Yoga for chronic non-specific low back pain.

BACKGROUND: Non-specific low back pain is a common, potentially disabling condition usually treated with self-care and non-prescription medication. For chronic low back pain, current guidelines recommend exercise therapy. Yoga is a mind-body exercise sometimes used for non-specific low back pain. OBJECTIVES: To evaluate the benefits and harms of yoga for treating chronic non-specific low back pain in adults compared to sham yoga, no specific treatment, a minimal intervention (e.g. education), or another active treatment, focusing on pain, function, quality of life, and adverse events. SEARCH METHODS: We used standard, extensive Cochrane search methods. The latest search date was 31 August 2021 without language or publication status restrictions. SELECTION CRITERIA: We included randomized controlled trials of yoga compared to sham yoga, no intervention, any other intervention and yoga added to other therapies. DATA COLLECTION AND ANALYSIS: We followed standard Cochrane methods. Our major outcomes were 1. back-specific function, 2. pain, 3. clinical improvement, 4. mental and physical quality of life, 5. depression, and 6. ADVERSE EVENTS: Our minor outcome was 1. work disability. We used GRADE to assess certainty of evidence for the major outcomes. MAIN RESULTS: We included 21 trials (2223 participants) from the USA, India, the UK, Croatia, Germany, Sweden, and Turkey. Participants were recruited from both clinical and community settings. Most were women in their 40s or 50s. Most trials used iyengar, hatha, or viniyoga yoga. Trials compared yoga to a non-exercise control including waiting list, usual care, or education (10 trials); back-focused exercise such as physical therapy (five trials); both exercise and non-exercise controls (four trials); both non-exercise and another mind-body exercise (qigong) (one trial); and yoga plus exercise to exercise alone (one trial). One trial comparing yoga to exercise was an intensive residential one-week program, and we analyzed this trial separately. All trials were at high risk of performance and detection bias because participants and providers were not blinded to treatment, and outcomes were self-assessed. We found no trials comparing yoga to sham yoga. Low-certainty evidence from 11 trials showed that there may be a small clinically unimportant improvement in back-specific function with yoga (mean difference [MD] -1.69, 95% confidence interval [CI] -2.73 to -0.65 on the 0- to 24-point Roland-Morris Disability Questionnaire [RMDQ], lower = better, minimal clinically important difference [MCID] 5 points; 1155 participants) and moderate-certainty evidence from nine trials showed a clinically unimportant improvement in pain (MD -4.53, 95% CI -6.61 to -2.46 on a 0 to 100 scale, 0 no pain, MCID 15 points; 946 participants) compared to no exercise at three months. Low-certainty evidence from four trials showed that there may be a clinical improvement with yoga (risk ratio [RR] 2.33, 95% CI 1.46 to 3.71; assessed as participant rating that back pain was improved or resolved; 353 participants). Moderate-certainty evidence from six trials showed that there is probably a small improvement in physical and mental quality of life (physical: MD 1.80, 95% CI 0.27 to 3.33 on the 36-item Short Form [SF-36] physical health scale, higher = better; mental: MD 2.38, 95% CI 0.60 to 4.17 on the SF-36 mental health scale, higher = better; both 686 participants). Low-certainty evidence from three trials showed little to no improvement in depression (MD -1.25, 95% CI -2.90 to 0.46 on the Beck Depression Inventory, lower = better; 241 participants). There was low-certainty evidence from eight trials that yoga increased the risk of adverse events, primarily increased back pain, at six to 12 months (RR 4.76, 95% CI 2.08 to 10.89; 43/1000 with yoga and 9/1000 with no exercise; 1037 participants). For yoga compared to back-focused exercise controls (8 trials, 912 participants) at three months, we found moderate-certainty evidence from four trials for little or no difference in back-specific function (MD -0.38, 95% CI -1.33 to 0.62 on the RMDQ, lower = better; 575 participants) and very low-certainty evidence from two trials for little or no difference in pain (MD 2.68, 95% CI -2.01 to 7.36 on a 0 to 100 scale, lower = better; 326 participants). We found very low-certainty evidence from three trials for no difference in clinical improvement assessed as participant rating that back pain was improved or resolved (RR 0.97, 95% CI 0.72 to 1.31; 433 participants) and very low-certainty evidence from one trial for little or no difference in physical and mental quality of life (physical: MD 1.30, 95% CI -0.95 to 3.55 on the SF-36 physical health scale, higher = better; mental: MD 1.90, 95% CI -1.17 to 4.97 on the SF-36 mental health scale, higher = better; both 237 participants). No studies reported depression. Low-certainty evidence from five trials showed that there was little or no difference between yoga and exercise in the risk of adverse events at six to 12 months (RR 0.93, 95% CI 0.56 to 1.53; 84/1000 with yoga and 91/1000 with non-yoga exercise; 640 participants). AUTHORS' CONCLUSIONS: There is low- to moderate-certainty evidence that yoga compared to no exercise results in small and clinically unimportant improvements in back-related function and pain. There is probably little or no difference between yoga and other back-related exercise for back-related function at three months, although it remains uncertain whether there is any difference between yoga and other exercise for pain and quality of life. Yoga is associated with more adverse events than no exercise, but may have the same risk of adverse events as other exercise. In light of these results, decisions to use yoga instead of no exercise or another exercise may depend on availability, cost, and participant or provider preference. Since all studies were unblinded and at high risk of performance and detection bias, it is unlikely that blinded comparisons would find a clinically important benefit.

