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Chemico-biological Interactions Sep 2019Anthraquinones constitute an important class of natural and synthetic compounds with a broad scope of pharmacological including anti-bacterial, antioxidant, laxative,... (Review)
Review
Anthraquinones constitute an important class of natural and synthetic compounds with a broad scope of pharmacological including anti-bacterial, antioxidant, laxative, anti-tumor and other activities. Physcion and physcion 8-O-β-glucopyranoside (PG) are common anthraquinones existed in various plants. Emerging studies suggested that physcion and PG not only exert anti-tumor, anti-microbial, anti-inflammatory, anti-oxidant, optical-related, enzyme inhibitory, lipid regulation and neuroprotective activities, but also lead to hepatotoxicity, renal toxicity and genetic damage. Besides, a growing number of pharmacokinetics researches of physcion and PG also have been conducted. However, no review of physcion or PG have been published by now, so the aim of present review is to give a comprehensive summary and analysis of the pharmacology, toxicity and pharmacokinetics of physcion and PG by consulting all the currently available literatures published in PubMed then give a future prospects about it.
Topics: Anthraquinones; Emodin; Glucosides; Phytochemicals
PubMed: 31226286
DOI: 10.1016/j.cbi.2019.06.035 -
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 -
Journal of Neuroimmunology Jul 2019The review assessed the efficacy and tolerability of mitoxantrone in patients with neuromyelitis optica spectrum disorder (NMOSD). Eight articles were reviewed with a...
The review assessed the efficacy and tolerability of mitoxantrone in patients with neuromyelitis optica spectrum disorder (NMOSD). Eight articles were reviewed with a total of 117 patients. Annualized relapse rate and progression of disability dramatically decreased post-treatment in most studies. Mitoxantrone was generally tolerated. Only one patient developed acute myeloid leukemia, which lead to septicemia and death. No serious cardiotoxicity was reported. Mitoxantrone may be effective in reducing the frequency of relapse and slowing down the progression of disability in patients with NMOSD. The risk of cardiotoxicity and leukemia detains it as a second-line agent for NMOSD.
Topics: Cardiomyopathies; Disease Progression; Epidemiologic Studies; Humans; Immunosuppressive Agents; Infections; Intercalating Agents; Leukemia, Myeloid, Acute; Leukopenia; Mitoxantrone; Neuromyelitis Optica; Randomized Controlled Trials as Topic; Recurrence; Topoisomerase II Inhibitors; Treatment Outcome
PubMed: 31005713
DOI: 10.1016/j.jneuroim.2019.04.007 -
Medicine Jan 2019There are many trials on the combination of Pinaverium bromide (PB) and Flupentixol-melitracen (FM) in the treatment of diarrhea-type irritable bowel syndrome (IBS-D),... (Meta-Analysis)
Meta-Analysis
BACKGROUND
There are many trials on the combination of Pinaverium bromide (PB) and Flupentixol-melitracen (FM) in the treatment of diarrhea-type irritable bowel syndrome (IBS-D), but the sample sizes are small, and the research conclusions are inconsistent. Thus, a meta-analysis was performed, aiming to evaluate the efficacy and safety of this combination therapy in patients with IBS-D.
METHODS
A systematic literature search was conducted in 7 databases covering the period up to July 2018 to identify randomized controlled trials (RCTs) of PB combined with FM versus PB alone for IBS-D. The primary outcome was the total symptom relief rate. The other outcomes were the adverse events rate, HAMA/SAS score, and HAMD/SDS score. The methodological quality of the RCTs was assessed independently using 6 criteria according to the Cochrane Collaboration. All data were analyzed using Review Manager 5.3.
RESULTS
Fifteen RCTs with 1487 participants were identified from 2005 to 2018. Compared with PB alone, 15 RCTs showed significant effects of PB plus FM in terms of improved symptom relief in patients with IBS-D (n = 1487, OR = 5.17, 95%CI, 3.79-7.07, P < .00001). Eleven RCTs reported adverse effects in both the PB plus FM and PB groups, there was no statistically significant difference in the adverse events rate between the 2 groups (n = 1207, OR = 2.91, 95%CI, 0.91-9.28, P = 0.07). Two RCTs and 3 RCTs reported HAMA and HAMD scores respectively, and 3 RCTs reported both SAS and SDS scores. After treatment, the above scores in the PB plus FM group were significantly lower than the PB group (all P < .01). However, the trials were deemed to have a medium risk of bias.
CONCLUSIONS
The efficacy of PB combined with FM is superior to PB alone in the treatment of IBS-D, and it is safe for clinical use. However, the conclusions still need to be verified by conducting more large-scale and high-quality RCTs.
