Comparative effectiveness of types of denture adhesives in enhancing retention and function of complete dentures: a systematic review with network meta-analysis.

OBJECTIVES: The purpose of this systematic review with network meta-analysis was to assess the comparative efficacy of various types of denture adhesives in complete denture patients. 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 < .05) as well as premolar and molar regions (RR = 33.66[95%CI: 15.15, 52.16]). Cream adhesives significantly improved retention of dentures as assessed by the reduced number of denture dislodgments (RR = -5.35[95%CI: -9.93, -0.77]) (P = 0.022), Kapur's index of retention (maxillary denture) (RR = 0.80[95%CI: 0.18, 1.42]) (P = 0.012) and Kapur's index of retention (mandibular denture) (RR = 1.27[95%CI: 0.67, 1.87]) (P < .05). Powder adhesives significantly increased premolar and molar bite force (RR = 36.00[95%CI: 16.20, 55.79]) (P < .05) and Kapur's index of retention (mandibular denture) (RR = 1.54[95%CI: 0.58, 2.49]) (P = 0.002). None of the adhesives were statistically significant for remaining outcomes. CONCLUSIONS: Cream and powder denture adhesives are effective in enhancing the retention of mandibular dentures (Kapur's index) and bite force in the premolar/molar region in complete denture wearers (moderate level of certainty of evidence). CLINICAL RELEVANCE: Cream and powder denture adhesives are effective in improving the retention and function of complete dentures.

Comparative effectiveness of interventions for the treatment of peri-implantitis: A systematic review with network meta-analysis.

STATEMENT OF PROBLEM: Extensive research has been carried out on the various aspects of diagnosing and treating peri-implantitis. However, clinical guidelines for the management of peri-implantitis based on high quality evidence are lacking. PURPOSE: The purpose of this systematic review with network meta-analysis was to analyze the current evidence on nonsurgical and surgical interventions for the treatment of peri-implantitis and synthesize clinical guidelines based on high quality evidence. MATERIAL AND METHODS: A search was conducted for trials published in Medline, Scopus, PubMed, and Cochrane Central Register of Controlled Trials from inception until July 2023. The study was registered with the International Prospective Register of Systematic Reviews (PROSPERO) (CRD42023451056). A network meta-analysis was performed on data from randomized controlled trials that assessed nonsurgical and surgical interventions for the treatment of peri-implantitis. The interventions were ranked according to their efficacy using 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: A total of 45 articles were included in the quantitative analysis. The GRADE approach determined a moderate to high level of certainty of evidence. Among the nonsurgical interventions, mechanical debridement with adjunctive systemic antibiotics was significant in improving probing depth at 3 months and beyond 6 months, clinical attachment loss at 3 months, and clinical attachment loss beyond 6 months. Mechanical debridement with adjunctive topical antibiotics was significant in improving probing depth beyond 6 months, clinical attachment loss at 3 months, clinical attachment loss beyond 6 months, and radiographic bone loss beyond 6 months. Mechanical debridement with adjunctive photodynamic therapy was significant in improving probing depth beyond 6 months, clinical attachment loss at 3 months, clinical attachment loss beyond 6 months, and radiographic bone loss beyond 6 months. Mechanical debridement with adjunctive systemic antibiotics and photodynamic therapy was significant in improving probing depth beyond 6 months. Among surgical interventions, open flap debridement with implant surface decontamination and open flap debridement with decontamination and adjunctive photodynamic therapy were significant in improving probing depth at 3 months. CONCLUSIONS: Mechanical debridement with adjunctive systemic antibiotics or photodynamic therapy results in improved clinical outcomes.

Effects of ketogenic diet on health outcomes: an umbrella review of meta-analyses of randomized clinical trials.

