Predictors of incident depression after hip fracture surgery.

OBJECTIVE: Depression after hip fracture surgery is prevalent and associated with increased mortality rates and impaired functional recovery. The incidence of new-onset depressive symptoms in patients initially not depressed after hip fracture surgery and their relationship with functional recovery is unknown. METHODS: A cohort of 139 nondepressed elderly patients (>60 years) hospitalized for hip fracture surgery were followed up for six months. Clinically significant depressive symptoms were defined as a score of 7 or more on the 15-item Geriatric Depression Scale. RESULTS: The authors found a cumulative incidence rate of 20.5% adjusted for dropouts. Multiple Cox-regression analyses yielded the presence of subthreshold symptoms of depression, anxiety, pain, and cognitive impairment at baseline, the premorbid level of mobility, and a history of (treated) depression as risk factors for incident depression (p <0.05). A forward, conditional procedure identified postoperative pain (hazard ratio [HR] = 1.32, 95% confidence interval [CI]: 1.14-1.53, Wald chi(2) = 13.57, df = 1, p <0.001) and baseline anxiety (HR = 1.25, 95% CI: 1.08-1.44, Wald chi(2) = 8.86, df = 1, p = 0.003) as the strongest independent risk factors. Incident depression was associated with a less favorable outcome at 3 months follow-up. CONCLUSION: This exploratory study identified two treatable baseline characteristics that predicted incident depression in nondepressed patients after hip-fracture surgery.     

Tacrolimus metabolite cross-reactivity in different tacrolimus assays

Objectives: Tacrolimus (FK506) is an immunosuppressive drug with great clinical promise. There is a controversy regarding the role of tacrolimus metabolites in immunosuppression and toxicity, and immunoassays and immunophilin binding assays have not been adequately tested for metabolite cross-reactivity. Methods are limited to HPLC and HPLC-MS for quantifying the parent drug. Mixed lymphocyte culture assay (MLC) is the preferred functional bioassay for the measurement of parent drug and active metabolites but it is not practical for routine laboratory use. Due to differences in assay methods and reagent specificity, the concentration of tacrolimus in a given specimen may vary among different assay kit manufacturers. The objective of this study was to evaluate the degree of cross-reactivity or interference of the three first-generation tacrolimus metabolites [13-O-demethyl (M-I), 31-O-demethyl (M-II) and 15-O-demethyl (M-III)] among two different tacrolimus immunoassays (Immunoassay: PRO-Trac II FK506, Abbott IMx tacrolimus-II); and the radioreceptor assays (RRA) using minor immunophilins (14, 37, and 52 kDa immunophilins) and tacrolimus binding protein (FKBP12).

Methods: First-generation tacrolimus metabolites (M-I, M-II, and M-III) spiked in drug-free whole blood were assayed with RRA using three minor immunophilins (14, 37, and 52 kDa) and two commercial immunoassay procedures (Incstar PRO-Trac II tacrolimus, Abbott IMx tacrolimus II). The results were compared to previously published FKBP-12 RRA data and their immunosuppressive potency.

Results and conclusion: The first generation tacrolimus metabolites (M-I, M-II, and M-III) were tested using concentrations of 10 and 20 ng/mL. The significance of the metabolite interference (% of the total interference) was calculated based on the relative concentration of each metabolite present at steady-state trough concentrations in renal transplant recipients [22]. Metabolite I, which has no functional immunosuppressive activity showed minimal interference compared to M-II and M-III in all assays except the 14 kDa RRA. The Incstar PRO-Trac II tacrolimus assay showed the least M-I interference. Metabolite-II, which has a pharmacologic potency similar to the parent drug, showed a significant interference in the immunoassays and significant interference in radioreceptor assays. Metabolite III, which is pharmacologically inactive, produces 3–10% interference in the different assays if its presence in the blood is 6% of the parent drug. The total interference from these three metabolites was greater in the immunoassays than in the receptor assays. Receptor assays for tacrolimus provide results closer to the target value than do immunoassays.     

MR susceptometry: an external-phantom method for measuring bulk susceptibility from field-echo phase reconstruction maps

A novel method for estimating the susceptibility of an object by using the magnetic resonance (MR) imaging field distortions in an external-reference water bath next to the object is described. The field measurement was obtained with a phase reconstruction from a gradient-echo acquisition. A field model of an arbitrary object in a static magnetic field was discretely calculated from geometry determined from the magnitude reconstruction. Least-squares estimation yields the susceptibility of the object. Required (and proven) assumptions include validity of superposition, object homogeneity, negligible higher-order field terms, field-model accuracy, geometric-model accuracy, and correlation of gradient-echo phase to field distortion. MR susceptometry estimation of phantoms yielded susceptibility estimates that correlated well with known values (r >.9975). This MR susceptometry method is a first step toward quantitation of iron levels through MR imaging phase information in patients with iron overload.