METHODS: A systematic search was performed in Ovid Medline PubMed, Cochrane Central Register of Controlled Trials (CENTRAL), Scopus and Clinicaltrials.gov for randomized controlled trials (RCTs) reporting a comparison of antiviral agents in the management and prevention of herpes labialis in healthy/immunocompetent adults. The data extracted from the selected RCTs were assessed and a network meta-analysis (NMA) was performed. The interventions were ranked according to the surface under the cumulative ranking (SUCRA).
RESULTS: A total of 52 articles were included for qualitative synthesis and for the quantitative part, 26 articles were analyzed for the primary treatment outcome and 7 studies were analyzed for the primary prevention outcome. The combination therapy of oral valacyclovir and topical clobetasol was the best ranked with a mean reduction in healing time of -3.50 (95% CI -5.22 to -1.78) followed by vidarabine monophosphate of -3.22 (95% CI -4.59 to -1.85). No significant inconsistencies, heterogeneity, and publication bias were reported for TTH outcome analysis. For primary prevention outcomes, only 7 RCTs fulfilled the inclusion criteria, and none of the interventions was shown to be superior to each other. The absence of adverse events was reported by 16 studies, whereas other studies reported mild side effects only.
CONCLUSION: NMA highlighted that several agents were effective in the management of herpes labialis among which the combination of oral valacyclovir with topical clobetasol therapy was the most effective in reducing the time to heal. However, further studies are required to determine which intervention is the most effective in preventing the recurrence of herpes labialis.
METHODS: The current investigation extends a recently published study in the International Endodontic Journal (Nagendrababu V, Faggion Jr CM, Pulikkotil SJ, Alatta A, Dummer PM Methodological assessment and overall confidence in the results of systematic reviews with network meta-analyses in Endodontics. International Endodontic Journal 2022;55:393-404) that assessed the methodological quality of systematic reviews with NMAs in Endodontics using the A MeaSurement Tool to Assess systematic Reviews (AMSTAR 2) tool. In the present study, the PRISMA for NMA checklist with 32 items was used to assess the reporting quality of the systematic reviews with NMAs (n = 12). Two independent assessors assigned '1' when an item was completely addressed, '0.5' when it was partially addressed, and '0' when it was not addressed. Disagreements were resolved through reviewer discussion until consensus was reached. If conflicts persisted, a third reviewer made the final decision. The PRISMA for NMA scores were shared with the relevant authors of the individual reviews to reduce the likelihood of misinterpretation and verify the scores assigned. The results for each individual item of the PRISMA-NMA items were calculated by summing the individual scores awarded; the maximum score for each item was 12.
RESULTS: All the systematic reviews with NMAs adequately reported the following items: Title, Introduction section (Objectives), Methods section (Eligibility criteria and Information sources), Results section (Study selection, Study characteristics and Risk of bias within studies), and Discussion section (Summary of evidence). The items that were reported least often were the "geometry of the network" and "the summary of network geometry" with only 2 manuscripts (17%) including these items.
CONCLUSION: A number of the items in the PRISMA-NMA checklist were adequately addressed in the NMAs; however, none adequately reported all the PRISMA-NMA items. The inadequacies of published NMAs that have been identified should be taken into consideration by authors of NMAs in Endodontics and by editors when managing the peer review process. In future, researchers who are writing systematic reviews with NMAs should comply with the PRISMA-NMA checklist.
CLINICAL RELEVANCE: None of the included systematic reviews with NMA adequately reported all the PRISMA-NMA items. Inadequate reporting of a systematic review with NMA increases the possibility that it will provide invalid results. Therefore, authors should follow the PRISMA-NMA guidelines when reporting systematic reviews with NMA in Endodontics.
MATERIALS AND METHODS: An electronic search of 3 databases (Medline, CENTRAL, Scopus) was performed to identify randomized control trials evaluating the efficacy of RAU interventions published until December 2022. A network meta-analysis (NMA) was conducted on 4 outcomes: reduction in pain, duration of ulceration, the diameter of ulceration, and area of ulceration. The interventions are then arranged using the surface area under cumulative ranking (SUCRA).
RESULTS: A total of 38 trials involving 2773 patients were included were included in quantitative synthesis by NMA. Our analysis showed that Diode laser [MD, -4.865 ± 1.951 (95%CI = (-8.690, -1.041)] was the most effective in reducing the pain score followed by Amlexanox [MD, -2.673 ± 1.075 (95%CI = -4.779, -0.566)]. Iralvex performed the best in reducing the duration of ulceration [MD, -6.481 ± 1.841 (95%CI = -10.090, -2.872)]. Diode laser, acacia nilotica with licorice formulation, and amlexanox were the most effective interventions for reduction of ulcer diameter. Majority of the trials reported absence of any adverse effects and those reported were mild.
