Exercise Therapy for Treatment of Acute Non-specific Low Back Pain: A Cochrane Systematic Review and Meta-analysis of Randomized Controlled Trials.

OBJECTIVE: To assess the effectiveness of exercise for acute non-specific low back pain (LBP) vs our main comparisons: (1) sham treatment and (2) no treatment at short term (main follow-up time). DATA SOURCES AND STUDY SELECTION: A comprehensive search up till November 2021 was conducted in numerous databases for randomized controlled trials on the effectiveness of exercise in adults with acute LBP (<6 weeks). Studies examining LBP with a specific etiology were excluded. The primary outcomes were back pain, back-specific functional status, and recovery. DATA EXTRACTION: Two review authors independently conducted the study selection, risk of bias assessment, and data extraction. GRADE was used to assess the certainty of the evidence. DATA SYNTHESIS: We identified 23 randomized controlled trials (2674 participants). There is very low-certainty evidence that exercise therapy compared with sham/placebo treatment has no clinically relevant effect on pain (mean difference [MD] -0.80, 95% confidence interval [CI] -5.79 to 4.19; 1 study, 299 participants) and on functional status (MD 2.00, 95% CI -2.20 to 6.20; 1 study, 299 participants) in the short term. There is very low-quality evidence which suggests no difference in effect on pain and functional status for exercise vs no treatment (2 studies; n=157, not pooled due to heterogeneity) at short-term follow-up. Similar results were found for the other follow-up moments. The certainty of the evidence was downgraded because many randomized controlled trials had a high risk of bias, were small in size, and/or there was substantial heterogeneity. CONCLUSION: Exercise therapy compared with sham/placebo and no treatment may have no clinically relevant effect on pain or functional status in the short term in people with acute non-specific LBP, but the evidence is very uncertain. Owing to insufficient reporting of adverse events, we were unable to reach any conclusions on the safety or harms related to exercise therapy.

Effectiveness of Pilates compared with home-based exercises in individuals with chronic non-specific low back pain: Randomised controlled trial.

OBJECTIVE: To investigate the effectiveness of a Pilates exercise program compared with home-based exercises in individuals with chronic non-specific low back pain. DESIGN: A randomised controlled trial with a six-month follow-up. SETTING: Rehabilitation clinic. PARTICIPANTS: One hundred and forty-five individuals (18-50 years of age) with low back pain for ≥ 12 consecutive weeks were enrolled and randomly allocated to either Pilates (n = 72) or home-based exercise groups (n = 73). INTERVENTIONS: Method Pilates (Mat Pilates exercises using accessories) versus home-based exercise (postural exercises, muscle stretching and strengthening, and spine stabilisation/mobilisation), twice a week, for 6 weeks. MAIN MEASURES: Assessments were performed at baseline, post-intervention, and six months follow-up. Outcomes were pain intensity, disability, and health-related quality of life. RESULTS: At post-intervention, the Pilates group had significantly lower pain intensity (mean difference = -1.14; 95% CI -2.05; -0.23), less disability (mean difference = -6.7; 95% CI -11.3; -2.0), and higher health-related quality of life (mean difference = 0.102; 95% CI 0.054; 0151) compared to the home-based exercise group. At follow-up, the Pilates group had a significantly higher health-related quality of life (mean difference = 0.055; 95% CI 0.003; 0.106) compared with the home-based exercise group but there were no significant differences in pain and disability. A significant overall effect of Pilates compared to home-based exercise was found for disability (mean difference = -4.4; 95% CI -7.6; -1.1), and health-related quality of life (mean difference = 0.049; 95% CI 0.022; 0.076), but not for pain. CONCLUSION: Although Pilates was significantly superior to home exercise for pain and disability, the differences were not considered clinically relevant. However, Pilates did provide significant and clinically relevant differences in utility.

Dealing with confounding in observational studies: A scoping review of methods evaluated in simulation studies with single-point exposure.

The aim of this article was to perform a scoping review of methods available for dealing with confounding when analyzing the effect of health care treatments with single-point exposure in observational data. We aim to provide an overview of methods and their performance assessed by simulation studies indexed in PubMed. We searched PubMed for simulation studies published until January 2021. Our search was restricted to studies evaluating binary treatments and binary and/or continuous outcomes. Information was extracted on the methods' assumptions, performance, and technical properties. Of 28,548 identified references, 127 studies were eligible for inclusion. Of them, 84 assessed 14 different methods (ie, groups of estimators that share assumptions and implementation) for dealing with measured confounding, and 43 assessed 10 different methods for dealing with unmeasured confounding. Results suggest that there are large differences in performance between methods and that the performance of a specific method is highly dependent on the estimator. Furthermore, the methods' assumptions regarding the specific data features also substantially influence the methods' performance. Finally, the methods result in different estimands (ie, target of inference), which can even vary within methods. In conclusion, when choosing a method to adjust for measured or unmeasured confounding it is important to choose the most appropriate estimand, while considering the population of interest, data structure, and whether the plausibility of the methods' required assumptions hold.

Mapping Oswestry Disability Index Responses to EQ-5D-3L Utility Values: Are Cost-Utility Results Valid?

OBJECTIVES: To develop and validate approaches for mapping Oswestry Disability Index responses to 3-level version of EQ-5D utility values and to evaluate the impact of using mapped utility values on cost-utility results compared with published regression models. METHODS: Three response mapping approaches were developed in a random sample of 70% of 18 692 patients with low back pain: nonparametric approach (Non-p), nonparametric approach excluding logical inconsistencies (Non-peLI), and ordinal logistic regression (OLR). Performance was assessed in the remaining 30% using R-square (R2), root mean square error (RMSE), and mean absolute error (MAE). To evaluate whether MAEs and their 95% limits of agreement (LA) were clinically relevant, a minimally clinically important difference of 0.074 was used. Probabilities of cost-effectiveness estimated using observed and mapped utility values were compared in 2 economic evaluations. RESULTS: The Non-p performed the best (R2 = 0.43; RMSE = 0.22; MAE = 0.03; 95% LA = -0.40 to 0.47) compared with the Non-peLI (R2 = 0.07; RMSE = 0.29; MAE = -0.15; 95% LA = -0.63 to 0.34) and OLR (R2 = 0.22; RMSE = 0.26; MAE = 0.02; 95% LA = -0.49 to 0.53). MAEs were lower than the minimally clinically important difference for the Non-p and OLR but not for the Non-peLI. Differences in probabilities of cost-effectiveness ranged from 1% to 4% (Non-p), 0.1% to 9% (Non-peLI), and 0.1% to 20% (OLR). CONCLUSIONS: Results suggest that the developed response mapping approaches are not valid for estimating individual patients' 3-level version of EQ-5D utility values, and-depending on the approach-may considerably affect cost-utility results. The developed approaches did not perform better than previously published regression-based models and are therefore not recommended for use in economic evaluations.

