Benedict M Wand

Rethinking Clinical Trials of Transcranial Direct Current Stimulation: Participant and Assessor Blinding Is Inadequate at Intensities of 2mA

Background Many double-blind clinical trials of transcranial direct current stimulation (tDCS) use stimulus intensities of 2 mA despite the fact that blinding has not been formally validated under these conditions. The aim of this study was to test the assumption that sham 2 mA tDCS achieves effective blinding. Methods A randomised double blind crossover trial. 100 tDCS-naïve healthy volunteers were incorrectly advised that they there were taking part in a trial of tDCS on word memory. Participants attended for two separate sessions. In each session, they completed a word memory task, then received active or sham tDCS (order randomised) at 2 mA stimulation intensity for 20 minutes and then repeated the word memory task. They then judged whether they believed they had received active stimulation and rated their confidence in that judgement. The blinded assessor noted when red marks were observed at the electrode sites post-stimulation. Results tDCS at 2 mA was not effectively blinded. That is, participants correctly judged the stimulation condition greater than would be expected to by chance at both the first session (kappa level of agreement (κ) 0.28, 95% confidence interval (CI) 0.09 to 0.47 p = 0.005) and the second session (κ = 0.77, 95%CI 0.64 to 0.90), p = <0.001) indicating inadequate participant blinding. Redness at the reference electrode site was noticeable following active stimulation more than sham stimulation (session one, κ = 0.512, 95%CI 0.363 to 0.66, p<0.001; session two, κ = 0.677, 95%CI 0.534 to 0.82) indicating inadequate assessor blinding. Conclusions Our results suggest that blinding in studies using tDCS at intensities of 2 mA is inadequate. Positive results from such studies should be interpreted with caution.

Evaluation of a Treatment-Based Classification Algorithm for Low Back Pain: A Cross-Sectional Study

Background Several studies have investigated criteria for classifying patients with low back pain (LBP) into treatment-based subgroups. A comprehensive algorithm was created to translate these criteria into a clinical decision-making guide. Objective This study investigated the translation of the individual subgroup criteria into a comprehensive algorithm by studying the prevalence of patients meeting the criteria for each treatment subgroup and the reliability of the classification. Design This was a cross-sectional, observational study. Methods Two hundred fifty patients with acute or subacute LBP were recruited from the United States and Australia to participate in the study. Trained physical therapists performed standardized assessments on all participants. The researchers used these findings to classify participants into subgroups. Thirty-one participants were reassessed to determine interrater reliability of the algorithm decision. Results Based on individual subgroup criteria, 25.2% (95% confidence interval [CI]=19.8%–30.6%) of the participants did not meet the criteria for any subgroup, 49.6% (95% CI=43.4%–55.8%) of the participants met the criteria for only one subgroup, and 25.2% (95% CI=19.8%–30.6%) of the participants met the criteria for more than one subgroup. The most common combination of subgroups was manipulation + specific exercise (68.4% of the participants who met the criteria for 2 subgroups). Reliability of the algorithm decision was moderate (kappa=0.52, 95% CI=0.27–0.77, percentage of agreement=67%). Limitations Due to a relatively small patient sample, reliability estimates are somewhat imprecise. Conclusions These findings provide important clinical data to guide future research and revisions to the algorithm. The finding that 25% of the participants met the criteria for more than one subgroup has important implications for the sequencing of treatments in the algorithm. Likewise, the finding that 25% of the participants did not meet the criteria for any subgroup provides important information regarding potential revisions to the algorithms bottom table (which guides unclear classifications). Reliability of the algorithm is sufficient for clinical use.

Primary Somatosensory Cortex Function in Complex Regional Pain Syndrome: A Systematic Review and Meta-Analysis

UNLABELLED That complex regional pain syndrome (CRPS) is associated with functional reorganization in the primary somatosensory cortex (S1) is widely accepted and seldom questioned. Despite more than a decade of research, there has been no systematic review of the CRPS literature concerning the changes in S1 function, and therefore the extent of these changes is unclear. Here we conduct a systematic review and meta-analysis to quantify the spatial and temporal aspects of S1 function in CRPS. A comprehensive search strategy identified functional neuroimaging studies of S1 in CRPS. We adhered to a rigorous systematic review protocol when extracting data and appraising risk of bias. Outcomes were grouped into spatial representation; activation levels, including disinhibition; peak latency of activation; and glucose metabolism. Meta-analysis was conducted where possible. Fifteen studies were included, all investigating upper-extremity CRPS. In patients with CRPS, the S1 spatial representation of the affected hand is smaller than that of the unaffected hand and that of non-CRPS controls; however, this evidence comes from only a few studies. There is no difference in activation, disinhibition, or latency of peripherally evoked S1 responses in CRPS. The risk of bias was high across studies, mainly from unclear sampling methods and unblinded analysis of outcomes. PERSPECTIVE The evidence for a difference in function of the primary somatosensory cortex in CRPS compared with controls is clouded by high risk of bias and conflicting results, but reduced representation size seems consistent.

