Antiinflammatory Therapy with Canakinumab for Atherosclerotic Disease

Background: Experimental and clinical data suggest that reducing inflammation without affecting lipid levels may reduce the risk of cardiovascular disease. Yet, the inflammatory hypothesis of atherothrombosis has remained unproved. Methods: We conducted a randomized, double-blind trial of canakinumab, a therapeutic monoclonal antibody targeting interleukin-1β, involving 10,061 patients with previous myocardial infarction and a high-sensitivity C-reactive protein level of 2 mg or more per liter. The trial compared three doses of canakinumab (50 mg, 150 mg, and 300 mg, administered subcutaneously every 3 months) with placebo. The primary efficacy end point was nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. RESULTS: At 48 months, the median reduction from baseline in the high-sensitivity C-reactive protein level was 26 percentage points greater in the group that received the 50-mg dose of canakinumab, 37 percentage points greater in the 150-mg group, and 41 percentage points greater in the 300-mg group than in the placebo group. Canakinumab did not reduce lipid levels from baseline. At a median follow-up of 3.7 years, the incidence rate for the primary end point was 4.50 events per 100 person-years in the placebo group, 4.11 events per 100 person-years in the 50-mg group, 3.86 events per 100 person-years in the 150-mg group, and 3.90 events per 100 person-years in the 300-mg group. The hazard ratios as compared with placebo were as follows: in the 50-mg group, 0.93 (95% confidence interval [CI], 0.80 to 1.07; P = 0.30); in the 150-mg group, 0.85 (95% CI, 0.74 to 0.98; P = 0.021); and in the 300-mg group, 0.86 (95% CI, 0.75 to 0.99; P = 0.031). The 150-mg dose, but not the other doses, met the prespecified multiplicity-adjusted threshold for statistical significance for the primary end point and the secondary end point that additionally included hospitalization for unstable angina that led to urgent revascularization (hazard ratio vs. placebo, 0.83; 95% CI, 0.73 to 0.95; P = 0.005). Canakinumab was associated with a higher incidence of fatal infection than was placebo. There was no significant difference in all-cause mortality (hazard ratio for all canakinumab doses vs. placebo, 0.94; 95% CI, 0.83 to 1.06; P = 0.31). Conclusions: Antiinflammatory therapy targeting the interleukin-1β innate immunity pathway with canakinumab at a dose of 150 mg every 3 months led to a significantly lower rate of recurrent cardiovascular events than placebo, independent of lipid-level lowering. (Funded by Novartis; CANTOS ClinicalTrials.gov number, NCT01327846.

Endogenous Regional Agricultural Production Technologies

Technical relationships between six productive factors for ten agricultural production regions in the continental United States are examined. The applied methodology provides a departure from conventional production methodologies contained in the literature by allowing aggregate technical relationships to be endogenized within the economic system

ENDOGENOUS REGIONAL AGRICULTURAL PRODUCTION TECHNOLOGIES

This research ·examines and compares estimates of technical bias for each of ten multistate farm production regions comprising the contiguous 48 states of the United States. The applied methodology allows for price-dependent aggregate technical choice and stochastic variation of the production technology in computing measures of technical bias

Health Care Pricing Strategies: A Case Study of Orthopedics in Utah

This paper attempts to evaluate the underlying the economic incentives for different health care pricing schemes currently utilized in U.S. and Canadian health care. The paper motivates the idea that medical providers have strong economic incentives to introduce new technology and undertake invasive surgical procedures as often as possible, as opposed to treating patients conservatively. The specific case of orthopedics in the state of Utah is studied. A supply side model of physician behavior is used to study the evolution of reimbursement levels from payers per surgical procedure. The results suggest that physicians have acted strategically by presenting more procedures to payers as the reimbursement level per procedure have dropped over time. Also, traditional health insurance has been unsuccessful in limiting the growth in health care costs while capitation may lead to the undertreatment of patients who may require invasive surgical care. The authors advance the idea that invasive surgical care. The authors advance the idea that invasive surgical care can be more efficiently organized into episodes of care by controlling health care expenditure levels while providing adequate surgical care