Diabetic retinopathy : economic evaluation and cellular functions
- Publication Type:
- Thesis
- Issue Date:
- 2008
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This thesis reports an investigation from the “bedside” back to the “bench”. That
is, from the economic evaluation of a medical intervention to basic research and
development of a contractility assay. The underlying theme of this thesis is
cellular contractility, which was stimulated from our laboratory’s work in the
microvascular complications of Diabetic Retinopathy (DR).
The health economic perspective of this thesis evaluates the cost effectiveness
and cost utility of DR prognosis using the prog-DR test. This novel prognostic
test developed in our laboratory relies on the contractile response of blood
vessels to detect subjects with high risk of developing DR. Markov modeling
based on information in the literature was used to estimate the outcomes of a
hypothetical population. The costs, health and utility outcomes of DR were
compared to the potential outcomes if the prog-DR test was used. The model
show that the prog-DR test can improve the health of the hypothetical
population as measured in the number of life years (LY), sight years (SY) and
quality-adjusted life years (QALY). The prog-DR test was more cost effective
than the benchmark of annual or bi-annual screening and the incremental cost
effectiveness ratio (ICER) appears to be at an acceptable level. Scenario and
sensitivity analysis also show that the cost effectiveness of the prog-DR test
can be improved by (i) better blood glucose management post prog-DR test, (ii)
targeted screening (as opposed to population-wide screening) and (iii) reduced
costs of both screening and management of DM and DR.
The physiological perspective of the thesis aimed to develop a contractility
assay for DR that was based on a 3D scaffold, which was affordable, easy to
make and mimicked the three dimensional physiological environment of blood
vessels. The contractility assay was developed using a 3D, hollow scaffold
(PE-PAH capsule) and involved (i) the selection of the optimal core material, (ii)
optimisation of the manufacturing process, (iii) characterisation of the scaffold
and (iv) ensuring that cells can be grown on it. The cyto-biocompatibility of the
candidate polyelectrolyte Poly(Sodium 4-Styrene Sulfonate) (PSS) and
Poly(Allylamine Hydrochloride) (PAH) in the thin films format were investigated
using three different cell lines and the effects of these thin films were also
compared to titanium and titanium nitride thin films. In essence, PSS and PAH
are not cytotoxic and was used to develop the contractile scaffold, PE-PAH
capsule. This scaffold is relative elastic and the contractile force exerted by the
3T3-L1 cells was calculated based on the deformation of the PE-PAH capsule.
The contractility assay was sufficiently sensitive to detect the nano-Newton
magnitude of force developed by individual cells and discriminated the change
in force due to disruption of the F-actin cytoskeleton by forskolin and
cytochalasin D.
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