External validation and revision of Penn incisional hernia prediction model: A large-scale retrospective cohort of abdominal operations.

BACKGROUND: Incisional hernia (IH) manifests in 10%-15% of abdominal surgeries and patients at elevated risk of this complication should be identified for prophylactic intervention. This study aimed to externally validate the Penn hernia risk calculator. METHODS: The Ramathibodi abdominal surgery cohort was constructed by linking relevant hospital databases from 2010 to 2021. Penn hernia risk scores were calculated according to the original model which was externally validated using a seven-step approach. An updated model which included four additional predictor variables (i.e., age, immunosuppressive medication, ostomy reversal, and transfusion) added to those of the three original predictors (i.e., body mass index, chronic liver disease, and open surgery) was also evaluated. The area under the receiver operating characteristic curve (AUC) was estimated, and calibration performance was compared using the Hosmer-Lemeshow goodness-of-fit method for the observed/expected (O/E) ratio. RESULTS: A total of 12,155 abdominal operations were assessed. The original Penn model yielded fair discrimination with an AUC (95% confidence interval (CI)) of 0.645 (0.607, 0.683). The updated model that included the additional predictor variables achieved an acceptable AUC (95% CI) of 0.733 (0.698, 0.768) with the O/E ratio of 0.968 (0.848, 1.088). CONCLUSION: The updated model achieved improved discrimination and calibration performance, and should be considered for the identification of high-risk patients for further hernia prevention strategy.

Long-term outcomes of anti-thyroid drug treatment in childhood-onset Graves' disease.

OBJECTIVE: Outcomes of childhood-onset Graves' disease (GD) and suggested duration of anti-thyroid drug (ATD) therapy have been controversial. This study aimed to determine long-term outcomes following ATD therapy, including remission and relapse rates. DESIGN, PATIENTS AND MEASUREMENTS: A retrospective study of 265 paediatric patients with GD who were initially treated with ATD was conducted. Long-term outcomes were analysed. RESULTS: Median (IQR) age at diagnosis was 11.5 (9.4, 13.7) years. Duration of ATD treatment was 4.3 (2.3, 6.7) years and time since diagnosis to the enrolment was 7.1 (3.8, 10.9) years. There were 77, 93 and 95 patients who underwent definitive treatment, had ATD discontinuation, and were still being treated with ATD, respectively. The remission rate was 21% (56 out of 265 patients) and relapse rate was 40% (37 out of 93 patients). Cumulative incidence of first remission increased with the duration of ATD treatment with maximum remission rate at 5.3 years following ATD therapy. Among patients who experienced relapse, approximately 50% had disease relapse which occurred within 1 year after ATD discontinuation. Patients with goitre size of less than 3.5 cm, thyroid-stimulating hormone receptor antibody of less than 10 IU/L, no ophthalmopathy at diagnosis and methimazole dose requirement of less than 0.25 mg/kg/day at 1 year after treatment were more likely to achieve remission. CONCLUSIONS: Remission rate of childhood-onset GD was relatively low following ATD treatment. Longer-term ATD therapy was associated with increased remission rate. Approximately 50% of patients with relapse had disease relapse within 1 year following ATD discontinuation.

Cost-effectiveness analysis of isolation strategies for asymptomatic and mild symptom COVID-19 patients.

BACKGROUND: Management of COVID-19 patients with mild and moderate symptoms could be isolated at home isolation (HI), community isolation (CI) or hospitel. However, it was still unclear which strategy was more cost-effective. Therefore, this study was conducted to evaluate this. METHODS: This study used data from patients who initially stayed at HI, CI, and hospitel under supervision of Ramathibodi Hospital between April and October 2021. Outcomes of interest were hospitalisation and mortality. An incremental cost-effectiveness ratios (ICER) was calculated based on hospital perspective using home isolation as the reference. RESULTS: From 7,077 patients, 4,349 2,356, and 372 were admitted at hospitel, HI, and CI, respectively. Most patients were females (57.04%) and the mean age was 40.42 (SD = 16.15). Average durations of stay were 4.47, 3.35, and 3.91 days for HI, CI, and hospitel, respectively. The average cost per day for staying in these corresponding places were 24.22, 63.69, and 65.23 US$. For hospitalisation, the ICER for hospitel was at 41.93 US$ to avoid one hospitalisation in 1,000 patients when compared to HI, while CI had more cost, but less cases avoided. The ICER for hospitel and CI were at 46.21 and 866.17 US$ to avoid one death in 1,000 patients. CONCLUSIONS: HI may be cost-effective isolated strategy for preventing hospitalisation and death in developing countries with limited resources.

