Assessment of the appropriateness of serum digoxin concentration measurement in a medical group setting.

BACKGROUND: Recent quality initiatives require that the routine annual therapeutic drug-monitoring (TDM) parameters for the high-risk medication digoxin include a measure of renal function and a serum potassium level but not a serum digoxin concentration (SDC) measurement. Several studies have shown that the majority of the SDCs obtained in hospital settings provide little clinically actionable information. OBJECTIVE: To evaluate the appropriateness and utility of SDCs ordered in a medical group practice setting by categorizing the reason the SDC was ordered and identifying action taken in response to the result. METHODS: The descriptive study was conducted as a retrospective, electronic medical record (EMR) review of 90 primary care patients with continuous prescriptions for digoxin current on their medication profile with no gaps in therapy for at least 2 years prior to an SDC result entered into the EMR between January 1, 2009, and September 30, 2009. The reason the SDC was ordered was abstracted independently by 2 reviewers, who then assigned it to 1 of 8 predefined indication categories based on previously published criteria and practice guidelines. A third reviewer resolved inter-reviewer discrepancy (n = 1). RESULTS: A total of 90 patients with at least 1 SDC met inclusion criteria. Routine monitoring was the most frequent SDC order indication category with 35 patients (38.9%), 17 (48.6%) of whom did not have the recommended monitoring measures of potassium or renal function drawn concurrently. Patients were included in other categories as follows: confirmation of signs/symptoms of toxicity 30 (33.3%); assessment of factors altering pharmacokinetics 5 (5.6%); assessment of dosage change 5 (5.6%); assessment of drug interaction 3 (3.3%); assessment of clinical response 3 (3.3%); assessment of adherence 1 (1.1%); and other 2 (2.2%). Across all categories, a total of 19 (21.1%) of SDC results were outside the therapeutic range of 0.5 nanograms (ng) per mL and 2.0 ng per mL, 18 of which were below 0.5 ng per mL, with none of the subtherapeutic levels leading to a change in digoxin therapy. Only 1 patient (1.1%) had therapy changed in response to an elevated abnormal SDC result of 2.1 ng per mL and was in the routine monitoring category. CONCLUSIONS: The majority of SDC results obtained in our medical group setting did not lead to clinical action, such as dose adjustment or drug discontinuation. SDCs were commonly measured as part of routine monitoring, which is considered an inappropriate indication, and often without being accompanied by better markers for digoxin toxicity such as serum potassium levels and measures of renal function as recommended by drug-monitoring quality initiatives. Provider education is needed regarding the most indicative digoxin TDM parameters to obtain in order to satisfy quality initiatives.

Tenting volume: three-dimensional assessment of geometric perturbations in functional mitral regurgitation and implications for surgical repair.

BACKGROUND AND AIM OF THE STUDY: Functional mitral regurgitation (FMR) often complicates dilated cardiomyopathy (DCM), and portends a poor prognosis. Debate over the optimal treatment continues, underscoring the present incomplete understanding of the patho-anatomic mechanisms of this disease. Studies of mitral tenting volume and tenting area, and echocardiographic measures of abnormal apical systolic leaflet geometry have linked mitral leaflet deformation with subvalvular left ventricular (LV) remodeling in chronic ischemic MR. The relative contributions of annular versus subvalvular remodeling in FMR due to DCM are less clear. Here, the validity of 3-D measurement of mitral deformation, tenting volume, as a correlate of MR in DCM, was tested. The ability of annular and subvalvular remodeling to predict mitral deformation was then determined. METHODS: Eight sheep underwent placement of radiopaque markers on the mitral annulus and leaflets. Global LV, annular and subvalvular geometry, as well as mitral tenting height, area and volume were calculated before (Control) and after the development of pacing-induced cardiomyopathy and MR (DCM). Multivariable regression determined which measure of mitral deformation was the best predictor of MR. Regression analysis was also used to find geometric predictors of mitral tenting volume. RESULTS: In a multivariable analysis, mitral tenting volume was the only independent predictor of severity of MR (r(2) = 0.79, standard error of estimate (SEE) = 0.58). Increased tenting volume correlated best with increased mitral annular septal-lateral diameter (r(2) = 0.67, SEE = 0.72). CONCLUSION: The 3-D tenting volume correlates best with severity of FMR. Mitral deformation (increased tenting volume) observed in DCM is predicted by annular dilation, but not by subvalvular LV remodeling. These data support the use of an undersized annuloplasty in DCM complicated by FMR, and may guide the rational design of new therapies for this vexing disease.

A conserved carboxylesterase is a SUPPRESSOR OF AVRBST-ELICITED RESISTANCE in Arabidopsis.

AvrBsT is a type III effector from Xanthomonas campestris pv vesicatoria that is translocated into plant cells during infection. AvrBsT is predicted to encode a Cys protease that targets intracellular host proteins. To dissect AvrBsT function and recognition in Arabidopsis thaliana, 71 ecotypes were screened to identify lines that elicit an AvrBsT-dependent hypersensitive response (HR) after Xanthomonas campestris pv campestris (Xcc) infection. The HR was observed only in the Pi-0 ecotype infected with Xcc strain 8004 expressing AvrBsT. To create a robust pathosystem to study AvrBsT immunity in Arabidopsis, the foliar pathogen Pseudomonas syringae pv tomato (Pst) strain DC3000 was engineered to translocate AvrBsT into Arabidopsis by the Pseudomonas type III secretion (T3S) system. Pi-0 leaves infected with Pst DC3000 expressing a Pst T3S signal fused to AvrBsT-HA (AvrBsTHYB-HA) elicited HR and limited pathogen growth, confirming that the HR leads to defense. Resistance in Pi-0 is caused by a recessive mutation predicted to inactivate a carboxylesterase known to hydrolyze lysophospholipids and acylated proteins in eukaryotes. Transgenic Pi-0 plants expressing the wild-type Columbia allele are susceptible to Pst DC3000 AvrBsTHYB-HA infection. Furthermore, wild-type recombinant protein cleaves synthetic p-nitrophenyl ester substrates in vitro. These data indicate that the carboxylesterase inhibits AvrBsT-triggered phenotypes in Arabidopsis. Here, we present the cloning and characterization of the SUPPRESSOR OF AVRBST-ELICITED RESISTANCE1.