Citations

Venous thromboembolism (VTE), encompassing pulmonary embolism (PE) and deep venous thrombosis (DVT), is a major cause of morbidity and mortality of particular relevance for intensivists and hospitalists. Acute VTE is usually managed with parenteral unfractionated heparin or low-molecular-weight heparin, followed by an oral vitamin K antagonist. Data are lacking for optimal treatment of less common occurrences, such as upper extremity DVT, and for approaches such as thrombolysis for PE associated with early signs of hemodynamic compromise or inferior vena cava filters when anticoagulation is contraindicated. Direct oral anticoagulants (DOACs) including apixaban, dabigatran, edoxaban, and rivaroxaban are now added to the armamentarium of agents available for acute management of VTE and/or reducing the risk of recurrence. This review outlines an algorithmic approach to acute VTE treatment: from aggressive therapies when anticoagulation may be inadequate, to alternative choices when anticoagulation is contraindicated, to anticoagulant options in the majority of patients in whom anticoagulation is appropriate. Evidence-based guidelines and the most recent DOAC clinical trial data are discussed in the context of the standard of care. Situations and treatment approaches for which data are unavailable or insufficient are identified. VTE therapy in care transitions is discussed, as are choices for secondary prevention.

Abstract Identifying genetic variants with pleiotropic associations can uncover common pathways influencing multiple cancers. We took a two-stage approach to conduct genome-wide association studies for lung, ovary, breast, prostate, and colorectal cancer from the GAME-ON/GECCO Network (61,851 cases, 61,820 controls) to identify pleiotropic loci. Findings were replicated in independent association studies (55,789 cases, 330,490 controls). We identified a novel pleiotropic association at 1q22 involving breast and lung squamous cell carcinoma, with eQTL analysis showing an association with ADAM15/THBS3 gene expression in lung. We also identified a known breast cancer locus CASP8/ALS2CR12 associated with prostate cancer, a known cancer locus at CDKN2B-AS1 with different variants associated with lung adenocarcinoma and prostate cancer, and confirmed the associations of a breast BRCA2 locus with lung and serous ovarian cancer. This is the largest study to date examining pleiotropy across multiple cancer-associated loci, identifying common mechanisms of cancer development and progression. Cancer Res; 76(17); 5103–14. ©2016 AACR.

Abstract BACKGROUND We assessed the impact of clinical decision support (CDS) rules within the electronic health record for ionized calcium (iCa), serum magnesium (Mg), and N-terminal pro-B-type natriuretic peptide (NT-proBNP) in intensive care unit (ICU) inpatients at a large academic center. METHODS A repeat order for measurement of iCa or Mg placed within 24 (iCa) or 48 (Mg) h of a previously nonactionable result, or additional orders for NT-proBNP beyond 1 within a single hospitalization, triggered a CDS pop-up alert showing the prior result and offering the opportunity to cancel the order or to place the order after entering an indication for repeat testing. The number of tests performed for each of these analytes and incidence of adverse clinical outcomes potentially associated with hypocalcemia or hypomagnesemia were compared between the 90-day period before CDS implementation and two 90-day periods immediately following. RESULTS iCa test volumes decreased by 48%, Mg by 39%, and NT-proBNP by 28% in the 90-day period immediately following implementation and remained decreased by 54%, 49%, and 22%, respectively, during the following 90-day period (all P values <0.0002). Adverse clinical outcomes potentially associated with hypocalcemia or hypomagnesemia did not increase (all P-values >0.17). CONCLUSIONS Implementation of CDS dramatically decreased repeat testing of iCa, Mg, and NT-proBNP without adversely impacting clinical outcomes in the ICU. Expansion of the rules from the ICU units to include the entire hospitalized patient population and expansion to additional analytes is expected to lead to further reductions in testing.

