCTs) fulfilling the inclusion criteria. We updated this search in June 2015, but we have not yet incorporated these results. SELECTION CRITERIA: We included RCTs of RF denervation for patients with CLBP who had a positive response to a diagnostic block or discography. We applied no language or date restrictions. DATA COLLECTION AND ANALYSIS: Pairs of review authors independently selected RCTs, extracted data and assessed risk of bias (RoB) and clinical relevance using standardised forms. We performed meta-analyses with clinically homogeneous studies and assessed the quality of evidence for each outcome using the Grades of Recommendation, Assessment, Development and Evaluation (GRADE) approach. MAIN RESULTS: In total, we included 23 RCTs (N = 1309), 13 of which (56%) had low RoB. We included both men and women with a mean age of 50.6 years. We assessed the overall quality of the evidence as very low to moderate. Twelve studies examined suspected facet joint pain, five studies disc pain, two studies SI joint pain, two studies radicular CLBP, one study suspected radiating low back pain and one study CLBP with or without suspected radiation. Overall, moderate evidence suggests that facet joint RF denervation has a greater effect on pain compared with placebo over the short term (mean difference (MD) -1.47, 95% confidence interval (CI) -2.28 to -0.67). Low-quality evidence indicates that facet joint RF denervation is more effective than placebo for function over the short term (MD -5.53, 95% CI -8.66 to -2.40) and over the long term (MD -3.70, 95% CI -6.94 to -0.47). Evidence of very low to low quality shows that facet joint RF denervation is more effective for pain than steroid injections over the short (MD -2.23, 95% CI -2.38 to -2.08), intermediate (MD -2.13, 95% CI -3.45 to -0.81), and long term (MD -2.65, 95% CI -3.43 to -1.88). RF denervation used for disc pain produces conflicting results, with no effects for RF denervation compared with placebo over the short and intermediate term, and small effects for RF denervation over the long term for pain relief (MD -1.63, 95% CI -2.58 to -0.68) and improved function (MD -6.75, 95% CI -13.42 to -0.09). Lack of evidence of short-term effectiveness undermines the clinical plausibility of intermediate-term or long-term effectiveness. When RF denervation is used for SI joint pain, low-quality evidence reveals no differences from placebo in effects on pain (MD -2.12, 95% CI -5.45 to 1.21) and function (MD -14.06, 95% CI -30.42 to 2.30) over the short term, and one study shows a small effect on both pain and function over the intermediate term. RF denervation is an invasive procedure that can cause a variety of complications. The quality and size of original studies were inadequate to permit assessment of how often complications occur. AUTHORS' CONCLUSIONS: The review authors found no high-quality evidence suggesting that RF denervation provides pain relief for patients with CLBP. Similarly, we identified no convincing evidence to show that this treatment improves function. Overall, the current evidence for RF denervation for CLBP is very low to moderate in quality; high-quality evidence is lacking. High-quality RCTs with larger patient samples are needed, as are data on long-term effects.

Red flags to screen for malignancy and fracture in patients with low back pain.

STUDY QUESTION: What are the best red flags to indicate the possibility of fracture or malignancy in patients presenting with low back pain in primary, secondary, or tertiary care? SUMMARY ANSWER: Older age, prolonged corticosteroid use, severe trauma, and presence of a contusion or abrasion increase the likelihood of spinal fracture (likelihood was higher with multiple red flags); a history of malignancy increases the likelihood of spinal malignancy.

Multidisciplinary biopsychosocial rehabilitation for chronic low back pain.