CONCLUSION: Our NMA has identified several interventions to be more effective than a placebo. Laser therapy may be an option for promoting pain management, however, most have only been tested in 1 or 2 trials. Further studies with rigorous methodology on larger samples are recommended to strengthen the current evidence.
METHODS: We performed a systematic review and network meta-analysis based on randomised controlled trials that compared antifungal agents to placebo or other antifungal agents used in patients undergoing cancer treatment. Relative ranking of antifungal agents was evaluated with surface under the cumulative ranking (SUCRA) probability score. A total of 20 randomised controlled trials (3,215 participants) comparing 11 interventions were included.
RESULTS: Compared with placebo, clotrimazole was ranked the best agent for preventing the incidence of oral candidiasis (risk ratio (RR), 0.21 [95% CI 0.08 to 0.55]; SUCRA = 0.89). Fluconazole was ranked the safest among other antifungal agents (SUCRA = 0.80), whereas clotrimazole (SUCRA = 0.36) and amphotericin B (SUCRA = 0.18) were ranked low for safety. Amphotericin B was associated with highest risk of adverse events (RR, 3.52 [95% CI 1.27 to 9.75]).
CONCLUSION: Clotrimazole is the most effective in preventing oral candidiasis, whereas fluconazole has the most favourable risk-benefit profile in patients undergoing cancer treatment. However, we are unable to recommend clotrimazole as the best choice to prevent oral candidiasis due to unavailability of studies comparing clotrimazole with other antifungal agents.
MATERIAL AND METHODS: A search was conducted for trials published in Scopus, PubMed, and Cochrane Central Register of Controlled Trials from inception until July 2023 (PROSPERO: CRD42023451045). A network meta-analysis was performed to assess the comparative efficacy of different denture adhesive types and ranked using the Surface Under the Cumulative Ranking (SUCRA) system. The Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) approach was used to assess the level of certainty of evidence.
RESULTS: Seventeen articles were included in the quantitative analysis. Cream denture adhesives significantly increased bite force in both incisal region (RR = 7.63[95%CI: 3.34, 11.91]) (P
AIM: To perform a systematic review with network meta-analysis to resolve this uncertainty.
METHODS: We searched the medical literature through July 2020 for randomised controlled trials (RCTs) assessing efficacy of drugs for adults with FD, compared with each other, or placebo. Trials reported a dichotomous assessment of symptom status after completion of therapy. We pooled data using a random effects model. Efficacy was reported as a pooled relative risk (RR) of remaining symptomatic with a 95% confidence interval (CI) to summarise efficacy of each comparison tested. Relative ranking was assessed with surface under the cumulative ranking curve (SUCRA) probabilities.
RESULTS: We identified 71 eligible RCTs (19 243 participants). Tricyclic antidepressants (TCAs) were ranked second for efficacy (RR of remaining symptomatic = 0.71; 95% CI 0.58-0.87, SUCRA 0.87), and first when only low risk of bias trials were included. Most RCTs that used TCAs recruited patients who were refractory to other drugs included in the network. Although sulpiride or levosulpiride were ranked first for efficacy (RR = 0.49; 95% CI 0.36-0.69, SUCRA 0.99), trial quality was low and only 86 patients received active therapy. TCAs were more likely to cause adverse events than placebo.
CONCLUSIONS: TCAs, histamine-2 receptor antagonists, standard- and low-dose proton pump inhibitors, sulpiride or levosulpiride, itopride and acotiamide were all more efficacious than placebo for FD.
METHODS: Systematic review and NMA of randomised controlled trials were performed, and the most suitable CPA was chosen based on efficacy and the most favourable risk-benefit profile. The economic benefits of CPA alone, 3 yearly SC alone, and a combination of CPA and SC were determined using the cost-effectiveness analysis (CEA) in the Malaysian health-care perspective. Outcomes were reported as incremental cost-effectiveness ratios (ICERs) in 2018 US Dollars ($) per quality-adjusted life-year (QALY), and life-years (LYs) gained.