Tactile thresholds are preserved yet complex sensory function is impaired over the lumbar spine of chronic non-specific low back pain patients: a preliminary investigation

OBJECTIVES To investigate impairments in sensory function in chronic non-specific low back pain patients, and the relationship between any impairment and the clinical features of the condition. DESIGN A cross-sectional case-control study. SETTING Laboratory-based study. PARTICIPANTS Nineteen chronic non-specific low back pain patients and 19 healthy controls. MAIN OUTCOME MEASURES Tactile threshold, two-point discrimination distance and accuracy at a task involving recognising letters drawn over the skin of the lower back (graphaesthesia) were assessed over the lumbar spine in both groups. Pain duration, pain intensity, physical function, anxiety and depression were assessed by questionnaire in the back pain group. RESULTS No difference was found in tactile threshold between the two groups [median difference 0.0mg, 95% confidence interval (CI) -0.04 to 0.04]. There was a significant difference between controls and back pain patients for two-point discrimination (mean difference 17.9mm, 95% CI 5.9 to 29.8) and graphaesthesia accuracy (mean difference 6.1, 95% CI 1.3 to 11.0). Low back pain patients had a larger lumbar two-point discrimination distance threshold and a greater letter recognition error rate. In the back pain group, no relationship was found between clinical profile and sensory function, and no relationship was found between the sensory tests. CONCLUSIONS These data support existing findings of perceptual abnormalities in chronic non-specific low back pain patients, and are suggestive of cortical rather than peripheral sensory dysfunction. Amelioration of these abnormalities may present a target for therapeutic intervention.

Assessing tactile acuity in rheumatology and musculoskeletal medicine—how reliable are two-point discrimination tests at the neck, hand, back and foot?

OBJECTIVE Chronic pain from rheumatic and musculoskeletal conditions is associated with cortical changes and altered tactile acuity. Tactile acuity is considered a clinical signature of primary somatosensory representation. The two-point discrimination (TPD) threshold is increasingly used both clinically and in research. Remarkably, the reliability and precision of the measure at commonly used sites has not been determined. This study aimed to determine the utility, intra- and inter-rater reliability, bias and variability of TPD threshold assessment at the neck, back, hand and foot using mechanical callipers. METHODS Intra- and inter-rater reliability of TPD was assessed at the back, neck, hand and foot of 28 healthy young adults by 28 clinicians. Each clinician received training in the assessment of TPD using mechanical callipers and following a standardized protocol. Intraclass correlation coefficients (ICCs) and Bland-Altman plots were used to assess reliability, bias and variability. RESULTS Intra-rater assessments in all four regions and inter-rater assessments at the neck and foot were reliable (ICC range 0.79-0.86), but large variability was seen in all assessments. Inter-rater assessment of the back (ICC = 0.66) and hand (ICC = 0.62) was deemed unreliable. Negligible systematic bias suggested learning did not affect reliability. CONCLUSION Individual clinicians are able to reliably assess TPD threshold at the neck, back, hand and foot using mechanical callipers. Measures obtained by different clinicians were only reliable for the neck and foot. Large variability was observed in all assessments, which suggests clinicians should be cautious when interpreting changes in tactile acuity in individual patients.

Managing Chronic Nonspecific Low Back Pain With a Sensorimotor Retraining Approach: Exploratory Multiple-Baseline Study of 3 Participants

Background Current approaches to the management of chronic nonspecific low back pain (CNSLBP) have shown limited effectiveness. It appears that disruption of cortical structure and function is a feature of CNSLBP and that these changes may contribute to current treatment failures. Sensorimotor retraining approaches have been shown to be effective in the management of other long-standing pain problems that are characterized by cortical dysfunction. Similar treatments may be an option for people with CNSLBP. Objective The objectives of this study were to describe the effects of participation in a graded sensorimotor retraining program on pain intensity, interference of pain with daily life (pain interference), and self-reported disability and to evaluate the safety of the program. Design A multiple-baseline, replicated, single-case design was used for this study. Methods Three people with disabling CNSLBP were assessed weekly during a no-treatment baseline period. Each person then participated in a graded sensorimotor retraining program for a minimum of 10 weeks, during which clinical status was assessed weekly. Data collection continued weekly for 1 month after the end of formal treatment. Results Pain intensity, pain interference, and disability all were reduced, and the improvements were maintained throughout the follow-up period. No adverse reactions to treatment were reported. Limitations The findings are preliminary and were based on a single-case design. The observed improvements in clinical status may have been attributable to the effects of factors other than treatment, such as the effect of time and other, nonspecific effects. Conclusions Positive outcomes were reported for 3 participants with CNSLBP after the completion of a graded sensorimotor retraining program. However, the findings are only preliminary and require replication with more-robust study designs.

