Effects of Modified Ramadan Fasting on Mental Well-Being and Biomarkers in Healthy Adult Muslims - A Randomised Controlled Trial.

BACKGROUND: Ramadan fasting has seen increased attention in research, often with inconsistent findings. This study aims to investigate whether dietary and lifestyle modifications during Ramadan can improve well-being and health in healthy adult Muslims. METHOD: A randomised controlled trial with two parallel groups was conducted in an outpatient clinic of a university hospital in Essen, Germany, in 2016. Healthy adult Muslims (n = 114) aged 18-60 years were randomised to a modified fasting group; i.e., they received educational material prompting dietary and lifestyle modifications pre-Ramadan, and a control group who undertook Ramadan fasting as usual. Primary outcome was quality of life (WHO-5 Well-Being Index). Secondary outcomes included sleep quality, spirituality, and mindfulness (all self-report), body weight, body mass index, body fat, waist circumference, hip circumference, blood pressure, and heart rate, as well as blood serum biomarkers. Safety was examined via adverse events. RESULTS: The modified fasting group reported significantly higher quality of life (WHO-5) compared to the control after Ramadan (MD 5.9; 95% CI, 0.02-11.8; p < 0.05). Group differences in favour of the modified fasting were also found for satisfaction with health (MD 5.9, 95% CI 0.19-11.67), ease of life (MD 4.1, 95% CI 0.38-7.80) and mindfulness (MD 7.6, 95% CI 2.68-12.52), reductions in weight (MD, - 0.9 kg; 95% CI - 1.39 to - 0.42), BMI (MD - 0.3 kg/m2, 95% CI - 0.50 to - 0.15), hip circumference (MD - 0.3 kg/m2, 95% CI - 0.50 to - 0.15), and diastolic blood pressure (MD - 2.8 mmHg, 95% CI - 5.15 to - 0.43). About 60% of participants reported adverse events, mostly headaches/migraines, dizziness/fatigue, common cold, and gastrointestinal symptoms, with no group differences. One serious non-related adverse event each occurred in both groups. CONCLUSION: Pre-Ramadan dietary and lifestyle advice can lead to short-term improvements in mental and physical well-being of adult Muslims observing Ramadan. As such, this study demonstrates the potential benefits of culturally appropriate health interventions in a religious context. TRIAL REGISTRATION: ClinicalTrials.gov (Identifier NCT02775175).

Naturopathy, complementary and integrative medicine in medical education - position paper by the GMA Committee Integrative Medicine and Perspective Pluralism.

Background: A large part of the population in Germany makes use of naturopathic, complementary and integrative medical treatments. There are now numerous scientific studies that provide evidence of efficacy for certain indications. At German medical faculties, selected procedures and their application are taught within the cross-sectoral unit called QB 12 and some elective courses, with a focus on specific aspects are offered. So far, however, there has been no structured curriculum that longitudinally anchors teaching across medical studies and enables all students to consider naturopathic and complementary medical options for patient care later on and to integrate them effectively into the diagnostic and treatment process. Objective: The aim of this position paper is to show the relevance of this topic for medical education, to clarify terminology and to present core competencies and possible implementation options for training. Method: The Integrative Medicine and Perspective Pluralism Committee of the German Association for Medical Education developed this position paper in a multi-stage consensual process, in cooperation with the Forum of University Work Groups on Naturopathic Treatment and Complementary Medicine. Results: First, different umbrella terms were discussed and an existing definition of integrative medicine and health was chosen for subsequent use. Building on this step, the status of education and its scientific foundation in Germany was considered in an international context. In the next step, a competency profile for medical training, consisting of seven areas of competency, was developed and described in detail with regard to naturopathic, complementary and integrative medicine. Implementation options were identified using possible starting points in the curriculum and using established examples of best practice. Conclusion: Despite different priorities at each faculty, it was possible to find an agreement on the development of competencies and anchoring them in medical education on the basis of a common definition of terms. Currently, the implementation in the mandatory and elective areas is very heterogeneous. As part of the current revision of the Medical Licensure Act, there are many possible starting points for the integration of naturopathic and complementary medical teaching content, especially in interprofessional and general practice courses. The implementation and accompanying research of targeted teaching settings should lay the foundations for a long-term and binding integration into medical education. Overall, it is clear that medical education in the field of naturopathy and complementary and integrative medicine has the potential to develop comprehensive core medical competencies.

Long-term observational studies with cannabis-based medicines for chronic non-cancer pain: A systematic review and meta-analysis of effectiveness and safety.