BACKGROUND: Low back pain (LBP) is responsible for considerable personal suffering worldwide. Those with persistent disabling symptoms also contribute to substantial costs to society via healthcare expenditure and reduced work productivity. While there are many treatment options, none are universally endorsed. The idea that chronic LBP is a condition best understood with reference to an interaction of physical, psychological and social influences, the 'biopsychosocial model', has received increasing acceptance. This has led to the development of multidisciplinary biopsychosocial rehabilitation (MBR) programs that target factors from the different domains, administered by healthcare professionals from different backgrounds. OBJECTIVES: To review the evidence on the effectiveness of MBR for patients with chronic LBP. The focus was on comparisons with usual care and with physical treatments measuring outcomes of pain, disability and work status, particularly in the long term. SEARCH METHODS: We searched the CENTRAL, MEDLINE, EMBASE, PsycINFO and CINAHL databases in January and March 2014 together with carrying out handsearches of the reference lists of included and related studies, forward citation tracking of included studies and screening of studies excluded in the previous version of this review. SELECTION CRITERIA: All studies identified in the searches were screened independently by two review authors; disagreements regarding inclusion were resolved by consensus. The inclusion criteria were published randomised controlled trials (RCTs) that included adults with non-specific LBP of longer than 12 weeks duration; the index intervention targeted at least two of physical, psychological and social or work-related factors; and the index intervention was delivered by clinicians from at least two different professional backgrounds. DATA COLLECTION AND ANALYSIS: Two review authors extracted and checked information to describe the included studies, assessed risk of bias and performed the analyses. We used the Cochrane risk of bias tool to describe the methodological quality. The primary outcomes were pain, disability and work status, divided into the short, medium and long term. Secondary outcomes were psychological functioning (for example depression, anxiety, catastrophising), healthcare service utilisation, quality of life and adverse events. We categorised the control interventions as usual care, physical treatment, surgery, or wait list for surgery in separate meta-analyses. The first two comparisons formed our primary focus. We performed meta-analyses using random-effects models and assessed the quality of evidence using the GRADE method. We performed sensitivity analyses to assess the influence of the methodological quality, and subgroup analyses to investigate the influence of baseline symptom severity and intervention intensity. MAIN RESULTS: From 6168 studies identified in the searches, 41 RCTs with a total of 6858 participants were included. Methodological quality ratings ranged from 1 to 9 out 12, and 13 of the 41 included studies were assessed as low risk of bias. Pooled estimates from 16 RCTs provided moderate to low quality evidence that MBR is more effective than usual care in reducing pain and disability, with standardised mean differences (SMDs) in the long term of 0.21 (95% CI 0.04 to 0.37) and 0.23 (95% CI 0.06 to 0.4) respectively. The range across all time points equated to approximately 0.5 to 1.4 units on a 0 to 10 numerical rating scale for pain and 1.4 to 2.5 points on the Roland Morris disability scale (0 to 24). There was moderate to low quality evidence of no difference on work outcomes (odds ratio (OR) at long term 1.04, 95% CI 0.73 to 1.47). Pooled estimates from 19 RCTs provided moderate to low quality evidence that MBR was more effective than physical treatment for pain and disability with SMDs in the long term of 0.51 (95% CI -0.01 to 1.04) and 0.68 (95% CI 0.16 to 1.19) respectively. Across all time points this translated to approximately 0.6 to 1.2 units on the pain scale and 1.2 to 4.0 points on the Roland Morris scale. There was moderate to low quality evidence of an effect on work outcomes (OR at long term 1.87, 95% CI 1.39 to 2.53). There was insufficient evidence to assess whether MBR interventions were associated with more adverse events than usual care or physical interventions.Sensitivity analyses did not suggest that the pooled estimates were unduly influenced by the results from low quality studies. Subgroup analyses were inconclusive regarding the influence of baseline symptom severity and intervention intensity. AUTHORS' CONCLUSIONS: Patients with chronic LBP receiving MBR are likely to experience less pain and disability than those receiving usual care or a physical treatment. MBR also has a positive influence on work status compared to physical treatment. Effects are of a modest magnitude and should be balanced against the time and resource requirements of MBR programs. More intensive interventions were not responsible for effects that were substantially different to those of less intensive interventions. While we were not able to determine if symptom intensity at presentation influenced the likelihood of success, it seems appropriate that only those people with indicators of significant psychosocial impact are referred to MBR.

