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The American Journal of Gastroenterology Jun 2021Constipation is commonly treated with over-the-counter (OTC) products whose efficacy and safety remain unclear. We performed a systematic review of OTC therapies for...
INTRODUCTION
Constipation is commonly treated with over-the-counter (OTC) products whose efficacy and safety remain unclear. We performed a systematic review of OTC therapies for chronic constipation and provide evidence-based recommendations.
METHODS
We searched PubMed and Embase for randomized controlled trials of ≥4-week duration that evaluated OTC preparations between 2004 and 2020. Studies were scored using the US Preventive Services Task Force criteria (0-5 scale) including randomization, blinding, and withdrawals. The strengths of evidence were adjudicated within each therapeutic category, and recommendations were graded (A, B, C, D, and I) based on the level of evidence (level I, good; II, fair; or III, poor).
RESULTS
Of 1,297 studies identified, 41 met the inclusion criteria. There was good evidence (grade A recommendation) for the use of the osmotic laxative polyethylene glycol (PEG) and the stimulant senna; moderate evidence (grade B) for psyllium, SupraFiber, magnesium salts, stimulants (bisacodyl and sodium picosulfate), fruit-based laxatives (kiwi, mango, prunes, and ficus), and yogurt with galacto-oligosaccharide/prunes/linseed oil; and insufficient evidence (grade I) for polydextrose, inulin, and fructo-oligosaccharide. Diarrhea, nausea, bloating, and abdominal pain were common adverse events, but no serious adverse events were reported.
DISCUSSION
The spectrum of OTC products has increased and quality of evidence has improved, but methodological issues including variability in study design, primary outcome measures, trial duration, and small sample sizes remain. We found good evidence to recommend polyethylene glycol or senna as first-line laxatives and moderate evidence supporting fiber supplements, fruits, stimulant laxatives, and magnesium-based products. For others, further validation with more rigorously designed studies is warranted.
Topics: Bisacodyl; Cathartics; Chronic Disease; Citrates; Constipation; Defecation; Fruit; Gastrointestinal Agents; Glucans; Humans; Inulin; Laxatives; Magnesium; Nonprescription Drugs; Oligosaccharides; Organometallic Compounds; Picolines; Polyethylene Glycols; Psyllium; Senna Extract; Yogurt
PubMed: 33767108
DOI: 10.14309/ajg.0000000000001222 -
The Cochrane Database of Systematic... Aug 2016Constipation within childhood is an extremely common problem. Despite the widespread use of osmotic and stimulant laxatives by health professionals to manage... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Constipation within childhood is an extremely common problem. Despite the widespread use of osmotic and stimulant laxatives by health professionals to manage constipation in children, there has been a long standing paucity of high quality evidence to support this practice.
OBJECTIVES
We set out to evaluate the efficacy and safety of osmotic and stimulant laxatives used to treat functional childhood constipation.
SEARCH METHODS
We searched MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials, and the Cochrane IBD Group Specialized Trials Register from inception to 10 March 2016. There were no language restrictions. We also searched the references of all included studies, personal contacts and drug companies to identify studies.
SELECTION CRITERIA
Randomised controlled trials (RCTs) which compared osmotic or stimulant laxatives to placebo or another intervention, with participants aged 0 to 18 years old were considered for inclusion. The primary outcome was frequency of defecation. Secondary endpoints included faecal incontinence, disimpaction, need for additional therapies and adverse events.
DATA COLLECTION AND ANALYSIS
Relevant papers were identified and two authors independently assessed the eligibility of trials, extracted data and assessed methodological quality using the Cochrane risk of bias tool. The primary outcome was frequency of defecation. Secondary endpoints included faecal incontinence, disimpaction, need for additional therapies and adverse events. For continuous outcomes we calculated the mean difference (MD) and 95% confidence interval (CI) using a fixed-effect model. For dichotomous outcomes we calculated the risk ratio (RR) and 95% CI using a fixed-effect model. The Chi(2) and I(2) statistics were used to assess statistical heterogeneity. A random-effects model was used in situations of unexplained heterogeneity. We assessed the overall quality of the evidence supporting the primary and secondary outcomes using the GRADE criteria.
