Cardiovascular Disease Burden Attributable to High Body Mass Index in Taiwan.

Background: Studies on disease burden in Taiwan are lacking. We aimed to quantify the burden of cardiovascular disease (CVD) attributable to high body mass index (BMI) in Taiwan. Methods: Using a comparative risk assessment approach from the Global Burden of Disease study, we estimated the population attributable fraction (PAF), attributable CVD burden, and disability-adjusted life years (DALYs) according to sex, age, and area of residence in Taiwan. The BMI distribution for the population was obtained from the National Health Interview Survey in 2013. CVD was defined as an ischemic heart disease or stroke. Results: The attributable PAF for CVD from high BMI was 18.0% (19.6% in men and 15.6% in women), and it was highest (42.7%) in those aged 25-30 years. Adults aged 60-65 years had the highest absolute DALYs (11,546). The average relative age-standardized attributable burden was 314 DALYs per 100,000 person-years, and it was highest in those aged 75-80 years (1,407 DALYs per 100,000 person-years). Those living in Taitung County had the highest PAF of 21.9% and the highest age-standardized attributable burden (412 DALYs). Conclusions: In Taiwan, an 18% reduction in CVDs could be achieved if obesity/overweight was prevented. Prevention was most effective in early adulthood. The absolute CVD burden from obesity/overweight was highest in middle-aged men, and the relative burden was highest in older adults. Resource allocation in targeted populations and specific areas to eliminate CVD and health inequities is urgently required.

Disease Attribution to Multiple Exposures Using Aggregate Data.

BACKGROUND: Identifying which exposures cause disease and quantifying their impacts is essential in promoting and monitoring public health. When multiple exposures are involved, measuring individual contributions becomes challenging. METHODS: The authors propose a disease attribution method based on aggregate data or summary statistics of individual-level data, possibly from multiple data sources. RESULTS: Using the proposed method, the burden of disease is apportioned to the independent and interaction effects of each of its major risk factors and all the other factors as a whole. This scheme guarantees that 100% is the total share of the burden. CONCLUSION: The calculation is simple and straightforward; therefore, it is recommended for use in studies on disease burden.

The Incidence of Contrast-Induced Nephropathy and the Need of Dialysis in Patients Receiving Angiography: A Systematic Review and Meta-Analysis.

Objectives: The risk of dialysis following contrast exposure is unclear. We aimed to examine the overall risk of contrast induced nephropathy and the need of dialysis based on a systematic review with random-effects meta-analysis. Methods: We searched the electronic database including PubMed, Medline, Embase, and Cochrane Library from inception to 31 October, 2020 with predetermined search term to identify relevant studies. Observational studies investigating the association between contrast induced nephropathy after angiography and the need of dialysis were included, and summary risks were estimated. Two independent reviewers extracted the data, followed with random effects model to calculate the overall pooled incidence of contrast induced nephropathy and the need of dialysis after angiography. Subgroup-analysis and meta-regression were performed to assess heterogeneity of incidence across studies. Results: Of 2,243 identified articles, 259 met our inclusion criteria were included in the meta-analysis after screening. Pooled effect estimates had the following summary incidence proportion for contrast induced nephropathy after angiography: 9.06% (95% CI: 8.53-9.58%; derived from 120 studies) and 0.52% (95% CI: 0.37-0.70%; derived from 110 studies) for the need of dialysis, respectively. The stratified summary incidence proportion of contrast induced nephropathy after contrast administration via intra-arterial route was 9.60% (95% CI: 9.0-10.2%; derived from 106 studies) and was 0.6% (95% CI: 0.40-0.80%; derived from 100 studies) for the need of dialysis, respectively. Our meta-regressions found that the amount of contrast medium exposure was associated with contrast-induced nephropathy. Conclusion: The potential risk of dialysis needs to be communicated to patients undergoing procedures requiring contrast, especially via intra-arterial exposure. Systematic Review Registration: [https://reurl.cc/8Wrlry], identifier [CRD42020170702].

Acupuncture Point Stimulation Treatments Combined With Conventional Treatment in Chronic Obstructive Pulmonary Disease: A Systematic Review and Network Meta-Analysis.