Topics: Anthracenes; Diarrhea; Drug Combinations; Drug Therapy, Combination; Flupenthixol; Gastrointestinal Agents; Humans; Irritable Bowel Syndrome; Morpholines; Randomized Controlled Trials as Topic
PubMed: 30633208
DOI: 10.1097/MD.0000000000014064 -
Journal of Clinical Oncology : Official... Feb 2019Several studies have reported that among patients with localized prostate cancer, black men have a shorter overall survival (OS) time than white men, but few data exist... (Meta-Analysis)
Meta-Analysis
PURPOSE
Several studies have reported that among patients with localized prostate cancer, black men have a shorter overall survival (OS) time than white men, but few data exist for men with advanced prostate cancer. The primary goal of this analysis was to compare the OS in black and white men with metastatic castration-resistant prostate cancer (mCRPC) who were treated in phase III clinical trials with docetaxel plus prednisone (DP) or a DP-containing regimen.
METHODS
Individual participant data from 8,820 men with mCRPC randomly assigned in nine phase III trials to DP or a DP-containing regimen were combined. Race was based on self-report. The primary end point was OS. The Cox proportional hazards regression model was used to assess the prognostic importance of race (black v white) adjusted for established risk factors common across the trials (age, prostate-specific antigen, performance status, alkaline phosphatase, hemoglobin, and sites of metastases).
RESULTS
Of 8,820 men, 7,528 (85%) were white, 500 (6%) were black, 424 (5%) were Asian, and 368 (4%) were of unknown race. Black men were younger and had worse performance status, higher testosterone and prostate-specific antigen, and lower hemoglobin than white men. Despite these differences, the median OS was 21.0 months (95% CI, 19.4 to 22.5 months) versus 21.2 months (95% CI, 20.8 to 21.7 months) in black and white men, respectively. The pooled multivariable hazard ratio of 0.81 (95% CI, 0.72 to 0.91) demonstrates that overall, black men have a statistically significant decreased risk of death compared with white men ( P < .001).
CONCLUSION
When adjusted for known prognostic factors, we observed a statistically significant increased OS in black versus white men with mCRPC who were enrolled in these clinical trials. The mechanism for these differences is not known.
Topics: Antineoplastic Combined Chemotherapy Protocols; Black People; Clinical Trials, Phase III as Topic; Docetaxel; Humans; Male; Mitoxantrone; Neoplasm Metastasis; Prednisone; Prostatic Neoplasms, Castration-Resistant; Randomized Controlled Trials as Topic; White People
PubMed: 30576268
DOI: 10.1200/JCO.18.01279 -
PloS One 2018Treatment of metastatic prostate cancer is associated with high personal and economic burden. Recently, new treatment options for castration-resistant prostate cancer...
BACKGROUND
Treatment of metastatic prostate cancer is associated with high personal and economic burden. Recently, new treatment options for castration-resistant prostate cancer became available with promising survival advantages. However, cost-effectiveness of those new treatment options is sometimes ambiguous or given only under certain circumstances. The aim of this study was to systematically review studies on the cost-effectiveness of treatments and costs of castration-resistant prostate cancer (CRPC) and metastasizing castration-resistant prostate cancer (mCRPC) on their methodological quality and the risk of bias.
METHODS
A systematic literature search was performed in the databases PubMed, CINAHL Complete, the Cochrane Library and Web of Science Core Collection for costs-effectiveness analyses, model-based economic evaluations, cost-of-illness analyses and budget impact analyses. Reported costs were inflated to 2015 US$ purchasing power parities. Quality assessment and risk of bias assessment was performed using the Consolidated Health Economic Evaluation Reporting Standards checklist and the Bias in Economic Evaluations checklist, respectively.
RESULTS
In total, 38 articles were identified by the systematic literature search. The methodological quality of the included studies varied widely, and there was considerable risk of bias. The cost-effectiveness treatments for CRPC and mCRPC was assessed with incremental cost-effectiveness ratios ranging from dominance for mitoxantrone to $562,328 per quality-adjusted life year gained for sipuleucel-T compared with prednisone alone. Annual costs for the treatment of castration-resistant prostate cancer ranged from $3,067 to $77,725.
CONCLUSION
The cost-effectiveness of treatments of CRPC strongly depended on the willingness to pay per quality-adjusted life year gained/life-year saved throughout all included costs-effectiveness analyses and model-based economic evaluations. High-quality cost-effectiveness analyses based on randomized controlled trials are needed in order to make informed decisions on the management of castration-resistant prostate cancer and the resulting financial impact on the healthcare system.