BACKGROUND AND OBJECTIVE: This systematic review evaluated the effectiveness, tolerability and safety of cannabis-based medicines (CbMs) for chronic non-cancer pain (CNCP) in long-term observational studies. DATABASES AND DATA TREATMENT: CENTRAL, EMBASE and MEDLINE were searched until December 2021. We included prospective observational studies with a study duration ≥26 weeks. Pooled estimates of event rates of categorical data and standardized mean differences (SMD) of continuous variables were calculated using a random effects model. RESULTS: Six studies were included with 2686 participants, with study duration ranging between 26 and 52 weeks. Pain conditions included nociceptive, nociplastic, neuropathic and mixed pain mechanisms. The certainty of evidence for every outcome was very low. The weighted mean difference of mean pain reduction was 1.75 (95% confidence interval [CI] 0.72 to 2.78) on a 0-10 scale. 20.8% (95% CI 10.2% to 34.0%) of patients reported pain relief of 50% or greater. The effect size for sleep problems was moderate and for depression and anxiety was low. Study completions was reported for 53.3% (95% CI 26.8% to 79.9%) of patients, with dropouts of 6.8% (95% CI 4.3% to 9.7%) due to adverse events. Serious adverse events occurred in 3.0% (95 CI 0.02% to 12.8%) and 0.3% (95% CI 0.1% to 0.6%) of patients died. CONCLUSIONS: Information included in observational studies should be regarded with caution. Within the context of observational studies. CbMs had positive effects on multiple symptoms for some CNCP patients and were generally well tolerated and safe. SIGNIFICANCE: There is very low quality evidence for the long-term effectiveness (pain, sleep, mood, health-related quality of life), tolerability and safety of medical cannabis for chronic non-cancer pain (CNCP) according to reports of prospective observational studies. Predefined criteria of a large magnitude of effect size in these types of studies were not met. Nevertheless, long-term medical cannabis therapy can be considered in some carefully selected and monitored patients with CNCP.

Perimenopause and Postmenopause - Diagnosis and Interventions. Guideline of the DGGG and OEGGG (S3-Level, AWMF Registry Number 015-062, September 2020).

Aim The aim of the interdisciplinary S3-guideline Perimenopause and Postmenopause - Diagnosis and Interventions is to provide help to physicians as they inform women about the physiological changes which occur at this stage of life and the treatment options. The guideline should serve as a basis for decisions taken during routine medical care. This short version lists the statements and recommendations given in the long version of the guideline together with the evidence levels, the level of recommendation, and the strength of consensus. Methods The statements and recommendations are largely based on methodologically high-quality publications. The literature was evaluated by experts and mandate holders using evidence-based medicine (EbM) criteria. The search for evidence was carried out by the Essen Research Institute for Medical Management (EsFoMed). To some extent, this guideline also draws on an evaluation of the evidence used in the NICE guideline on Menopause and the S3-guidelines of the AWMF and has adapted parts of these guidelines. Recommendations Recommendations are given for the following subjects: diagnosis and therapeutic interventions for perimenopausal and postmenopausal women, urogynecology, cardiovascular disease, osteoporosis, dementia, depression, mood swings, hormone therapy and cancer risk, as well as primary ovarian insufficiency.

Comparative efficacy of different exercise interventions in chronic non-specific low back pain: protocol of a systematic review and network meta-analysis.

INTRODUCTION: Chronic non-specific low back pain is a major public health problem. Evidence supports the effectiveness of exercise as an intervention. Due to a paucity of direct comparisons of different exercise categories, medical guidelines were unable to make specific recommendations regarding the type of exercise working best in improving chronic low back pain. This network meta-analysis (NMA) of randomised controlled trials aims to investigate the comparative efficacy of different exercise interventions in patients with chronic non-specific low back pain. METHODS AND ANALYSIS: MEDLINE, Scopus, Cochrane Central Register of Controlled Trials, Physiotherapy Evidence Database, SPORTDiscus, Clinicaltrials.gov and the WHO International Clinical Trials Registry Platform search portal were searched on November 2019 and without language restrictions. The search will be updated after data analysis. Studies on adults with non-specific low back pain of at least 12 weeks duration comparing exercise to either no specific intervention (ie, no treatment, wait-list or usual care at the treating physician's discretion) and/or functionally inert interventions (ie, sham or attention control interventions) will be eligible. Pain intensity and back-specific disability are defined as primary outcomes. Secondary outcomes will include health-related physical and mental quality of life, work disability, frequency of analgesic use and adverse events. All outcomes will be analysed short-term, intermediate-term and long-term. Data will be extracted independently by two review authors. Risk of bias will be assessed using the recommendations by the Cochrane Back and Neck Group and be based on an adaptation of the Cochrane Risk of Bias tool. ETHICS AND DISSEMINATION: This NMA will be reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses_NMA checklist. The results will be presented in peer-reviewed journals, implemented in existing national and international guidelines and will be presented to health care providers and decision makers. The planned completion date of the study is 1 July 2021. PROSPERO REGISTRATION NUMBER: CRD42020151472.

[Method report of the second update of the guidelines on long-term opioid therapy for chronic noncancer pain]. / Leitlinienreport der zweiten Aktualisierung der S3-Leitlinie "Langzeitanwendung von Opioiden bei nicht-tumorbedingten Schmerzen ­ LONTS".