The Choice Point Model of Acceptance and Commitment Therapy With Inpatient Substance Use and Co-occurring Populations: A Pilot Study.

Objectives: Acceptance and Commitment Therapy (ACT) is an empirically supported treatment which aims to enhance self-acceptance and a commitment to core values. The present study examined the effectiveness of the Choice Point model of ACT in a residential substance use disorder (SUD) setting. Choice Point is a contemporary approach to ACT and targets transdiagnostic processes. Methods: This uncontrolled quasi-experimental design assessed 47 participants taking part in Choice Point for Substances (CHOPS) in order to investigate its influence on psychological inflexibility, values-based action, and self-compassion over time. The study additionally assessed for sleeper effects and associations between transdiagnostic processes and warning signs of relapse. Results: Findings demonstrated a decrease in psychological inflexibility and increases in values-based action and self-compassion over time. Gains were maintained at follow-up, and sleeper effects were observed for psychological inflexibility and mindfulness. Correlational analysis suggested that all transdiagnostic processes were related to warning signs of relapse at follow-up. Conclusion: These results provide preliminary evidence for the feasibility, acceptability, and effectiveness of CHOPS for SUD. Observed sleeper effects in psychological inflexibility and mindfulness indicate that CHOPS may provide longer-term benefits critical to a population where relapse is common. While encouraging, these findings should be interpreted with caution. Future research should utilize comparison groups when investigating CHOPS.

Natural Products for the Treatment of Autoimmune Arthritis: Their Mechanisms of Action, Targeted Delivery, and Interplay with the Host Microbiome.

Rheumatoid arthritis (RA) is a chronic, debilitating illness characterized by painful swelling of the joints, inflammation of the synovial lining of the joints, and damage to cartilage and bone. Several anti-inflammatory and disease-modifying drugs are available for RA therapy. However, the prolonged use of these drugs is associated with severe side effects. Furthermore, these drugs are effective only in a proportion of RA patients. Hence, there is a need to search for new therapeutic agents that are effective yet safe. Interestingly, a variety of herbs and other natural products offer a vast resource for such anti-arthritic agents. We discuss here the basic features of RA pathogenesis; the commonly used animal models of RA; the mainstream drugs used for RA; the use of well-characterized natural products possessing anti-arthritic activity; the application of nanoparticles for efficient delivery of such products; and the interplay between dietary products and the host microbiome for maintenance of health and disease induction. We believe that with several advances in the past decade in the characterization and functional studies of natural products, the stage is set for widespread clinical testing and/or use of these products for the treatment of RA and other diseases.

Acupuncture for hip osteoarthritis.