Fascial Dehiscence and Incisional Hernia Prediction Models: A Systematic Review and Meta-analysis.

BACKGROUND: Fascial dehiscence (FD) and incisional hernia (IH) pose considerable risks to patients who undergo abdominal surgery, and many preventive strategies have been applied to reduce this risk. An accurate predictive model could aid identification of high-risk patients, who could be targeted for particular care. This study aims to systematically review existing FD and IH prediction models. METHODS: Prediction models were identified using pre-specified search terms on SCOPUS, PubMed, and Web of Science. Eligible studies included those conducted in adult patients who underwent any kind of abdominal surgery, and reported model performance. Data from the eligible studies were extracted, and the risk of bias (RoB) was assessed using the PROBAST tool. Pooling of C-statistics was performed using a random-effect meta-analysis. [Registration: PROSPERO (CRD42021282463)]. RESULTS: Twelve studies were eligible for review; five were FD prediction model studies. Most included studies had high RoB, especially in the analysis domain. The C-statistics of the FD and IH prediction models ranged from 0.69 to 0.92, but most have yet to be externally validated. Pooled C-statistics (95% CI) were 0.80 (0.74, 0.86) and 0.81 (0.75, 0.86) for the FD (external-validation) and IH prediction model, respectively. Some predictive factors such as body mass index, smoking, emergency operation, and surgical site infection were associated with FD or IH occurrence and were included in multiple models. CONCLUSIONS: Several models have been developed as an aid for FD and IH prediction, mostly with modest performance and lacking independent validation. New models for specific patient groups may offer clinical utility.

Efficacy and safety of urate-lowering agents in asymptomatic hyperuricemia: systematic review and network meta-analysis of randomized controlled trials.

BACKGROUND: Asymptomatic hyperuricemia was found to be associated with increased cardiovascular disease risk but the potential benefits of urate-lowering therapy (ULT) remain controversial. We conducted a systematic review and network meta-analysis (NMA) with frequentist model to estimate the efficacy and safety of ULT in asymptomatic hyperuricemia. METHODS: MEDLINE, Embase, and Scopus were searched without language restrictions. Randomized controlled trials (RCT) of adults with asymptomatic hyperuricemia were eligible if they compared any pair of ULTs (i.e., allopurinol, febuxostat, probenecid, benzbromarone, sulfinpyrazone, rasburicase, lesinurad, and topiroxostat) and placebo or no ULT, and had outcomes of interest, including composite renal events, major adverse cardiovascular events, serum urate levels, estimated glomerular filtration rate (eGFR), systolic blood pressure, and adverse events. RESULTS: NMA with frequentist approach was applied to estimate relative treatment effects, i.e., risk ratio (RR) and mean difference (MD). A total of 23 RCTs were eligible. NMA identified beneficial effects of ULT on composite renal events and eGFR but not for other outcomes. Allopurinol and febuxostat had significantly lower composite renal events than placebo (RR 0.39, 95% confidence interval [CI] 0.23 to 0.66, and RR 0.68, 95% CI 0.46 to 0.99, respectively). Both treatments also resulted in significantly higher eGFR than placebo (MD 3.69 ml/min/1.73 m2, 95% CI 1.31 to 6.08, and MD 2.89 ml/min/1.73 m2, 95% CI 0.69 to 5.09, respectively). No evidence of inconsistency was identified. CONCLUSIONS: Evidence suggests that allopurinol and febuxostat are the ULTs of choice in reducing composite renal events and improving renal function. TRIAL REGISTRATION: This study was registered with PROSPERO: CRD42019145908. The date of the first registration was 12th November 2019.

