Cost-Effective Use of Silver Dressings for the Treatment of Hard-to-Heal Chronic Venous Leg Ulcers

Aim To estimate the cost-effectiveness of silver dressings using a health economic model based on time-to-wound-healing in hard-to-heal chronic venous leg ulcers (VLUs). Background Chronic venous ulceration affects 1–3% of the adult population and typically has a protracted course of healing, resulting in considerable costs to the healthcare system. The pathogenesis of VLUs includes excessive and prolonged inflammation which is often related to critical colonisation and early infection. The use of silver dressings to control this bioburden and improve wound healing rates remains controversial. Methods A decision tree was constructed to evaluate the cost-effectiveness of treatment with silver compared with non-silver dressings for four weeks in a primary care setting. The outcomes: ‘Healed ulcer’, ‘Healing ulcer’ or ‘No improvement’ were developed, reflecting the relative reduction in ulcer area from baseline to four weeks of treatment. A data set from a recent meta-analysis, based on four RCTs, was applied to the model. Results Treatment with silver dressings for an initial four weeks was found to give a total cost saving (£141.57) compared with treatment with non-silver dressings. In addition, patients treated with silver dressings had a faster wound closure compared with those who had been treated with non-silver dressings. Conclusion The use of silver dressings improves healing time and can lead to overall cost savings. These results can be used to guide healthcare decision makers in evaluating the economic aspects of treatment with silver dressings in hard-to-heal chronic VLUs

Complete Protection against Lethal Toxoplasma gondii Infection in Mice Immunized with a Plasmid Encoding the SAG1 Gene

Infection with the protozoan parasite Toxoplasma gondii is transmitted to humans from infected animals by tissue cysts and oocysts excreted by cats. Immunization with inactivated parasites or recombinant proteins has at best shown partial protection. We constructed a plasmid expressing the SAG1 surface antigen of T. gondii, p1tPASAG1, and showed that animals immunized with the plasmid produce anti-SAG1 antibodies which recognize the native SAG1. Mice immunized with p1tPASAG1 showed 80 to 100% protection against challenge with the non-cyst-producing, virulent RH isolate, compared to an 80% mortality in mice immunized with empty plasmid, which is the greatest efficacy of any vaccine against T. gondii produced so far. The SAG1 molecule was analyzed for potential cytotoxic T-lymphocyte (CTL) epitopes, and four peptides with the best fit were synthesized. The ability of the peptides to stimulate gamma interferon production by CD8(+) T cells from p1tPASAG1-immunized mice was tested in an ELISPOT assay, and one new CTL epitope was identified. Adoptive transfer of CD8(+) T cells from p1tPASAG1-immunized to naïve mice showed partial protection. In conclusion, DNA vaccination with p1tPASAG1 gave effective protection in mice against T. gondii infection and the protection could be adoptively transferred by purified CD8(+) T cells

Sensitivity analysis. Change in incremental cost (£) per patient (silver treatment versus non-silver treatment) when changing key assumptions ±50%.

<p>The figure includes the assumptions that ‘Dressing change per week. Normal wound’; ‘Cost of primary care visit. Normal wound’; ‘Cost of silver dressing’; have the highest impact on the incremental cost per patient. For example if the ‘cost of silver dressing’ was higher (turquoise bar) the incremental cost per patient would be reduced, nevertheless, even if the price of silver dressing is 50% more expensive the incremental cost would remain below zero (i.e. be cost-saving).</p

Comparison of cost of wound management (£) using a four week silver treatment compared with non-silver treatment in primary care.

<p>*Based on linear extrapolation of wound closure during first 4 weeks observed in the meta-analysis <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0100582#pone.0100582-Leaper2" target="_blank">[22]</a>.</p><p>**Unit cost of initial assessment/follow up (From <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0100582#pone-0100582-t001" target="_blank">Table 1:</a> £103.47 initial assessment + £84.04 follow-up visit + £29.95 ABPI assessment + £5.50 Duplex scan (10% of patients assumed to be referred to duplex scan)).</p><p>***Total healing time was assumed equal to average time to healing in patients with non-expanding wound estimated in the meta-analysis (minimum of healing time estimated for silver treatment respectively non-silver treatment arm). The split between weeks with complicated wound and normally healing wound was equal in both silver treatment and non-silver treatment arms.</p>†<p>High frequency dressing change (4 times/week).</p>‡<p>Low frequency dressing change (2 times/week).</p

Framework for health economic model. The patient cohort consisted of 659 patients with hard-to-heal VLUs.

<p>Framework for health economic model. The patient cohort consisted of 659 patients with hard-to-heal VLUs.</p

Patient outcome after four weeks silver dressing compared with non-silver wound management in pooled data set from four clinical trials.

<p>*Applies to 'Healing ulcer' only. Number of weeks after week 4. Estimates truncated at 1 year.</p>†<p>Data from meta-analysis <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0100582#pone.0100582-Leaper2" target="_blank">[22]</a>.</p>‡<p>Unpublished data.</p