Physical activity and education about physical activity for chronic musculoskeletal pain in children and adolescents.

BACKGROUND: Chronic pain is a major health and socioeconomic burden, which is prevalent in children and adolescents. Among the most widely used interventions in children and adolescents are physical activity (including exercises) and education about physical activity. OBJECTIVES: To evaluate the effectiveness of physical activity, education about physical activity, or both, compared with usual care (including waiting-list, and minimal interventions, such as advice, relaxation classes, or social group meetings) or active medical care in children and adolescents with chronic musculoskeletal pain. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, CINAHL, PsycINFO, PEDro, and LILACS from the date of their inception to October 2022. We also searched the reference lists of eligible papers, ClinicalTrials.gov, and the World Health Organization (WHO) International Clinical Trials Registry Platform. SELECTION CRITERIA: We included randomised controlled trials (RCTs) that compared physical activity or education about physical activity, or both, with usual care (including waiting-list and minimal interventions) or active medical care, in children and adolescents with chronic musculoskeletal pain. DATA COLLECTION AND ANALYSIS: Two review authors independently determined the eligibility of the included studies. Our primary outcomes were pain intensity, disability, and adverse events. Our secondary outcomes were depression, anxiety, fear avoidance, quality of life, physical activity level, and caregiver distress. We extracted data at postintervention assessment, and long-term follow-up. Two review authors independently assessed risk of bias for each study, using the RoB 1. We assessed the overall certainty of the evidence using the GRADE approach. We reported continuous outcomes as mean differences, and determined clinically important differences from the literature, or 10% of the scale. MAIN RESULTS: We included four studies (243 participants with juvenile idiopathic arthritis). We judged all included studies to be at unclear risk of selection bias, performance bias, and detection bias, and at high risk of attrition bias. We downgraded the certainty of the evidence for each outcome to very low due to serious or very serious study limitations, inconsistency, and imprecision. Physical activity compared with usual care Physical activity may slightly reduce pain intensity (0 to 100 scale; 0 = no pain) compared with usual care at postintervention (standardised mean difference (SMD) -0.45, 95% confidence interval (CI) -0.82 to -0.08; 2 studies, 118 participants; recalculated as a mean difference (MD) -12.19, 95% CI -21.99 to -2.38; I² = 0%; very low-certainty evidence). Physical activity may slightly improve disability (0 to 3 scale; 0 = no disability) compared with usual care at postintervention assessment (MD -0.37, 95% CI -0.56 to -0.19; I² = 0%; 3 studies, 170 participants; very low-certainty evidence). We found no clear evidence of a difference in quality of life (QoL; 0 to 100 scale; lower scores = better QoL) between physical activity and usual care at postintervention assessment (SMD -0.46, 95% CI -1.27 to 0.35; 4 studies, 201 participants; very low-certainty evidence; recalculated as MD -6.30, 95% CI -18.23 to 5.64; I² = 91%). None of the included studies measured adverse events, depression, or anxiety for this comparison. Physical activity compared with active medical care We found no studies that could be analysed in this comparison. Education about physical activity compared with usual care or active medical care We found no studies that could be analysed in this comparison. Physical activity and education about physical activity compared with usual care or active medical care We found no studies that could be analysed in this comparison. AUTHORS' CONCLUSIONS: We are unable to confidently state whether interventions based on physical activity and education about physical activity are more effective than usual care for children and adolescents with chronic musculoskeletal pain. We found very low-certainty evidence that physical activity may reduce pain intensity and improve disability postintervention compared with usual care, for children and adolescents with juvenile idiopathic arthritis. We did not find any studies reporting educational interventions; it remains unknown how these interventions influence the outcomes in children and adolescents with chronic musculoskeletal pain. Treatment decisions should consider the current best evidence, the professional's experience, and the young person's preferences. Further randomised controlled trials in other common chronic musculoskeletal pain conditions, with high methodological quality, large sample size, and long-term follow-up are urgently needed.

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.

Interventions for treating pain and disability in adults with complex regional pain syndrome- an overview of systematic reviews.

BACKGROUND: Complex regional pain syndrome (CRPS) is a chronic pain condition that usually occurs in a limb following trauma or surgery. It is characterised by persisting pain that is disproportionate in magnitude or duration to the typical course of pain after similar injury. There is currently no consensus regarding the optimal management of CRPS, although a broad range of interventions have been described and are commonly used. This is the first update of the original Cochrane review published in Issue 4, 2013. OBJECTIVES: To summarise the evidence from Cochrane and non-Cochrane systematic reviews of the efficacy, effectiveness, and safety of any intervention used to reduce pain, disability, or both, in adults with CRPS. METHODS: We identified Cochrane reviews and non-Cochrane reviews through a systematic search of Ovid MEDLINE, Ovid Embase, Cochrane Database of Systematic Reviews, CINAHL, PEDro, LILACS and Epistemonikos from inception to October 2022, with no language restrictions. We included systematic reviews of randomised controlled trials that included adults (≥18 years) diagnosed with CRPS, using any diagnostic criteria.  Two overview 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 respectively. We extracted data for the primary outcomes pain, disability and adverse events, and the secondary outcomes quality of life, emotional well-being, and participants' ratings of satisfaction or improvement with treatment.  MAIN RESULTS: We included six Cochrane and 13 non-Cochrane systematic reviews in the previous version of this overview and five Cochrane and 12 non-Cochrane reviews in the current version. Using the AMSTAR 2 tool, we judged Cochrane reviews to have higher methodological quality than non-Cochrane reviews. The studies in the included reviews were typically small and mostly at high risk of bias or of low methodological quality. We found no high-certainty evidence for any comparison.  There was low-certainty evidence that bisphosphonates may reduce pain intensity post-intervention (standardised mean difference (SMD) -2.6, 95% confidence interval (CI) -1.8 to -3.4, P = 0.001; I2 = 81%; 4 trials, n = 181) and moderate-certainty evidence that they are probably associated with increased adverse events of any nature (risk ratio (RR) 2.10, 95% CI 1.27 to 3.47; number needed to treat for an additional harmful outcome (NNTH) 4.6, 95% CI 2.4 to 168.0; 4 trials, n = 181).  There was moderate-certainty evidence that lidocaine local anaesthetic sympathetic blockade probably does not reduce pain intensity compared with placebo, and low-certainty evidence that it may not reduce pain intensity compared with ultrasound of the stellate ganglion. No effect size was reported for either comparison. There was low-certainty evidence that topical dimethyl sulfoxide may not reduce pain intensity compared with oral N-acetylcysteine, but no effect size was reported. There was low-certainty evidence that continuous bupivacaine brachial plexus block may reduce pain intensity compared with continuous bupivacaine stellate ganglion block, but no effect size was reported. For a wide range of other commonly used interventions, the certainty in the evidence was very low and provides insufficient evidence to either support or refute their use. Comparisons with low- and very low-certainty evidence should be treated with substantial caution. We did not identify any RCT evidence for routinely used pharmacological interventions for CRPS such as tricyclic antidepressants or opioids. AUTHORS' CONCLUSIONS: Despite a considerable increase in included evidence compared with the previous version of this overview, we identified no high-certainty evidence for the effectiveness of any therapy for CRPS. Until larger, high-quality trials are undertaken, formulating an evidence-based approach to managing CRPS will remain difficult. Current non-Cochrane systematic reviews of interventions for CRPS are of low methodological quality and should not be relied upon to provide an accurate and comprehensive summary of the evidence.

Physiotherapy for pain and disability in adults with complex regional pain syndrome (CRPS) types I and II.

