***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: Aims /hypothesisThe aim of the present study was to investigate re source utilisation and associated costs in patients with diabetic foot ulcers and to analyse differences in re source utilisation between individuals with or without peripheral arterial disease ( PAD ) and /or infection . Methods Data on re source utilisation were collected prospect ively in a European multicentre study . Data on 1,088 patients were available for the analysis of re source use , and data on 821 patients were included in the costing analysis . Costs were calculated for each patient by multiplying the country-specific direct and indirect unit costs by the number of re sources used from inclusion into the study up to a defined endpoint . Country-specific costs were converted into purchasing power st and ards . Results Re source use and costs varied between outcome groups and between disease severity groups . The highest costs per patient were for hospitalisation , antibiotics , amputations and other surgery . All types of re source utilisation and costs increased with the severity of disease . The total cost per patient was more than four times higher for patients with infection and PAD at inclusion than for patients in the least severe group , who had neither . Conclusions /interpretationImportant differences in re source use and costs were found between different patient groups . The costs are highest for individuals with both peripheral arterial disease and infection , and these are mainly related to substantial costs for hospitalisation . In view of the magnitude of the costs associated with in-hospital stay , reducing the number and duration of hospital admissions seems an attractive option to decrease costs in diabetic foot disease A numerical-experimental approach has been developed to characterize heel-pad deformation at the material level . Left and right heels of 20 diabetic subjects and 20 nondiabetic subjects matched for age , gender and body mass index were indented using force-controlled ultrasound . Initial tissue thickness and deformation were measured using M-mode ultrasound ; indentation forces were recorded simultaneously . An inverse finite-element analysis of the indentation protocol using axisymmetric models adjusted to reflect individual heel thickness was used to extract nonlinear material properties describing the hyperelastic behavior of each heel . Student 's t-tests revealed that heel pads of diabetic subjects were not significantly different in initial thickness nor were they stiffer than those from nondiabetic subjects . Another heel-pad model with anatomically realistic surface representations of the calcaneus and soft tissue was developed to estimate peak pressure prediction errors when average rather than individualized material properties were used . Root-mean-square errors of up to 7 % were calculated , indicating the importance of subject-specific modeling of the nonlinear elastic behavior of the heel pad . Indentation systems combined with the presented numerical approach can provide this information for further analysis of patient-specific foot pathologies and therapeutic footwear design OBJECTIVE To assess the efficacy of in-shoe orthoses that were design ed based on shape and barefoot plantar pressure in reducing the incidence of submetatarsal head plantar ulcers in people with diabetes , peripheral neuropathy , and a history of similar prior ulceration . RESEARCH DESIGN AND METHODS Single-blinded multicenter r and omized controlled trial with subjects r and omized to wear shape- and pressure-based orthoses ( experimental , n = 66 ) or st and ard-of-care A5513 orthoses ( control , n = 64 ) . Patients were followed for 15 months , until a study end point ( forefoot plantar ulcer or nonulcerative plantar forefoot lesion ) or to study termination . Proportional hazards regression was used for analysis . RESULTS There was a trend in the composite primary end point ( both ulcers and nonulcerative lesions ) across the full follow-up period ( P = 0.13 ) in favor of the experimental orthoses . This trend was due to a marked difference in ulcer occurrence ( P = 0.007 ) but no difference in the rate of nonulcerative lesions ( P = 0.76 ) . At 180 days , the ulcer prevention effect of the experimental orthoses was already significant ( P = 0.003 ) when compared with control , and the benefit of the experimental orthoses with respect to the composite end point was also significant ( P = 0.042 ) . The hazard ratio was 3.4 ( 95 % CI 1.3–8.7 ) for the occurrence of a submetatarsal head plantar ulcer in the control compared with experimental arm over the duration of the study . CONCLUSIONS We conclude that shape- and barefoot plantar pressure – based orthoses were more effective in reducing submetatarsal head plantar ulcer recurrence than current st and ard-of-care orthoses , but they did not significantly reduce nonulcerative lesions A major goal of therapeutic footwear in patients with pain or those at risk for skin injury is to relieve focal loading under prominent metatarsal heads . One frequent approach is to place plugs of compliant material into the midsole of the shoe . This study investigated 36 plug design s , a combination of three material s , six geometries , and two placements using a two-dimensional ( 2D ) finite element model . Realistic loading conditions were obtained from plantar pressures ( PP ) recorded during walking in five subjects who wore control midsoles manufactured using Microcell Puff .  Measured peak pressures underneath the second metatarsal head were similar to the results of the control model . PP obtained from simulations with the plugs built into a firm midsole were compared to the simulation results of the control midsole . Large plugs ( e.g. 40 mm width ) , made out of Microcell Puff Lite or Plastazote Medium , placed at peak pressure sites , result ed in highest reductions in peak pressures ( 18 - 28 % ) . Smaller plugs benefited from tapering when placed at high pressure areas . Case studies were completed on a healthy male subject and a diabetic female patient to address the efficacy of a plug design favored by our simulations ( pressure based placement , 40 x 20 mm , Plastazote Medium ) . Successful reductions of second metatarsal head pressures were observed with a mediolateral load redistribution that was not represented by our model . 2D computer simulations allowed systematic investigation of plug properties without the need for high volume experimentation on human subjects and established basic guidelines for plug selection . In particular , plugs that are placed based on plantar pressure measurements were proven to be more effective when compared to those positioned according to the projection of the bony l and mark on the foot-shoe plantar contact area 
    Output:
    
RESULTS Method ological studies illustrated appropriate use of FE analysis for simulation of foot mechanics , incorporating nonlinear tissue mechanics , contact and rigid body movements .
FE studies of pathomechanics have provided estimates of internal soft tissue stresses , and suggest that such stresses may often be considerably larger than those measured at the plantar surface and are proportionally greater in the diabetic foot compared to controls .
FE analysis allowed evaluation of insole performance and development of new insole design s , footwear and corrective surgery to effectively provide intervention strategies .
The technique also presents the opportunity to simulate the effect of changes associated with the diabetic foot on non-mechanical factors such as blood supply to local tissues .