MAIN RESULTS
Twenty-five RCTs (2310 participants) were included in the review. Fourteen studies were judged to be at high risk of bias due to lack of blinding, incomplete outcome data and selective reporting. Meta-analysis of two studies (101 patients) comparing polyethylene glycol (PEG) with placebo showed a significantly increased number of stools per week with PEG (MD 2.61 stools per week, 95% CI 1.15 to 4.08). Common adverse events in the placebo-controlled studies included flatulence, abdominal pain, nausea, diarrhoea and headache. Participants receiving high dose PEG (0.7 g/kg) had significantly more stools per week than low dose PEG (0.3 g/kg) participants (1 study, 90 participants, MD 1.30, 95% 0.76 to 1.84). Meta-analysis of 6 studies with 465 participants comparing PEG with lactulose showed a significantly greater number of stools per week with PEG (MD 0.70 , 95% CI 0.10 to 1.31), although follow-up was short. Patients who received PEG were significantly less likely to require additional laxative therapies. Eighteen per cent (27/154) of PEG patients required additional therapies compared to 31% (47/150) of lactulose patients (RR 0.55, 95% CI 0.36 to 0.83). No serious adverse events were reported with either agent. Common adverse events in these studies included diarrhoea, abdominal pain, nausea, vomiting and pruritis ani. Meta-analysis of 3 studies with 211 participants comparing PEG with milk of magnesia showed that the stools per week were significantly greater with PEG (MD 0.69, 95% CI 0.48 to 0.89). However, the magnitude of this difference was quite small and may not be clinically significant. One child was noted to be allergic to PEG, but there were no other serious adverse events reported. One study found a significant difference in stools per week favouring milk of magnesia over lactulose (MD -1.51, 95% CI -2.63 to -0.39, 50 patients), Meta-analysis of 2 studies with 287 patients comparing liquid paraffin (mineral oil) with lactulose revealed a relatively large statistically significant difference in the number of stools per week favouring liquid paraffin (MD 4.94 , 95% CI 4.28 to 5.61). No serious adverse events were reported. Adverse events included abdominal pain, distention and watery stools. No statistically significant differences in the number of stools per week were found between PEG and enemas (1 study, 90 patients, MD 1.00, 95% CI -1.58 to 3.58), dietary fibre mix and lactulose (1 study, 125 patients, P = 0.481), senna and lactulose (1 study, 21 patients, P > 0.05), lactitol and lactulose (1 study, 51 patients, MD -0.80, 95% CI -2.63 to 1.03), hydrolyzed guar gum and lactulose (1 study, 61 patients, MD 1.00, 95% CI -1.80 to 3.80), PEG and flixweed (1 study, 109 patients, MD 0.00, 95% CI -0.33 to 0.33), PEG and dietary fibre (1 study, 83 patients, MD 0.20, 95% CI -0.64 to 1.04), and PEG and liquid paraffin (2 studies, 261 patients, MD 0.35, 95% CI -0.24 to 0.95).
AUTHORS' CONCLUSIONS
The pooled analyses suggest that PEG preparations may be superior to placebo, lactulose and milk of magnesia for childhood constipation. GRADE analyses indicated that the overall quality of the evidence for the primary outcome (number of stools per week) was low or very low due to sparse data, inconsistency (heterogeneity), and high risk of bias in the studies in the pooled analyses. Thus, the results of the pooled analyses should be interpreted with caution because of quality and methodological concerns, as well as clinical heterogeneity, and short follow-up. There is also evidence suggesting the efficacy of liquid paraffin (mineral oil). There is no evidence to demonstrate the superiority of lactulose when compared to the other agents studied, although there is a lack of placebo controlled studies. Further research is needed to investigate the long term use of PEG for childhood constipation, as well as the role of liquid paraffin. The optimal dose of PEG also warrants further investigation.