BACKGROUND: Systematic reviews and meta-analyses of randomized clinical trials (RCTs) have reported the benefits of ketogenic diets (KD) in various participants such as patients with epilepsy and adults with overweight or obesity. Nevertheless, there has been little synthesis of the strength and quality of this evidence in aggregate. METHODS: To grade the evidence from published meta-analyses of RCTs that assessed the association of KD, ketogenic low-carbohydrate high-fat diet (K-LCHF), and very low-calorie KD (VLCKD) with health outcomes, PubMed, EMBASE, Epistemonikos, and Cochrane database of systematic reviews were searched up to February 15, 2023. Meta-analyses of RCTs of KD were included. Meta-analyses were re-performed using a random-effects model. The quality of evidence per association provided in meta-analyses was rated by the GRADE (Grading of Recommendations, Assessment, Development, and Evaluations) criteria as high, moderate, low, and very low. RESULTS: We included 17 meta-analyses comprising 68 RCTs (median [interquartile range, IQR] sample size of 42 [20-104] participants and follow-up period of 13 [8-36] weeks) and 115 unique associations. There were 51 statistically significant associations (44%) of which four associations were supported by high-quality evidence (reduced triglyceride (n = 2), seizure frequency (n = 1) and increased low-density lipoprotein cholesterol (LDL-C) (n = 1)) and four associations supported by moderate-quality evidence (decrease in body weight, respiratory exchange ratio (RER), hemoglobin A1c, and increased total cholesterol). The remaining associations were supported by very low (26 associations) to low (17 associations) quality evidence. In overweight or obese adults, VLCKD was significantly associated with improvement in anthropometric and cardiometabolic outcomes without worsening muscle mass, LDL-C, and total cholesterol. K-LCHF was associated with reduced body weight and body fat percentage, but also reduced muscle mass in healthy participants. CONCLUSIONS: This umbrella review found beneficial associations of KD supported by moderate to high-quality evidence on seizure and several cardiometabolic parameters. However, KD was associated with a clinically meaningful increase in LDL-C. Clinical trials with long-term follow-up are warranted to investigate whether the short-term effects of KD will translate to beneficial effects on clinical outcomes such as cardiovascular events and mortality.

Pneumococcal Vaccination in Children: A Systematic Review and Meta-Analysis of Cost-Effectiveness Studies.

OBJECTIVES: Pneumococcal conjugate vaccines (PCVs) have significantly reduced disease burden caused by Streptococcus pneumoniae, a leading cause of childhood morbidity and mortality globally. This systematic review and meta-analysis aimed to assess the incremental net benefit (INB) of the 13-valent PCV (PCV13) and 10-valent PCV (PCV10) in children. METHODS: We performed a comprehensive search in several databases published before May 2022. Studies were included if they were cost-effectiveness or cost-utility analyses of PCV13 or PCV10 compared with no vaccination or with each other in children. Various monetary units were converted to purchasing power parity, adjusted to 2021 US dollars. The INBs were calculated and then pooled across studies stratified by country income level, perspective, and consideration of herd effects, using a random-effect model. RESULTS: Seventy studies were included. When herd effects were considered, PCV13 was cost-effective compared with PCV10 from the payer perspective in both high-income countries (HICs) (INB, $103.94; 95% confidence interval, $75.28-$132.60) and low- and middle-income countries (LMICs) (INB, $53.49; 95% confidence interval, $30.42-$76.55) with statistical significance. These findings were robust across a series of sensitivity analyses. PCV13 was cost-effective compared with no vaccination across perspectives and consideration of herd effects in both HICs and LMICs, whereas findings were less consistent for PCV10. CONCLUSION: PCVs were generally cost-effective compared with no vaccination in HICs and LMICs. Our study found that PCV13 was cost-effective compared with PCV10 when herd effects were considered from the payer perspective in both HICs and LMICs. The results are sensitive to the consideration of herd effects.

Incremental net monetary benefit of biologic therapies in moderate to severe asthma: a systematic review and meta-analysis of economic evaluation studies.

