Influences of age and mechanical stability on volume, microstructure, and mineralization of the fracture callus during bone healing : Is osteoclast activity the key to age-related impaired healing?

Earlier studies have shown that the influence of fixation stability on bone healing diminishes with advanced age. The goal of this study was to unravel the relationship between mechanical stimulus and age on callus competence at a tissue level. Using 3D in vitro micro-computed tomography derived metrics, 2D in vivo radiography, and histology, we investigated the influences of age and varying fixation stability on callus size, geometry, microstructure, composition, remodeling, and vascularity. Compared were four groups with a 1.5-mm osteotomy gap in the femora of Sprague–Dawley rats: Young rigid (YR), Young semirigid (YSR), Old rigid (OR), Old semirigid (OSR). Hypothesis was that calcified callus microstructure and composition is impaired due to the influence of advanced age, and these individuals would show a reduced response to fixation stabilities. Semirigid fixations resulted in a larger ΔCSA (Callus cross-sectional area) compared to rigid groups. In vitro μCT analysis at 6 weeks postmortem showed callus bridging scores in younger animals to be superior than their older counterparts (pb0.01). Younger animals showed (i) larger callus strut thickness (pb0.001), (ii) lower perforation in struts (pb0.01), and (iii) higher mineralization of callus struts (pb0.001). Callus mineralization was reduced in young animals with semirigid fracture fixation but remained unaffected in the aged group. While stability had an influence, age showed none on callus size and geometry of callus. With no differences observed in relative osteoid areas in the callus ROI, old as well as semirigid fixated animals showed a higher osteoclast count (pb0.05). Blood vessel density was reduced in animals with semirigid fixation (pb0.05). In conclusion, in vivo monitoring indicated delayed callus maturation in aged individuals. Callus bridging and callus competence (microstructure and mineralization) were impaired in individuals with an advanced age. This matched with increased bone resorption due to higher osteoclast numbers. Varying fixator configurations in older individuals did not alter the dominant effect of advanced age on callus tissue mineralization, unlike in their younger counterparts. Age-associated influences appeared independent from stability. This study illustrates the dominating role of osteoclastic activity in age-related impaired healing, while demonstrating the optimization of fixation parameters such as stiffness appeared to be less effective in influencing healing in aged individuals.

VO2max in overweight and obese adults

Purpose: The purpose of this study was to determine whether adiposity affects the attainment of VO2max. Methods: Sixty-seven male and 68 female overweight (body mass index (BMI) = 25-29.9 kg·m-2) and obese (BMI >= 30 kg·m-2) participants undertook a graded treadmill test to volitional exhaustion (phase 1) followed by a verification test (phase 2) to determine the proportion who could achieve a plateau in VO2 and other "maximal" markers (RER, lactate, HR, RPE). Results: At the end of phase 1, 46% of the participants reached a plateau in VO2, 83% increased HR to within 11 beats of age-predicted maximum, 89% reached an RER of >=1.15, 70% reached a blood lactate concentration of >=8 mmol·L-1, and 74% reached an RPE of >=18. No significant differences between genders and between BMI groups were found with the exception of blood lactate concentration (males = 84% vs females = 56%, P < 0.05). Neither gender nor fatness predicted the number of other markers attained, and attainment of other markers did not differentiate whether a VO2 plateau was achieved. The verification test (phase 2) revealed that an additional 52 individuals (39%) who did not exhibit a plateau in V·O2 in phase 1 had no further increase in VO2 in phase 2 despite an increase in workload. Conclusions: These findings indicate that the absence of a plateau in VO2 alone is not indicative of a failure to reach a true maximal VO2 and that individuals with excessive body fat are no less likely than "normal-weight" individuals to exhibit a plateau in VO2 provided that the protocol is appropriate and encouragement to exercise to maximal exertion is provided.

