Objectives Men treated with androgen deprivation therapy (ADT) or radiation therapy (RT) for prostate cancer have an increased risk for fractures. Given uncertainty as to whether specific clinical factors can identify men at increased risk, we sought to develop a prognostic index for risk of fracture in this population. Materials and methods We used the Surveillance, Epidemiology, and End Results-Medicare database to identify men who received ADT or RT after being diagnosed with localized prostate cancer in 2007-2009. Cox proportional hazards models tested the association of potential risk factors with fracture. In a derivation group, hazard ratios were used to assign points for factors independently related to fracture. The prognostic index was then applied to a validation group. Results The sample of 5,824 men had a median age of 73.0 years; 82.9% were white and 8.6% had a fracture within 2 years of treatment for prostate cancer. The Cox model identified 8 variables (age, race, hormone treatment, Elixhauser score, anxiety, Parkinson's, fall-inducing medications and disability status) independently associated with fracture. In the derivation cohort, 4.3% of the sample experienced a fracture in the low-risk group, 8.9% in the intermediate group, and 19.2% in the high-risk group (C statistic, 0.749). The index was applied to the validation cohort (C statistic, 0.782). Conclusion The prognostic index can help to identify patients at increased risk for fracture. This underscores the importance of identifying risk factors for fracture, given the substantial variation in fracture risk in men treated with ADT or RT.

Clinicians must be aware of the pharmacokinetic effects of therapeutic hypothermia to prevent potential drug-therapy interactions. It may be prudent to avoid the use of CYP3A4 substrates that are not essential treatments in patients undergoing therapeutic hypothermia until more information is known about their safety in this patient population.

Abbreviations: (IU) international units, (NPH) neutral protamine Hagedorn, isophane insulinKeywords: administration, insulin, isophane, mixing, pharmacodynamics, pharmacokinetics AbstractIn this issue of Journal of Diabetes Science and Technology, Kaiser and colleagues conducted an investigation to identify variations in the delivered dose of several different isophane insulin (neutral protamine Hagedorn, NPH) brands that use glass and metal bodies ("bullets") to facilitate mixing. Using a strategy where multiple pens from each of five different NPH insulin products (Insuman Basal, sanofi-aventis, three metal bullets; Humulin N, Lilly, one glass bullet; Berlinsulin H Basal, Berlin-Chemie, one glass bullet; Insulin B. Braun Basal, two glass bullets; and Protaphane Penfill, NovoNordisk, one glass bullet) were compared at multiple sampling points and over a range of mixing procedures (3, 6, 10, and 20 times), the authors identified deviations in the delivered dose of insulin at initial use and with repeated dosing. At the initial dose, adhering with manufacturer recommendations to conduct the mixing procedure 10-20 times was found to demonstrate minimal deviation and there was no pronounced difference among the products. Decreasing the number of mixing procedures from 10-20 to 3-6 times, a more profound deviation was noted, with the Insuman Basal product demonstrating less variability in comparison to all other products evaluated. A repeated dose study (1, 2, 6, and 10) with only six mixing procedures revealed that the insulin concentration of each dose increased for all products except Insuman Basal. Clinically, numerous factors may contribute to variability observed with subcutaneous administration of isophane insulin. While data presented by Kaiser and colleagues demonstrated that the issue of proper mixing is not trivial, the modest differences observed between and within products both at the initial dose and with repeated dosing may indicate that the clinical relevance of these findings is most applicable to those requiring large doses or, alternatively, those who have otherwise unexplained hypoglycemic episodes.

Objectives-Men treated with androgen deprivation therapy (ADT) or radiation therapy (RT) for prostate cancer have an increased risk for fractures. Given uncertainty as to whether specific clinical factors can identify men at increased risk, we sought to develop a prognostic index for risk of fracture in this population. Materials and methods-We used the Surveillance, Epidemiology, and End Results-Medicare database to identify men who received ADT or RT after being diagnosed with localized prostate cancer in 2007-2009. Cox proportional hazards models tested the association of potential risk factors with fracture. In a derivation group, hazard ratios were used to assign points for factors independently related to fracture. The prognostic index was then applied to a validation group.