OBJECTIVES: This meta-analysis was conducted to quantitatively pool the incremental net benefit (INB) of using biologic therapies as an add-on treatment to standard therapy in patients with moderate to severe asthma. METHODS: We performed a comprehensive search in several databases published until April 2022. Studies were included if they were cost-effectiveness analyses reporting cost per quality-adjusted life-year or life-year on any biologic therapies as an add-on treatment for moderate to severe asthma in patients of all ages. Various monetary units were converted to purchasing power parity, adjusted to 2021 US dollars. The INBs were pooled across studies using a random-effects model, stratified by country income level (high-income countries (HICs) and low- and middle-income countries (LMICs)) and perspectives (health care or payer perspective (HCPP) and societal perspective (SP)) and age group (>12 years and 6-11 years). Heterogeneity was assessed using the I2 statistic. RESULTS: A total of 32 comparisons from 25 studies were included. Pooled INB indicated that the use of omalizumab as an add-on treatment to standard therapy in those aged >12 years was not cost-effective in HICs from the HCPP (n = 8, INB, -6,341 (95% CI, -$25,000 to $12,210), I2=86.18%) and SP (n = 5, -$14,000 (-$170,000 to $140,000), I2=75.64%). A similar finding was observed in those aged 6-11 years from the HCPP in LMICs (n = 2, -$45,000 (-$73,000 to $17,000), I2=00.00%). Subgroup analyses provided no explanations of the potential sources of heterogeneity. CONCLUSION: The use of biologic therapies in moderate to severe asthma is not cost-effective compared to standard treatment alone.

The economic burden associated with stillbirth: A systematic review.

BACKGROUND: Evidence on the economic burden of stillbirth is limited. In this systematic review, we aimed to identify studies focusing on the economic burden of stillbirth, describe the methods used, and summarize the findings. METHOD: We performed a systematic search in Medline, EMBASE, Cochrane library, and EconLit from inception to July 2021. Original studies reporting the cost of illness, economic burden, or health care expenditures related to stillbirth were included. Two reviewers independently extracted data and evaluated study quality using the Larg and Moss checklist. A narrative synthesis was performed. Costs were presented in US dollars (US$) in 2020. RESULTS: From the 602 records identified, a total of four studies were included. Eligible studies were from high-income countries. Only one study estimated both direct and indirect costs. Among three cost-of-illness studies, two studies undertook a prevalence-based approach. The quality of these studies varied and was substantially under-reported. Four studies describing direct costs ranged from $6934 to $9220 per stillbirth. Indirect costs account for around 97% of overall costs. No studies have incorporated intangible cost components. CONCLUSIONS: The economic burden of stillbirth has been underestimated and not extensively studied. There are no data on the cost of stillbirth from countries that bear a higher burden of stillbirth. Extensive variation in methodologies and cost components was observed in the studies reviewed. Future research should incorporate all costs, including intangible costs, to provide a comprehensive picture of the true economic impact of stillbirth on society.

Clinical and economic implications of increasing access to herpes zoster vaccination rate in community pharmacies.

BACKGROUND: A community pharmacist plays an important role in providing vaccination to the general public in the United States. No economic models have been used to assess the impact of these services on public health and economic benefits. OBJECTIVE: This study aimed to estimate the clinical and economic implications of community pharmacy-based herpes zoster (HZ) vaccination services with a hypothetical scenario of nonpharmacy-based vaccination in the State of Utah. METHODS: A hybrid model of decision tree and Markov models was used to estimate lifetime cost and health outcomes. This open-cohort model was populated based on Utah population statistics and included a population of 50 years and older who were eligible for HZ vaccination between the years 2010 and 2020. Data were derived from the U.S. Bureau of Labor Statistics, the Utah Immunization Coverage Report, the Centers for Disease Control and Prevention (CDC) Behavioral Risk Factor Surveillance System, the CDC National Health Interview Survey, and existing literature. The analysis was performed from a societal perspective. A lifetime time horizon was used. The primary outcomes were the number of vaccination cases increased and the number of shingles and postherpetic neuralgia (PHN) cases averted. Total costs and quality-adjusted life-years (QALYs) were also estimated. RESULTS: Based on a cohort of 853,550 people eligible for HZ vaccination in Utah, an additional 11,576 individuals were vaccinated in the community pharmacy-based scenario compared with the nonpharmacy-based vaccination, resulting in 706 averted cases of shingles and 143 averted cases of PHN. Community pharmacy-based HZ vaccination was less costly (-$131,894) and gained more QALYs (52.2) compared with the nonpharmacy-based vaccination. A series of sensitivity analyses showed that the findings were robust. CONCLUSIONS: Community pharmacy-based HZ vaccination was less costly and gained more QALYs and was associated with improved other clinical outcomes in the State of Utah. This study might be used as a model for future evaluations of other community pharmacy-based vaccination programs in the United States.

