Age-related macular degeneration: cost-of-illness issues

Macular degeneration refers to the breakdown of cells in the centre of the retina. Some degeneration is an inevitable consequence of the aging process; however, when this is associated with loss of sight in the central part of the field of vision an underlying pathology is considered present. Among those aged 55 years, the prevalence of the disease in the US was estimated at 1% rising to approximately 15% among those aged 80 years. Other studies estimate the prevalence of the disease to be higher and to be increasing. The main effect of the disease is to reduce the ability of the individual to engage in everyday activities that require clear central vision. It may also be associated with elevated risks of depression and increased levels of dependency. Currently there is no effective treatment for the majority of patients. For a minority (< 10%) laser photocoagulation therapy may be effective in reducing the risk of severe vision loss. Another treatment, photodynamic therapy, is in development and many others are at an experimental stage. This review sought to establish current knowledge on the cost of illness associated with age-related macular degeneration (ARMD). A search of the literature, together with direct communication with researchers in related fields and patient support/advocacy groups, was undertaken to ascertain current knowledge on the cost of illness of ARMD. While literature on the disease is extensive and literature on treatments is emerging, no substantive information on direct or indirect costs was found although evidence that loss of earnings may occur is beginning to emerge. Some information does exist on cost of illness in diabetic retinopathy, a disease with similarities to ARMD, though even for this disease gaps in knowledge are apparent and wide variations exhibited. Given current knowledge, it is not possible to report on the cost of illness for ARMD with confidence. The lack of information on the cost of illness in ARMD presents difficulties for researchers and policy makers in assessing the cost effectiveness of the existing treatment, as well as new treatments as they become available. Given developments in treatments and the increasing prevalence of the disease, it is important that cost-of-illness information is gathered for ARMD.     

Improving accuracy of burn referrals through the use of an internet-based burns chart

A study was performed to compare the efficacy of an internet-based burns assessment form in communicating burns referral data with conventional phone and fax data transfer. An internet-based data collection form was developed in consultation with the multidisciplinary team at our centre with the aim of efficient data collection whilst minimising the time burden on the referring clinician. Through our website, an interactive Lund and Browder chart, is readily accessible which allows the user to mark on the chart itself the areas that have been injured. The ‘Burnschart’ system was incorporated into the referral process at Concord Hospital from January to June 2009 in addition to the conventional referral system. A review was conducted comparing a group of patients prior to and post implementation of the online referral system. The study population consisted of two groups of 25 patients that had been referred using Burnschart (group 1), or the conventional referring system (group 2). A significant difference between the two groups of 2.71% in the mean TBSA estimation error was found when comparing the two groups (p < 0.05). These results indicate that a simple web-based program to assist in accurately conveying summary data of site, size and severity of burn injury may be a useful tool in improving quality of communication between referring and receiving clinicians.     

Improved drug targeting of cancer cells by utilizing actively targetable folic acid-conjugated albumin nanospheres

Folic acid-conjugated albumin nanospheres (FA-AN) have been developed to provide an actively targetable drug delivery system for improved drug targeting of cancer cells with reduced side effects. The nanospheres were prepared by conjugating folic acid onto the surface of albumin nanospheres using 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDAC) as a catalyst. To test the efficacy of these nanospheres as a potential delivery platform, doxorubicin-loaded albumin nanospheres (DOX-AN) and doxorubicin-loaded FA-AN (FA-DOX-AN) were prepared by entrapping DOX (an anthracycline, antibiotic drug widely used in cancer chemotherapy that works by intercalating DNA) into AN and FA-AN nanoparticles. Cell uptake of the DOX was then measured. The results show that FA-AN was incorporated into HeLa cells (tumor cells) only after 2.0 h incubation, whereas HeLa cells failed to incorporate albumin nanospheres without conjugated folic acid after 4.0 h incubation. When HeLa cells were treated with the DOX-AN, FA-DOX-AN nanoparticles or free DOX, cell viability decreased with increasing culture time (i.e. cell death increases with time) over a 70 h period. Cell viability was always the lowest for free DOX followed by FA-DOX-AN4 and then DOX-AN. In a second set of experiments, HeLa cells washed to remove excess DOX after an initial incubation for 2 h were incubated for 70 h. The corresponding cell viability was slightly higher when the cells were treated with FA-DOX-AN or free DOX whilst cells treated with DOX-AN nanoparticles remained viable. The above experiments were repeated for non-cancerous, aortic smooth muscle cells (AoSMC). As expected, cell viability of the HeLa cells (with FA receptor alpha, FRα) and AoSMC cells (without FRα) decreased rapidly with time in the presence of free DOX, but treatment with FA-DOX-AN resulted in selective killing of the tumor cells. These results indicated that FA-AN may be used as a promising actively targetable drug delivery system to improve drug targeting to cancer cells.     

