Adjuvant Treatments of Adult Melanoma: A Systematic Review and Network Meta-Analysis.
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ABSTRACT:
SUBMITTER: Jing M
PROVIDER: S-EPMC9247312 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundImmune checkpoint inhibitors and targeted therapies are approved for adjuvant treatment of patients with resected melanoma; however, they have not been compared in randomized controlled trials (RCTs). We compared the efficacy and safety of adjuvant nivolumab with other approved treatments using available evidence from RCTs in a Bayesian network meta-analysis (NMA).MethodsA systematic literature review was conducted through May 2019 to identify relevant RCTs evaluating approved adjuvant treatments. Outcomes of interest included recurrence-free survival (RFS)/disease-free survival (DFS), distant metastasis-free survival (DMFS), all-cause grade 3/4 adverse events (AEs), discontinuations, and discontinuations due to AEs. Time-to-event outcomes (RFS/DFS and DMFS) were analyzed both assuming that hazard ratios (HRs) are constant over time and that they vary.ResultsOf 26 identified RCTs, 19 were included in the NMA following a feasibility assessment. Based on HRs for RFS/DFS, the risk of recurrence with nivolumab was similar to that of pembrolizumab and lower than that of ipilimumab 3?mg/kg, ipilimumab 10?mg/kg, or interferon. Risk of recurrence with nivolumab was similar to that of dabrafenib plus trametinib at 12?months, however, was lower beyond 12?months (HR [95% credible interval] at 24?months, 0.46 [0.27-0.78]; at 36?months, 0.28 [0.14-0.59]). Based on HRs for DMFS, the risk of developing distant metastases was lower with nivolumab than with ipilimumab 10?mg/kg or interferon and was similar to dabrafenib plus trametinib.ConclusionAdjuvant therapy with nivolumab provides an effective treatment option with a promising risk-benefit profile.
| S-EPMC7784366 | biostudies-literature
Project description:The goal of nonrestorative or non- and microinvasive caries treatment (fluoride- and nonfluoride-based interventions) is to manage the caries disease process at a lesion level and minimize the loss of sound tooth structure. The purpose of this systematic review and network meta-analysis was to summarize the available evidence on nonrestorative treatments for the outcomes of 1) arrest or reversal of noncavitated and cavitated carious lesions on primary and permanent teeth and 2) adverse events. We included parallel and split-mouth randomized controlled trials where patients were followed for any length of time. Studies were identified with MEDLINE and Embase via Ovid, Cochrane CENTRAL, and Cochrane Database of Systematic Reviews. Pairs of reviewers independently conducted the selection of studies, data extraction, risk-of-bias assessments, and assessment of the certainty in the evidence with the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach. Data were synthesized with a random effects model and a frequentist approach. Forty-four trials (48 reports) were eligible, which included 7,378 participants and assessed the effect of 22 interventions in arresting or reversing noncavitated or cavitated carious lesions. Four network meta-analyses suggested that sealants + 5% sodium fluoride (NaF) varnish, resin infiltration + 5% NaF varnish, and 5,000-ppm F (1.1% NaF) toothpaste or gel were the most effective for arresting or reversing noncavitated occlusal, approximal, and noncavitated and cavitated root carious lesions on primary and/or permanent teeth, respectively (low- to moderate-certainty evidence). Study-level data indicated that 5% NaF varnish was the most effective for arresting or reversing noncavitated facial/lingual carious lesions (low certainty) and that 38% silver diamine fluoride solution applied biannually was the most effective for arresting advanced cavitated carious lesions on any coronal surface (moderate to high certainty). Preventing the onset of caries is the ultimate goal of a caries management plan. However, if the disease is present, there is a variety of effective interventions to treat carious lesions nonrestoratively.
