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.
DESIGN: Network meta-analysis.
DATA SOURCES: PubMed, Embase, Scopus, Cochrane Library and Web of Science from database inception to January 2022.
ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Randomised controlled trials (RCTs) comparing exercise therapy with oral NSAIDs and paracetamol directly or indirectly in knee or hip OA.
RESULTS: A total of n=152 RCTs (17 431 participants) were included. For pain relief, there was no difference between exercise and oral NSAIDs and paracetamol at or nearest to 4 (standardised mean difference (SMD)=-0.12, 95% credibility interval (CrI) -1.74 to 1.50; n=47 RCTs), 8 (SMD=0.22, 95% CrI -0.05 to 0.49; n=2 RCTs) and 24 weeks (SMD=0.17, 95% CrI -0.77 to 1.12; n=9 RCTs). Similarly, there was no difference between exercise and oral NSAIDs and paracetamol in functional improvement at or nearest to 4 (SMD=0.09, 95% CrI -1.69 to 1.85; n=40 RCTs), 8 (SMD=0.06, 95% CrI -0.20 to 0.33; n=2 RCTs) and 24 weeks (SMD=0.05, 95% CrI -1.15 to 1.24; n=9 RCTs).
CONCLUSIONS: Exercise has similar effects on pain and function to that of oral NSAIDs and paracetamol. Given its excellent safety profile, exercise should be given more prominence in clinical care, especially in older people with comorbidity or at higher risk of adverse events related to NSAIDs and paracetamol.CRD42019135166.
METHODS: Randomized trials, assessing the efficacy of antiviral drugs for HBV and HIV co-infected patients were searched in health-related databases. The methodological quality of the included trials was evaluated using the Cochrane risk of bias tool. Main outcome in this meta-analysis study was the success of treatment by antivirals as determined by virologic response. We performed pairwise and network meta-analysis of these trials and assessed the quality of evidence using the GRADE approach.
RESULTS: Seven randomized trials (329 participants) were included in this network meta-analysis study. A network geometry was formed with six treatment options including four antiviral drugs, adefovir (ADV), emtricitabine (FTC), lamivudine (LMV) and tenofovir disoproxil fumarate (TDF), combination treatment of TDF plus LMV, and placebo. The weighted percentage contributions of each comparison distributed fairly equally in the entire network of evidence. An assumption of consistency required for network meta-analysis was not violated (the global Wald test for inconsistency: Chi2(4) = 3.63, p = 0.46). The results of estimates showed no differences between the treatment regimens in terms of viral response for treating HBV and HIV co-infected patients, which spanned both benefit and harm (e.g. LMV vs TDF plus LMV: OR: 0.37, 95%CI: 0.06-2.41). Overall, the certainty of evidence was very low in all comparisons (e.g. LMV vs TDF plus LMV: 218 fewer per 1000,121 more to 602 fewer, very low certainty). Therefore, we remained uncertain to the true ranking of the antiviral treatments in HBV/ HIV co-infected patients.
CONCLUSIONS: The findings suggest that the evidence is insufficient to provide guidance to the relative effectiveness of currently available antiviral drugs with dual activity in treating co-infection of HBV/HIV. Well-designed, large clinical trials in this field to address other important outcomes from different epidemiological settings are recommended.
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.
METHODS: We searched PubMed, Embase and the Cochrane Central systematically for the randomised control trials (RCTs) of interventions for preventing OM. Network meta-analysis (NMA) was performed to estimate risk ratios (RR) and 95% confidence intervals (CI) from both direct and indirect evidence. The primary outcome was any grade of OM. Secondary outcomes were mild-moderate OM, severe OM and adverse events, such as taste disturbance and gastrointestinal adverse events. This study was registered with PROSPERO, number CRD42016052489.
