Surface Under The Cumulative Ranking Area Research Articles

Efficacy and Safety of Peripherally Acting Mu-Opioid Receptor Antagonists for the Treatment of Opioid-Induced Constipation: A Bayesian Network Meta-analysis.

To assess the efficacy and safety of peripherally acting mu-opioid receptor antagonists (PAMORAs) for the treatment of opioid-induced constipation (OIC). Randomized controlled trials (RCTs) were searched for OIC therapy comparing PAMORAs with placebo. Both a pairwise and network meta-analysis were performed. The surface under the cumulative ranking area (SUCRA) was used to determine the efficacy and safety of OIC treatment using different PAMORAs. The primary target outcome was a response that achieves an average of three or more bowel movements (BMs) per week. In the network meta-analysis, four PAMORAs (naldemedine, naloxone, methylnaltrexone, and alvimopan) showed a better BM response than the placebo. Naldemedine was ranked first (odds ratio [OR] = 2.8, 95% credible interval [CrI] = 2-4.5, SUCRA = 89.42%), followed by naloxone (OR = 2.9, 95% CrI = 1.6-5.3, SUCRA = 87.44%), alvimopan (OR = 2.2, 95% CrI = 1.3-3.5, SUCRA = 68.02%), and methylnaltrexone (OR = 1.7, 95% CrI = 1.0-2.8, SUCRA = 46.09%). There were no significant differences in safety found between the PAMORAs and the placebo. We found that PAMORAs are effective and can be safely used for the treatment of OIC. In network meta-analysis, naldemedine and naloxone appear to be the most effective PAMORAs for the treatment of OIC.

Efficacy and safety of over-the-counter analgesics for primary dysmenorrhea

Background:Primary dysmenorrhea is common and troublesome. The comparative efficacy of over-the-counter analgesics (OTCAs) for dysmenorrhea is unclear. This study was aimed at conducting a network meta-analysis to assess the efficacy and safety of 5 OTCAs – naproxen, ibuprofen,diclofenac, aspirin, and ketoprofen – in patients with primary dysmenorrhea.Methods:The study was registered with PROSPERO (number: CRD42019133556). The search strategy involved a review of PubMed, Embase, Cochrane Library, Web of Science, and CINAHL for relative randomized controlled trials of the 5 analgesics from the date of database establishment to July 2019. The outputs are presented as odds ratios (ORs), their corresponding 95% confidence intervals (CIs), and the surface under the cumulative ranking area (SUCRA) probabilities.Results:Thirty-five trials with 4383 participants were included in our study. As for efficacy outcomes, all the included analgesics except aspirin were more effective than placebo in treating dysmenorrhea [naproxen (OR 3.99, 95% CI 2.18–7.30), ibuprofen (OR 10.08, 95% CI 3.29–30.85), diclofenac (OR 11.82, 95% CI 2.66–52.48), and ketoprofen (OR 5.12, 95% CI 1.57–16.69). The OTCAs were superior to the placebo in terms of pain relief in primary dysmenorrhea. Aspirin was less effective than ibuprofen (OR 0.17, 95% CI 0.04–0.73) and diclofenac (OR 1.17, 95% CI 0.02–0.85). The SUCRA curves showed that diclofenac and ibuprofen were the most and second most effective (85.1% and 83.8%, respectively), followed by ketoprofen, naproxen, and aspirin. Regarding safety, there was no significant difference between the 5 OTCAs included and the placebo. Diclofenac versus ibuprofen (OR 4.31, 95% CI 1.18–15.67), ketoprofen versus diclofenac (OR 0.18, 95% CI 0.04–0.78), and ketoprofen versus aspirin (OR 0.41, 95% CI 0.18–0.97) presented statistically significant differences. Ketoprofen and ibuprofen were ranked the best (SUCRA 90.6% and 79.6%), followed by naproxen, aspirin, and diclofenac.Conclusion:Considering the efficacy and safety, ibuprofen is recommended as the optimal OTCA for primary dysmenorrhea. Further well-designed studies that directly compare these analgesics are needed to support our conclusion.

