There is increasing evidence that innervation, possibly mediated via neuropeptides, promotes wound healing. This study presents data on the early cellular events during healing in denervated tissue. Free oblique groin flaps were raised on 25 adult Sprague-Dawley rats. Excisional wounds were placed within the flap and in two control sites, the contralateral inguinal region and the thorax. The absence of innervation in the free flap wounds was confirmed 10 days after surgery by indirect immunofluorescence with a pan-neuronal marker. The cellular infiltrate of the wounds was analysed immunohistochemically with a panel of antibodies to rat macrophages and monocytes (ED1), rat B lymphocytes (CD45R) and T lymphocytes (CD2). The immunostained cellular infiltrate was quantified at 2, 4, 7 and 10 days postoperatively. Our results show that denervated wounds have a significantly lower macrophage and T-lymphocyte count at day 4 of wound healing (P < 0.05). Inflammatory cells, particularly macrophages, are known to play an important part in wound healing and their reduced chemotaxis in denervated tissue may be related to the observed delay in wound closure.

No abstract

Thirty-eight fingers in 27 patients with Dupuytren's contracture of the proximal interphalangeal joint (PIPJ) in excess of 70° were treated using a staged technique. The first stage involved applying a mini external fixator across the PIPJ for continuous extension over 6 weeks with intensive hand therapy to maintain mobility of the joint and help correct the deformity. Twice weekly during hand therapy sessions the tension of the elastic band across the mini ex-fix was increased, allowing that full active flexion of the PIPJ against the elastic band could still be achieved. The second stage, 4 weeks after the external fixator was applied, involved an open palm technique of fasciectomy for the contracted cords restricting metacarpophalangeal joint movement and dermofasciectomy with full-thickness skin grafting over the proximal phalanx for bands restricting PIPJ movement. The external fixator was used to maintain active extension force until the graft healed. It was generally removed in the outpatient clinic under ring block 2 weeks after the second stage procedure. The patients were followed for a mean of 20.6 (6-48) months. The mean preoperative PIPJ deformity improved from 75° to 37° postoperatively. Overall, 69% of results were rated as good to excellent. Only one patient reported any on-going functional problems. There were eight cases of pin site infections and one case each of loose pins, osteoarthritics at the PIPJ, reflex sympathetic dystrophy, and disease recurrence needing PIPJ fusion. We conclude that our simple staged procedure is a valid alternative in the management of severe Dupuytren's PIPJ contracture.

Orphan drugs (ODs) are intended for the diagnosis, prevention, or treatment of rare diseases. Many cancer subtypes, including all childhood cancers, are defined as rare diseases, and over one-third of ODs are now intended to treat oncology indications. However, market access for oncology ODs is becoming increasingly challenging; ODs are prone to significant uncertainty around their cost-effectiveness, while payers must balance the need for these vital innovations with growing sensitivity to rising costs. The objective of this review was to evaluate different mechanisms that have been introduced to facilitate patient access to oncology ODs in five different countries (Australia, Canada, England, France, and Sweden), using eight oncology ODs and non-orphan oncology drugs as examples of their application. A targeted literature review of health technology assessment (HTA) agency websites was undertaken to identify country-specific guidance and HTA documentation for recently evaluated oncology ODs and non-orphan oncology drugs. None of these countries were found to have explicit HTA criteria for the assessment of ODs, and therefore, oncology ODs are assessed through the usual HTA process. However, distinct and additional processes are adopted to facilitate access to oncology ODs. Review of eight case-study drugs showed that these additional assessment processes were rarely used, and decisions were largely driven by proving cost-effectiveness using standard incremental cost-effectiveness ratio (ICER) thresholds. The predominant implication arising from this study is that application of standard HTA criteria to oncology ODs in many countries fails to take into account any uncertainties around their clinical- and cost-effectiveness, resulting in disparities in HTA reimbursement decisions based on differences in addressing or accepting uncertainty. In order to address this issue, HTA agencies should adopt a more flexible approach to cost-effectiveness, as typified by the Tandvårds-och Läkemedelsförmånsverket in Sweden, which takes into account the small patient numbers involved, limited budget impact, and high unmet medical needs.