PEER systematic review of randomized controlled trials: Management of chronic low back pain in primary care

ObjectiveTo determine the proportion of chronic low back pain patients who achieve a clinically meaningful response from different pharmacologic and nonpharmacologic treatments.Data sourcesMEDLINE, EMBASE, Cochrane Library, and gray literature search.Study selectionPublished randomized controlled trials (RCTs) that reported a responder analysis of adults with chronic low back pain treated with any of the following 15 interventions: oral or topical nonsteroidal anti-inflammatory drugs (NSAIDs), exercise, acupuncture, spinal manipulation therapy, corticosteroid injections, acetaminophen, oral opioids, anticonvulsants, tricyclic antidepressants, serotonin-norepinephrine reuptake inhibitors (SNRIs), selective serotonin reuptake inhibitors, cannabinoids, oral muscle relaxants, or topical rubefacients.SynthesisA total of 63 RCTs were included. There was moderate certainty that exercise (risk ratio [RR] of 1.71; 95% CI 1.37 to 2.15; number needed to treat [NNT] of 7), oral NSAIDs (RR = 1.44; 95% CI 1.17 to 1.78; NNT = 6), and SNRIs (duloxetine; RR = 1.25; 95% CI 1.13 to 1.38; NNT = 10) provide clinically meaningful benefits to patients with chronic low back pain. Exercise was the only intervention with sustained benefit (up to 48 weeks). There was low certainty that spinal manipulation therapy and topical rubefacients benefit patients. The benefit of acupuncture disappeared in higher-quality, longer (> 4 weeks) trials. Very low-quality evidence demonstrated that corticosteroid injections are ineffective. Patients treated with opioids had a greater likelihood of discontinuing treatment owing to an adverse event (number needed to harm of 5) than continuing treatment to derive any clinically meaningful benefit (NNT = 16), while those treated with SNRIs (duloxetine) had a similar likelihood of continuing treatment to attain benefit (NNT = 10) as those discontinuing the medication owing to an adverse event (number need to harm of 11). One trial each of anticonvulsants and topical NSAIDs found similar benefit to that of placebo. No RCTs of acetaminophen, cannabinoids, muscle relaxants, selective serotonin reuptake inhibitors, or tricyclic antidepressants met the inclusion criteria.ConclusionExercise, oral NSAIDs, and SNRIs (duloxetine) provide a clinically meaningful reduction in pain, with exercise being the only intervention that demonstrated sustained benefit after the intervention ended. Future high-quality trials that report responder analyses are required to provide a better understanding of the benefits and harms of interventions for patients with chronic low back pain.     

PEER umbrella systematic review of systematic reviews: Management of osteoarthritis in primary care

ObjectiveTo determine how many patients with chronic osteoarthritis pain respond to various non-surgical treatments.Data sourcesPubMed and the Cochrane Library.Study selection Published systematic reviews of randomized controlled trials (RCTs) that included meta-analysis of responder outcomes for at least 1 of the following interventions were included: acetaminophen, oral nonsteroidal anti-inflammatory drugs (NSAIDs), topical NSAIDs, serotonin-norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants, cannabinoids, counseling, exercise, platelet-rich plasma, viscosupplementation, glucosamine, chondroitin, intra-articular corticosteroids, rubefacients, or opioids.Synthesis In total, 235 systematic reviews were included. Owing to limited reporting of responder meta-analyses, a post hoc decision was made to evaluate individual RCTs with responder analysis within the included systematic reviews. New meta-analyses were performed where possible. A total of 155 RCTs were included. Interventions that led to more patients attaining meaningful pain relief compared with control included exercise (risk ratio [RR] of 2.36; 95% CI 1.79 to 3.12), intra-articular corticosteroids (RR = 1.74; 95% CI 1.15 to 2.62), SNRIs (RR = 1.53; 95% CI 1.25 to 1.87), oral NSAIDs (RR = 1.44; 95% CI 1.36 to 1.52), glucosamine (RR = 1.33; 95% CI 1.02 to 1.74), topical NSAIDs (RR = 1.27; 95% CI 1.16 to 1.38), chondroitin (RR = 1.26; 95% CI 1.13 to 1.41), viscosupplementation (RR = 1.22; 95% CI 1.12 to 1.33), and opioids (RR = 1.16; 95% CI 1.02 to 1.32). Preplanned subgroup analysis demonstrated no effect with glucosamine, chondroitin, or viscosupplementation in studies that were only publicly funded. When trials longer than 4 weeks were analyzed, the benefits of opioids were not statistically significant.ConclusionInterventions that provide meaningful relief for chronic osteoarthritis pain might include exercise, intra-articular corticosteroids, SNRIs, oral and topical NSAIDs, glucosamine, chondroitin, viscosupplementation, and opioids. However, funding of studies and length of treatment are important considerations in interpreting these data.     

