PURPOSE: The purpose of this network meta-analysis was to assess the comparative efficacy of interventions used for the treatment of DS.
MATERIAL AND METHODS: A search was conducted for trials published in Medline, Scopus, PubMed, and Cochrane Central Register of Controlled Trials from inception until February 2022 (PROSPERO Reg no: CRD42021271366). Network meta-analysis was performed on data from randomized controlled trials that assessed the comparative efficacy of any form of intervention for the treatment of DS in denture wearers. Agents were ranked according to their effectiveness in the treatment of DS based on outcomes using surface under the cumulative ranking (SUCRA).
RESULTS: A total of 25 articles were included in the quantitative analysis. Topical antifungal agents (risk ratio [RR]=4.37[95% confidence interval [CI]: 2.15,8.90), topical antimicrobial agents used along with systemic antifungal agents (RR=4.25[95% CI: 1.79,10.33]), systemic antifungal agents (RR=4.25[95% CI: 1.79,10.10]), photodynamic therapy (RR=4.25[95% CI: 1.75,8.98]), and topical plant products (RR=3.40[95% CI: 1.59,7.26]) were found to effectively improve DS. Microwave disinfection concurrently administered with topical antifungal agents (RR=7.38(95% CI: 2.75,19.81), microwave disinfection 7.38[95% CI: 2.75,19.81]), topical antifungal agents (RR=4.88[95% CI: 1.92,12.42]), topical plant products (RR=4.49[95% CI: 1.70,11.82]), systemic antifungal agents together with topical antimicrobial agents (RR=3.85[95% CI: 1.33,11.10]), topical antimicrobial agents (RR=3.39[95% CI: 1.17,9.81]), systemic antifungal agents (RR=3.37[95% CI: 1.21,9.34]), and photodynamic therapy or photochemotherapy (PDT) (RR=2.93[95% CI: 1.01,8.47]) were found to effectively resolve mycological DS. Topical antifungals ranked highest in the SUCRA ranking for clinical improvement, whereas microwave disinfection concurrently administered with topical antifungal agents ranked highest for mycological resolution. None of the agents demonstrated significant side effects except for topical antimicrobial agents which demonstrated altered taste and staining of oral structures.
CONCLUSIONS: Available evidence suggests that topical antifungals, microwave, and systemic antifungals are effective in the treatment of DS, but confidence in these findings is low because of the limited number of studies and a high risk of bias. Additional clinical trials are needed on photodynamic therapy, topical plant products, and topical antimicrobials.
METHODS: A search for economic evaluation studies was conducted from inception to 30 September 2022, on PubMed, Embase, Cost-Effectiveness Analysis (CEA) Registry by Tufts Medical Centre, EconLit and the NHS Economic Evaluation Database (NHS EED). Eligible studies were included if they were (1) conducted among adults ages 18 years old and older who were smokers attempting to quit for the first time; (2) compared varenicline to behaviour support with bupropion or NRT, behaviour support alone and unaided cessation; and (3) performed a CEA or cost-utility analysis. The INBs were calculated and pooled across studies stratified by country income level and study perspective using the random-effects model. Statistical heterogeneity between studies was assessed using the I2 statistic and Cochrane Q statistic.
RESULTS: Of the 1433 identified studies, 18 studies were included in our review. Our findings from healthcare system/payer perspective suggested that the use of varenicline is statistically significantly cost-effective compared with bupropion (pooled INB, $830.75 [95% confidence interval, $208.23, $1453.28]), NRTs ($636.16 [$192.48, $1079.84]) and unaided cessation ($4212.35 [$1755.79, $6668.92]) in high-income countries. Similarly, varenicline is also found to be cost-effective compared to bupropion ($2706.27 [$1284.44, $4128.11]), NRTs ($3310.01 [$1781.53, $4838.50]) and behavioural support alone ($5438.22 [$4105.99, $6770.46]) in low- and middle-income countries.
CONCLUSION: Varenicline is cost-effective as a smoking cessation aid when compared with behavioural support with bupropion or nicotine replacement therapies and behavioural support alone in both high-income countries and low- and middle-income countries, from the healthcare system/payer perspective in adult smokers who attempt to quit for the first time.
METHODS: PubMed, Cochrane CENTRAL, and EMBASE were searched for randomized trials comparing pharmacologic or surgical obesity interventions to usual care, placebo, or no treatment in adults with OSA. The association between percentage weight loss and AHI change between randomization and last follow-up was evaluated using meta-regression.
PROSPERO: CRD42022378853.
