A health economic analysis of the use of rhBMP-2 in Gustilo–Anderson grade III open tibial fractures for the UK, Germany, and France

The purpose of this study was to determine the cost savings from a societal perspective for recombinant human Bone Morphogenetic Protein-2 (rhBMP-2) in grade III A and B open tibial fractures treated with a locked intramedullary nail and soft-tissue management in the UK, Germany, and France. Health care system costs (direct health care costs) and costs for productivity losses (indirect health care costs) were calculated using the raw data from the Bone Morphogenetic Protein Evaluation Group in Surgery for Tibial Trauma “BESTT study”. Return-to-work time for estimation of productivity losses was assumed to correspond with the time of fracture healing. For calculation of secondary interventions costs and productivity losses the respective 2007/2008 national tariffs for surgical procedures and average national wages for the UK, Germany, and France were used. For a 1 year perspective, overall treatment costs per patient after the initial surgery of the control vs. the rhBMP-2 group were €44,757 vs. €36,847 for the UK, €50,197 vs. €40,927 for Germany and €48,766 vs. €39,474 for France in favour of rhBMP-2 with overall savings overall savings per case of rhBMP-2 treatment of €7911 for the UK, €9270 for Germany, and €9291 for France which was mainly due to reduced productivity losses by significant faster fracture healing in the rhBMP-2 group (p = 0.01). These savings largely offset the upfront price of rhBMP-2 of €2266 (£1790) in the UK, €2970 in Germany, and €2950 in France. Total net savings can be estimated to be €9.6 million for the UK, €14.5 million for Germany, and €11.4 million for France. The results depend on the methodology used particularly for calculation of productivity losses and return-to-work time which was assumed to correspond with fracture healing time. In summary, despite the apparent high direct cost of rhBMP-2 in grade III A and B open tibial fractures, at a national level there are net cost savings from a societal perspective for all three countries.     

Cost‐effectiveness of treating vascular leg ulcers with UrgoStart® and UrgoCell® Contact

Although chronic wounds have a high socio‐economic impact, data on comparative effectiveness of treatments are rare. UrgoStart^® is a hydroactive dressing containing a nano‐oligosaccharide factor (NOSF). This study aimed at evaluating the cost‐effectiveness of this NOSF‐containing wound dressing in vascular leg ulcers compared with a similar neutral foam dressing (UrgoCell^® Contact) without NOSF. Cost‐effectiveness analysis from the perspective of the German statutory health care system was performed using a decision tree model for a period of 8 weeks. Cost and outcome data were derived from the clinical study ‘Challenge’ suggesting a response rate (≥40% wound size reduction) of UrgoStart^® of 65·6% versus 39·4% for the comparator. In the treatment model, effect‐adjusted costs of €849·86 were generated after 8 weeks for treatment with UrgoStart^® versus €1335·51 for the comparator resulting in an effect‐adjusted cost advantage of €485·64 for UrgoStart^®. In linear sensitivity analyses, the outcomes were stable for varying assumptions on prices and response rates. In an 8‐week period of treatment for vascular leg ulcers, UrgoStart^® shows superior cost‐effectiveness when compared with the similar neutral foam dressing without any active component (NOSF). As demonstrated within a randomised, double‐blind clinical trial, UrgoStart^® is also more effective in wound area reduction than the neutral foam dressing. Wound healing was not addressed in this clinical trial. Follow‐up data of 12 months to allow for reulceration assessment were not generated.     

The multiply injured child

The treatment of multiple traumas in children requires knowledge of common injury patterns, incidence, mortality, and the consequences and differences between these injuries in children and adult patients. However, epidemiological studies concerning pediatric multiple trauma are rare. To address this, data were collected and analyzed from 682 multiple trauma patients treated at a Level I trauma center. The patients were divided into four age-related groups (< 6 years, 6-12 years, 13-18 years, and 18-40 years) and were evaluated for trauma mechanism, injury distribution, and cause of death. Children aged 6 to 17 years mostly were injured as pedestrians and cyclists whereas infants, preschoolers, and adults more commonly were injured as car passengers. Pediatric patients suffered a significantly higher mortality than adults, with a threefold increased risk of death when injured as passengers in car accidents. Injuries to the head and the legs were most common. A lower incidence of thoracic (28% versus. 62%), abdominal (20% versus 36%), pelvic (22% versus 35%), and upper limb (32% versus 43%) trauma was observed in children (< 18 years) than in adults (18-40 years). Nevertheless, trauma to the thorax, abdomen, and head were associated with a high risk of death in all groups. Spinal cord injuries, especially in the cervical region, also carried a high risk of mortality (36.8 in the group of patients younger than 18 years and 18.9 in the group of patients 18-40 years). Children younger than 6 years had the most severe head injuries. The data show that there are important differences in incidence, mortality, and injury patterns between pediatric and adult patients with multiple traumas.     

Effect of Temperature on the Longitudinal Variability of Quantitative Ultrasound Variables

It is unclear whether longitudinal change in phantom measurements bears any relation to the long-term in vivo instrument performance of quantitative ultrasound devices. Longitudinal quantitative ultrasound phantom data were obtained by measuring the manufacturer-provided phantom at ambient temperature and two different sets of Leeds phantoms at either ambient temperature or following a phantom temperature-control protocol. Measurements were performed using the Achilles Plus bone densitometer. Changes in longitudinal phantom data were compared to in vivo quantitative ultrasound data obtained from seven healthy, young volunteers. A cosinor model with linear trend and Hotelling's T2-test were used to quantify seasonal rhythms and long-term drift in quantitative ultrasound variables. Temperature effects and marked seasonal rhythms on quantitative ultrasound phantom measurements were evident but were far less apparent in vivo. Longitudinal precision of quantitative ultrasound variables was poorer for the manufacturer-provided phantom than for phantoms that were subjected to a temperature-control protocol or for healthy volunteers. This study has shown that longitudinal precision and longitudinal change differs between in vivo and phantom data. Longitudinal quantitative ultrasound measurements for monitoring change in skeletal status cannot, as yet, be properly controlled.     