Manual therapies for primary chronic headaches: a systematic review of randomized controlled trials

This is to our knowledge the first systematic review regarding the efficacy of manual therapy randomized clinical trials (RCT) for primary chronic headaches. A comprehensive English literature search on CINHAL, Cochrane, Medline, Ovid and PubMed identified 6 RCTs all investigating chronic tension-type headache (CTTH). One study applied massage therapy and five studies applied physiotherapy. Four studies were considered to be of good methodological quality by the PEDro scale. All studies were pragmatic or used no treatment as a control group, and only two studies avoided co-intervention, which may lead to possible bias and makes interpretation of the results more difficult. The RCTs suggest that massage and physiotherapy are effective treatment options in the management of CTTH. One of the RCTs showed that physiotherapy reduced headache frequency and intensity statistical significant better than usual care by the general practitioner. The efficacy of physiotherapy at post-treatment and at 6 months follow-up equals the efficacy of tricyclic antidepressants. Effect size of physiotherapy was up to 0.62. Future manual therapy RCTs are requested addressing the efficacy in chronic migraine with and without medication overuse. Future RCTs on headache should adhere to the International Headache Society’s guidelines for clinical trials, i.e. frequency as primary end-point, while duration and intensity should be secondary end-point, avoid co-intervention, includes sufficient sample size and follow-up period for at least 6 months.     

How is radiating leg pain defined in randomized controlled trials of conservative treatments in primary care? A systematic review

Many terms exist to describe radiating leg pain or symptoms associated with back pain (e.g., sciatica or radiculopathy) and it appears that these terms are used inconsistently. We examined the terms used to describe, and the eligibility criteria used to define, radiating leg pain in randomized controlled trials of conservative treatments, and evaluated how the eligibility criteria compared to an international pain taxonomy. Eligible studies were identified from two systematic reviews and an updated search of their search strategy. Studies were included if they recruited adults with radiating leg pain associated with back pain. Two independent reviewers screened the studies and extracted data. Studies were grouped according to the terms used to describe radiating leg pain. Thirty‐one of the seventy‐seven included studies used multiple terms to describe radiating leg pain; the most commonly used terms were sciatica (60 studies) and disc herniation (19 studies). Most studies that used the term sciatica included pain distribution in the eligibility criteria, but studies were inconsistent in including signs (e.g., neurological deficits) and imaging findings. Similarly, studies that used other terms to describe radiating leg pain used inconsistent eligibility criteria between studies and to the pain taxonomy, except that positive imaging findings were required for almost all studies that used disc herniation to describe radiating leg pain. In view of the varying terms to describe, and eligibility criteria to define, radiating leg pain, consensus needs to be reached for each of communication and comparison between studies.     

