High-Sensitivity C Reactive Protein: Associations with Cardiovascular Risk Factors and Tracking in Female Adolescents and Young Adults

Objective. We assessed adolescent anthropometry, lipids, insulin, glucose, and blood pressures to identify factors associated with high-sensitivity C-reactive protein (hsCRP) and its tracking in young adults. Methods. Ten-year prospective study of 589 schoolgirls, 321 black, 268 white. Results. HsCRP did not differ (P > .08) by race or oral contraceptive use. HsCRP tracked from age 16 to 25 (r = 0.77), 16 to 26 (r = 0.50), 24 to 26 (r = 0.66), and 25 to 26 (r = 0.71), all P ≤ .02. By stepwise regression, at age 16, waist circumference accounted for 44.8% of hsCRP variance; BMI accounted for 33.1%, 34.4%, and 31.1% at ages 24, 25, and 26, P < .0001 for all. Changes in cholesterol and BMI were associated with change in hsCRP from age 24–26 (partial R2 = 12.3%  P < .0001, 6.6%  P = .0012). Changes in BMI and triglyceride (partial R2 = 8.5%  P = .0001, 3.3%, P = .0045) were associated with change in hsCRP from age 25 to 26. Conclusions. HsCRP tracks from age 16 to 26, with BMI, waist circumference, and cholesterol as major determinants

Alirocumab in high-risk patients: Observations from the open-label expanded use program

BACKGROUND: The alirocumab expanded use program provided open-label access to alirocumab before its commercial availability to patients with severe hypercholesterolemia not controlled with maximally tolerated doses of standard-of-care lipid-lowering therapy. OBJECTIVE: To describe the safety and lipid-lowering efficacy of alirocumab in high-risk patients who were likely to be early users of proprotein convertase subtilisin/kexin type 9 inhibitors after approval. METHODS: Patients with heterozygous familial hypercholesterolemia (HeFH) and/or coronary heart disease (CHD) and baseline low-density lipoprotein cholesterol (LDL-C) of ≥160 mg/dL on maximally tolerated lipid-lowering therapy were enrolled and received alirocumab 150 mg every 2 weeks for 24 weeks. Patients were permitted use of all available statins; those not taking any dose of statin could also be enrolled. RESULTS: Of 100 enrolled patients, 93 were white, 62 were women, and overall mean age was 58 years; 61 had HeFH, 3 had unknown type of familial hypercholesterolemia, 66 had CHD, and 30 had both familial hypercholesterolemia and CHD. Sixty-four patients were identified by their providers to have some level of statin intolerance; of these, 47 were not on statin. Alirocumab reduced LDL-C on average from 221 mg/dL at baseline to 102 mg/dL by week 24 (-55%). Treatment-emergent adverse events were experienced in 61% of patients and treatment-emergent adverse events leading to permanent treatment discontinuation in 3% of patients; no deaths occurred. CONCLUSIONS: Safety and efficacy observations from the open-label alirocumab expanded use program of very high-risk patients with HeFH and/or CHD and baseline LDL-C of ≥160 mg/dL uncontrolled by maximally tolerated lipid-lowering therapy were consistent with those in the placebo/ezetimibe-controlled ODYSSEY trials

Empirical Legal Studies Before 1940: A Bibliographic Essay

The modern empirical legal studies movement has well-known antecedents in the law and society and law and economics traditions of the latter half of the 20th century. Less well known is the body of empirical research on legal phenomena from the period prior to World War II. This paper is an extensive bibliographic essay that surveys the English language empirical legal research from approximately 1940 and earlier. The essay is arranged around the themes in the research: criminal justice, civil justice (general studies of civil litigation, auto accident litigation and compensation, divorce, small claims, jurisdiction and procedure, civil juries), debt and bankruptcy, banking, appellate courts, legal needs, legal profession (including legal education), and judicial staffing and selection. Accompanying the essay is an extensive bibliography of research articles, books, and reports

Testosterone Therapy, Thrombophilia, Venous Thromboembolism, and Thrombotic Events

In our sequential studies of 67 and 21 patients, testosterone therapy (TT) interacted with thrombophilia&ndash;hypofibrinolysis, leading to venous thromboembolism (VTE). Compared to 111 VTE controls not taking TT (VTE-no TT), the 67 and 21 cases were more likely (p &lt; 0.05 for all) to have Factor V Leiden (FVL) heterogeneity (24% and 33% vs. 12%), the lupus anticoagulant (14% and 33% vs. 4%), and high lipoprotein(a) (33% vs. 13%, n = 21). After a first VTE and continuing TT, 11 thrombophilic cases had a second VTE despite adequate anticoagulation, 6 of whom, still anticoagulated, had a third VTE. The greatest density of thrombotic events was at three months after starting TT, with a rapid decline by 10 months. From &lt;1 to 8 months after starting TT, 65% of VTE occurred, which may reflect TT-induced depletion of susceptible thrombophilic patients, leaving a winnowed residual group with fewer VTE events despite the continuation of TT. Before starting TT, we suggest screening for FVL, lipoprotein(a), and the lupus anticoagulant to identify patients at increased VTE risk, with an adverse risk-to-benefit ratio for TT. We suggest that TT should not be started in patients with known thrombophilia&ndash;hypofibrinolysis, and should not be continued after a first VTE. When TT is given to patients with thrombophilia&ndash;hypofibrinolysis, VTE may occur and then recur despite adequate anticoagulation

Amaurosis fugax caused by heritable thrombophilia-hypofibrinolysis in cases without carotid atherosclerosis: thromboprophylaxis prevents subsequent transient monocular partial blindness

Nineteen patients (age 60 +/- 14) with amaurosis fugax associated with heritable thrombophilia-hypofibrinolysis without ipsilateral atherosclerotic carotid plaque or other causes of amaurosis fugax were studied. Our hypothesis was that case-specific thromboprophylaxis would prevent subsequent amaurosis fugax episodes. Prospective treatment data were available for 13 cases. Thrombophilic disorders included high Factors VIII and XI, G20210A prothrombin heterozygosity, low proteins C and S, MTHFR mutations, and the PL A1/A2 mutation. Hypofibrinolytic disorders included plasminogen activator inhibitor-1 4G4G, and high lipoprotein (a). Treatments included Coumadin; Lovenox, folic acid-vitamin B6-vitamin B12, discontinuation of estrogens-selective estrogen receptor modulators, Glucophage, and aspirin, as appropriate. Usually within 1 month on therapy, patients became asymptomatic and have remained asymptomatic for \u3e or = 1 year on therapy, without adverse treatment side effects. When amaurosis fugax occurs without carotid artery atherosclerosis or other known causes, thrombophilia or hypofibrinolysis, or both are nearly universal, safely treatable, reversible pathoetiologies