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Safety of red yeast rice supplementation: A systematic review and meta-analysis of randomized controlled trials.
Fogacci, F, Banach, M, Mikhailidis, DP, Bruckert, E, Toth, PP, Watts, GF, Reiner, Ž, Mancini, J, Rizzo, M, Mitchenko, O, et al
Pharmacological research. 2019;:1-16
Abstract
Recently, concerns regarding the safety of red yeast rice (RYR) have been raised after the publication of some case reports claiming toxicity. Since the previous meta-analyses on the effects of RYR were mainly focused on its efficacy to improve lipid profile and other cardiovascular parameters, we carried out a meta-analysis on safety data derived from the available randomized controlled clinical trials (RCTs). Primary outcomes were musculoskeletal disorders (MuD). Secondary outcomes were non-musculoskeletal adverse events (Non-MuD) and serious adverse events (SAE). Subgroups analyses were carried out considering the intervention (RYR alone or in association with other nutraceutical compounds), monacolin K administered daily dose (≤3, 3.1-5 or >5 mg/day), follow-up (>12 or ≤12 weeks), with statin therapy or statin-intolerance and type of control treatment (placebo or statin treatment). Data were pooled from 53 RCTs comprising 112 treatment arms, which included 8535 subjects, with 4437 in the RYR arm and 4303 in the control one. Monacolin K administration was not associated with increased risk of MuD (odds ratio (OR) = 0.94, 95% confidence interval (CI) 0.53,1.65). Moreover, we showed reduced risk of Non-MuD (OR = 0.59, 95%CI 0.50, 0.69) and SAE (OR = 0.54, 95%CI 0.46, 0.64) vs. control. Subgroups analyses confirmed the high tolerability profile of RYR. Furthermore, increasing daily doses of monacolin K were negatively associated with increasing risk of Non-MuD (slope: -0.10; 95%CI: -0.17, -0.03; two-tailed p < 0.01). Based on our data, RYR use as lipid-lowering dietary supplement seems to be overall tolerable and safe in a large kind of moderately hypercolesterolaemic subjects.
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Systematic review, and meta-analysis of steroid-sparing effect, of biologic agents in randomized, placebo-controlled phase 3 trials for systemic lupus erythematosus.
Oon, S, Huq, M, Godfrey, T, Nikpour, M
Seminars in arthritis and rheumatism. 2018;(2):221-239
Abstract
OBJECTIVES To systematically review, and conduct a meta-analysis of steroid-sparing effect in, phase 3 randomized, placebo-controlled trials of biologic therapies for systemic lupus erythematosus (SLE). METHODS Studies were identified by searching Medline (via Pubmed), EMBASE, CINAHL and SCOPUS databases, the Cochrane library, and clinicaltrials.gov. Adult human studies published in English in the last ten years (until 18/04/2017) were included. A random-effects meta-analysis comparing a common corticosteroid-reduction endpoint in the trials of rituximab, belimumab, tabalumab and epratuzumab in SLE, was conducted. RESULTS Twenty-eight studies were identified; nine were conducted in SLE, five in lupus nephritis and the remaining 14 were post hoc analyses of phase 3 trials in SLE. All therapies trialed targeted B-cells (rituximab (anti-CD20 monoclonal antibody (mAb)), belimumab (anti-BAFF mAb), tabalumab (anti-BAFF mAb), epratuzumab (anti-CD22 mAb), atacicept (TACI-Ig), ocrelizumab (anti-CD20 mAb)), except for abetimus sodium and abatacept (CTLA4-Ig). Only the three trials of belimumab met their primary endpoints, although benefit in secondary endpoints and reduction in serological activity was often seen in the other studies. Meta-analysis showed that most therapies (belimumab, tabalumab, and epratuzumab) had a steroid-sparing effect, compared to placebo (pooled RR 1.36 (1.19, 1.56), I2 = 0, p < 0.67). Therapies were generally well tolerated; however, three studies were terminated prematurely due to serious side effects. CONCLUSIONS With the exception of belimumab, none of the phase 3 trials of biologic therapy in SLE have met their primary endpoint. However, the significant steroid-sparing effect of these agents suggests that future trials may need to include steroid dose in a composite primary endpoint.