The efficacy of traction for back pain: a systematic review of randomized controlled trials

OBJECTIVE: To assess the efficacy of traction for patients with low back pain (LBP) with or without radiating pain, taking into account the clinical technique or parameters used. DATA SOURCES: A computer-aided search of MEDLINE, CINAHL, AMED, and the Cochrane Collaboration was conducted for randomized controlled trials (RCTs) in the English language, from 1966 to December 2001. STUDY SELECTION: RCTs were included if: participants were over the age of 18 years, with LBP with or without radiating pain; the intervention group received traction as the main or sole treatment; the comparison group received sham traction or another conservative treatment; and the study used 1 of 4 primary outcome measures. DATA EXTRACTION: The study was conducted in 2 strands. Strand 1 assessed methodologic quality using a specific criteria list recommended by the Cochrane Back Review Group. The strength of the evidence was then rated using the Agency for Health Care Policy and Research system. Strand 2 applied further inclusion criteria based on recommended clinical parameters. One reviewer conducted the selection and data extraction. DATA SYNTHESIS: Strand 1: 1 study scored 9 points (maximum score, 10 points); the other 12 scored between 0 and 3 points, indicating that most were of poor quality. Nine studies reported negative findings, but only 1 study was of a high quality. Three studies reported positive findings and 1 study was inconclusive. Strand 2: only 4 trials having low methodologic quality were included, 2 of which reported negative findings, and 2 positive findings. CONCLUSION: The evidence for the use of traction in LBP remains inconclusive because of the continued lack of methodologic rigor and the limited application of clinical parameters as used in clinical practice. Further trials, which give attention to these areas, are needed before any firm conclusions and recommendations may be made.     

Efficacy of mu-opioid agonists in the treatment of evoked neuropathic pain: Systematic review of randomized controlled trials

Several reviews of randomized controlled trials (RCTs) have shown the efficacy of mu-opioids in reducing spontaneous neuropathic pain (NP). However, relatively little is known about their specific efficacy for evoked pain, which is a significant problem for many patients with NP. The present systematic review assesses the efficacy of opioid agonists for the treatment of evoked NP based upon published RCTs. We searched articles in any language using the MEDLINE database (1966 to December 2004), the Cochrane Central Register of Controlled Trials (4th quarter, 2004) and the reference lists of retrieved papers, employing search terms for RCTs, opioids and NP. Only RCTs in which opioid agonists were given to treat NP of any etiology, and evoked pain was assessed were included. Data were extracted by two independent investigators. Nine articles met inclusion criteria and were classified as short-term (less than 24h; n=7) or intermediate-term trials (4 weeks; n=2). Although the scarcity of retrieved data precluded formal meta-analysis of short-term trials, we found that the intensity of dynamic mechanical allodynia was significantly attenuated by opioids relative to placebo in all studies. In contrast, no consistent effects on the magnitude of static allodynia, the threshold for mechanical allodynia or the threshold or magnitude of heat allodynia were found. The threshold and magnitude of cold-induced allodynia generally responded positively to opioid treatments in patients with peripheral pain syndromes, but not central pain syndromes. Evoked pain was studied in only two intermediate-term trials, in both of which oxycodone was significantly superior to placebo. The results of the two trials were combinable for a meta-analysis that showed an overall 24 points difference in endpoint pain intensities between patients given opioids and those treated with placebo (95% CI -33 to -15; p<0.00001). In conclusion: short-term studies show that opioids can reduce the intensity of dynamic mechanical allodynia and perhaps of cold allodynia in peripheral NP. Insufficient evidence precludes drawing conclusions regarding the effect of opioids on other forms of evoked NP. A meta-analysis of intermediate-term studies demonstrates the efficacy of opioids over placebo for evoked NP. These findings are clinically relevant because dynamic mechanical allodynia and cold allodynia are the most prevalent types of evoked pain in NP.     

Gabapentin for neuropathic pain: systematic review of controlled and uncontrolled literature.