BACKGROUND: Complex regional pain syndrome (CRPS) is a painful and disabling condition that usually manifests in response to trauma or surgery and is associated with significant pain and disability. CRPS can be classified into two types: type I (CRPS I) in which a specific nerve lesion has not been identified and type II (CRPS II) where there is an identifiable nerve lesion. Guidelines recommend the inclusion of a variety of physiotherapy interventions as part of the multimodal treatment of people with CRPS. This is the first update of the review originally published in Issue 2, 2016. OBJECTIVES: To determine the effectiveness of physiotherapy interventions for treating pain and disability associated with CRPS types I and II in adults. SEARCH METHODS: For this update we searched CENTRAL (the Cochrane Library), MEDLINE, Embase, CINAHL, PsycINFO, LILACS, PEDro, Web of Science, DARE and Health Technology Assessments from February 2015 to July 2021 without language restrictions, we searched the reference lists of included studies and we contacted an expert in the field. We also searched additional online sources for unpublished trials and trials in progress. SELECTION CRITERIA: We included randomised controlled trials (RCTs) of physiotherapy interventions compared with placebo, no treatment, another intervention or usual care, or other physiotherapy interventions in adults with CRPS I and II. Primary outcomes were pain intensity and disability. Secondary outcomes were composite scores for CRPS symptoms, health-related quality of life (HRQoL), patient global impression of change (PGIC) scales and adverse effects. DATA COLLECTION AND ANALYSIS: Two review authors independently screened database searches for eligibility, extracted data, evaluated risk of bias and assessed the certainty of evidence using the GRADE system. MAIN RESULTS: We included 16 new trials (600 participants) along with the 18 trials from the original review totalling 34 RCTs (1339 participants). Thirty-three trials included participants with CRPS I and one trial included participants with CRPS II. Included trials compared a diverse range of interventions including physical rehabilitation, electrotherapy modalities, cortically directed rehabilitation, electroacupuncture and exposure-based approaches. Most interventions were tested in small, single trials. Most were at high risk of bias overall (27 trials) and the remainder were at 'unclear' risk of bias (seven trials). For all comparisons and outcomes where we found evidence, we graded the certainty of the evidence as very low, downgraded due to serious study limitations, imprecision and inconsistency. Included trials rarely reported adverse effects. Physiotherapy compared with minimal care for adults with CRPS I One trial (135 participants) of multimodal physiotherapy, for which pain data were unavailable, found no between-group differences in pain intensity at 12-month follow-up. Multimodal physiotherapy demonstrated a small between-group improvement in disability at 12 months follow-up compared to an attention control (Impairment Level Sum score, 5 to 50 scale; mean difference (MD) -3.7, 95% confidence interval (CI) -7.13 to -0.27) (very low-certainty evidence). Equivalent data for pain were not available. Details regarding adverse events were not reported. Physiotherapy compared with minimal care for adults with CRPS II We did not find any trials of physiotherapy compared with minimal care for adults with CRPS II. AUTHORS' CONCLUSIONS: The evidence is very uncertain about the effects of physiotherapy interventions on pain and disability in CRPS. This conclusion is similar to our 2016 review. Large-scale, high-quality RCTs with longer-term follow-up are required to test the effectiveness of physiotherapy-based interventions for treating pain and disability in adults with CRPS I and II.

Effect of Graded Sensorimotor Retraining on Pain Intensity in Patients With Chronic Low Back Pain: A Randomized Clinical Trial.

Importance: The effects of altered neural processing, defined as altering neural networks responsible for perceptions of pain and function, on chronic pain remains unclear. Objective: To estimate the effect of a graded sensorimotor retraining intervention (RESOLVE) on pain intensity in people with chronic low back pain. Design, Setting, and Participants: This parallel, 2-group, randomized clinical trial recruited participants with chronic (>3 months) nonspecific low back pain from primary care and community settings. A total of 276 adults were randomized (in a 1:1 ratio) to the intervention or sham procedure and attention control groups delivered by clinicians at a medical research institute in Sydney, Australia. The first participant was randomized on December 10, 2015, and the last was randomized on July 25, 2019. Follow-up was completed on February 3, 2020. Interventions: Participants randomized to the intervention group (n = 138) were asked to participate in 12 weekly clinical sessions and home training designed to educate them about and assist them with movement and physical activity while experiencing lower back pain. Participants randomized to the control group (n = 138) were asked to participate in 12 weekly clinical sessions and home training that required similar time as the intervention but did not focus on education, movement, and physical activity. The control group included sham laser and shortwave diathermy applied to the back and sham noninvasive brain stimulation. Main Outcomes and Measures: The primary outcome was pain intensity at 18 weeks, measured on an 11-point numerical rating scale (range, 0 [no pain] to 10 [worst pain imaginable]) for which the between-group minimum clinically important difference is 1.0 point. Results: Among 276 randomized patients (mean [SD] age, 46 [14.3] years; 138 [50%] women), 261 (95%) completed follow-up at 18 weeks. The mean pain intensity was 5.6 at baseline and 3.1 at 18 weeks in the intervention group and 5.8 at baseline and 4.0 at 18 weeks in the control group, with an estimated between-group mean difference at 18 weeks of -1.0 point ([95% CI, -1.5 to -0.4]; P = .001), favoring the intervention group. Conclusions and Relevance: In this randomized clinical trial conducted at a single center among patients with chronic low back pain, graded sensorimotor retraining, compared with a sham procedure and attention control, significantly improved pain intensity at 18 weeks. The improvements in pain intensity were small, and further research is needed to understand the generalizability of the findings. Trial Registration: ANZCTR Identifier: ACTRN12615000610538.

Implanted spinal neuromodulation interventions for chronic pain in adults.

BACKGROUND: Implanted spinal neuromodulation (SNMD) techniques are used in the treatment of refractory chronic pain. They involve the implantation of electrodes around the spinal cord (spinal cord stimulation (SCS)) or dorsal root ganglion (dorsal root ganglion stimulation (DRGS)), and a pulse generator unit under the skin. Electrical stimulation is then used with the aim of reducing pain intensity. OBJECTIVES: To evaluate the efficacy, effectiveness, adverse events, and cost-effectiveness of implanted spinal neuromodulation interventions for people with chronic pain. SEARCH METHODS: We searched CENTRAL, MEDLINE Ovid, Embase Ovid, Web of Science (ISI), Health Technology Assessments, ClinicalTrials.gov and World Health Organization International Clinical Trials Registry from inception to September 2021 without language restrictions, searched the reference lists of included studies and contacted experts in the field. SELECTION CRITERIA: We included randomised controlled trials (RCTs) comparing SNMD interventions with placebo (sham) stimulation, no treatment or usual care; or comparing SNMD interventions + another treatment versus that treatment alone. We included participants ≥ 18 years old with non-cancer and non-ischaemic pain of longer than three months duration. Primary outcomes were pain intensity and adverse events. Secondary outcomes were disability, analgesic medication use, health-related quality of life (HRQoL) and health economic outcomes. DATA COLLECTION AND ANALYSIS: Two review authors independently screened database searches to determine inclusion, extracted data and evaluated risk of bias for prespecified results using the Risk of Bias 2.0 tool. Outcomes were evaluated at short- (≤ one month), medium- four to eight months) and long-term (≥12 months). Where possible we conducted meta-analyses. We used the GRADE system to assess the certainty of evidence. MAIN RESULTS: We included 15 unique published studies that randomised 908 participants, and 20 unique ongoing studies. All studies evaluated SCS. We found no eligible published studies of DRGS and no studies comparing SCS with no treatment or usual care. We rated all results evaluated as being at high risk of bias overall. For all comparisons and outcomes where we found evidence, we graded the certainty of the evidence as low or very low, downgraded due to limitations of studies, imprecision and in some cases, inconsistency. Active stimulation versus placebo SCS versus placebo (sham) Results were only available at short-term follow-up for this comparison. Pain intensity Six studies (N = 164) demonstrated a small effect in favour of SCS at short-term follow-up (0 to 100 scale, higher scores = worse pain, mean difference (MD) -8.73, 95% confidence interval (CI) -15.67 to -1.78, very low certainty). The point estimate falls below our predetermined threshold for a clinically important effect (≥10 points). No studies reported the proportion of participants experiencing 30% or 50% pain relief for this comparison. Adverse events (AEs) The quality and inconsistency of adverse event reporting in these studies precluded formal analysis. Active stimulation + other intervention versus other intervention alone SCS + other intervention versus other intervention alone (open-label studies) Pain intensity Mean difference Three studies (N = 303) demonstrated a potentially clinically important mean difference in favour of SCS of -37.41 at short term (95% CI -46.39 to -28.42, very low certainty), and medium-term follow-up (5 studies, 635 participants, MD -31.22 95% CI -47.34 to -15.10 low-certainty), and no clear evidence for an effect of SCS at long-term follow-up (1 study, 44 participants, MD -7 (95% CI -24.76 to 10.76, very low-certainty). Proportion of participants reporting ≥50% pain relief We found an effect in favour of SCS at short-term (2 studies, N = 249, RR 15.90, 95% CI 6.70 to 37.74, I2 0% ; risk difference (RD) 0.65 (95% CI 0.57 to 0.74, very low certainty), medium term (5 studies, N = 597, RR 7.08, 95 %CI 3.40 to 14.71, I2 = 43%; RD 0.43, 95% CI 0.14 to 0.73, low-certainty evidence), and long term (1 study, N = 87, RR 15.15, 95% CI 2.11 to 108.91 ; RD 0.35, 95% CI 0.2 to 0.49, very low certainty) follow-up. Adverse events (AEs) Device related No studies specifically reported  device-related adverse events at short-term follow-up. At medium-term follow-up, the incidence of lead failure/displacement (3 studies N = 330) ranged from 0.9 to 14% (RD 0.04, 95% CI -0.04 to 0.11, I2 64%, very low certainty). The incidence of infection (4 studies, N = 548) ranged from 3 to 7% (RD 0.04, 95%CI 0.01, 0.07, I2 0%, very low certainty). The incidence of reoperation/reimplantation (4 studies, N =5 48) ranged from 2% to 31% (RD 0.11, 95% CI 0.02 to 0.21, I2 86%, very low certainty). One study (N = 44) reported a 55% incidence of lead failure/displacement (RD 0.55, 95% CI 0.35, 0 to 75, very low certainty), and a 94% incidence of reoperation/reimplantation (RD 0.94, 95% CI 0.80 to 1.07, very low certainty) at five-year follow-up. No studies provided data on infection rates at long-term follow-up. We found reports of some serious adverse events as a result of the intervention. These included autonomic neuropathy, prolonged hospitalisation, prolonged monoparesis, pulmonary oedema, wound infection, device extrusion and one death resulting from subdural haematoma. Other No studies reported the incidence of other adverse events at short-term follow-up. We found no clear evidence of a difference in otherAEs at medium-term (2 studies, N = 278, RD -0.05, 95% CI -0.16 to 0.06, I2 0%) or long term (1 study, N = 100, RD -0.17, 95% CI -0.37 to 0.02) follow-up. Very limited evidence suggested that SCS increases healthcare costs. It was not clear whether SCS was cost-effective. AUTHORS' CONCLUSIONS: We found very low-certainty evidence that SCS may not provide clinically important benefits on pain intensity compared to placebo stimulation. We found low- to very low-certainty evidence that SNMD interventions may provide clinically important benefits for pain intensity when added to conventional medical management or physical therapy. SCS is associated with complications including infection, electrode lead failure/migration and a need for reoperation/re-implantation. The level of certainty regarding the size of those risks is very low. SNMD may lead to serious adverse events, including death. We found no evidence to support or refute the use of DRGS for chronic pain.