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Impact of biological therapy on work outcomes in patients with axial spondyloarthritis: results from the British Society for Rheumatology Biologics Register (BSRBR-AS) and meta-analysis.
Shim, J, Jones, GT, Pathan, EMI, Macfarlane, GJ
Annals of the rheumatic diseases. 2018;(11):1578-1584
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Abstract
OBJECTIVES To quantify, among patients with axial spondyloarthritis (axSpA), the benefit on work outcomes associated with commencing biologic therapy. METHODS The British Society for Rheumatology Biologics Register in Axial Spondyloarthritis (BSRBRAS) recruited patients meeting Assessment of SpondyloArthritis International Society criteria for axSpA naïve to biological therapy across 83 centres in Great Britain. Work outcomes (measured using the Work Productivity and Activity Impairment Index) were compared between those starting biological therapy at the time of recruitment and those not. Differences between treatment groups were adjusted using propensity score matching. Results from BSRBR-AS were combined with other studies in a meta-analysis to calculate pooled estimates. RESULTS Of the 577 participants in this analysis who were in employment, 27.9% were starting biological therapy at the time of recruitment. After propensity score adjustment, patients undergoing biological therapy, at 12-month follow-up, experienced significantly greater improvements (relative to non-biological therapy) in presenteeism (-9.4%, 95% CI -15.3% to -3.5%), overall work impairment (-13.9%, 95% CI -21.1% to -6.7%) and overall activity impairment (-19.2%, 95% CI -26.3% to -12.2%). There was no difference in absenteeism (-1.5%, 95% CI -8.0 to 4.9). Despite these improvements, impact on work was still greater in the biological treated cohort at follow-up. In the meta-analysis including 1109 subjects across observational studies and trials, treatment with biological therapy was associated with significantly greater improvements in presenteeism, work impairment and activity impairment, but there was no difference in absenteeism. CONCLUSIONS There is consistent evidence that treatment with biological therapy significantly improves work productivity and activity impairment in people with axSpA. However, there remain substantial unmet needs in relation to work.
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Efficacy and Safety of Cissus quadrangularis L. in Clinical Use: A Systematic Review and Meta-analysis of Randomized Controlled Trials.
Sawangjit, R, Puttarak, P, Saokaew, S, Chaiyakunapruk, N
Phytotherapy research : PTR. 2017;(4):555-567
Abstract
Cissus quadrangularis L. (Cissus) is a medicinal plant commonly used for centuries for various conditions, but lacks critical appraisal of its clinical effects. This study aimed to determine the efficacy and safety of Cissus in all conditions. Publications from 12 electronic databases were searched from inception through November 2016. A total of nine studies with 1108 patients were included. Each outcome was pooled using a random effects model. Effects of Cissus on hemorrhoid symptoms were not different from any comparators but had significant effects on bone pain. Effects of Cissus combination products on body weight reduction, low-density lipoprotein, triglyceride, total cholesterol, and fasting blood sugar were superior to placebo, with weighted mean difference of -5.19 kg (-8.82, -1.55), -14.43 mg/dl (-20.06, -8.80), -37.50 mg/dl (-48.71, -26.29), -50.50 mg/dl (-70.97, -30.04), and -10.39 mg/dl (-14.60, -6.18), respectively. No serious adverse effects were reported. Quality of evidence based on Grades of Recommendations Assessment Development and Evaluation (GRADE) indicated low (bone fractures) to high quality (hemorrhoids, body weight reduction).In conclusion, Cissus had benefit for bone fractures, but not for hemorrhoids. For obesity/overweight, only combination products are pooled and show benefit. However, high-quality studies remain needed. Copyright © 2017 John Wiley & Sons, Ltd.
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Original Research: The Effects of Red Yeast Rice Supplementation on Cholesterol Levels in Adults.
