Placental gene transfer: transgene screening in mice for trophic effects on the placenta.

OBJECTIVE: We hypothesized that gene transfer of select growth factors to the placenta may enhance placental and fetal growth. Thus, we examined the effect of 8 growth factor transgenes on murine placenta. STUDY DESIGN: Adenoviral-mediated site-specific intraplacental gene transfer of 8 different growth factor transgenes at embryonic day (e) 14 was performed. Transgenes included angiopoietin-1, angiopoietin-2 (Ang-2), basic fibroblast growth factor, hepatocyte growth factor, insulin-like growth factor-1 (IGF-1), placenta growth hormone, platelet-derived growth factor-B (PDGF-B), and vascular endothelial growth factor(121). Fetuses and placentas were harvested at e17 and assessed for survival, gene transfer efficiency, placenta area, and fetal and placental weights. RESULTS: Efficient gene transfer to the placenta was detected with minimal dissemination to the fetus. Overexpression of IGF-1, PDGF-B, and Ang-2 resulted in an increase in placenta cross-sectional area. Only Ang-2 gene transfer resulted in increased fetal weight, and only Ang-2 and basic fibroblast growth factor resulted in a change in placental weight. CONCLUSION: Site-specific placental gene transfer results in efficient gene transfer with minimal dissemination to the fetus. Adenoviral-mediated IGF-1, adenoviral-mediated PDGF-B, and adenoviral-mediated Ang-2 significantly increase placenta growth.

Contingent Valuation Analysis of an Otolaryngology and Ophthalmology Emergency Department: The Value of Acute Specialty Care.

Importance: Specialty emergency departments (EDs) provide a unique mechanism of health care delivery, but the value that they add to the medical system is not known. Evaluation of patient preferences to determine value can have a direct impact on resource allocation and direct-to-specialist care. Objective: To assess the feasibility of contingent valuation (CV) methodology using a willingness-to-pay (WTP) survey to evaluate specialty emergency services, in the context of an ophthalmology- and otolaryngology-specific ED. Design, Setting, and Participants: Contingent valuation analysis of a standalone otolaryngology and ophthalmology ED. Participants were English-speaking adults presenting to a dedicated otolaryngology and ophthalmology ED. The WTP questions were assessed using a payment card format, with reference to an alternative modality of treatment (ie, general ED), and were analyzed with multivariate regression. Intervention: Validated WTP survey administered from October 14, 2014, through October 1, 2015. Main Outcomes and Measures: Sociodemographic data, level of distress, referral data, income, and WTP. Results: A total of 327 of 423 (77.3%) ED patients responded to the WTP survey, with 116 ophthalmology and 211 otolaryngology patients included (52.3% female; mean [range] age, 46 [18-90] years). The most common reason for seeking care at this facility was a reputation for specialty care for both ear, nose, and throat (80 [37.9%]) and ophthalmology (43 [37.1%]). Mean WTP for specialty-specific ED services was $377 for ophthalmology patients, and $321 for otolaryngology patients ($340 overall; 95% CI, $294 to $386), without significant difference between groups (absolute difference, $56; 95% CI, $-156 to $43). Self-reported level of distress was higher among ear, nose, and throat vs ophthalmology patients (absolute difference, 0.47 on a Likert scale of 1-7; 95% CI, 0.10 to 0.84). Neither level of distress, income, nor demographic characteristics influenced WTP, but patients with higher estimates of total visit cost were more likely to have higher WTP (ß coefficient, 0.27; SE, 0.05; adjusted R2 = 0.17 for model). Conclusions and Relevance: Patients with eye and ear, nose, and throat complaints place a mean explicit value on specialty emergency services of $340 per visit, relative to general emergency care. Ultimately, CV data using WTP methodology are useful in valuing patient preferences in monetary terms and can help inform state-wide resource allocation and the availability of direct-to-specialist care.

Cost-Benefit Analysis of an Otolaryngology Emergency Room Using a Contingent Valuation Approach.

OBJECTIVES: Dedicated otolaryngology emergency rooms (ERs) provide a unique mechanism of health care delivery. Relative costs and willingness to pay (WTP) for these services have not been studied. This study aims to provide a cost-benefit analysis of otolaryngology-specific ER care. STUDY DESIGN: Cost-benefit analysis based on contingent valuation surveys. SETTING: An otolaryngology-specific ER in a tertiary care academic medical center. SUBJECTS AND METHODS: Adult English-speaking patients presenting to an otolaryngology ER were included. WTP questions were used to assess patient valuations of specialty emergency care. Sociodemographic data, income, and self-reported levels of distress were assessed. State-level and institution-specific historical cost data were merged with WTP data within a cost-benefit analysis framework. RESULTS: The response rate was 75.6%, and 199 patients were included in the final analysis. Average WTP for otolaryngology ER services was $319 greater than for a general ER (95% CI: $261 to $377), with a median value of $200. The historical mean cost per visit at a general ER was $575, and mean cost at the specialty ER was $551 (95% CI: $529 to $574). Subtracting incremental cost from incremental WTP yielded a net benefit of $343. CONCLUSION: Dedicated otolaryngology ER services are valued by patients for acute otolaryngologic problems and have a net benefit of $343 per patient visit. They appear to be a cost-beneficial method for addressing acute otolaryngologic conditions. This study has implications for ER-based otolaryngologic care and direct-to-specialist services.

Enhanced epithelial gap closure and increased angiogenesis in wounds of diabetic mice treated with adult murine bone marrow stromal progenitor cells.

The direct application of bone marrow (BM) can accelerate the healing of chronic wounds. We hypothesized that this effect is due to the presence of stromal progenitor cells (SPCs) found within whole BM preparations. To test this hypothesis, we isolated adult murine SPCs from whole BM and examined their ability to enhance impaired wound healing compared with ficoll separated BM cells in the diabetic (db/db) mouse model. SPCs significantly enhanced reepithelialization, granulation tissue formation, and neovascularization compared with control wounds treated with BM or PBS alone. Higher frequencies of donor SPC cells compared with donor BM cells were observed in treated wounds at 7 days. Transdifferentiation into GFP-positive mature endothelial cells was not observed. These observations suggest that SPCs improve wound healing through indirect mechanisms which lead to enhanced vascularization rather than through direct participation and incorporation into tissue. We conclude that topical application of BM-derived SPCs may represent an effective strategy for the treatment of chronic diabetic wounds.