OBJECTIVE: To assess the efficacy/effectiveness and side effects of gabapentin for the treatment of neuropathic pain. DESIGN: Systematic review of the literature. METHODS: Extensive search of several electronic databases located both controlled and uncontrolled studies. Efficacy was assessed through meta-analysis of randomized controlled trials (RCTs), whereas the effectiveness of gabapentin in uncontrolled studies was assessed via a novel system of dichotomous classification of "bad" versus "good" results. FINDINGS: Thirty-five papers involving 727 patients with multiple neuropathic pain conditions met the inclusion criteria. The meta-analysis of the 2 high-quality, placebo-controlled RCTs showed positive effect of gabapentin in diabetic neuropathy and post-herpetic neuralgia. The addition of 2 low-quality, placebo-controlled RCTs did not alter the magnitude or direction of observed effect. The uncontrolled studies demonstrated positive effect on pain in different neuropathic syndromes, as well as benefit on different types of neuropathic pain; highest dose administered and rate-of-dose escalation showed wide variability between prescribers. Fewer and less severe side effects were reported in the uncontrolled studies. CONCLUSIONS: Gabapentin seems to be effective in multiple painful neuropathic conditions. The variable prescribing patterns of the uncontrolled studies raise the suspicion that effectiveness may be reduced if one limits administration of the drug to very low doses, whereas rapid dose escalation may be associated with increased central nervous system side effects. Well-designed controlled trials may provide insight into differential symptom sensitivity to the drug.     

Gabapentin and postoperative pain--a systematic review of randomized controlled trials

The objective of this systematic review was to evaluate the efficacy and tolerability of perioperative gabapentin administration for the control of acute postoperative pain. We searched Medline (1966-2006), the Cochrane Library (2006), Scopus, CINAHL and bibliographies from clinical trials and review articles. We included randomized controlled trials (RCTs) comparing gabapentin with inactive controls in surgical patients. Sixteen valid RCTs were included. Weighted mean difference (WMD) for postoperative pain intensity (0-100 mm visual analogue scale) was -16.55 mm at 6 h and -10.87 mm at 24 h for treatment with a single preoperative dose of gabapentin 1200 mg. Cumulative opioid consumption at 24 h was also significantly decreased with gabapentin (WMD, -27.90 mg). When gabapentin was administered at doses less than 1200 mg, pain intensity was also lower at 6 h (WMD, -22.43 mm) and 24 h (WMD, -13.18 mm). Cumulative 24 h opioid consumption was also lower (WMD, -7.25 mg). Gabapentin was associated with an increased risk of sedation (Peto OR 3.86; 95% CI 2.50-5.94) but less opioid-related side effects such as vomiting (Peto OR 0.58; 95% CI 0.39-0.86) and pruritus (Peto OR 0.27; 95% CI 0.10-0.74). In conclusion, gabapentin has an analgesic and opioid-sparing effect in acute postoperative pain management when used in conjunction with opioids.     

Acupuncture for recurrent headaches: a systematic review of randomized controlled trials

Objective : To assess whether there is evidence that acupuncture is effective in the treatment of recurrent headaches. Design :Systematic review. Study selection :Randomized or quasi-randomized clinical trials comparing acupuncture with any type of control intervention for the treatment of recurrent headaches. Data sources : Electronic databases (Medline, Embase, Cochrane Field for Complementary Medicine, Cochrane Controlled Trials Register), personal communications and bibliographies. Data collection and analysis : Information on patients, interventions, methods, and results were extracted by at least two independent reviewers using a pretested form. A pooled estimate of the responder rate ratio (responder rate in treatment group/responder rate in control group) was calculated as a crude indicator of trial results as meta-analysis of more specific outcome data was impossible due to heterogeneity and insufficient reporting. Results :Twenty-two trials, including a total of 1042 patients (median 36, range 10–150), met the inclusion criteria. Fifteen trials were in migraine patients, six in tension-headache patients, and in one trial patients with various headaches were included. The majority of the 14 trials comparing true and sham acupuncture showed at least a trend in favor of true acupuncture. The pooled responder rate ratio was 1.53 (95% confidence interval 1.11 to 2.11). The eight trials comparing acupuncture and other treatment forms had contradictory results. Conclusions :Overall, the existing evidence suggests that acupuncture has a role in the treatment of recurrent headaches. However, the quality and amount of evidence is not fully convincing. There is urgent need for well-planned, large-scale studies to assess effectiveness and efficiency of acupuncture under real life conditions.