A systematic review exploring the evidence reported to underpin exercise dose in clinical trials of rheumatoid arthritis.

We aimed to evaluate the evidence reported to underpin exercise dose in randomised controlled trials (RCTs) using strengthening exercise in RA. We searched six different databases between 1 January 2000 and 3 April 2019. We included RCTs, where a main component of the intervention and/or control used strengthening exercise. Evidence sources cited to underpin dose were judged for their quality, consistency and applicability. Thirty-two RCTs were reviewed. Four (12.5%) piloted the intervention without using dose-escalation designs to determine optimal dose-response. Twenty (62.5%) reported no evidence underpinning dose. Where reported, quality, consistency and applicability of the underpinning evidence was a cause for methodological concern. The majority of RCTs did not report the evidence underpinning dose. When reported, the evidence was often not applicable to the clinical population. Frequently, the dose used differed to the dose reported/recommended by the underpinning evidence. Our findings illustrate exercise dose may not be optimised for use with clinical populations prior to evaluation by RCT.

Mortality due to cardiovascular disease, respiratory disease, and cancer in adults with cerebral palsy.

AIM: To compare mortality rates for cardiovascular disease, cancer, and respiratory disease between adults with cerebral palsy (CP) and the general population. METHOD: A cohort study was conducted using data from adults with CP in England, identified through a primary care data set (the Clinical Practice Research Datalink), with linked data on death registrations from the Office for National Statistics. Cause of death was categorized according to International Classification of Diseases codes. Standardized mortality ratios (SMRs) were calculated to compare mortality rates between adults with CP and the general population, adjusted for age, sex, and calendar year. RESULTS: Nine hundred and fifty-eight adults with CP were identified (52.5% males, 47.5% females; median age at start of follow-up 31y [interquartile range 22-43y]) and followed for a total of 7693 person-years. One hundred and forty-two patients (15%) died during follow-up. Adults with CP had an increased risk of death due to cardiovascular disease (SMR: 3.19, 95% confidence interval [CI] 2.20-4.62) and respiratory disease (SMR: 13.59, 95% CI 9.89-18.67), but not from malignant neoplasms (SMR: 1.42, 95% CI 0.83-2.45). INTERPRETATION: We found that adults with CP in England have increased risk of death due to diseases of the circulatory and respiratory systems, supporting findings from two studies that compared cause-specific mortality rates between adults with CP in the USA and the general population. Further research is required into primary and secondary prevention of cardiovascular and respiratory disease in people with CP worldwide. WHAT THIS PAPER ADDS: Adults with cerebral palsy (CP) in England have 14-fold increased risk of mortality due to diseases of the respiratory system. They have a 3-fold increased risk of mortality due to diseases of the circulatory system. Adults with CP had an increased risk of death due to cerebrovascular disease and ischaemic heart disease. The elevated risk of ischaemic heart disease, however, did not reach statistical significance at the 5% per cent level.

MORTALIDAD POR ENFERMEDAD CARDIOVASCULAR, ENFERMEDAD RESPIRATORIA Y CÁNCER EN ADULTOS CON PARÁLISIS CEREBRAL: OBJETIVO: Comparar tasas de mortalidad por enfermedad cardiovascular, cáncer y enfermedad respiratoria entre adultos con parálisis cerebral (PC) y la población general. MÉTODO: Se llevó a cabo un estudio de cohorte utilizando datos de adultos con PC en Inglaterra, identificados a través de un set de datos de atención primaria (the Clinical Practice Research Datalink) con datos vinculados sobre los registros de defunciones de la Oficina Nacional de Estadísticas. Las causas de muertes fueron categorizadas de acuerdo con los códigos de la Clasificación Internacional de Enfermedades. Las tasas de mortalidad estandarizadas (TME) fueron calculadas a fin de comparar las tasas de mortalidad entre adultos con PC y la población general, ajustadas por edad, sexo y año calendario. RESULTADOS: Se identificaron 958 adultos con PC (52,5% varones, 47,5% mujeres; edad mediana al comienzo del seguimiento 31 años [rango intercuartilo 22-43 años] y fueron seguidos por un total de 7.693 años-persona. Ciento cuarenta y dos pacientes (15%) fallecieron durante el seguimiento. Los adultos con PC tuvieron un mayor riesgo de muerte por enfermedad cardiovascular (TME:3,19, 95% intervalo de confidencia [IC] 2,20-4,62) y enfermedad respiratoria (TME:13,59,95% IC 9,89-18,67), pero no tuvieron mayor riesgo de neoplasias malignas (TME:1,42, 95% IC 0,83-2,45). INTERPRETACIÓN: Encontramos que los adultos con PC en Inglaterra tienen un riesgo incrementado de muerte por enfermedades de los sistemas circulatorio y respiratorio, sosteniendo los hallazgos con dos estudios que compararon tasas de mortalidad causa-específicas entre adultos con PC en los EEUU y la población general. Se necesita avanzar con la investigación hacia prevención primaria y secundaria de enfermedades cardiovascular y respiratoria en personas con PC en todo el mundo.

MORTALIDADE DEVIDO A DOENÇA CARDIOVASCULAR, RESPIRATÓRIA, E CÂNCER EM ADULTOS COM PARALISIA CEREBRAL: OBJETIVO: Comparar as taxas de mortalidade por doença cardiovascular, câncer, e doença respiratória em adultos com paralisia cerebral (PC) e a população em geral. MÉTODO: Um estudo de coorte foi realizado usando dados de adultos com PC na Inglaterra, identificados por meio de um conjunto de dados de atenção primária (o Datalink Pesquisa em Prática Clínica,), com dados sobre registros de óbitos do Escritório Nacional de Estatística. A causa da morte foi categorizada de acordo com os códigos da Classificação Internacional de Doenças. Taxas de mortalidade padronizadas (TMPs) foram calculadas para comparar as taxas de mortalidade entre adultos com PC e a população em geral, ajustadas por idade, sexo e ano calendário. RESULTADOS: Novecentos e cinquenta e oito adultos com PC foram identificados (52,5% do sexo masculino, 47,5% do sexo feminino; idade mediana no início do acompanhamento 31a [intervalo interquartil 22-43a]) e acompanhados por um total de 7,693 anos-pessoa. Cento e quarenta e dois pacientes (15%) morreram durante o acompanhamento. Adultos com PC tiveram risco aumentado de morte por doença (TMP: 3,19, intervalo de confiança [IC] a 95% 2,20-4,62) e doença respiratória (TMP: 13,59, IC 95% 9,89-18,67), mas não por neoplasias malignas (TMP: 1,42, IC 95% 0,83-2,45). INTERPRETAÇÃO: Observamos que adultos com PC na Inglaterra têm risco aumentado de more por doenças dos sistemas circulatório e respiratório, o que apóia achados de dois estudos qu compararam taxas de mortalidade causa-específica em adultos com PC nos EUA e na população em geral. Mais pesquisas são necessárias sobre a prevenção primária e secundária de doenças cardiovasculares e respiratórias em pessoas com PC em todo o mundo.