Efficacy and safety of conventional antiviral agents in preventive strategies for cytomegalovirus infection after kidney transplantation: a systematic review and network meta-analysis.

Cytomegalovirus (CMV) infection is common in kidney transplantation (KT). Antiviral-agents are used as universal prophylaxis. Our purpose aimed to compare and rank efficacy and safety. MEDLINE, Embase, SCOPUS, and CENTRAL were used from inception to September 2020 regardless language restriction. We included randomized clinical trials (RCTs) comparing the CMV infection/disease prophylaxis among antiviral-agents in adult KT recipients. Of 24 eligible RCTs, prophylactic valganciclovir (VGC) could significantly lower the overall CMV infection and disease risks than placebo with pooled risk differences (RDs) [95% confidence interval (CI)] of -0.36 (-0.54, -0.18) and -0.28 (-0.48, -0.08), respectively. Valacyclovir (VAC) and ganciclovir (GC) significantly decreased risks with the corresponding RDs of -0.25 (-0.32, -0.19) and -0.30 (-0.37, -0.22) for CMV infection and -0.26 (-0.40, -0.12) and -0.22 (-0.31, -0.12) for CMV disease. For subgroup analysis by seropositive-donor and seronegative-recipient (D+/R-), VGC and GC significantly lowered the risk of CMV infection/disease with RDs of -0.42 (-0.84, -0.01) and -0.35 (-0.60, -0.12). For pre-emptive strategies, GC lowered the incidence of CMV disease significantly with pooled RDs of -0.33 (-0.47, -0.19). VGC may be the best in prophylaxis of CMV infection/disease follow by GC. VAC might be an alternative where VGC and GC are not available.

Incidence of thromboembolism in patients with COVID-19: a systematic review and meta-analysis.

BACKGROUND: Since the beginning of the coronavirus disease 2019 (COVID-19) pandemic, the incidence of thromboembolism has been increasingly reported. The aim of this systematic review was to explore the incidence of venous and arterial thromboembolism among COVID-19 patients requiring hospitalization. METHODS: Medline, Embase, Scopus, and grey literature were searched until June 2020. Observational studies reported on the incidence of venous thromboembolism (VTE), including pulmonary embolism (PE) and deep vein thrombosis (DVT) or arterial thromboembolism (ATE) were included. The pool incidences and their 95% confidence intervals (CI) were calculated using the random-effects model. RESULTS: A total of 36 studies were included. In the intensive care unit (ICU) setting, the pooled incidence of VTE was 28% (95% CI, 22-34%). Subgroups based on compression ultrasound (CUS) screening revealed a higher incidence of DVT in the CUS screening group than in the no CUS screening group (32% [95% CI, 18-45%] vs. 6% [95% CI, 4-9%]). The pooled incidence of ATE in ICU was 3% (95% CI, 2-5%). In the non-ICU setting, the pooled incidence of VTE was 10% (95% CI, 6-14%,). CONCLUSIONS: The incidence of VTE in COVID-19 patients was higher in the ICU setting than in the non-ICU setting, and also significantly higher in studies that incorporated the CUS screening protocol. The incidence of ATE in the ICU setting was low. VTE prophylactic measures should be given to all hospitalized patients diagnosed with COVID-19.

The association between serum squamous cell carcinoma antigen and recurrence and survival of patients with cervical squamous cell carcinoma: A systematic review and meta-analysis.