Effectiveness of adding motivational interviewing or a stratified vocational advice intervention to usual case management on return to work for people with musculoskeletal disorders: the MI-NAV randomised controlled trial.

OBJECTIVES: To evaluate if adding motivational interviewing (MI) or a stratified vocational advice intervention (SVAI) to usual case management (UC), reduced sickness absence over 6 months for workers on sick leave due to musculoskeletal disorders. METHODS: We conducted a three-arm parallel pragmatic randomised controlled trial including 514 employed workers (57% women, median age 49 (range 24-66)), on sick leave for at least 50% of their contracted work hours for ≥7 weeks. All participants received UC. In addition, those randomised to UC+MI were offered two MI sessions from social insurance caseworkers and those randomised to UC+SVAI were offered vocational advice from physiotherapists (participants with low/medium-risk for long-term sickness absence were offered one to two sessions, and those with high-risk were offered three to four sessions). RESULTS: Median sickness absence was 62 days, (95% CI 52 to 71) in the UC arm (n=171), 56 days (95% CI 43 to 70) in the UC+MI arm (n=169) and 49 days (95% CI 38 to 60) in the UC+SVAI arm (n=169). After adjusting for predefined potential confounding factors, the results showed seven fewer days in the UC+MI arm (95% CI -15 to 2) and the UC+SVAI arm (95% CI -16 to 1), compared with the UC arm. The adjusted differences were not statistically significant. CONCLUSIONS: The MI-NAV trial did not show effect on return to work of adding MI or SVAI to UC. The reduction in sickness absence over 6 months was smaller than anticipated, and uncertain due to wide CIs. TRIAL REGISTRATION NUMBER: NCT03871712.

The McKenzie method for (sub)acute non-specific low back pain.

BACKGROUND: There is widespread agreement amongst clinicians that people with non-specific low back pain (NSLBP) comprise a heterogeneous group and that their management should be individually tailored. One treatment known by its tailored design is the McKenzie method (e.g. an individualized program of exercises based on clinical clues observed during assessment). OBJECTIVES: To evaluate the effectiveness of the McKenzie method in people with (sub)acute non-specific low back pain. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase and two trials registers up to 15 August 2022. SELECTION CRITERIA: We included randomized controlled trials (RCTs) investigating the effectiveness of the McKenzie method in adults with (sub)acute (less than 12 weeks) NSLBP. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. MAIN RESULTS: This review included five RCTs with a total of 563 participants recruited from primary or tertiary care. Three trials were conducted in the USA, one in Australia, and one in Scotland. Three trials received financial support from non-commercial funders and two did not provide information on funding sources. All trials were at high risk of performance and detection bias. None of the included trials measured adverse events. McKenzie method versus minimal intervention (educational booklet; McKenzie method as a supplement to other intervention - main comparison) There is low-certainty evidence that the McKenzie method may result in a slight reduction in pain in the short term (MD -7.3, 95% CI -12.0 to -2.56; 2 trials, 377 participants) but not in the intermediate term (MD -5.0, 95% CI -14.3 to 4.3; 1 trial, 180 participants). There is low-certainty evidence that the McKenzie method may not reduce disability in the short term (MD -2.5, 95% CI -7.5 to 2.0; 2 trials, 328 participants) nor in the intermediate term (MD -0.9, 95% CI -7.3 to 5.6; 1 trial, 180 participants). McKenzie method versus manual therapy There is low-certainty evidence that the McKenzie method may not reduce pain in the short term (MD -8.7, 95% CI -27.4 to 10.0; 3 trials, 298 participants) and may result in a slight increase in pain in the intermediate term (MD 7.0, 95% CI 0.7 to 13.3; 1 trial, 235 participants). There is low-certainty evidence that the McKenzie method may not reduce disability in the short term (MD -5.0, 95% CI -15.0 to 5.0; 3 trials, 298 participants) nor in the intermediate term (MD 4.3, 95% CI -0.7 to 9.3; 1 trial, 235 participants). McKenzie method versus other interventions (massage and advice) There is very low-certainty evidence that the McKenzie method may not reduce disability in the short term (MD 4.0, 95% CI -15.4 to 23.4; 1 trial, 30 participants) nor in the intermediate term (MD 10.0, 95% CI -8.9 to 28.9; 1 trial, 30 participants). AUTHORS' CONCLUSIONS: Based on low- to very low-certainty evidence, the treatment effects for pain and disability found in our review were not clinically important. Thus, we can conclude that the McKenzie method is not an effective treatment for (sub)acute NSLBP.

Exercise therapy for treatment of acute non-specific low back pain.