Transcutaneous electrical nerve stimulation (TENS) for chronic pain - an overview of Cochrane Reviews.

BACKGROUND: Chronic pain, considered to be pain lasting more than three months, is a common and often difficult to treat condition that can significantly impact upon function and quality of life. Treatment typically includes pharmacological and non-pharmacological approaches. Transcutaneous electrical nerve stimulation (TENS) is an adjunct non-pharmacological treatment commonly recommended by clinicians and often used by people with pain. OBJECTIVES: To provide an overview of evidence from Cochrane Reviews of the effectiveness of TENS to reduce pain in adults with chronic pain (excluding headache or migraine).To provide an overview of evidence from Cochrane Reviews of the safety of TENS when used to reduce pain in adults with chronic pain (excluding headache or migraine).To identify possible sources of inconsistency in the approaches taken to evaluating the evidence related to TENS for chronic pain (excluding headache or migraine) in the Cochrane Library with a view to recommending strategies to improve consistency in methodology and reporting.To highlight areas of remaining uncertainty regarding the effectiveness of TENS for chronic pain (excluding headache or migraine) with a view to recommending strategies to reduce any uncertainty. METHODS: Search methodsWe searched the Cochrane Database of Systematic Reviews (CDSR), in the Cochrane Library, across all years up to Issue 11 of 12, 2018.Selection of reviewsTwo authors independently screened the results of the electronic search by title and abstract against inclusion/exclusion criteria. We included all Cochrane Reviews of randomised controlled trials (RCTs) assessing the effectiveness of TENS in people with chronic pain. We included reviews if they investigated the following: TENS versus sham; TENS versus usual care or no treatment/waiting list control; TENS plus active intervention versus active intervention alone; comparisons between different types of TENS; or TENS delivered using different stimulation parameters.Data extraction and analysisTwo authors independently extracted relevant data, assessed review quality using the AMSTAR checklist and applied GRADE judgements where required to individual reviews. Our primary outcomes included pain intensity and nature/incidence of adverse effects; our secondary outcomes included disability, health-related quality of life, analgesic medication use and participant global impression of change. MAIN RESULTS: We included nine reviews investigating TENS use in people with defined chronic pain or in people with chronic conditions associated with ongoing pain. One review investigating TENS for phantom or stump-associated pain in people following amputation did not have any included studies. We therefore extracted data from eight reviews which represented 51 TENS-related RCTs representing 2895 TENS-comparison participants entered into the studies.The included reviews followed consistent methods and achieved overall high scores on the AMSTAR checklist. The evidence reported within each review was consistently rated as very low quality. Using review authors' assessment of risk of bias, there were significant methodological limitations in included studies; and for all reviews, sample sizes were consistently small (the majority of studies included fewer than 50 participants per group).Six of the eight reviews presented a narrative synthesis of included studies. Two reviews reported a pooled analysis.Primary and secondary outcomes One review reported a beneficial effect of TENS versus sham therapy at reducing pain intensity on a 0 to 10 scale (MD -1.58, 95% CI -2.08 to -1.09, P < 0.001, I² = 29%, P = 0.22, 5 studies, 207 participants). However the quality of the evidence was very low due to significant methodological limitations and imprecision. A second review investigating pain intensity performed a pooled analysis by combining studies that compared TENS to sham with studies that compared TENS to no intervention (SMD -0.85, 95% CI -1.36 to -0.34, P = 0.001, I² = 83%, P < 0.001). This pooled analysis was judged as offering very low quality evidence due to significant methodological limitations, large between-trial heterogeneity and imprecision. We considered the approach of combining sham and no intervention data to be problematic since we would predict these different comparisons may be estimating different true effects. All remaining reviews also reported pain intensity as an outcome measure; however the data were presented in narrative review form only.Due to methodological limitation and lack of useable data, we were unable to offer any meaningful report on the remaining primary outcome regarding nature/incidence of adverse effects, nor for the remaining secondary outcomes: disability, health-related quality of life, analgesic medication use and participant global impression of change for any comparisons.We found the included reviews had a number of inconsistencies when evaluating the evidence from TENS studies. Approaches to assessing risk of bias around the participant, personnel and outcome-assessor blinding were perhaps the most obvious area of difference across included reviews. We also found wide variability in terms of primary and secondary outcome measures, and inclusion/exclusion criteria for studies varied with respect to including studies which assessed immediate effects of single interventions. AUTHORS' CONCLUSIONS: We found the methodological quality of the reviews was good, but quality of the evidence within them was very low. We were therefore unable to conclude with any confidence that, in people with chronic pain, TENS is harmful, or beneficial for pain control, disability, health-related quality of life, use of pain relieving medicines, or global impression of change. We make recommendations with respect to future TENS study designs which may meaningfully reduce the uncertainty relating to the effectiveness of this treatment in people with chronic pain.

Transcutaneous electrical nerve stimulation (TENS) for chronic pain - an overview of Cochrane Reviews.

BACKGROUND: Chronic pain, considered to be pain lasting more than three months, is a common and often difficult to treat condition that can significantly impact upon function and quality of life. Treatment typically includes pharmacological and non-pharmacological approaches. Transcutaneous electrical nerve stimulation (TENS) is an adjunct non-pharmacological treatment commonly recommended by clinicians and often used by people with pain. OBJECTIVES: To provide an overview of evidence from Cochrane Reviews of the effectiveness of TENS to reduce pain in adults with chronic pain (excluding headache or migraine).To provide an overview of evidence from Cochrane Reviews of the safety of TENS when used to reduce pain in adults with chronic pain (excluding headache or migraine).To identify possible sources of inconsistency in the approaches taken to evaluating the evidence related to TENS for chronic pain (excluding headache or migraine) in the Cochrane Library with a view to recommending strategies to improve consistency in methodology and reporting.To highlight areas of remaining uncertainty regarding the effectiveness of TENS for chronic pain (excluding headache or migraine) with a view to recommending strategies to reduce any uncertainty. METHODS: Search methodsWe searched the Cochrane Database of Systematic Reviews (CDSR), in the Cochrane Library, across all years up to Issue 11 of 12, 2018.Selection of reviewsTwo authors independently screened the results of the electronic search by title and abstract against inclusion/exclusion criteria. We included all Cochrane Reviews of randomised controlled trials (RCTs) assessing the effectiveness of TENS in people with chronic pain. We included reviews if they investigated the following: TENS versus sham; TENS versus usual care or no treatment/waiting list control; TENS plus active intervention versus active intervention alone; comparisons between different types of TENS; or TENS delivered using different stimulation parameters.Data extraction and analysisTwo authors independently extracted relevant data, assessed review quality using the AMSTAR checklist and applied GRADE judgements where required to individual reviews. Our primary outcomes included pain intensity and nature/incidence of adverse effects; our secondary outcomes included disability, health-related quality of life, analgesic medication use and participant global impression of change. MAIN RESULTS: We included nine reviews investigating TENS use in people with defined chronic pain or in people with chronic conditions associated with ongoing pain. One review investigating TENS for phantom or stump-associated pain in people following amputation did not have any included studies. We therefore extracted data from eight reviews which represented 51 TENS-related RCTs representing 2895 TENS-comparison participants entered into the studies.The included reviews followed consistent methods and achieved overall high scores on the AMSTAR checklist. The evidence reported within each review was consistently rated as very low quality. Using review authors' assessment of risk of bias, there were significant methodological limitations in included studies; and for all reviews, sample sizes were consistently small (the majority of studies included fewer than 50 participants per group).Six of the eight reviews presented a narrative synthesis of included studies. Two reviews reported a pooled analysis.Primary and secondary outcomes One review reported a beneficial effect of TENS versus sham therapy at reducing pain intensity on a 0 to 10 scale (MD -1.58, 95% CI -2.08 to -1.09, P < 0.001, I² = 29%, P = 0.22, 5 studies, 207 participants). However the quality of the evidence was very low due to significant methodological limitations and imprecision. A second review investigating pain intensity performed a pooled analysis by combining studies that compared TENS to sham with studies that compared TENS to no intervention (SMD -0.85, 95% CI -1.36 to -0.34, P = 0.001, I² = 83%, P < 0.001). This pooled analysis was judged as offering very low quality evidence due to significant methodological limitations, large between-trial heterogeneity and imprecision. We considered the approach of combining sham and no intervention data to be problematic since we would predict these different comparisons may be estimating different true effects. All remaining reviews also reported pain intensity as an outcome measure; however the data were presented in narrative review form only.Due to methodological limitation and lack of useable data, we were unable to offer any meaningful report on the remaining primary outcome regarding nature/incidence of adverse effects, nor for the remaining secondary outcomes: disability, health-related quality of life, analgesic medication use and participant global impression of change for any comparisons.We found the included reviews had a number of inconsistencies when evaluating the evidence from TENS studies. Approaches to assessing risk of bias around the participant, personnel and outcome-assessor blinding were perhaps the most obvious area of difference across included reviews. We also found wide variability in terms of primary and secondary outcome measures, and inclusion/exclusion criteria for studies varied with respect to including studies which assessed immediate effects of single interventions. AUTHORS' CONCLUSIONS: We found the methodological quality of the reviews was good, but quality of the evidence within them was very low. We were therefore unable to conclude with any confidence that, in people with chronic pain, TENS is harmful, or beneficial for pain control, disability, health-related quality of life, use of pain relieving medicines, or global impression of change. We make recommendations with respect to future TENS study designs which may meaningfully reduce the uncertainty relating to the effectiveness of this treatment in people with chronic pain.