RESULTS: According to NMA, the risk-benefit profile favours the use of aspirin at very-low-dose (ASAVLD, ≤ 100 mg/day) for secondary prevention in individuals with previous ACAs. Celecoxib is the most effective CPA but the cardiovascular adverse events are of concern. According to CEA, the combination strategy (ASAVLD with 3-yearly SC) was cost-saving and dominates its competitors as the best buy option. The probability of being cost-effective for ASAVLD alone, 3-yearly SC alone, and combination strategy were 22%, 26%, and 53%, respectively. Extending the SC interval to five years in combination strategy was more cost-effective when compared to 3-yearly SC alone (ICER of $484/LY gain and $1875/QALY). However, extending to ten years in combination strategy was not cost-effective.
CONCLUSION: ASAVLD combined with 3-yearly SC in individuals with ACAs may be a cost-effective strategy for CRC prevention. An extension of SC intervals to five years can be considered in resource-limited countries.
METHODS: Relevant randomized trials that assessed efficacy of antimalarial drugs for patients having uncomplicated falciparum malaria in Asian region were searched in health-related databases. We evaluated the methodological quality of the included studies with the Cochrane risk of bias tool. Main outcome was treatment success at day 28 as determined by the absence of parasiteamia. We performed network meta-analysis of the interventions in the trials, and assessed the overall quality of evidence using the GRADE approach.
RESULTS: Seventeen randomized trials (n = 5043) were included in this network meta-analysis study. A network geometry was formed with 14 antimalarial treatment options such as artemether-lumefantrine (AL), artemisinin-piperaquine, artesunate-amodiaquine, artesunate-mefloquine (ASMQ), artesunate-chloroquine, artesunate-mefloquine home treatment, artesunate-mefloquine 2-day course, artesunate plus sulfadoxine-pyrimethamine, chloroquine, dihydroartemisinin-piperaquine (DHP), dihydroartemisinin-piperaquine home treatment, dihydroartemisinin-piperaquine 4-day course, dihydroartemisinin-piperaquine and added artesunate, sulfadoxine-pyrimethamine. A maximum number of trials included was DHP compared to ASMQ (n = 5). In general, DHP had better efficacy than AL at day 28 (DHP vs AL: OR 2.5, 95%CI:1.08-5.8). There is low certainty evidence due to limited number of studies and small trials.
DISCUSSION/ CONCLUSIONS: The findings suggest the superiority of DHP (3-day course) to AL and other comparator ACTs are with the overall low/very low quality of evidence judgements. Moreover, one drug regimen is better than another is only if current drug-resistance patterns are at play. For example, the AL might be better than DHP in areas where both artemisinin and piperaquine resistance patterns are prevalent. For substantiation, well-designed larger trials from endemic countries are needed. In the light of benefit versus harm concept, future analysis with safety information is recommended.
METHODS: This study will include only RCTs published in peer-reviewed journals. A systematic search will be conducted in several electronic databases and other relevant online resources. No limitations are imposed on language or publication date. Participants must be explicitly identified by authors as having OA. Interventions that involved exercise or comparators in any form will be included. Pain is the primary outcome of interest; secondary outcomes will include function and quality of life measures. Quality assessment of studies will be based on the modified Cochrane's risk of bias assessment tool. At least two investigators will be involved throughout all stages of screening and data acquisition. Conflicts will be resolved through discussion. Conventional meta-analysis will be performed based on random effects model and network meta-analysis on a Bayesian model. Subgroup analysis will also be conducted based on study, patient and disease characteristics.
DISCUSSION: This study will provide for the first time comprehensive research evidence for the relative efficacy of different exercise regimens for treatment of OA. We will use network meta-analysis of existing RCT data to answer this question.
SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42016033865.
METHODS: We searched PubMed, Embase, and CENTRAL from inception until August 2020 for randomized controlled trials comparing both techniques. The primary outcome was cumulative morphine consumption at 24 h. Secondary pain-related outcomes included pain score at rest and on movement at 2, 6, 12, and 24 h; postoperative nausea and vomiting; and length of hospital stay.
RESULTS: We included 23 studies with a total of 2,178 patients. TAP block is superior to control in reducing opioid consumption at 24 h, improving pain scores at all the time points and postoperative nausea and vomiting. The cumulative opioid consumption at 24 h for IPLA is less than control, while the indirect comparison between IPLA with PSI and control showed a significant reduction in pain scores at rest, at 2 h, and on movement at 12 h, and 24 h postoperatively.
CONCLUSIONS: Transversus abdominis plane block is effective for reducing pain intensity and has superior opioid-sparing effect compared to control. Current evidence is insufficient to show an equivalent analgesic benefit of IPLA to TAP block.
AIM: To summarize and rank the effectiveness of clinical interventions using different agents for primary prevention of early childhood caries (ECC).