BACKGROUND: Low back pain (LBP) is the leading cause of disability globally. It generates considerable direct costs (healthcare) and indirect costs (lost productivity). The many available treatments for LBP include exercise therapy, which is practised extensively worldwide. OBJECTIVES: To evaluate the benefits and harms of exercise therapy for acute non-specific low back pain in adults compared to sham/placebo treatment or no treatment at short-term, intermediate-term, and long-term follow-up. SEARCH METHODS: This is an update of a Cochrane Review first published in 2005. We conducted an updated search for randomised controlled trials (RCTs) in CENTRAL, MEDLINE, Embase, four other databases, and two trial registers. We screened the reference lists of all included studies and relevant systematic reviews published since 2004. SELECTION CRITERIA: We included RCTs that examined the effects of exercise therapy on non-specific LBP lasting six weeks or less in adults. Major outcomes for this review were pain, functional status, and perceived recovery. Minor outcomes were return to work, health-related quality of life, and adverse events. Our main comparisons were exercise therapy versus sham/placebo treatment and exercise therapy versus no treatment. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods. We evaluated outcomes at short-term follow-up (time point within three months and closest to six weeks after randomisation; main follow-up), intermediate-term follow-up (between nine months and closest to six months), and long-term follow-up (after nine months and closest to 12 months); and we used GRADE to assess the certainty of the evidence for each outcome. MAIN RESULTS: We included 23 studies (13 from the previous review, 10 new studies) that involved 2674 participants and provided data for 2637 participants. Three small studies are awaiting classification, and four eligible studies are ongoing. Included studies were conducted in Europe (N = 9), the Asia-Pacific region (N = 9), and North America (N = 5); and most took place in a primary care setting (N = 12), secondary care setting (N = 6), or both (N = 1). In most studies, the population was middle-aged and included men and women. We judged 10 studies (43%) at low risk of bias with regard to sequence generation and allocation concealment. Blinding is not feasible in exercise therapy, introducing performance and detection bias. There is very low-certainty evidence that exercise therapy compared with sham/placebo treatment has no clinically relevant effect on pain scores in the short term (mean difference (MD) -0.80, 95% confidence interval (CI) -5.79 to 4.19; 1 study, 299 participants). The absolute difference was 1% less pain (95% CI 4% more to 6% less), and the relative difference was 4% less pain (95% CI 20% more to 28% less). The mean pain score was 20.1 (standard deviation (SD) 21) for the intervention group and 20.9 (SD 23) for the control group. There is very low-certainty evidence that exercise therapy compared with sham/placebo treatment has no clinically relevant effect on functional status scores in the short term (MD 2.00, 95% CI -2.20 to 6.20; 1 study, 299 participants). The absolute difference was 2% worse functional status (95% CI 2% better to 6% worse), and the relative difference was 15% worse (95% CI 17% better to 47% worse). The mean functional status score was 15.3 (SD 19) for the intervention group and 13.3 (SD 18) for the control group. We downgraded the certainty of the evidence for pain and functional status by one level for risk of bias and by two levels for imprecision (only one study with fewer than 400 participants). There is very low-certainty evidence that exercise therapy compared with no treatment has no clinically relevant effect on pain or functional status in the short term (2 studies, 157 participants). We downgraded the certainty of the evidence by two levels for imprecision and by one level for inconsistency. One study associated exercise with small benefits and the other found no differences. The first study was conducted in an occupational healthcare centre, where participants received one exercise therapy session. The other study was conducted in secondary and tertiary care settings, where participants received treatment three times per week for six weeks. We did not pool data from these studies owing to considerable clinical heterogeneity. In two studies, there were no reported adverse events. One study reported adverse events unrelated to exercise therapy. The remaining studies did not report whether any adverse events had occurred. Owing to insufficient reporting of adverse events, we were unable to reach any conclusions on the safety or harms related to exercise therapy. AUTHORS' CONCLUSIONS: Exercise therapy compared to sham/placebo treatment may have no clinically relevant effect on pain or functional status in the short term in people with acute non-specific LBP, but the evidence is very uncertain. Exercise therapy compared to no treatment may have no clinically relevant effect on pain or functional status in the short term in people with acute non-specific LBP, but the evidence is very uncertain. We downgraded the certainty of the evidence to very low for inconsistency, risk of bias concerns, and imprecision (few participants).

Red flags to screen for vertebral fracture in patients presenting with low-back pain.

EDITORIAL NOTE: See https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD014461.pub2/full for a more recent review that covers this topic and has superseded this review. BACKGROUND: Low-back pain (LBP) is a common condition seen in primary care. A principal aim during a clinical examination is to identify patients with a higher likelihood of underlying serious pathology, such as vertebral fracture, who may require additional investigation and specific treatment. All 'evidence-based' clinical practice guidelines recommend the use of red flags to screen for serious causes of back pain. However, it remains unclear if the diagnostic accuracy of red flags is sufficient to support this recommendation. OBJECTIVES: To assess the diagnostic accuracy of red flags obtained in a clinical history or physical examination to screen for vertebral fracture in patients presenting with LBP. SEARCH METHODS: Electronic databases were searched for primary studies between the earliest date and 7 March 2012. Forward and backward citation searching of eligible studies was also conducted. SELECTION CRITERIA: Studies were considered if they compared the results of any aspect of the history or test conducted in the physical examination of patients presenting for LBP or examination of the lumbar spine, with a reference standard (diagnostic imaging). The selection criteria were independently applied by two review authors. DATA COLLECTION AND ANALYSIS: Three review authors independently conducted 'Risk of bias' assessment and data extraction. Risk of bias was assessed using the 11-item QUADAS tool. Characteristics of studies, patients, index tests and reference standards were extracted. Where available, raw data were used to calculate sensitivity and specificity with 95% confidence intervals (CI). Due to the heterogeneity of studies and tests, statistical pooling was not appropriate and the analysis for the review was descriptive only. Likelihood ratios for each test were calculated and used as an indication of clinical usefulness. MAIN RESULTS: Eight studies set in primary (four), secondary (one) and tertiary care (accident and emergency = three) were included in the review. Overall, the risk of bias of studies was moderate with high risk of selection and verification bias the predominant flaws. Reporting of index and reference tests was poor. The prevalence of vertebral fracture in accident and emergency settings ranged from 6.5% to 11% and in primary care from 0.7% to 4.5%. There were 29 groups of index tests investigated however, only two featured in more than two studies. Descriptive analyses revealed that three red flags in primary care were potentially useful with meaningful positive likelihood ratios (LR+) but mostly imprecise estimates (significant trauma, older age, corticosteroid use; LR+ point estimate ranging 3.42 to 12.85, 3.69 to 9.39, 3.97 to 48.50 respectively). One red flag in tertiary care appeared informative (contusion/abrasion; LR+ 31.09, 95% CI 18.25 to 52.96). The results of combined tests appeared more informative than individual red flags with LR+ estimates generally greater in magnitude and precision. AUTHORS' CONCLUSIONS: The available evidence does not support the use of many red flags to specifically screen for vertebral fracture in patients presenting for LBP. Based on evidence from single studies, few individual red flags appear informative as most have poor diagnostic accuracy as indicated by imprecise estimates of likelihood ratios. When combinations of red flags were used the performance appeared to improve. From the limited evidence, the findings give rise to a weak recommendation that a combination of a small subset of red flags may be useful to screen for vertebral fracture. It should also be noted that many red flags have high false positive rates; and if acted upon uncritically there would be consequences for the cost of management and outcomes of patients with LBP. Further research should focus on appropriate sets of red flags and adequate reporting of both index and reference tests.