Topics: Aged; Antineoplastic Agents; Bias; Cost-Benefit Analysis; Humans; Male; Middle Aged; Mitoxantrone; Neoplasm Metastasis; Prednisone; Prostatic Neoplasms, Castration-Resistant; Quality-Adjusted Life Years; Tissue Extracts
PubMed: 30517165
DOI: 10.1371/journal.pone.0208063 -
Pediatric Dermatology May 2018Psoriasis is one of the most common chronic skin diseases, affecting 1%-3% of the general population. It can have a significant negative impact on a patient's quality of... (Review)
Review
Psoriasis is one of the most common chronic skin diseases, affecting 1%-3% of the general population. It can have a significant negative impact on a patient's quality of life, and in approximately 30% of patients first symptoms can be traced back to childhood. We have performed a comprehensive literature search using the MEDLINE database in order to ascertain the efficacy and adverse reactions of topical treatments in pediatric psoriasis. A total of 13 relevant articles were identified on the following topical agents: corticosteroids, calcineurin inhibitors, vitamin D analogs, and dithranol. Corticosteroids achieved clearance in 72.7% of patients. Calcitriol lead to a 57.2%-100% mean improvement in severity, and calcipotriol to 52%-64%. Combination of calcipotriol and corticosteroids achieved an improvement in mean severity ranging between 32.1% and 80%. Treatment with tacrolimus lead to an >50% improvement. Finally, short contact dithranol lead to a variable response in clearance between different studies, ranging between 3.7% and 81%. No serious adverse reactions were documented, the most common local reaction being irritation. Pediatric psoriasis is a common and challenging condition with no easy and definitive solution. Topical agents are safe, easy to use, readily available and cheap. However, they need to be applied repeatedly, may cause skin irritation, and can be messy. Based on the results presented above, we recommend utilizing all the available topical options before escalating to systemic treatments.
Topics: Administration, Cutaneous; Adolescent; Anthralin; Calcineurin Inhibitors; Child; Dermatologic Agents; Glucocorticoids; Humans; Psoriasis; Treatment Outcome; Vitamin D
PubMed: 29493005
DOI: 10.1111/pde.13422 -
Journal of the American Academy of... Mar 2018
Review
Topics: 11-beta-Hydroxysteroid Dehydrogenases; Alopecia Areata; Anthralin; Bimatoprost; Cyclopropanes; Dermatologic Agents; Drug Therapy, Combination; Eyebrows; Eyelashes; Facial Dermatoses; Humans; Latanoprost; Minoxidil; Photosensitizing Agents; Prostaglandins F, Synthetic
PubMed: 28987491
DOI: 10.1016/j.jaad.2017.09.054 -
The Journal of Dermatological Treatment Aug 2017To review published literature describing the global use of topical antipsoriatics. (Review)
Review
OBJECTIVE
To review published literature describing the global use of topical antipsoriatics.
MATERIALS AND METHODS
Search for English-language articles in Embase, Pubmed, PsycINFO and Cochrane Library.
RESULTS
Fifty-four selected publications were found, describing psoriasis patients' use of topical antipsoriatics, using six different methods to collect data. The eight most frequently used topical treatments from the regions North/South America, North/Central/South Europe, Asia, Middle East and Australia were: corticosteroids used by 16-79%, complementary and alternative medicines used by 10-62%, phototherapies used by 0.4-75%, calcipotriol used by 4.2-73%, corticosteroid/calcipotriol combinations used by 3.3-71%, tar used by 0.8-66%, anthralin used by 15% and emollients used as monotherapy by 1-23%. Rates of patient-reported adherence to topical remedies ranged from 51% to 90% and rates of patient-reported satisfaction with topical as it pertains to symptom control ranged from 12% to 52%.
CONCLUSION
The identified use patterns are varying and reflect a lack of data from large parts of the world and noncomparable studies using heterogeneous study designs. However, this study emphasizes the importance of medical professionals involvement of the patient with respect to choosing prescribed topical treatment and the possibility of patients' use of alternative treatments. More drug utilization studies, both survey and register based, from different parts of the world are needed to provide more conclusive evidence about patients' use of topical antipsoriatics.
Topics: Administration, Topical; Adrenal Cortex Hormones; Anthralin; Calcitriol; Dermatologic Agents; Drug Therapy, Combination; Humans; Patient Compliance; Psoriasis
PubMed: 27786594
DOI: 10.1080/09546634.2016.1254331 -
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