OBJECTIVE: The aim of this systematic review and meta-analysis was to pool association effects of serum squamous cell carcinoma antigen (SCC-Ag) on recurrence and mortality in mainly squamous cell cervical cancer patients. METHODS: MEDLINE and Scopus databases were searched up to June 29, 2016. Studies assessing effects of SCC-Ag on recurrence and death in cervical cancer patients were included. Data extraction was independently performed by two reviewers. A meta-analysis was applied for pooling the effects (i.e., risk ratio (RR), hazard ratio (HR), and unstandardized mean difference (USMD)) of SCC-Ag measured before and after treatment on recurrence and death. RESULTS: A total of 61 studies were included. For pretreatment SCC-Ag and recurrence, the pooled RR, HR, and USMD for high versus low serum SCC-Ag were 2.44(95% CI: 1.91, 3.13), 2.23(95% CI: 2.03, 2.45), -7.7(95% CI: -31.7, 16.4), respectively. The corresponding effects for the posttreatment period were 3.91(95% CI: 2.96, 5.16), 3.14(95% CI: 1.29, 7.65), and 3.2(95% CI: -10.6, 17.0), respectively. In addition, patients with high level of pretreatment serum SCC-Ag were also at a higher risk for death than patients with low serum SCC-Ag with a pooled RR of 3.66(95% CI: 2.24, 5.98), pooled HR of 2.50(95% CI: 1.85, 3.37), and pooled USMD of 7.10(95% CI: 4.26, 9.94). The posttreatment serum SCC-Ag effects also reflected a similar trend. CONCLUSIONS: The serum SCC-Ag was consistently associated with recurrence and mortality of newly diagnosed cervical cancer. This marker may be useful in monitoring disease progression in cervical cancer patients. Prospero registration number is: CRD42016044024.

The validity and reliability of Thai Sinonasal Outcome Test-22.

Chronic rhinosinusitis (CRS) symptoms can significantly reduce quality of life. The Sinonasal Outcome Test-22 (SNOT-22) is frequently used to assess this disease-specific quality of life, although it has not been translated into Thai language. We translated the original SNOT-22 questionnaire to Thai using forward-backward technique, and validated it in CRS patients [n = 229, mean age of 52.6 (SD = 15.9)] recruited at outpatient Otolaryngology clinic, Faculty of Medicine Ramathibodi Hospital, Bangkok, Thailand. A construct validity was assessed using factor analysis, reliability was assessed using intra-class correlation coefficient (ICC) after 3 days of taking the first questionnaire, and internal consistency was assessed using Cronbach's alpha. A total of 201 out of 229 patients completed SNOT-22 questionnaire. Factor analysis with oblique rotation was applied and yielded three domains with eigenvalue of 1 or higher. These domains were named as nasal-related, ear-general-psychological, and sleep-related domains. Estimated ICC ranged from 0.49 to 0.71 with a median of 0.64, and Cronbach's alpha was 0.94. The Thai SNOT-22 questionnaire is reliable and valid with three domains. Thai SNOT-22 may be used in research and clinical practice to assess disease-specific quality of life and aid in management plan at CRS clinic.

Efficacy of migraine prophylaxis treatments for treatment-naïve patients and those with prior treatment failure: a protocol for systematic review and network meta-analysis of randomised controlled trials.

INTRODUCTION: Migraine headache is a significant health problem affecting patients' psychological well-being and quality of life. Several network meta-analyses (NMAs) have compared the efficacy of migraine prophylaxis medications. However, some have focused exclusively on oral medications, while others were limited to injectable medications. Moreover, none of these NMAs conducted a stratified analysis between treatment-naïve patients and those with prior treatment failure. Therefore, this systematic review and NMA will compare the efficacy among all treatments for migraine prophylaxis, stratified by the treatment status of patients (ie, treatment-naïve and previous treatment failure). METHODS AND ANALYSIS: Randomised-controlled trials that included patients with chronic or episodic migraine, assessed the efficacy of oral or injectable treatments for migraine prophylaxis and measured the outcomes as monthly migraine day, monthly headache day, migraine-related disability, health-related quality of life or adverse drug events will be eligible for inclusion in this review. Relevant studies will be searched from Medline, Scopus, the US National Institutes of Health Register, and the World Health Organization International Clinical Trials Registry Platform (WHO-ICTRP) databases since inception through 15 August 2023. Risk of bias assessment will be performed using a revised tool for assessing the risk of bias in randomised trials. Two-stage NMA will be applied to compare relative treatment effects among all treatments of migraine prophylaxis. Surface under the cumulative ranking curve will be applied to estimate and rank the probability to be the best treatment. Consistency assumption will be assessed using a design-by-treatment interaction model. Publication bias will be assessed by comparison-adjusted funnel plot. All analyses will be stratified according to patients' status (ie, treatment-naïve and prior treatment failure). ETHICS AND DISSEMINATION: This study is a systematic review protocol collecting data from published literature and does not require approval from an institutional review board. Results from this systematic review will be published in a peer-reviewed journal. PROSPERO REGISTRATION NUMBER: CRD42020171843.