Background: Chronic obstructive pulmonary disease (COPD), which is a disease characterized by dyspnea, cough, and respiratory symptoms, leading to impaired health-related quality of life (HRQL) and exercise capacity, is highly prevalent worldwide. Some studies demonstrated that acupuncture point stimulation treatments (APSTs) are effective and safe in treating patients with COPD. The aim of this systematic review and network meta-analysis is to analyze the effects on HRQL and FEV1% predicted of diverse APSTs in treating patients with COPD. Materials and Methods: We searched seven electronic databases. Randomized controlled trials (RCTs) with stable COPD patients comparing APSTs and conventional treatment (Tx) were included. The primary outcome was HRQL measured by COPD Assessment Test or St. George's Respiratory Questionnaire. The secondary outcome was FEV1% predicted. We performed random effect network meta-analysis using a consistency model. Results: This network meta-analysis analyzed 21 RCTs with 1,577 stable COPD participants. In comparison with Tx, acupressure massage (AM) + Tx [-5.11; 95% confidence interval (CI), -6.65 to -3.57] was the most effective intervention in improving HRQL, followed by moxibustion (Mx) + Tx (-2.86; 95% CI, -3.86 to -1.86). Moreover, in comparison with Tx, Mx + Tx (7.79; 95% CI, 2.16 to 13.42) was the most effective intervention in improving FEV1% predicted, followed by acupuncture (A) + Tx (5.79; 95% CI, 2.90 to 8.68). Conclusions: Combined interventions (APSTs + Tx) are more effective than single intervention in improving both HRQL and FEV1% predicted. AM, Mx, and A can be considered effective non-pharmacological complementary interventions in treating patients with COPD under Tx.

Prevalence and risk factors for myopia in Taiwanese diabetes mellitus patients: a multicenter case-control study in Taiwan.

This population-based retrospective cohort study investigated the prevalence of myopia among patients with Type 1 and Type 2 diabetes mellitus (DM) and evaluate risk factors for myopia in these groups. Records from 2000 to 2012 with at least one year of follow-up from the Taiwan National Health Insurance Research Database were included. This study included 35,538 patients with DM and 71,076 patients without DM. Patients with DM had a significantly higher adjusted hazard ratio for myopia in all age groups and both sexes compared with patients without DM. The subgroup analysis results revealed that the rates of myopia and astigmatism were significantly higher among patients with DM compared with patients without DM aged < 60 years. However, the rates of high myopia or myopia progression to high myopia did not differ significantly between the two groups. These findings indicate that DM is a critical risk factor for myopia and astigmatism among patients aged < 60 years. Therefore, active surveillance and earlier treatment of myopia are critical for patients with DM.

Using Normalized Entropy to Measure Uncertainty of Rankings for Network Meta-analyses.

Ranking of treatments offers a straightforward interpretation of results derived from network meta-analysis. However, some published network meta-analyses have overemphasized treatment ranking without paying attention to its uncertainty. According to a review of 91 network meta-analyses, 52 reported treatment ranking, but 43 of them did not report the uncertainty of ranking. Without reporting the uncertainty, small differences in the ranking of treatments may be overinterpreted. Rankograms, cumulative rankograms, the credible/confidence interval of mean rank, the surface under the cumulative ranking curve (SUCRA), and the interquartile range of median rank have been used to show the uncertainty of rankings. However, it is not always straightforward to compare the differences in the distribution of probabilities by inspecting rankograms or to compare the intervals or ranges of treatment ranks. We therefore proposed normalized entropy, which transforms the distribution of ranking probabilities into a single quantitative measure, to facilitate a refined interpretation of uncertainty of treatment ranking. We used 4 real examples to demonstrate the uncertainty of ranking quantified by ranking probabilities, 95% confidence interval of SUCRA, and normalized entropy. We showed that as normalized entropy ranges from 0 to 1 and is independent of the number of treatments, it can be used to compare the uncertainty of treatment ranking within a network meta-analysis (NMA) and between different NMAs. Normalized entropy is an alternative tool for measuring the uncertainty of treatment ranking by improving the translation of results from NMAs to clinical practice and avoiding naïve interpretation of treatment ranking. We therefore recommend normalized entropy to be included in the presentation and interpretation of results from NMAs.

Mortality, morbidity, and risk factors in Taiwan, 1990-2017: findings from the Global Burden of Disease Study 2017.