Topics: Adolescent; Child; Child, Preschool; Constipation; Defecation; Dietary Fiber; Enema; Female; Humans; Infant; Infant, Newborn; Lactulose; Laxatives; Magnesium Hydroxide; Male; Mineral Oil; Osmosis; Polyethylene Glycols; Randomized Controlled Trials as Topic; Senna Extract; Sennosides; Treatment Outcome
PubMed: 27531591
DOI: 10.1002/14651858.CD009118.pub3 -
Phytotherapy Research : PTR Mar 2022This systematic review and meta-analysis were conducted to determine the effects of anthraquinone (AQ) laxatives on colorectal cancer (CRC). We searched PubMed, Embase,... (Meta-Analysis)
Meta-Analysis Review
This systematic review and meta-analysis were conducted to determine the effects of anthraquinone (AQ) laxatives on colorectal cancer (CRC). We searched PubMed, Embase, Google Scholar, and CENTRAL from inception until March 2021, for randomized controlled trials (RCTs) and observational studies. Through the systematic review, we identified 8 observational studies evaluating AQ laxatives use as a risk factor for CRC development, and 5 studies on CRC risk were included in the meta-analysis using a random-effects model. Through the meta-analysis, we found that a history of AQ laxatives use compared with "other" and "no laxatives" use was associated with CRC development (OR: 1.41; 95% CI: 0.94-2.11), although not at a statistically significant level. The possible association persists even after removal of the outlier studies (OR: 1.51; 95% CI: 0.97-2.34). Selection of cases and controls was judged at low or unclear risk of bias across almost all studies, and the quality of evidence was from moderate to low. In conclusion, it is not possible to associate the use of AQ laxatives with the development of CRC. However, the trend toward an increased risk of CRC provides a strong indication for investigating this issue by performing further high-quality studies.
Topics: Anthraquinones; Colorectal Neoplasms; Constipation; Humans; Laxatives
PubMed: 35040201
DOI: 10.1002/ptr.7373 -
BMC Cancer Sep 2023Cardiotoxicity is among the most important adverse effects of childhood cancer treatment. Anthracyclines, mitoxantrone and radiotherapy involving the heart are its main...
BACKGROUND
Cardiotoxicity is among the most important adverse effects of childhood cancer treatment. Anthracyclines, mitoxantrone and radiotherapy involving the heart are its main causes. Subclinical cardiac dysfunction may over time progress to clinical heart failure. The majority of previous studies have focused on late-onset cardiotoxicity. In this systematic review, we discuss the prevalence and risk factors for acute and early-onset cardiotoxicity in children and adolescents with cancer treated with anthracyclines, mitoxantrone or radiotherapy involving the heart.
METHODS
A literature search was performed within PubMed and reference lists of relevant studies. Studies were eligible if they reported on cardiotoxicity measured by clinical, echocardiographic and biochemical parameters routinely used in clinical practice during or within one year after the start of cancer treatment in ≥ 25 children and adolescents with cancer. Information about study population, treatment, outcomes of diagnostic tests used for cardiotoxicity assessment and risk factors was extracted and risk of bias was assessed.
RESULTS
Our PubMed search yielded 3649 unique publications, 44 of which fulfilled the inclusion criteria. One additional study was identified by scanning the reference lists of relevant studies. In these 45 studies, acute and early-onset cardiotoxicity was studied in 7797 children and adolescents. Definitions of acute and early-onset cardiotoxicity prove to be highly heterogeneous. Prevalence rates varied for different cardiotoxicity definitions: systolic dysfunction (0.0-56.4%), diastolic dysfunction (30.0-100%), combinations of echocardiography and/or clinical parameters (0.0-38.1%), clinical symptoms (0.0-25.5%) and biomarker levels (0.0-37.5%). Shortening fraction and ejection fraction significantly decreased during treatment. Cumulative anthracycline dose proves to be an important risk factor.