Effects of short-term propofol administration on pancreatic enzymes and triglyceride levels in children

This prospective, clinical trial evaluated the effects of short-term propofol administration on triglyceride levels and serum pancreatic enzymes in children undergoing sedation for magnetic resonance imaging. Laboratory parameters of 40 children, mean age (SD; range) 67 (66; 4-178) months undergoing short-term sedation were assessed before and 4 h after having received propofol. Mean (SD) propofol loading dose was 2.2 (1.1) mg.kg(-1) followed by continuous propofol infusion of 6.9 (0.9) mg.kg(-1).h(-1). Serum lipase levels (p = 0.035) and serum triglyceride levels (p = 0.003) were raised significantly after propofol administration but remained within normal limits. No significant changes in serum pancreatic-amylase levels were seen (p = 0.127). In two (5%) children, pancreatic enzymes and in four (10%) children triglyceride levels were raised above normal limits; however, no child showed clinical symptoms of pancreatitis. We conclude that even short-term propofol administration with standard doses of propofol may have a significant effect on serum triglyceride and pancreatic enzyme levels in children.     

Antigen recognition induces phosphatidylserine exposure on the cell surface of human CD8+ T cells

In eukaryotic cells the phospholipid phosphatidylserine (PS) is restricted to the inner plasma-membrane leaflet. This lipid asymmetry, which is maintained by the concerted action of phospholipid transport proteins, is mainly lost during apoptosis. Here, we demonstrate that primary human CD8+ cytotoxic T lymphocytes (CTLs) expose PS on T-cell receptor (TCR)-mediated antigen (Ag) recognition. In contrast to PS externalization on apoptotic cells, activation-induced PS exposure is less pronounced and reversible. Fluorescence microscopic analysis revealed that PS is distributed nonhomogenously over the plasma membrane and concentrated in membrane lipid raft domains at the immunologic synapse. By studying the activity of PS transport proteins using a fluorescence-labeled PS analogue, we found that activation of CTLs inhibited the flippase-mediated inward-directed PS transport without affecting the outward transport. Shielding of exposed PS by annexin V protein during Ag recognition diminished cytokine secretion, activation, and cell-to-cell clustering of Ag-specific CTLs. In summary, our data demonstrate for the first time that externalized PS on Ag-stimulated CTLs is linked to T-cell activation and probably involved in cell-to-cell contact formation at the immunologic synapse.     

Penetrating keratoplasty in patients with atopic dermatitis with and without systemic cyclosporin A

PURPOSE: Clinical experience suggests that atopic dermatitis is a considerable risk factor in penetrating keratoplasty. The scientific evidence, however, has been equivocal. Systemic cyclosporin A reduces the threat of immune reactions and simultaneously improves atopic dermatitis. The purpose of this study was to evaluate to what extent and for how long systemic cyclosporin A improves graft prognosis in patients with atopic dermatitis. PATIENTS AND METHODS: Between November 1986 and July 1994, 173 penetrating keratoplasties were performed on keratoconus patients without skin disease (I). Fifteen penetrating keratoplasties were performed on patients with keratoconus associated with slight atopic dermatitis (II), 24 on patients with keratoconus associated with severe atopic dermatitis (III), and 13 on patients with keratitis in atopic dermatitis but without keratoconus (IV). Systemic cyclosporin A was administered for at least 6 months in groups III and IV. Clear graft survival was estimated according to Kaplan and Meier, and statistical significance was evaluated via log-rank test. RESULTS: Six months/6 years postoperatively 99.5 and 96.5% (I), 80 and 80% (II), 96 and 83.2% (III), and 100 and 65.8% (IV) of the grafts were clear. Only the differences between the survival curve of group I and the curves of each of groups II-IV were statistically significant (p < 0.001). CONCLUSIONS: To our knowledge, this is the first study proving that atopic dermatitis with and without keratoconus deteriorates graft prognosis statistically significantly. The application of systemic cyclosporin A improves graft prognosis in atopic dermatitis as long as the drug is applied, and this effect slowly fades thereafter.     

Eccentric fixation in Stargardt's disease assessed by Tübingen perimetry

PURPOSE: To measure eccentric fixation characteristics in visual fields of patients with Stargardt's disease. METHODS: The positions of fixation loci (FL) in the visual field were determined by Tübingen perimetry (TP), using the position of the blind spots in 173 patients. Altogether, 669 visual fields were measured at baseline and during follow-up. Twenty patients were also examined by scanning laser ophthalmoscope (SLO). RESULTS: Ninety-five of 173 patients showed a ring scotoma with central fixation in at least one test, which could persist for up to 18.8 years. The median age for a 50% chance of the development of eccentric fixation was 23.6 years. One hundred four patients (203 eyes) used eccentric fixation in at least one eye; in 154 eyes, the FL was placed below the scotoma and in 33 eyes to the left of it, in 11 to the right of it, and in 5 above it. Once the FL was chosen, it remained within the same visual field area at subsequent tests, varying on average by 1.76 degrees. Compared with SLO results, the mean distance between FL and PRL was 1.90 degrees. CONCLUSIONS: It is possible to determine the position of the FL by perimetry with sufficient accuracy if the blind spot is well delimited. Stargardt patients can keep central fixation for different time intervals before changing to an eccentric FL. Most of them show an FL below the central scotoma, which is considered favorable for horizontal reading.