Non-invasive brain stimulation techniques for chronic pain.

BACKGROUND: This is an updated version of the original Cochrane Review published in 2010, Issue 9, and last updated in 2014, Issue 4. Non-invasive brain stimulation techniques aim to induce an electrical stimulation of the brain in an attempt to reduce chronic pain by directly altering brain activity. They include repetitive transcranial magnetic stimulation (rTMS), cranial electrotherapy stimulation (CES), transcranial direct current stimulation (tDCS), transcranial random noise stimulation (tRNS) and reduced impedance non-invasive cortical electrostimulation (RINCE). OBJECTIVES: To evaluate the efficacy of non-invasive cortical stimulation techniques in the treatment of chronic pain. SEARCH METHODS: For this update we searched CENTRAL, MEDLINE, Embase, CINAHL, PsycINFO, LILACS and clinical trials registers from July 2013 to October 2017. SELECTION CRITERIA: Randomised and quasi-randomised studies of rTMS, CES, tDCS, RINCE and tRNS if they employed a sham stimulation control group, recruited patients over the age of 18 years with pain of three months' duration or more, and measured pain as an outcome. Outcomes of interest were pain intensity measured using visual analogue scales or numerical rating scales, disability, quality of life and adverse events. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted and verified data. Where possible we entered data into meta-analyses, excluding studies judged as high risk of bias. We used the GRADE system to assess the quality of evidence for core comparisons, and created three 'Summary of findings' tables. MAIN RESULTS: We included an additional 38 trials (involving 1225 randomised participants) in this update, making a total of 94 trials in the review (involving 2983 randomised participants). This update included a total of 42 rTMS studies, 11 CES, 36 tDCS, two RINCE and two tRNS. One study evaluated both rTMS and tDCS. We judged only four studies as low risk of bias across all key criteria. Using the GRADE criteria we judged the quality of evidence for each outcome, and for all comparisons as low or very low; in large part this was due to issues of blinding and of precision.rTMSMeta-analysis of rTMS studies versus sham for pain intensity at short-term follow-up (0 to < 1 week postintervention), (27 studies, involving 655 participants), demonstrated a small effect with heterogeneity (standardised mean difference (SMD) -0.22, 95% confidence interval (CI) -0.29 to -0.16, low-quality evidence). This equates to a 7% (95% CI 5% to 9%) reduction in pain, or a 0.40 (95% CI 0.53 to 0.32) point reduction on a 0 to 10 pain intensity scale, which does not meet the minimum clinically important difference threshold of 15% or greater. Pre-specified subgroup analyses did not find a difference between low-frequency stimulation (low-quality evidence) and rTMS applied to the prefrontal cortex compared to sham for reducing pain intensity at short-term follow-up (very low-quality evidence). High-frequency stimulation of the motor cortex in single-dose studies was associated with a small short-term reduction in pain intensity at short-term follow-up (low-quality evidence, pooled n = 249, SMD -0.38 95% CI -0.49 to -0.27). This equates to a 12% (95% CI 9% to 16%) reduction in pain, or a 0.77 (95% CI 0.55 to 0.99) point change on a 0 to 10 pain intensity scale, which does not achieve the minimum clinically important difference threshold of 15% or greater. The results from multiple-dose studies were heterogeneous and there was no evidence of an effect in this subgroup (very low-quality evidence). We did not find evidence that rTMS improved disability. Meta-analysis of studies of rTMS versus sham for quality of life (measured using the Fibromyalgia Impact Questionnaire (FIQ) at short-term follow-up demonstrated a positive effect (MD -10.80 95% CI -15.04 to -6.55, low-quality evidence).CESFor CES (five studies, 270 participants) we found no evidence of a difference between active stimulation and sham (SMD -0.24, 95% CI -0.48 to 0.01, low-quality evidence) for pain intensity. We found no evidence relating to the effectiveness of CES on disability. One study (36 participants) of CES versus sham for quality of life (measured using the FIQ) at short-term follow-up demonstrated a positive effect (MD -25.05 95% CI -37.82 to -12.28, very low-quality evidence).tDCSAnalysis of tDCS studies (27 studies, 747 participants) showed heterogeneity and a difference between active and sham stimulation (SMD -0.43 95% CI -0.63 to -0.22, very low-quality evidence) for pain intensity. This equates to a reduction of 0.82 (95% CI 0.42 to 1.2) points, or a percentage change of 17% (95% CI 9% to 25%) of the control group outcome. This point estimate meets our threshold for a minimum clinically important difference, though the lower confidence interval is substantially below that threshold. We found evidence of small study bias in the tDCS analyses. We did not find evidence that tDCS improved disability. Meta-analysis of studies of tDCS versus sham for quality of life (measured using different scales across studies) at short-term follow-up demonstrated a positive effect (SMD 0.66 95% CI 0.21 to 1.11, low-quality evidence).Adverse eventsAll forms of non-invasive brain stimulation and sham stimulation appear to be frequently associated with minor or transient side effects and there were two reported incidences of seizure, both related to the active rTMS intervention in the included studies. However many studies did not adequately report adverse events. AUTHORS' CONCLUSIONS: There is very low-quality evidence that single doses of high-frequency rTMS of the motor cortex and tDCS may have short-term effects on chronic pain and quality of life but multiple sources of bias exist that may have influenced the observed effects. We did not find evidence that low-frequency rTMS, rTMS applied to the dorsolateral prefrontal cortex and CES are effective for reducing pain intensity in chronic pain. The broad conclusions of this review have not changed substantially for this update. There remains a need for substantially larger, rigorously designed studies, particularly of longer courses of stimulation. Future evidence may substantially impact upon the presented results.

Non-invasive brain stimulation techniques for chronic pain.