Comparative effectiveness of fiber and metal posts in the restoration of endodontically treated teeth: A systematic review with network meta-analysis.

STATEMENT OF PROBLEM: Different varieties of fiber and metal intraradicular posts have been used for the restoration of endodontically treated teeth with insufficient sound tooth structure. Evidence on the comparative efficacy of posts in a clinical setting is insufficient to provide clear clinical guidelines and recommendations. PURPOSE: The purpose of this systematic review with network meta-analysis was to assess the comparative efficacy of fiber and metal posts used for the restoration of endodontically treated teeth. MATERIAL AND METHODS: A search was conducted for trials published in Medline, Scopus, PubMed, and Cochrane Central Register of Controlled Trials from inception until November 2022. The study was registered with the International Prospective Register of Systematic Reviews (PROSPERO) (CRD42022384340). A network meta-analysis was performed on data from randomized controlled trials that assessed the comparative efficacy of fiber posts and metal posts for the restoration of endodontically treated teeth. Subgroup analyses were performed to compare all the varieties of fiber and metal posts. The types of posts were ranked according to their efficacy 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: Twenty-five articles were included in the quantitative analysis. Fiber posts (RR=0.15 [95% CI: 0.06, 0.33]) significantly prevented tooth fracture as compared with no posts. Prefabricated carbon fiber posts (RR=0.06 [95% CI: 0, 0.54]) ranked highest followed by custom glass fiber posts (RR=0.15 [95% CI: 0.04, 0.52]) and prefabricated glass fiber posts (RR=0.22 [95% CI: 0.07, 0.62]) in the outcome of tooth fracture. Metal posts (RR=0.24 [95% CI: 0.12, 0.46]) ranked higher than fiber posts (RR=0.39 [95% CI: 0.27, 0.56]) in the outcome of debonding. Custom gold alloy posts (RR=0.12 [95% CI: 0.03, 0.48]), prefabricated gold alloy posts (RR=0.04 [95% CI: 0.00, 0.87]), and prefabricated titanium posts (RR=0.21 [95% CI: 0.10, 0.45]) had higher rankings in the outcome of debonding or loss of retention of a post followed by custom glass fiber posts (RR=0.37 [95% CI: 0.21, 0.63]) and prefabricated glass fiber posts (RR=0.38 [95%CI: 0.25, 0.58]). Prefabricated glass fiber posts (RR=0.40 [95% CI: 0.20, 0.81]) had statistically significant differences in the outcome of secondary caries. The GRADE approach determined a moderate level of certainty of evidence. CONCLUSIONS: The use of a fiber post when indicated results in reduced risk of tooth fracture as compared with no post. Prefabricated carbon fiber posts, prefabricated glass fiber posts, and custom glass fiber posts reveal a lower risk of tooth fracture. Overall, the use of prefabricated glass fiber posts had a lower risk of tooth fracture, debonding, and secondary caries. However, more trials with longer follow-up periods are recommended to enhance the certainty of evidence.

Comparative effectiveness of interventions for the treatment of denture stomatitis: A systematic review with network meta-analysis.

STATEMENT OF PROBLEM: Symptomatic denture stomatitis (DS) is a painful oral mucosal disorder that can impair quality of life in denture wearers. A complete cure of DS is difficult to achieve, and the most efficacious regimen to treat DS has not yet been conclusively established. 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.

COMPARATIVE EFFICACY OF ANTIVIRAL AGENTS FOR PREVENTION AND MANAGEMENT OF HERPES LABIALIS: A SYSTEMATIC REVIEW AND NETWORK META-ANALYSIS.

OBJECTIVE: To compare the relative efficacy and safety of antiviral agents used in the prevention and management of herpes labialis through a network meta-analysis of clinical trials. 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.

COMPARATIVE EFFICACY OF THERAPEUTIC INTERVENTIONS FOR THE MANAGEMENT OF RECURRENT APHTHOUS ULCERS: A SYSTEMATIC REVIEW AND NETWORK META-ANALYSIS.

BACKGROUND: Recurrent aphthous ulceration (RAU) is an oral condition cavity affecting 2.5 billion people worldwide. We aimed to assess the comparative efficacy and safety of available interventions in the management of RAU. 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.

