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.

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.

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.

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.

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.

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).

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.

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.

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.

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.

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 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.

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.

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.

Midline incisional hernia prophylaxis using synthetic mesh in an emergency or urgent gastrointestinal tract surgery: a protocol for multicentre randomised clinical trial.

INTRODUCTION: Between 5% and 30% of abdominal incisions eventually result in incisional hernias (IHs) that can lead to severe complications and impaired quality of life. Unfortunately, IH repair is often unsuccessful; therefore, hernia prophylaxis is an important issue. The efficacy of mesh augmentation has been proven for hernia prophylaxis in high-risk patients, but no randomised clinical trial has evaluated prophylactic mesh placement in emergency/urgent gastrointestinal operations. METHODS AND ANALYSIS: A multicentre, prospective randomised, open and patient-assessor blinded endpoint design will be conducted. A total of 470 patients will be enrolled and randomly allocated to retrorectus mesh augmentation with lightweight polypropylene mesh or primary suture closure. The primary outcome is IH occurrence within 24 months of follow-up, while other clinical outcomes are secondary endpoints. A cost-effectiveness analysis will be conducted from the societal and provider perspectives. ETHICS AND DISSEMINATION: Ethics approval was obtained from Ramathibodi Hospital (MURA2020/1478) and Vajira Hospital (COA164/2563). The protocol is on the process of submission to the local ethics committee of the other study sites. Results will be submitted for publication in a peer-reviewed journal. TRIAL REGISTRATION NUMBER: TCTR20200924002.

Risk-benefit assessment of onlay and retrorectus mesh augmentation for incisional hernia prophylaxis: A secondary analysis from network meta-analysis.

BACKGROUND: Mesh augmentation has proved efficacious for the prevention of incisional hernia (IH). A recent network meta-analysis (NMA) identified onlay and retrorectus mesh (OM and RM) as the most effective therapeutic options, but the risk of surgical site infection (SSI) and other complications require additional consideration. METHODS: The NMA generated pooled risk differences (RD) for the benefits of reducing IH and the risk of SSI and composite seroma/hematoma (CSH) for use in Monte-Carlo data simulations with 1000 replications. Mean incremental risk-benefit ratios (IRBR), i.e., the ratio of incremental risk (or RD) and incremental benefit, and 95% confidence intervals (95% CI) were estimated with a probability of risk-benefits (PRB) across risk-benefit acceptability thresholds from the acceptability curves generated. RESULTS: The RDs of IH were 0.237 and 0.201 lower in OM and RM than primary suture closure, compared to 0.027 and -0.001 for SSI. IRBRs (95% CI) for SSI risk were -0.118 (-0.124, -0.112) and 0.006 (-0.002, 0.013) for OM and RM, respectively. PRBs were much higher in RM than OM, especially at low acceptability thresholds of 0.05 and 0.1. IRBRs (95% CI) for CSH were -0.388 (-0.395, -0.381) and -0.105 (-0.111, -0.100) for OM and RM, respectively. RM yielded a PRB of 0.87 at an acceptability threshold of 0.2, in contrast to OM, which did not. CONCLUSION: Overall, RM offered improved benefit in IH prophylaxis over the risk of complications relative to OM and appeared to be the preferred treatment option for this indication.

Medical and non-medical interventions for post-operative urinary retention prevention: network meta-analysis and risk-benefit analysis.

AIMS: To assess the efficacy in lowering post-operative urinary retention, urinary tract infection and lower urinary tract symptoms and the incidence of adverse events among 12 interventions and to perform risk-benefit analysis. METHODS: Previous randomized controlled trials were identified from MEDLINE, Scopus and CENTRAL database up to January 2020. The interventions of interest included early ambulation, fluid adjustment, neuromodulation, acupuncture, cholinergic drugs, benzodiazepine, antispasmodic agents, opioid antagonist agents, alpha-adrenergic antagonists, non-steroidal anti-inflammatory drugs (NSAIDs) and combination of any interventions. The comparators were placebo or standard care or any of these interventions. Network meta-analysis was performed. The probability of being the best intervention was estimated and ranked using rankogram and surface under the cumulative ranking curve. Risk-benefit analysis was done. Incremental risk-benefit ratio (IRBR) was calculated and risk-benefit acceptability curve was constructed. RESULTS: A total of 45 randomized controlled trials with 5387 patients was included in the study. Network meta-analysis showed that early ambulation, acupuncture, alpha-blockers and NSAIDs significantly reduced the post-operative urinary retention. Regarding urinary tract infection and lower urinary tract symptoms, no statistical significance was found among interventions. Regarding the side effects, only alpha-adrenergic antagonists significantly increased the adverse events compared with acupuncture and opioid antagonist agents from the indirect comparison. According to the cluster ranking plot, acupuncture and early ambulation were considered high efficacy with low adverse events, corresponding to the IRBR. CONCLUSION: Early ambulation, acupuncture, opioid antagonist agents, alpha-adrenergic antagonists and NSAIDs significantly reduce the incidence of post-operative urinary retention with no difference in adverse events. Regarding the risk-benefit analysis of the medical treatment, alpha-adrenergic antagonists have the highest probability of net benefit at the acceptable threshold of side effect of 15%, followed by opioid antagonist agents, NSAIDs and cholinergic drugs.

Comparison of treatment efficacy between 100% platelet-rich plasma and 100% serum eye drops in moderate-to-severe dry eye disease: a randomised controlled trial protocol.

INTRODUCTION: Dry eye disease (DED) is a common eye problem. Although the disease is not fatal, it substantially reduces quality of life and creates a high economic burden, especially in patients with moderate-to-severe DED. Several biological tear substitutes (eg, autologous serum (AS), autologous platelet-rich plasma (APRP) and autologous platelet lysate) could effectively improve dry eyes. However, evidence on their comparative efficacy is controversial. This study aims to compare the efficacy of 100% APRP with 100% AS eye drops in patients with moderate-to-severe DED. METHODS AND ANALYSIS: The study is a single-centre, double-blinded randomised, parallel, non-inferiority trial. One hundred and thirty patients with moderate-to-severe DED, aged 18-70 years will be recruited from outpatient clinic, Department of Ophthalmology, Ramathibodi Hospital, Bangkok from February 2021 to January 2023. Patients will be randomised to receive either 100% APRP or 100% AS eye drops (1:1 ratio) for 4 weeks. The primary outcomes are ocular surface disease index (OSDI) and ocular surface staining (OSS) evaluated using the Oxford scale. Secondary outcomes are fluorescein break-up time, Schirmer's I test, meibomian gland parameters and adverse events. Other measured outcomes include best-corrected visual acuity, intraocular pressure and compliance. ETHICS AND DISSEMINATION: The study protocol and any supplements used in conducting this trial have been approved by the Ethics Committee of Faculty of Medicine, Ramathibodi Hospital, Mahidol University (MURA2020/1930). Informed consent will be obtained from all patients before study entry. Results will be presented in peer-reviewed journals and international conferences. TRIAL REGISTRATION NUMBER: NCT04683796.