Improving risk stratification among veterans diagnosed with prostate cancer: impact of the 17-gene prostate score assay.

BACKGROUND: Active surveillance (AS) has been widely implemented within Veterans Affairs' medical centers (VAMCs) as a standard of care for low-risk prostate cancer (PCa). Patient characteristics such as age, race, and Agent Orange (AO) exposure may influence advisability of AS in veterans. The 17-gene assay may improve risk stratification and management selection. OBJECTIVES: To compare management strategies for PCa at 6 VAMCs before and after introduction of the Oncotype DX Genomic Prostate Score (GPS) assay. STUDY DESIGN: We reviewed records of patients diagnosed with PCa between 2013 and 2014 to identify management patterns in an untested cohort. From 2015 to 2016, these patients received GPS testing in a prospective study. Charts from 6 months post biopsy were reviewed for both cohorts to compare management received in the untested and tested cohorts. SUBJECTS: Men who just received their diagnosis and have National Comprehensive Cancer Network (NCCN) very low-, low-, and select cases of intermediate-risk PCa. RESULTS: Patient characteristics were generally similar in the untested and tested cohorts. AS utilization was 12% higher in the tested cohort compared with the untested cohort. In men younger than 60 years, utilization of AS in tested men was 33% higher than in untested men. AS in tested men was higher across all NCCN risk groups and races, particular in low-risk men (72% vs 90% for untested vs tested, respectively). Tested veterans exposed to AO received less AS than untested veterans. Tested nonexposed veterans received 19% more AS than untested veterans. Median GPS results did not significantly differ as a factor of race or AO exposure. CONCLUSIONS: Men who receive GPS testing are more likely to utilize AS within the year post diagnosis, regardless of age, race, and NCCN risk group. Median GPS was similar across racial groups and AO exposure groups, suggesting similar biology across these groups. The GPS assay may be a useful tool to refine risk assessment of PCa and increase rates of AS among clinically and biologically low-risk patients, which is in line with guideline-based care.

Development of a new risk score for hospital-associated venous thromboembolism in critically-ill children not undergoing cardiothoracic surgery.

BACKGROUND: Although risk of hospital-associated venous thromboembolism (HA-VTE) differs between critically and non-critically ill children, studies to date have not led to distinct, pragmatic risk scores. OBJECTIVE: To determine risk factors for HA-VTE in critically ill children not undergoing cardiothoracic surgery, in order to derive a novel HA-VTE risk score for this population. METHODS: We conducted a retrospective analysis from January 2006 through April 2013 at All Children's Hospital Johns Hopkins Medicine. HA-VTE cases were identified using ICD-9 discharge diagnosis codes, with subsequent validation via radiologic record review. Cases were restricted to Pediatric Intensive Care Unit (PICU) admissions. Patients who underwent cardiothoracic surgery were excluded; cardiac catheterization per se was not exclusionary. For each case, three non-HA-VTE PICU controls were randomly selected. Data were abstracted on putative risk factors, and associations between risk factors and HA-VTE were estimated using odds ratios (ORs) and 95% confidence intervals (95%CIs). RESULTS: There were 57 HA-VTE cases and 171 controls. HA-VTE occurrence was 3 per 1000 PICU admissions (0.3%). Central venous catheter (CVC) (OR:26.64; 95%CI:7.46-95.13), length of stay (LOS) ≥4days (OR:20.22; 95%CI:2.27-180.07), and significant infection (OR:3.41; 95%CI:1.13-10.29) were independent, statistically-significant risk factors for HA-VTE in a multivariate model. A risk score was derived in which HA-VTE risk exceeded 2% (threshold for anticoagulant thromboprophylaxis in hospitalized adults) with a score of 15, and was >1% but <2% (risk zone for mechanical thromboprophylaxis in hospitalized adults) with scores of 7-14. CONCLUSION: The presence of a CVC, LOS≥4days and infection are significant risk factors for HA-VTE in critically ill children not undergoing cardiothoracic surgery, forming the basis for a new risk score that warrants prospective validation.

Development of a new risk score for hospital-associated venous thromboembolism in noncritically ill children: findings from a large single-institutional case-control study.

OBJECTIVE: To determine risk factors for pediatric hospital-associated venous thromboembolism (HA-VTE) in noncritically ill children to derive a novel HA-VTE risk model for this population. STUDY DESIGN: Patients with HA-VTE were identified retrospectively via the electronic health record at All Children's Hospital Johns Hopkins Medicine from April 10, 2013 through January 1, 2006. Seven contemporaneous, noncritically ill control children were randomly selected for each case of HA-VTE. The association between putative risk factors and HA-VTE was estimated with ORs and 95% CIs, which were calculated using the Wald method. A P-value threshold ≤.2 was used in univariate analysis for inclusion into a multivariate (adjusted) model. RESULTS: Fifty cases of HA-VTE occurred in noncritically ill children. The presence of a central venous catheter (OR 27.67, 95% CI, 8.40-91.22), infection (OR 10.40, 95% CI, 3.46-31.25), and length of stay ≥4 days (OR 5.26, 95% CI, 1.74-15.88) were found to be statistically significant risk factors for HA-VTE. An 8-point risk score was derived in which scores of 8 points, 7 points, and ≤6 points corresponded to venous thromboembolism risks of 12.5%, 1.1%, and 0.1%, respectively. CONCLUSION: The presence of a central venous catheter, infection, and length of stay ≥4 days are significant risk factors for HA-VTE in noncritically ill children, forming the basis for a new risk score that could inform venous thromboembolism prophylaxis decision-making. These findings warrant prospective validation.

Risk factors for hospital-sssociated venous thromboembolism in the neonatal intensive care unit.

OBJECTIVE: To determine hospital-associated venous thromboembolism (HA-VTE) risk factors in critically ill neonates. METHODS: We conducted a case-control study in the neonatal intensive care unit (NICU) of All Children's Hospital Johns Hopkins Medicine (St. Petersburg, FL), from January 1, 2006 - April 10, 2013. We identified HA-VTE cases using electronic health record. Four NICU controls were randomly selected for each HA-VTE case. Associations between putative risk factors and HA-VTE were estimated using odds ratios (ORs) and ninety-five percent confidence intervals (95%CIs) from univariate and multivariate regression analyses. RESULTS: Twenty-three HA-VTE cases and 92 controls were included. The annual HA-VTE incidence was approximately 1.4 HA-VTE cases per 1,000 NICU admissions. In univariate analyses, mechanical ventilation (OR=7.27, 95%CI=2.02-26.17, P=0.002), central venous catheter (CVC; OR=52.95, 95%CI=6.80-412.71, P<0.001), infection (OR=7.24, 95%CI=2.66-19.72, P<0.001), major surgery (OR=5.60, 95%CI=1.82-17.22, P=0.003) and length of stay ≥15days (OR=6.67, 95%CI=1.85-23.99, P=0.004) were associated with HA-VTE. Only CVC (OR=29.04, 95%CI=3.18-265.26, P=0.003) remained an independent risk factor in the multivariate analysis. Based on this result, the estimated risk of HA-VTE in NICU patients with a CVC was 0.9%. CONCLUSION: This study identifies CVC as an independent risk factor for HA-VTE in critically ill neonates. However, the level of risk associated with CVC is below the conventional threshold for primary anticoagulation thromboprophylaxis. Larger studies are needed to substantiate these findings and identify novel putative risk factors to further distinguish NICU patients at highest HA-VTE risk.