American journal of therapeutics最新文献

Background: Chronic kidney disease can lead to end-stage renal disease, and the prevalence is increasing. Many patients starting hemodialysis require central venous catheters (CVCs). Catheter-related bloodstream infections (CRBSIs) are a common complication and lead to significant morbidity and mortality. Interventions to prevent CRBSI include antimicrobial lock therapy but concern for the development of antimicrobial resistance and adverse effects. Nonantimicrobial antiseptics as catheter lock solutions have also been used. Taurolidine and heparin catheter lock solution is first approved by the Food and Drug Administration for the prevention of CRBSI in patients on hemodialysis. Taurolidine has a unique mechanism of action and favorable safety profile.

Mechanism of action, pharmacodynamics, and pharmacokinetics: Taurolidine and heparin catheter lock solution have both antimicrobial and anticoagulant properties. Taurolidine is derivative of the amino acid taurine, and heparin is derived from porcine intestinal mucosa. Taurolidine not only damages microbial cell walls but also prevents the adherence of microorganisms to biological surfaces, preventing biofilm formation. Taurolidine and heparin catheter lock solution is intended to be used intraluminally within the catheter and should be aspirated. Because it is used locally, limited pharmacokinetic and pharmacodynamic data are available.

Clinical trials: The LOCK-IT-100 trial is a randomized, double-blind, phase 3 study, which included 795 end-stage renal disease patients on hemodialysis with CVC. Taurolidine and heparin was compared with the control heparin alone. The results of the study showed a 71% risk reduction in CRBSI for taurolidine and heparin arm (95% confident interval, 38%-86%, P = 0.0006). Other studies have also shown that taurolidine lock solution leads to decreased CRBSI episodes. Several systematic reviews and meta-analysis consisted of taurolidine in adult, and pediatric populations also showed reduction in the incidence of CRBSIs.

Therapeutic advance: Taurolidine and heparin lock solution represents a novel preventive strategy for those undergoing hemodialysis through a CVC by reducing the risk of CRBSI. This is significant progress because there are no other similar options available for patients for whom catheters are the only options for their life-saving treatment.

Background: Loop diuretic therapy effectively treats edema related to heart failure, chronic kidney disease, and liver impairment; however, evidence supporting other indications is lacking. For indications such as hypertension or dependent edema or treatment of adverse events associated with other medications, the benefits likely do not outweigh the risks, putting patients at an unacceptably high risk of poor outcomes.

Study question: What is the proportion of loop diuretic prescribing that occurs in the absence of a diagnosis of heart failure, chronic kidney disease, liver impairment, or other evidence-based indications?

Study design: This was a national, retrospective, cross-sectional investigation conducted using the National Ambulatory Care Survey from 2013 to 2016. Outpatient visits for patients aged 18 years or older prescribed with loop diuretics were included.

Measures and outcomes: The primary end point was the frequency of potentially inappropriate loop diuretic prescribing. The secondary end point was a multivariable regression model that identified predictors of potentially inappropriate loop diuretic utilization.

Results: This analysis identified 5261 outpatient visits conducted during the study period in which loop diuretics were prescribed. Of these, 3648 visits (65.8% of weighted visits) were of patients without a history of heart failure, chronic kidney disease, or liver impairment. Positive predictors included age older than 65 years (odds ratio [OR] 1.71; 95% confidence interval [CI] 1.38-2.13), concomitant calcium channel blocker (OR 1.42; 95% CI, 1.09-1.84), sodium-containing medication use (OR 2.78; 95% CI, 1.23-6.25), and office visit with a cardiology specialist (OR 2.84; 95% CI, 2.31-3.50).

Conclusions: This analysis identified that loop diuretics are prescribed in the absence of evidence-based indications more frequently than they are prescribed for them. This prescribing pattern creates a unique opportunity for clinicians to optimize patient care. Further study of the outcomes associated with this prescribing pattern is warranted.