Pharmacological treatments for low back pain in adults: an overview of Cochrane Reviews.

BACKGROUND: Pharmacological interventions are the most used treatment for low back pain (LBP). Use of evidence from systematic reviews of the effects of pharmacological interventions for LBP published in the Cochrane Library, is limited by lack of a comprehensive overview. OBJECTIVES: To summarise the evidence from Cochrane Reviews of the efficacy, effectiveness, and safety of systemic pharmacological interventions for adults with non-specific LBP. METHODS: The Cochrane Database of Systematic Reviews was searched from inception to 3 June 2021, to identify reviews of randomised controlled trials (RCTs) that investigated systemic pharmacological interventions for adults with non-specific LBP. Two authors independently assessed eligibility, extracted data, and assessed the quality of the reviews and certainty of the evidence using the AMSTAR 2 and GRADE tools. The review focused on placebo comparisons and the main outcomes were pain intensity, function, and safety. MAIN RESULTS: Seven Cochrane Reviews that included 103 studies (22,238 participants) were included. There is high confidence in the findings of five reviews, moderate confidence in one, and low confidence in the findings of another. The reviews reported data on six medicines or medicine classes: paracetamol, non-steroidal anti-inflammatory drugs (NSAIDs), muscle relaxants, benzodiazepines, opioids, and antidepressants. Three reviews included participants with acute or sub-acute LBP and five reviews included participants with chronic LBP. Acute LBP Paracetamol There was high-certainty evidence for no evidence of difference between paracetamol and placebo for reducing pain intensity (MD 0.49 on a 0 to 100 scale (higher scores indicate worse pain), 95% CI -1.99 to 2.97), reducing disability (MD 0.05 on a 0 to 24 scale (higher scores indicate worse disability), 95% CI -0.50 to 0.60), and increasing the risk of adverse events (RR 1.07, 95% CI 0.86 to 1.33). NSAIDs There was moderate-certainty evidence for a small between-group difference favouring NSAIDs compared to placebo at reducing pain intensity (MD -7.29 on a 0 to 100 scale (higher scores indicate worse pain), 95% CI -10.98 to -3.61), high-certainty evidence for a small between-group difference for reducing disability (MD -2.02 on a 0-24 scale (higher scores indicate worse disability), 95% CI -2.89 to -1.15), and very low-certainty evidence for no evidence of an increased risk of adverse events (RR 0.86, 95% CI 0. 63 to 1.18). Muscle relaxants and benzodiazepines There was moderate-certainty evidence for a small between-group difference favouring muscle relaxants compared to placebo for a higher chance of pain relief (RR 0.58, 95% CI 0.45 to 0.76), and higher chance of improving physical function (RR 0.55, 95% CI 0.40 to 0.77), and increased risk of adverse events (RR 1.50, 95% CI 1. 14 to 1.98). Opioids None of the included Cochrane Reviews aimed to identify evidence for acute LBP. Antidepressants No evidence was identified by the included reviews for acute LBP. Chronic LBP Paracetamol No evidence was identified by the included reviews for chronic LBP. NSAIDs There was low-certainty evidence for a small between-group difference favouring NSAIDs compared to placebo for reducing pain intensity (MD -6.97 on a 0 to 100 scale (higher scores indicate worse pain), 95% CI -10.74 to -3.19), reducing disability (MD -0.85 on a 0-24 scale (higher scores indicate worse disability), 95% CI -1.30 to -0.40), and no evidence of an increased risk of adverse events (RR 1.04, 95% CI -0.92 to 1.17), all at intermediate-term follow-up (> 3 months and ≤ 12 months postintervention). Muscle relaxants and benzodiazepines There was low-certainty evidence for a small between-group difference favouring benzodiazepines compared to placebo for a higher chance of pain relief (RR 0.71, 95% CI 0.54 to 0.93), and low-certainty evidence for no evidence of difference between muscle relaxants and placebo in the risk of adverse events (RR 1.02, 95% CI 0.67 to 1.57). Opioids There was high-certainty evidence for a small between-group difference favouring tapentadol compared to placebo at reducing pain intensity (MD -8.00 on a 0 to 100 scale (higher scores indicate worse pain), 95% CI -1.22 to -0.38), moderate-certainty evidence for a small between-group difference favouring strong opioids for reducing pain intensity (SMD -0.43, 95% CI -0.52 to -0.33), low-certainty evidence for a medium between-group difference favouring tramadol for reducing pain intensity (SMD -0.55, 95% CI -0.66 to -0.44) and very low-certainty evidence for a small between-group difference favouring buprenorphine for reducing pain intensity (SMD -0.41, 95% CI -0.57 to -0.26). There was moderate-certainty evidence for a small between-group difference favouring strong opioids compared to placebo for reducing disability (SMD -0.26, 95% CI -0.37 to -0.15), moderate-certainty evidence for a small between-group difference favouring tramadol for reducing disability (SMD -0.18, 95% CI -0.29 to -0.07), and low-certainty evidence for a small between-group difference favouring buprenorphine for reducing disability (SMD -0.14, 95% CI -0.53 to -0.25). There was low-certainty evidence for a small between-group difference for an increased risk of adverse events for opioids (all types) compared to placebo; nausea (RD 0.10, 95% CI 0.07 to 0.14), headaches (RD 0.03, 95% CI 0.01 to 0.05), constipation (RD 0.07, 95% CI 0.04 to 0.11), and dizziness (RD 0.08, 95% CI 0.05 to 0.11). Antidepressants There was low-certainty evidence for no evidence of difference for antidepressants (all types) compared to placebo for reducing pain intensity (SMD -0.04, 95% CI -0.25 to 0.17) and reducing disability (SMD -0.06, 95% CI -0.40 to 0.29). AUTHORS' CONCLUSIONS: We found no high- or moderate-certainty evidence that any investigated pharmacological intervention provided a large or medium effect on pain intensity for acute or chronic LBP compared to placebo. For acute LBP, we found moderate-certainty evidence that NSAIDs and muscle relaxants may provide a small effect on pain, and high-certainty evidence for no evidence of difference between paracetamol and placebo. For safety, we found very low- and high-certainty evidence for no evidence of difference with NSAIDs and paracetamol compared to placebo for the risk of adverse events, and moderate-certainty evidence that muscle relaxants may increase the risk of adverse events. For chronic LBP, we found low-certainty evidence that NSAIDs and very low- to high-certainty evidence that opioids may provide a small effect on pain. For safety, we found low-certainty evidence for no evidence of difference between NSAIDs and placebo for the risk of adverse events, and low-certainty evidence that opioids may increase the risk of adverse events.