BACKGROUND: The update of the German S3 guidelines on long-term opioid therapy of chronic noncancer pain (CNCP), the LONTS (AWMF registration number 145/003), was scheduled for February 2020 due to the expiry of the validity period. METHODS: The guidelines were updated by 28 scientific societies and 2 patient self-help organizations under the coordination of the German Pain Society and the Association of the Scientific Medical Societies in Germany (AWMF). RESULTS: A systematic literature search was performed in the CENTRAL, MEDLINE and Scopus databases from October 2013 to December 2018. The previous meta-analyses of randomized controlled trials (RCT) of opioids in CNPC syndromes with a study duration of ≥4 weeks were updated. Levels of evidence were assigned according to the Oxford Centre for Evidence-Based Medicine version 2009 classification system. The formulation and strength of recommendations was established in a multistep formalized consensus procedure, in accordance with AWMF rules and standards. The guidelines were reviewed by four experts not involved in the development of the guidelines. The public was given the opportunity to comment on the guidelines. The guidelines were approved by the executive boards of the societies that were engaged in development of the guidelines. CONCLUSION: The guidelines will be published in several forms: complete and short scientific versions as well as clinical practice and patient versions.

Cupping for Patients With Chronic Pain: A Systematic Review and Meta-Analysis.

There is a growing interest in nonpharmacological pain treatment options such as cupping. This meta-analysis aimed to assess the effectiveness and safety of cupping in chronic pain. PubMed, Cochrane Library, and Scopus were searched through November 2018 for randomized controlled trials on effects of cupping on pain intensity and disability in patients with chronic pain. Risk of bias was assessed using the Cochrane risk of bias tool. Of the 18 included trials (n =1,172), most were limited by clinical heterogeneity and risk of bias. Meta-analyses found large short-term effects of cupping on pain intensity compared to no treatment (standardized mean difference [SMD] = -1.03; 95% confidence interval [CI] = -1.41, -.65), but no significant effects compared to sham cupping (SDM = -.27; 95% CI = -.58, .05) or other active treatment (SMD = -.24; 95% CI = -.57, .09). For disability, there were medium-sized short-term effects of cupping compared to no treatment (SMD = -.66; 95% CI = -.99, -.34), and compared to other active treatments (SMD = -.52; 95% CI = -1.03, -.0028), but not compared to sham cupping (SMD = -.26; 95% CI = -.57,.05). Adverse events were more frequent among patients treated with cupping compared to no treatment; differences compared to sham cupping or other active treatment were not statistically significant. Cupping might be a treatment option for chronic pain, but the evidence is still limited by the clinical heterogeneity and risk of bias. Perspective: This article presents the results of a meta-analysis aimed to assess the effectiveness and safety of cupping with chronic pain. The results suggest that cupping might be a treatment option; however, the evidence is still limited due to methodical limitations of the included trials. High-quality trials seem warranted.

Opioids for chronic low back pain: An updated systematic review and meta-analysis of efficacy, tolerability and safety in randomized placebo-controlled studies of at least 4 weeks of double-blind duration.

BACKGROUND AND OBJECTIVE: This updated systematic review evaluated the efficacy, tolerability and safety of opioids compared to placebo in non-malignant chronic low back pain. DATABASES AND DATA TREATMENT: Clinicaltrials.gov, CENTRAL, MEDLINE and PsycINFO were searched from October 2013 to May 2019. Randomized controlled trials comparing opioids with placebo and at least 4 weeks of double-blinded duration were analysed. Primary outcomes were pain relief of 50% or greater, disability, tolerability and safety. Effects were summarized by a random effects model using risk differences or standardized mean differences. We added nine new studies with 2,980 participants for a total of 21 studies with 7,650 participants. Study duration ranged between 4 and 15 weeks. Studies with a parallel and cross-over design: Based on very low to low-quality evidence, opioids provided no clinically relevant pain relief of 50% or greater, but a clinically relevant reduction of disability compared to placebo. Enriched enrolment randomized withdrawal (EERW) design: Based on very low to low-quality evidence, opioids provided a clinically relevant pain relief of 50% or greater, but not a clinically relevant reduction of disability compared to placebo. There was no clinically relevant harm with regard to serious adverse events by opioids compared to placebo in studies with parallel/cross-over and EERW design. There was a relevant harm with regard to drop out rates due to adverse events in studies with parallel/cross-over, but not in studies with EERW design. CONCLUSIONS: Opioids may provide a safe and clinically relevant pain relief for 4-15 weeks in highly selected patients. SIGNIFICANCE: Within the context of randomized controlled trials of 4-15 weeks, opioids provided a clinically relevant pain relief of 30% or greater and a clinically relevant reduction of disability compared to placebo in non-malignant chronic low back pain. Number needed to treat for an additional drop out due to side effects was 11 (95% confidence interval: 6-33). Assessment of abuse and addiction was incomplete. The frequency of serious adverse events including deaths did not differ from placebo.