Effects of pharmacist interventions on cardiovascular risk factors and outcomes: An umbrella review of meta-analysis of randomized controlled trials.

AIMS: To grade the evidence from published meta-analyses of randomized controlled trials (RCTs) that assessed effects of pharmacist intervention on cardiovascular risk factors and cardiovascular outcomes. METHODS: MEDLINE, Embase, and the Cochrane Library were searched from database inception to July 2021. Meta-analyses of RCTs were eligible. Quality of evidence were assessed by GRADE approach. RESULTS: From 9308 publications, 149 full-text articles were evaluated for eligibility, and 24 studies with 85 unique meta-analyses that assessed effects of pharmacist intervention on cardiovascular risk factors and cardiovascular outcomes were selected. Overall, 71.7% (61/85) of unique meta-analyses showed significant impacts of pharmacist intervention. For the quality of evidence, 63.4% of meta-analyses had large heterogeneity (I2 > 50%) while 1.2, 16.5, 32.9 and 49.4% of meta-analyses were graded as high, moderate, low and very low quality based on GRADE approach, respectively. Among meta-analyses with moderate quality, pharmacist interventions significantly mitigated risk factors (including 6/3 mmHg reduction of blood pressure, increased the rate of lipid control, glucose control and smoking cessation (pooled odds ratio, [95% confidence interval] 1.91 [1.55, 2.35], 3.11 [2.3, 4.3] and 2.3 [1.33, 3.97], respectively) and improved medication adherence (1.67 [1.38, 2.02]). Furthermore, pharmacist interventions significantly reduced all-cause mortality (0.72 [0.58, 0.89]) and improved quality of life in patients suffering from chronic heart failure. CONCLUSION: This umbrella review found convincing evidence that pharmacist intervention can provide a wide range of benefits in cardiovascular disease management, ranging from risk factor control, improvement in medication adherence and, in some settings, reduction in morbidity and mortality.

Association of proton-pump inhibitor use with adverse health outcomes: A systematic umbrella review of meta-analyses of cohort studies and randomised controlled trials.

AIMS: The aim was to perform an umbrella review to summarise the existing evidence on proton-pump inhibitor (PPI) use and adverse outcomes and to grade the certainty of evidence. 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.

The impact of pharmacist involvement on immunization uptake and other outcomes: An updated systematic review and meta-analysis.

BACKGROUND: The underutilization of immunization services remains a big public health concern. Pharmacists can address this concern by playing an active role in immunization administration. OBJECTIVE: We performed a systematic review and meta-analysis to assess the impact of pharmacist-involved interventions on immunization rates and other outcomes indirectly related to vaccine uptake. METHODS: A systematic literature search was conducted using MEDLINE, Embase, and Cochrane Central Register of Controlled Trials databases from inception to February 2022 to identify randomized controlled trials (RCTs) and observational studies in which pharmacists were involved in the immunization process. Studies were excluded if no comparator was reported. Two reviewers independently completed data extraction and bias assessments using standardized forms. Meta-analyses were performed using a random-effects model. RESULTS: A total of 14 RCTs and 79 observational studies were included. Several types of immunizations were provided, including influenza, pneumococcal, herpes zoster, Tdap, and others in a variety of settings (community pharmacy, hospital, clinic, others). Pooled analyses from RCTs indicated that a pharmacist as immunizer (risk ratio 1.14 [95% CI 1.12-1.15]), advocator (1.31 [1.17-1.48]), or both (1.14 [1.12-1.15]) significantly increased immunization rates compared with usual care or non-pharmacist-involved interventions. The quality of evidence was assessed as moderate or low for those meta-analyses. Evidence from observational studies was consistent with the results found in the analysis of the RCTs. CONCLUSION: Pharmacist involvement as immunizer, advocator, or both roles has favorable effects on immunization uptake, especially with influenza vaccines in the United States and some high-income countries. As the practice of pharmacists in immunization has been expanded globally, further research on investigating the impact of pharmacist involvement in immunization in other countries, especially developing ones, is warranted.