BACKGROUND: This is an updated version of the original Cochrane Review published in 2010, Issue 9, and last updated in 2014, Issue 4. Non-invasive brain stimulation techniques aim to induce an electrical stimulation of the brain in an attempt to reduce chronic pain by directly altering brain activity. They include repetitive transcranial magnetic stimulation (rTMS), cranial electrotherapy stimulation (CES), transcranial direct current stimulation (tDCS), transcranial random noise stimulation (tRNS) and reduced impedance non-invasive cortical electrostimulation (RINCE). OBJECTIVES: To evaluate the efficacy of non-invasive cortical stimulation techniques in the treatment of chronic pain. SEARCH METHODS: For this update we searched CENTRAL, MEDLINE, Embase, CINAHL, PsycINFO, LILACS and clinical trials registers from July 2013 to October 2017. SELECTION CRITERIA: Randomised and quasi-randomised studies of rTMS, CES, tDCS, RINCE and tRNS if they employed a sham stimulation control group, recruited patients over the age of 18 years with pain of three months' duration or more, and measured pain as an outcome. Outcomes of interest were pain intensity measured using visual analogue scales or numerical rating scales, disability, quality of life and adverse events. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted and verified data. Where possible we entered data into meta-analyses, excluding studies judged as high risk of bias. We used the GRADE system to assess the quality of evidence for core comparisons, and created three 'Summary of findings' tables. MAIN RESULTS: We included an additional 38 trials (involving 1225 randomised participants) in this update, making a total of 94 trials in the review (involving 2983 randomised participants). This update included a total of 42 rTMS studies, 11 CES, 36 tDCS, two RINCE and two tRNS. One study evaluated both rTMS and tDCS. We judged only four studies as low risk of bias across all key criteria. Using the GRADE criteria we judged the quality of evidence for each outcome, and for all comparisons as low or very low; in large part this was due to issues of blinding and of precision.rTMSMeta-analysis of rTMS studies versus sham for pain intensity at short-term follow-up (0 to < 1 week postintervention), (27 studies, involving 655 participants), demonstrated a small effect with heterogeneity (standardised mean difference (SMD) -0.22, 95% confidence interval (CI) -0.29 to -0.16, low-quality evidence). This equates to a 7% (95% CI 5% to 9%) reduction in pain, or a 0.40 (95% CI 0.53 to 0.32) point reduction on a 0 to 10 pain intensity scale, which does not meet the minimum clinically important difference threshold of 15% or greater. Pre-specified subgroup analyses did not find a difference between low-frequency stimulation (low-quality evidence) and rTMS applied to the prefrontal cortex compared to sham for reducing pain intensity at short-term follow-up (very low-quality evidence). High-frequency stimulation of the motor cortex in single-dose studies was associated with a small short-term reduction in pain intensity at short-term follow-up (low-quality evidence, pooled n = 249, SMD -0.38 95% CI -0.49 to -0.27). This equates to a 12% (95% CI 9% to 16%) reduction in pain, or a 0.77 (95% CI 0.55 to 0.99) point change on a 0 to 10 pain intensity scale, which does not achieve the minimum clinically important difference threshold of 15% or greater. The results from multiple-dose studies were heterogeneous and there was no evidence of an effect in this subgroup (very low-quality evidence). We did not find evidence that rTMS improved disability. Meta-analysis of studies of rTMS versus sham for quality of life (measured using the Fibromyalgia Impact Questionnaire (FIQ) at short-term follow-up demonstrated a positive effect (MD -10.80 95% CI -15.04 to -6.55, low-quality evidence).CESFor CES (five studies, 270 participants) we found no evidence of a difference between active stimulation and sham (SMD -0.24, 95% CI -0.48 to 0.01, low-quality evidence) for pain intensity. We found no evidence relating to the effectiveness of CES on disability. One study (36 participants) of CES versus sham for quality of life (measured using the FIQ) at short-term follow-up demonstrated a positive effect (MD -25.05 95% CI -37.82 to -12.28, very low-quality evidence).tDCSAnalysis of tDCS studies (27 studies, 747 participants) showed heterogeneity and a difference between active and sham stimulation (SMD -0.43 95% CI -0.63 to -0.22, very low-quality evidence) for pain intensity. This equates to a reduction of 0.82 (95% CI 0.42 to 1.2) points, or a percentage change of 17% (95% CI 9% to 25%) of the control group outcome. This point estimate meets our threshold for a minimum clinically important difference, though the lower confidence interval is substantially below that threshold. We found evidence of small study bias in the tDCS analyses. We did not find evidence that tDCS improved disability. Meta-analysis of studies of tDCS versus sham for quality of life (measured using different scales across studies) at short-term follow-up demonstrated a positive effect (SMD 0.66 95% CI 0.21 to 1.11, low-quality evidence).Adverse eventsAll forms of non-invasive brain stimulation and sham stimulation appear to be frequently associated with minor or transient side effects and there were two reported incidences of seizure, both related to the active rTMS intervention in the included studies. However many studies did not adequately report adverse events. AUTHORS' CONCLUSIONS: There is very low-quality evidence that single doses of high-frequency rTMS of the motor cortex and tDCS may have short-term effects on chronic pain and quality of life but multiple sources of bias exist that may have influenced the observed effects. We did not find evidence that low-frequency rTMS, rTMS applied to the dorsolateral prefrontal cortex and CES are effective for reducing pain intensity in chronic pain. The broad conclusions of this review have not changed substantially for this update. There remains a need for substantially larger, rigorously designed studies, particularly of longer courses of stimulation. Future evidence may substantially impact upon the presented results.

Transcutaneous electrical nerve stimulation (TENS) for neuropathic pain in adults.

BACKGROUND: Neuropathic pain, which is due to nerve disease or damage, represents a significant burden on people and society. It can be particularly unpleasant and achieving adequate symptom control can be difficult. Non-pharmacological methods of treatment are often employed by people with neuropathic pain and may include transcutaneous electrical nerve stimulation (TENS). This review supersedes one Cochrane Review 'Transcutaneous electrical nerve stimulation (TENS) for chronic pain' (Nnoaham 2014) and one withdrawn protocol 'Transcutaneous electrical nerve stimulation (TENS) for neuropathic pain in adults' (Claydon 2014). This review replaces the original protocol for neuropathic pain that was withdrawn. OBJECTIVES: To determine the analgesic effectiveness of TENS versus placebo (sham) TENS, TENS versus usual care, TENS versus no treatment and TENS in addition to usual care versus usual care alone in the management of neuropathic pain in adults. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, PsycINFO, AMED, CINAHL, Web of Science, PEDro, LILACS (up to September 2016) and various clinical trials registries. We also searched bibliographies of included studies for further relevant studies. SELECTION CRITERIA: We included randomised controlled trials where TENS was evaluated in the treatment of central or peripheral neuropathic pain. We included studies if they investigated the following: TENS versus placebo (sham) TENS, TENS versus usual care, TENS versus no treatment and TENS in addition to usual care versus usual care alone in the management of neuropathic pain in adults. DATA COLLECTION AND ANALYSIS: Two review authors independently screened all database search results and identified papers requiring full-text assessment. Subsequently, two review authors independently applied inclusion/exclusion criteria to these studies. The same review authors then independently extracted data, assessed for risk of bias using the Cochrane standard tool and rated the quality of evidence using GRADE. MAIN RESULTS: We included 15 studies with 724 participants. We found a range of treatment protocols in terms of duration of care, TENS application times and intensity of application. Briefly, duration of care ranged from four days through to three months. Similarly, we found variation of TENS application times; from 15 minutes up to hourly sessions applied four times daily. We typically found intensity of TENS set to comfortable perceptible tingling with very few studies titrating the dose to maintain this perception. Of the comparisons, we had planned to explore, we were only able to undertake a quantitative synthesis for TENS versus sham TENS. Insufficient data and large diversity in the control conditions prevented us from undertaking a quantitative synthesis for the remaining comparisons.For TENS compared to sham TENS, five studies were suitable for pooled analysis. We described the remainder of the studies in narrative form. Overall, we judged 11 studies at high risk of bias, and four at unclear risk. Due to the small number of eligible studies, the high levels of risk of bias across the studies and small sample sizes, we rated the quality of the evidence as very low for the pooled analysis and very low individual GRADE rating of outcomes from single studies. For the individual studies discussed in narrative form, the methodological limitations, quality of reporting and heterogeneous nature of interventions compared did not allow for reliable overall estimates of the effect of TENS.Five studies (across various neuropathic conditions) were suitable for pooled analysis of TENS versus sham TENS investigating change in pain intensity using a visual analogue scale. We found a mean postintervention difference in effect size favouring TENS of -1.58 (95% confidence interval (CI) -2.08 to -1.09, P < 0.00001, n = 207, six comparisons from five studies) (very low quality evidence). There was no significant heterogeneity in this analysis. While this exceeded our prespecified minimally important difference for pain outcomes, we assessed the quality of evidence as very low meaning we have very little confidence in this effect estimate and the true effect is likely to be substantially different from that reported in this review. Only one study of these five investigated health related quality of life as an outcome meaning we were unable to report on this outcome in this comparison. Similarly, we were unable to report on global impression of change or changes in analgesic use in this pooled analysis.Ten small studies compared TENS to some form of usual care. However, there was great diversity in what constituted usual care, precluding pooling of data. Most of these studies found either no difference in pain outcomes between TENS versus other active treatments or favoured the comparator intervention (very low quality evidence). We were unable to report on other primary and secondary outcomes in these single trials (health-related quality of life, global impression of change and changes in analgesic use).Of the 15 included studies, three reported adverse events which were minor and limited to 'skin irritation' at or around the site of electrode placement (very low quality evidence). Three studies reported no adverse events while the remainder did not report any detail with regard adverse events. AUTHORS' CONCLUSIONS: In this review, we reported on the comparison between TENS and sham TENS. The quality of the evidence was very low meaning we were unable to confidently state whether TENS is effective for pain control in people with neuropathic pain. The very low quality of evidence means we have very limited confidence in the effect estimate reported; the true effect is likely to be substantially different. We make recommendations with respect to future TENS study designs which may meaningfully reduce the uncertainty relating to the effectiveness of this treatment modality.

Exercise interventions for cerebral palsy.

