Ethnicity-specific associations between the promoter region G-308A polymorphism (rs1800629) of the TNF-α gene and the development of end-stage renal disease: An evidence-based meta-analysis and trial sequential analysis

Abstract Tumor necrosis factor-alpha (TNF-α), is partly attributed to pathogenesis of end-stage renal disease (ESRD). Inconsistency of reported associations between TNF-α G-308A polymorphism (rs1800629) and ESRD prompted a meta-analysis to obtain more precise estimates. Eleven case-control studies from 11 articles were included. Pooled odds ratios (OR) and 95% confidence intervals (95% CIs) were estimated to evaluate the association. Subgroup analysis was based on ethnicity (Caucasian and Asian). Multiple comparisons were Bonferroni-corrected. Trial sequential analysis (TSA) was implemented to ascertain the reliability of results. Sensitivity analyses and publication bias tests were performed on significant results. There were no significant association (pa >0.05) in the overall and ethnic subgroup. Indians, three significant pool ORs (pa < 0.01-0.03) showed increased susceptibility to ESRD in homozygous (OR, 6.57; 95% CI, 1.45 to 29.75; pa = 0.01), recessive (OR, 6.75; 95% CI, 1.44 to 31.56; pa = 0.02), and codominant (OR, 2.06; 95% CI, 1.08 to 3.94; pa = 0.03) models. TSA indicated the robustness of such association in the Indian population. The main outcomes were robust without evidence of publication bias. This study showed associations between TNF-α G-308A and ESRD are confined to Indians, which are susceptible to ESRD up to approximately 7 times

Nucleotide Analogue-Related Proximal Renal Tubular Dysfunction during Long-Term Treatment of Chronic Hepatitis B: A Cross-Sectional Study

Background. There have been few reports of nucleotide analogue-related renal tubular dysfunction (RTD) in CHB patients. We assessed the prevalence and presentation of nucleotide analogue-related proximal RTD. Methods. A cross-sectional study was performed in CHB patients taking nucleotide analogues. Inclusion criteria were patients who were on adefovir or tenofovir as mono- or add-on therapy with lamivudine (LAM) >1 year. Serum and urine were collected. Fractional excretion of phosphate (FEPO4), uric acid (FEUA), and potassium was calculated. Renal losses were defined based on the criteria: protein (24-hour urine protein >150 mg), glucose (glycosuria with normoglycemia), phosphate (FEPO4 >18%), uric acid (FEUA >15%), potassium (renal potassium losses with hypokalemia), and bicarbonate (normal gap acidosis). Subclinical and overt proximal RTD were defined when 2 and ≥3 criteria presented. Results. Ninety-two patients were enrolled. The mean duration of nucleotide analogue taking was 55.1±29.6 months. Proximal RTD was found in 24 (26.1%) patients (subclinical 15 (16.3%) and overt 9 (9.8%)). The severity of RTD was associated with the duration of nucleotide analogue (P=0.01). Conclusions. The prevalence of proximal RTD in CHB patients taking nucleotide analogues was 26%. The severity of RTD was associated with the treatment duration. Comprehensive testing is necessary for early detecting nucleotide analogue-related nephrotoxicity

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. </jats:sec

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 &gt;one SRMA), tested for excessive significance (i.e., observed number of statistically significant studies &gt; 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

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.</p

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.</jats:sec

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

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

ObjectiveBody 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.MethodsA 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.ResultsAmong 2305 participants, the mean eGFR at baseline decreased from 98.7 ± 23.6 mL/minute/1.73 m2in 2009 to 92.4 ± 22.9 mL/minute/1.73 m2in 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.ConclusionsOur 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.</jats:sec