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Broad synthesis / Overview of systematic reviews

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Journal The Cochrane database of systematic reviews
Year 2023
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BACKGROUND: Complex regional pain syndrome (CRPS) is a chronic pain condition that usually occurs in a limb following trauma or surgery. It is characterised by persisting pain that is disproportionate in magnitude or duration to the typical course of pain after similar injury. There is currently no consensus regarding the optimal management of CRPS, although a broad range of interventions have been described and are commonly used. This is the first update of the original Cochrane review published in Issue 4, 2013. OBJECTIVES: To summarise the evidence from Cochrane and non-Cochrane systematic reviews of the efficacy, effectiveness, and safety of any intervention used to reduce pain, disability, or both, in adults with CRPS. METHODS: We identified Cochrane reviews and non-Cochrane reviews through a systematic search of Ovid MEDLINE, Ovid Embase, Cochrane Database of Systematic Reviews, CINAHL, PEDro, LILACS and Epistemonikos from inception to October 2022, with no language restrictions. We included systematic reviews of randomised controlled trials that included adults (≥18 years) diagnosed with CRPS, using any diagnostic criteria.  Two overview authors independently assessed eligibility, extracted data, and assessed the quality of the reviews and certainty of the evidence using the AMSTAR 2 and GRADE tools respectively. We extracted data for the primary outcomes pain, disability and adverse events, and the secondary outcomes quality of life, emotional well-being, and participants' ratings of satisfaction or improvement with treatment.  MAIN RESULTS: We included six Cochrane and 13 non-Cochrane systematic reviews in the previous version of this overview and five Cochrane and 12 non-Cochrane reviews in the current version. Using the AMSTAR 2 tool, we judged Cochrane reviews to have higher methodological quality than non-Cochrane reviews. The studies in the included reviews were typically small and mostly at high risk of bias or of low methodological quality. We found no high-certainty evidence for any comparison.  There was low-certainty evidence that bisphosphonates may reduce pain intensity post-intervention (standardised mean difference (SMD) -2.6, 95% confidence interval (CI) -1.8 to -3.4, P = 0.001; I2 = 81%; 4 trials, n = 181) and moderate-certainty evidence that they are probably associated with increased adverse events of any nature (risk ratio (RR) 2.10, 95% CI 1.27 to 3.47; number needed to treat for an additional harmful outcome (NNTH) 4.6, 95% CI 2.4 to 168.0; 4 trials, n = 181).  There was moderate-certainty evidence that lidocaine local anaesthetic sympathetic blockade probably does not reduce pain intensity compared with placebo, and low-certainty evidence that it may not reduce pain intensity compared with ultrasound of the stellate ganglion. No effect size was reported for either comparison. There was low-certainty evidence that topical dimethyl sulfoxide may not reduce pain intensity compared with oral N-acetylcysteine, but no effect size was reported. There was low-certainty evidence that continuous bupivacaine brachial plexus block may reduce pain intensity compared with continuous bupivacaine stellate ganglion block, but no effect size was reported. For a wide range of other commonly used interventions, the certainty in the evidence was very low and provides insufficient evidence to either support or refute their use. Comparisons with low- and very low-certainty evidence should be treated with substantial caution. We did not identify any RCT evidence for routinely used pharmacological interventions for CRPS such as tricyclic antidepressants or opioids. AUTHORS' CONCLUSIONS: Despite a considerable increase in included evidence compared with the previous version of this overview, we identified no high-certainty evidence for the effectiveness of any therapy for CRPS. Until larger, high-quality trials are undertaken, formulating an evidence-based approach to managing CRPS will remain difficult. Current non-Cochrane systematic reviews of interventions for CRPS are of low methodological quality and should not be relied upon to provide an accurate and comprehensive summary of the evidence.