Abstract Background: Many epithelial ovarian cancer (EOC) risk factors relate to hormone exposure and elevated estrogen levels are associated with obesity in postmenopausal women. Therefore, we hypothesized that gene–environment interactions related to hormone-related risk factors could differ between obese and non-obese women. Methods: We considered interactions between 11,441 SNPs within 80 candidate genes related to hormone biosynthesis and metabolism and insulin-like growth factors with six hormone-related factors (oral contraceptive use, parity, endometriosis, tubal ligation, hormone replacement therapy, and estrogen use) and assessed whether these interactions differed between obese and non-obese women. Interactions were assessed using logistic regression models and data from 14 case–control studies (6,247 cases; 10,379 controls). Histotype-specific analyses were also completed. Results: SNPs in the following candidate genes showed notable interaction: IGF1R (rs41497346, estrogen plus progesterone hormone therapy, histology = all, P = 4.9 × 10−6) and ESR1 (rs12661437, endometriosis, histology = all, P = 1.5 × 10−5). The most notable obesity–gene–hormone risk factor interaction was within INSR (rs113759408, parity, histology = endometrioid, P = 8.8 × 10−6). Conclusions: We have demonstrated the feasibility of assessing multifactor interactions in large genetic epidemiology studies. Follow-up studies are necessary to assess the robustness of our findings for ESR1, CYP11A1, IGF1R, CYP11B1, INSR, and IGFBP2. Future work is needed to develop powerful statistical methods able to detect these complex interactions. Impact: Assessment of multifactor interaction is feasible, and, here, suggests that the relationship between genetic variants within candidate genes and hormone-related risk factors may vary EOC susceptibility. Cancer Epidemiol Biomarkers Prev; 25(5); 780–90. ©2016 AACR.

Background: Hospitals’ risk-standardized mortality rates and outlier status (significantly higher/lower rates) are reported by the Centers for Medicare and Medicaid Services (CMS) for acute myocardial infarction (AMI) patients using Medicare claims data. New York now has AMI claims data with blood pressure and heart rate added. Objective: The objective of this study was to see whether the appended database yields different hospital assessments than standard claims data. Methods: New York State clinically appended claims data for AMI were used to create 2 different risk models based on CMS methods: 1 with and 1 without the added clinical data. Model discrimination was compared, and differences between the models in hospital outlier status and tertile status were examined. Results: Mean arterial pressure and heart rate were both significant predictors of mortality in the clinically appended model. The C statistic for the model with the clinical variables added was significantly higher (0.803 vs. 0.773, P<0.001). The model without clinical variables identified 10 low outliers and all of them were percutaneous coronary intervention hospitals. When clinical variables were included in the model, only 6 of those 10 hospitals were low outliers, but there were 2 new low outliers. The model without clinical variables had only 3 high outliers, and the model with clinical variables included identified 2 new high outliers. Conclusion: Appending even a small number of clinical data elements to administrative data resulted in a difference in the assessment of hospital mortality outliers for AMI. The strategy of adding limited but important clinical data elements to administrative datasets should be considered when evaluating hospital quality for procedures and other medical conditions.

SummaryObjectivePolycystic ovarian syndrome (PCOS) is estimated to affect up to 20% of women. PCOS is associated with insulin resistance and cardiovascular (CV) risk factors. We aimed to evaluate the impact of race/ethnicity on the prevalence of CV risk factors and subclinical predictors of CV events.DesignCross‐sectional analysis of data collected by the Dallas Heart Study, an urban, population‐based cohort oversampled for blacks.PatientsA previously described cohort of women with PCOS and control subjects of the same racial/ethnic group, matched for age and body mass index.MeasurementsHormonal and clinical measures associated with PCOS and CV risk factors.ResultsThe study included 117 women with PCOS and 204 controls. Women with PCOS had significant differences across racial/ethnic groups in the prevalence of hypertension, hypercholesterolaemia, hypertriglyceridaemia and impaired fasting glucose (P < 0·05). Controls showed significant racial/ethnic differences in the prevalence of hypertension and impaired fasting glucose (P < 0·05). The odds of hypertension were significantly greater among women with PCOS than controls after adjusting for race/ethnicity (odds ratio, 1·50 [95% CI, 1·03–2·30]; P = 0·04). However, we did not see an interaction of race/ethnicity that significantly changed CV risk factor prevalence between PCOS and controls. In addition, subclinical measures of CV disease were not different between women with PCOS vs controls, even among hypertensive women.ConclusionsRace/ethnicity affects the prevalence of CV risk factors for women with and without PCOS. However, race/ethnicity does not interact with PCOS to additionally increase CV risk factor prevalence or subclinical CV disease.

Abstract The progressive establishment of endovascular management in treating intracranial aneurysms had lead to continuous technique advancements and development of innovative technologies. Flow diverters are “stent-like” devices currently used for complex unruptured aneurysms allowing endoluminal reconstruction of the parent artery and occlusion of the aneurysm sac. In the present article, we review the development of flow diversion devices through in vitro and in vivo studies to clinical practice and summarize recent clinical data.

