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.
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 searched 4 electronic databases (Medline, the Cochrane Central Register of Controlled Trials, Embase, CINAHL) and internet sources for randomized controlled trials, ongoing clinical trials, and unpublished studies up to August 2016. Studies that assessed CVCs with antimicrobial impregnation with nonimpregnated catheters or catheters with another impregnation were included. Primary outcomes were clinically diagnosed sepsis, catheter-related bloodstream infection (CRBSI), and all-cause mortality. We performed a network meta-analysis to estimate risk ratio (RR) with 95% confidence interval (CI).
Results: Sixty studies with 17255 catheters were included. The effects of 14 impregnations were investigated. Both CRBSI and catheter colonization were the most commonly evaluated outcomes. Silver-impregnated CVCs significantly reduced clinically diagnosed sepsis compared with silver-impregnated cuffs (RR, 0.54 [95% CI, .29-.99]). When compared to no impregnation, significant CRBSI reduction was associated with minocycline-rifampicin (RR, 0.29 [95% CI, .16-.52]) and silver (RR, 0.57 [95% CI, .38-.86]) impregnations. No impregnations significantly reduced all-cause mortality. For catheter colonization, significant decreases were shown by miconazole-rifampicin (RR, 0.14 [95% CI, .05-.36]), 5-fluorouracil (RR, 0.34 [95% CI, .14-.82]), and chlorhexidine-silver sulfadiazine (RR, 0.60 [95% CI, .50-.72]) impregnations compared with no impregnation. None of the studies evaluated antibiotic/antiseptic resistance as the outcome.
Conclusions: Current evidence suggests that the minocycline-rifampicin-impregnated CVC appears to be the most effective in preventing CRBSI. However, its overall benefits in reducing clinical sepsis and mortality remain uncertain. Surveillance for antibiotic resistance attributed to the routine use of antimicrobial-impregnated CVCs should be emphasized in future trials.
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.
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
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.
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.
METHODS: We did a network meta-analysis based on a systematic review of randomised controlled trials comparing fibrinolytic drugs in patients with STEMI. Several databases were searched from inception up to Feb 28, 2017. We included only randomised controlled trials that compared fibrinolytic agents as a reperfusion therapy in adult patients with STEMI, whether given alone or in combination with adjunctive antithrombotic therapy, against other fibrinolytic agents, a placebo, or no treatment. Only trials investigating agents with an approved indication of reperfusion therapy in STEMI (streptokinase, tenecteplase, alteplase, and reteplase) were included. The primary efficacy outcome was all-cause mortality within 30-35 days and the primary safety outcome was major bleeding. This study is registered with PROSPERO (CRD42016042131).
FINDINGS: A total of 40 eligible studies involving 128 071 patients treated with 12 different fibrinolytic regimens were assessed. Compared with accelerated infusion of alteplase with parenteral anticoagulants as background therapy, streptokinase and non-accelerated infusion of alteplase were significantly associated with an increased risk of all-cause mortality (risk ratio [RR] 1·14 [95% CI 1·05-1·24] for streptokinase plus parenteral anticoagulants; RR 1·26 [1·10-1·45] for non-accelerated alteplase plus parenteral anticoagulants). No significant difference in mortality risk was recorded between accelerated infusion of alteplase, tenecteplase, and reteplase with parenteral anticoagulants as background therapy. For major bleeding, a tenecteplase-based regimen tended to be associated with lower risk of bleeding compared with other regimens (RR 0·79 [95% CI 0·63-1·00]). The addition of glycoprotein IIb or IIIa inhibitors to fibrinolytic therapy increased the risk of major bleeding by 1·27-8·82-times compared with accelerated infusion alteplase plus parenteral anticoagulants (RR 1·47 [95% CI 1·10-1·98] for tenecteplase plus parenteral anticoagulants plus glycoprotein inhibitors; RR 1·88 [1·24-2·86] for reteplase plus parenteral anticoagulants plus glycoprotein inhibitors).
INTERPRETATION: Significant differences exist among various fibrinolytic regimens as reperfusion therapy in STEMI and alteplase (accelerated infusion), tenecteplase, and reteplase should be considered over streptokinase and non-accelerated infusion of alteplase. The addition of glycoprotein IIb or IIIa inhibitors to fibrinolytic therapy should be discouraged.
FUNDING: None.
Methods: This study is a review of relevant publications about the effects of raloxifene on sleep disorder, depression, venous thromboembolism, the plasma concentration of lipoprotein, breast cancer, and cognitive function among menopausal women.