CONCLUSIONS
Various definitions have been used to describe acute and early-onset cardiotoxicity due to childhood cancer treatment, complicating the establishment of its exact prevalence. Our findings underscore the importance of uniform international guidelines for the monitoring of cardiac function during and shortly after childhood cancer treatment.
Topics: Humans; Adolescent; Child; Cardiotoxicity; Mitoxantrone; Neoplasms; Heart; Anthracyclines; Polyketides
PubMed: 37710224
DOI: 10.1186/s12885-023-11353-9 -
The Cochrane Database of Systematic... Feb 2014Osteoarthritis (OA) is one of the most prevalent musculoskeletal diseases. There is currently no consensus on what is the best treatment to improve OA symptoms and slow... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Osteoarthritis (OA) is one of the most prevalent musculoskeletal diseases. There is currently no consensus on what is the best treatment to improve OA symptoms and slow disease progression. Diacerein is an anthraquinone synthesised in 1980 that interferes with interleukin-1, an inflammatory mediator. It has been proposed that diacerein acts as a slow-acting, symptom-modifying and perhaps disease-structure-modifying drug for OA. This is an update of a Cochrane review first published in 2006.
OBJECTIVES
To assess the benefits and harms of diacerein for the treatment of adults with OA when compared with placebo and other pharmacologically active interventions (nonsteroidal anti-inflammatory drugs (NSAIDs) and other symptom-modifying, slow-acting drugs) for OA.
SEARCH METHODS
We searched the Cochrane Central Register of Controlled Trials (CENTRAL) - The Cochrane Library, Issue 10, 2013, MEDLINE (1966 to 2013), EMBASE (1980 to 2013), LILACS (1982 to 2013), and ACP Journal Club, and we handsearched reference lists of published articles. We also searched the World Health Organization International Clinical Trials Platform ( http://www.who.int/trialsearch/Default.aspx) to identify ongoing trials and screened reference lists of retrieved review articles and trials to identify potentially relevant studies. All searches were up to date as of March 2013. Pharmaceutical companies and authors of published articles were contacted. We searched the websites of the regulatory agencies using the keyword 'diacerein' in November 2013. No language restrictions were applied.
SELECTION CRITERIA
Studies were included if they were randomised or quasi-randomised controlled trials that compared diacerein with placebo or another active pharmacological intervention in participants with OA.
DATA COLLECTION AND ANALYSIS
Data abstraction and quality assessment were performed by two independent investigators, and their results were compared. The Cochrane risk of bias tool was used. The quality of evidence obtained was assessed using the GRADE approach.
MAIN RESULTS
We identified three new trials (141 participants), and this updated review now includes 10 trials, totalling 2,210 participants. The most frequent risk of bias was incomplete outcome data, identified in approximately 80% of the studies. Allocation concealment and random sequence generation were unclear in 90% and 40% of the studies, respectively, because of poor reporting.Low-quality evidence from six trials (1,283 participants) indicates that diacerein has a small beneficial effect on overall pain (measured on a 100 mm visual analogue scale) at three to 36 months (mean difference (MD) -8.65, 95% confidence interval (CI) -15.62 to -1.68), which is equivalent to a 9% pain reduction in the diacerein group (95% CI -16% to -2%) compared with the placebo group. This benefit may not be clinically significant.No statistically significant differences in physical function (4 studies, 1006 participants) were noted between the diacerein and placebo groups (Lequesne impairment index, 0 to 24 points) (MD -0.29, 95% CI -0.87 to 0.28).Low-quality evidence from two trials (616 participants) on slowing of joint space narrowing (a decrease greater than 0.50 mm) in the knee or hip favoured diacerein over