BACKGROUND: Taiwan has implemented a national health insurance system since 1995 with high coverage and utilization rate. However, the health care system in Taiwan is facing immense challenges due to rapid population ageing. We have evaluated the landscape of population health by revisiting the results of GBD 2017 study. METHODS: Taiwan vital registration data (1980-2016) and Taiwan national health insurance database (2016) were used. We also conducted benchmarking comparisons with selected countries in East Asia from 1990 to 2017. RESULTS: The age-standardized disability-adjusted life-year (DALY) rates decreased by one-quarter from 1990 to 2017; however, progress was relatively slow compared to the comparator countries and has been stagnant recently. The Social-demographic Index (SDI) level in Taiwan in 2017 was 0.86, which is similar to Japan, Singapore, and South Korea in 2017, while the SDI level of China in 2017 was similar to that of Taiwan (0.69) in 1990. Although Taiwan's SDI reached the same level as those in Japan, Singapore, and South Korea in 2017, modifiable risk factors still contributed to nearly half of Taiwan's total disease burden. Five leading risk factors (high fasting plasma glucose, high body-mass index, alcohol use, illicit drug use, and impaired kidney function) accounted for a higher DALY rate in Taiwan than comparator countries in 2017. CONCLUSION: Taiwan made marked progress in health from 1990 to 2017. However, interventions targeted on major modifiable disease risk factors should be prioritized to realize the full potential of heath improvement in the process of rapid socioeconomic development.

Author Correction: Angiotensin-converting enzyme inhibitors or angiotensin receptor blocker monotherapy retard deterioration of renal function in Taiwanese chronic kidney disease population.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Disease burden from foodborne illnesses in Taiwan, 2012-2015.

BACKGROUND/PURPOSE: Foodborne disease is a global health problem. We aim to provide the first national estimate on disease burden from foodborne illnesses in Taiwan. METHODS: We adopted the World Health Organization (WHO) Foodborne Disease Burden Epidemiology Reference Group (FERG) methodology framework, and used a hazard-based incidence approach to calculate disability-adjusted life year (DALY) lost to foodborne diseases. Estimated annual incidences and associated medical costs are based on the National Health Insurance research database. We redistributed incidence of unspecified acute gastroenteritis to specific foodborne pathogens, using reported bacteria, virus, parasite survey results in such cases as the reference. The percentage of foodborne illnesses not seeking medical attention is based on data reported from a nationwide survey. RESULTS: During 2012-2015, 3,895,914 (90% confidence interval [CI]: 3,493,530-4,442,690) foodborne illnesses (1,445,384 sought medical care, with 50 deaths) occurred annually, which caused a total loss of 4974 (90%CI: 4671-5367) DALYs in Taiwan. The annual medical cost was NT$1.3 billion. Young (<5 years) children had the highest incidence. Among the 53% of foodborne illnesses cases with identifiable causal microorganisms, non-typhoid Salmonella, norovirus, and Vibrio parahaemolyticus were leading pathogens (annual foodborne incidence: 185,977, 157,656, and 99,351, respectively). Cases caused by non-typhoid Salmonella peaked in summer, while that caused by norovirus peaked in winter. CONCLUSION: Foodborne illnesses cause a substantial disease burden in Taiwan. Establishment of active surveillance and investigation mechanisms for the leading foodborne pathogens is warranted.

Author Correction: Relationship between body mass index and renal function deterioration among the Taiwanese chronic kidney disease population.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Correction: Effects and safety of oral tolvaptan in patients with congestive heart failure: A systematic review and network meta-analysis.

[This corrects the article DOI: 10.1371/journal.pone.0184380.].

Diabetic Retinopathy as a Risk Factor for Chronic Kidney Disease Progression: A Multicenter Case⁻Control Study in Taiwan.

It has rarely been studied whether the presence and severity of diabetic retinopathy (DR) could influence the renal disease progression among all chronic kidney disease (CKD) diabetic patients. This study investigates the characteristics of diabetic patients, with different stages of chronic kidney disease (CKD), according to the occurrence of diabetic retinopathy and determines the influence of retinopathy in the deterioration of renal function. We conduct a multicenter, longitudinal cohort study based on the Epidemiology and Risk Factors Surveillance of the CKD project (2008⁻2013) and the National Health Insurance Research Database (NHIRD) (2001⁻2013). A total of 4050 diabetic patients with CKD, 20⁻85 years of age, from 14 hospitals and the community are included in this study. As compared to CKD patients without DR, CKD patients with DR have a lower baseline estimated glomerular filtration rate (eGFR) (39.17 ± 30.36 mL/min per 1.73 m² vs. 54.38 ± 33.67 mL/min per 1.73 m² ); poorer glycemic control (higher glycated hemoglobin (HbA1c) 7.85 ± 4.97 vs. 7.29 ± 4.02, p < 0.01); higher proteinuria (urine protein-to-creatinine ratio (UPCR )1.94 ± 2.96 g/dL vs. 0.91 ± 2.11 g/dL, p < 0.01); more anemia (Hb 11.22 ± 2.43 g/dL vs. 12.39 ± 3.85 g/dL, p < 0.01), and more hypoalbuminemia (3.88 ± 0.95 g/dL vs. 4.16 ± 1.74 g/dL, p < 0.01). Later stage (stage 3b⁻5) CKD patients with DR had significantly higher CKD progression compared with patients without DR (OR (odds ratio) 1.66 (1.36⁻2.02)). Patients with proliferative DR had significantly higher CKD progression events compared to patients with non-proliferative DR (OR 2.18 (1.71⁻2.78)). The presence and severity of DR is a risk factor for CKD progression among our Taiwanese CKD patients with diabetes. Prevention and early detection of DR are important and DR should be routinely screened as early as possible among diabetic CKD patients.