A scoping review of statistical methods for trial-based economic evaluations: The current state of play.

The statistical quality of trial-based economic evaluations is often suboptimal, while a comprehensive overview of available statistical methods is lacking. Therefore, this review summarized and critically appraised available statistical methods for trial-based economic evaluations. A literature search was performed to identify studies on statistical methods for dealing with baseline imbalances, skewed costs and/or effects, correlated costs and effects, clustered data, longitudinal data, missing data and censoring in trial-based economic evaluations. Data was extracted on the statistical methods described, their advantages, disadvantages, relative performance and recommendations of the study. Sixty-eight studies were included. Of them, 27 (40%) assessed methods for baseline imbalances, 39 (57%) assessed methods for skewed costs and/or effects, 27 (40%) assessed methods for correlated costs and effects, 18 (26%) assessed methods for clustered data, 7 (10%) assessed methods for longitudinal data, 26 (38%) assessed methods for missing data and 10 (15%) assessed methods for censoring. All identified methods were narratively described. This review provides a comprehensive overview of available statistical methods for dealing with the most common statistical complexities in trial-based economic evaluations. Herewith, it can provide valuable input for researchers when deciding which statistical methods to use in a trial-based economic evaluation.

Can EQ-5D-3L utility values of low back pain patients be validly predicted by the Oswestry Disability Index for use in cost-effectiveness analyses?

PURPOSE: To assess whether regression modeling can be used to predict EQ-5D-3L utility values from the Oswestry Disability Index (ODI) in low back pain (LBP) patients for use in cost-effectiveness analysis. METHODS: EQ-5D-3L utility values of LBP patients were estimated using their ODI scores as independent variables using regression analyses, while adjusting for case-mix variables. Six different models were estimated: (1) Ordinary Least Squares (OLS) regression, with total ODI score, (2) OLS, with ODI item scores as continuous variables, (3) OLS, with ODI item scores as ordinal variables, (4) Tobit model, with total ODI score, (5) Tobit model, with ODI item scores as continuous variables, and (6) Tobit model, with ODI item scores as ordinal variables. The models' performance was assessed using explained variance (R2) and root mean squared error (RMSE). The potential impact of using predicted instead of observed EQ-5D-3L utility values on cost-effectiveness outcomes was evaluated in two empirical cost-effectiveness analysis. RESULTS: Complete individual patient data of 18,692 low back pain patients were analyzed. All models had a more or less similar R2 (range 45-52%) and RMSE (range 0.21-0.22). The two best performing models produced similar probabilities of cost-effectiveness for a range of willingness-to-pay (WTP) values compared to those based on the observed EQ-5D-3L values. For example, the difference in probabilities ranged from 2 to 5% at a WTP of 50,000 €/QALY gained. CONCLUSION: Results suggest that the ODI can be validly used to predict low back pain patients' EQ-5D-3L utility values and QALYs for use in cost-effectiveness analyses.

Spinal manipulative therapy in older adults with chronic low back pain: an individual participant data meta-analysis.

PURPOSE: Many systematic reviews have reported on the effectiveness of spinal manipulative therapy (SMT) for low back pain (LBP) in adults. Much less is known about the older population regarding the effects of SMT. OBJECTIVE: To assess the effects of SMT on pain and function in older adults with chronic LBP in an individual participant data (IPD) meta-analysis. SETTING: Electronic databases from 2000 until June 2020, and reference lists of eligible trials and related reviews. DESIGN AND SUBJECTS: Randomized controlled trials (RCTs) which examined the effects of SMT in adults with chronic LBP compared to interventions recommended in international LBP guidelines. METHODS: Authors of trials eligible for our IPD meta-analysis were contacted to share data. Two review authors conducted a risk of bias assessment. Primary results were examined in a one-stage mixed model, and a two-stage analysis was conducted in order to confirm findings. MAIN OUTCOMES AND MEASURES: Pain and functional status examined at 4, 13, 26, and 52 weeks. RESULTS: 10 studies were retrieved, including 786 individuals, of which 261 were between 65 and 91 years of age. There is moderate-quality evidence that SMT results in similar outcomes at 4 weeks (pain: mean difference [MD] - 2.56, 95% confidence interval [CI] - 5.78 to 0.66; functional status: standardized mean difference [SMD] - 0.18, 95% CI - 0.41 to 0.05). Second-stage and sensitivity analysis confirmed these findings. CONCLUSION: SMT provides similar outcomes to recommended interventions for pain and functional status in the older adult with chronic LBP. SMT should be considered a treatment for this patient population.

Surgeons preference for lumbar disk surgery: a discrete choice experiment.