Peng, D, Fong, A, Pelt, AV
The American journal of nursing. 2017;(8):46-54
Abstract
UNLABELLED : Purpose: Red yeast rice (RYR) supplementation has become a popular alternative to statin therapy in treating hypercholesterolemia. This state-of-the-science review seeks to explore the most recent evidence on the effectiveness and safety of RYR supplementation in treating dyslipidemic adults. METHODS This review extends the time frame of a meta-analysis performed by Li and colleagues in 2014; specifically, we looked at the literature published between September 2013 and April 2016. We conducted a search of four electronic databases-PsycINFO, CINAHL, PubMed, and Scopus-using the terms red yeast rice and cholesterol. We excluded studies that included berberine or lovastatin. RESULTS Fifteen articles met the inclusion criteria. Eleven articles reported on randomized controlled trials, one reported on an open-label pilot study, and one reported on an open-label clinical trial. Two articles were meta-analyses. The 13 studies involved a total of 1,246 participants, with an additional 7,467 participants reported in the two meta-analyses. Significant reductions in low-density lipoprotein cholesterol and total cholesterol levels with RYR supplementation were observed in all trials. There were no significant changes in liver and kidney function, and 10 studies noted no significant changes in creatine kinase levels. CONCLUSIONS Although RYR appears to be a safe and effective lipid-lowering agent, there is insufficient evidence to support the recommendation of RYR supplementation to patients. Further research is needed, including long-term studies, studies that include participants with comorbidities and complex medical histories, and studies that take into account the variability of formulation and dosage of RYR in the marketplace.
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Cereal Lignans, Natural Compounds of Interest for Human Health?
Zanella, I, Biasiotto, G, Holm, F, di Lorenzo, D
Natural product communications. 2017;(1):139-146
Abstract
Cereals are suggested to be the most important sources of lignan in the diets of western populations. Recent epidemiological studies show that European subpopulations in which the major source of lignans are cereals, display lower disease frequency regarding metabolic and cardiovascular diseases. The biological mechanisms of lignan are several. Beyond their antioxidant and anti-inflammatory actions at nutritional doses some lignans regulate the activity of specific nuclear receptors (NRs), such as the estrogen receptors (ERs), and also NRs that are central switches in glucose and fatty acid metabolism such as PPARα, PPARγ and LXRs, highlighting them as selective nuclear receptor modulators (SNRMs). These include enterodiol (END) and enterolactone (ENL), the metabolites produced by the gut microbiota from food lignans. The available knowledge suggests that given some additional research it should be possible to make 'function' claims for a regular intake of lignans-rich foods related to maintaining a healthy metabolism.
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Canadian Network for Mood and Anxiety Treatments (CANMAT) 2016 Clinical Guidelines for the Management of Adults with Major Depressive Disorder: Section 5. Complementary and Alternative Medicine Treatments.
Ravindran, AV, Balneaves, LG, Faulkner, G, Ortiz, A, McIntosh, D, Morehouse, RL, Ravindran, L, Yatham, LN, Kennedy, SH, Lam, RW, et al
Canadian journal of psychiatry. Revue canadienne de psychiatrie. 2016;(9):576-87
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BACKGROUND The Canadian Network for Mood and Anxiety Treatments (CANMAT) conducted a revision of the 2009 guidelines by updating the evidence and recommendations. The scope of the 2016 guidelines remains the management of major depressive disorder (MDD) in adults, with a target audience of psychiatrists and other mental health professionals. METHODS Using the question-answer format, we conducted a systematic literature search focusing on systematic reviews and meta-analyses. Evidence was graded using CANMAT-defined criteria for level of evidence. Recommendations for lines of treatment were based on the quality of evidence and clinical expert consensus. "Complementary and Alternative Medicine Treatments" is the fifth of six sections of the 2016 guidelines. RESULTS Evidence-informed responses were developed for 12 questions for 2 broad categories of complementary and alternative medicine (CAM) interventions: 1) physical and meditative treatments (light therapy, sleep deprivation, exercise, yoga, and acupuncture) and 2) natural health products (St. John's wort, omega-3 fatty acids; S-adenosyl-L-methionine [SAM-e], dehydroepiandrosterone, folate, Crocus sativus, and others). Recommendations were based on available data on efficacy, tolerability, and safety. CONCLUSIONS For MDD of mild to moderate severity, exercise, light therapy, St. John's wort, omega-3 fatty acids, SAM-e, and yoga are recommended as first- or second-line treatments. Adjunctive exercise and adjunctive St. John's wort are second-line recommendations for moderate to severe MDD. Other physical treatments and natural health products have less evidence but may be considered as third-line treatments. CAM treatments are generally well tolerated. Caveats include methodological limitations of studies and paucity of data on long-term outcomes and drug interactions.