Yoga for Treating Headaches: a Systematic Review and Meta-analysis.

BACKGROUND: Headache disorders are currently the sixth leading cause of disability across the globe and therefore carry a significant disease burden. This systematic review and meta-analysis aims to investigate the effects of yoga on headache disorders. METHODS: MEDLINE/PubMed, Scopus, the Cochrane Library, and PsycINFO were screened through May 2019. Randomized controlled trials (RCTs) were included when they assessed the effects of yoga in patients with a diagnosis of chronic or episodic headache (tension-type headache and/or migraine). Usual care (no specific treatment) or any active treatments were acceptable as control interventions. Primary outcome measures were headache frequency, headache duration, and pain intensity. For each outcome, standardized mean differences (SMD) and 95% confidence intervals (CI) were calculated. RESULTS: Meta-analysis revealed a statistically significant overall effect in favor of yoga for headache frequency (5 RCTs; standardized mean difference (SMD) = - 1.97; 95% confidence interval (CI) - 2.75 to - 1.20; I2 = 63.0%, τ2 = 0.25, P = 0.03), headache duration (4 RCTs; SMD = - 1.45; 95% CI - 2.54 to - 0.37; I2 = 69.0%, τ2 = 0.33, P = 0.02), and pain intensity (5 RCTs; SMD = - 3.43; 95% CI - 6.08 to - 0.70, I2 = 95.0%, τ2 = 4.25, P < 0.01). The significant overall effect was mainly due to patients with tension-type headaches. For patients with migraine, no statistically significant effect was observed. DISCUSSION: Despite discussed limitations, this review found preliminary evidence of short-term efficacy of yoga in improving headache frequency, headache duration, and pain intensity in patients suffering from tension-type headaches. Further studies are urgently needed to draw deeper conclusions from the available results.

Efficacy and harms of long-term opioid therapy in chronic non-cancer pain: Systematic review and meta-analysis of open-label extension trials with a study duration ≥26 weeks.

BACKGROUND AND OBJECTIVE: This updated systematic review evaluated the efficacy, acceptability and safety of long-term opioid therapy (LTOT) for chronic non-cancer pain (CNCP). DATABASES AND DATA TREATMENT: Clinicaltrials.gov, CENTRAL and MEDLINE until June 2019. We included open-label extension trials with a study duration ≥26 weeks of RCTs with ≥2 weeks duration. Pooled estimates of event rates of categorical data and standardized mean differences (SMD) of continuous variables were calculated using a random effects model. RESULTS: We added four new studies with 1,154 participants for a total of 15 studies with 3,590 participants. Study duration ranged between 26 and 156 weeks. Studies included patients with low back, osteoarthritis and neuropathic pain. The quality of evidence for every outcome was very low. 31.1% (95% Confidence interval [CI] 23.0%-40.7%) of patients randomized at baseline finished the open label period. 14.1% (95% CI 10.9%-19.4%) of patients dropped out to due adverse events. In 6.3% (95 CI 3.9%-10.1%) of patients serious adverse events and in 2.7% (95% CI 1.5%-4.7%) aberrant drug behaviour were noted. 0.5% (95% CI 0.2%-1.4%) of patients died. CONCLUSIONS: Within the context of open-label extension studies, opioids maintain reduction of pain and disability and are rather well tolerated and safe. LTOT can be considered in carefully selected and monitored patients with low back, osteoarthritis and neuropathic pain who experience a clinically meaningful pain reduction with at least tolerable adverse events in short-term opioid therapy. SIGNIFICANCE: There is very low quality evidence of the long-term efficacy, tolerability and safety of opioids for chronic low back, osteoarthritis and diabetic polyneuropathic pain within the context of open-label extension studies of randomized controlled trials. Drop out rate due to adverse events and deaths increase with study duration. One-third of patients profit from LTOT. Long-term opioid therapy can be considered in some carefully selected and monitored patients.

Opioids for chronic non-cancer neuropathic pain. An updated systematic review and meta-analysis of efficacy, tolerability and safety in randomized placebo-controlled studies of at least 4 weeks duration.