Delayed versus primary closure to minimize risk of surgical-site infection for complicated appendicitis: A secondary analysis of a randomized trial using counterfactual prediction modeling.

OBJECTIVE: To evaluate the risk of surgical site infection (SSI) following complicated appendectomy in individual patients receiving delayed primary closure (DPC) versus primary closure (PC) after adjustment for individual risk factors. DESIGN: Secondary analysis of randomized controlled trial (RCT) with prediction model. SETTING: Referral centers across Thailand. PARTICIPANTS: Adult patients who underwent appendectomy via a lower-right-quadrant abdominal incision due to complicated appendicitis. METHODS: A secondary analysis of a published RCT was performed applying a counterfactual prediction model considering interventions (PC vs DPC) and other significant predictors. A multivariable logistic regression was applied, and a likelihood-ratio test was used to select significant predictors to retain in a final model. Factual versus counterfactual SSI risks for individual patients along with individual treatment effect (iTE) were estimated. RESULTS: In total, 546 patients (271 PC vs 275 DPC) were included in the analysis. The individualized prediction model consisted of allocated intervention, diabetes, type of complicated appendicitis, fecal contamination, and incision length. The iTE varied between 0.4% and 7% for PC compared to DPC; ∼38.1% of patients would have ≥2.1% lower SSI risk following PC compared to DPC. The greatest risk reduction was identified in diabetes with ruptured appendicitis, fecal contamination, and incision length of 10 cm, where SSI risks were 47.1% and 54.1% for PC and DPC, respectively. CONCLUSIONS: In this secondary analysis, we found that most patients benefited from early PC versus DPC. Findings may be used to inform SSI prevention strategies for patients with complicated appendicitis.

Efficacy of Treatment for Metastatic Hormone-Sensitive Prostate Cancer: An Umbrella Review of Systematic Reviews and Meta-Analyses.

PURPOSE: This umbrella review focused on evaluating the efficacy and adverse events of the metastatic hormone-sensitive prostate cancer patients receiving any treatment regimens, including ADT alone or combination treatments. METHODS: This study conducted an umbrella review following the PRISMA 2020 checklist, aiming to summarize the available studies to evaluate the efficacy of medical treatments for metastatic hormone-sensitive prostate cancer. A literature search was performed to identify systematic reviews and meta-analyses (SRMAs) that included only randomized controlled trials (RCTs) up to September 2023. This study summarized their findings, evaluated overlapping data (i.e., the same RCTs were included in >one SRMA), tested for excessive significance (i.e., observed number of statistically significant studies > expected number by chance) and assessed the quality of the studies. RESULTS: A total of 4191 studies were identified, but only 27 were included. Among those 27 studies, 12 were network meta-analyses and 15 were direct meta-analyses. Most studies showed no statistically significant difference in overall mortality among GnRH agonists, antagonists and bilateral orchiectomy. Combination treatment is more beneficial than ADT alone in both OS and PFS outcomes with more adverse events. Nevertheless, there is no OS advantage of any combination regimen over the others. CONCLUSION: Combination treatments demonstrated clear benefits in OS and PFS over ADT alone with more AEs. Further studies are needed to compare among combination treatments.

The effect of curcumin supplementation on weight loss and anthropometric indices: an umbrella review and updated meta-analyses of randomized controlled trials.

