ABSTRACT:Expression and activity of drug-metabolizing enzymes are decreased in severe kidney disease; however, only a small percentage of patients with chronic kidney disease (CKD) are at the final stage of the disease. This study aimed to determine the changes in drug-metabolizing enzyme function and expression in rats with varying degrees of kidney disease. Sprague-Dawley rats were subjected to surgical procedures that allowed the generation of three distinct models of kidney function: normal kidney function, moderate kidney function, and severe kidney disease. Forty-two days after surgery, rats were sacrificed and hepatic CYP3A and CYP2C expression was determined. In addition, enzymatic activity was determined in liver microsomes by evaluating midazolam (CYP3A), testosterone (CYP3A and CYP2C), and tolbutamide (CYP2C) enzyme kinetics. Both moderate and severe kidney disease were associated with a reduction in CYP3A2 and CYP2C11 expression (p < 0.05). Likewise, moderate kidney disease resulted in more than a 60% decrease in enzyme activity (V max ) for CYP2C11 and CYP3A, compared with controls (p < 0.05). When the degree of kidney disease was correlated with metabolic activity, an exponential decline in CYP2C-and CYP3A-mediated metabolism was observed. Our results demonstrate that CYP3A and CYP2C expression and activity are decreased in both moderate and severe CKD. Our data suggest that drug metabolism is significantly decreased in the earlier stages of CKD and imply that patients with moderate CKD may be subject to unpredictable pharmacokinetics.
Background. Ophthalmic viscoelastic devices (OVDs) used during small-incision cataract surgery have numerous advantages. However, OVDs have longer retention time in an eye after surgery resulting in intraocular pressure (IOP) spikes. The purpose of this study is to analyze and quantify the effect of various OVDs on both IOP and best corrected visual acuity (BCVA) by systematically reviewing the literature and performing meta-analysis. Methods. Numerous databases from January 1, 1985, to present were systematically searched. Thirty-six (3893 subjects) of 3313 studies identified were included for analysis. Standardized mean difference (SMD) was computed, and meta-analysis was performed. Results. A total of 3313 records were retrieved including 1114 from database search and 2199 from grey literature search. Significant increase in postoperative IOP in 1-day follow-up with Healon (SMD = 0.37, CI: [0.07, 0.67]), Viscoat (SMD = 0.29, CI: [0.13, 0.45]), Provisc (SMD = 0.46, CI: [0.17, 0.76]), and Soft Shell (SMD = 0.58, CI: [0.30, 0.86]) was computed. On the other hand, results implied a nonsignificant increase in postoperative IOP with Healon GV (SMD = 0.07, CI: [−0.28, 0.41]), Healon5 (SMD = 0.15, CI: [−0.33, 0.64]), 2% HPMC (SMD = 0.32, CI: [−0.0, 0.64]), and OcuCoat (SMD = 0.26, CI: [−0.37, 0.9]). Additionally, a nonsignificant reduction in postoperative IOP was inferred with Viscoat + Provisc (SMD = −0.28, CI: [−2.23, 1.68]). Conclusion. Improvement in IOP was shown with Viscoat + Provisc. Additionally, IOP nonsignificant upsurge was observed with Healon GV, Healon5, 2% HPMC, and OcuCoat compared to significant upsurge with Healon, Viscoat, and Soft Shell.
The risk of bleeding and ischemic complications among patients on TT is similar between those on ticagrelor and clopidogrel. However, caution with use of bridging anticoagulation should be taken when using ticagrelor.
Background: Management of ST-elevated myocardial infarction (STEMI) necessitates rapid reperfusion. Delays prolong myocardial ischemia and increase the risk of complications, including death. The COVID-19 pandemic may have affected management of STEMI. We evaluated the relative volume of hospitalizations and clinical time intervals within a regional STEMI system. Methods: Four hundred ninety-four patients with STEMI were grouped into prelockdown, lockdown, and reopening cohorts. Clinical, temporal, and outcome data were collected and compared among groups for R ESUM EContexte : La prise en charge de l'infarctus du myocarde avec el evation du segment ST (STEMI) n ecessite une reperfusion rapide. Tout retard de reperfusion prolonge l'isch emie myocardique et augmente le risque de complications, y compris le risque de d ecès. Il est possible que la pand emie de COVID-19 ait nui à la prise en charge du STEMI. Nous avons donc evalu e le nombre relatif d'hospitalisations et le temps ecoul e avant la reperfusion au sein d'un système r egional de traitement des STEMI. M ethodologie : Au total, 494 patients ayant pr esent e un STEMI ont et e divis es en trois cohortes : pr econfinement, confinement et During the COVID-19 pandemic, a reduction in patients presenting with ST-elevated myocardial infarction (STEMI) has been reported. 1,2 These studies lacked data on important areas including impact of the COVID-19 lockdown on STEMI care in regions with low incidence of disease, granular details regarding reperfusion management during lockdown, effect of the pandemic on STEMI care in rural regions, and patterns of STEMI volume posteCOVID-19 lockdown. It is imperative to study the effects of COVID-19 comprehensively, so that lessons can be learned for a potential second wave or future pandemics.From March 11, 2020, to August 16, 2020, the Ottawa regions recorded 2761 cases of In response to the initial outbreak, the Ontario Ministry of Health declared a state of emergency and instituted lockdown measures on March 17, 2020. 4 Various restrictions were imposed including closure of nonessential businesses, limits on social gatherings, and cancellation of elective medical procedures. 4 These interventions were successful in limiting the spread of COVID-19; however, concerns regarding an unintended impact on STEMI care were raised. 3,
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