Broad synthesis

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Journal Osteoarthritis and cartilage open
Year 2022
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OBJECTIVE: To conduct a network meta-analysis comparing all treatments for osteoarthritis (OA) pain in the Cochrane Library. DESIGN: The Cochrane Library and Epistemonikos were searched for randomized controlled trials (RCTs) about treatments for hip and knee OA. We constructed 17 broad categories, comprising drug treatments, exercise, surgery, herbs, orthotics, passive treatments, regenerative medicine, diet/weight loss, combined treatments, and controls. In addition to a full network analysis, we compared the direct/indirect effects, and studies with shorter-/longer follow-up. CINeMA software was used for assessing confidence in network meta-analysis estimates. RESULTS: We included 35 systematic reviews including 445 RCTs. There were 153 treatments for OA. In total, 491 comparisons were related to knee OA, less on hip OA, and only nine on hand OA. Six treatment categories showed clinically significant effects favoring treatment over control on pain. "Diet/weight loss" and "Surgery" had effect sizes close to zero. The network as a whole was not coherent. Of 136 treatment comparisons, none were rated as high confidence, six as moderate, 13 as low, and 117 as very low. CONCLUSIONS: Direct comparison of different available treatment options for OA is desirable, however not currently feasible in practice, due to heterogeneous study populations and lack of clear descriptions of control interventions. We found that many treatments were effective, but since the network as a whole was not coherent and lacked high confidence in the treatment comparisons, we could not produce a ranking of effects.

Broad synthesis

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Journal RMD Open
Year 2021
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OBJECTIVES: To summarise, by a systematic literature review (SLR), the evidence regarding pharmacological and non-pharmacological therapeutic strategies in difficult-to-treat rheumatoid arthritis (D2T RA), informing the EULAR recommendations for the management of D2T RA. METHODS: PubMed, Embase and Cochrane databases were searched up to December 2019. Relevant papers were selected and appraised. RESULTS: Two hundred seven (207) papers studied therapeutic strategies. Limited evidence was found on effective and safe disease-modifying antirheumatic drugs (DMARDs) in patients with comorbidities and other contraindications that limit DMARD options (patients with obesity, hepatitis B and C, risk of venous thromboembolisms, pregnancy and lactation). In patients who previously failed biological (b-)DMARDs, all currently used b/targeted synthetic (ts-)DMARDs were found to be more effective than placebo. In patients who previously failed a tumour necrosis factor inhibitor (TNFi), there was a tendency of non-TNFi bDMARDs to be more effective than TNFis. Generally, effectiveness decreased in patients who previously failed a higher number of bDMARDs. Additionally, exercise, psychological, educational and self-management interventions were found to improve non-inflammatory complaints (mainly functional disability, pain, fatigue), education to improve goal setting, and self-management programmes, educational and psychological interventions to improve self-management.The identified evidence had several limitations: (1) no studies were found in patients with D2T RA specifically, (2) heterogeneous outcome criteria were used and (3) most studies had a moderate or high risk of bias. CONCLUSIONS: This SLR underscores the scarcity of high-quality evidence on the pharmacological and non-pharmacological treatment of patients with D2T RA. Effectiveness of b/tsDMARDs decreased in RA patients who had failed a higher number of bDMARDs and a subsequent b/tsDMARD of a previously not targeted mechanism of action was somewhat more effective. Additionally, a beneficial effect of non-pharmacological interventions was found for improvement of non-inflammatory complaints, goal setting and self-management.

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ABSTRACT: Cannabis is the third most used psychoactive substance worldwide. The legal status of cannabis is changing in many Western countries, while we have very limited knowledge of the public health impact of cannabis-related harms. There is a need for a summary of the evidence of harms and risks attributed to cannabis use, in order to inform the definition of cannabis risky use. We have conducted a systematic review of systematic reviews, aiming to define cannabis-related harms. We included systematic reviews published until July 2018 from six different databases and following the PRISMA guidelines. To assess study quality we applied the AMSTAR 2 tool. A total of 44 systematic reviews, including 1,053 different studies, were eligible for inclusion. Harm was categorized in three dimensions: mental health, somatic harm and physical injury (including mortality). Evidence shows a clear association between cannabis use and psychosis, affective disorders, anxiety, sleep disorders, cognitive failures, respiratory adverse events, cancer, cardiovascular outcomes, and gastrointestinal disorders. Moreover, cannabis use is a risk factor for motor vehicle collision, suicidal behavior and partner and child violence. Cannabis use is a risk factor for several medical conditions and negative social consequences. There is still little data on the dose-dependency of these effects; evidence that is essential in order to define, from a public health perspective, what can be considered risky use of cannabis. This definition should be based on quantitative and qualitative criteria that informs and permits the evaluation of current approaches to a regulated cannabis market. (PsycINFO Database Record (c) 2020 APA, all rights reserved)