BACKGROUND: Hip osteoarthritis (OA) is a major cause of pain and functional limitation. Few hip OA treatments have been evaluated for safety and effectiveness. Acupuncture is a traditional Chinese medical therapy which aims to treat disease by inserting very thin needles at specific points on the body. OBJECTIVES: To assess the benefits and harms of acupuncture in patients with hip OA. SEARCH METHODS: We searched Cochrane CENTRAL, MEDLINE, and Embase all through March 2018. SELECTION CRITERIA: We included randomized controlled trials (RCTs) that compared acupuncture with sham acupuncture, another active treatment, or no specific treatment; and RCTs that evaluated acupuncture as an addition to another treatment. Major outcomes were pain and function at the short term (i.e. < 3 months after randomization) and adverse events. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. MAIN RESULTS: Six RCTs with 413 participants were included. Four RCTs included only people with OA of the hip, and two included a mix of people with OA of the hip and knee. All RCTs included primarily older participants, with a mean age range from 61 to 67 years, and a mean duration of hip OA pain from two to eight years. Approximately two-thirds of participants were women. Two RCTs compared acupuncture versus sham acupuncture; the other four RCTs were not blinded. All results were evaluated at short term (i.e. four to nine weeks after randomization).In the two RCTs that compared acupuncture to sham acupuncture, the sham acupuncture control interventions were judged believable, but each sham acupuncture intervention was also judged to have a risk of weak acupuncture-specific effects, due to placement of non-penetrating needles at the correct acupuncture points in one RCT, and the use of penetrating needles not inserted at the correct points in the other RCT. For these two sham-controlled RCTs, the risk of bias was low for all outcomes.The combined analysis of two sham-controlled RCTs gave moderate quality evidence of little or no effect in reduction in pain for acupuncture relative to sham acupuncture. Due to the small sample sizes in the studies, the confidence interval includes both the possibility of moderate benefit and the possibility of no effect of acupuncture (120 participants; Standardized Mean Difference (SMD) -0.13, (95% Confidence Interval (CI) -0.49 to 0.22); 2.1 points greater improvement with acupuncture compared to sham acupuncture on 100 point scale (i.e., absolute percent change -2.1% (95% CI -7.9% to 3.6%)); relative percent change -4.1% (95% CI -15.6% to 7.0%)). Estimates of effect were similar for function (120 participants; SMD -0.15, (95% CI -0.51 to 0.21)). No pooled estimate, representative of the two sham-controlled RCTs, could be calculated or reported for the quality of life outcome.The four other RCTs were unblinded comparative effectiveness RCTs, which compared (additional) acupuncture to four different active control treatments.There was low quality evidence that addition of acupuncture to the routine primary care that RCT participants were receiving from their physicians was associated with statistically significant and clinically relevant benefits, compared to the routine primary physician care alone, in pain (1 RCT; 137 participants; mean percent difference -22.9% (95% CI -29.2% to -16.6%); relative percent difference -46.5% (95% CI -59.3% to -33.7%)) and function (mean percent difference -19.0% (95% CI -24.41 to -13.59); relative percent difference -38.6% (95% CI -49.6% to -27.6%)). There was no statistically significant difference for mental quality of life and acupuncture showed a small, significant benefit for physical quality of life.The effects of acupuncture compared with either advice plus exercise or NSAIDs are uncertain.We are also uncertain whether acupuncture plus patient education improves pain, function, and quality of life, when compared to patient education alone.In general, the overall quality of the evidence for the four comparative effectiveness RCTs was low to very low, mainly due to the potential for biased reporting of patient-assessed outcomes due to lack of blinding and sparse data.Information on safety was reported in four RCTs. Two RCTs reported minor side effects of acupuncture, which were primarily minor bruising, bleeding, or pain at needle insertion sites. Four RCTs reported on adverse events, and none reported any serious adverse events attributed to acupuncture. AUTHORS' CONCLUSIONS: Acupuncture probably has little or no effect in reducing pain or improving function relative to sham acupuncture in people with hip osteoarthritis. Due to the small sample size in the studies, the confidence intervals include both the possibility of moderate benefits and the possibility of no effect of acupuncture. One unblinded trial found that acupuncture as an addition to routine primary physician care was associated with benefits on pain and function. However, these reported benefits are likely due at least partially to RCT participants' greater expectations of benefit from acupuncture. Possible side effects associated with acupuncture treatment were minor.

A Summer Health Program for African-American High School Students in Baltimore, Maryland: Community Partnership for Integrative Health.

CONTEXT: Physical inactivity, poor nutrition, and chronic stress threaten the health of African-American youth in urban environments. Conditions often worsen in summer with diminished access to healthy foods and safe venues for physical activity. OBJECTIVE: A public-private partnership was formed to develop and evaluate an integrative health intervention entitled "Mission Thrive Summer" (MTS). METHODS: The MTS setting was an urban farm and adjacent school in a low-income community in Baltimore, Maryland. The intervention included farming, nutrition education, cooking, physical activity, yoga, mindfulness, and employment. Mixed-methods outcomes evaluation was conducted. Quantitative measures included accelerometry and self-reported health behaviors, using the Child and Adolescent Mindfulness Measure, Perceived Stress Scale, Physical Activity Questionnaire for Adolescents (PAQA), CDC Youth Risk Behavior Survey, and Block Kids Food Screener (BKFS). Outcomes were compared pre- and post-intervention using paired t-tests. Qualitative evaluation was based on participant and parent interviews. PARTICIPANTS: In total, 36 African-American 9th- and 10th-grade students joined MTS (17 in 2013, 26 in 2014, and 7 participating both years). RESULTS: In total, 88% of participants completed MTS. Accelerometry revealed that participants took 7158 steps and burned 544 calories per day during MTS. Participants experienced statistically significant improvements in self-reported physical activity (PAQA) and dietary habits (BKFS). Surveys did not detect changes in stress or mindfulness (P > .05). Qualitative data demonstrated new knowledge and skills, increased self-efficacy, health behavior change, and program enjoyment. CONCLUSIONS: MTS was feasible among African-American high school students in Baltimore. Mixed-methods outcomes evaluation provided preliminary evidence of health behavior change during the summer and at follow-up.

Yoga treatment for chronic non-specific low back pain.

