Effect of Low-Intensity vs Standard-Intensity Warfarin Prophylaxis on Venous Thromboembolism or Death Among Patients Undergoing Hip or Knee Arthroplasty: A Randomized Clinical Trial.

Importance: The optimal international normalized ratio (INR) to prevent venous thromboembolism (VTE) in warfarin-treated patients with recent arthroplasty is unknown. Objective: To determine the safety and efficacy of a target INR of 1.8 vs 2.5 for VTE prophylaxis after orthopedic surgery. Design, Setting, and Participants: The randomized Genetic Informatics Trial (GIFT) of Warfarin to Prevent Deep Vein Thrombosis enrolled 1650 patients aged 65 years or older initiating warfarin for elective hip or knee arthroplasty at 6 US medical centers. Enrollment began in April 2011 and follow-up concluded in October 2016. Interventions: In a 2 × 2 factorial design, participants were randomized to a target INR of 1.8 (n = 823) or 2.5 (n = 827) and to either genotype-guided or clinically guided warfarin dosing. For the first 11 days of therapy, open-label warfarin dosing was guided by a web application. Main Outcomes and Measures: The primary outcome was the composite of VTE (within 60 days) or death (within 30 days). Participants underwent screening duplex ultrasound postoperatively. The hypothesis was that an INR target of 1.8 would be noninferior to an INR target of 2.5, using a noninferiority margin of 3% for the absolute risk of VTE. Secondary end points were bleeding and INR values of 4 or more. Results: Among 1650 patients who were randomized (mean age, 72.1 years; 1049 women [63.6%]; 1502 white [91.0%]), 1597 (96.8%) received at least 1 dose of warfarin and were included in the primary analysis. The rate of the primary composite outcome of VTE or death was 5.1% (41 of 804) in the low-intensity-warfarin group (INR target, 1.8) vs 3.8% (30 of 793) in the standard-treatment-warfarin group (INR target, 2.5), for a difference of 1.3% (1-sided 95% CI, -∞ to 3.05%, P = .06 for noninferiority). Major bleeding occurred in 0.4% of patients in the low-intensity group and 0.9% of patients in the standard-intensity group, for a difference of -0.5% (95% CI, -1.6% to 0.4%). The INR values of 4 or more occurred in 4.5% of patients in the low-intensity group and 12.2% of the standard-intensity group, for a difference of -7.8% (95% CI, -10.5% to -5.1%). Conclusions and Relevance: Among older patients undergoing hip or knee arthroplasty and receiving warfarin prophylaxis, an international normalized ratio goal of 1.8 compared with 2.5 did not meet the criterion for noninferiority for risk of the composite outcome of VTE or death. However, the trial may have been underpowered to meet this criterion and further research may be warranted. Trial Registration: ClinicalTrials.gov Identifier: NCT01006733.

The prevalence of congenital C1 arch anomalies.

PURPOSE: To determine the prevalence, radiographic features and reporting rate of, and the association between the congenital anterior and posterior C1 arch anomalies. METHODS: The computed tomography (CT) images of the cervical spines of all patients over 18 years who had CT examinations in our hospital during the study period were reviewed to evaluate for congenital anomalies of the anterior and posterior C1 arches. Radiology reports of the corresponding CT examinations were reviewed to determine the reporting rate of these defects. RESULTS: Of 3273 subjects, 185 (5.65%) had congenital atlas anomalies: 169 isolated posterior (5.16%), 15 combined anterior and posterior (bipartite, 0.46%), and one isolated anterior (0.031%) arch defects. Females had a higher prevalence than males (7.46 versus 4.72%, P = 0.0013). Eighty-three cases (44.9%) of C1 arch anomalies were not reported. The Currarino type A, B, C and E posterior arch defects accounted for 81.6, 8.1, 1.1, and 0.5% of all arch anomalies while type D was not observed. Fifteen patients (0.46%) had combined anterior and posterior arch anomalies (bipartite atlas) versus only one with an isolated anterior C1 defect, indicating a significant association between the anterior and posterior arch defects (P < 0.0001). CONCLUSIONS: Although some types of congenital C1 arch anomalies are rare, type A defects are relatively common radiological findings that are unreported approximately 45% of the time. Based on the significant association between the anterior and posterior arch defects, we propose possible mechanisms for the formation of the bipartite atlas.

Effect of Genotype-Guided Warfarin Dosing on Clinical Events and Anticoagulation Control Among Patients Undergoing Hip or Knee Arthroplasty: The GIFT Randomized Clinical Trial.