Rehabilitation after lumbar disc surgery.

BACKGROUND: Several rehabilitation programmes are available for individuals after lumbar disc surgery. OBJECTIVES: To determine whether active rehabilitation after lumbar disc surgery is more effective than no treatment, and to describe which type of active rehabilitation is most effective. This is the second update of a Cochrane Review first published in 2002.First, we clustered treatments according to the start of treatment.1. Active rehabilitation that starts immediately postsurgery.2. Active rehabilitation that starts four to six weeks postsurgery.3. Active rehabilitation that starts longer than 12 months postsurgery.For every cluster, the following comparisons were investigated.A. Active rehabilitation versus no treatment, placebo or waiting list control.B. Active rehabilitation versus other kinds of active rehabilitation.C. Specific intervention in addition to active rehabilitation versus active rehabilitation alone. SEARCH METHODS: We searched CENTRAL (2013, Issue 4) and MEDLINE, EMBASE, CINAHL, PEDro and PsycINFO to May 2013. SELECTION CRITERIA: We included only randomised controlled trials (RCTs). DATA COLLECTION AND ANALYSIS: Pairs of review authors independently assessed studies for eligibility and risk of bias. Meta-analyses were performed if studies were clinically homogeneous. The GRADE approach was used to determine the overall quality of evidence. MAIN RESULTS: In this update, we identified eight new studies, thereby including a total of 22 trials (2503 participants), 10 of which had a low risk of bias. Most rehabilitation programmes were assessed in only one study. Both men and women were included, and overall mean age was 41.4 years. All participants had received standard discectomy, microdiscectomy and in one study standard laminectomy and (micro)discectomy. Mean duration of the rehabilitation intervention was 12 weeks; eight studies assessed six to eight-week exercise programmes, and eight studies assessed 12 to 13-week exercise programmes. Programmes were provided in primary and secondary care facilities and were started immediately after surgery (n = 4) or four to six weeks (n = 16) or one year after surgery (n = 2). In general, the overall quality of the evidence is low to very low. Rehabilitation programmes that started immediately after surgery were not more effective than their control interventions, which included exercise. Low- to very low-quality evidence suggests that there were no differences between specific rehabilitation programmes (multidisciplinary care, behavioural graded activity, strength and stretching) that started four to six weeks postsurgery and their comparators, which included some form of exercise. Low-quality evidence shows that physiotherapy from four to six weeks postsurgery onward led to better function than no treatment or education only, and that multidisciplinary rehabilitation co-ordinated by medical advisors led to faster return to work than usual care. Statistical pooling was performed only for three comparisons in which the rehabilitation programmes started four to six weeks postsurgery: exercise programmes versus no treatment, high- versus low-intensity exercise programmes and supervised versus home exercise programmes. Very low-quality evidence (five RCTs, N = 272) shows that exercises are more effective than no treatment for pain at short-term follow-up (standard mean difference (SMD) -0.90; 95% confidence interval (CI) -1.55 to -0.24), and low-quality evidence (four RCTs, N = 252) suggests that exercises are more effective for functional status on short-term follow-up (SMD -0.67; 95% CI -1.22 to -0.12) and that no difference in functional status was noted on long-term follow-up (three RCTs, N = 226; SMD -0.22; 95% CI -0.49 to 0.04). None of these studies reported that exercise increased the reoperation rate. Very low-quality evidence (two RCTs, N = 103) shows that high-intensity exercise programmes are more effective than low-intensity exercise programmes for pain in the short term (weighted mean difference (WMD) -10.67; 95% CI -17.04 to -4.30), and low-quality evidence (two RCTs, N = 103) shows that they are more effective for functional status in the short term (SMD -0.77; 95% CI -1.17 to -0.36). Very low-quality evidence (four RCTs, N = 154) suggests no significant differences between supervised and home exercise programmes for short-term pain relief (SMD -0.76;  95% CI -2.04 to 0.53) or functional status (four RCTs, N = 154; SMD -0.36; 95% CI -0.88 to 0.15). AUTHORS' CONCLUSIONS: Considerable variation was noted in the content, duration and intensity of the rehabilitation programmes included in this review, and for none of them was high- or moderate-quality evidence identified. Exercise programmes starting four to six weeks postsurgery seem to lead to a faster decrease in pain and disability than no treatment, with small to medium effect sizes, and high-intensity exercise programmes seem to lead to a slightly faster decrease in pain and disability than is seen with low-intensity programmes, but the overall quality of the evidence is only low to very low. No significant differences were noted between supervised and home exercise programmes for pain relief, disability or global perceived effect. None of the trials reported an increase in reoperation rate after first-time lumbar surgery. High-quality randomised controlled trials are strongly needed.