BACKGROUND: Non-specific low back pain is a common, potentially disabling condition usually treated with self-care and non-prescription medication. For chronic low back pain, current guidelines state that exercise therapy may be beneficial. Yoga is a mind-body exercise sometimes used for non-specific low back pain. OBJECTIVES: To assess the effects of yoga for treating chronic non-specific low back pain, compared to no specific treatment, a minimal intervention (e.g. education), or another active treatment, with a focus on pain, function, and adverse events. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, five other databases and four trials registers to 11 March 2016 without restriction of language or publication status. We screened reference lists and contacted experts in the field to identify additional studies. SELECTION CRITERIA: We included randomized controlled trials of yoga treatment in people with chronic non-specific low back pain. We included studies comparing yoga to any other intervention or to no intervention. We also included studies comparing yoga as an adjunct to other therapies, versus those other therapies alone. DATA COLLECTION AND ANALYSIS: Two authors independently screened and selected studies, extracted outcome data, and assessed risk of bias. We contacted study authors to obtain missing or unclear information. We evaluated the overall certainty of evidence using the GRADE approach. MAIN RESULTS: We included 12 trials (1080 participants) carried out in the USA (seven trials), India (three trials), and the UK (two trials). Studies were unfunded (one trial), funded by a yoga institution (one trial), funded by non-profit or government sources (seven trials), or did not report on funding (three trials). Most trials used Iyengar, Hatha, or Viniyoga forms of yoga. The trials compared yoga to no intervention or a non-exercise intervention such as education (seven trials), an exercise intervention (three trials), or both exercise and non-exercise interventions (two trials). All trials were at high risk of performance and detection bias because participants and providers were not blinded to treatment assignment, and outcomes were self-assessed. Therefore, we downgraded all outcomes to 'moderate' certainty evidence because of risk of bias, and when there was additional serious risk of bias, unexplained heterogeneity between studies, or the analyses were imprecise, we downgraded the certainty of the evidence further.For yoga compared to non-exercise controls (9 trials; 810 participants), there was low-certainty evidence that yoga produced small to moderate improvements in back-related function at three to four months (standardized mean difference (SMD) -0.40, 95% confidence interval (CI) -0.66 to -0.14; corresponding to a change in the Roland-Morris Disability Questionnaire of mean difference (MD) -2.18, 95% -3.60 to -0.76), moderate-certainty evidence for small to moderate improvements at six months (SMD -0.44, 95% CI -0.66 to -0.22; corresponding to a change in the Roland-Morris Disability Questionnaire of MD -2.15, 95% -3.23 to -1.08), and low-certainty evidence for small improvements at 12 months (SMD -0.26, 95% CI -0.46 to -0.05; corresponding to a change in the Roland-Morris Disability Questionnaire of MD -1.36, 95% -2.41 to -0.26). On a 0-100 scale there was very low- to moderate-certainty evidence that yoga was slightly better for pain at three to four months (MD -4.55, 95% CI -7.04 to -2.06), six months (MD -7.81, 95% CI -13.37 to -2.25), and 12 months (MD -5.40, 95% CI -14.50 to -3.70), however we pre-defined clinically significant changes in pain as 15 points or greater and this threshold was not met. Based on information from six trials, there was moderate-certainty evidence that the risk of adverse events, primarily increased back pain, was higher in yoga than in non-exercise controls (risk difference (RD) 5%, 95% CI 2% to 8%).For yoga compared to non-yoga exercise controls (4 trials; 394 participants), there was very-low-certainty evidence for little or no difference in back-related function at three months (SMD -0.22, 95% CI -0.65 to 0.20; corresponding to a change in the Roland-Morris Disability Questionnaire of MD -0.99, 95% -2.87 to 0.90) and six months (SMD -0.20, 95% CI -0.59 to 0.19; corresponding to a change in the Roland-Morris Disability Questionnaire of MD -0.90, 95% -2.61 to 0.81), and no information on back-related function after six months. There was very low-certainty evidence for lower pain on a 0-100 scale at seven months (MD -20.40, 95% CI -25.48 to -15.32), and no information on pain at three months or after seven months. Based on information from three trials, there was low-certainty evidence for no difference in the risk of adverse events between yoga and non-yoga exercise controls (RD 1%, 95% CI -4% to 6%).For yoga added to exercise compared to exercise alone (1 trial; 24 participants), there was very-low-certainty evidence for little or no difference at 10 weeks in back-related function (SMD -0.60, 95% CI -1.42 to 0.22; corresponding to a change in the Oswestry Disability Index of MD -17.05, 95% -22.96 to 11.14) or pain on a 0-100 scale (MD -3.20, 95% CI -13.76 to 7.36). There was no information on outcomes at other time points. There was no information on adverse events.Studies provided limited evidence on risk of clinical improvement, measures of quality of life, and depression. There was no evidence on work-related disability. AUTHORS' CONCLUSIONS: There is low- to moderate-certainty evidence that yoga compared to non-exercise controls results in small to moderate improvements in back-related function at three and six months. Yoga may also be slightly more effective for pain at three and six months, however the effect size did not meet predefined levels of minimum clinical importance. It is uncertain whether there is any difference between yoga and other exercise for back-related function or pain, or whether yoga added to exercise is more effective than exercise alone. Yoga is associated with more adverse events than non-exercise controls, but may have the same risk of adverse events as other back-focused exercise. Yoga is not associated with serious adverse events. There is a need for additional high-quality research to improve confidence in estimates of effect, to evaluate long-term outcomes, and to provide additional information on comparisons between yoga and other exercise for chronic non-specific low back pain.

