The use of a binary chelate formulation: Could gadolinium based linear contrast agents be rescued by the addition of zinc selective chelates?

Tissue and bone retention of gadolinium based contrast agents (GBCAs) has become a clinical concern because of the potential short and long term toxic effects of free gadolinium. This is a critical problem for most open-chain agents that more readily transmetallate in vivo, in comparison to macrocyclic compounds. Gadolinium diethylene tri-aminepentaacetic acid bis-glucosamide (Gd-DTPA-BIGA) is an experimental, open-chain contrast agent which has a significantly increased relaxivity coefficient in comparison to other GBCAs. This results in greater signal intensity and improved contrast enhancement. These superior imaging qualities initiated a search for a solution to the transmetallation of this agent. Plasma zinc is a well-known GBCA transmettalation agent. Since the base chelate of Gadodiamide (Gd-DPTA-Bis-Methylamide or Omniscan), DTPA-Bis-Methylamide (DTPA-BMA), readily transmettalates with and binds serum zinc, we hypothesized that a plasma "zinc sink," may significantly reduce transmetallation of linear agents. 5% DTPA-BMA was added to a formulation of Gd-DTPA-BIGA, which was tested against the original formulation of Gd-DTPA-BIGA with 0.2% of the base chelate DTPA-BIGA. These formulations, including gadodiamide, were labeled with 153GdCl3 followed by infusion into cohorts of Sprague Dawley rats which were sacrificed at 1, 30 and 60 days. Internal organs were harvested, along with blood, skin and femur, and analyzed for residual gadolinium. A subset of tissues were also interrogated with ICP-MS. Labeled Gadodiamide and saline where used as controls. Conclusion: The addition of 5% DTPA-BMA, as a zinc binding agent, reduced the transmetallation of the linear agent Gd-DTPA-BIGA, in comparison to its original formulation supplemented with 0.2% BIGA. This result indicates that supplementing linear GBCAs with ancillary chelates may hold promise for reducing, or eliminating the biological archiving of gadolinium in tissues. In addition, this paper provides valuable animal data on the long term retention of gadolinium from linear based contrast agents.

Self-rated job performance and absenteeism according to employee engagement, health behaviors, and physical health.

OBJECTIVE: To better understand the combined influence of employee engagement, health behavior, and physical health on job performance and absenteeism. METHODS: Analyses were based on 20,114 employees who completed the Healthways Well-Being Assessment from 2008 to 2010. Employees represented three geographically dispersed companies in the United States. RESULTS: Employee engagement, health behavior, and physical health indices were simultaneously significantly associated with job performance and also with absenteeism. Employee engagement had a greater association with job performance than did the health behavior or physical health indices, whereas the physical health index was more strongly associated with absenteeism. Specific elements of the indices were evaluated for association with self-rated job performance and absenteeism. CONCLUSION: Efforts to improve worker productivity should take a holistic approach encompassing employee health improvement and engagement strategies.

A comparison of religious orientation and health between Whites and Hispanics.

The study of religious orientation thus far has neglected the influence of race/ethnicity as well as all four religious orientations (intrinsic, extrinsic, pro-religious and nonreligious) in explaining differences in both physical and psychological health. A representative sample of 250 Hispanics and 236 non-Hispanic Whites in Utah was drawn and analysed for differences in health (self-rated health, life satisfaction, exercise) according to race/ethnicity, religious orientation and religious attendance. Responses to the Religious Orientation Scale differed significantly by race/ethnicity, indicating that future studies of religious orientation should take cultural context into account. For both Whites and Hispanics, pro-religious individuals reported the highest life satisfaction scores, which highlight the utility of employing the fourfold religious orientation typology.

The Coronary Health Improvement Project (CHIP) for lowering weight and improving psychosocial health.

This study extends previous research evaluating the association between the CHIP intervention, change in body weight, and change in psychological health. A randomized controlled health intervention study lasting 4 wk. was used with 348 participants from metropolitan Rockford, Illinois; ages ranged from 24 to 81 yr. Participants were assessed at baseline, 6 wk., and 6 mo. The Beck Depression Inventory (BDI) and three selected psychosocial measures from the SF-36 Health Survey were used. Significantly greater decreases in Body Mass Index (BMI) occurred after 6 wk. and 6 mo. follow-up for the intervention group compared with the control group, with greater decreases for participants in the overweight and obese categories. Significantly greater improvements were observed in BDI scores, role-emotional and social functioning, and mental health throughout follow-up for the intervention group. The greater the decrease in BMI through 6 wk., the better the chance of improved BDI score, role-emotional score, social functioning score, and mental health score, with odds ratios of 1.3 to 1.9. Similar results occurred through 6 mo., except the mental health variable became nonsignificant. These results indicate that the CHIP intervention significantly improved psychological health for at least six months afterwards, in part through its influence on lowering BMI.

The diminishing role of transurethral resection of the prostate.

