Background/aimsTo evaluate the cost-effectiveness of ranibizumab as either monotherapy or combined with laser therapy, compared with laser monotherapy, in the treatment of diabetic macular oedema (DME) causing visual impairment from a UK healthcare payer perspective.MethodsA Markov model simulated long-term outcomes and costs of treating DME in one eye (BCVA ≤75 letters) based on data from the RESTORE Phase III trial. Outcomes measured in quality-adjusted life-years (QALYs) were simulated for a 15-year time horizon based on 12-month follow-up from RESTORE and published long-term data. Costs included treatment, disease monitoring, visual impairment and blindness (at 2010 price levels).ResultsRanibizumab monotherapy resulted in a 0.17 QALY gain at an incremental cost of £4191 relative to laser monotherapy, yielding an incremental cost-effectiveness ratio (ICER) of £24 028. Probabilistic sensitivity analysis showed a 64% probability of being cost-effective at a threshold of £30 000 per QALY. Combined ranibizumab and laser therapy resulted in a 0.13 QALY gain at an incremental cost of £4695 relative to laser monotherapy (ICER £36 106; 42% probability of ICER <£30 000).ConclusionsBased on RESTORE 1-year follow-up data, ranibizumab monotherapy appears to be cost-effective relative to laser monotherapy, the current standard of care. Cost-effectiveness of combination therapy is less certain. Ongoing studies will further inform on disease progression and the need for additional ranibizumab treatment.

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Nonlinear finite element (FE) static analyses of top-and seat-angle connections were performed using ABAQUS standard to investigate the influence of connection parameters and its properties on prying action developed due to the interaction between column flange and top angle's vertical leg. Contact phenomenon between two interfaces with finite sliding and bolt pretension in the initial step of analysis was considered in the FE model. FE analysis results were compared with the experimental ones to examine the applicability of the FE model. Then, the location of plastic hinges in connection assemblages was investigated at the ultimate state of the connection and a parametric study was performed varying connection parameters, material properties of connection assemblages, and magnitude of bolt pretension to visualize their effects on prying force and on the position of prying force on top angle's vertical leg. Current study shows that plastic hinges not only develop at top angle's heel and bolt hole region but also in the bolt shank that differs from some assumptions of power model (Kishi and Chen 1990): (1) top angle thickness and gage distance from angle heel to bolt hole center line have an distinct effect on prying action; and (2) distributed prying force developed near the region of the top edge of tension angle's leg adjacent to column flange can contribute to the failure of the connection. Finally, a mathematical formulation to identify the location of prying force action point is proposed.

Two recent developments have come into the forefront with reference to updating the seismic design provisions for codes: (1) publication of new seismic hazard maps for Canada by the Geological Survey of Canada, and (2) emergence of the concept of new spectral format outdating the conventional standardized spectral format. The fourth-generation seismic hazard maps are based on enriched seismic data, enhanced knowledge of regional seismicity and improved seismic hazard modeling techniques. Therefore, the new maps are more accurate and need to incorporate into the Canadian Highway Bridge Design Code (CHBDC) for its next edition similar to its building counterpart National Building Code of Canada (NBCC). In fact, the code writers expressed similar intentions with comments in the commentary of CHBCD 2006. During the process of updating codes, NBCC, and AASHTO Guide Specifications for LRFD Seismic Bridge Design, American Association of State Highway and Transportation Officials, Washington (2009) lowered the probability level from 10 to 2% and 10 to 5%, respectively. This study has brought five sets of hazard maps corresponding to 2%, 5% and 10% probability of exceedance in 50 years developed by the GSC under investigation. To have a sound statistical inference, 389 Canadian cities are selected. This study shows the implications of the changes of new hazard maps on the design process (i.e., extent of magnification or reduction of the design forces).