Herbal Medicine for Low Back Pain: A Cochrane Review.

STUDY DESIGN: Systematic review of randomized controlled trials (RCTs). OBJECTIVES: To determine the effectiveness of herbal medicine for nonspecific low back pain (LBP). SUMMARY OF BACKGROUND DATA: Many people with chronic LBP use complementary and alternative medicine (CAM), visit CAM practitioners, or both. Several herbal medicines have been purported for use in treating people with LBP. This is an update of a Cochrane Review first published in 2006. METHODS: We searched numerous electronic databases up to September 2014; checked reference lists in review articles, guidelines and retrieved trials; and personally contacted individuals with expertise in this area. We included RCTs examining adults (over 18 years of age) suffering from acute, sub-acute, or chronic nonspecific LBP. The interventions were herbal medicines that we defined as plants used for medicinal purposes in any form. Primary outcome measures were pain and function. Two review authors assessed risk of bias, GRADE criteria (GRADE 2004), and CONSORT compliance and a random subset were compared with assessments by a third individual. Two review authors assessed clinical relevance and resolved any disagreements by consensus. RESULTS: Fourteen RCTs (2050 participants) were included. Capsicum frutescens (cayenne) reduces pain more than placebo. Although Harpagophytum procumbens (devil's claw), Salix alba (white willow bark), Symphytum officinale L. (comfrey), Solidago chilensis (Brazilian arnica), and lavender essential oil also seem to reduce pain more than placebo, evidence for these substances was of moderate quality at best. No significant adverse events were noted within the included trials. CONCLUSIONS: Additional well-designed large trials are needed to test these herbal medicines against standard treatments. In general, the completeness of reporting in these trials was poor. Trialists should refer to the CONSORT statement extension for reporting trials of herbal medicine interventions. LEVEL OF EVIDENCE: N/A.

Herbal medicine for low-back pain.

BACKGROUND: Low-back pain (LBP) is a common condition and imposes a substantial economic burden upon people living in industrialized societies. A large proportion of people with chronic LBP use complementary and alternative medicine (CAM), visit CAM practitioners, or both. Several herbal medicines have been purported for use in treating people with LBP. This is an update of a Cochrane Review first published in 2006. OBJECTIVES: To determine the effectiveness of herbal medicine for non-specific LBP. SEARCH METHODS: We searched the following electronic databases up to September 2014: MEDLINE, EMBASE, CENTRAL, CINAHL, Clinical Trials.gov, World Health Organization International Clinical Trials Registry Portal and PubMed; checked reference lists in review articles, guidelines and retrieved trials; and personally contacted individuals with expertise in this area. SELECTION CRITERIA: We included randomized controlled trials (RCTs) examining adults (over 18 years of age) suffering from acute, sub-acute, or chronic non-specific LBP. The interventions were herbal medicines which we defined as plants used for medicinal purposes in any form. Primary outcome measures were pain and function. DATA COLLECTION AND ANALYSIS: A library scientist with the Cochrane Back Review Group conducted the database searches. One review author contacted content experts and acquired relevant citations. We downloaded full references and abstracts of the identified studies and retrieved a hard copy of each study for final inclusion decisions. Two review authors assessed risk of bias, GRADE criteria (GRADE 2004), and CONSORT compliance and a random subset were compared to assessments by a third individual. Two review authors assessed clinical relevance and resolved any disagreements by consensus. MAIN RESULTS: We included 14 RCTs (2050 participants) in this review. One trial on Solidago chilensis M. (Brazilian arnica) (20 participants) found very low quality evidence of reduction in perception of pain and improved flexibility with application of Brazilian arnica-containing gel twice daily as compared to placebo gel. Capsicum frutescens cream or plaster probably produces more favourable results than placebo in people with chronic LBP (three trials, 755 participants, moderate quality evidence). Based on current evidence, it is not clear whether topical capsicum cream is more beneficial for treating people with acute LBP compared to placebo (one trial, 40 participants, low quality evidence). Another trial found equivalence of C. frutescens cream to a homeopathic ointment (one trial, 161 participants, very low quality evidence). Daily doses of Harpagophytum procumbens (devil's claw), standardized to 50 mg or 100 mg harpagoside, may be better than placebo for short-term improvements in pain and may reduce use of rescue medication (two trials, 315 participants, low quality evidence). Another H. procumbens trial demonstrated relative equivalence to 12.5 mg per day of rofecoxib (Vioxx®) but was of very low quality (one trial, 88 participants, very low quality). Daily doses of Salix alba (white willow bark), standardized to 120 mg or 240 mg salicin, are probably better than placebo for short-term improvements in pain and rescue medication (two trials, 261 participants, moderate quality evidence). An additional trial demonstrated relative equivalence to 12.5 mg per day of rofecoxib (one trial, 228 participants) but was graded as very low quality evidence. S. alba minimally affected platelet thrombosis versus a cardioprotective dose of acetylsalicylate (one trial, 51 participants). One trial (120 participants) examining Symphytum officinale L. (comfrey root extract) found low quality evidence that a Kytta-Salbe comfrey extract ointment is better than placebo ointment for short-term improvements in pain as assessed by VAS. Aromatic lavender essential oil applied by acupressure may reduce subjective pain intensity and improve lateral spine flexion and walking time compared to untreated participants (one trial, 61 participants,very low quality evidence). No significant adverse events were noted within the included trials. AUTHORS' CONCLUSIONS: C. frutescens (Cayenne) reduces pain more than placebo. Although H. procumbens, S. alba, S. officinale L., S. chilensis, and lavender essential oil also seem to reduce pain more than placebo, evidence for these substances was of moderate quality at best. Additional well-designed large trials are needed to test these herbal medicines against standard treatments. In general, the completeness of reporting in these trials was poor. Trialists should refer to the CONSORT statement extension for reporting trials of herbal medicine interventions.