Minimally invasive surgery for lumbar disc herniation: a systematic review and meta-analysis.

PURPOSE: Assessing the benefits of surgical treatments for sciatica is critical for clinical and policy decision-making. To compare minimally invasive (MI) and conventional microdiscectomy (MD) for patients with sciatica due to lumbar disc herniation. METHODS: A systematic review and meta-analysis of controlled clinical trials including patients with sciatica due to lumbar disc herniation. Conventional microdiscectomy was compared separately with: (1) Interlaminar MI discectomy (ILMI vs. MD); (2) Transforaminal MI discectomy (TFMI vs. MD). OUTCOMES: Back pain, leg pain, function, improvement, work status, operative time, blood loss, length of hospital stay, complications, reoperations, analgesics and cost outcomes were extracted and risk of bias assessed. Pooled effect estimates were calculated using random effect meta-analysis. RESULTS: Twenty-nine studies, 16 RCTs and 13 non-randomised studies (n = 4,472), were included. Clinical outcomes were not different between the surgery types. There is low quality evidence that ILMI takes 11 min longer, results in 52 ml less blood loss and reduces mean length of hospital stay by 1.5 days. There were no differences in complications or reoperations. The main limitations were high risk of bias, low number of studies and small sample sizes comparing TF with MD. CONCLUSIONS: There is moderate to low quality evidence of no differences in clinical outcomes between MI surgery and conventional microdiscectomy for patients with sciatica due to lumbar disc herniation. Studies comparing transforaminal MI with conventional surgery with sufficient sample size and methodological robustness are lacking.

Red flags to screen for malignancy and fracture in patients with low back pain: systematic review.

OBJECTIVE: To review the evidence on diagnostic accuracy of red flag signs and symptoms to screen for fracture or malignancy in patients presenting with low back pain to primary, secondary, or tertiary care. DESIGN: Systematic review. DATA SOURCES: Medline, OldMedline, Embase, and CINAHL from earliest available up to 1 October 2013. INCLUSION CRITERIA: Primary diagnostic studies comparing red flags for fracture or malignancy to an acceptable reference standard, published in any language. REVIEW METHODS: Assessment of study quality and extraction of data was conducted by three independent assessors. Diagnostic accuracy statistics and post-test probabilities were generated for each red flag. RESULTS: We included 14 studies (eight from primary care, two from secondary care, four from tertiary care) evaluating 53 red flags; only five studies evaluated combinations of red flags. Pooling of data was not possible because of index test heterogeneity. Many red flags in current guidelines provide virtually no change in probability of fracture or malignancy or have untested diagnostic accuracy. The red flags with the highest post-test probability for detection of fracture were older age (9%, 95% confidence interval 3% to 25%), prolonged use of corticosteroid drugs (33%, 10% to 67%), severe trauma (11%, 8% to 16%), and presence of a contusion or abrasion (62%, 49% to 74%). Probability of spinal fracture was higher when multiple red flags were present (90%, 34% to 99%). The red flag with the highest post-test probability for detection of spinal malignancy was history of malignancy (33%, 22% to 46%). CONCLUSIONS: While several red flags are endorsed in guidelines to screen for fracture or malignancy, only a small subset of these have evidence that they are indeed informative. These findings suggest a need for revision of many current guidelines.