BACKGROUND: Curcumin supplementation may promote weight loss and ameliorate obesity-related complications through its antioxidative and anti-inflammatory properties. OBJECTIVE: An umbrella review and updated meta-analysis of randomized controlled trials (RCTs) was conducted to evaluate the effect of curcumin supplementation on anthropometric indices. METHODS: Systematic reviews and meta-analyses (SRMAs) of RCTs were identified from electronic databases (Medline, Scopus, Cochrane, and Google Scholar) up to 31 March, 2022, without language restriction. SRMAs were included if they assessed curcumin supplementation on any of the following: BMI, body weight (BW), or waist circumference (WC). Subgroup analyses were performed, stratifying by patient types, severity of obesity, and curcumin formula. The study protocol was a priori registered. RESULTS: From an umbrella review, 14 SRMAs with 39 individual RCTs were included with a high degree of overlap. In addition, searching was updated from the last search of included SRMAs in April 2021 up to 31 March, 2022, and we found 11 additional RCTs, bringing the total up to 50 RCTs included in the updated meta-analyses. Of these, 21 RCTs were deemed of high risk of bias. Curcumin supplementation significantly reduced BMI, BW, and WC with mean differences (MDs) of -0.24 kg/m2 (95% CI: -0.32, -0.16 kg/m2), -0.59 kg (95% CI: -0.81, -0.36 kg), and -1.32 cm (95% CI: -1.95, -0.69 cm), respectively. The bioavailability-enhanced form reduced BMI, BWs, and WC more, with MDs of -0.26 kg/m2 (95% CI: -0.38, -0.13 kg/m2), -0.80 kg (95% CI: -1.38, -0.23 kg) and -1.41 cm (95% CI: -2.24, -0.58 cm), respectively. Significant effects were also seen in subgroups of patients, especially in adults with obesity and diabetes. CONCLUSIONS: Curcumin supplementation significantly reduces anthropometric indices, and bioavailability-enhanced formulas are preferred. Augmenting curcumin supplement with lifestyle modification should be an option for weight reduction. This trial was registered at PROSPERO as CRD42022321112 (https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022321112).

Comparative cardiovascular outcomes of novel drugs as an addition to conventional triple therapy for heart failure with reduced ejection fraction (HFrEF): a network meta-analysis of randomised controlled trials.

BACKGROUND: Currently, there is no head-to-head comparison of novel pharmacological treatments for heart failure with reduced ejection fraction (HFrEF). A network meta-analysis aimed to compare effects of both conventional and alternative drug combinations on time to develop primary composite outcome of cardiovascular death or heart failure hospitalisation (PCO). METHODS: Randomised controlled trials (RCTs) were identified from Medline, Scopus up to June 2021. The RCTs were included if comparing any single or combination of drugs, that is, ACE inhibitors (ACEI), angiotensin receptor blockers, beta-blockers (BB), mineralocorticoid receptor antagonists (MRA), ivabradine (IVA), angiotensin receptor blocker/neprilysin inhibitors (ARNI) and sodium-glucose cotransporter-2 inhibitors (SGLT2i), soluble guanylyl cyclase and omecamtiv mecarbil and reporting PCO. Data were extracted from Kaplan-Meier curves, individual patient data were generated. A mixed-effect Weibull regression was applied. Median time to PCO, HRs with 95% CI were estimated accordingly. Our findings suggested that ACEI+BB+MRA+SGLT2i, BB+MRA+ARNI, and ACEI+BB+MRA+IVA had lower probability of PCOs than the conventional triple therapy (ACEI+BB+MRA). RESULTS: Median time to PCOs of ACEI+BB+MRA was 57.7 months whereas median times to those new combinations were longer than 57.7 months. In addition, the three new regimens had a significantly lower PCO risks than ACEI+BB+MRA, with the HRs (95% CI) of 0.51 (0.43 to 0.61), 0.55 (0.46 to 0.65) and 0.56 (0.47 to 0.67), accordingly. CONCLUSION: This study suggested that SGLT2i, ARNI and IVA in addition to ACEI+BB+MRA may be better in prolonging time to develop PCO in HFrEF patients.

Comparison of the Cerumenolytic Activities of New and Currently Used Agents.