Broad synthesis / Overview of systematic reviews

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Journal Journal of alternative and complementary medicine (New York, N.Y.)
Year 2019
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OBJECTIVES: Massage therapy has been proposed for painful conditions, but it can be difficult to understand the breadth and depth of evidence, as various painful conditions may respond differently to massage. The authors conducted an evidence mapping process and generated an "evidence map" to visually depict the distribution of evidence available for massage and various pain indications to identify gaps in evidence and to inform future research priorities. DESIGN: The authors searched PubMed, Embase, and Cochrane for systematic reviews reporting pain outcomes for massage therapy. The authors assessed the quality of each review using the Assessing the Methodological Quality of Systematic Reviews (AMSTAR) criteria. The authors used a bubble plot to depict the number of included articles, pain indication, effect of massage for pain, and strength of findings for each included systematic review. RESULTS: The authors identified 49 systematic reviews, of which 32 were considered high quality. Types of pain frequently included in systematic reviews were cancer pain, low back pain, and neck pain. High quality reviews concluded that there was low strength of evidence of potential benefits of massage for labor, shoulder, neck, low back, cancer, arthritis, postoperative, delayed onset muscle soreness, and musculoskeletal pain. Reported attributes of massage interventions include style of massage, provider, co-interventions, duration, and comparators, with 14 high-quality reviews reporting all these attributes in their review. CONCLUSION: Prior reviews have conclusions of low strength of evidence because few primary studies of large samples with rigorous methods had been conducted, leaving evidence gaps about specific massage type for specific pain. Primary studies often do not provide adequate details of massage therapy provided, limiting the extent to which reviews are able to draw conclusions about characteristics such as provider type.

Broad synthesis / Living FRISBEE

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Authors Peña J , Jiménez C , Schmidt J
Journal Medwave
Year 2018
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INTRODUCTION: The use of cannabinoids in diverse clinical conditions is today a subject of debate. Its use has been proposed for the control of glaucoma. However, there is controversy about its real effectiveness and safety.; METHODS: To answer this question we used Epistemonikos, the largest database of systematic reviews in health, which is maintained by screening multiple information sources, including MEDLINE, EMBASE, Cochrane, among others. We extracted data from the systematic reviews, reanalyzed data of primary studies and generated a summary of findings table using the GRADE approach.; RESULTS AND CONCLUSIONS: We identified five systematic reviews including three studies overall, all of them randomized controlled trials. We concluded that although cannabinoids could decrease intraocular pressure, the effect would be transient and associated with frequent adverse effects.; INTRODUCCIÓN: El uso de cannabinoides en diversas condiciones clínicas es hoy un tema de debate. Se ha planteado su uso para el control del glaucoma. Sin embargo, existe controversia sobre su real efectividad y seguridad.; MÉTODOS: Para responder esta pregunta utilizamos Epistemonikos, la mayor base de datos de revisiones sistemáticas en salud, la cual es mantenida mediante búsquedas en múltiples fuentes de información, incluyendo MEDLINE, EMBASE, Cochrane, entre otras. Extrajimos los datos desde las revisiones identificadas, reanalizamos los datos de los estudios primarios y preparamos una tabla de resumen de los resultados utilizando el método GRADE.; RESULTADOS Y CONCLUSIONES: Identificamos cinco revisiones sistemáticas que en conjunto incluyen 3 estudios primarios, todos correspondientes a ensayos aleatorizados. Concluimos que, si bien los cannabinoides podrían disminuir la presión intraocular, lo hacen de forma transitoria y se asocian a efectos adversos frecuentes.

Broad synthesis / Overview of systematic reviews

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Journal European journal of pain (London, England)
Year 2018
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Medicinal cannabis has already entered mainstream medicine in some countries. This systematic review (SR) aimed at evaluating the efficacy, acceptability and safety of cannabis-based medicines for chronic pain management. Qualitative systematic review of SRs of randomized controlled trials with cannabis-based medicines for chronic pain management. The Cochrane databases of SRs, Database of Abstracts of Reviews of Effects and PubMed were searched for SR published in the period January 2009 to January 2017. Assessment of the methodological quality of SR was performed by the AMSTAR checklist. Out of 748 papers identified, 10 SRs met the inclusion criteria. The methodological quality was high in four and moderate in six SRs. There were inconsistent findings of four SRs on the efficacy of cannabis-based medicines in neuropathic pain and of one SR for painful spasms in multiple sclerosis. There were consistent results that there was insufficient evidence of any cannabis-based medicine for pain management in patients with rheumatic diseases (three SRs) and in cancer pain (two SRs). Cannabis-based medicines undoubtedly enrich the possibilities of drug treatment of chronic pain conditions. It remains the responsibility of the health care community to continue to pursue rigorous study of cannabis-based medicines to provide evidence that meets the standard of 21st century clinical care. Significance: We provide an overview of systematic reviews on the efficacy, tolerability and safety of cannabis-based medicines for chronic pain management. There are inconsistent findings of the efficacy of cannabinoids in neuropathic pain and painful spasms in multiple sclerosis. There are inconsistent results on tolerability and safety of cannabis-based medicines for any chronic pain. (PsycInfo Database Record (c) 2022 APA, all rights reserved)

