OBJECTIVES: This study aims (i) to investigate the effects of EGCG on nadolol pharmacokinetics (maximum plasma concentration, time to achieve maximum concentration, area under the time-plasma concentration curve, plasma half-life and total clearance) and subsequently its impact on blood pressure control; and (ii) to identify transcriptional regulatory roles of EGCG on the nadolol intestinal and hepatic drug-transporters in SHR.
METHODS: Male SHR were pre-treated with a daily dose of EGCG (10 mg/kg body weight, i.g.) for 13 days. On day-14, a single dose of nadolol (10 mg/kg body weight) was given to the rats 30 min after the last dose of EGCG administration. Systolic blood pressure (SBP) was measured at 6-h and 22-h post-nadolol administration. Plasma and urinary nadolol concentrations were quantified using high-performance liquid chromatography, and pharmacokinetic parameters were analyzed by using non-compartmental analysis. Hepatic and ileal Oatp1a5, P-gp, and Oct1 mRNA expressions were determined by real-time PCR.
RESULTS: SBP of SHR pre-treated with EGCG and received nadolol was significantly higher than those which were not pre-treated with EGCG but received nadolol. Pre-treatment of EGCG resulted in a marked reduction of plasma nadolol maximum concentration (Cmax) and area under the time-plasma concentration curve (AUC) by 53% and 51% compared to its control. The 14-day treatment with oral EGCG led to a significant downregulation of mRNA levels of ileal Oatp1a5, P-gp, and Oct1 genes by 4.03-, 8.01- and 4.03-fold; and hepatic P-gp, and Oct1 genes by 2.61- and 2.66-fold.
CONCLUSION: These data concluded that exposure to EGCG could lead to reduced nadolol bioavailability and therefore, uncontrolled raised blood pressure and higher risks of cardiovascular events. Our data suggest that the reduced nadolol bioavailability is associated with the downregulation of ileal Oatp1a5 and Oct1 mRNA levels that subsequently lead to poor absorption of nadolol to the systemic circulation.
METHODOLOGY: Five electronic databases were searched for studies that compared implant outcomes in patients with differing HbA1c values. Research quality was evaluated using Risk of Bias in Nonrandomized Studies of Interventions (ROBINS-I) tool. Narrative synthesis and meta-analysis were performed for survival rate, plaque index (PI), bleeding on probing (BOP), probing pocket depth, and marginal bone loss (MBL). Categorical dose-response meta-analysis (DRMA) was conducted according to length of follow-up.
RESULTS: Twenty-two studies met the inclusion criteria. Prospective studies were mostly of moderate quality, but non-prospective papers had serious to critical risk of bias. Survival rate was high for the first 3 years (92.6%-100%) for patients with HbA1c less than 8%. Meta-analysis revealed worsening clinical parameters with increasing HbA1c. DRMA further established a significant dose-response relationship between glycemic control with BOP (10% more bleeding, 95% CI 0.05-0.16, P = .008) and MBL (0.05 mm more bone loss, 95% CI 0.01-0.09, P = .002) per HbA1c category, but no association with probing pocket depth. Osseointegration progressed at a slower rate, and inflammatory cytokines and bone biomarkers were adversely affected in patients with HbA1c above 8%.
CONCLUSION: Moderate evidence suggests a high short-term survival but possible dose-response trend of worsening BOP and MBL in association with glycemic control. Clinically, HbA1c values must be considered for risk assessment before placement and throughout the lifespan of the implant placed in a patient with diabetes.
Methods: The medical records of 95 older patients (age ≥ 65) who attended the GMC from 16 December 2019 to 10 January 2020 were reviewed. Frailty was identified using the FRAIL scale and the CFS. Patient characteristics were investigated for their association with frailty and their difference in the prevalence of frailty by the FRAIL scale and CFS.
Results: The CFS identified nonsignificant higher prevalence of frailty compared to the FRAIL scale (21/95; 22.1% vs. 17/95; 17.9%, ratio of prevalence = 1.235, p=0.481). Minimal agreement was found between the FRAIL scale and the CFS (Kappa = 0.272, p < 0.001). Three out of 5 components of the FRAIL scale (resistance, ambulation, and loss of weight) were associated with frailty by the CFS. Higher prevalence of frailty was identified by the CFS in those above 70 years of age. The FRAIL scale identified more patients with frailty in ischaemic heart disease patients.
Conclusion: Patient characteristics influenced the choice of the frailty assessment tool. The FRAIL scale and the CFS may complement each other in providing optimized care to older patients who attended the GMC.
METHODS: : Our prospective observational study consists of 257 patients without known thyroid diseases admitted to the medical ICU. The baseline characteristics of the patients were recorded, including the APACHE II score and thyroid hormone levels at ICU admission. Based on the primary outcome of mortality, we analyzed the data by appropriate statistical methods. A P < 0.05 was considered significant.
Results: Of the 257 patients included in the study, 47 (18.28%) succumbed to their illnesses. A significant difference in T3 levels (P < 0.001), T4 levels (P < 0.001), and APACHE II score (P < 0.001) was found between the survivors and the nonsurvivors. There was negative correlation observed between T3 and APACHE II score (r = -0.448, P < 0.001) and T4 and APACHE II score (r = -0.221, P ≤ 0.001). Multivariate logistic regression analysis determined T3 to be the only independent predictor of ICU mortality among thyroid hormones. The area under the curve (AUC) for T3 (0.811 ± 0.04) was almost equal to that of the APACHE II score (0.858 ± 0.029). The duration of ICU stay and hospital stay in patients with low T3 was significantly higher compared to patients with normal T3.
Conclusion: Serum T3 is a good indicator for predicting mortality and morbidity among critically ill patients.
Methods: Eight databases, including MEDLINE, EMBASE, Science Direct, Scopus, Cochrane, CINAHL, Open Grey, and Dart-Europe, were systematically searched from the inception of the database up to August 21, 2020. Studies evaluating the effectiveness of thiamine on mortality rate in septic shock patients compared between thiamine and placebo were included. We used random-effects model to analyze the mortality with risk ratio (RR) and 95% confidence interval (95% CI). The subgroup and sensitivity analysis were performed to examine the influence of variables. Publication bias was considered using funnel plot, Begg's test, and Egger's test.
Results: A total of 3,658 studies were retrieved and reviewed. Five studies were included for meta-analysis. In random-effects meta-analysis of the randomized controlled trials, although not statistically significant, there was a trend which suggested that thiamine may reduce mortality rate in septic shock patients (RR, 0.96; 95% CI: 0.72-1.28, P = 0.774). The result of sensitivity and subgroup analyses also supported the suggestion that thiamine may decrease mortality in septic shock patients. The Begg's test (P = 0.624) and Egger's test (P = 0.777) revealed no publication bias.
Conclusions: Although not statistically significant, thiamine may reduce mortality rate in septic shock patients. Further prospective studies with larger sample size are warranted.