The Impact of Iron Supplementation for Treating Anemia in Patients with Chronic Kidney Disease: Results from Pairwise and Network Meta-Analyses of Randomized Controlled Trials.

After relative erythropoietin deficiency, iron deficiency is the second most important contributing factor for anemia in chronic kidney disease (CKD) patients. Iron supplementation is a crucial part of the treatment of anemia in CKD patients, and intravenous (IV) iron supplementation is considered to be superior to per os (PO) iron supplementation. The differences between the available formulations are poorly characterized. This report presents results from pairwise and network meta-analyses carried out after a comprehensive search in sources of published and unpublished studies, according to the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) recommendations (International prospective register of systematic reviews PROSPERO reference ID: CRD42020148155). Meta-analytic calculations were performed for the outcome of non-response to iron supplementation (i.e., hemoglobin (Hgb) increase of <0.5–1.0 g/dL, or initiation/intensification of erythropoiesis-stimulating agent (ESA) therapy, or increase/change of iron supplement, or requirements of blood transfusion). A total of 34 randomized controlled trials (RCT) were identified, providing numerical data for analyses covering 93.7% (n = 10.097) of the total study population. At the network level, iron supplementation seems to have a more protective effect against the outcome of non-response before the start of dialysis than once dialysis is initiated, and some preparations seem to be more potent (e.g., ferumoxytol, ferric carboxymaltose), compared to the rest of iron supplements assessed (surface under the cumulative ranking area (SUCRA) > 0.8). This study provides parameters for adequately following-up patients requiring iron supplementation, by presenting the most performing preparations, and, indirectly, by making it possible to identify good responders among all patients treated with these medicines.

Efficacy and safety of oral anticoagulants in atrial fibrillation patients with cancer-a network meta-analysis.

There are no guideline recommendations for the use of anticoagulant therapy in atrial fibrillation (AF) patients with cancer, which creates uncertainty about the optimal antithrombotic treatment in these patients. We conducted a network meta-analysis for the first time to assess the efficacy and safety of anticoagulant drugs in patients with AF and concurrent cancer. The PubMed, EMBASE, and Cochrane databases were searched up to March 2019. A search was made for the main anticoagulant drugs (warfarin, dabigatran, apixaban, rivaroxaban, and edoxaban). Outputs were presented as odds ratios (ORs), their corresponding 95% confidence intervals (CIs), and the surface under the cumulative ranking area (SUCRA) probabilities. We identified 414 relevant studies and included 5 trials involving 31,660 participants. In reducing the risk of stroke or systemic embolism, rivaroxaban and apixaban ranked the best and second best (SUCRA, 25.2% and 29.3%, respectively), followed by dabigatran, edoxaban, and warfarin. Apixaban and dabigatran were associated with lower probability of achieving at venous thromboembolism (VTE) (OR 0.12, 95% CI 0.05-0.52, SUCRA, 0.1%; and OR 0.24, 95% CI 0.07-1.00, SUCRA, 33.3%, respectively) than warfarin (SUCRA, 100.0%). For the prevention of all-cause death, apixaban was nonsignificantly less likely than warfarin. In addition, there were nonsignificant differences among all interventions in major bleeding, with the exception of apixaban vs. warfarin (OR 0.39, 95% CI 0.18-0.79; SUCRA 4.9%). In AF patients with cancer, nonvitamin K antagonist oral anticoagulants showed a lower incidence of stroke/systemic embolism, VTE, all-cause death, and major bleeding than warfarin, with apixaban being the best of those studied.

Efficacy and Safety of Agents in IgA Nephropathy: An Update Network Meta-Analysis