placebo (risk ratio (RR) 0.85, 95% CI 0.72 to 0.99), with an absolute risk difference of -6% (95% CI -15% to 2%) and a number needed to treat for an additional beneficial outcome (NNTB) of 14 (95% CI 8 to 203). Analysis of the knee joint alone (1 study, 170 participants) did not reach statistical significance (RR 0.94, 95% CI 0.51 to 1.74).None of the trials of diacerein versus placebo measured quality of life. According to one trial (161 participants), which compared diacerein versus non-steroidal anti-inflammatory drugs (NSAIDs), the quality of life of participants in the two groups (as assessed by the Short Form (SF)-36 health survey questionnaire (0 to 800 sum score)) did not differ significantly (MD -40.70, 95% CI -85.20 to 3.80).Low-quality evidence from seven trials showed significantly more adverse events in the diacerein group compared with the placebo group after two to 36 months, mainly diarrhoea (RR 3.52, 95% CI 2.42 to 5.11), with an absolute risk increase of 24% (95% CI 12% to 35%), and a number needed to treat for an additional harmful outcome (NNTH) of 4 (95% CI 3 to 7).No statistically significant differences in participant withdrawal due to adverse events were seen at two to 36 months for diacerein compared with placebo (RR 1.29, 95% CI 0.83 to 2.01).A search of regulatory websites found a recommendation from the European Medicines Agency (EMA) Pharmacovigilance Risk Assessment Committee (PRAC) that the marketing authorization of diacerein should be suspended across Europe because of harms (particularly the risk of severe diarrhoea and potentially harmful effects on the liver) outweighing benefits. However, this guidance is not final as the PRAC recommendation will be re-examined.
AUTHORS' CONCLUSIONS
In this update, the strength of evidence for effectiveness outcomes was low to moderate. We confirmed that symptomatic benefit provided by diacerein in terms of pain reduction is minimal. The small benefit derived in terms of joint space narrowing is of questionable clinical relevance and was observed only for OA of the hip. With respect to adverse effects of diacerein, diarrhoea was most frequent. Given the recent guidance issued by the EMA recommending suspension of diacerein in Europe, the EMA website should be consulted for further recommendations regarding the use of diacerein.
Topics: Anthraquinones; Anti-Inflammatory Agents, Non-Steroidal; Humans; Osteoarthritis; Randomized Controlled Trials as Topic
PubMed: 24515444
DOI: 10.1002/14651858.CD005117.pub3 -
Breastfeeding Medicine : the Official... Dec 2012Despite popular and historical use, there has been little modern research conducted to determine the safety and efficacy of herb use during breastfeeding. The purpose of... (Review)
Review
OBJECTIVES
Despite popular and historical use, there has been little modern research conducted to determine the safety and efficacy of herb use during breastfeeding. The purpose of this study was to systematically review the clinical literature on herbal medicine and lactation.
METHODS
The databases PubMed, CAB Abstracts, Cochrane Central Register of Controlled Trials, HealthSTAR, Cumulative Index to Nursing and Allied Health Literature, and Reprotox were systematically searched for human trials from 1970 until 2010. Reference lists from relevant articles were hand-searched.
RESULTS
Thirty-two studies met the inclusion criteria. Clinical studies were divided into three categories: survey studies (n=11), safety studies (n=8), and efficacy studies (n=13). Six studies were randomized controlled trials. The most common herbs studied were St. John's wort (Hypericum perforatum L.) (n=3), garlic (Allium sativum L.) extract (n=2), and senna (Cassia senna L.) (n=2). Studies were very heterogeneous with regard to study design, herbal intervention, and outcome measures. Overall, poor methodological quality predominated among the studies.
CONCLUSIONS
Our review concludes that further research is needed to assess the prevalence, efficacy, and safety of commonly used herbs during breastfeeding.