OBJECTIVES: This study compared the cerumen dissolution activities of 7.5% sodium bicarbonate, 5% potassium hydroxide, 10% lactic acid, 3% salicylic acid, 10% glycolic acid, and distilled water. METHODS: An in vitro study was conducted with 36 cerumen samples. The cerumenolytic activities of the 6 agents were assessed by recording the degree of cerumen disintegration using digital photography at 15 minutes, 30 minutes, 1 hour, 2 hours, and 12 hours. The undissolved cerumen that remained after 12 hours was removed from the solutions and weighed after drying. RESULTS: Potassium hydroxide showed the fastest cerumenolytic activity, dissolving a moderate amount of cerumen at 30 minutes, while glycolic acid and salicylic acid caused no visible changes in the cerumen samples. Samples treated with potassium hydroxide and sodium bicarbonate exhibited higher degrees of disintegration compared to samples treated with distilled water (odds ratio and 95% CI: 273.237 [0.203-367 470.4] and 1.129 [0.002-850.341], respectively). The greatest reduction in cerumen weight was associated with the use of sodium bicarbonate; however, this result did not reach statistical significance. CONCLUSIONS: Among the solutions tested, 5% potassium hydroxide showed the fastest dissolution activity, yielding moderate disintegration within only 30 minutes. In terms of residual cerumen weight within 12 hours, all solutions exhibited equivalent effectiveness in the disintegration of cerumen.

Causal association pathways between fetuin-A and kidney function: a mediation analysis.

OBJECTIVE: Body mass index (BMI), uric acid, diabetes mellitus, and hypertension are risk factors for reduced kidney function and are associated with fetuin-A levels, but their causal pathways remain unclear. The objective of this study was to investigate this knowledge gap. METHODS: A repeated cross-sectional design was used to assess causal pathway effects of fetuin-A on the estimated glomerular filtration rate (eGFR), which is mediated through BMI, uric acid, diabetes mellitus, and hypertension. RESULTS: Among 2305 participants, the mean eGFR at baseline decreased from 98.7 ± 23.6 mL/minute/1.73 m2 in 2009 to 92.4 ± 22.9 mL/minute/1.73 m2 in 2014. Fetuin-A was significantly associated with eGFR , suggesting that increasing fetuin-A levels predict a decrease in eGFR. Additionally, the indirect effect of fetuin-A on eGFR, as assessed through BMI, was also significant. The effects of fetuin-A on eGFR through other mediation pathways showed variable results. CONCLUSIONS: Our study revealed a possible role of fetuin-A in the etiology of declining renal function through mediating body mass index, uric acid, diabetes mellitus, and hypertension via complex causal pathways. Further studies to clarify these mediated effects are recommended.

Comparison of Various Pharmacologic Agents in the Management of Hemodynamically Significant Patent Ductus Arteriosus in Preterm: A Network Meta-Analysis and Risk-Benefit Analysis.

Introduction: Various pharmacological treatments are available for preterm infants with patent ductus arteriosus (PDA), but their risks and benefits are controversial. This study aimed to identify the best treatment for PDA using network meta-analysis (NMA) and risk-benefit assessment (RBA). Methods: Relevant randomized controlled trials (RCTs) were identified from MEDLINE, Scopus, and the Cochrane Library. RCTs were eligible if they were studied for preterm or low birth weight infants with presymptomatic PDA and hemodynamically significant PDA (hsPDA). The outcomes were PDA closure for a benefit and the composite risk outcome of adverse effects (AEs) for risk. An NMA was used to estimate the treatment effects of benefit and risk. The RBA helped to incorporate the risk and benefits of multiple treatments. Then, an incremental risk-benefit ratio was calculated by dividing the incremental risk by benefit using data from NMA, and they were jointly simulated using Monte Carlo methods. Finally, net clinical benefit (NCB) probability curves were constructed at varying acceptability thresholds. Results: Seventy RCTs with hsPDA were eligible considering 13 different interventions, but data on presymptomatic PDA were not enough for pooling. The clustered ranking plot from NMA indicated that 3 interventions (i.e., high-dose oral ibuprofen, standard-dose oral acetaminophen, and standard-dose oral ibuprofen) yielded high PDA closure and low AE. These three treatments and additional commonly used indomethacin were considered in the RBA. Given an acceptable threshold of 25% or having one AE out of four PDA closures, high-dose oral ibuprofen had a 36% chance of having the highest NCB, followed by standard-dose oral acetaminophen (27%), and oral ibuprofen (23.7%). Subgroup analysis indicated that the chances of having the highest NCB of GA ≥28 weeks were similar to that of all available studies. The best for GA <28 weeks, no data for high-dose oral ibuprofen, was standard-dose oral acetaminophen, followed by standard-dose oral ibuprofen. Conclusions: Trade-off RBA indicated that high-dose oral ibuprofen might be the best treatment for preterm, GA ≥28 weeks, with hsPDA followed by the standard-dose oral acetaminophen and ibuprofen. Preferably, optimal high doses, postnatal age to start treatment, and long-term outcomes are needed to study in the future.