Seeing it helps: Movement-related back pain is reduced by visualization of the back during movement

Objectives: The aim of this study was to determine whether visualization of the back influenced parameters of movement-related pain in people with chronic nonspecific low back pain. Methods: We used a randomized cross-over experiment in which 25 participants performed repeated lumbar spine movements under 2 conditions. In the visual feedback condition, patients were able to visualize their back as it moved by the use of mirrors. In the control condition, the mirror was covered so no visualization of the back was possible. Results: The average postmovement pain intensity after participants had moved with visual feedback was less (35.5±22.8 mm) than when they moved without visual feedback (44.7±26.0 mm). This difference was statistically significant (mean difference=9.3, 95% confidence interval: 2.8-15.7 F(1,22)=8.82, P=0.007). The average time to ease after participants had moved with visual feedback was shorter (44.5 s±53.8) than when they moved without visual feedback (94.4 s±80.7). This difference was also statistically significantly (mean difference=49.9, 95% confidence interval: 19.3-80.6, F(1,22)=8.82, P=0.003). Discussion: Patients with chronic nonspecific low back pain reported less increase in pain and faster resolution of pain when moving in an environment that enabled them to visualize their back. This is consistent with emerging research on the use of mirror visual feedback in other long-standing pain problems and suggests that similar lines of inquiry may be worth pursuing in the chronic nonspecific low back pain population.

Transcranial direct current stimulation of the motor cortex in the treatment of chronic nonspecific low back pain: a randomized, double-blind exploratory study.

Objectives:To test the proof of principle that active anodal transcranial direct current stimulation (tDCS) applied to the motor cortex reduces pain significantly more than sham stimulation in a group of participants with chronic nonspecific low back pain. Methods:The study utilized a within-participants sham-controlled, interrupted time series design. A sample of 8 participants was recruited. After 3 days of baseline measures, patients entered a 15-day experimental period (Mondays to Fridays) for 3 consecutive weeks. During this period each patient received sham stimulation daily until a randomly allocated day when active stimulation was commenced. Active stimulation was then given daily for the remaining days of the experimental period. Both the participants and the assessors were blinded. The primary outcomes were average pain intensity and unpleasantness in the last 24 hours measured using a visual analogue scale. Secondary outcomes included self-reported disability, depression and anxiety, a battery of cognitive tests to monitor for unwanted effects of stimulation, and patients’ perceptions of whether they had received active or sham stimulation. Data were analyzed using generalized estimating equations. Results:No significant effect was seen in the primary outcomes between active and sham stimulation (average pain intensity P=0.821, unpleasantness P=0.937) or across any other clinical variables. There was evidence that patients may have been able to distinguish between the active and sham conditions (P=0.035). Discussion:These results do not provide evidence that tDCS is effective in the treatment of chronic back pain. The use of a small convenience sample limits the generalizability of these findings and precludes definitive conclusions on the efficacy of tDCS in chronic nonspecific low back pain.

Should we abandon cervical spine manipulation for mechanical neck pain? Yes.

Benedict Wand and colleagues argue that the risks of cervical spine manipulation are not justified, but David Cassidy and colleagues (doi:10.1136/bmj.e3680) think it is a valuable addition to patient care

Interpretive bias in acupuncture research? A case study

Acupuncture is one of the most widely used and broadly researched of the complementary and alternative therapies, but high-quality trials generally show no benefit over sham acupuncture. Many would view this result as evidence of ineffectiveness for this intervention. This discussion article focuses on the report of a large multicenter randomized controlled trial of acupuncture for chronic low-back pain (CLBP) in the lay and academic press, the ensuing discussion, and its impact on both clinical practice and service provision. The authors suggest that interpretive bias has affected reporting, leading to questionable conclusions and advocacy in favor of this form of care that may exceed the evidence. They also suggest that a lack of understanding of research into the placebo effect may have contributed to confusion in the interpretation of these trials.