Broad synthesis

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Authors Abrams DI
Journal European journal of internal medicine
Year 2018
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The National Academies of Sciences, Engineering and Medicine conducted a rapid turn-around comprehensive review of recent medical literature on The Health Effects of Cannabis and Cannabinoids. The 16-member committee adopted the key features of a systematic review process, conducting an extensive search of relevant databases and considered 10,000 recent abstracts to determine their relevance. Primacy was given to recently published systematic reviews and primary research that studied one of the committee's 11 prioritized health endpoints- therapeutic effects; cancer incidence; cardiometabolic risk; respiratory disease; immune function; injury and death; prenatal, perinatal and postnatal outcomes; psychosocial outcomes; mental health; problem Cannabis use; and Cannabis use and abuse of other substances. The committee developed standard language to categorize the weight of evidence regarding whether Cannabis or cannabinoids use for therapeutic purposes are an effective or ineffective treatment for the prioritized health endpoints of interest. In the Therapeutics chapter reviewed here, the report concluded that there was conclusive or substantial evidence that Cannabis or cannabinoids are effective for the treatment of pain in adults; chemotherapy-induced nausea and vomiting and spasticity associated with multiple sclerosis. Moderate evidence was found for secondary sleep disturbances. The evidence supporting improvement in appetite, Tourette syndrome, anxiety, posttraumatic stress disorder, cancer, irritable bowel syndrome, epilepsy and a variety of neurodegenerative disorders was described as limited, insufficient or absent. A chapter of the NASEM report enumerated multiple barriers to conducting research on Cannabis in the US that may explain the paucity of positive therapeutic benefits in the published literature to date.

Broad synthesis / Overview of systematic reviews

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OBJECTIVE: To determine the effects of medical cannabinoids on pain, spasticity, and nausea and vomiting, and to identify adverse events. DATA SOURCES: MEDLINE, the Cochrane Database, and the references of included studies were searched. STUDY SELECTION: Systematic reviews with 2 or more randomized controlled trials (RCTs) that focused on medical cannabinoids for pain, spasticity, or nausea and vomiting were included. For adverse events, any meta-analysis for the conditions listed or of adverse events of cannabinoids was included. SYNTHESIS: From 1085 articles, 31 relevant systematic reviews were identified including 23 for pain, 5 for spasticity, 6 for nausea and vomiting, and 12 for adverse events. Meta-analysis of 15 RCTs found more patients taking cannabinoids attained at least a 30% pain reduction: risk ratio (RR) of 1.37 (95% CI 1.14 to 1.64), number needed to treat (NNT) of 11. Sensitivity analysis found study size and duration affected findings (subgroup differences, CONCLUSION: There is reasonable evidence that cannabinoids improve nausea and vomiting after chemotherapy. They might improve spasticity (primarily in multiple sclerosis). There is some uncertainty about whether cannabinoids improve pain, but if they do, it is neuropathic pain and the benefit is likely small. Adverse effects are very common, meaning benefits would need to be considerable to warrant trials of therapy.

Broad synthesis / Living FRISBEE

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Authors Rocco M , Rada G
Journal Medwave
Year 2018
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INTRODUCTION: Cannabinoids have been proposed as a therapeutic alternative for fibromyalgia. However, their clinical effectiveness is a matter of debate. METHODS: To answer this question we used Epistemonikos, the largest database of systematic reviews in health, which is maintained by screening multiple information sources, including MEDLINE, EMBASE, Cochrane, among others. We extracted data from the systematic reviews, reanalyzed data of primary studies and generated a summary of findings table using the GRADE approach. RESULTS AND CONCLUSIONS: We identified fifteen systematic reviews including two randomized trials overall. We concluded it is not clear whether cannabinoids have any benefit in fibromyalgia because the certainty of the evidence is very low. On the other hand, they are associated to frequent adverse effects.