BACKGROUND AND OBJECTIVE: This updated systematic review evaluated the efficacy, tolerability and safety of opioids compared to placebo in chronic non-cancer neuropathic pain. DATABASES AND DATA TREATMENT: Clinicaltrials.gov, CENTRAL, PubMed and PsycINFO were searched from October 2013 to June 2019. Randomized controlled trials comparing opioids with placebo and at least 4 weeks double-blinded duration were analysed. Primary outcomes were pain relief of 50% or greater, disability, tolerability and safety. Effects were summarized by a random effects model using risk differences (RD) or standardized mean differences (SMD). We added four new studies with 662 participants for a total of 16 included studies with 2,199 participants. Study duration ranged between 4 and 12 weeks. Studies with a parallel and cross-over design: Based on low to moderate quality evidence, opioids (buprenorphine, hydromorphone, morphine, oxycodone, tramadol) provided a clinically relevant pain relief of 50% or greater and reduction of disability compared to placebo. There was no clinically relevant harm with regards to the drop out rate due to adverse and serious adverse events by opioids compared to placebo. Enriched enrolment randomized withdrawal design: Based on low to moderate quality evidence, tapentadol provided a clinically relevant pain relief of 50% or greater and reduction of disability compared to placebo in diabetic polyneuropathy. There was no clinically relevant harm with regards to the drop out rate due to adverse and serious adverse events by tapentadol compared to placebo. CONCLUSIONS: Some opioids provided a short-term substantial pain relief in highly selected patients in some neuropathic pain syndromes. SIGNIFICANCE: Some opioids (buprenorphine, morphine, oxycodone, tramadol, tapentadol) provide substantial pain relief compared to placebo in postherpetic neuralgia and peripheral neuropathies of different aetiologies for 4-12 weeks. There is insufficient evidence to support or refute the suggestion that these drugs are effective in other neuropathic pain conditions. The safety of opioids with regards to abuse and deaths in the studies analysed cannot be extrapolated to routine clinical care.

Opioids for chronic osteoarthritis pain: An updated systematic review and meta-analysis of efficacy, tolerability and safety in randomized placebo-controlled studies of at least 4 weeks double-blind duration.

BACKGROUND AND OBJECTIVE: This updated systematic review evaluated the efficacy and safety of opioids compared with placebo for chronic osteoarthritis pain. DATABASES AND DATA TREATMENT: Clinicaltrials.gov, CENTRAL, MEDLINE and PsycINFO were searched from October 2013 to July 2019. Randomized controlled trials comparing opioids with placebo and at least 4 weeks double-blinded duration were analysed. Primary outcomes were pain relief of 50% or greater, disability, tolerability and safety. Effects were summarized by a random effects model using risk differences or standardized mean differences with 95% confidence intervals. We added two new studies with 397 participants for a total of 22 studies with 8,942 participants. Study duration ranged between 4 and 24 weeks. Studies with a parallel and cross-over design: Based on very low- to low-quality evidence, opioids provided no clinically relevant pain relief of 50% or greater and no clinically relevant reduction in disability compared with placebo. There was a clinically relevant harm related to the dropout rate due to adverse events. The frequency of serious adverse events did not differ from placebo. Enriched enrolment randomized withdrawal design: Based on very low- to low-quality evidence, opioids provided no clinically relevant pain relief of 50% or greater and no clinically relevant reduction in disability compared with placebo. Dropout rates due to adverse events and frequency of serious adverse events did not differ from placebo. CONCLUSIONS: Tolerability of opioids is low and efficacy is not clinically relevant in controlled studies from 4 to 24 weeks for osteoarthritis pain. SIGNIFICANCE: Within the context of randomized controlled trials (4-24 weeks), opioids provided no clinically relevant pain relief and no clinically relevant reduction in disability compared with placebo in chronic osteoarthritis pain (hip, knee). Number needed to treat for an additional dropout due to side effects was 5 (95% confidence interval 4-7). Two studies found no signals of abuse and addiction. The frequency of serious adverse events including deaths did not differ from placebo.

The risks and benefits of yoga for patients with chronic obstructive pulmonary disease: a systematic review and meta-analysis.

OBJECTIVES: To determine the effectiveness and safety of yoga interventions on disease symptoms, quality of life and function in patients diagnosed with chronic obstructive pulmonary disease (COPD). DATA SOURCES: Medline/PubMed, Scopus, and CENTRAL (Cochrane Central Register of Controlled Trials) were searched through 6 June 2019. REVIEW METHODS: Randomized controlled trials assessing the effects of yoga on quality of life, dyspnea, exercise capacity, and pulmonary function (FEV1) in patients with COPD were included. Safety was defined as secondary outcome. Mean differences (MD) and standardized mean differences (SMD) with 95% confidence intervals (CIs) were computed. Risk of bias was assessed using the Cochrane tool. RESULTS: Eleven randomized controlled trials with a total of 586 patients were included. Meta-analysis revealed evidence for effects of yoga compared to no treatment on quality of life on the COPD Assessment Test (MD = 3.81; 95% CI = 0.97 to 6.65; P = 0.009, I2 = 70%), exercise capacity assessed by the 6-minute walk test (MD = 25.53 m; 95% CI = 12.16 m to 38.90 m; P = 0.001, I2 = 0%), and pulmonary function assessed by FEV1 predicted (MD = 3.95%; 95% CI = 2.74% to 5.17%; P < 0.001, I2 = 0%). Only the effects on exercise capacity and pulmonary function were robust against methodological bias. Effects were only present in breathing-focused yoga interventions but not in interventions including yoga postures. Adverse events were reported infrequently. CONCLUSION: This meta-analysis found robust effects of yoga on exercise capacity and pulmonary function in patients with COPD. Yoga, specifically yoga breathing techniques, can be an effective adjunct intervention for patients with COPD. Yoga's safety needs to be assessed in more depth in future studies.