| S-EPMC6304695 | biostudies-literature
Project description:BackgroundInfantile hemangioma (IH) is common in children, which may bring about cosmetically disfiguring, functional impairment, and exhibiting complications. There had been various therapies and we aimed to assess the efficacy and adverse effects of different therapies through network meta-analysis.MethodsWe searched PubMed, Embase, Cochrane Library and Web of Science (from database inception to April 11, 2020) for studies assessing the efficacy, success rate and adverse effects. Direct pairwise comparison and a network meta-analysis under random effects were performed. We also assessed the ranking probability.FindingsA total of 30 randomized clinical trials with more than 20 different therapeutic regimens were identified. Treatment combined propranolol orally with laser could improve the curative effect than monotherapy. Laser with topical β blockers showed more efficiency than others whether in children under 6 months or not. The long-pulsed dye laser might be the best laser therapy. A higher dose and a longer treatment duration of propranolol orally achieved a higher success rate and increased side effects. Plus pulse dye laser with propranolol had the lowest incidence of adverse reactions, such as ulcer, color sink and color reduction.InterpretationA combination of β blockers and laser might be the first-line treatment of IHs and a longer pulsed dye laser is preferred.FundingNo funding was received.
| S-EPMC7565185 | biostudies-literature
Project description: Not available
| S-EPMC7390912 | biostudies-literature
Project description:ImportanceIncidence of neonatal abstinence syndrome is rising rapidly, and optimal pharmacotherapy may meaningfully reduce length of treatment.ObjectiveTo compare pharmacological therapies for neonatal abstinence syndrome.Data sourcesSystematic review and network meta-analysis of Medline (1946-June 2018), Embase (1974-June 2018), Cochrane CENTRAL (1966-June 2018), Web of Science (1900-June 2018), and ClinicalTrials.gov (June 2018).Study selectionRandomized clinical trials of pharmacological treatments for neonatal abstinence syndrome alone or in combination with adjuvant treatments. Abstract, title, and full-text screening were conducted independently by 2 reviewers (T.D. and C.G.).Data extraction and synthesisData extraction was conducted independently by 2 reviewers (T.D. and C.G.) according to Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA)-Network Meta-Analyses guidelines. Quality was assessed with the Cochrane Risk of Bias tool and data were pooled with fixed-effect models as a result of the low number of trials that were included in the analysis.Main outcomes and measuresThe primary outcome was the length of treatment. The length of stay, need for adjuvant therapy, and adverse events were considered as secondary outcomes.ResultsEighteen trials (N?=?1072) were eligible for inclusion. The treatments that were included in the length of treatment analysis were buprenorphine, clonidine, diluted tincture of opium and clonidine, diluted tincture of opium, morphine, methadone, and phenobarbital. Sublingual buprenorphine was considered the optimal treatment for a reduction in the length of treatment (days: mean difference vs morphine, -12.75 [95% CI, -17.97 to -7.58]; median rank, 1 [3-1]) and length of stay (days: mean difference vs morphine, -11.43 [95% CI, -16.95 to -5.82]; median rank, 1 [3-1]) but not the need for adjuvant treatment (odds ratio vs morphine, 1.23 [95% CI, 0.46-3.44]; median rank, 3 [5-1]). The results were robust to bias but sensitive to imprecision.Conclusions and relevanceThe current evidence suggests that buprenorphine is the optimal treatment for neonatal abstinence treatment, but limitations are considerable and wide-scale adoption requires a large multisite trial. Morphine, which is considered standard of care in most hospitals, was the lowest-ranked opioid for length of treatment and length of stay.
| S-EPMC6439896 | biostudies-literature
Project description:Study designSystematic review with network meta-analysis.ObjectiveTo compare patient outcomes of lumbar discectomy with bone-anchored annular closure (LD + AC), lumbar discectomy (LD), and continuing conservative care (CC) for treatment of lumbar disc herniation refractory to initial conservative management.Summary of background dataSeveral treatment options are available to patients with refractory symptoms of lumbar disc herniation, but their comparative efficacy is unclear.MethodsA systematic review was performed to compare efficacy of LD + AC, LD, and CC for treatment of lumbar disc herniation. Outcomes included leg pain, back pain, disability (each reported on a 0-100 scale), reherniation, and reoperation. Data were analyzed using random effects network meta-analysis.ResultsThis review included 14 comparative studies (8 randomized) involving 3947 patients-11 studies of LD versus CC (3232 patients), 3 studies of LD + AC versus LD (715 patients), and no studies of LD + AC versus CC. LD was more effective than CC in reducing leg pain (mean difference [MD] -10, P < .001) and back pain (MD -7, P < .001). LD + AC was more effective than LD in reducing risk of reherniation (odds ratio 0.38, P < .001) and reoperation (odds ratio 0.33, P < .001). There was indirect evidence that LD + AC was more effective than CC in reducing leg pain (MD -25, P = .003), back pain (MD -20, P = .02), and disability (MD -13, P = .02) although the treatment effect was smaller in randomized trials.ConclusionsResults of a network meta-analysis show LD is more effective than CC in alleviating symptoms of lumbar disc herniation refractory to initial conservative management. Further, LD + AC lowers risk of reherniation and reoperation versus LD and may improve patient symptoms more than CC.