Background/Aims: The present network meta-analysis of randomized controlled trials (RCTs) was to explore the efficacy and safety of different pharmacologic interventions in IgA nephropathy with proteinuria more than 0.75 g/d. Methods: We systematically searched the Cochrane Library, Embase, and PubMed database for studies compared the rate of clinical remission and/or serious adverse events in IgA nephropathy patients with proteinuria (> 0.75 g/d) up to August 1, 2018. We ranked the comparative effects of all drugs against placebo on the surface under the cumulative ranking area (SUCRA) probabilities. Results: There were 29 RCTs comprising 2517 participants included for the comparisons of 9 interventions. The rank of the most effective treatments for inducing clinical remission was renin-angiotensin system inhibitors (RASi) in combination with steroid, tonsillectomy combined with steroid pulse therapy, and azathioprine plus RASi with SUCRA of 82.9%, 80.5%, and 67.6%, respectively. RASi in combination with steroid (SUCRA 3.9%) was the most effective in prevention of end-stage renal disease or doubling serum creatinine, followed by RASi monotherapy (SUCRA 38.4%) and azathioprine combined with steroid (SUCRA 49.0%). As for the occurrence of serious adverse events, azathioprine combined with RASi (SUCRA 88.0%) and steroid plus RASi (SUCRA 74.6%) showed the first and second highest incidence of adverse events, respectively. Conclusion: RASi combined with steroid demonstrated the most effective therapeutic approach for IgA nephropathy patients in terms of reducing proteinuria and stabilizing renal function.

Efficacy and safety of rectal 5-aminosalicylic acid versus corticosteroids in active distal ulcerative colitis: a systematic review and network meta-analysis

Topical 5-aminosalicylic acid (5-ASA) and corticosteroids are used frequently in the treatment of active distal ulcerative colitis (UC). Our study aimed to determine the efficacy and safety of different topical drugs used to treat active distal UC. A random-effects model within a Bayesian framework was utilized to compare treatment effects and safety as odds ratios (ORs) with corresponding 95% credible intervals (CrI). The surface under the cumulative ranking area (SUCRA) and median rank (MR) with corresponding 95% CrI were calculated to rank the treatment outcomes. In the induction of clinical and endoscopic remission, most regimens showed significant advantages over placebo except topical budesonide 0.5 mg/d and hydrocortisone 100 mg/d. According to SUCRA and MR values, rectal 5-ASA 1.5 to 2.0 g/d + Beclomethasone dipropionate (BDP) 3 mg/d rendered the highest probability of being the best regimen to achieve clinical and endoscopic remission, followed by the separate use of 5-ASA 4 g/d and BDP 3 mg/d. The occurrence of adverse events was not significantly different between each treatments and placebo. In conclusion, the combined use of topical 5-ASA and BDP proved to be the best choice for active distal UC and further well-designed researches are warranted to assess its efficacy and safety.

Efficacy and safety of medical therapy for low bone mineral density in patients with Crohn disease: A systematic review with network meta-analysis.

Low bone mineral density (BMD) is a frequent complication of inflammatory bowel disease (IBD), particularly in patients with Crohn disease (CD). The aim of our study is to determine the efficacy and safety of different drugs used to treat low BMD in patients with CD. PUBMED/MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials were searched for eligible studies. A random-effects model within a Bayesian framework was applied to compare treatment effects as standardized mean difference (SMD) with their corresponding 95% credible interval (CrI), while odds ratio (OR) was applied to compare adverse events with 95% CrI. The surface under the cumulative ranking area (SUCRA) was calculated to make the ranking of the treatments for outcomes. Twelve randomized controlled trials (RCTs) were eligible. Compared with placebo, zoledronate (SMDs 2.74, 95% CrI 1.36-4.11) and sodium-fluoride (SMDs 1.23, 95% CrI 0.19-2.26) revealed statistical significance in increasing lumbar spine BMD (LSBMD). According to SUCRA ranking, zoledronate (SUCRA = 2.5%) might have the highest probability to be the best treatment for increasing LSBMD in CD patients among all agents, followed by sodium-fluoride (27%). For safety assessment, the incidence of adverse events (AEs) demonstrated no statistical difference between agents and placebo. The corresponding SUCRA values indicated that risedronate (SUCRA = 77%) might be the most safe medicine for low BMD in CD patients and alendronate ranked the worst (SUCRA = 16%). Zoledronate might have the highest probability to be the best therapeutic strategy for increasing LSBMD. For the safety assessment, risedronate showed the greatest trend to decrease the risk of AEs. In the future, more RCTs with higher qualities are needed to make head-to-head comparison between 2 or more treatments.