Efficacy, tolerability and safety of cannabis-based medicines for cancer pain : A systematic review with meta-analysis of randomised controlled trials.

BACKGROUND: The importance of medical cannabis and cannabis-based medicines for cancer pain management needs to be determined. METHODS: A systematic literature search until December 2018 included CENTRAL, PubMed, SCOPUS and trial registers. Randomised controlled trials (RCTs) investigating medical cannabis and/or pharmaceutical cannabinoids for pain control in cancer patients with a study duration of at least 2 weeks and a sample size of at least 20 participants per study arm were included. Clinical outcomes comprised efficacy (pain intensity, patient impression of improvement, combined responder, sleep problems, psychological distress, opioid maintenance and breakthrough dosage), tolerability (dropout rate due to adverse events) and safety (nervous system, psychiatric and gastrointestinal side effects; serious adverse events). The quality of evidence was assessed using Grading of Recommendations Assessment, Development and Evaluation (GRADE). RESULTS: Five RCTs with oromucosal nabiximols or tetrahydrocannabinol (THC) including 1534 participants with moderate and severe pain despite opioid therapy were identified. Double blind period of the RCTs ranged between 2 and 5 weeks. Four studies with a parallel design and 1333 patients were available for meta-analysis. The quality of evidence was very low for all comparisons. Oromucosal nabiximols and THC did not differ from placebo in reducing pain, sleep problems, opioid dosages and in the frequency of combined responder, serious adverse events and psychiatric disorders side effects. The number of patients who reported to be much or very much improved was higher with oromucosal nabiximols and THC than with placebo (number needed to treat for an additional benefit 16; 95% confidence interval [CI] 8 to infinite). The dropout rates due to adverse events (number needed to treat for an additional harm [NNTH]: 20; 95% CI 11-100), the frequency of nervous system (NNTH: 10; 95% CI 7-25) and of gastrointestinal side effects (NNTH: 11; 95% CI 7-33) was higher with oromucosal nabiximols and THC than with placebo. CONCLUSIONS: Very low quality evidence suggests that oromucosal nabiximols and THC have no effect on pain, sleep problems and opioid consumption in patients with cancer pain with insufficient pain relief from opioids. The complete manuscript is written in English.

Mindfulness-based stress reduction for treating chronic headache: A systematic review and meta-analysis.

BACKGROUND: Mindfulness-based stress reduction/cognitive therapy are frequently used for pain-related conditions, but their effects on headache remain uncertain. This review aimed to assess the efficacy and safety of mindfulness-based stress reduction/cognitive therapy in reducing the symptoms of chronic headache. DATA SOURCES AND STUDY SELECTION: MEDLINE/PubMed, Scopus, CENTRAL, and PsychINFO were searched to 16 June 2017. Randomized controlled trials comparing mindfulness-based stress reduction/cognitive therapy with usual care or active comparators for migraine and/or tension-type headache, which assessed headache frequency, duration or intensity as a primary outcome, were eligible for inclusion. Risk of bias was assessed using the Cochrane Tool. RESULTS: Five randomized controlled trials (two on tension-type headache; one on migraine; two with mixed samples) with a total of 185 participants were included. Compared to usual care, mindfulness-based stress reduction/cognitive therapy did not improve headache frequency (three randomized controlled trials; standardized mean difference = 0.00; 95% confidence interval = -0.33,0.32) or headache duration (three randomized controlled trials; standardized mean difference = -0.08; 95% confidence interval = -1.03,0.87). Similarly, no significant difference between groups was found for pain intensity (five randomized controlled trials; standardized mean difference = -0.78; 95% confidence interval = -1.72,0.16). CONCLUSIONS: Due to the low number, small scale and often high or unclear risk of bias of included randomized controlled trials, the results are imprecise; this may be consistent with either an important or negligible effect. Therefore, more rigorous trials with larger sample sizes are needed.

Serotonin and noradrenaline reuptake inhibitors (SNRIs) for fibromyalgia.

