Vertebral fracture assessment (VFA) by lateral DXA scanning may be cost-effective when used as part of fracture liaison services or primary care screening

Summary

We identified that use of VFA may be cost-effective in either selected women from primary care or women attending after a low trauma fracture.

Introduction

Lateral DXA scanning of the spine for vertebral fracture assessment (VFA) is used for research, but its wider role is unclear. We aimed to establish whether VFA is cost-effective in women based on two different scenarios: following a low-trauma fracture, and after screening of high-risk women identified in primary care.

Methods

The fracture cohort (FC) consisted of 377 women and the primary care cohort (PCC) of 251. Vertebral fractures were identified on VFA images by quantitative morphometry (QM). Outcome was cost-effectiveness of VFA, based on predicted change in clinical management defined as the identification of a vertebral fracture in a patient who otherwise falls below the threshold for treatment. FRAX treatment thresholds assessed were (1) 20/3 % thresholds and (2) National Osteoporosis Guidelines Group (NOGG) thresholds.

Results

As a result, 9.8 % from FC and 13.9 % from PCC were identified with vertebral fractures. Management was changed in 21 to 22/377 (5.6–5.8 %) in FC and 12 to 26/251 (4.8–10.4 %) from PCC depending on which thresholds were used. Sensitivity analyses identified medication adherence as the assumption which most influenced the model. The best-estimate cost-per-QALY for use of VFA in FC was £3,243 for 20/3 threshold and £2,130 for NOGG; for PCC, this was £7,831 for 20/3 and was cost-saving for NOGG. Further analyses to adjust for potential false-positive vertebral fracture identification with QM showed VFA was no longer cost-effective.

Conclusion

VFA appears to be cost-effective in routine clinical practise, particularly when relatively inaccurate methods of identification of vertebral fractures are used such as QM.     

Isolation and characterization of orbivirus genotypic variants

Orbivirus variants containing either RNA deletions or concatemeric RNAs have been isolated. A variant of Ibaraki virus (a member of the epizootic hemorrhagic disease of deer serogroup) contained an RNA 9 segment which had terminal sequences identical to RNA 9 of wild type virus but was approximately 140 base pairs (bp) shorter. In vitro translation showed that whereas RNA 9 of wild type virus generated the minor structural protein VP6 (molecular weight 38 K), the variant RNA 9 coded for a 32 K protein. Analysis of hybrid molecules formed after melting and reannealing mixtures of [32P]-pCp-labeled wild type and variant RNA 9 molecules indicated that generation of variant RNA 9 may have involved the loss of approximately 150 bp at a location 148 bp from one end of the wild type RNA molecule. Analysis of minor proteins generated by premature termination during in vitro translation of wild type and variant RNA 9 suggested that the deletion occurred towards the 3' end of the positive strand of wild type RNA 9. RNA genome segments 10 and 9 of bluetongue virus type 21 and Bunyip Creek (a Palyam serogroup member) respectively, were observed to form concatemers. Molecular weight estimates and T1 RNase mapping suggested that the concatemers were dimers in a 5'-3' to 5'-3' orientation. In vitro translation of dimeric RNAs yielded products apparently identical to those generated by monomeric RNAs. The possible ramifications of these results with respect to orbivirus evolution are discussed.     

The development of hemoglobin solutions as red cell substitutes: hemoglobin solutions

Although the efficacy of hemoglobin-based oxygen carriers was established more than 60 years ago, all prior clinical trials have demonstrated significant toxicity characterized by renal dysfunction, gastrointestinal distress, and systemic vasoconstriction. The mechanisms of these toxicities now appear to be understood. Tetrameric forms of the hemoglobin molecule extravasate from the circulation and interact with endothelial derived relaxing factor, leading to unopposed vasoconstriction. Although numerous efforts are underway to chemically modify the native tetramer, it is likely that all tetrameric forms of the hemoglobin molecule will continue to extravasate. We have focused on developing a polymerized form of hemoglobin that is virtually free of unreacted tetramer. The development and characterization of this polymerized pyridoxylated hemoglobin solution (Poly SFH-P) is described. Clinical trials have been completed successfully in volunteers, and are now underway to assess the safety and efficacy of Poly SFH-P as a clinically useful red cell substitute in the treatment of acute blood loss in the setting of trauma and surgery.