AbstractBackground: Hormonal and reproductive history has been associated with risk of some hematologic malignancies, but their role in myeloproliferative neoplasms (MPN) is largely unknown.Methods: Using a population-based cohort study, we evaluated the association of these factors with risk of MPN overall, and for essential thrombocythemia (ET) and polycythemia vera (PV) specifically. Incident MPN cases from 1993 to 2004 were identified via linkage to Medicare. RR and 95% confidence intervals (CI) were estimated utilizing Cox proportional hazard regression.Results: After &gt;250,000 person-years of follow-up, 257 cases of MPN were identified (172 ET, 64 PV). Ever use of hormone therapy (HT) was associated with an increased risk of ET (RR = 1.63; 95% CI, 1.19–2.23) but a decreased risk of PV (RR = 0.58; 95% CI, 0.34–0.98). There were no statistically significant associations of oral contraceptives or reproductive factors with MPN risk overall, or by MPN subtype. Bilateral oophorectomy was associated with increased risk of ET (RR = 1.58; 95% CI, 1.11–2.25) and decreased risk of PV (RR = 0.32; 95% CI, 0.12–0.88). There was no association of ovulatory years with ET risk; however, there was increased risk of PV (RR = 1.68 for &gt;36.8 compared with ≤27.6 years; P trend = 0.045). Adjustment for potential confounding factors did not alter these associations.Conclusions: HT use and bilateral oophorectomy had opposite associations for ET and PV. Except for ovulatory years and PV risk, reproductive history did not appear to play a role in the etiology of MPN.Impact: This study suggests different mechanistic impacts of estrogen, and perhaps distinct etiologies, for the two major MPN subtypes. Cancer Epidemiol Biomarkers Prev; 25(1); 151–7. ©2015 AACR.

Objective The objective of this study was to determine whether dynamic magnetic resonance imaging (dMRI) enhancement parameters could predict dopamine agonist (DA) resistance in prolactinomas. Methods We retrospectively identified patients with prolactinomas who were treated with DA and underwent dMRI from 2001 through 2012 at Mayo Clinic (Rochester, MN). Intensities of the adenoma and pituitary gland were measured by drawing regions of interest on the images. Enhancement ratio, enhancement peak, prepeak slope (PPS), and enhancement time were compared between DA-resistant and DA-responsive groups, between DA-treated and DA-naive groups, and between the first and follow-up dMRIs. Results We identified 49 patients with prolactinomas, with 6 (12.2%) showing DA resistance. Thirty-seven patients (75.5%) underwent dMRI while receiving treatment, 12 (25.5%) underwent dMRI before starting therapy, and 10 (20.4%) had follow-up dMRI after DA therapy. The PPS of the tumor was higher in the treatment-resistant group versus the responsive group (mean [SD], 4.42 [3.19] vs 2.65 [1.59]; P = 0.03), whereas no difference was noted in the pituitary gland (5.79 [2.21] vs 4.06 [2.48]; P = 0.11). Logistic regression analysis indicated that tumor PPS was associated with DA resistance (odds ratio, 1.71; 95% confidence interval, 1.07–3.27; P = 0.02). Conclusions Dynamic MRI with PPS analysis potentially can be used early in the treatment course to evaluate DA resistance in pituitary prolactinomas.

Objective The aim of this study was to determine if differences in coronary endothelial function are observed between asymptomatic women with type 2 diabetes mellitus (DM) and control subjects using coronary phase contrast flow velocity magnetic resonance imaging in response to cold pressor stress, an established endothelium-dependent vasodilatory stress. Methods Phase contrast flow velocity imaging of the right coronary artery was performed in 7 asymptomatic premenopausal women with DM and 8 healthy female participants in response to the cold pressor test at 3 T. Results There was no significant difference in percent increase in coronary flow velocity from rest to peak flow velocity between DM and control subjects (32% ± 22% vs 46% ± 17%; P = 0.11). However, percent increase in coronary flow velocity was lower in DM than in control subjects (−3% ± 14% vs 31% ± 30%; P = 0.01) during the second minute of cold pressor stress, when endothelial-mediated vasodilation should occur. Conclusions Asymptomatic women with DM demonstrate reduced coronary flow velocity during the second minute of cold pressor stress, indicating coronary endothelial dysfunction.