PURPOSE: Multiple surgical techniques are practiced to treat sciatica caused by lumbar disk herniation. It is unknown which factors surgeons find important when offering certain surgical techniques. The objective of this study is threefold: 1) determine the relative weight surgeons place on various characteristics of sciatica treatment, 2) determine the trade-offs surgeons make between these characteristics and 3) identify preference heterogeneity for sciatica treatment. METHODS: A discrete choice experiment was conducted among members of two international neurosurgical organizations. Surgeons were asked on their preferences for surgical techniques using specific scenarios based on five characteristics: effectiveness on leg pain, risk of recurrent disk herniation, duration of postoperative back pain, risk of complications and recovery period. RESULTS: Six-hundred and forty-one questionnaires were filled in, the majority by neurosurgeons. All characteristics significantly influenced the preferences of the respondents. Overall, the risk of complications was the most important characteristic in the decision to opt-in or opt-out for surgery (35.7%). Risk of recurrent disk herniation (19.6%), effectiveness on leg pain (18.8%), postoperative back pain duration (13.5%) and length of recovery period (12.4%) followed. Four latent classes were identified, which was partly explained by the tenure of the surgeon. Surgeons were willing to trade-off 57.8% of effectiveness on leg pain to offer a treatment that has a 1% complication risk instead of 10%. CONCLUSION: In the context of this discrete choice experiment, it is shown that neurosurgeons consider the risk of complications as most important when a surgical technique is offered to treat sciatica, while the risk of recurrent disk herniation and effectiveness are also important factors. Neurosurgeons were prepared to trade off substantial amounts of effectiveness to achieve lower complication rates.

The introduction of advanced practice physiotherapy within Dutch primary care is a quest for possibilities, added value, and mutual trust: a qualitative study amongst advanced practice physiotherapists and general practitioners.

BACKGROUND: Despite the increased deployment and added value of Advanced Practitioner Physiotherapy (APP) in musculoskeletal care internationally, APP is not yet widely accepted within Dutch primary care. This may be due to specific constraints in the implementation of APP within the Dutch healthcare system. This study aimed to explore the experiences and perceptions of Advanced Practitioner Physiotherapists (APPs) and General Practitioners (GPs) with respect to implementing APP within Dutch primary care. METHODS: This explorative and interpretive qualitative study included 12 APPs and 3 GPs who were in various stages of implementing an APP care model. Semi-structured interviews were conducted between January and March 2021. The topic list was based on existing literature, the personal input of researchers, and the Constellation Approach framework. Data were analysed using a thematic inductive approach. RESULTS: Four main themes emerged from the data; 1) Both GPs' trust in APP and a clear added value of APP are critical for starting implementation, 2) APPs need continuous support from GPs, 3) APPs believe that their position needs strengthening, and 4) Implementation of the APP model creates tension over ownership. These four themes highlight the perceived difficulties in gaining trust, lack of clarity over the added value of APP, ambiguity over APPs' professional profile and positioning, a need on behalf of GPs to maintain authority, lack of reimbursement structure, and the struggle APPs face to strike a balance with current care. CONCLUSION: This study demonstrates that implementing an APP model of care is challenging, in part, because the deployment of APP does not sufficiently align with the core values of GPs, while GPs appear reluctant to hand over control of elements of patient care to APPs. APPs do not appear to have ownership over the implementation, given their strong dependence on the practice, values and needs of GPs. TRIAL REGISTRATION: Ethical approval was obtained from the Medical Ethics Committee of VU University Medical Centre in Amsterdam; reference number 2020.17 . All participants were asked to provide written informed consent prior to participating in the study.

Implementation of a lifestyle intervention for people with a severe mental illness (SMILE): a process evaluation.

BACKGROUND: Several interventions have been developed to improve physical health and lifestyle behaviour of people with a severe mental illness (SMI). Recently, we conducted a pragmatic cluster-randomised controlled trial which evaluated the effects of the one-year Severe Mental Illness Lifestyle Evaluation (SMILE) lifestyle intervention compared with usual care in clients with SMI. The SMILE intervention is a 12-month group-based lifestyle intervention with a focus on increased physical activity and healthy food intake. The aim of the current study was to explore the experiences of people with SMI and healthcare professionals (HCPs) regarding implementation feasibility of the SMILE intervention and the fidelity to the SMILE intervention. METHODS: A process evaluation was conducted alongside the pragmatic randomized controlled trial. The experiences of clients and HCPs in the lifestyle intervention group were studied. First, descriptive data on the implementation of the intervention were collected. Next, semi-structured interviews with clients (n = 15) and HCPs (n = 13) were performed. Interviews were audiotaped and transcribed verbatim. A thematic analysis of the interview data was performed using MAXQDA software. In addition, observations of group sessions were performed to determine the fidelity to the SMILE intervention using a standardised form. RESULTS: Ten out of 26 HCPs who conducted the group sessions discontinued their involvement with the intervention, primarily due to changing jobs. 98% of all planned group sessions were performed. Four main themes emerged from the interviews: 1) Positive appraisal of the SMILE intervention, 2) Suggestions for improvement of the SMILE intervention 3) Facilitators of implementation and 4) Barriers of implementation. Both clients and HCPs had positive experiences regarding the SMILE intervention. Clients found the intervention useful and informative. The intervention was found suitable and interesting for all people with SMI, though HCPs sometimes had to tailor the intervention to individual characteristics of patients (e.g., with respect to cognitive functioning). The handbook of the SMILE intervention was perceived as user-friendly and helpful by HCPs. Combining SMILE with daily tasks, no support from other team members, and lack of staff and time were experienced as barriers for the delivery of the intervention. CONCLUSION: The SMILE intervention was feasible and well-perceived by clients and HCPs. However, we also identified some aspects that may have hindered effective implementation and needs to be considered when implementing the SMILE intervention in daily practice.

Cost-effectiveness of full endoscopic versus open discectomy for sciatica.