| S-EPMC6408089 | biostudies-literature
Project description:AimsTo determine the most efficacious and acceptable treatments of agitation in dementia.MethodsMEDLINE, EMBASE, PsycINFO, CENTRAL and clinicaltrials.gov were searched up to 7 February 2017. Two independent reviewers selected randomized controlled trials (RCTs) of treatments to alleviate agitation in people with all-types dementia. Data were extracted using standardized forms and study quality was assessed using the revised Cochrane Risk of Bias Tool for RCTs. Data were pooled using meta-analysis. The primary outcome, efficacy, was 8-week response rates defined as a 50% reduction in baseline agitation score. The secondary outcome was treatment acceptability defined as treatment continuation for 8 weeks.ResultsThirty-six RCTs comprising 5585 participants (30.9% male; mean ± standard deviation age, 81.8 ± 4.9 years) were included. Dextromethorphan/quinidine [odds ratio (OR) 3.04; 95% confidence interval (CI), 1.63-5.66], risperidone (OR 1.96; 95% CI, 1.49-2.59) and selective serotonin reuptake inhibitors as a class (OR 1.61; 95% CI, 1.02-2.53) were found to be significantly more efficacious than placebo. Haloperidol appeared less efficacious than nearly all comparators. Most treatments had noninferior treatment continuation compared to placebo, except oxcarbazepine, which was inferior. Findings were supported by subgroup and sensitivity analyses.ConclusionsRisperidone, serotonin reuptake inhibitors as a class and dextromethorphan/quinidine demonstrated evidence of efficacy for agitation in dementia, although findings for dextromethorphan/quinidine were based on a single RCT. Our findings do not support prescribing haloperidol due to lack of efficacy, or oxcarbazepine due to lack of acceptability. The decision to prescribe should be based on comprehensive consideration of the benefits and risks, including those not evaluated in this meta-analysis.
| S-EPMC6005613 | biostudies-literature
Project description:ImportanceZenker diverticulum (ZD) can cause significant dysphagia, and symptoms can return or persist after surgery. This systematic review and network meta-analysis is the first to our knowledge to compare 3 common surgical techniques for ZD.ObjectiveTo compare the 3 most common surgical techniques-endoscopic laser-assisted diverticulotomy, endoscopic stapler-assisted diverticulotomy, and transcervical diverticulectomy with cricopharyngeal myotomy-in adult patients with ZD.Data sourcesThe published literature was searched using strategies designed by a medical librarian (search performed September 21, 2018). Strategies were established using a combination of controlled vocabulary terms and keywords and were executed in Ovid MEDLINE (1946 to September 21, 2018), Embase (1947 to September 21, 2018), Scopus (1823 to September 21, 2018), Cochrane Library, and ClinicalTrials.gov. Results were limited to English using database-supplied filters, which generated studies from 1997 to 2017.Study selectionInclusion criteria were cohort studies or randomized clinical trials. Studies that included patients needing revision surgery or undergoing an alternative technique were excluded.Data extraction and synthesisThe Preferred Reporting Items for Systematic Reviews and Meta-analyses-Network Meta-analyses (PRISMA-NMA) checklist was used to report the study findings. Two authors independently reviewed the studies.Main outcome and measureThe primary outcome measure was the incidence of persistent or recurrent symptoms following surgery. The primary study outcome was planned before data collection began.ResultsThe search generated 529 studies. After applying inclusion and exclusion criteria, 9 cohort studies remained, consisting of 903 patients treated with either laser-assisted diverticulotomy (n = 283), transcervical diverticulectomy (n = 150), or stapler-assisted diverticulotomy (n = 470). A network meta-analysis was performed. Between endoscopic laser-assisted diverticulotomy and open diverticulectomy, the open approach showed a statistically lower likelihood of persistent/recurrent symptoms following treatment (odds ratio [OR], 0.20; 95% CI, 0.04-0.91). Comparing laser-assisted diverticulotomy with the stapler-assisted technique, there was not a significant difference between the 2 techniques (OR, 0.83; 95% CI, 0.43-1.60). The consistency model for the network meta-analysis was supported (χ21 = 0.12; P = .73).Conclusions and relevanceThis systematic review and meta-analysis compared 3 common techniques for treating ZD. The open approach showed a decreased likelihood of persistent or recurrent symptoms following surgery compared with the 2 other techniques.