Effects of pharmacist interventions on pain intensity: Systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Pharmacists can play an important role in pain management. OBJECTIVE(S): This review aims to summarize the effects of any type of pharmacist intervention, whether led by a pharmacist or in a supportive role, on pain intensity over time in individuals with pain of any etiology. METHODS: Three electronic databases (MEDLINE, Embase, and Cochrane Central Register of Controlled Trials) were searched from inception to the end of May 2021 to identify randomized controlled trials (RCTs) that reported the effect of pharmacist interventions on pain intensity. Two reviewers independently extracted data and evaluated study quality. The analyses used a random-effects models and the Grading of Recommendations, Assessment, Development and Evaluation to rate the certainty of the evidence. The primary outcome was reduction in pain intensity and presented as standardized mean differences (SMD). RESULTS: Twelve RCTs including 1710 participants were included. Pooled estimate of 12 studies demonstrated a statistically significant reduction in pain intensity compared with control (SMD -0.22 [95% CI -0.31 to -0.12], I2 = 0%, low certainty). The intervention was more effective when a pharmacist delivered a combination of services comprising educational interventions, medication review, and pharmaceutical care services (SMD -0.24 [95% CI -0.35 to -0.13], I2 = 0%, moderate certainty). For educational interventions alone, no statistically significant difference was observed (SMD -0.15 [95% CI -0.45 to 0.15], I2 = 47.6%, low certainty). Pharmacist intervention was also effective in reducing pain intensity for patients with cancer-related pain (SMD -0.76 [95% CI -1.17 to -0.36], I2 = 0%, moderate certainty). CONCLUSION: There is some promising evidence to suggest that multicomponent pharmacist interventions including medication review or any other pharmaceutical care services, rather than merely educational interventions, are beneficial in reducing pain intensity, particularly in patients with chronic pain. High-quality RCTs are required to confirm the clinical significance of this findings before advocating for its widespread implication in clinical practice.

COMPARING THE CLINICAL AND RADIOGRAPHIC OUTCOMES OF PULPOTOMIES IN PRIMARY MOLARS USING BIOACTIVE ENDODONTIC MATERIALS AND FERRIC SULFATE - A SYSTEMATIC REVIEW AND META-ANALYSIS OF RANDOMIZED CLINICAL TRIALS.

OBJECTIVE: To compare the clinical and radiographic outcomes of pulpotomies in primary molars using bioactive endodontic materials and ferric sulfate. DESIGN: The search was conducted in PubMed, Ebscohost, ProQuest, and Scopus databases till June 2021. Children undergoing pulpotomy therapy in primary molars treated with ferric sulfate (FS) and bioactive endodontic materials were evaluated for clinical and radiographic success. Meta-analysis was performed on a random-effects model to assess the success at 6,12,18, and 24 months. The quality of studies was evaluated using the Cochrane risk of bias tool for randomized trials RESULTS: No significant difference was observed between Mineral trioxide aggregate (MTA) and FS at 24 months for both clinical [RR0.98 (95%CI 0.15,6.34), I2 = 0%] and radiographic [RR0.74 (95%CI: 0.23,2.43), I2 = 0%] success. At 6 months [RR1.36 (95%CI: 0.10,19.34), I2 = 33%], no difference was observed in the clinical [RR1.00 (95%CI: 0.95,1.05), I2 = 0%] and radiographic success [RR0.99 (95%CI: 0.88,1.11), I2 = 51%] between Biodentine (BD), FS and radiographic success of calcium enriched cement and FS [RR0.25 (95%CI: 0.03, 2.22), I2 = 0%]. CONCLUSION: Amongst bioactive materials, MTA and FS demonstrated equal success rates in both clinical and radiographic outcomes with follow-up periods of up to 24 months. Future, high-quality trials are required to verify the result of the current review.

Very-low-dose aspirin and surveillance colonoscopy is cost-effective in secondary prevention of colorectal cancer in individuals with advanced adenomas: network meta-analysis and cost-effectiveness analysis.

BACKGROUND: Individuals with advanced colorectal adenomas (ACAs) are at high risk for colorectal cancer (CRC), and it is unclear which chemopreventive agent (CPA) is safe and cost-effective for secondary prevention. We aimed to determine, firstly, the most suitable CPA using network meta-analysis (NMA) and secondly, cost-effectiveness of CPA with or without surveillance colonoscopy (SC). 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.