BACKGROUND: This study provides an update of patterns in transurethral resection of the prostate (TURP) rates in the United States and the extent of TURP-detected prostate cancer incidence rates. METHODS: Analyses are based on data from the National Hospital Discharge Survey, the Surveillance, Epidemiology, and End Results Program, and the U.S. Census Bureau for the years 1996 through 2006. RESULTS: TURP procedure rates were 6, 14, and 18 times greater in men aged 60 to 69, 70 to 79, and >or=80 years compared with men aged 50 to 59, respectively. During 1996-2006, the estimated annual percentage change in TURP rates was -10.5 (95% confidence interval [95% CI] -14.1 to -6.7) for ages 50 to 59, -7.4 (95% CI -9.2 to -5.6) for ages 60 to 69, -6.2 (95% CI -7.6 to -4.8) for ages 70 to 79, and -7.7 (95% CI -9.5 to -5.8) for ages >or=80 years. TURP-detected prostate cancer incidence rates were 2, 7, and 17 times greater in men aged 60 to 69, 70 to 79, and >or=80 years compared with men aged 50 to 59, respectively. The estimated annual percentage change in trend was -17.8 (-20.6, -15.0) for ages 50 to 59, -14.8 (-16.6, -13.0) for ages 60 to 69, -10.8 (-12.0, -9.7) for ages 70 to 79, and -8.2 (-10.0, -6.5) for ages >or=80 years. Trends in prostate cancer incidence rates peaked in 2002 and decreased thereafter. Some of the decreasing trend in rates among older age groups is because of a decrease in TURPs and consequently a decrease in incidental TURP-detected cases. CONCLUSIONS: TURP procedure rates and incidental TURP-detected prostate cancer incidence rates have declined and will likely continue to decline in the future.

Toward a better understanding of the comparatively high prostate cancer incidence rates in Utah.

BACKGROUND: This study assesses whether comparatively high prostate cancer incidence rates among white men in Utah represent higher rates among members of the Church of Jesus Christ of Latter-day Saints (LDS or Mormons), who comprise about 70% of the state's male population, and considers the potential influence screening has on these rates. METHODS: Analyses are based on 14,693 histologically confirmed invasive prostate cancer cases among men aged 50 years and older identified through the Utah Cancer Registry between 1985 and 1999. Cancer records were linked to LDS Church membership records to determine LDS status. Poisson regression was used to derive rate ratios of LDS to nonLDS prostate cancer incidence, adjusted for age, disease stage, calendar time, and incidental detection. RESULTS: LDS men had a 31% (95% confidence interval, 26%-36%) higher incidence rate of prostate cancer than nonLDS men during the study period. Rates were consistently higher among LDS men over time (118% in 1985-88, 20% in 1989-92, 15% in 1993-1996, and 13% in 1997-99); age (13% in ages 50-59, 48% in ages 60-69, 28% in ages 70-79, and 16% in ages 80 and older); and stage (36% in local/regional and 17% in unstaged). An age- and stage-shift was observed for both LDS and nonLDS men, although more pronounced among LDS men. CONCLUSIONS: Comparatively high prostate cancer incidence rates among LDS men in Utah are explained, at least in part, by more aggressive screening among these men.

Incidental detection of population-based prostate cancer incidence rates through transurethral resection of the prostate.

OBJECTIVE: To provide an updated assessment of the influence transurethral resection of the prostate (TURP) has on incidental detection of prostate cancer and to characterize stage, histologic grade, and treatment patterns among these cases. METHODS: Analyses were based on 17,310 histologically confirmed prostate cancer cases ages 45 years and older recorded in the Utah Cancer Registry between 1980 and 1999 and 6426 TURP procedures recorded in the Utah Hospital Discharge Database from 1992 through 1999. An algorithm was developed for identifying TURP-detected prostate cancer incidence. RESULTS: Age-specific TURP-detected prostate cancer incidence rates tended to be flat between 1980 and 1990, decline through 1994, and then level off. Much of the decrease corresponds to the prostate-specific antigen (PSA) screening induced peak and subsequent fall in total prostate cancer incidence rates. Leveling off in the TURP-detected rates between 1994 and 1999 corresponds with a leveling off in the total prostate cancer incidence rates. The percentage of prostate cancer detected by TURP significantly increases with age, within each age group, but decreases over calendar years. For ages 45 years and older, the percentage of TURP-detected cases was 39.0% in 1980 to 1984, 33.9% in 1985 to 1989, 12.2% in 1990 to 1994, and 7.4% in 1995 to 1999. TURP-detected cases were significantly less likely to undergo radical prostatectomy or radiation therapy across age groups, despite having lower stage and histologic grade at diagnosis. CONCLUSION: TURP-detected prostate cancer rates have leveled off in the latter part of the 1990s, explaining about 10% of all detected cases. These cases have relatively good biologic potential and are less likely to pursue aggressive therapy.