What can comparative effectiveness research contribute to integrative health in international perspective?

The interest in Comparative Effectiveness Research (CER) in the international community is growing. A panel titled "What Can Comparative Effectiveness Research Contribute to Integrative Health in International Perspective?" took place at the 3rd International Research Congress on Integrative Medicine and Health in Portland, Oregon, in 2012. The presentations at this panel highlighted different perspectives on CER, including the funders' and the stakeholders' perspectives from the United States, as well as experiences with economic evaluations from Australia and pragmatic trials in Europe. The funders' perspective emphasized the need for innovation and controlling costs in large-scale studies. The stakeholder's perspective stressed the need to gather the input of stakeholders in shaping the framework for more informative, more decision-maker-driven research. Several examples of cost-effectiveness analyses were offered from Australia. The importance of balancing rigor and pragmatism was also discussed in a presentation of the efficacy-effectiveness continuum. A wide-ranging discussion explored additional questions concerning the translation of evidence into practice; the effect of pragmatic trials on funding or policy; evidentiary distinctions between and among pragmatic trials and traditional randomized clinical trials; and the multiple roles of stakeholders, particularly in generating new information and knowledge. The presentations and discussions showed that more development of methods is needed. This includes developments on study design and statistical approaches, as well as methods for stakeholder involvement and mechanisms to bring these results into practice.

Effectiveness guidance document (EGD) for Chinese medicine trials: a consensus document.

BACKGROUND: There is a need for more Comparative Effectiveness Research (CER) on Chinese medicine (CM) to inform clinical and policy decision-making. This document aims to provide consensus advice for the design of CER trials on CM for researchers. It broadly aims to ensure more adequate design and optimal use of resources in generating evidence for CM to inform stakeholder decision-making. METHODS: The Effectiveness Guidance Document (EGD) development was based on multiple consensus procedures (survey, written Delphi rounds, interactive consensus workshop, international expert review). To balance aspects of internal and external validity, multiple stakeholders, including patients, clinicians, researchers and payers were involved in creating this document. RESULTS: Recommendations were developed for "using available data" and "future clinical studies". The recommendations for future trials focus on randomized trials and cover the following areas: designing CER studies, treatments, expertise and setting, outcomes, study design and statistical analyses, economic evaluation, and publication. CONCLUSION: The present EGD provides the first systematic methodological guidance for future CER trials on CM and can be applied to single or multi-component treatments. While CONSORT statements provide guidelines for reporting studies, EGDs provide recommendations for the design of future studies and can contribute to a more strategic use of limited research resources, as well as greater consistency in trial design.

Traditional Chinese medicine: potential for clinical treatment of rheumatoid arthritis.

Rheumatoid arthritis (RA) is a chronic debilitating autoimmune disease affecting people worldwide. Increasing numbers of RA patients in the west are resorting to various complementary and alternative medicine modalities for relief of symptoms and well-being. Herbal products and acupuncture representing traditional Chinese medicine (TCM) are two of the most commonly used forms of complementary and alternative medicine. Frequently, their efficacy against RA and safety have been inferred from anecdotal experience or pilot testing on a relatively small number of patients following inadequate study designs. Accordingly, significant efforts need to be invested in objectively testing TCM in clinical trials that are sufficiently powered, randomized, blinded, possess appropriate controls and follow standard criteria for assessment of the outcomes. In addition, the mechanisms underlying the immunomodulatory and other antiarthritic activities of TCM modalities need to be better defined. These efforts would help validate the scientific rationale for the use of TCM for the management of RA.

Mechanisms of acupuncture-electroacupuncture on persistent pain.