Angiotensin-converting enzyme inhibitors or angiotensin receptor blocker monotherapy retard deterioration of renal function in Taiwanese chronic kidney disease population.

It remains unclear how different uses of angiotensin-converting inhibitors (ACEIs) or angiotensin receptor blockers (ARBs) influence the progression of chronic kidney disease (CKD). This study explored CKD progression in a multicentre, longitudinal cohort study that included 2639 patients with CKD stage 1-5 and hypertension. Patients treated with ACEI or ARB for ≥90 days during a 6-mo period comprised the study group, or no treatment, comprised the control group. The study group was subdivided on the basis of treatment: ACEI monotherapy or ARB monotherapy. Progression of renal deterioration was defined by an average eGFR decline of more than 5 mL/min/1.73 m2/yr or the commencement of dialysis. With at least 1-year follow up, a progression of renal deterioration was demonstrated in 29.70% of the control group and 25.09% of the study group. Patients in the study group had significantly reduced progression of CKD with adjusted odds ratio 0.79 (95% confidence interval: 0.63-0.99). However, when ACEI monotherapy and ARB monotherapy were analyzed separately, none of their associations with CKD progression was statistically significant. In conclusion, ACEI or ARB monotherapy may retard the deterioration of renal function among patients with CKD and hypertension.

Short-term efficacy of minimally invasive treatments for adult obstructive sleep apnea: A systematic review and network meta-analysis of randomized controlled trials.

Many treatments have been proposed for adult obstructive sleep apnea (OSA), but no comprehensive comparison of all interventions has been performed. We aimed to compare and rank the effectiveness of all minimally invasive treatments for adult OSA in a systematic review and network meta-analysis. Literature was searched within Ovid MedLine, EMBASE Classic+Embase, Cochrane library, and Cochrane Database of Systematic Reviews from inception to Aug 9th, 2016 for randomized controlled trials comparing minimally invasive treatments for adult OSA. The outcomes were the changes in apnea-hypopnea index (AHI) and Epworth sleepiness scale (ESS). Frequentist approach to network meta-analysis was used and treatment hierarchy was summarized according to the surfaces under the cumulative ranking curves. Eighty-nine randomized controlled trials comprising 6346 adult OSA participants and comparing 18 different interventions were included. In comparison with no treatment, positive airway pressure (PAP) was most effective in reducing AHI (23.28 [weighted mean difference]; 95% confidence interval: 19.20-27.35). PAP was ranked first followed by mandibular advancement device (MAD) in reducing AHI. Exercise was ranked first followed by cervico-mandibular support collar in reducing ESS. Considering the effectiveness in reducing both AHI and ESS, PAP was ranked the best, followed by MAD and positional therapy, while lifestyle modification alone was the least effective intervention. Interventions that are highly effective in reducing objective laboratory-derived AHI do not demonstrate equivalent effectiveness in improving patients' subjective sleepiness. Future improvement of the interventions is necessary to simultaneously improve both objective and subjective outcomes.

Phase II study of metabolic response to one-cycle chemotherapy in patients with locally advanced esophageal squamous cell carcinoma.