Topics: Beverages; Breast Feeding; Dietary Supplements; Female; Garlic; Humans; Hypericum; Infant; Infant, Newborn; Lactation; Phytotherapy; Plant Preparations; Safety; Senna Extract; Senna Plant
PubMed: 22686865
DOI: 10.1089/bfm.2011.0122 -
Drugs & Aging Apr 2019Symptomatic slow-acting drugs for osteoarthritis (SYSADOAs) are an important drug class in the treatment armamentarium for osteoarthritis (OA). (Meta-Analysis)
Meta-Analysis
BACKGROUND
Symptomatic slow-acting drugs for osteoarthritis (SYSADOAs) are an important drug class in the treatment armamentarium for osteoarthritis (OA).
OBJECTIVE
We aimed to re-assess the safety of various SYSADOAs in a comprehensive meta-analysis of randomized placebo-controlled trials, using, as much as possible, data from full safety reports.
METHODS
We performed a systematic review and random-effects meta-analyses of randomized, double-blind, placebo-controlled trials that assessed adverse events (AEs) with various SYSADOAs in patients with OA. The databases MEDLINE, Cochrane Central Register of Controlled Trials (Ovid CENTRAL) and Scopus were searched. The primary outcomes were overall severe and serious AEs, as well as AEs involving the following Medical Dictionary for Regulatory Activities (MedDRA) system organ classes (SOCs): gastrointestinal, cardiac, vascular, nervous system, skin and subcutaneous tissue, musculoskeletal and connective tissue, renal and urinary system.
RESULTS
Database searches initially identified 3815 records. After exclusions according to the selection criteria, 25 studies on various SYSADOAs were included in the qualitative synthesis, and 13 studies with adequate data were included in the meta-analyses. Next, from the studies previously excluded according to the protocol, 37 with mainly oral nonsteroidal anti-inflammatory drugs (NSAIDs) permitted as concomitant medication were included in a parallel qualitative synthesis, from which 18 studies on various SYSADOAs were included in parallel meta-analyses. This post hoc parallel inclusion was conducted because of the high number of studies allowing concomitant anti-OA medications. Indeed, primarily excluding studies with concomitant anti-OA medications was crucial for a meta-analysis on safety. The decision for parallel inclusion was made for the purpose of comparative analyses. Glucosamine sulfate (GS), chondroitin sulfate (CS) and avocado soybean unsaponifiables (ASU; Piascledine) were not associated with increased odds for any type of AEs compared with placebo. Overall, with/without concomitant OA medication, diacerein was associated with significantly increased odds of total AEs (odds ratio [OR] 2.22; 95% confidence interval [CI] 1.58-3.13; I = 52.8%), gastrointestinal disorders (OR 2.85; 95% CI 2.02-4.04; I = 62.8%) and renal and urinary disorders (OR 3.42; 95% CI 2.36-4.96; I = 17.0%) compared with placebo. In studies that allowed concomitant OA medications, diacerein was associated with significantly more dermatological disorders (OR 2.47; 95% CI 1.42-4.31; I = 0%) and more dropouts due to AEs (OR 3.18; 95% CI 1.85-5.47; I = 13.4%) than was placebo. No significant increase in serious or severe AEs was found with diacerein versus placebo.
CONCLUSIONS
GS and CS can be considered safe treatments for patients with OA. All eligible studies on ASU included in our analysis used the proprietary product Piascledine and allowed other anti-OA medications; thus, the safety of ASU must be confirmed in future studies without concomitant anti-OA medications. Given the safety concerns with diacerein, its usefulness in patients with OA should be assessed, taking into account individual patient characteristics.
Topics: Anthraquinones; Anti-Inflammatory Agents, Non-Steroidal; Delayed-Action Preparations; Drug Combinations; Drug-Related Side Effects and Adverse Reactions; Humans; Osteoarthritis; Phytosterols; Plant Extracts; Randomized Controlled Trials as Topic; Treatment Outcome; Vitamin E
PubMed: 31073924
DOI: 10.1007/s40266-019-00662-z -
PloS One 2024In the search for better anticancer drugs, computer-aided drug design (CADD) techniques play an indispensable role in facilitating the lengthy and costly drug discovery...