RESULTS: Ten eligible trials (n = 854 patients) were included. Four (n = 211) assessed bariatric surgery, and 6 (n = 643) assessed pharmacologic interventions over a median follow-up of 13 months (interquartile range 6-26 months). The linear best estimate of the change in AHI is 0.45 events per hour (95% Confidence Interval 0.18 to 0.73 events per hour) for every 1% body weight lost.
CONCLUSIONS: Weight loss caused by medication or surgery caused a proportionate improvement of the AHI. Providers could consider extrapolating from this relationship when advising patients of the expected effects of other pharmacologic or surgical interventions without direct evidence in OSA.
METHODS: Electronic databases were searched up to March 2024 for randomised controlled trials (RCTs) comparing the use of any type or concentration of TCSs with placebo or no treatment in boys with any degree of physician diagnosed phimosis. A random-effects network meta-analysis (NMA) using a consistency model within a frequentist approach was employed. The primary outcome was partial or complete resolution of phimosis reported as a pooled risk ratio (RR) with 95% CI. Relative ranking was assessed with surface under the cumulative ranking curve (SUCRA) probabilities.
RESULTS: Seventeen RCTs, containing 2057 participants were identified. NMA suggested that, compared with control, the high (RR 3.19 (95% CI 1.42 to 7.16), moderate (RR 2.68 (95% CI 1.87 to 3.83) and low (RR 3.05 (95% CI 1.63 to 5.71) potency TCSs statistically significantly increased complete or partial clinical resolution of phimosis. The SUCRA plot revealed that high potency (SUCRA = 0.76) was ranked first followed by low and moderate TCSs. When we assessed comparative efficacy among TCSs based on potency, none of the classes were superior to others. The certainty of the evidence for an effect of moderate potent TCSs was that of moderate GRADE quality.
CONCLUSION: Moderate to low potency TCSs are of comparable therapeutic effect in the treatment of phimosis to that of highly potent formulations. More high-quality RCTs are warranted.
METHODS: Electronic databases were searched up to March 2024 for randomized controlled trials (RCTs) recruiting adults with FD. Data of overall symptoms improved between the antidepressants and placebo groups was pooled to obtain risk ratio (RR) employing the random-effects model. The effect of random errors was evaluated with TSA. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach was used to assess the certainty of evidence. Analyses were performed using STATA version 16.0.
RESULTS: Nine RCTs with 924 patients met the eligible criteria. The RRs of FD symptoms improving with any antidepressants, tricyclic antidepressants (TCAs) and selective serotonin reuptake inhibitors were (n = 9, RR = 1.30 [95% CI, 1.02-1.67]), (n = 5, RR = 1.41 [95% CI, 1.07-1.85]) and (n = 2, RR = 0.97 [95% CI, 0.72-1.29]), respectively. TSA demonstrated conclusive evidence for the beneficial effect of TCAs. The number needed to treat (NNT) with any depressants and TCAs were 11 (95% CI, 7-36) and 6 (95% CI, 4-15), respectively. The certainty of the evidence for an effect of TCAs was that of moderate GRADE quality. The benefit, however, was limited to the western population (n = 3, RR = 1.43 [95% CI, 1.04-1.96]) and did not extend to the Asian population (n = 2, RR = 1.32 [95% CI, 0.75-2.32]). Conversely, antidepressant-using patients experienced adverse events more frequently. However, no statistically significant association was found between TCAs and any adverse events (n = 3; RR = 1.36 [95% CI, 0.91-2.04]).
CONCLUSION: Evidence was obtained suggesting TCAs can be an effective alternative in the treatment of FD, but more evidence from high-quality large trials is required to support their use, especially in the Asian population.
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 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: We did a network meta-analysis based on a systematic review of randomized controlled trials (RCTs) that compared at least one CPA (aspirin, antioxidants, folic acid, vitamin B6, vitamin B12, calcium, vitamin D, alone or in combination) to placebo or other CPA in persons without history of CRC. Several databases were searched from inception up to March 2017. Primary outcomes were early and long-term CRC incidence and mortality.
Results: Twenty-one RCTs comprising 281,063 participants, 9 RCTS comprising 160,101 participants, and 7 RCTs comprising 24,001 participants were included in the network meta-analysis for early risk of CRC incidence, long-term risk of CRC incidence and mortality, respectively. For early CRC incidence, no CPAs were found to be effective. For long-term CRC incidence and mortality, aspirin was the only intervention that showed protective effects with potential dose-dependent effects (risk ratio [RR], 0.74 [95% CI, 0.57-0.97] for high-dose [≥325 mg/day] and RR, 0.81 [95% CI, 0.67-0.98] for very-low-dose [≤100 mg/day]). Similar trend was found for mortality (RR, 0.43 [95% CI, 0.23-0.81] for low-dose [>100-325 mg/day] and RR, 0.65 [95% CI, 0.45-0.94] for very-low-dose). However, in net clinical benefit analysis, when combining risk estimates on mortality from CRC, cardiovascular disease, and pooled risk estimates of major gastrointestinal bleeding, low-dose aspirin provided the highest net survival gain (%) of 1.736 [95% CI, 1.010-2.434].