DESIGN: Two reviewers independently searched PubMed, Embase, and Cochrane Library to identify randomized controlled trials with at least 12-month follow-up. The network meta-analysis (NMA) on different agents was based on a random-effects model and frequentist approach. Standardized mean differences (SMD) with 95% CI of the caries increment were calculated in terms of either dmft or dmfs and used in the NMA. Caries incidences at the child level were compared using odds ratios (ORs) with 95% CI. The effectiveness of the agents was ranked using the surface under the cumulative ranking curve (SUCRA).
RESULTS: After screening 3807 publications and selection, the NMA finally included 33 trials. These trials used either a single or combination of agents such as fluorides, chlorhexidine, casein phosphopeptide-amorphous calcium phosphate, probiotics, xylitol, and triclosan. Compared with control, fluoride foam (FF; SMD -0.69, 95% CI: -1.06, -0.32) and fluoride salt (F salt; SMD -0.66, 95% CI: -1.20, -0.13) were effective in preventing caries increment. Probiotic milk plus low fluoride toothpaste (PMLFTP; OR 0.34, 95% CI: 0.15, 0.77), FF (OR 0.48, 95% CI: 0.37, 0.63), fluoride varnish (FV; OR 0.63, 95% CI: 0.48, 0.81), and fluoride varnish plus high fluoride toothpaste (FVHFTP; OR 0.73, 95% CI: 0.57, 0.93) were effectively preventing caries incidence. According to the SUCRA, FF ranked first in preventing caries increment, whereas PMLFTP ranked first in preventing caries incidence.
CONCLUSION: Fluoride foam, F salt, PMLFTP, FV, and FVHFTP all effectively reduce caries increment or caries incidence in preschool children, but the evidence indicates low degree of certainty. Considering the relatively small number of studies, confidence in the findings, and limitations in the study, clinical practitioners and readers should exercise caution when interpreting the NMA results.
OBJECTIVES: To assess the comparative efficacy and safety of different types of systemic immunosuppressive treatments for moderate to severe eczema using NMA and to generate rankings of available systemic immunosuppressive treatments for eczema according to their efficacy and safety.
SEARCH METHODS: We searched the following databases up to August 2019: the Cochrane Skin Specialised Register, CENTRAL, MEDLINE, and Embase.
SELECTION CRITERIA: All randomised controlled trials (RCTs) of systemic immunosuppressive agents for moderate to severe atopic eczema when compared against placebo or any other eligible eczema treatment.
DATA COLLECTION AND ANALYSIS: We synthesised data using pair-wise analysis and NMA to compare treatments and rank them according to their effectiveness. Effectiveness was assessed primarily by determining the proportion of participants who achieved at least 75% improvement in the Eczema Area and Severity Index (EASI75) and improvement in the Patient-Oriented Eczema Measure (POEM). Safety was evaluated primarily by considering the proportion of participants with serious adverse events (SAEs) and infection. We deemed short-term follow-up as ≤ 16 weeks and long-term follow-up as > 16 weeks. We assessed the certainty of the body of evidence from the NMA for these primary outcomes using six domains of CiNEMA grading.
MAIN RESULTS: We included a total of 74 studies, with 8177 randomised participants. Approximately 55% of participants were male, with average age of 32 years (range 2 to 84 years), although age and gender were unreported for 419 and 902 participants, respectively. Most of the included trials were placebo controlled (65%), 34% were head-to-head studies (15% assessed the effects of different doses of the same drug), and 1% were multi-armed studies with both an active comparator and a placebo. All trials included participants with moderate to severe eczema, but 62% of studies did not separate data by severity; 38% of studies assessed only severe eczema. The total duration of included trials ranged from 2 weeks to 60 months, whereas treatment duration varied from a single dose (CIM331, KPL-716) to 60 months (methotrexate (MTX)). Seventy studies were available for quantitative synthesis; this review assessed 29 immunosuppressive agents from three classes of interventions. These included (1) conventional treatments, with ciclosporin assessed most commonly; (2) small molecule treatments, including phosphodiesterase (PDE)-4 inhibitors, tyrosine kinase inhibitors, and Janus kinase (JAK) inhibitors; and (3) biological treatments, including anti-CD31 receptors, anti-interleukin (IL)-22, anti-IL-31, anti-IL-13, anti-IL-12/23p40, anti-OX40, anti-TSLP, anti-CRTH2, and anti-immunoglobulin E (IgE) monoclonal antibodies, but most commonly dupilumab. Most trials (73) assessed outcomes at a short-term duration ranging from 2 to 16 weeks, whereas 33 trials assessed long-term outcomes, with duration ranging from 5 to 60 months. All participants were from a hospital