In the last decade, preclinical investigations of electroacupuncture mechanisms on persistent tissue injury (inflammatory), nerve injury (neuropathic), cancer, and visceral pain have increased. These studies show that electroacupuncture activates the nervous system differently in health than in pain conditions, alleviates both sensory and affective inflammatory pain, and inhibits inflammatory and neuropathic pain more effectively at 2 to 10 Hz than at 100 Hz. Electroacupuncture blocks pain by activating a variety of bioactive chemicals through peripheral, spinal, and supraspinal mechanisms. These include opioids, which desensitize peripheral nociceptors and reduce proinflammatory cytokines peripherally and in the spinal cord, and serotonin and norepinephrine, which decrease spinal N-methyl-D-aspartate receptor subunit GluN1 phosphorylation. Additional studies suggest that electroacupuncture, when combined with low dosages of conventional analgesics, provides effective pain management which can forestall the side effects of often-debilitating pharmaceuticals.

[Which research is needed to support clinical decision-making on integrative medicine? Can comparative effectiveness research close the gap?].

In clinical research on complementary and integrative medicine, experts and scientists have often pursued a research agenda in spite of an incomplete understanding of the needs of end users. Consequently, the majority of previous clinical trials have mainly assessed the efficacy of interventions. Scant data is available on their effectiveness. Comparative effectiveness research (CER) promises to support decision makers by generating evidence that compares the benefits and harms of best care options. This evidence, more generalizable than evidence generated by traditional randomized clinical trials (RCTs), is better suited to inform real-world care decisions. An emphasis on CER supports the development of the evidence base for clinical and policy decision-making. Whereas in most areas of complementary and integrative medicine data on CER is scarce, available acupuncture research already contributes to CER evidence. This paper will introduce CER and make suggestions for future research.

Microarray analysis reveals the molecular basis of antiarthritic activity of huo-luo-xiao-ling dan.

Rheumatoid arthritis (RA) is a chronic inflammatory disease of autoimmune origin. Huo-luo-xiao-ling dan (HLXL) is an herbal mixture that has been used in traditional Chinese medicine over several decades to treat chronic inflammatory diseases including RA. However, the mechanism of the anti-arthritic action of this herbal remedy is poorly understood at the molecular level. In this study, we determined by microarray analysis the effects of HLXL on the global gene expression profile of the draining lymph node cells (LNC) in the rat adjuvant arthritis (AA) model of human RA. In LNC restimulated in vitro with the disease-related antigen mycobacterial heat-shock protein 65 (Bhsp65), 84 differentially expressed genes (DEG) (64 upregulated and 20 downregulated) versus 120 DEG (94 upregulated and 26 downregulated) were identified in HLXL-treated versus vehicle (Water)-treated rats, respectively, and 62 DEG (45 upregulated and 17 downregulated) were shared between the two groups. The most affected pathways in response to HLXL treatment included immune response, inflammation, cellular proliferation and apoptosis, and metabolic processes, many of which are directly relevant to arthritis pathogenesis. These results would advance our understanding of the mechanisms underlying the anti-arthritic activity of HLXL.

The effects of acupuncture on rates of clinical pregnancy among women undergoing in vitro fertilization: a systematic review and meta-analysis.

BACKGROUND Recent systematic reviews of adjuvant acupuncture for IVF have pooled heterogeneous trials, without examining variables that might explain the heterogeneity. The aims of our meta-analysis were to quantify the overall pooled effects of adjuvant acupuncture on IVF clinical pregnancy success rates, and evaluate whether study design-, treatment- and population-related factors influence effect estimates. METHODS We included randomized controlled trials that compared needle acupuncture administered within 1 day of embryo transfer, versus sham acupuncture or no adjuvant treatment. Our primary outcome was clinical pregnancy rates. We obtained from all investigators additional methodological details and outcome data not included in their original publications. We analysed sham-controlled and no adjuvant treatment-controlled trials separately, but since there were no large or significant differences between these two subsets, we pooled all trials for subgroup analyses. We prespecified 11 subgroup variables (5 clinical and 6 methodological) to investigate sources of heterogeneity, using single covariate meta-regressions. RESULTS Sixteen trials (4021 participants) were included in the meta-analyses. There was no statistically significant difference between acupuncture and controls when combining all trials [risk ratio (RR) 1.12, 95% confidence interval (CI), 0.96-1.31; I(2) = 68%; 16 trials; 4021 participants], or when restricting to sham-controlled (RR 1.02, 0.83-1.26; I(2) = 66%; 7 trials; 2044 participants) or no adjuvant treatment-controlled trials (RR 1.22, 0.97-1.52; I(2) = 67%; 9 trials; 1977 participants). The type of control used did not significantly explain the statistical heterogeneity (interaction P = 0.27). Baseline pregnancy rate, measured as the observed rate of clinical pregnancy in the control group of each trial, was a statistically significant effect modifier (interaction P < 0.001), and this covariate explained most of the heterogeneity of the effects of adjuvant acupuncture across all trials (adjusted R(2) = 93%; I(2) residual = 9%). Trials with lower control group rates of clinical pregnancy showed larger effects of adjuvant acupuncture (RR 1.53, 1.28-1.84; 7 trials; 1732 participants) than trials with higher control group rates of clinical pregnancy (RR 0.90, 0.80-1.01; 9 trials; 2289 participants). The asymmetric funnel plot showed a tendency for the intervention effects to be more beneficial in smaller trials. CONCLUSIONS We found no pooled benefit of adjuvant acupuncture for IVF. The subgroup finding of a benefit in trials with lower, but not higher, baseline pregnancy rates (the only statistically significant subgroup finding in our earlier review) has been confirmed in this update, and was not explained by any confounding variables evaluated. However, this baseline pregnancy rate subgroup finding among published trials requires further confirmation and exploration in additional studies because of the multiple subgroup tests conducted, the risk of unidentified confounders, the multiple different factors that determine baseline rates, and the possibility of publication bias.

