Development of a routine bedside CYP2C19 genotype assessment program for antiplatelet therapy guidance in a community hospital catheterization laboratory.

Genotype based personalized antiplatelet therapy in the setting of percutaneous coronary intervention (PCI) has been studied in clinical trials. Despite the demonstrated risk associated with CYP2C19 loss-of-function (LoF) carriage in clopidogrel-treated PCI patients, real-world implementation of genotyping for PCI has been low. The goal of the current study was to provide CYP2C19 genotype information to the interventionalist prior to the completion of the catheterization to facilitate immediate personalized antiplatelet therapy. Routine personalization of P2Y12 inhibitor therapy for PCI in a community hospital cardiac catheterization laboratory by POC genotyping with the SpartanRx system was first offered in February 2017. A best practice advisory (BPA) based on the Clinical Pharmacogenetics Implementation Consortium Guideline for CYP2C19 genotype and clopidogrel therapy was placed in the electronic health record prescription medication ordering system. By December 2019, 1,052 patients had CYP2C19 genotype testing, 429 patients underwent PCI with genotype guided antiplatelet therapy, and 250 patients underwent PCI without genotype testing and received antiplatelet therapy at the discretion of the treating physician. BPA compliance was 93. 87% of LoF allele carriers were prescribed ticagrelor or prasugrel whereas 96% of non-LoF allele carriers were prescribed clopidogrel. The genotyping results were available within 1 h and made immediately available for decision making by the interventional cardiologist. POC CYP2C19 genotyping is feasible in a community hospital catheterization laboratory and is associated with high rate of best practice compliance.Clinical Trial Registration: https://clinicaltrials.gov/ct2/show/NCT03040622.

Early assessment of the pharmacokinetic and pharmacodynamic effects following acetylsalicylic acid loading: toward a definition for acute therapeutic response.

Despite decades of investigations, the optimal assessment of the "therapeutic response" to early after loading dose of acetylsalicylic acid (ASA) remains unclear. Limited information is available on the relation between pharmacodynamic (PD) and pharmacokinetic (PK) measurements assessed immediately after ASA administration. Serial PD and PK analyses were performed immediately after a single 162 or 650 mg dose of chewed and swallowed ASA in ten healthy adults. ASA response was defined as > 95% inhibition of serum thromboxane (Tx)B2, < 550 aspirin reaction units (ARU) by VerifyNow Aspirin (VN) test, and ≤ 20% arachidonic acid (AA)-induced platelet aggregation (PA). Correlation analyses between PK and PD measurements and receiver operating characteristic (ROC) curve analyses were performed. ASA response measured by VN test and AA-induced PA was achieved within 30 min of ASA administration. A correlation was observed between ARU and AA-induced maximum PA (r = 0.69, p < 0.001), serum TxB2 (r = 0.74 and p < 0.001), and serum TxB2 inhibition (r = 0.79, p < 0.001). In ROC curve analyses, ≤ 558 ARU and ≤ 7% AA-induced PA were associated with > 95% inhibition of TxB2. 686 ng/ml plasma ASA cut-off point was associated with > 95% inhibition of serum TxB2, ≤ 7% 1 mM AA-induced PA, and ≤ 585 ARU. A modest ~ 50% inhibition of TxB2 inhibition was associated with marked inhibition of 1 mM AA-induced platelet aggregation by LTA. Our analyses demonstrated important relationships between pharmacodynamic, and pharmacokinetic parameters measured immediately following oral ASA and cutoff values for ARU and AA-induced PA that is associated with > 95% inhibition of serum TxB2.

Serial assessment of thrombogenicity and hemodynamics in patients with type II diabetes in a clinical research unit: Evidence for circadian variations in clot formation.

BACKGROUND: Circadian fluctuations in thrombogenicity and hemostasis play a role in acute cardiovascular thrombotic events occurring in the early morning hours. There is a lack of data assessing thrombogenicity, platelet function, and hemodynamics to investigate diurnal variations in a high cardiovascular risk population. METHODS: This was an exploratory, single-center study conducted in aspirin-treated patients with Type II Diabetes Mellitus (T2DM) (n = 37) with documented vascular disease and/or multiple cardiovascular risk factors. Hemodynamic monitoring and blood sample collection for thromboelastography (TEG) and platelet function testing were done serially at 7-9 AM (morning), 7-9 PM (evening), 11 PM-1 AM (night), and at 5-7 AM (awakening). RESULTS: R-value measured by TEG was shorter during awakening hours than during the night and day hours (p < 0.05). There were no changes in platelet reactivity in response to arachidonic acid, adenosine diphosphate, and collagen between time points. Pulse pressure (PP) was highest during awakening hours (p < 0.05). CONCLUSION: Study findings provide a mechanistic explanation for increased thrombotic events observed in the early waking hours among diabetics with multiple cardiovascular risk factors. The role of chronotherapy in reducing coagulability and PP to improve clinical outcomes should be explored.

