Search

Abstract —The plethora of failed clinical trials with neuroprotective drugs for acute ischemic stroke have raised justifiable concerns about how best to proceed for the future development of such interventions. Preclinical testing of neuroprotective drugs is an important aspect of assessing their therapeutic potential, but guidelines concerning how to perform preclinical development of purported neuroprotective drugs for acute ischemic stroke are lacking. This conference of academicians and industry representatives was convened to suggest such guidelines for the preclinical evaluation of neuroprotective drugs and to recommend to potential clinical investigators the data they should review to reassure themselves that a particular neuroprotective drug has a reasonable chance to succeed in an appropriately designed clinical trial. Without rigorous, robust, and detailed preclinical evaluation, it is unlikely that novel neuroprotective drugs will prove to be effective when tested in large, time-consuming, and expensive clinical trials. Additionally, similar recommendations are provided for drugs with the potential to enhance recovery after acute ischemic stroke, a burgeoning new field with great potential but little currently available data. The suggestions contained in this document are meant to serve as overall guidelines that must be adapted to the individual characteristics related to particular drugs and their preclinical and clinical development needs.

Current use of oral contraceptives among 71 women aged 17 to 45 diagnosed for the first time as having definite or probable rheumatoid arthritis at Group Health Cooperative of Puget Sound was compared with oral contraceptive use among matched controls. Twenty-three percent of cases and 13% of controls were current users of oral contraceptives at the index date (relative risk estimate = 2.0, 95% CI = 0.97-4.21). We conclude that current oral contraceptive use was not protective against the development of rheumatoid arthritis in this population.A possible association between oral contraceptive (OC) use and rheumatoid arthritis was investigated in the 71 women aged 17-45 years of age enrolled at Washington's Group Health Cooperative who were newly diagnosed with this condition in the period 1977-86. 280 matched controls were randomly selected for the Cooperative's file of pharmacy users. Among women with rheumatoid arthritis, 16 (23%) were current OC users, 10 (14%) were past users, and 45 (63%) were never-users. Among controls, 37 (13%) were current users, 44 (16%) were past users, and 203 (71%) were never-users. The relative risk of rheumatoid arthritis was 2.0 (95% confidence interval, 0.97-4.2) in current OC users compared with never-users. The relative risk for past use compared with never-use was 1.0 (0.4-2.2). The duration of OC use or the OC's estrogen content did not have a significant impact on the risk of rheumatoid arthritis. These findings suggest that there is no association between OC use and rheumatoid arthritis and contradict earlier studies that found OC use to exert a protective effect on the development of rheumatoid arthritis. The only factor identified as predictive of a new diagnosis of rheumatoid arthritis was pregnancy completion within the past 24 months (relative risk, 4.1; 95% confidence interval, 1.5-11.2).