Early detection of cancer-associated gene alterations in DNA isolated from rat feces during intestinal tumor-induction with 1,2-dimethylhydrazine

A highly sensitive mutation detection method was applied to reveal tarry K-ras alterations in exfoliated intestinal epithelium of Fischer-344 rats during the course of 1,2-dimethylhydrazine (DMH)-induced carcinogenesis. Ten weekly s.c. injections of DMH (50 mg/kg) in combination with consumption of a low-fiber diet resulted in 100% incidence of intestinal tumors at 20 weeks after initial DMH injection. Analysis of DNA extracted from fresh fecal samples obtained individually showed that proportion of codon 12 K-ras oncogene mutant alleles (G-->A transition at the second position of codon 12) was increased in some rats at 4 weeks and clearly in all rats at 8 weeks after initial DMH injection, i.e. much earlier than the first tumors appeared (14 weeks). A gradual increase of mutant K-ras fraction in DNA samples extracted from feces led to an extremely high level of the mutant reaching 10% of the oncogene alleles at the end of the experiment (20 weeks). K- and H-ras oncogene and p53 tumor suppressor gene mutations were analyzed in the resulting colon and duodenal tumors. 14 of 17 colon tumors had K-P as mutations (11 - G-->A transition at codon 12 second base; 3 - G-->A transition at codon 13 second base). G-->A transitions at codon 12 first base of H-ras were detected in 3 colon tumors. All 5 duodenal tumors induced in the experiment had G-->A transition at codon 12 second base of K-ras. 3 of these tumors also had H-ras mutations. No mutation was detected within exons 4-7 of p53 gene indicating that p53 alterations may not be involved in the rapid development of tumors induced by high doses of DMH. Our observations suggest that detection of K-ras mutations in stool samples are predictive of later tumor development from a very early stage.     

Clinical Utility of Doppler Echocardiography in Assessing Aortic Stenosis Severity and Predicting Need for Intervention in Children

The optimal echocardiographic methodology for predicting need for intervention in children with valvar aortic stenosis (VAS) is not known. We reviewed echocardiograms and catheterization reports of 79 children (aged 9.5 +/- 5.9 years) with isolated VAS. The maximum and mean Doppler-predicted gradients from the apical (MIGAP), MEGAP)) and the suprasternal or right parasternal (MIGHP), MEGHP)) windows were measured. The peak-to-peak catheterization gradient and the intervention (if any) were recorded. All sites and methods of Doppler estimation of VAS gradient correlated in a linear fashion with the invasive gradient (R2 = 0.34-0.50) and with one another (R2 = 0.48-0.86). MIGAP and MIGHP overestimated the invasive gradient in 60% and 86% of patients, whereas MEGAP and MEGHP underestimated the invasive gradient in 94% and 83% of patients, respectively. Age and diameter of the ascending aorta had small but significant effects on the level of agreement. A MIGHP < or = 55 mm Hg predicted no intervention with 100% accuracy, whereas the specificities of a MIGHP > 90 mm Hg, a MEGAP > 50 mm Hg, and a (MIGAP + MIGHP)/2 > 70 mm Hg for intervention were 94%, 100%, and 92%, respectively. The magnitude of overestimation was significantly lower from the apical window. In children with VAS, the best prediction of the catheterization gradient could be based on the average of MIGAP and MIGHP.