BACKGROUND: Fibromyalgia is a clinically defined chronic condition of unknown etiology characterized by chronic widespread pain that often co-exists with sleep disturbances, cognitive dysfunction and fatigue. People with fibromyalgia often report high disability levels and poor quality of life. Drug therapy, for example, with serotonin and noradrenaline reuptake inhibitors (SNRIs), focuses on reducing key symptoms and improving quality of life. This review updates and extends the 2013 version of this systematic review. OBJECTIVES: To assess the efficacy, tolerability and safety of serotonin and noradrenaline reuptake inhibitors (SNRIs) compared with placebo or other active drug(s) in the treatment of fibromyalgia in adults. SEARCH METHODS: For this update we searched CENTRAL, MEDLINE, Embase, the US National Institutes of Health and the World Health Organization (WHO) International Clinical Trials Registry Platform for published and ongoing trials and examined the reference lists of reviewed articles, to 8 August 2017. SELECTION CRITERIA: We selected randomized, controlled trials of any formulation of SNRIs against placebo or any other active treatment of fibromyalgia in adults. DATA COLLECTION AND ANALYSIS: Three review authors independently extracted data, examined study quality, and assessed risk of bias. For efficacy, we calculated the number needed to treat for an additional beneficial outcome (NNTB) for pain relief of 50% or greater and of 30% or greater, patient's global impression to be much or very much improved, dropout rates due to lack of efficacy, and the standardized mean differences (SMD) for fatigue, sleep problems, health-related quality of life, mean pain intensity, depression, anxiety, disability, sexual function, cognitive disturbances and tenderness. For tolerability we calculated number needed to treat for an additional harmful outcome (NNTH) for withdrawals due to adverse events and for nausea, insomnia and somnolence as specific adverse events. For safety we calculated NNTH for serious adverse events. We undertook meta-analysis using a random-effects model. We assessed the evidence using GRADE and created a 'Summary of findings' table. MAIN RESULTS: We added eight new studies with 1979 participants for a total of 18 included studies with 7903 participants. Seven studies investigated duloxetine and nine studies investigated milnacipran against placebo. One study compared desvenlafaxine with placebo and pregabalin. One study compared duloxetine with L-carnitine. The majority of studies were at unclear or high risk of bias in three to five domains.The quality of evidence of all comparisons of desvenlafaxine, duloxetine and milnacipran versus placebo in studies with a parallel design was low due to concerns about publication bias and indirectness, and very low for serious adverse events due to concerns about publication bias, imprecision and indirectness. The quality of evidence of all comparisons of duloxetine and desvenlafaxine with other active drugs was very low due to concerns about publication bias, imprecision and indirectness.Duloxetine and milnacipran had no clinically relevant benefit over placebo for pain relief of 50% or greater: 1274 of 4104 (31%) on duloxetine and milnacipran reported pain relief of 50% or greater compared to 591 of 2814 (21%) participants on placebo (risk difference (RD) 0.09, 95% confidence interval (CI) 0.07 to 0.11; NNTB 11, 95% CI 9 to 14). Duloxetine and milnacipran had a clinically relevant benefit over placebo in patient's global impression to be much or very much improved: 888 of 1710 (52%) on duloxetine and milnacipran (RD 0.19, 95% CI 0.12 to 0.26; NNTB 5, 95% CI 4 to 8) reported to be much or very much improved compared to 354 of 1208 (29%) of participants on placebo. Duloxetine and milnacipran had a clinically relevant benefit compared to placebo for pain relief of 30% or greater. RD was 0.10; 95% CI 0.08 to 0.12; NNTB 10, 95% CI 8 to 12. Duloxetine and milnacipran had no clinically relevant benefit for fatigue (SMD -0.13, 95% CI -0.18 to -0.08; NNTB 18, 95% CI 12 to 29), compared to placebo. There were no differences between either duloxetine or milnacipran and placebo in reducing sleep problems (SMD -0.07; 95 % CI -0.15 to 0.01). Duloxetine and milnacipran had no clinically relevant benefit compared to placebo in improving health-related quality of life (SMD -0.20, 95% CI -0.25 to -0.15; NNTB 11, 95% CI 8 to 14).There were 794 of 4166 (19%) participants on SNRIs who dropped out due to adverse events compared to 292 of 2863 (10%) of participants on placebo (RD 0.07, 95% CI 0.04 to 0.10; NNTH 14, 95% CI 10 to 25). There was no difference in serious adverse events between either duloxetine, milnacipran or desvenlafaxine and placebo (RD -0.00, 95% CI -0.01 to 0.00).There was no difference between desvenlafaxine and placebo in efficacy, tolerability and safety in one small trial.There was no difference between duloxetine and desvenlafaxine in efficacy, tolerability and safety in two trials with active comparators (L-carnitine, pregabalin). AUTHORS' CONCLUSIONS: The update did not change the major findings of the previous review. Based on low- to very low-quality evidence, the SNRIs duloxetine and milnacipran provided no clinically relevant benefit over placebo in the frequency of pain relief of 50% or greater, but for patient's global impression to be much or very much improved and in the frequency of pain relief of 30% or greater there was a clinically relevant benefit. The SNRIs duloxetine and milnacipran provided no clinically relevant benefit over placebo in improving health-related quality of life and in reducing fatigue. Duloxetine and milnacipran did not significantly differ from placebo in reducing sleep problems. The dropout rates due to adverse events were higher for duloxetine and milnacipran than for placebo. On average, the potential benefits of duloxetine and milnacipran in fibromyalgia were outweighed by their potential harms. However, a minority of people with fibromyalgia might experience substantial symptom relief without clinically relevant adverse events with duloxetine or milnacipran.We did not find placebo-controlled studies with other SNRIs than desvenlafaxine, duloxetine and milnacipran.

