To compare hazard ratios obtained by using time on study (conventional) versus biological age as the time-scale in survival analyses for a known age-dependent association between an exposure and outcome.
 
  We conducted a retrospective cohort study of 9 million people in Ontario, Canada who were followed from 2003 to 2018 to identify incident ischemic stroke using linked administrative health data. Using cause-specific hazards models, we calculated hazard ratios (HR) of ischemic stroke in women compared to men using the two different time scales. By using piecewise estimates and interaction terms, we evaluate the effect of sex on stroke incidence across age groups.
 
  In unadjusted analyses, the reduction in the hazard of ischemic stroke in women compared to men was greater with age as time-scale (HR 0.77; 0.76-0.78) compared to conventional time-scale (HR 0.93; 0.92-0.93); however, the estimates were similar (HR 0.78 with age vs. 0.77 with conventional) in multivariable adjusted analyses. The estimates obtained by two methods across different age groups varied modestly, except in those under 30 years (HR 1.47; 1.19-1.83 with age vs. 1.08; 0.99-1.17 with conventional).
 
  When evaluating age-dependent association between an exposure and outcome, estimates of association vary based on the time-scale used in survival analysis, requiring thoughtful consideration.
 When evaluating age-dependent association between an exposure and outcome, estimates of association vary based on the time-scale used in survival analysis, requiring thoughtful consideration.The aim of this study was to investigate the association between vancomycin trough level and clinical outcomes (mortality and nephrotoxicity) among infected paediatric patients with Gram-positive pathogens. We systematically searched the Scopus, EMBASE, Cochrane Central Register of Controlled Trials, PubMed and CINAHL databases up to March 2020. A total of seven retrospective cohort or case-control studies were included to compare clinical effects and safety three studies set the threshold of vancomycin trough level at 10 mg/L and the others set it at 15 mg/L.  https://www.selleckchem.com/products/c75.html  Our analysis showed that vancomycin trough level of 10-15 mg/L was associated with significantly lower mortality [ less then 10 mg/L vs. ≥10 mg/L, odds ratio (OR) = 3.21, 95% confidence interval (CI) 1.74-5.91; and less then 15 mg/L vs. ≥15 mg/L, OR = 0.31, 95% CI 0.10-0.95). The high vancomycin trough group (≥10 mg/L or ≥15 mg/L) showed a higher incidence of nephrotoxicity ( less then 10 mg/L vs. ≥10 mg/L, OR = 0.06, 95% CI 0.03-0.12; and less then 15 mg/L vs. ≥15 mg/L, OR = 0.28, 95% CI 0.12-0.65). This is the first meta-analysis to reveal the optimal therapeutic range of vancomycin trough level in children. Our findings strongly suggest a superior benefit of vancomycin trough of 10-15 mg/L for paediatric patients.
  Airport quarantine is required to reduce the risk of entry of travelers infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, it is challenging for both high accuracy and rapid turn-around time to coexist in testing; polymerase chain reaction (PCR) is time-consuming with high accuracy, while antigen testing is rapid with less accuracy. However, there are few data on the concordance between PCR and antigen testing.
 
  Arrivals at three international airports in Japan between July 29 and September 30, 2020 were tested for SARS-CoV-2 using self-collected saliva by a screening strategy with initial chemiluminescent enzyme immunoassay (CLEIA) followed by confirmatory nucleic acid amplification tests (NAAT) only for intermediate range antigen concentrations.
 
  Among the 95,457 persons entering Japan during the period, 88,924 (93.2%) were tested by CLEIA, and 0.29% (254/88,924) were found to be SARS-CoV-2 antigen positive (≥4.0pg/mL). NAAT was required for confirmatory testing in 0.58at large venues.Bioprosthetic aortic valve replacement (bAVR) in patients with congenital heart disease is challenging due to age, size and complexity. Our objective was to assess survival and identify predictors of re-operation. Data were retrospectively collected for 314 patients undergoing bAVR at 8 centers from 2000-2014. Kaplan-Meier estimation of time to re-operation and Cox regression were utilized. Average age was 45.2 years (IQR 17.8-71.1) and 30% were less then 21. Indications were stenosis (48%), regurgitation (28%) and mixed (18%). Twenty-eight (9%) underwent prior AVR. Median valve size was 23mm (IQR 21, 25). Implanted valves included CE (Carpentier-Edwards) Perimount (47%), CE Magna/Magna Ease (29%), Sorin Mitroflow (9%), St Jude (2%) and other (13%). Median follow-up was 2.9 (IQR 1.2, 5.7) years. Overall, 11% required re-operation, 35% of whom had a Mitroflow and 65% were less then 21 years old. Time to re-operation varied among valve type (p=0.020). Crude 3-year rate was 20% in patients ≤21. Smaller valve size indexed to BSA was associated with re-operation (21.7 vs. 23.5 mm/m2). Predictors of reintervention by multivariable analysis were younger age (29% increase in hazard per 5-year decrease, p less then 0.001), Mitroflow (HR=4 to 8 versus other valves), and smaller valve size (20% increase in hazard per 1 mm decrease, p=0.002). The overall 1, 3 and 5-year survival rates were 94%, 90% and 85% without differences by valve (p=0.19). A concerning reduction in 5-year survival after bAVR is shown. Re-operation is common and varies by age and valve type. Further research is needed to guide valve choice and improve survival.Acute myeloid leukemia (AML) is characterized by the disruption of myeloid differentiation and accumulation of blast cells in the bone marrow. While AML patients respond favorably to induction chemotherapy, long-term outcomes remain poor due to a high rate of chemoresistance. Advances with targeted therapies, which can be used in combination with conventional chemotherapy, have expanded therapeutic options for patients. However, remission is often short-lived and followed by disease relapse and drug resistance. Therefore, there is a substantial need to improve treatment options by identifying novel molecular and cellular targets that regulate AML chemosensitivity. Membrane scaffolds such as the tetraspanin family of proteins often serve as signaling mediators, translating extracellular signaling cues into intracellular signaling cascades. In this review, we discuss the conventional and targeted treatment strategies for AML and review chemoresistance mechanisms with a focus on the tetraspanin family of membrane scaffold proteins.