Falls on an inpatient rehabilitation spinal injuries unit: the characteristics, circumstances, and consequences.

STUDY DESIGN: Retrospective audit OBJECTIVES: To describe the nature of falls and fallers in a spinal injuries unit (SIU) and identify factors associated with having more than one fall (recurrent fallers) and falls with physical or psychological consequences (consequential falls). SETTING: An Australian inpatient rehabilitation SIU. METHODS: Data were retrospectively extracted from falls incident reports and electronic medical records over a 5-year period. Data were analysed descriptively to summarise participant and fall details. Univariate analyses identified candidate variables for further investigation in a multivariate model for recurrent fallers and consequential falls. RESULTS: Of the 566 persons admitted to the SIU, 132 (23%) participants experienced 207 falls over the 5 years. Of the fallers, 41 (31%) were recurrent fallers experiencing between 2 and 7 falls and 78 (59%) experienced a consequential fall. No significant variables were identified for recurrent fallers. For consequential falls, older age (OR = 1.038, 95% CI, 1.012 to 1.064, p = 0.004) and female gender (OR = 3.581, 95% CI, 1.269 to 10.103, p = 0.016) were significant, as well as falls that occurred on a Sunday (OR = 0.196, 95% CI, 0.061 to 0.630, p = 0.006). Falls while transferring were less likely to be consequential (OR = 4.100, 95% CI, 1.706 to 9.856, p = 0.002). CONCLUSIONS: Nearly one quarter of SIU inpatients experienced a fall with almost a third of those who fell experiencing recurrent falls. Older age, female gender, and Sundays were risk factors for falls with consequence.

Diagnostic performance of prospective same-day 18F-FDG PET/MRI and 18F-FDG PET/CT in the staging and response assessment of lymphoma.

BACKGROUND: Accurate staging and response assessment are essential for prognosis and to guide treatment in patients with lymphoma. The aim of this study was to compare the diagnostic performance of FDG PET/MRI versus FDG PET/CT in adult patients with newly diagnosed Hodgkin and Non- Hodgkin lymphoma. METHODS: In this single centre study, 50 patients were prospectively recruited. FDG PET/MRI was performed after staging FDG PET/CT using a single injection of 18F-FDG. Patients were invited to complete same-day FDG PET/MRI with FDG PET/CT at interim and end of treatment response assessments. Performance was assessed using PET/CT as the reference standard for disease site identification, staging, response assessment with Deauville score and concordance in metabolic activity. RESULTS: Staging assessment showed perfect agreement (κ = 1.0, P = 0) between PET/MRI and PET/CT using Ann Arbor staging. There was excellent intermodality correlation with disease site identification at staging (κ = 0.976, P < 0.001) with FDG PET/MRI sensitivity of 96% (95% CI, 94-98%) and specificity of 100% (95% CI, 99-100%). There was good correlation of disease site identification at interim assessment (κ = 0.819, P < 0.001) and excellent correlation at end-of-treatment assessment (κ = 1.0, P < 0.001). Intermodality agreement for Deauville scores was good at interim assessment (κ = 0.808, P < 0.001) and excellent at end-of-treatment assessment (κ = 1.0, P = 0). There was good-excellent concordance in SUV max and mean between modalities across timepoints. Minimum calculated radiation patient effective dose saving was 54% between the two modalities per scan. CONCLUSION: With high concordance in disease site identification, staging and response assessment, PET/MR is a potentially viable alternative to PET/CT in lymphoma that minimises radiation exposure.

Assessment of arginine 97 and lysine 72 as determinants of substrate specificity in cytochrome P450 2C9 (CYP2C9).

CYP2C9 is distinguished by a preference for substrates bearing a negative charge at physiological pH. Previous studies have suggested that CYP2C9 residues R97 and K72 may play roles in determining preference for anionic substrates by interaction at the active site or in the access channel. The aim of the present study was to assess the role of these two residues in determining substrate selectivity. R97 and K72 were substituted with negative, uncharged polar and hydrophobic residues using a degenerate polymerase chain reaction-directed strategy. Wild-type and mutant enzymes were expressed in bicistronic format with human cytochrome P450 reductase in Escherichia coli. Mutation of R97 led to a loss of holoenzyme expression for R97A, R97V, R97L, R97T, and R97E mutants. Low levels of hemoprotein were detected for R97Q, R97K, R97I, and R97P mutants. Significant apoenzyme was observed, suggesting that heme insertion or protein stability was compromised in R97 mutants. These observations are consistent with a structural role for R97 in addition to any role in substrate binding. By contrast, all K72 mutants examined (K72E, K72Q, K72V, and K72L) could be expressed as hemoprotein at levels comparable to wild-type. Type I binding spectra were obtained with wild-type and K72 mutants using diclofenac and ibuprofen. Mutation of K72 had little or no effect on the interaction with these substrates, arguing against a critical role in determining substrate specificity. Thus, neither residue appears to play a role in determining substrate specificity, but a structural role for R97 can be proposed consistent with recently published crystallographic data for CYP2C9 and CYP2C5.