BACKGROUND
In the search for better anticancer drugs, computer-aided drug design (CADD) techniques play an indispensable role in facilitating the lengthy and costly drug discovery process especially when natural products are involved. Anthraquinone is one of the most widely-recognized natural products with anticancer properties. This review aimed to systematically assess and synthesize evidence on the utilization of CADD techniques centered on the anthraquinone scaffold for cancer treatment.
METHODS
The conduct and reporting of this review were done in accordance to the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) 2020 guideline. The protocol was registered in the "International prospective register of systematic reviews" database (PROSPERO: CRD42023432904) and also published recently. The search strategy was designed based on the combination of concept 1 "CADD or virtual screening", concept 2 "anthraquinone" and concept 3 "cancer". The search was executed in PubMed, Scopus, Web of Science and MedRxiv on 30 June 2023.
RESULTS
Databases searching retrieved a total of 317 records. After deduplication and applying the eligibility criteria, the final review ended up with 32 articles in which 3 articles were found by citation searching. The CADD methods used in the studies were either structure-based alone (69%) or combined with ligand-based methods via parallel (9%) or sequential (22%) approaches. Molecular docking was performed in all studies, with Glide and AutoDock being the most popular commercial and public software used respectively. Protein data bank was used in most studies to retrieve the crystal structure of the targets of interest while the main ligand databases were PubChem and Zinc. The utilization of in-silico techniques has enabled a deeper dive into the structural, biological and pharmacological properties of anthraquinone derivatives, revealing their remarkable anticancer properties in an all-rounded fashion.
CONCLUSION
By harnessing the power of computational tools and leveraging the natural diversity of anthraquinone compounds, researchers can expedite the development of better drugs to address the unmet medical needs in cancer treatment by improving the treatment outcome for cancer patients.
Topics: Anthraquinones; Humans; Neoplasms; Antineoplastic Agents; Drug Design; Molecular Docking Simulation; Computer-Aided Design; Drug Discovery
PubMed: 38776291
DOI: 10.1371/journal.pone.0301396 -
European Journal of Medical Research Mar 2015To conduct a systematic review and network meta-analysis of randomized controlled trials (RCTs) with the aims of comparing relevant clinical outcomes (that is, visual... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
To conduct a systematic review and network meta-analysis of randomized controlled trials (RCTs) with the aims of comparing relevant clinical outcomes (that is, visual analog scores (VAS), total and sub-Western Ontario and McMaster Universities Osteoarthritis index (WOMAC) scores, Lequesne algofunctional index, joint space width change, and adverse events) between diacerein, glucosamine, and placebo.
METHODS
Medline and Scopus databases were searched from inception to 29 August 2014, using PubMed and Scopus search engines and included RCTs or quasi-experimental designs comparing clinical outcomes between treatments. Data were extracted from original studies. A network meta-analysis was performed by applying weight regression for continuous outcomes and a mixed-effect Poisson regression for dichotomous outcomes.
RESULTS
Thirty-one of 505 identified studies were eligible. Compared to placebo, glucosamine showed a significant improvement with unstandardized mean differences (UMD) in total WOMAC, pain WOMAC, function WOMAC, and Lequesne score of -2.49 (95% confidence interval (CI) -4.14, -0.83), -0.75 (95% CI: -1.18, -0.32), -4.78 (95% CI: -5.96, -3.59), and -1.03 (95% CI: -1.34, -0.72), respectively. Diacerein clinically improves visual analog scores, function WOMAC, and stiffness WOMAC with UMD values of -2.23 (95% CI: -2.82, -1.64), -6.64 (95% CI: -10.50, -2.78), and -0.68 (95% CI: -1.20, -0.16) when compared to placebo.
CONCLUSIONS
The network meta-analysis suggests that diacerein and glucosamine are equally efficacious for symptom relief in knee OA, but that the former has more side effects.