Probability Distribution of Pixel Intensities of EBT3 Films and its Application in the Correction of Uncertainty Budget.

BACKGROUND AND AIM: Modern radiotherapy modalities, such as Intensity-Modulated Radiotherapy and Volumetric Modulated Arc Therapy involve complex dose delivery. The dose delivery is complex as it involves beam modulation, hence, manual dose calculations for these techniques are not possible. Film dosimetry is commonly used method of dose verification for these modalities because of the advantages associated with it. The quantification of uncertainty associated with a film dosimetry system under clinical use becomes important for accurate dosimetry. The spread in the distribution of the pixel values (PV) of the irradiated film contributes to the uncertainty. The probability distribution (PD) of the PV was studied for the clinical photon beam energies of 6, 10, and 15 MV. METHODS AND MATERIALS: Gafchromic EBT3 film and EPSON 10000XL flatbed scanner were used for this purpose and using the resulting PD, the uncertainty budgets for these energies in the red, green and blue color channels were estimated. RESULTS: The PV of exposed films for the energies studied follows t-distribution, the sum of the squares of the deviation of the measured data from the fitted value was of the order of 10-7, this indicates the goodness of fit. The "t" value corrected combined standard uncertainty (CSU) at 1σ confidence level for exposed film and dose measurement at 200 cGy were 1.42%, 1.48%, and 1.63% and 1.99%, 3.23%, and 5.08% for 6, 10, and 15 MV energies, respectively, in the red colour channel. CONCLUSION: In the case of the limited number of measurements of a quantity, the SU values must be corrected using the "t" value to get the correct CSU.

Venous Thromboembolism Prophylaxis: Need for Continuous Assessment Due to Changes in Risk During the Same Hospitalization.

OBJECTIVE: To explore the role of venous thromboembolism (VTE) risk reassessment in hospitalized medically ill patients without a change in level of care. PATIENTS AND METHODS: In this exploratory retrospective study, the medical records of 171 consecutive adult patients (≥18 years) hospitalized under the medicine service for more than 3 days without a change in the level of care from January 1, 2015, to March 1, 2015, were reviewed. The primary outcome was a change in the risk score between day 1 and day 3 of hospital stay (using the Padua Prediction Score). The secondary outcomes were changes in risk stratification class (low vs high) and cost-benefit analysis. RESULTS: The risk score was significantly different between day 1 and day 3 (4.7±1.7 vs 4.2±1.8; P=.008). All the patients with low risk on day 1 remained at low risk on day 3. However, 25 of 136 patients (18.4%) with high risk on day 1 were reclassified as low risk on day 3 (P<.001). No patients changed from low risk to high risk at day 3. The reclassification could have saved $35 per patient-day of inappropriate pharmacological prophylaxis in addition to patient discomfort, bleeding risk, and heparin-induced thrombocytopenia. CONCLUSION: This is the first study to suggest the need for regular assessment for VTE risk on medicine wards because of changing patient risk. Regular reassessment could reduce health care waste and patient discomfort.

Thirty-day readmissions after cardiac implantable electronic devices in the United States: Insights from the Nationwide Readmissions Database.

BACKGROUND: Limited data are available regarding true estimates of individual complications contributing to readmissions after cardiac implantable electronic device (CIED) implantation. OBJECTIVE: The purpose of this study was to identify predictors of 30-day readmission in patients admitted for CIED implantation. METHODS: The study cohort consisted of patients who underwent CIED implantation in 2014, identified from the National Readmission Database. Readmission was defined as a subsequent hospital admission within 30 days after the discharge day of index admission. If patients had more than 1 readmission within 30 days, only the first readmission was included. RESULTS: Our final cohort consisted of 70,223 cases, 61,738 (88%) in the no-readmission group and 8485 patients (12%) in the readmission group. Female gender (odds ratio [OR] 1.09; 95% confidence interval [CI] 1.04-1.14; P = .001), atrial fibrillation/flutter (OR 1.23; 95% CI 1.17-1.29, P <.001), acute renal failure (OR 1.65; 95% CI 1.56-1.74; P <.001), coronary artery disease (OR 1.09; 95% CI 1.03-1.14; P = .002), length of stay (OR 1.70; 95% CI 1.51-1.89; P <.001), device placement on the day of admission (OR 0.87; 95% CI 0.80-0.95, P = .001), and fourth quartile of hospital procedure volume (OR 0.91; 95% CI 0.84-0.99; P = .03; first quartile of hospital procedure volume as reference) were independent predictors of 30-day readmissions. The 30-day readmission resulted in additional median charges of $30,692 per patient. Device-related complications were seen in 10.7% of readmitted patients. The most common complications were mechanical (2.8%) and infectious (2.6%). CONCLUSION: Several patient and hospital-related factors were identified to be independent predictors of 30-day readmission, accounting for increased health care cost.