setting. Fifty-two studies declared a source of funding, and of these, pharmaceutical companies funded 88%. We rated 37 studies as high risk; 21, unclear risk, and 16, low risk of bias, with studies most commonly at high risk of attrition bias. Network meta-analysis suggests that dupilumab ranks first for effectiveness when compared with other biological treatments. Dupilumab is more effective than placebo in achieving EASI75 (risk ratio (RR) 3.04, 95% confidence interval (CI) 2.51 to 3.69) and improvement in POEM score (mean difference 7.30, 95% CI 6.61 to 8.00) at short-term follow-up (high-certainty evidence). Very low-certainty evidence means we are uncertain of the effects of dupilumab when compared with placebo, in terms of the proportion of participants who achieve EASI75 (RR 2.59, 95% CI 1.87 to 3.60) at longer-term follow-up. Low-certainty evidence indicates that tralokinumab may be more effective than placebo in achieving short-term EASI75 (RR 2.54, 95% CI 1.21 to 5.34), but there was no evidence for tralokinumab to allow us to assess short-term follow-up of POEM or long-term follow-up of EASI75. We are uncertain of the effect of ustekinumab compared with placebo in achieving EASI75 (long-term follow-up: RR 1.17, 95% CI 0.40 to 3.45; short-term follow-up: RR 0.91, 95% CI 0.28 to 2.97; both very low certainty). We found no evidence on ustekinumab for the POEM outcome. We are uncertain whether other immunosuppressive agents that targeted our key outcomes influence the achievement of short-term EASI75 compared with placebo due to low- or very low-certainty evidence. Dupilumab and ustekinumab were the only immunosuppressive agents evaluated for longer-term EASI75. Dupilumab was the only agent evaluated for improvement in POEM during short-term follow-up. Low- to moderate-certainty evidence indicates a lower proportion of participants with SAEs after treatment with QAW039 and dupilumab compared to placebo during short-term follow-up, but low- to very low-certainty evidence suggests no difference in SAEs during short-term follow-up of other immunosuppressive agents compared to placebo. Evidence for effects of immunosuppressive agents on risk of any infection during short-term follow-up and SAEs during long-term follow-up compared with placebo was of low or very low certainty but did not indicate a difference. We did not identify differences in other adverse events (AEs), but dupilumab is associated with specific AEs, including eye inflammation and eosinophilia.
AUTHORS' CONCLUSIONS: Our findings indicate that dupilumab is the most effective biological treatment for eczema. Compared to placebo, dupilumab reduces eczema signs and symptoms in the short term for people with moderate to severe atopic eczema. Short-term safety outcomes from clinical trials did not reveal new safety concerns with dupilumab. Overall, evidence for the efficacy of most other immunosuppressive treatments for moderate to severe atopic eczema is of low or very low certainty. Given the lack of data comparing conventional with newer biological treatments for the primary outcomes, there remains high uncertainty for ranking the efficacy and safety of conventional treatments such as ciclosporin and biological treatments such as dupilumab. Most studies were placebo-controlled and assessed only short-term efficacy of immunosuppressive agents. Further adequately powered head-to-head RCTs should evaluate comparative long-term efficacy and safety of available treatments for moderate to severe eczema.
OBJECTIVES: Our study used data from the most recent network meta-analysis (NMA) and local parameters to assess the cost effectiveness of non-statin agents in statin-treated patients with a history of CVD.
METHODS: A published Markov model was adopted to investigate lifetime outcomes: (1) number of recurrent CVD events prevented, (2) quality-adjusted life-years (QALYs) gained, (3) costs and (4) incremental cost-effectiveness ratios (ICERs) of proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) and ezetimibe added to statin therapy. Event rates and effectiveness inputs were obtained from the NMA. Cost and utility data were gathered from published studies conducted in Thailand. A series of sensitivity analyses were performed.
RESULTS: Patients receiving PCSK9i and ezetimibe experienced fewer recurrent CVD events (number needed to treat [NNT] 17 and 30) and more QALYs (0.168 and 0.096 QALYs gained per person). However, under the societal perspective and at current acquisition costs in 2018, ICERs of both agents were $US1,223,995 and 27,361 per QALY gained, respectively. Based on threshold analyses, the costs need to be reduced by 97 and 85%, respectively, for PCSK9i and ezetimibe to be cost-effective.
CONCLUSIONS: Despite the proven effectiveness of PCSK9i and ezetimibe, the costs of these agents need to reduce to a much greater extent than in HICs to be cost-effective in Thailand.