RESULTS: A total of 29 RCTs with 2348 patients (median age, 56.1 years; 57.5% male) were included. Cryotherapy was associated with a significantly lower risk of OM than control (RR 0.51, 95% CI 0.38 to 0.68), and zinc sulphate (RR 0.47, 95% CI 0.23 to 0.97), but not significantly lower than sucralfate and palifermin. No significant differences were observed between cryotherapy and control for taste disturbance and gastrointestinal adverse events. Palifermin was associated with the highest risk of taste disturbance.
CONCLUSIONS: This NMA suggests that cryotherapy was the most effective intervention for preventing chemotherapy-induced OM with a safety profile similar to control, but not significantly lower than sucralfate and palifermin. Large RCTs are needed to confirm these findings.
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: 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.
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.
Materials and Methods: We used three online databases, i.e., PubMed, ScienceDirect, and Cochrane Central Registry of Clinical Trials. Randomized controlled trials (RCTs) on the use of prophylactic chemotherapeutic agents used in treating nonpregnant women with recurrent urinary tract infections (RUTIs) published between 2002 and 2016 were selected. Only published papers in English were assessed for study quality, and meta-analyses were performed using fixed-effects model with NetMetaXL.
Results: Six RCTs fulfilled the criteria. When all three variables, i.e., efficacy, adverse effects and cost were considered, nitrofurantoin 50 mg once daily for 6 months appears to rank high for prophylaxis against RUTI. When efficacy was the only factor, fosfomycin had the highest superiority compared to D-mannose, nitrofurantoin, estriol, trimethoprim-sulfamethoxazole, and cranberry juice, respectively. However, fosfomycin was also ranked highest by adverse events. When cost alone is considered, nitrofurantoin appeared the most cost-effective agent while placed third for efficacy alone.
Conclusion: Selecting appropriate chemotherapeutic agents for RUTI will need to factor in effectiveness, adverse effects, and cost. While it is difficult to select an ideal drug, evaluation using network analysis may guide choice of medication for best practice.
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: We searched nine databases from inception to 8 February 2018 for randomized controlled trials evaluating pharmacological interventions and clinical outcomes in adult bacterial meningitis. An updated search from 9 February to 9 March 2020 was performed, and no new studies met the inclusion criteria. Study quality was assessed using the revised Cochrane Risk of Bias Tool. The Grading of Recommendations Assessment, Development and Evaluation system was used for quality of evidences evaluation. Meta-analyses were conducted to estimate the risk ratio with 95% confidence interval for both direct and indirect comparisons on the primary outcomes of all-cause mortality, neurologic sequelae and any hearing loss. The study was registered in PROSPERO (CRD42018108062).
RESULTS: Nine RCTs were included in systematic review, involving 1,002 participants with a mean age ranging between 25.3 to 50.56 years. Six RCTs were finally included in the network-meta analysis. No significant difference between treatment was noted in meta-analysis. Network meta-analysis suggests that corticosteroids in combination with antibiotic therapy was more effective in reducing the risk of any hearing loss compared to mono antibiotic therapy (RR 0.64; 95%CI, 0.45 to 0.91, 4 RCTs, moderate certainty of evidence). Numerical lower risk of mortality and neurological complications was also shown for adjunctive corticosteroids in combination with antibiotic therapy versus mono antibiotic therapy (RR 0.65; 95%CI, 0.42 to 1.02, 6 RCTs, moderate certainty of evidence; RR 0.75; 95%CI, 0.47 to 1.18, 6 RCTs, moderate certainty of evidence). No differences were noted in the adverse events between different therapies. The overall certainty of evidence was moderate to very low for all primary outcomes examined.
CONCLUSIONS: Results of this study suggest that corticosteroids therapy in combination with antibiotic is more effective than mono antibiotic therapy in reducing the risk of any hearing loss in adult patients with acute bacterial meningitis. More well-design RCTs to investigate relative effective treatments in acute bacterial meningitis particularly in adult population should be mandated to aid clinicians in treatment recommendations.
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.
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.