Results: Raloxifene showed no significant effect on depression and sleep disorder. Verbal memory improved with administration of 60 mg/day of raloxifene while a mild cognitive impairment risk reduction by 33% was observed with administration of 120 mg/day of raloxifene. Raloxifene was associated with a 50% decrease in the need for prolapse surgery. The result of a meta-analysis showed a significant decline in the plasma concentration of lipoprotein in the raloxifene group compared to placebo (standardized mean difference, -0.43; 10 trials). A network meta-analysis showed that raloxifene significantly decreased the risk of breast cancer (relative risk, 0.572; 95% confidence interval, 0.327-0.881; P = 0.01). In terms of adverse effects of raloxifene, the odds ratio (OR) was observed to be 1.54 (P = 0.006), indicating 54% increase in the risk of deep vein thrombosis (DVT) while the OR for pulmonary embolism (PE) was 1.05, suggesting a 91% increase in the risk of PE alone (P = 0.03).
Conclusions: Raloxifene had no significant effect on depression and sleep disorder but decreased the concentration of lipoprotein. Raloxifene administration was associated with an increased risk of DVT and PE and a decreased risk of breast cancer and pelvic organ prolapse in postmenopausal women.
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.
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.
METHODS: MEDLINE, 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.
RESULTS: Thirty-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.
CONCLUSIONS: Risperidone, 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.
METHODS: We did a genome-wide association study of NKTCL in multiple populations from east Asia. We recruited a discovery cohort of 700 cases with NKTCL and 7752 controls without NKTCL of Han Chinese ancestry from 19 centres in southern, central, and northern regions of China, and four independent replication samples including 717 cases and 12 650 controls. Three of these independent samples (451 cases and 5301 controls) were from eight centres in the same regions of southern, central, and northern China, and the fourth (266 cases and 7349 controls) was from 11 centres in Hong Kong, Taiwan, Singapore, and South Korea. All cases had primary NKTCL that was confirmed histopathologically, and matching with controls was based on geographical region and self-reported ancestry. Logistic regression analysis was done independently by geographical regions, followed by fixed-effect meta-analyses, to identify susceptibility loci. Bioinformatic approaches, including expression quantitative trait loci, binding motif and transcriptome analyses, and biological experiments were done to fine-map and explore the functional relevance of genome-wide association loci to the development of NKTCL.
FINDINGS: Genetic data were gathered between Jan 1, 2008, and Jan 23, 2019. Meta-analysis of all samples (a total of 1417 cases and 20 402 controls) identified two novel loci significantly associated with NKTCL: IL18RAP on 2q12.1 (rs13015714; p=2·83 × 10-16; odds ratio 1·39 [95% CI 1·28-1·50]) and HLA-DRB1 on 6p21.3 (rs9271588; 9·35 × 10-26 1·53 [1·41-1·65]). Fine-mapping and experimental analyses showed that rs1420106 at the promoter of IL18RAP was highly correlated with rs13015714, and the rs1420106-A risk variant had an upregulatory effect on IL18RAP expression. Cell growth assays in two NKTCL cell lines (YT and SNK-6 cells) showed that knockdown of IL18RAP inhibited cell proliferation by cell cycle arrest in NKTCL cells. Haplotype association analysis showed that haplotype 47F-67I was associated with reduced risk of NKTCL, whereas 47Y-67L was associated with increased risk of NKTCL. These two positions are component parts of the peptide-binding pocket 7 (P7) of the HLA-DR heterodimer, suggesting that these alterations might account for the association at HLA-DRB1, independent of the previously reported HLA-DPB1 variants.
INTERPRETATION: Our findings provide new insights into the development of NKTCL by showing the importance of inflammation and immune regulation through the IL18-IL18RAP axis and antigen presentation involving HLA-DRB1, which might help to identify potential therapeutic targets. Taken in combination with additional genetic and other risk factors, our results could potentially be used to stratify people at high risk of NKTCL for targeted prevention.
FUNDING: Guangdong Innovative and Entrepreneurial Research Team Program, National Natural Science Foundation of China, National Program for Support of Top-Notch Young Professionals, Chang Jiang Scholars Program, Singapore Ministry of Health's National Medical Research Council, Tanoto Foundation, National Research Foundation Singapore, Chang Gung Memorial Hospital, Recruitment Program for Young Professionals of China, First Affiliated Hospital and Army Medical University, US National Institutes of Health, and US National Cancer Institute.