BACKGROUND: Cerebral palsy (CP) is a neurodevelopmental disorder resulting from an injury to the developing brain. It is the most common form of childhood disability with prevalence rates of between 1.5 and 3.8 per 1000 births reported worldwide. The primary impairments associated with CP include reduced muscle strength and reduced cardiorespiratory fitness, resulting in difficulties performing activities such as dressing, walking and negotiating stairs.Exercise is defined as a planned, structured and repetitive activity that aims to improve fitness, and it is a commonly used intervention for people with CP. Aerobic and resistance training may improve activity (i.e. the ability to execute a task) and participation (i.e. involvement in a life situation) through their impact on the primary impairments of CP. However, to date, there has been no comprehensive review of exercise interventions for people with CP. OBJECTIVES: To assess the effects of exercise interventions in people with CP, primarily in terms of activity, participation and quality of life. Secondary outcomes assessed body functions and body structures. Comparators of interest were no treatment, usual care or an alternative type of exercise intervention. SEARCH METHODS: In June 2016 we searched CENTRAL, MEDLINE, Embase, nine other databases and four trials registers. SELECTION CRITERIA: We included randomised controlled trials (RCTs) and quasi-RCTs of children, adolescents and adults with CP. We included studies of aerobic exercise, resistance training, and 'mixed training' (a combination of at least two of aerobic exercise, resistance training and anaerobic training). DATA COLLECTION AND ANALYSIS: Two review authors independently screened titles, abstracts and potentially relevant full-text reports for eligibility; extracted all relevant data and conducted 'Risk of bias' and GRADE assessments. MAIN RESULTS: We included 29 trials (926 participants); 27 included children and adolescents up to the age of 19 years, three included adolescents and young adults (10 to 22 years), and one included adults over 20 years. Males constituted 53% of the sample. Five trials were conducted in the USA; four in Australia; two in Egypt, Korea, Saudi Arabia, Taiwan, the Netherlands, and the UK; three in Greece; and one apiece in India, Italy, Norway, and South Africa.Twenty-six trials included people with spastic CP only; three trials included children and adolescents with spastic and other types of CP. Twenty-one trials included people who were able to walk with or without assistive devices, four trials also included people who used wheeled mobility devices in most settings, and one trial included people who used wheeled mobility devices only. Three trials did not report the functional ability of participants. Only two trials reported participants' manual ability. Eight studies compared aerobic exercise to usual care, while 15 compared resistance training and 4 compared mixed training to usual care or no treatment. Two trials compared aerobic exercise to resistance training. We judged all trials to be at high risk of bias overall.We found low-quality evidence that aerobic exercise improves gross motor function in the short term (standardised mean difference (SMD) 0.53, 95% confidence interval (CI) 0.02 to 1.04, N = 65, 3 studies) and intermediate term (mean difference (MD) 12.96%, 95% CI 0.52% to 25.40%, N = 12, 1 study). Aerobic exercise does not improve gait speed in the short term (MD 0.09 m/s, 95% CI -0.11 m/s to 0.28 m/s, N = 82, 4 studies, very low-quality evidence) or intermediate term (MD -0.17 m/s, 95% CI -0.59 m/s to 0.24 m/s, N = 12, 1 study, low-quality evidence). No trial assessed participation or quality of life following aerobic exercise.We found low-quality evidence that resistance training does not improve gross motor function (SMD 0.12, 95% CI -0.19 to 0.43, N = 164, 7 studies), gait speed (MD 0.03 m/s, 95% CI -0.02 m/s to 0.07 m/s, N = 185, 8 studies), participation (SMD 0.34, 95% CI -0.01 to 0.70, N = 127, 2 studies) or parent-reported quality of life (MD 12.70, 95% CI -5.63 to 31.03, n = 12, 1 study) in the short term. There is also low-quality evidence that resistance training does not improve gait speed (MD -0.03 m/s, 95% CI -0.17 m/s to 0.11 m/s, N = 84, 3 studies), gross motor function (SMD 0.13, 95% CI -0.30 to 0.55, N = 85, 3 studies) or participation (MD 0.37, 95% CI -6.61 to 7.35, N = 36, 1 study) in the intermediate term.We found low-quality evidence that mixed training does not improve gross motor function (SMD 0.02, 95% CI -0.29 to 0.33, N = 163, 4 studies) or gait speed (MD 0.10 m/s, -0.07 m/s to 0.27 m/s, N = 58, 1 study) but does improve participation (MD 0.40, 95% CI 0.13 to 0.67, N = 65, 1 study) in the short-term.There is no difference between resistance training and aerobic exercise in terms of the effect on gross motor function in the short term (SMD 0.02, 95% CI -0.50 to 0.55, N = 56, 2 studies, low-quality evidence).Thirteen trials did not report adverse events, seven reported no adverse events, and nine reported non-serious adverse events. AUTHORS' CONCLUSIONS: The quality of evidence for all conclusions is low to very low. As included trials have small sample sizes, heterogeneity may be underestimated, resulting in considerable uncertainty relating to effect estimates. For children with CP, there is evidence that aerobic exercise may result in a small improvement in gross motor function, though it does not improve gait speed. There is evidence that resistance training does not improve gait speed, gross motor function, participation or quality of life among children with CP.Based on the evidence available, exercise appears to be safe for people with CP; only 55% of trials, however, reported adverse events or stated that they monitored adverse events. There is a need for large, high-quality, well-reported RCTs that assess the effectiveness of exercise in terms of activity and participation, before drawing any firm conclusions on the effectiveness of exercise for people with CP. Research is also required to determine if current exercise guidelines for the general population are effective and feasible for people with CP.

Physiotherapy for pain and disability in adults with complex regional pain syndrome (CRPS) types I and II.

BACKGROUND: Complex regional pain syndrome (CRPS) is a painful and disabling condition that usually manifests in response to trauma or surgery. When it occurs, it is associated with significant pain and disability. It is thought to arise and persist as a consequence of a maladaptive pro-inflammatory response and disturbances in sympathetically-mediated vasomotor control, together with maladaptive peripheral and central neuronal plasticity. CRPS can be classified into two types: type I (CRPS I) in which a specific nerve lesion has not been identified, and type II (CRPS II) where there is an identifiable nerve lesion. Guidelines recommend the inclusion of a variety of physiotherapy interventions as part of the multimodal treatment of people with CRPS, although their effectiveness is not known. OBJECTIVES: To determine the effectiveness of physiotherapy interventions for treating the pain and disability associated with CRPS types I and II. SEARCH METHODS: We searched the following databases from inception up to 12 February 2015: CENTRAL (the Cochrane Library), MEDLINE, EMBASE, CINAHL, PsycINFO, LILACS, PEDro, Web of Science, DARE and Health Technology Assessments, without language restrictions, for randomised controlled trials (RCTs) of physiotherapy interventions for treating pain and disability in people CRPS. We also searched additional online sources for unpublished trials and trials in progress. SELECTION CRITERIA: We included RCTs of physiotherapy interventions (including manual therapy, therapeutic exercise, electrotherapy, physiotherapist-administered education and cortically directed sensory-motor rehabilitation strategies) employed in either a stand-alone fashion or in combination, compared with placebo, no treatment, another intervention or usual care, or of varying physiotherapy interventions compared with each other in adults with CRPS I and II. Our primary outcomes of interest were patient-centred outcomes of pain intensity and functional disability. DATA COLLECTION AND ANALYSIS: Two review authors independently evaluated those studies identified through the electronic searches for eligibility and subsequently extracted all relevant data from the included RCTs. Two review authors independently performed 'Risk of bias' assessments and rated the quality of the body of evidence for the main outcomes using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. MAIN RESULTS: We included 18 RCTs (739 participants) that tested the effectiveness of a broad range of physiotherapy-based interventions. Overall, there was a paucity of high quality evidence concerning physiotherapy treatment for pain and disability in people with CRPS I. Most included trials were at 'high' risk of bias (15 trials) and the remainder were at 'unclear' risk of bias (three trials). The quality of the evidence was very low or low for all comparisons, according to the GRADE approach.We found very low quality evidence that graded motor imagery (GMI; two trials, 49 participants) may be useful for improving pain (0 to 100 VAS) (mean difference (MD) -21.00, 95% CI -31.17 to -10.83) and functional disability (11-point numerical rating scale) (MD 2.30, 95% CI 1.12 to 3.48), at long-term (six months) follow-up, in people with CRPS I compared to usual care plus physiotherapy; very low quality evidence that multimodal physiotherapy (one trial, 135 participants) may be useful for improving 'impairment' at long-term (12 month) follow-up compared to a minimal 'social work' intervention; and very low quality evidence that mirror therapy (two trials, 72 participants) provides clinically meaningful improvements in pain (0 to 10 VAS) (MD 3.4, 95% CI -4.71 to -2.09) and function (0 to 5 functional ability subscale of the Wolf Motor Function Test) (MD -2.3, 95% CI -2.88 to -1.72) at long-term (six month) follow-up in people with CRPS I post stroke compared to placebo (covered mirror).There was low to very low quality evidence that tactile discrimination training, stellate ganglion block via ultrasound and pulsed electromagnetic field therapy compared to placebo, and manual lymphatic drainage combined with and compared to either anti-inflammatories and physical therapy or exercise are not effective for treating pain in the short-term in people with CRPS I. Laser therapy may provide small clinically insignificant, short-term, improvements in pain compared to interferential current therapy in people with CRPS I.Adverse events were only rarely reported in the included trials. No trials including participants with CRPS II met the inclusion criteria of this review. AUTHORS' CONCLUSIONS: The best available data show that GMI and mirror therapy may provide clinically meaningful improvements in pain and function in people with CRPS I although the quality of the supporting evidence is very low. Evidence of the effectiveness of multimodal physiotherapy, electrotherapy and manual lymphatic drainage for treating people with CRPS types I and II is generally absent or unclear. Large scale, high quality RCTs are required to test the effectiveness of physiotherapy-based interventions for treating pain and disability of people with CRPS I and II. Implications for clinical practice and future research are considered.