Conclusion: Aspirin at the dose range of 75-325 mg/day is a safe and effective primary prevention for long-term CRC among people at average risk. None of the other CPAs were found to be effective. There may potentially be differential effects among various doses of aspirin that needs further investigation.
Methods: We reviewed the records of colorectal cancer patients treated in Hospital Tuanku Ja'afar Seremban, Malaysia from 2008 to 2012. Survival analysis at five years was performed using the Kaplan-Meier method. Cox proportional hazard regression analysis was carried out to determine the predictors of 5-year colorectal cancer survival.
Results: Of the 275 patients, 43.3% were colon cancers, 51.8% were rectal cancers. Only 2.2% were diagnosed in Stage I. 28.7%, 33.1%, and 16.7% were in Stage II, III and IV respectively; 62/79 (78%) of Stage II patients were in Stage IIb; 15.7% of patients were below the age of 50 and fewer of them presented early (P=0.002). The overall 5-year survival was 46.5%. It was 67.9%, 50.5% and 12.8% for Stage I&II, III and IV patients respectively. Early stage of cancer (P<0.001) and age below the mean (P=0.01) were the most significant factor in predicting better survival. Gender and ethnic group were not associated with late presentation nor survival. Neither was there a difference between colon and rectum cancers nor patients who received elective surgical treatment compared to patients receiving other treatment first (P=0.085).
Conclusions: Late presentation is the most important predictor for poor outcome for colorectal cancer in Seremban. Patients under the age of 50 years present late more often, but do not have poorer survival.
Objective: To grade the evidence from published meta-analyses of RCTs that assessed the associations of IF (zero-calorie alternate-day fasting, modified alternate-day fasting, the 5:2 diet, and time-restricted eating) with obesity-related health outcomes.
Evidence Review: PubMed, Embase, and Cochrane database of systematic reviews were searched from database inception to January 12, 2021. Data analysis was conducted from April 2021 through July 2021. Meta-analyses of RCTs investigating effects of IF in adults were included. The effect sizes of IF were recalculated using a random-effects model. We assessed the quality of evidence per association by applying the GRADE criteria (Grading of Recommendations, Assessment, Development, and Evaluations) as high, moderate, low, and very low.
Findings: A total of 11 meta-analyses comprising 130 RCTs (median [IQR] sample size, 38 [24-69] participants; median [IQR] follow-up period, 3 [2-5] months) were included describing 104 unique associations of different types of IF with obesity-related health outcomes (median [IQR] studies per association, 4 [3-5]). There were 28 statistically significant associations (27%) that demonstrated the beneficial outcomes for body mass index, body weight, fat mass, low-density lipoprotein cholesterol, total cholesterol, triglycerides, fasting plasma glucose, fasting insulin, homeostatic model assessment of insulin resistance, and blood pressure. IF was found to be associated with reduced fat-free mass. One significant association (1%) supported by high-quality evidence was modified alternate-day fasting for 1 to 2 months, which was associated with moderate reduction in body mass index in healthy adults and adults with overweight, obesity, or nonalcoholic fatty liver disease compared with regular diet. Six associations (6%) were supported by moderate quality evidence. The remaining associations found to be significant were supported by very low (75 associations [72%]) to low (22 associations [21%]) quality evidence.
Conclusions and Relevance: In this umbrella review, we found beneficial associations of IF with anthropometric and cardiometabolic outcomes supported by moderate to high quality of evidence, which supports the role of IF, especially modified alternate-day fasting, as a weight loss approach for adults with overweight or obesity. More clinical trials with long-term follow-up are needed to investigate the effects of IF on clinical outcomes such as cardiovascular events and mortality.
Objective: To grade the evidence from meta-analyses of randomized clinical trials (RCTs) and cohort studies that assessed the associations between hormonal contraceptive use and adverse health outcomes among women.
Data Sources: MEDLINE, Embase, and the Cochrane Database of Systematic Reviews were searched from database inception to August 2020. Search terms included hormonal contraception, contraceptive agents, progesterone, desogestrel, norethindrone, megestrol, algestone, norprogesterones, and levonorgestrel combined with terms such as systematic review or meta-analysis.