Effect of surgical approach on bone vascularisation, fracture and soft tissue healing : comparison of less invasive to open approach

Over the past ten years, minimally invasive plate osteosynthesis (MIPO) for the fixation of long bone fractures has become a clinically accepted method with good outcomes, when compared to the conventional open surgical approach (open reduction internal fixation, ORIF). However, while MIPO offers some advantages over ORIF, it also has some significant drawbacks, such as a more demanding surgical technique and increased radiation exposure. No clinical or experimental study to date has shown a difference between the healing outcomes in fractures treated with the two surgical approaches. Therefore, a novel, standardised severe trauma model in sheep has been developed and validated in this project to examine the effect of the two surgical approaches on soft tissue and fracture healing. Twenty four sheep were subjected to severe soft tissue damage and a complex distal femur fracture. The fractures were initially stabilised with an external fixator. After five days of soft tissue recovery, internal fixation with a plate was applied, randomised to either MIPO or ORIF. Within the first fourteen days, the soft tissue damage was monitored locally with a compartment pressure sensor and systemically by blood tests. The fracture progress was assessed fortnightly by x-rays. The sheep were sacrificed in two groups after four and eight weeks, and CT scans and mechanical testing performed. Soft tissue monitoring showed significantly higher postoperative Creatine Kinase and Lactate Dehydrogenase values in the ORIF group compared to MIPO. After four weeks, the torsional stiffness was significantly higher in the MIPO group (p=0.018) compared to the ORIF group. The torsional strength also showed increased values for the MIPO technique (p=0.11). The measured total mineralised callus volumes were slightly higher in the ORIF group. However, a newly developed morphological callus bridging score showed significantly higher values for the MIPO technique (p=0.007), with a high correlation to the mechanical properties (R2=0.79). After eight weeks, the same trends continued, but without statistical significance. In summary, this clinically relevant study, using the newly developed severe trauma model in sheep, clearly demonstrates that the minimally invasive technique minimises additional soft tissue damage and improves fracture healing in the early stage compared to the open surgical approach method.

A policy case study of blood in Australia

In 2008 the Australian government decided to remove white blood cells from all blood products. This policy of universal leucodepletion was a change to the existing policy of supplying leucodepleted products to high risk patients only. The decision was made without strong information about the cost-effectiveness of universal leucodepletion. The aims for this policy analysis are to generate cost-effectiveness data about universal leucodepletion, and to add to our understanding of the role of evidence and the political reality of healthcare decision-making in Australia. The cost-effectiveness analysis revealed universal leucodepletion costs $398,943 to save one year of life. This exceeds the normal maximum threshold for Australia. We discuss this result within the context of how policy decisions are made about blood, and how it relates to the theory and process of policy making. We conclude that the absence of a strong voice for cost-effectiveness was an important omission in this decision.

Repeat participation in colorectal cancer screening utilizing fecal occult blood testing : a community-based project in a rural setting

Background and Aim: To investigate participation in a second round of colorectal cancer screening using a fecal occult blood test (FOBT) in an Australian rural community, and to assess the demographic characteristics and individual perspectives associated with repeat screening. ---------- Methods: Potential participants from round 1 (50–74 years of age) were sent an intervention package and asked to return a completed FOBT (n = 3406). Doctors of participants testing positive referred to colonoscopy as appropriate. Following screening, 119 participants completed qualitative telephone interviews. Multivariable logistic regression models evaluated the association between round-2 participation and other variables.---------- Results: Round-2 participation was 34.7%; the strongest predictor was participation in round 1. Repeat participants were more likely to be female; inconsistent screeners were more likely to be younger (aged 50–59 years). The proportion of positive FOBT was 12.7%, that of colonoscopy compliance was 98.6%, and the positive predictive value for cancer or adenoma of advanced pathology was 23.9%. Reasons for participation included testing as a precautionary measure or having family history/friends with colorectal cancer; reasons for non-participation included apathy or doctors’ advice against screening.---------- Conclusion: Participation was relatively low and consistent across rounds. Unless suitable strategies are identified to overcome behavioral trends and/or to screen out ineligible participants, little change in overall participation rates can be expected across rounds.