OBJECTIVE: To assess the costs and cost-effectiveness of percutaneous transforaminal endoscopic discectomy (PTED) compared with open microdiscectomy among patients with sciatica. METHODS: This economic evaluation was conducted alongside a 12-month multicentre randomised controlled trial with a non-inferiority design, in which patients were randomised to PTED or open microdiscectomy. Patients were aged from 18 to 70 years and had at least 6 weeks of radiating leg pain caused by lumbar disc herniation. Effect measures included leg pain and quality-adjusted life years (QALYs), as derived using the EQ-5D-5L. Costs were measured from a societal perspective. Missing data were multiply imputed, bootstrapping was used to estimate statistical uncertainty, and various sensitivity analyses were conducted to determine the robustness. RESULTS: Of the 613 patients enrolled, 304 were randomised to PTED and 309 to open microdiscectomy. Statistically significant differences in leg pain and QALYs were found in favour of PTED at 12 months follow-up (leg pain: 6.9; 95% CI 1.3 to 12.6; QALYs: 0.040; 95% CI 0.007 to 0.074). Surgery costs were higher for PTED than for open microdiscectomy (ie, €4500/patient vs €4095/patient). All other disaggregate costs as well as total societal costs were lower for PTED than for open microdiscectomy. Cost-effectiveness acceptability curves indicated that the probability of PTED being less costly and more effective (ie, dominant) compared with open microdiscectomy was 99.4% for leg pain and 99.2% for QALYs. CONCLUSIONS: Our results suggest that PTED is more cost-effective from the societal perspective compared with open microdiscectomy for patients with sciatica. TRIAL REGISTRATION NUMBER: NCT02602093.

Diagnostic Imaging in Chiropractic Practice: A Survey of Opinions and Self-Reported Guideline Adherence of Dutch and Belgian Chiropractors.

OBJECTIVES: The purpose of this study was (1) to describe diagnostic imaging in Dutch and Belgian chiropractic practice in general, (2) to estimate adherence to the diagnostic imaging guidelines for patients with low back pain (LBP) via vignettes, and (3) to evaluate factors associated with diagnostic imaging and adherence to the guidelines. METHODS: We used a web-based survey to collect sociodemographic data, practice characteristics, amount of imaging, opinions, and indications for requesting imaging from registered Dutch and Belgian chiropractors in 2013. Additionally, adherence to imaging guidelines for LBP was assessed by 6 vignettes in patients with LBP. Multivariable regression analyses were conducted to explore associations between characteristics of chiropractors and the use of imaging. Generalized mixed models were used to explore guidelines adherence and their relationship with chiropractor's characteristics. RESULTS: The overall response rate was 60% (n = 203 out of 340). In total, 83% of chiropractors viewed diagnostic imaging in general as an important part of their practice. It is important to note that Dutch and Belgian chiropractors are not allowed to refer directly for imaging. Chiropractors reported that they would like to have imaging in 42% of their patients. Imaging had already been performed in 37% of patients before the first visit and was ordered by another health care provider (ie, general practitioner or medical specialist). The most common indication for ordering imaging was exclusion of contraindications (73%). The most common reason against imaging was the perceived limited value (45%). Many chiropractors (71%) were familiar with imaging guidelines. Adherence to the imaging guidelines for LBP based upon the vignettes was 66%. Dutch chiropractors and chiropractors with less than 10 years in practice demonstrated better adherence to guidelines and imaging use as compared with Belgian and those with more than 10 years of experience. CONCLUSIONS: Most Dutch and Belgian chiropractors reported that imaging in general was important in chiropractic practice. Self-reported indications for ordering diagnostic imaging were in line with the imaging guidelines in the majority of cases. We found some variances between Belgian and Dutch chiropractors and years of experience related to guideline adherence.

Assessing the Impact of EQ-5D Country-specific Value Sets on Cost-utility Outcomes.

PURPOSE: To assess the impact of EQ-5D country-specific value sets on cost-utility outcomes. METHODS: Data from 2 randomized controlled trials on low back pain (LBP) and depression were used. 3L value sets were identified from the EuroQol Web site. A nonparametric crosswalk was employed for each tariff to obtain the likely 5L values. Differences in quality-adjusted life years (QALYs) between countries were tested using paired t tests, with United Kingdom as reference. Cost-utility outcomes were estimated for both studies and both EQ-5D versions, including differences in QALYs and cost-effectiveness acceptability curves. RESULTS: For the 3L, QALYs ranged between 0.650 (Taiwan) and 0.892 (United States) in the LBP study and between 0.619 (Taiwan) and 0.879 (United States) in the depression study. In both studies, most country-specific QALY estimates differed statistically significantly from that of the United Kingdom. Incremental cost-effectiveness ratios ranged between &OV0556;2044/QALY (Taiwan) and &OV0556;5897/QALY (Zimbabwe) in the LBP study and between &OV0556;38,287/QALY (Singapore) and &OV0556;96,550/QALY (Japan) in the depression study. At the NICE threshold of &OV0556;23,300/QALY (≈£20,000/QALY), the intervention's probability of being cost-effective versus control ranged between 0.751 (Zimbabwe) and 0.952 (Taiwan) and between 0.230 (Canada) and 0.396 (Singapore) in the LBP study and depression study, respectively. Similar results were found for the 5L, with extensive differences in ICERs and moderate differences in the probability of cost-effectiveness. CONCLUSIONS: This study indicates that the use of different EQ-5D country-specific value sets impacts on cost-utility outcomes. Therefore, to account for the fact that health state preferences are affected by sociocultural differences, relevant country-specific value sets should be used.

Validity and reliability of the Norwegian version of the Musculoskeletal Health Questionnaire in people on sick leave.

