The Impact of Differential Cost Sharing of Non-Steroidal Anti-Inflammatory Agents on the Use and Costs of Analgesic Drugs

OBJECTIVE: To estimate the effect of differential cost sharing (DCS) schemes for non-steroidal anti-inflammatory drugs (NSAIDs) on drug subsidy program and beneficiary expenditures. DATA SOURCES/STUDY SETTING: Monthly aggregate claims data from Pharmacare, the public drug subsidy program for seniors in British Columbia, Canada over the period 1989-11 to 2001-06. STUDY DESIGN: DCS limits insurance reimbursement of a group of therapeutically similar drugs to the cost of the lowest priced drugs, with beneficiaries responsible for costs above the reimbursement limit. Pharmacare introduced two different forms of DCS, generic substitution (GS) and reference pricing (RP), in April 1994 and November 1995, respectively, to the NSAIDs. Under GS, generic and brand versions of the same NSAID are considered interchangeable, whereas under RP different NSAIDs are. We extrapolated average reimbursement per day of NSAID therapy over the months before GS and RP to estimate what expenditures would have been without the policies. These counterfactual predictions were compared to actual values to estimate the impact of the policies; the estimated impacts on reimbursement rates were multiplied by the post-policy volume of NSAIDS dispensed, which appeared unaffected by the policies, to estimate expenditure changes. DATA COLLECTION: The cleaned NSAID claims data, obtained from Pharmacare’s databases, were aggregated by month and by their reimbursement status under the GS and RP policies. PRINCIPAL FINDINGS: After RP, program expenditures declined by $22.7 million, or$4 million annually, cutting expenditure by half. Most savings accrued from the substitution of low cost NSAIDs for more costly alternatives. About 20% of savings represented expenditures by seniors who elected to pay for partially-reimbursed drugs. GS produced one quarter the savings of RP. CONCLUSIONS: RP of NSAIDs achieved its goal of reducing drug expenditures and was more effective than GS. The effects of RP on patient health and associated health care costs remain to be investigated.Reference pricing; generic substitution; prescription drugs; drug cost containment; NSAIDs.

Ebola Virus Localization in the Macaque Reproductive Tract during Acute Ebola Virus Disease.

Sexual transmission of Ebola virus (EBOV) has been demonstrated more than a year after recovery from the acute phase of Ebola virus disease (EVD). The mechanisms underlying EBOV persistence and sexual transmission are not currently understood. Using the acute macaque model of EVD, we hypothesized EBOV would infect the reproductive tissues and sought to localize the infection in these tissues using immunohistochemistry and transmission electron microscopy. In four female and eight male macaques that succumbed to EVD between 6 and 9 days after EBOV challenge, we demonstrate widespread EBOV infection of the interstitial tissues and endothelium in the ovary, uterus, testis, seminal vesicle, epididymis, and prostate gland, with minimal associated tissue immune response or organ pathology. Given the widespread involvement of EBOV in the reproductive tracts of both male and female macaques, it is reasonable to surmise that our understanding of the mechanisms underlying sexual transmission of EVD and persistence of EBOV in immune-privileged sites would be facilitated by the development of a nonhuman primate model in which the macaques survived past the acute stage into convalescence

Limited mantle hydration by bending faults at the Middle America Trench

Author Posting. © American Geophysical Union, 2021. This article is posted here by permission of American Geophysical Union for personal use, not for redistribution. The definitive version was published in Journal of Geophysical Research: Solid Earth 126(1),(2021): e2020JB020982, https://doi.org/10.1029/2020JB020982.Seismic anisotropy measurements show that upper mantle hydration at the Middle America Trench (MAT) is limited to serpentinization and/or water in fault zones, rather than distributed uniformly. Subduction of hydrated oceanic lithosphere recycles water back into the deep mantle, drives arc volcanism, and affects seismicity at subduction zones. Constraining the extent of upper mantle hydration is an important part of understanding many fundamental processes on Earth. Substantially reduced seismic velocities in tomography suggest that outer rise plate‐bending faults provide a pathway for seawater to rehydrate the slab mantle just prior to subduction. Estimates of outer‐rise hydration based on tomograms vary significantly, with some large enough to imply that, globally, subduction has consumed more than two oceans worth of water during the Phanerozoic. We found that, while the mean upper mantle wavespeed is reduced at the MAT outer rise, the amplitude and orientation of inherited anisotropy are preserved at depths >1 km below the Moho. At shallower depths, relict anisotropy is replaced by slowing in the fault‐normal direction. These observations are incompatible with pervasive hydration but consistent with models of wave propagation through serpentinized fault zones that thin to 1 km below Moho. Confining hydration to fault zones reduces water storage estimates for the MAT upper mantle from ∼3.5 wt% to <0.9 wt% H20. Since the intermediate thermal structure in the ∼24 Myr‐old MAT slab favors serpentinization, limited hydration suggests that fault mechanics are the limiting factor, not temperatures. Subducting mantle may be similarly dry globally.National Science Foundation. Grant Numbers: OCE-0625178, OCE-08410632021-06-1