Antifungal agents in preventing oral candidiasis in clinical oncology: A network meta-analysis.

OBJECTIVE: This review examined the comparative efficacy and safety of antifungal agents in preventing oral candidiasis among patients on cancer treatment. 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.

Horizon scanning of therapeutic modalities for nonalcoholic steatohepatitis.

Many interventions have been investigated for the treatment of nonalcoholic steatohepatitis (NASH). This study aims to summarize all investigated options to date and review the use of specific endpoints at different stages of ongoing trials of noncirrhotic NASH treatments. Using a horizon scanning approach, evidence were identified including meta-analyses of randomized controlled trials (RCTs) in PubMed, EMBASE, Cochrane, and AMED (up to February 2020), recently published RCTs in PubMed (2015-April 2020), RCTs presented at conferences (AASL and EASL, 2015-2020), and ongoing RCTs in ClincalTrials.gov (2015-November 2020). We included 6 meta-analyses of RCTs, 30 published RCTs, 11 conference abstracts, and 62 ongoing RCTs. An evidence map was created to demonstrate the treatment effects of 49 therapeutic modalities for NASH. Only six interventions (6/49, 12.24%) met the histological surrogate endpoints for potential conditional FDA approval. Obeticholic acid is the only therapy demonstrating positive benefits in ≥1-point improvement in fibrosis with no worsening of NASH in a phase 3 trial. The other therapies were all phase 2 studies. ≥1-point improvement in fibrosis with no worsening of NASH was shown in patients treated with cenicriviroc. NASH resolution with no worsening of fibrosis was shown in patients treated with liraglutide, semaglutide and resmetirom. Lanifibranor achieved both surrogate histological endpoints. Five ongoing RCTs (5/62, 8.06%) will investigate histological progression to cirrhosis, death, or liver-related clinical outcomes. In conclusion, some therapeutic modalities showed promising benefits, but further studies are warranted to find a definite treatment of NASH which prevents progression to cirrhosis and adverse liver outcomes.

Efficacy of Biodentine and Mineral Trioxide Aggregate in Primary Molar Pulpotomies-A Systematic Review and Meta-Analysis With Trial Sequential Analysis of Randomized Clinical Trials.

OBJECTIVES: Pulpotomy is the favored treatment for pulp exposure in carious primary teeth. This review aimed to compare the success rates of biodentine (BD) and mineral trioxide aggregate (MTA) pulpotomies in primary molars using meta-analysis (MA) and trial sequential analysis (TSA) and also to assess the quality of the results by Grading of Recommendations, Assessment, Development and Evaluation (GRADE). METHODS: PubMed, EBSCOhost, and Scopus databases were searched. Additional searching was performed in clinical trial registry, reference lists of systematic reviews, and textbooks. Randomized clinical trials (RCTs) published in the English language through October 2017 comparing the success of pulpotomies in vital primary molars with a follow-up of at least 6 months were selected. Study selection, data extraction, and risk of bias assessment were performed. MA by random effects model, TSA, and GRADE were performed. RESULTS: Eight RCTs (n = 474) were included. Two RCTs had low risk of bias. No significant difference was observed between MTA and BD in clinical success at 6 months (risk ratio [RR], 1.00; 95% confidence interval [95% CI], 0.97-1.02; I2 = 0%), 12 months (RR, 1.00; 95% CI, 0.96-1.05; I2 = 0%), and 18 months (RR, 1.00; 95% CI, 0.93-1.08; I2 = 0%). No difference was observed in radiographic success at follow-up of 6 months (RR, 0.99; 95% CI, 0.96-1.02; I2 = 0%), 12 months (RR, 1.02; 95% CI, 0.47-2.21; I2 = 0%), and 18 months (RR, 1.02; 95% CI, 0.91-1.15; I2 = 0%). TSA indicated lack of firm evidence for the results of the meta-analytic outcomes on clinical and radiographic success. GRADE assessed the evidence from the MA comparing the effect of MTA and BD in pulpotomy to be of low quality. CONCLUSION: BD and MTA have similar clinical and radiographic success rates based on limited and low-quality evidence. Future high-quality RCTs between MTA and BD is required to confirm the evidence.