Short-term Efficacy and Safety of Biological Tear Substitutes and Topical Secretagogues for Dry Eye Disease: A Systematic Review and Network Meta-analysis.

PURPOSE: The purpose of this study was to assess short-term efficacy and safety of tear promotion eye drops (biological tear substitutes and topical secretagogues) for treating dry eye disease. METHODS: Randomized controlled trials comparing short-term effects of biological tear substitutes or topical secretagogues versus placebo or other topical dry eye treatments in adults with dry eye disease were identified from the MEDLINE, Embase, Scopus, ClinicalTrials.gov , and World Health Organization International Clinical Trials Registry Platform databases. Pairwise meta-analysis and network meta-analysis were performed. Outcomes were ocular symptoms, ocular surface staining, tear break-up time, Schirmer test, and adverse events. The certainty of evidence was evaluated using the Grading of Recommendations, Assessment, Development, and Evaluations approach. RESULTS: Thirty-nine randomized controlled trials (3693 patients) were eligible. Using artificial tears as a reference, autologous platelet lysate was the most effective treatment for lowering ocular surface disease index (unstandardized mean difference [USMD] -31.85; 95% confidence interval [CI]: -43.19 to -20.51) and platelet rich plasma showed the most reduction in corneal fluorescein staining scores (standardized mean difference -2.52; 95% CI: -3.23 to -1.82). Cord blood serum was the most effective treatment for increasing tear break-up time (USMD 2.67; 95% CI: 0.53-4.82), and eledoisin was superior to others in improving Schirmer scores (USMD 2.28; 95% CI: 0.14-4.42). Most interventions did not significantly increase ocular adverse events compared with artificial tears. CONCLUSIONS: Biological tear substitutes, including autologous serum, autologous platelet lysate, platelet rich plasma, and cord blood serum, might be the most effective treatment among tear promotion eye drops in relieving dry eye symptoms without increasing adverse events. However, there remains uncertainty around these findings because of low/very low certainty of evidence.

Effectiveness and Safety of Direct Oral Anticoagulants in Thai Patients with Atrial Fibrillation: A Real-World Retrospective Cohort Study.

BACKGROUND: Direct oral anticoagulants (DOACs) are commonly used to prevent stroke and systemic embolism in patients with atrial fibrillation (AF). However, studies into their effectiveness and safety in the Thai population have so far been limited. OBJECTIVES: To study the effectiveness and safety of warfarin and DOACs among Thai AF patients. METHODS: A retrospective cohort study was conducted on AF patients at Ramathibodi Hospital from 2013 to 2018. All patients were followed for at least 1 year. Relevant clinical information was collected and compared between AF patient groups receiving warfarin, dabigatran, rivaroxaban, and apixaban. The primary outcome was a composite of major bleeding, ischemic stroke, and systemic thromboembolism. The secondary outcomes were all-cause mortality and disease-specific mortality caused by major bleeding, ischemic stroke, and systemic thromboembolism. RESULTS: A total of 1680 AF patients were enrolled in the study (warfarin 1193, apixaban 140, dabigatran 193, rivaroxaban 114). The estimated incidence of composite outcome was 16% [95% CI, 14-18%] and 12.4% [95% CI, 9.4-15.3%] in the warfarin and DOAC group, respectively, given a number needed to treat of 28 [95% CI, 3-52]. Compared with warfarin, DOACs were associated with both lower rate of all-cause mortality (4.9% [22/447] vs 8% [98/1193]) and lower disease-specific mortality (0.4% [2/447] and 1% [12/1193]). CONCLUSIONS: This study suggests DOACs were associated with a lower risk of major bleeding, ischemic stroke, and systemic thromboembolism compared to warfarin in Thai patients with AF. Patients receiving DOAC also had a lower rate of all-cause mortality and disease-specific mortality.