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Purpose: It is currently unknown whether the age of wheel exposure influences running wheel activity in mice. The purpose of this study was to determine whether the age at which a running wheel was introduced affected running wheel activity for a subsequent 15-wk period. Methods: Twenty female C57B1/6J mice (age 7 wk) were assigned to one of four experimental groups. Group 1 received a running wheel at 7 wk of age. Thereafter, groups 2, 3, and 4 received running wheels at 10, 13, and 16 wk of age, respectively. Daily running wheel activity (duration, distance, and velocity) was recorded from the time of running wheel exposure until 30 wk of age. Results: A repeated-measures MANOVA found significant differences between groups for distance (P = 0.02), duration (P = 0.04), and velocity (P = 0.001) during the 15-wk concurrent running period (age 16-30 wk). Post hoc tests revealed significantly greater distance and duration in group 4 compared with group 2 and significantly greater velocity in group 4 compared with each of the other groups. Significant interactions were found between groups over time for distance (P = 0.01) and duration (P = 0.05). No significant difference between groups was observed for body weight over the 24-wk period (P> 0.05). Conclusion: Although differences were found between groups 2 and 4, these data suggest that the age at which physical activity is introduced has little influence on the subsequent level of physical activity in C57B1/6J mice. However, it appears that introduction of the running wheel at 16 wk of age results in greater within group variance, suggestive of a greater environmental influence on daily running wheel activity. [ABSTRACT FROM AUTHOR]

Background: In 2006, the authors observed a cluster of three deaths, which circumstances suggested were opioid-related, within 1 day after placement of intrathecal opioid pumps for noncancer pain. Further investigation suggested that mortality among such patients was higher than previously appreciated. The authors performed investigations to quantify that mortality and compare the results to control populations, including spinal cord stimulation and low back surgery., Methods: After analyzing nine index cases--three sentinel cases and six identified by a prospective strategy--the authors used epidemiological methods to investigate whether mortality rates reflected patient- or therapy-related differences. Mortality rates after intrathecal opioid therapy and spinal cord stimulation were derived by correlating Medtronic device registration data with de-identified data from the Social Security Death Master File. Aggregate demographic and comorbidity data were obtained from Medicare and United Healthcare population databases to examine the influence of demographics and comorbidities on mortality., Results: Device registration and Social Security analyses revealed an intrathecal opioid therapy mortality rate of 0.088% at 3 days after implantation, 0.39% at 1 month, and 3.89% at 1 yr-a higher mortality than after spinal cord stimulation implants or after lumbar diskectomy in community hospitals. Demographic, illness profile, and mortality analyses of large databases suggest, despite limitations, that excess mortality was related to intrathecal opioid therapy, and could not be fully explained by other factors. These findings were consistent with the nine index cases that revealed that respiratory arrest caused or contributed to death in all patients. No device malfunctions associated with overinfusion were identified among cases where data were available., Conclusions: Patients with noncancer pain treated with intrathecal opioid therapy experience increased mortality compared to similar patients treated by using other therapies. Respiratory depression as a consequence of intrathecal drug overdosage or mixed intrathecal and systemic drug interactions is one plausible, but hypothetical mechanism. The exact causes for patient deaths and the proportion of those deaths attributable to intrathecal opioid therapy remain to be determined. These findings, although based on incomplete information, suggest that it may be possible to reduce mortality in noncancer intrathecal opioid therapy patients.