A randomized, double-blind, double-dummy comparison of the efficacy and tolerability of low-dose transdermal buprenorphine (BuTrans seven-day patches) with buprenorphine sublingual tablets (Temgesic) in patients with osteoarthritis pain.

CONTEXT: Osteoarthritis (OA) is a common cause of chronic pain, particularly in the older population. Modern approaches to the management of OA pain recommend tailoring treatment to the individual. This study examines treatment options for OA pain in the form of low-dose transdermal and sublingual opioid analgesia. OBJECTIVES: The aims of this trial were to compare the efficacy and tolerability of seven-day, low-dose transdermal buprenorphine patches (BuTrans, Napp Pharmaceuticals Limited UK) with sublingual buprenorphine (Temgesic, Schering-Plough Limited UK) in patients with moderate to severe pain caused by OA of the hip(s) and/or knee(s), and to establish analgesic equivalence of the two products. METHODS: Two hundred forty-six patients with OA pain in the hip(s) and/or knee(s) were enrolled in this randomized, double-blind, parallel-group study; 110 completed the study. Patients were randomized to receive transdermal buprenorphine patches (5, 10, and 20 microg/hour) or sublingual buprenorphine (200 and 400 microg tablets). Their medication was titrated to pain control and they were treated for up to seven weeks. The main outcome measures were pain intensity (primary outcome), sleep disturbance, quality of life, and safety assessments. RESULTS: Patients' Box Scale-11 pain scores decreased between entry and assessment in both treatment groups. During the 28-day assessment period, the estimated mean treatment differences (95% confidence intervals) were 0.00 (-0.68,0.69), -0.11 (-0.85,0.63), and -0.13 (-0.95,0.68), for the morning, midday, and evening scores, respectively. All the confidence intervals were within the prespecified limits for equivalence (-1.5, 1.5). Use of escape medication was low. In both treatment groups, sleep disturbance caused by pain decreased between entry and assessment. Patients' quality of life improved during the study. Significantly fewer patients receiving the transdermal buprenorphine patches reported nausea (P=0.035), dizziness (P=0.026), and vomiting (P=0.039). CONCLUSION: In conclusion, seven-day, low-dose transdermal buprenorphine patches are as effective as sublingual buprenorphine, with a better tolerability profile.

Plasmodium falciparum infection of splenectomized and intact Guyanan Saimiri monkeys

Spleen-intact and splenectomized Saimiri monkeys of Guyanan origin were examined for their potential suitability for Plasmodium falciparum protection studies. The animal could be readily infected with adapted strains of P. falciparium (Indochina 1/CDC and Uganda Palo Alto FUP strains), but spontaneously recovered without drug treatment and without development of severe clinical disease. In intact animals, peak parasitemia prior to recovery generally ranged from 0.1 percent to 10 percent, whereas in splenectomized animals the peak parasitemia was generally higher so that some animals were given drug treatment to assist in recovery from infection. In reinfection studies, previously infected spleen-intact monkeys demonstrated sterile immunity to the homologous parasite strain but not to a heterologous strain. However, in monkeys infected with the heterologous strain, the peak parasitemia was less than in the first infection and of shorter duration. Splenectomized animals did not demonstrate sterile immunity although the peak parasitemia achieved was less than in the previous infection of each of these monkeys. While the lack of major clinical disease indicated that these monkeys did not provide a good animal model for human malaria, the development of protective immunity was consistent with a useful role in evaluating candidate vaccine antigens (AU)