Low fermentable, oligo-, di-, mono-saccharides and polyol diet in the treatment of irritable bowel syndrome: A systematic review and meta-analysis.

OBJECTIVES: The aim of this review was to systematically assess and meta-analyze the effects of a low fermentable, oligo-, di-, mono-saccharides and polyol (FODMAP) diet (LFD) on the severity of symptoms, quality of life, and safety in patients with irritable bowel syndrome (IBS). METHODS: The MEDLINE/PubMed, Scopus, and Cochrane Library databases were screened through January 19, 2016. Randomized controlled trials (RCTs) that compared LFD to other diets were included if they assessed symptoms of IBS or abdominal pain in patients with IBS. Safety, quality of life, anxiety, depression, and effect on gut microbiota were defined as secondary outcomes. Standardized mean difference (SMD) and 95% confidence interval (CI) were calculated. RESULTS: Nine RCTs with a total of 596 subjects were included. Three RCTs compared LFD with a habitual diet, two RCTs provided all meals and compared LFD with a western diet, one RCT each compared LFD with a diet high in FODMAPs or a sham diet, and two RCTs compared with other diet recommendations for IBS. A meta-analysis revealed significant group differences for LFD compared with other diets with regard to gastrointestinal symptoms (SMD = -0.62; 95% CI = -0.93 to -0.31; P = 0.0001), abdominal pain (SMD = -0.50; 95% CI = -0.77 to -0.22; P = 0.008), and health-related quality of life (SMD = 0.36; 95% CI = 0.10-0.62; P = 0.007). Three studies reported a significant reduction in luminal bifidobacteria after LFD. Adverse events were assessed in three RCTs only and no intervention-related adverse events were reported. CONCLUSIONS: This meta-analysis found evidence of the short-term efficacy and safety of LFD in patients with IBS. However, only a preliminary recommendation for LFD can be made until long-term effects are investigated.

Effects of Cupping Therapy in Amateur and Professional Athletes: Systematic Review of Randomized Controlled Trials.

OBJECTIVE: Despite the recent re-emergence of the process of cupping by athletes, supporting evidence for its efficacy and safety remains scarce. This systematic review aims to summarize the evidence of clinical trials on cupping for athletes. METHODS: SCOPUS, Cochrane Library, PubMed, AMED, and CNKI databases were searched from their inception to December 10, 2016. Randomized controlled trials on cupping therapy with no restriction regarding the technique, or cointerventions, were included, if they measured the effects of cupping compared with any other intervention on health and performance outcomes in professionals, semi-professionals, and leisure athletes. Data extraction and risk of bias assessment using the Cochrane Risk of Bias Tool were conducted independently by two pairs of reviewers. RESULTS: Eleven trials with n = 498 participants from China, the United States, Greece, Iran, and the United Arab Emirates were included, reporting effects on different populations, including soccer, football, and handball players, swimmers, gymnasts, and track and field athletes of both amateur and professional nature. Cupping was applied between 1 and 20 times, in daily or weekly intervals, alone or in combination with, for example, acupuncture. Outcomes varied greatly from symptom intensity, recovery measures, functional measures, serum markers, and experimental outcomes. Cupping was reported as beneficial for perceptions of pain and disability, increased range of motion, and reductions in creatine kinase when compared to mostly untreated control groups. The majority of trials had an unclear or high risk of bias. None of the studies reported safety. CONCLUSIONS: No explicit recommendation for or against the use of cupping for athletes can be made. More studies are necessary for conclusive judgment on the efficacy and safety of cupping in athletes.

Effects of yoga on chronic neck pain: a systematic review and meta-analysis.

OBJECTIVE: The aim of this review was to systematically assess and meta-analyze the effectiveness of yoga in relieving chronic neck pain. METHODS: PubMed/MEDLINE, the Cochrane Library, Scopus, and IndMED were screened through January 2017 for randomized controlled trials assessing neck pain intensity and/or neck pain-related disability in chronic neck pain patients. Secondary outcome measures included quality of life, mood, and safety. Risk of bias was assessed using the Cochrane tool. RESULTS: Three studies on 188 patients with chronic non-specific neck pain comparing yoga to usual care were included. Two studies had overall low risk of bias; and one had high or unclear risk of bias for several domains. Evidence for short-term effects was found for neck pain intensity (standardized mean difference (SMD) = -1.28; 95% confidence interval (CI) = -1.18, -0.75; P < 0.001), neck pain-related disability (SMD = -0.97; 95% CI = -1.44, -0.50; P < 0.001), quality of life (SMD = 0.57; 95% CI = 0.17, 0.197; P = 0.005), and mood (SMD = -1.02; 95% CI = -1.38, -0.65; P < 0.001). Effects were robust against potential methodological bias and did not differ between different intervention subgroups. In the two studies that included safety data, no serious adverse events occurred. CONCLUSION: Yoga has short-term effects on chronic neck pain, its related disability, quality of life, and mood suggesting that yoga might be a good treatment option.