Load-adaptive scaffold architecturing: a bioinspired approach to the design of porous additively manufactured scaffolds with optimized mechanical properties

Computer-Aided Tissue Engineering (CATE) is based on a set of additive manufacturing techniques for the fabrication of patient-specific scaffolds, with geometries obtained from medical imaging. One of the main issues regarding the application of CATE concerns the definition of the internal architecture of the fabricated scaffolds, which, in turn, influences their porosity and mechanical strength. The present study envisages an innovative strategy for the fabrication of highly optimized structures, based on the a priori finite element analysis (FEA) of the physiological load set at the implant site. The resulting scaffold micro-architecture does not follow a regular geometrical pattern; on the contrary, it is based on the results of a numerical study. The algorithm was applied to a solid free-form fabrication process, using poly(ε-caprolactone) as the starting material for the processing of additive manufactured structures. A simple and intuitive geometry was chosen as a proof-of-principle application, on which finite element simulations and mechanical testing were performed. Then, to demonstrate the capability in creating mechanically biomimetic structures, the proximal femur subjected to physiological loading conditions was considered and a construct fitting a femur head portion was designed and manufactured.     

Overdiagnosis in breast cancer: design and methods of estimation in observational studies

Objectives

In recent years observational epidemiological studies have been used to estimate overdiagnosis in breast cancer screening. These estimates vary widely. In this paper we present some of the methodological issues which explain the large variability of the reported findings.

Methods

Different types of observational studies were identified according to study design, definition of the population, adjustment for breast cancer risk and adjustment for lead time.

Results

The majority of observational studies that have estimated breast cancer overdiagnosis have analyzed temporal trends or geographical differences in breast cancer incidence. Estimates of overdiagnosis in a dynamic population vary widely, from 4% to 52%. Only a few studies have used the cohort approach and they found estimates varying from 1% to 5%.

Conclusions

The cohort approach is preferable to the analysis of a dynamic population because it allows the follow-up of a group of women who have had the opportunity for screening and evaluates if there is sufficient follow-up after the last screen.     

A double-blind, randomized, multicenter, Italian study of frovatriptan versus almotriptan for the acute treatment of migraine

The objective of this study was to evaluate patients’ satisfaction with acute treatment of migraine with frovatriptan or almotriptan by preference questionnaire. One hundred and thirty three subjects with a history of migraine with or without aura (IHS 2004 criteria), with at least one migraine attack in the preceding 6 months, were enrolled and randomized to frovatriptan 2.5 mg or almotriptan 12.5 mg, treating 1–3 attacks. The study had a multicenter, randomized, double blind, cross-over design, with treatment periods lasting <3 months. At study end patients assigned preference to one of the treatments using a questionnaire with a score from 0 to 5 (primary endpoint). Secondary endpoints were pain free and pain relief episodes at 2 and 4 h, and recurrent and sustained pain free episodes within 48 h. Of the 133 patients (86%, intention-to-treat population) 114 of them expressed a preference for a triptan. The average preference score was not significantly different between frovatriptan (3.1 ± 1.3) and almotriptan (3.4 ± 1.3). The rates of pain free (30% frovatriptan vs. 32% almotriptan) and pain relief (54% vs. 56%) episodes at 2 h did not significantly differ between treatments. This was the case also at 4 h (pain free: 56% vs. 59%; pain relief: 75% vs. 72%). Recurrent episodes were significantly (P < 0.05) less frequent under frovatriptan (30% vs. 44%), also for the attacks treated within 30 min. No significant differences were observed in sustained pain free episodes (21% vs. 18%). The tolerability profile was similar between the two drugs. In conclusion, our study suggests that frovatriptan has a similar efficacy of almotriptan in the short-term, while some advantages are observed during long-term treatment.     

Endocrinology of the ageing female; the hypothalamic-pituitary-ovarian axis

The hypothalamic-pituitary-ovarian (HPO) axis goes through a series of complicated, but well coordinated changes as a women enters the menopausal transition. The reproductive consequences of these changes are obvious, but there are also a number of general health consequences as well. As our understanding of the complex inter-workings of the HPO axis evolves, we will be better able to predict menopausal events and create strategies and treatments to optimize women's health as the progress through the menopausal transition.