BACKGROUND: In the treatment of esophageal squamous cell carcinoma (ESCC), the optimal use of 18fluorodeoxyglucose positron emission tomography (PET) in measuring metabolic tumor response is undetermined. We launched a phase II trial to evaluate early metabolic response to one-cycle induction chemotherapy in patients with locally advanced ESCC. METHODS: ESCC patients in stage classification T3N0, N1M0, or M1a (American Joint Committee on Cancer, 6th edition) received one-cycle chemotherapy comprising paclitaxel, cisplatin, and 24-h infusional 5-fluorouracil and leucovorin on days 1 and 8, followed by neoadjuvant chemoradiotherapy, 40 Gy, with paclitaxel/cisplatin and then esophagectomy. PET was performed at baseline and day 14 of chemotherapy. The primary endpoint was pathologic complete response (pCR). We hypothesized early metabolic responders with >35% reduction in maximum standardized uptake value (SUVmax), would have better pCR Results. RESULTS: Sixty-six patients were enrolled. The median progression-free survival (PFS) and overall survival (OS) were 16 months (95% confidence interval [CI], 9-27) and 22 months (16-40), respectively. The early metabolic response rate was 55%; and the pCR rate was 34% in the esophagectomy population. The early metabolic response was not associated with pCR or survival. In an exploratory analysis, the postchemotherapy SUVmax was an independent prognostic factor for pCR, PFS, and OS. CONCLUSION: Our study failed to validate the predefined early metabolic response for pCR to neoadjuvant chemoradiotherapy in locally advanced ESCC patients. However, postchemotherapy SUVmax may be prognostic and predictive, and warrants further study.

Effect of Statins on Renal Function in Chronic Kidney Disease Patients.

Dyslipidemia is associated with glomerular injury. However, the effect of statins on chronic kidney disease (CKD) progression remains controversial. We aimed to investigate the efficacy of statins for renal protection in patients with CKD. The retrospective cohort study comprised 3441 patients diagnosed with CKD in multiple medical centers. We divided the patients into two cohorts based on statin prescription, and compared proportions and risks of CKD progression events between the two groups. CKD progression event was defined as an average annual decline of eGFR >5 mL/min/1.73 m2 or advancement to the dialysis stage. The result revealed that among all incident patients with CKD, 28.7% and 30.3% of the users and nonusers demonstrated CKD progression, respectively. The crude odds ratio (OR) of CKD progression was 0.93 [95% confidence interval (CI) 0.78-1.10]. After adjustment for baseline characteristics, the adjusted OR was 0.80 (95% CI 0.63-1.01). The sensitivity analysis results showed consistent OR for CKD progression, stratification by age, sex, Charlson score, and statins use within 1 year before index date. The effect of statins was significant in patients with CKD stage 3B-5 (OR 0.68, 95% CI 0.48-0.95), but not statistically significant in those with CKD stage 1-3A (OR 0.97, 95% CI 0.68-1.38). The effect of statins was significant in patients with proteinuria ≥1000 mg/day (OR 0.63, 95% CI 0.43-0.92), but not statistically significant in those with proteinuria <1000 mg/day (OR 1.02, 95% CI 0.74-1.41).

Relationship between body mass index and renal function deterioration among the Taiwanese chronic kidney disease population.

This study investigated the characteristics of patients with different chronic kidney disease (CKD) stages according to various body mass index (BMI) categories and determined the influence of BMI in renal function deterioration. We conducted a multicenter, longitudinal cohort study based on the Epidemiology and Risk Factors Surveillance of CKD project (2008-2013) and National Health Insurance Research Database (2001-2013). A total of 7357 patients with CKD aged 20-85 years from 14 hospitals were included in the study. A higher male sex, diabetes mellitus (DM) and hypertension were noted among overweight and obese CKD patients, while more cancer prevalence was noted among underweight CKD patients. Charlson comorbidity index was significantly higher and correlated with BMI among late CKD patients. Patients with BMI < 18.5 kg/m2 exhibited non-significantly higher events of eGFR decline events in both early and late CKD stages than other BMI groups. BMI alone is not a determinant of CKD progression among our Taiwanese CKD patients. Obesity should be re-defined and body weight manipulation should be individualized in CKD patients.

Salivary biomarker combination prediction model for the diagnosis of periodontitis in a Taiwanese population.