Bibliometric and content analysis of the Cochrane Complementary Medicine Field specialized register of controlled trials.

BACKGROUND: The identification of eligible controlled trials for systematic reviews of complementary and alternative medicine (CAM) interventions can be difficult. To increase access to these difficult to locate trials, the Cochrane Collaboration Complementary Medicine Field (CAM Field) has established a specialized register of citations of CAM controlled trials. The objective of this study is to describe the sources and characteristics of citations included in the CAM Field specialized register. METHODS: Between 2006 and 2011, regular searches for citations of CAM trials in MEDLINE and the Cochrane Central Register of Controlled Trials (CENTRAL) were supplemented with contributions of controlled trial citations from international collaborators. The specialized register was 'frozen' for analysis in 2011, and frequencies were calculated for publication date, language, journal, presence in MEDLINE, type of intervention, and type of medical condition. RESULTS: The CAM Field specialized register increased in size from under 5,000 controlled trial citations in 2006 to 44,840 citations in 2011. Most citations (60%) were from 2000 or later, and the majority (71%) were reported in English; the next most common language was Chinese (23%). The journals with the greatest number of citations were CAM journals published in Chinese and non-CAM nutrition journals published in English. More than one-third of register citations (36%) were not indexed in MEDLINE. The most common CAM intervention type in the register was non-vitamin, non-mineral dietary supplements (e.g., glucosamine, fish oil) (34%), followed by Chinese herbal medicines (e.g., Astragalus membranaceus, Schisandra chinensis) (27%). CONCLUSIONS: The availability of the CAM Field specialized register presents both opportunities and challenges for CAM systematic reviewers. While the register provides access to thousands of difficult to locate trial citations, many of these trials are of low quality and may overestimate treatment effects. When including these trials in systematic reviews, adequate analysis of their risk of bias is of utmost importance.

Chinese Herbal Formula Huo-Luo-Xiao-Ling Dan Protects against Bone Damage in Adjuvant Arthritis by Modulating the Mediators of Bone Remodeling.

Huo-luo-xiao-ling dan (HLXL) is an herbal mixture that has long been used in traditional Chinese medicine for the treatment of rheumatoid arthritis (RA) and other inflammatory disorders. Despite the availability of potent conventionally used drugs for RA, their limited efficacy in a proportion of patients coupled with their high cost and severe adverse effects has necessitated the search for novel therapeutics for this debilitating disease. Further, the control of both inflammation and bone damage is essential for effective management of arthritis. The aim of our study was to evaluate the efficacy of HLXL against arthritic bone damage in adjuvant arthritis (AA) model of RA. Our results show that HLXL treatment suppressed inflammatory arthritis and reduced bone and cartilage damage in the joints of arthritic Lewis rats. HLXL-induced protection against bone damage was mediated primarily via inhibition of mediators of osteoclastic bone remodeling (e.g., receptor activator of nuclear factor kappa-B ligand; RANKL), skewing of RANKL/osteoprotegerin (OPG) ratio in favor of antiosteoclastic activity, reduction in the number of osteoclasts in the arthrodial joint's bone, and inhibition of cytokine production and MMP activity. Our results suggest that HLXL might offer a promising alternative/adjunct treatment for both inflammation and bone damage in RA.

Effectiveness Guidance Document (EGD) for acupuncture research - a consensus document for conducting trials.

BACKGROUND: There is a need for more Comparative Effectiveness Research (CER) to strengthen the evidence base for clinical and policy decision-making. Effectiveness Guidance Documents (EGD) are targeted to clinical researchers. The aim of this EGD is to provide specific recommendations for the design of prospective acupuncture studies to support optimal use of resources for generating evidence that will inform stakeholder decision-making. METHODS: Document development based on multiple systematic consensus procedures (written Delphi rounds, interactive consensus workshop, international expert review). To balance aspects of internal and external validity, multiple stakeholders including patients, clinicians and payers were involved. RESULTS: Recommendations focused mainly on randomized studies and were developed for the following areas: overall research strategy, treatment protocol, expertise and setting, outcomes, study design and statistical analyses, economic evaluation, and publication. CONCLUSION: The present EGD, based on an international consensus developed with multiple stakeholder involvement, provides the first systematic methodological guidance for future CER on acupuncture.