Transdermal buprenorphine and fentanyl patches in cancer pain: a network systematic review.

Treatment of cancer pain is generally based on the three-step World Health Organization (WHO) pain relief ladder, which utilizes a sequential approach with drugs of increasing potency. Goals of pain management include optimization of analgesia, optimization of activities of daily living, minimization of adverse effects, and avoidance of aberrant drug taking. In addition, it is recommended that analgesic regimens are individualized and simplified to help ensure patient compliance and should provide the least invasive, easiest, and safest route of opioid administration to ensure adequate analgesia. Buprenorphine and fentanyl are two opioids available for the relief of moderate-to-severe cancer pain. Available clinical data regarding the transdermal (TD) formulations of these opioids and the extent to which they fulfill the recommendations mentioned earlier are systematically reviewed, with the aim of providing additional information for oncologists and pain specialists regarding their comparative use. Due to lack of studies directly comparing TD buprenorphine with TD fentanyl, data comparing these with other step-3 opioids are also evaluated in a network fashion.

Somatic cell mutations at the glycophorin a locus in erythrocytes of radiation workers from the Sellafield nuclear facility.

The glycophorin A (GPA) somatic mutation assay for N0 and NN mutant erythrocytes was performed on 245 current and 48 retired workers who had been occupationally exposed to radiation at the British Nuclear Fuels plc facility at Sellafield. A positive association with increasing age was found for current workers for both N0 and NN frequencies of 0.14 +/- 0.05 x 10(-6) (P = 0.012) and 0.25 +/- 0.07 x 10(-6) (P = 0.0003) per year, respectively. No association with age was found for the retired workers. In a comparison of ever-smokers with never-smokers, no difference was observed for N0 frequencies for current workers, but a significantly higher frequency was found for ever-smokers in the retired group (P = 0.001). NN mutant frequencies were slightly higher in ever-smokers than in never-smokers for both current and retired workers, but in neither case was the increase significant. In age-adjusted analyses for N0 mutant frequencies, a slight positive radiation dose response was found for current workers (1.6 +/- 3.8 x 10(-6) per Sv), for retired workers (2.9 +/- 2.5 x 10(-6) per Sv), and in the combined analysis (2.6 +/- 2.2 x 10(-6) per Sv), but in no case did this reach significance. Similar analyses for NN mutant frequencies revealed a positive dose response for current workers (4.7 +/- 4.6 x 10(-6) per Sv) and a negative response for retired workers (-2.4 +/- 3.6 x 10(-6) per Sv) that was maintained in the combined analysis (-1.4 +/- 2.8 x 10(-6) per Sv), but none of these slopes was significantly different from zero. The results suggest that the GPA mutation assay is insufficiently sensitive to be used as a biological marker of low-dose chronic exposure and provide further evidence that, in contrast to high acute radiation exposure, protracted exposure is much less effective at inducing somatic mutations in vivo.