Local anaesthetic sympathetic blockade for complex regional pain syndrome.

BACKGROUND: This review is an update of a previously published review in the Cochrane Database of Systematic Reviews, 2005, Issue 4 (and last updated in the Cochrane Database of Systematic Reviews, 2013 issue 8), on local anaesthetic blockade (LASB) of the sympathetic chain to treat people with complex regional pain syndrome (CRPS). OBJECTIVES: To assess the efficacy of LASB for the treatment of pain in CRPS and to evaluate the incidence of adverse effects of the procedure. SEARCH METHODS: For this update we searched the Cochrane Central Register of Controlled Trials (CENTRAL) (2015, Issue 9), MEDLINE (Ovid), EMBASE (Ovid), LILACS (Birme), conference abstracts of the World Congresses of the International Association for the Study of Pain, and various clinical trial registers up to September 2015. We also searched bibliographies from retrieved articles for additional studies. SELECTION CRITERIA: We considered randomised controlled trials (RCTs) that evaluated the effect of sympathetic blockade with local anaesthetics in children or adults with CRPS compared to placebo, no treatment, or alternative treatments. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. The outcomes of interest were reduction in pain intensity, the proportion who achieved moderate or substantial pain relief, the duration of pain relief, and the presence of adverse effects in each treatment arm. We assessed the evidence using GRADE (Grading of Recommendations Assessment, Development and Evaluation) and created a 'Summary of findings' table. MAIN RESULTS: We included an additional four studies (N = 154) in this update. For this update, we excluded studies that did not follow up patients for more than 48 hours. As a result, we excluded four studies from the previous review in this update. Overall we included 12 studies (N = 461), all of which we judged to be at high or unclear risk of bias. Overall, the quality of evidence was low to very low, downgraded due to limitations, inconsistency, imprecision, indirectness, or a combination of these.Two small studies compared LASB to placebo/sham (N = 32). They did not demonstrate significant short-term benefit for LASB for pain intensity (moderate quality evidence).One small study (N = 36) at high risk of bias compared thoracic sympathetic block with corticosteroid and local anaesthetic versus injection of the same agents into the subcutaneous space, reporting statistically significant and clinically important differences in pain intensity at one-year follow-up but not at short term follow-up (very low quality evidence).Of two studies that investigated LASB as an addition to rehabilitation treatment, the only study that reported pain outcomes demonstrated no additional benefit from LASB (very low quality evidence).Eight small randomised studies compared sympathetic blockade to various other active interventions. Most studies found no difference in pain outcomes between sympathetic block versus other active treatments (low to very low quality evidence).One small study compared ultrasound-guided LASB with non-guided LASB and found no clinically important difference in pain outcomes (very low quality evidence).Six studies reported adverse events, all with minor effects reported. AUTHORS' CONCLUSIONS: This update's results are similar to the previous versions of this systematic review, and the main conclusions are unchanged. There remains a scarcity of published evidence and a lack of high quality evidence to support or refute the use of local anaesthetic sympathetic blockade for CRPS. From the existing evidence, it is not possible to draw firm conclusions regarding the efficacy or safety of this intervention, but the limited data available do not suggest that LASB is effective for reducing pain in CRPS.

Non-invasive brain stimulation techniques for chronic pain.

BACKGROUND: This is an updated version of the original Cochrane review published in 2010, Issue 9. Non-invasive brain stimulation techniques aim to induce an electrical stimulation of the brain in an attempt to reduce chronic pain by directly altering brain activity. They include repetitive transcranial magnetic stimulation (rTMS), cranial electrotherapy stimulation (CES), transcranial direct current stimulation (tDCS) and reduced impedance non-invasive cortical electrostimulation (RINCE). OBJECTIVES: To evaluate the efficacy of non-invasive brain stimulation techniques in chronic pain. SEARCH METHODS: We searched CENTRAL (2013, Issue 6), MEDLINE, EMBASE, CINAHL, PsycINFO, LILACS and clinical trials registers. The original search for the review was run in November 2009 and searched all databases from their inception. To identify studies for inclusion in this update we searched from 2009 to July 2013. SELECTION CRITERIA: Randomised and quasi-randomised studies of rTMS, CES, tDCS or RINCE if they employed a sham stimulation control group, recruited patients over the age of 18 with pain of three months duration or more and measured pain as a primary outcome. DATA COLLECTION AND ANALYSIS: Two authors independently extracted and verified data. Where possible we entered data into meta-analyses. We excluded studies judged as being at high risk of bias from the analysis. We used the GRADE system to summarise the quality of evidence for core comparisons. MAIN RESULTS: We included an additional 23 trials (involving 773 participants randomised) in this update, making a total of 56 trials in the review (involving 1710 participants randomised). This update included a total of 30 rTMS studies, 11 CES, 14 tDCS and one study of RINCE(the original review included 19 rTMS, eight CES and six tDCS studies). We judged only three studies as being at low risk of bias across all criteria.Meta-analysis of studies of rTMS (involving 528 participants) demonstrated significant heterogeneity. Pre-specified subgroup analyses suggest that low-frequency stimulation is ineffective (low-quality evidence) and that rTMS applied to the dorsolateral prefrontal cortex is ineffective (very low-quality evidence). We found a short-term effect on pain of active high-frequency stimulation of the motor cortex in single-dose studies (low-quality evidence, standardised mean difference (SMD) 0.39 (95% confidence interval (CI) -0.27 to -0.51 P < 0.01)). This equates to a 12% (95% CI 8% to 15%) reduction in pain, which does not exceed the pre-established criteria for a minimal clinically important difference (≥ 15%). Evidence for multiple-dose studies was heterogenous but did not demonstrate a significant effect (very low-quality evidence).For CES (six studies, 270 participants) no statistically significant difference was found between active stimulation and sham (low-quality evidence).Analysis of tDCS studies (11 studies, 193 people) demonstrated significant heterogeneity and did not find a significant difference between active and sham stimulation (very low-quality evidence). Pre-specified subgroup analysis of tDCS applied to the motor cortex (n = 183) did not demonstrate a statistically significant effect and this lack of effect was consistent for subgroups of single or multiple-dose studies.One small study (n = 91) at unclear risk of bias suggested a positive effect of RINCE over sham stimulation on pain (very low-quality evidence).Non-invasive brain stimulation appears to be frequently associated with minor and transient side effects, though there were two reported incidences of seizure related to active rTMS in the included studies. AUTHORS' CONCLUSIONS: Single doses of high-frequency rTMS of the motor cortex may have small short-term effects on chronic pain. It is likely that multiple sources of bias may exaggerate this observed effect. The effects do not meet the predetermined threshold of minimal clinical significance and multiple-dose studies do not consistently demonstrate effectiveness. The available evidence suggests that low-frequency rTMS, rTMS applied to the pre-frontal cortex, CES and tDCS are not effective in the treatment of chronic pain. While the broad conclusions for rTMS and CES have not changed substantially, the addition of this new evidence and the application of the GRADE system has modified some of our interpretation and the conclusion regarding the effectiveness of tDCS has changed. We recommend that previous readers should re-read this update. There is a need for larger, rigorously designed studies, particularly of longer courses of stimulation. It is likely that future evidence may substantially impact upon the presented results.

Complex regional pain syndrome: advances in epidemiology, pathophysiology, diagnosis, and treatment.

Complex regional pain syndrome (CRPS) is a rare pain disorder that usually occurs in a limb after trauma. The features of this disorder include severe pain and sensory, autonomic, motor, and trophic abnormalities. Research from the past decade has offered new insights into CRPS epidemiology, pathophysiology, diagnosis, and treatment. Early identification of individuals at high risk of CRPS is improving, with several risk factors established and some others identified in prospective studies during the past 5 years. Better understanding of the pathophysiological mechanisms of CRPS has led to its classification as a chronic primary pain disorder, and subtypes of CRPS have been updated. Procedures for diagnosis have also been clarified. Although effective treatment of CRPS remains a challenge, evidence-based integrated management approaches provide new opportunities to improve patient care. Further advances in diagnosis and treatment of CRPS will require coordinated, international multicentre initiatives.