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Lipid profile changes in patients with chronic inflammatory arthritis treated with biologic agents and tofacitinib in randomized clinical trials: a systematic review and meta-analysis.
Souto, A, Salgado, E, Maneiro, JR, Mera, A, Carmona, L, Gómez-Reino, JJ
Arthritis & rheumatology (Hoboken, N.J.). 2015;(1):117-27
Abstract
OBJECTIVE To analyze lipid changes in patients with rheumatoid arthritis (RA) and patients with spondyloarthritis (SpA) treated with biologic agents or tofacitinib in randomized clinical trials (RCTs). METHODS A systematic literature search was performed, using the Medline, Embase, Cochrane Library, and Web of Knowledge databases. Meta-analyses were performed using random-effects models to assess changes in the percentage of patients with abnormal lipid values or in the mean percentage of increase in the cholesterol and triglycerides levels. RESULTS Twenty-five of 4,527 identified articles met the inclusion criteria. Compared with RA patients treated with placebo, those treated with tocilizumab were more likely to have hypercholesterolemia (odds ratio [OR] 4.64; 95% confidence interval [95% CI] 2.71, 7.95 [P < 0.001]), increased levels of high-density lipoprotein (HDL) cholesterol (OR 2.25; 95% CI 1.14, 4.44 [P = 0.020]), and increased levels of low-density lipoprotein (LDL) cholesterol (OR 4.80; 95% CI 3.27, 7.05 [P < 0.001]); this was not observed in patients treated with tumor necrosis factor (TNF) antagonists (OR 1.54; 95% CI 0.90, 2.66 [P = 0.119]) or tofacitinib (OR 3.4; 95% CI 0.62, 18.55 [P = 0.158]). Among patients receiving tofacitinib 5 mg twice daily, the mean percentage of increases in the HDL cholesterol level (weighted mean difference [WMD] 13.00 mg/dl; 95% CI 12.08, 13.93 [P < 0.001]) and the LDL cholesterol level (WMD 11.20 mg/dl; 95% CI 10.08, 12.32 [P < 0.001]) were higher than those in the comparator groups. Among patients treated with tofacitinib 10 mg twice daily, the mean percentage of increases in the HDL cholesterol level (WMD 15.21 mg/dl; 95% CI 13.28, 17.14 [P < 0.001]) and the LDL cholesterol level (WMD 15.42 mg/dl; 95% CI 11.77, 19.06 [P < 0.001]) were also higher than those in the comparator groups. No data were available for RA treated with other biologic agents or for SpA. CONCLUSION In patients with RA treated with tocilizumab or tofacitinib but not with TNF antagonists, moderate changes in lipids are observed. Whether these changes pertain to the control of inflammation or to the mechanism of action of the biologic agents or tofacitinib remains undetermined.
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[Large-joint synovectomy in the era of biological therapies].
Carl, HD, Rech, J
Zeitschrift fur Rheumatologie. 2011;(1):9-13
Abstract
Since the mid 1980s, a global decrease in surgical procedures related to rheumatoid arthritis (RA) has been documented for joint-preserving procedures such as synovectomy as well as joint replacement surgery. This reflects improvements in the early management of rheumatoid arthritis and availability of more effective medical treatment. The present review summarizes the recent literature on the frequency of orthopaedic surgery in RA patients as well as the role of synovectomy in the rheumatoid hip, knee and shoulder in times of biological RA therapy.