Topics: Anthraquinones; Anti-Inflammatory Agents, Non-Steroidal; Glucosamine; Humans; Osteoarthritis, Knee
PubMed: 25889669
DOI: 10.1186/s40001-015-0115-7 -
The Cochrane Database of Systematic... May 2013This is an updated Cochrane review of the previous published version.Mitoxantrone (MX) has been shown to be moderately effective in reducing the clinical outcome... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
This is an updated Cochrane review of the previous published version.Mitoxantrone (MX) has been shown to be moderately effective in reducing the clinical outcome measures of disease activity in multiple sclerosis (MS) patients.
OBJECTIVES
The main objective was to assess the efficacy and safety of MX compared to a control group in relapsing-remitting (RRMS), progressive relapsing (PRMS) and secondary progressive (SPMS) MS participants.
SEARCH METHODS
We searched the Cochrane Multiple Sclerosis and Rare Diseases of the Central Nervous System Group Specialised Register (June 2012) and reference lists of articles. We also undertook handsearching and contacted trialists and pharmaceutical companies.
SELECTION CRITERIA
Randomised, double-blinded, controlled trials (RCTs) comparing the administration of MX versus placebo or MX plus steroids treatment versus placebo plus steroids treatment were included.
DATA COLLECTION AND ANALYSIS
The review authors independently selected articles for inclusion. They independently extracted clinical, safety and magnetic resonance imaging (MRI) data, resolving disagreements by discussion. Risk of bias was evaluated to assess the quality of the studies. Treatment effect was measured using odds ratios (OR) with 95% confidence intervals (CI) for the binary outcomes and mean differences (MD) with 95% CI for the continuous outcomes. If heterogeneity was absent, a fixed-effect model was used.
MAIN RESULTS
Three trials were selected and 221 participants were included in the analyses. MX reduced the progression of disability at two years follow-up (proportion of participants with six months confirmed progression of disability (OR 0.30, 95% CI 0.09 to 0.99 and MD -0.36, 95% CI- 0.70 to -0.02; P = 0.04)). Significant results were found regarding the reduction in annualised relapse rate (MD -0.85, 95% CI -1.47 to -0.23; P = 0.007), the proportion of patients free from relapses at one year (OR 7.13, 95% CI 2.06 to 24.61; P = 0.002) and two years (OR 2.82, 95% CI 1.54 to 5.19; P = 0.0008), and the number of patients with active MRI lesions at six months or one year only (OR 0.24, 95% CI 0.10 to 0.57; P = 0.001). Side effects reported in the trials (amenorrhoea, nausea and vomiting, alopecia and urinary tract infections) were more frequent in treated patients than in controls, while no major adverse events have been reported. These results should be considered with caution because of the heterogeneous characteristics of included trials in term of drug dosage, inclusion criteria and quality of included trials. Moreover, it was not possible to estimate the long-term efficacy and safety of MX.
AUTHORS' CONCLUSIONS
MX shows a significant but partial efficacy in reducing the risk of MS progression and the frequency of relapses in patients affected by worsening RRMS, PRMS and SPMS in the short-term follow-up (two years). No major neoplastic events or symptomatic cardiotoxicity related to MX have been reported; however studies with longer follow-up (not included in this review) have raised concerns about the risk of systolic disfunction (˜12%) and therapy-related acute leukaemias (0.8%), which are increasingly reported in the literature.MX should be limited to treating patients with worsening RRMS and SPMS and with evidence of persistent inflammatory activity after a careful assessment of the individual patients' risk and benefit profiles. Assessment should also consider the present availability of alternative therapies with less severe adverse events.
Topics: Disease Progression; Humans; Immunosuppressive Agents; Mitoxantrone; Multiple Sclerosis; Multiple Sclerosis, Chronic Progressive; Multiple Sclerosis, Relapsing-Remitting; Randomized Controlled Trials as Topic
PubMed: 23728638
DOI: 10.1002/14651858.CD002127.pub3