| S-EPMC7716255 | biostudies-literature
Project description:BackgroundCurrently, preoperative chemoradiotherapy, perioperative chemotherapy and preoperative chemotherapy are recommended by NCCN, ESMO and Japanese guidelines respectively for resectable esophageal and junctional cancer. However, these recommendations are mainly based on esophageal cancer research. Therefore, specific for esophagogastric junction cancer, we conducted the first systematic review and network meta-analysis to rank all potential treatments simultaneously and hierarchically.MethodsRecord retrieval was conducted in PubMed, Web of Science, Cochrane Central Register of Controlled Trials, Embase, ASCO and ESMO Meeting Library from inception to September 2018. Regarding time-to-event survival data, randomized controlled trials featuring comparisons between different multimodal treatments against resectable esophagogastric junction cancer were eligible. Overall survival was the endpoint. Network calculation was based on a random-effects model and the relative ranking of each node was numerically indicated by P-score (CRD42018110369, registration identifier of the meta-analysis in PROSPERO.).ResultsEight studies were included in our systematic review, corresponding to 1218 patients. Regarding overall survival, 'PreCRT' (preoperative chemoradiotherapy) topped the hierarchy (HR 1.00, P-score = 0.823), better than 'PeriCT' (perioperative chemotherapy; HR 1.32, P-score = 0.591) and 'PreCT' (preoperative chemotherapy; HR 1.54, P-score = 0.428). In sensitivity analyses, irrespective of interchanging to fixed-effects model or removing potentially heterogeneous studies, relative rankings remained stable and 'PreCRT' was still the optimal node.ConclusionPreoperative chemoradiotherapy could potentially be the optimal multimodal treatment, which displayed more overall survival benefits than perioperative chemotherapy and preoperative chemotherapy among resectable esophagogastric junction cancer patients. To further verify our pooled results, more randomized trials will be needed to compare preoperative chemoradiotherapy with perioperative chemotherapy (especially FLOT-based regimens).
| S-EPMC6446435 | biostudies-literature
Project description:INTRODUCTION:There are numerous new systemic treatments for atopic dermatitis in various stages of development and most are being compared with placebo rather than active comparators. In order to understand the relative efficacy and safety of existing and new treatments for atopic dermatitis, robust mixed comparisons (ie, direct and indirect) would be beneficial. To address this gap, this protocol describes methods for a systematic review and network meta-analysis of systemic treatments for atopic dermatitis. METHODS AND ANALYSIS:We will update the search of a previous systematic review, including searches of the Cochrane Central Register of Controlled Trials, MEDLINE, Embase, Latin American and Caribbean Health Science Information database and the Global Resource of EczemA Trials database in addition to clinical trial protocol registries. Title, abstract and full paper screening as well as data extraction will be conducted in duplicate by independent researchers. Primary outcomes include efficacy with regards to clinician-reported signs and patient-reported symptoms and safety with regards to withdrawal from treatment due to adverse events and the occurrence of serious adverse events. Secondary outcomes will include change in quality of life and itch severity. Where possible and appropriate, network meta-analysis will be performed for each outcome using a random-effects model within a Bayesian framework. If appropriate, the review will be transitioned to a living review with continuous updating of the analysis. ETHICS AND DISSEMINATION:Dissemination in a peer-reviewed scientific journal is planned. PROSPERO REGISTRATION NUMBER:CRD42018088112; Pre-results.
| S-EPMC6119412 | biostudies-literature