BACKGROUND: The Musculoskeletal Health Questionnaire (MSK-HQ) is a recently developed generic questionnaire that consists of 14 items assessing health status in people with musculoskeletal disorders. The objective was to translate and cross-culturally adapt the MSK-HQ into Norwegian and to examine its construct validity and reliability in people on sick leave with musculoskeletal disorders. METHODS: A prospective cohort study was carried out in Norway on people between 18 and 67 years of age and sick leave due to a musculoskeletal disorder. The participants were recruited through the Norwegian Labour and Welfare Administration during November 2018-January 2019 and responded to the MSK-HQ at inclusion and after four weeks. Internal consistency was assessed by Cronbach's alpha, and structural validity with a factor analysis. Construct validity was assessed by eight "a priori" defined hypotheses regarding correlations between the MSK-HQ and other reference scales. Correlations were analyzed by Spearman's- or Pearson's correlation coefficient and interpreted as high with values ≥ 0.50, moderate between 0.30-0.49, and low < 0.29. Reliability was tested with test-retest, standard error of measurement (SEM) and smallest detectable change (SDC). RESULTS: A total of 549 patients, mean age (SD) 48.6 (10.7), 309 women (56.3%), were included. The mean (SD) MSK-HQ sum scores (min-max 3-56) were 27.7 (8.2). Internal consistency was 0.86 and a three-factor structure was determined by factor analysis. Construct validity was supported by the confirmation of all hypotheses; high correlation with HRQOL, psychosocial risk profile, and self-perceived health; moderate correlation with physical activity, self-perceived work ability, and work presenteeism; and low correlation with the number of sick days. The test-retest reliability was good with an intraclass correlation coefficient of 0.83 (95% CI, 0.74-0.89), SEM was 2.3 and SDC 6.5. CONCLUSIONS: The Norwegian version of the MSK-HQ demonstrated high internal consistency, a three-factor structure, good construct validity and good test-retest reliability when used among people on sick leave due to musculoskeletal disorders.

Exercise therapy for chronic low back pain.

BACKGROUND: Low back pain has been the leading cause of disability globally for at least the past three decades and results in enormous direct healthcare and lost productivity costs. OBJECTIVES: The primary objective of this systematic review is to assess the impact of exercise treatment on pain and functional limitations in adults with chronic non-specific low back pain compared to no treatment, usual care, placebo and other conservative treatments. SEARCH METHODS: We searched CENTRAL (which includes the Cochrane Back and Neck trials register), MEDLINE, Embase, CINAHL, PsycINFO, PEDro, SPORTDiscus, and trials registries (ClinicalTrials.gov and World Health Organization International Clinical Trials Registry Platform), and conducted citation searching of relevant systematic reviews to identify additional studies. The review includes data for trials identified in searches up to 27 April 2018. All eligible trials have been identified through searches to 7 December 2020, but have not yet been extracted; these trials will be integrated in the next update. SELECTION CRITERIA: We included randomised controlled trials that assessed exercise treatment compared to no treatment, usual care, placebo or other conservative treatment on the outcomes of pain or functional limitations for a population of adult participants with chronic non-specific low back pain of more than 12 weeks' duration. DATA COLLECTION AND ANALYSIS: Two authors screened and assessed studies independently, with consensus. We extracted outcome data using electronic databases; pain and functional limitations outcomes were re-scaled to 0 to 100 points for meta-analyses where 0 is no pain or functional limitations. We assessed risk of bias using the Cochrane risk of bias (RoB) tool and used GRADE to evaluate the overall certainty of the evidence. When required, we contacted study authors to obtain missing data. To interpret meta-analysis results, we considered a 15-point difference in pain and a 10-point difference in functional limitations outcomes to be clinically important for the primary comparison of exercise versus no treatment, usual care or placebo. MAIN RESULTS: We included 249 trials of exercise treatment, including studies conducted in Europe (122 studies), Asia (38 studies), North America (33 studies), and the Middle East (24 studies). Sixty-one per cent of studies (151 trials) examined the effectiveness of two or more different types of exercise treatment, and 57% (142 trials) compared exercise treatment to a non-exercise comparison treatment. Study participants had a mean age of 43.7 years and, on average, 59% of study populations were female. Most of the trials were judged to be at risk of bias, including 79% at risk of performance bias due to difficulty blinding exercise treatments. We found moderate-certainty evidence that exercise treatment is more effective for treatment of chronic low back pain compared to no treatment, usual care or placebo comparisons for pain outcomes at earliest follow-up (MD -15.2, 95% CI -18.3 to -12.2), a clinically important difference. Certainty of evidence was downgraded mainly due to heterogeneity. For the same comparison, there was moderate-certainty evidence for functional limitations outcomes (MD -6.8 (95% CI -8.3 to -5.3); this finding did not meet our prespecified threshold for minimal clinically important difference. Certainty of evidence was downgraded mainly due to some evidence of publication bias.  Compared to all other investigated conservative treatments, exercise treatment was found to have improved pain (MD -9.1, 95% CI -12.6 to -5.6) and functional limitations outcomes (MD -4.1, 95% CI -6.0 to -2.2). These effects did not meet our prespecified threshold for clinically important difference. Subgroup analysis of pain outcomes suggested that exercise treatment is probably more effective than education alone (MD -12.2, 95% CI -19.4 to -5.0) or non-exercise physical therapy (MD -10.4, 95% CI -15.2 to -5.6), but with no differences observed for manual therapy (MD 1.0, 95% CI -3.1 to 5.1). In studies that reported adverse effects (86 studies), one or more adverse effects were reported in 37 of 112 exercise groups (33%) and 12 of 42 comparison groups (29%). Twelve included studies reported measuring adverse effects in a systematic way, with a median of 0.14 (IQR 0.01 to 0.57) per participant in the exercise groups (mostly minor harms, e.g. muscle soreness), and 0.12 (IQR 0.02 to 0.32) in comparison groups. AUTHORS' CONCLUSIONS: We found moderate-certainty evidence that exercise is probably effective for treatment of chronic low back pain compared to no treatment, usual care or placebo for pain. The observed treatment effect for the exercise compared to no treatment, usual care or placebo comparisons is small for functional limitations, not meeting our threshold for minimal clinically important difference. We also found exercise to have improved pain (low-certainty evidence) and functional limitations outcomes (moderate-certainty evidence) compared to other conservative treatments; however, these effects were small and not clinically important when considering all comparisons together. Subgroup analysis suggested that exercise treatment is probably more effective than advice or education alone, or electrotherapy, but with no differences observed for manual therapy treatments.