Red flags to screen for malignancy in patients with low-back pain.

BACKGROUND: The identification of serious pathologies, such as spinal malignancy, is one of the primary purposes of the clinical assessment of patients with low-back pain (LBP). Clinical guidelines recommend awareness of "red flag" features from the patient's clinical history and physical examination to achieve this. However, there are limited empirical data on the diagnostic accuracy of these features and there remains very little information on how best to use them in clinical practice. OBJECTIVES: To assess the diagnostic performance of clinical characteristics identified by taking a clinical history and conducting a physical examination ("red flags") to screen for spinal malignancy in patients presenting with LBP. SEARCH METHODS: We searched electronic databases for primary studies (MEDLINE, EMBASE, and CINAHL) and systematic reviews (PubMed and Medion) from the earliest date until 1 April 2012. Forward and backward citation searching of eligible articles was also performed. SELECTION CRITERIA: We considered studies if they compared the results of history taking and physical examination on patients with LBP with those of diagnostic imaging (magnetic resonance imaging, computed tomography, myelography). DATA COLLECTION AND ANALYSIS: Two review authors independently assessed the quality of each included study with the QUality Assessment of Diagnostic Accuracy Studies (QUADAS) tool and extracted details on patient characteristics, study design, index tests, and reference standard. Diagnostic accuracy data were presented as sensitivities and specificities with 95% confidence intervals for all index tests. MAIN RESULTS: We included eight cohort studies of which six were performed in primary care (total number of patients; n = 6622), one study was from an accident and emergency setting (n = 482), and one study was from a secondary care setting (n = 257). In the six primary care studies, the prevalence of spinal malignancy ranged from 0% to 0.66%. Overall, data from 20 index tests were extracted and presented, however only seven of these were evaluated by more than one study. Because of the limited number of studies and clinical heterogeneity, statistical pooling of diagnostic accuracy data was not performed.There was some evidence from individual studies that having a previous history of cancer meaningfully increases the probability of malignancy. Most "red flags" such as insidious onset, age > 50, and failure to improve after one month have high false positive rates.All of the tests were evaluated in isolation and no study presented data on a combination of positive tests to identify spinal malignancy. AUTHORS' CONCLUSIONS: For most "red flags," there is insufficient evidence to provide recommendations regarding their diagnostic accuracy or usefulness for detecting spinal malignancy. The available evidence indicates that in patients with LBP, an indication of spinal malignancy should not be based on the results of one single "red flag" question. Further research to evaluate the performance of different combinations of tests is recommended.

Computed tomography for the diagnosis of lumbar spinal pathology in adult patients with low back pain or sciatica: a diagnostic systematic review.

AIM: In low back pain if serious pathology is suspected diagnostic imaging could be performed. One of the imaging techniques available for this purpose is computed tomography (CT), however, insight in the diagnostic performance of CT is unclear. METHOD: Diagnostic systematic review. Studies assessing the diagnostic accuracy of CT in adult patients suggested having low back pain caused by specific pathology were selected. Two review authors independently selected studies for inclusion, extracted data and assessed risk of bias. Pooled summary estimates of sensitivity and specificity with 95% CI were calculated. RESULTS: Seven studies were included, all describing the diagnostic accuracy of CT in identifying lumbar disc herniation. Six studies used surgical findings as the reference standard and were considered sufficiently homogenous to carry out a meta-analysis. The pooled summary estimate of sensitivity was 77.4% and specificity was 73.7%. CONCLUSIONS: We found no studies evaluating the accuracy of CT for pathologies such as vertebral cancer, infection and fractures and this remains unclear. Our results should be interpreted with some caution. Sensitivity and specificity, regarding the detection of lumbar disc herniation, showed that a substantial part of the patients is still classified as false-negative and false-positive. In future, the diagnostic performance of CT must be assessed in high quality prospective cohort studies with an unselected population of patients with low back pain.