Importance: Warfarin use accounts for more medication-related emergency department visits among older patients than any other drug. Whether genotype-guided warfarin dosing can prevent these adverse events is unknown. Objective: To determine whether genotype-guided dosing improves the safety of warfarin initiation. Design, Setting, and Patients: The randomized clinical Genetic Informatics Trial (GIFT) of Warfarin to Prevent Deep Vein Thrombosis included patients aged 65 years or older initiating warfarin for elective hip or knee arthroplasty and was conducted at 6 US medical centers. Enrollment began in April 2011 and follow-up concluded in October 2016. Interventions: Patients were genotyped for the following polymorphisms: VKORC1-1639G>A, CYP2C9*2, CYP2C9*3, and CYP4F2 V433M. In a 2 × 2 factorial design, patients were randomized to genotype-guided (n = 831) or clinically guided (n = 819) warfarin dosing on days 1 through 11 of therapy and to a target international normalized ratio (INR) of either 1.8 or 2.5. The recommended doses of warfarin were open label, but the patients and clinicians were blinded to study group assignment. Main Outcomes and Measures: The primary end point was the composite of major bleeding, INR of 4 or greater, venous thromboembolism, or death. Patients underwent a screening lower-extremity duplex ultrasound approximately 1 month after arthroplasty. Results: Among 1650 randomized patients (mean age, 72.1 years [SD, 5.4 years]; 63.6% women; 91.0% white), 1597 (96.8%) received at least 1 dose of warfarin therapy and completed the trial (n = 808 in genotype-guided group vs n = 789 in clinically guided group). A total of 87 patients (10.8%) in the genotype-guided group vs 116 patients (14.7%) in the clinically guided warfarin dosing group met at least 1 of the end points (absolute difference, 3.9% [95% CI, 0.7%-7.2%], P = .02; relative rate [RR], 0.73 [95% CI, 0.56-0.95]). The numbers of individual events in the genotype-guided group vs the clinically guided group were 2 vs 8 for major bleeding (RR, 0.24; 95% CI, 0.05-1.15), 56 vs 77 for INR of 4 or greater (RR, 0.71; 95% CI, 0.51-0.99), 33 vs 38 for venous thromboembolism (RR, 0.85; 95% CI, 0.54-1.34), and there were no deaths. Conclusions and Relevance: Among patients undergoing elective hip or knee arthroplasty and treated with perioperative warfarin, genotype-guided warfarin dosing, compared with clinically guided dosing, reduced the combined risk of major bleeding, INR of 4 or greater, venous thromboembolism, or death. Further research is needed to determine the cost-effectiveness of personalized warfarin dosing. Trial Registration: clinicaltrials.gov Identifier: NCT01006733.

Myocardial ischaemia after hip and knee arthroplasty: incidence and risk factors.

PURPOSE: Because the occurrence of postoperative myocardial ischaemia (MI) predicts subsequent cardiac morbidity and mortality, we determined the prevalence of and risk factors for MI in hip and knee arthroplasty patients. METHODS: High-sensitivity cardiac troponin T (hs-cTnT) was measured on stored samples from postoperative day two in 394 hip and knee arthroplasty patients ≥ 65 years of age enrolled in the Genetics-InFormatics Trial (GIFT). RESULTS: Fifty-three (13.5 %) participants had MI, of whom only three were diagnosed clinically during their hospitalisation. The risk of MI increased with age [odds ratio (OR) 3.52 per decade, 95 % confidence interval (CI) 2.00-6.19] and diabetes (OR 2.23, 95 % CI 1.04-4.77). MI was rarer with statins (OR 0.74, 95 % CI 0.40-1.35) and more common with hypertension, coronary artery disease and tobacco use, although these were not statistically significant. CONCLUSIONS: Subclinical MI occurs frequently after arthroplasty. Diabetic and elderly patients are at highest risk.

A case series on the role of 18F-FDG PET/CT-guided biopsy of osseous metastases.

PURPOSE: This case series explores the utility of positron emission tomography (PET)/computed tomography (CT) guidance for biopsy of 18F-fludeoxyglucose (FDG)-avid osseous lesions that are inconspicuous on CT. METHODS: PET/CT-guided core biopsies were performed in four patients with suspected malignancies given 18F-FDG-avid osseous lesions that were inconspicuous on CT alone. The final diagnosis for each patient was determined by histopathological and molecular testing. RESULTS: PET/CT-guided biopsy yielded accurate sampling via core needle biopsy (CNB) with histopathological confirmation of osseous metastases of the primary malignancy as opposed to a secondary malignancy in three patients and ruled-out metastatic spread in the fourth. CONCLUSION: PET/CT-guided biopsy of hypermetabolic osseous lesions that are inconspicuous on CT alone is an effective and safe diagnostic tool in patients with suspected malignancy.

Trends in the Usage of Contrast Allergy Prophylaxis for Endourologic Procedures.

OBJECTIVE: To characterize current practice patterns of urologists in the management of intravenous (IV) contrast allergy in the setting of endourologic procedures. METHODS: A survey was administered to all members of the Endourological Society to assess management of IV contrast allergy prior to ureteroscopy (URS) and percutaneous nephrolithotomy (PCNL). Treatment regimens, reports of adverse outcomes, and demographics of respondents were also collected. Data were analyzed using chi-square tests. RESULTS: The response rate was 15% (325/2100). A total of 21% and 28% of respondents reported giving prophylaxis prior to URS and PCNL, respectively. Nearly 3% of respondents reported having observed a severe adverse reaction to intraluminal contrast in the past. Approximately half reported giving prophylaxis only 1 hour prior to the procedure. Most respondents (77%) completed a fellowship, the most common being endourology. Chi-square analysis revealed a significant difference between giving prophylaxis for URS or PCNL and the respective case volumes (for URS, X2 = 8.3, P= .004; for PCNL, X2 = 8.5, P= .003) where urologists with the lowest and highest case volumes were more likely to give prophylaxis (Fig. 1). There was no significant difference between giving prophylaxis for URS or PCNL and recency of residency, fellowship training, practice setting, or practice type. CONCLUSION: Most urologists do not give prophylaxis for patients with IV contrast allergy prior to URS and PCNL. Further studies are needed to evaluate the necessity of prophylaxis as well as to establish clear guidelines.