BACKGROUND/PURPOSE: This study aimed at screening the diagnostic potential of salivary biomarkers and pairing them to establish a prediction model with higher accuracy in diagnosing periodontitis in the Taiwanese population. METHODS: Fifty-seven participants were divided into a non-periodontitis group and a periodontitis group. Salivary biomarkers CRP, IL-6, IL-8, IL-1ß, IL-1ra, lactoferrin, MMP-8, MMP-9, PDGF-BB, TNF-α, and VEGF, were analyzed. The potential and reliability of the biomarkers for diagnosing periodontitis were analyzed dichotomously. The correlation of individual biomarkers with periodontitis was assessed using the Spearman rank correlation coefficient with logistic regression. The combinational prediction model was evaluated using the area under the receiver operating characteristic curve (AUC). RESULTS: Regarding individual biomarkers, IL-1ß and MMP-9 levels were significantly higher, and TNF-α was significantly lower in the periodontitis group. IL-1ß, MMP-8, and MMP-9 exhibited a greater odds ratio with statistical significance in the dichotomous table. The combination of three biomarkers yielded AUCs of 0.821-0.853, and the combination of IL-1ß, IL-1ra, and MMP-9 exhibited the highest AUC (0.853), with high sensitivity (73.3%) and specificity (88.9%). CONCLUSION: Regarding individual biomarkers, IL-1ß, MMP-8, and MMP-9 showed potential for identifying patients with periodontitis. The combination of IL-1ß, IL-1ra, and MMP-9 might be feasible for developing a future point-of-care device for diagnosing periodontitis.

Effects and safety of oral tolvaptan in patients with congestive heart failure: A systematic review and network meta-analysis.

AIMS: Several studies reported treatment benefits of tolvaptan in patients with congestive heart failure (CHF). However, the optimal dosage remains unclear. We aimed to compare different dosage of tolvaptan to determine the optimal dosage in terms of the efficacy and safety. METHODS: We searched MEDLINE, PubMed, EMBASE, Cochrane CENTRAL and ClinicalTrials.gov through Aug 31, 2016. Randomized controlled trials (RCTs) comparing tolvaptan of different dosages or to placebo in patients with CHF were included. We used network meta-analysis to look for the optimal dosage in terms of effectiveness and safety. Urine output, body weight change and change in serum sodium were the main outcomes of efficacy. Adverse effects were the secondary outcomes. Quality was assessed by Cochrane risk-of-bias tool. RESULTS: Twelve RCTs reporting 14 articles with 5793 patients (mean age, 65.7 ± 11.9 years; 73.7% man) were included. Compared with placebo, the tolvaptan 30 mg had similar effects to tolvaptan 45-90 mg in terms of urine output (mean difference [MD] 2.03 liter; 95% confidence interval [CI] 1.3 to 2.71), body weight change (MD -1.12 kg; 95% CI -1.37 to -0.88) and change in serum sodium (MD 3.06 meq/L; 95% CI 2.43 to 3.68). Compared with placebo, tolvaptan of different dosage showed a non-significant higher risk of adverse effects. CONCLUSIONS: These findings suggest that tolvaptan 30 mg and 45 mg may be the optimum dosage for CHF patients, because of its ability to provide favourable clinical results without greater adverse effects. However, tolvaptan is not beneficial for reducing all-cause mortality in CHF patients.

Using structural equation modeling for network meta-analysis.

BACKGROUND: Network meta-analysis overcomes the limitations of traditional pair-wise meta-analysis by incorporating all available evidence into a general statistical framework for simultaneous comparisons of several treatments. Currently, network meta-analyses are undertaken either within the Bayesian hierarchical linear models or frequentist generalized linear mixed models. Structural equation modeling (SEM) is a statistical method originally developed for modeling causal relations among observed and latent variables. As random effect is explicitly modeled as a latent variable in SEM, it is very flexible for analysts to specify complex random effect structure and to make linear and nonlinear constraints on parameters. The aim of this article is to show how to undertake a network meta-analysis within the statistical framework of SEM. METHODS: We used an example dataset to demonstrate the standard fixed and random effect network meta-analysis models can be easily implemented in SEM. It contains results of 26 studies that directly compared three treatment groups A, B and C for prevention of first bleeding in patients with liver cirrhosis. We also showed that a new approach to network meta-analysis based on the technique of unrestricted weighted least squares (UWLS) method can also be undertaken using SEM. RESULTS: For both the fixed and random effect network meta-analysis, SEM yielded similar coefficients and confidence intervals to those reported in the previous literature. The point estimates of two UWLS models were identical to those in the fixed effect model but the confidence intervals were greater. This is consistent with results from the traditional pairwise meta-analyses. Comparing to UWLS model with common variance adjusted factor, UWLS model with unique variance adjusted factor has greater confidence intervals when the heterogeneity was larger in the pairwise comparison. The UWLS model with unique variance adjusted factor reflects the difference in heterogeneity within each comparison. CONCLUSION: SEM provides a very flexible framework for univariate and multivariate meta-analysis, and its potential as a powerful tool for advanced meta-analysis is still to be explored.