Evidence Review: The methodological quality of each meta-analysis was graded using the Assessment of Multiple Systematic Reviews, version 2, which rated quality as critically low, low, moderate, or high. The Grading of Recommendation, Assessment, Development and Evaluations approach was used to assess the certainty of evidence in meta-analyses of RCTs, with evidence graded as very low, low, moderate, or high. Evidence of associations from meta-analyses of cohort studies was ranked according to established criteria as nonsignificant, weak, suggestive, highly suggestive, or convincing.
Results: A total of 2996 records were screened; of those, 310 full-text articles were assessed for eligibility, and 58 articles (13 meta-analyses of RCTs and 45 meta-analyses of cohort studies) were selected for evidence synthesis. Sixty associations were described in meta-analyses of RCTs, and 96 associations were described in meta-analyses of cohort studies. Among meta-analyses of RCTs, 14 of the 60 associations were nominally statistically significant (P ≤ .05); no associations between hormonal contraceptive use and adverse outcomes were supported by high-quality evidence. The association between the use of a levonorgestrel-releasing intrauterine system and reductions in endometrial polyps associated with tamoxifen use (odds ratio [OR], 0.22; 95% CI, 0.13-0.38) was graded as having high-quality evidence, and this evidence ranking was retained in the subgroup analysis. Among meta-analyses of cohort studies, 40 of the 96 associations were nominally statistically significant; however, no associations between hormonal contraceptive use and adverse outcomes were supported by convincing evidence in the primary and subgroup analyses. The risk of venous thromboembolism among those using vs not using oral contraception (OR, 2.42; 95% CI, 1.76-3.32) was initially supported by highly suggestive evidence, but this evidence was downgraded to weak in the sensitivity analysis.
Conclusions And Relevance: The results of this umbrella review supported preexisting understandings of the risks and benefits associated with hormonal contraceptive use. Overall, the associations between hormonal contraceptive use and cardiovascular risk, cancer risk, and other major adverse health outcomes were not supported by high-quality evidence.
METHODS: In this umbrella review, we searched four databases (Pubmed, Embase, the Cochrane Database of Systematic Reviews, and Epistemonikos) from database inception to April 2022. The methodological quality of each meta-analysis was assessed using the Assessment of Multiple Systematic Reviews, version 2 (AMSTAR-2). The strength of evidence of the associations between race and ethnicity with outcomes was ranked according to established criteria as convincing, highly suggestive, suggestive, weak, or non-significant. The study protocol was registered with PROSPERO, CRD42022336805.
RESULTS: Of 880 records screened, we selected seven meta-analyses for evidence synthesis, with 42 associations examined. Overall, 10 of 42 associations were statistically significant (p ≤ 0.05). Two associations were highly suggestive, two were suggestive, and two were weak, whereas the remaining 32 associations were non-significant. The risk of COVID-19 infection was higher in Black individuals compared to White individuals (risk ratio, 2.08, 95% Confidence Interval (CI), 1.60-2.71), which was supported by highly suggestive evidence; with the conservative estimates from the sensitivity analyses, this association remained suggestive. Among those infected with COVID-19, Hispanic individuals had a higher risk of COVID-19 hospitalization than non-Hispanic White individuals (odds ratio, 2.08, 95% CI, 1.60-2.70) with highly suggestive evidence which remained after sensitivity analyses.
CONCLUSION: Individuals of Black and Hispanic groups had a higher risk of COVID-19 infection and hospitalization compared to their White counterparts. These associations of race and ethnicity and COVID-19 outcomes existed more obviously in the pre-hospitalization stage. More consideration should be given in this stage for addressing health inequity.
METHODS: Electronic databases were searched up to July 2021 for meta-analyses of cohort studies and/or randomised controlled trials (RCTs). Summary effect sizes from a random-effects model, between-study heterogeneity, 95% prediction interval, small-study effect, excess significance and credibility ceilings were devised to classify the credibility of evidence from meta-analyses of cohort studies, whereas the GRADE approach was used for meta-analyses of RCTs.
RESULTS: In meta-analyses of cohort studies, 52 of the 91 examined associations were statistically significant (P ≤ .05). Convincing evidence emerged from main analysis for the association between PPI use and risk of all-site fracture and chronic kidney disease in the elderly population. However, none of these associations remained supported by convincing evidence after sensitivity analyses. The use of PPI is also associated with an increased risk of mortality due to COVID-19 infection and other related adverse outcomes, but the quality of evidence was weak. In meta-analyses of RCTs, 38 of the 63 examined associations were statistically significant. However, no associations were supported by high or moderate-quality evidence.
CONCLUSION: This study's findings imply that most putative adverse outcomes associated with PPI use may not be supported by high-quality evidence and are likely to have been affected by underlying confounding factors. Future research is needed to confirm the causal association between PPI use and risk of fracture and chronic kidney disease.