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Adverse effects of biologics: a network meta-analysis and Cochrane overview.
Singh, JA, Wells, GA, Christensen, R, Tanjong Ghogomu, E, Maxwell, L, Macdonald, JK, Filippini, G, Skoetz, N, Francis, D, Lopes, LC, et al
The Cochrane database of systematic reviews. 2011;(2):CD008794
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BACKGROUND Biologics are used for the treatment of rheumatoid arthritis and many other conditions. While the efficacy of biologics has been established, there is uncertainty regarding the adverse effects of this treatment. Since serious risks such as tuberculosis (TB) reactivation, serious infections, and lymphomas may be common to the biologics but occur in small numbers across the various indications, we planned to combine the results from biologics used in many conditions to obtain the much needed risk estimates. OBJECTIVES To compare the adverse effects of tumor necrosis factor blocker (etanercept, adalimumab, infliximab, golimumab, certolizumab), interleukin (IL)-1 antagonist (anakinra), IL-6 antagonist (tocilizumab), anti-CD28 (abatacept), and anti-B cell (rituximab) therapy in patients with any disease condition except human immunodeficiency disease (HIV/AIDS). METHODS Randomized controlled trials (RCTs), controlled clinical trials (CCTs) and open-label extension (OLE) studies that studied one of the nine biologics for use in any indication (with the exception of HIV/AIDS) and that reported our pre-specified adverse outcomes were considered for inclusion. We searched The Cochrane Library, MEDLINE, and EMBASE (to January 2010). Identifying search results and data extraction were performed independently and in duplicate. For the network meta-analysis, we performed mixed-effects logistic regression using an arm-based, random-effects model within an empirical Bayes framework. MAIN RESULTS We included 163 RCTs with 50,010 participants and 46 extension studies with 11,954 participants. The median duration of RCTs was six months and 13 months for OLEs. Data were limited for tuberculosis (TB) reactivation, lymphoma, and congestive heart failure. Adjusted for dose, biologics as a group were associated with a statistically significant higher rate of total adverse events (odds ratio (OR) 1.19, 95% CI 1.09 to 1.30; number needed to treat to harm (NNTH) = 30, 95% CI 21 to 60) and withdrawals due to adverse events (OR 1.32, 95% CI 1.06 to 1.64; NNTH = 37, 95% CI 19 to 190) and an increased risk of TB reactivation (OR 4.68, 95% CI 1.18 to 18.60; NNTH = 681, 95% CI 143 to 14706) compared to control.The rate of serious adverse events, serious infections, lymphoma, and congestive heart failure were not statistically significantly different between biologics and control treatment. Certolizumab pegol was associated with significantly higher risk of serious infections compared to control treatment (OR 3.51, 95% CI 1.59 to 7.79; NNTH = 17, 95% CI 7 to 68). Infliximab was associated with significantly higher risk of withdrawals due to adverse events compared to control (OR 2.04, 95% CI 1.43 to 2.91; NNTH = 12, 95% CI 8 to 28). Indirect comparisons revealed that abatacept and anakinra were associated with a significantly lower risk of serious adverse events compared to most other biologics. Although the overall numbers are relatively small, certolizumab pegol was associated with significantly higher odds of serious infections compared to etanercept, adalimumab, abatacept, anakinra, golimumab, infliximab, and rituximab; abatacept was significantly less likely than infliximab and tocilizumab to be associated with serious infections. Abatacept, adalimumab, etanercept and golimumab were significantly less likely than infliximab to result in withdrawals due to adverse events. AUTHORS' CONCLUSIONS Overall, in the short term biologics were associated with significantly higher rates of total adverse events, withdrawals due to adverse events and TB reactivation. Some biologics had a statistically higher association with certain adverse outcomes compared to control, but there was no consistency across the outcomes so caution is needed in interpreting these results.There is an urgent need for more research regarding the long-term safety of biologics and the comparative safety of different biologics. National and international registries and other types of large databases are relevant sources for providing complementary evidence regarding the short- and longer-term safety of biologics.