Delayed delivery of second twin: a multicentre study of 35 cases.

OBJECTIVE: The aim of this study was to conduct a statistical analysis to determine the outcome of conservative treatment after delivery of a first fetus in multiple pregnancy and thus define new prognostic factors. STUDY DESIGN: Multicentre retrospective study involving 12 centers over a 10-year period. RESULTS: Twenty-eight twin pregnancies and seven triplet pregnancies which were managed conservatively. In twin pregnancies, 79% of the delayed-delivery fetuses survived; only 7% of the first delivered fetuses survived. The mean interval between deliveries was 47 days. No statistical difference was found concerning cerclage, antibiotic therapy, tocolysis and hospitalization. Earlier delivery of the first twin and premature rupture of membranes for the second twin were significantly related to a longer interval between deliveries. CONCLUSION: Delayed delivery in multifetal pregnancies can be successful if there are no contraindications and these pregnancies are managed in a tertiary perinatal center. Publications limited to successful cases have undoubtedly introduced some bias in assessment.

The impact of information on patient preferences in different delivery patterns: a contingent valuation study of prescription versus OTC drugs.

OBJECTIVES: Our analysis assessed the impact of information on patients' preferences in prescription versus over-the-counter (OTC) delivery systems. METHODS: A contingent valuation (CV) study was implemented, randomly assigning 534 lay people into the receipt of limited or extended information concerning new influenza drugs. In each information arm, people answered two questions: the first asked about willingness to pay (WTP) for the new prescription drug; the second asked about WTP for the same drug sold OTC. RESULTS: We show that WTP is higher for the OTC scenario and that the level of information plays a significant role in the evaluation of the OTC scenario, with more information being associated with an increase in the WTP. In contrast, the level of information provided has no impact on WTP for prescription medicine. Thus, for the kind of drug considered here (i.e. safe, not requiring medical supervision), a switch to OTC status can be expected to be all the more beneficial, as the patient is provided with more information concerning the capability of the drug. CONCLUSIONS: Our results shed light on one of the most challenging issues that health policy makers are currently faced with, namely the threat of a bird flu pandemic. Drug delivery is a critical component of pandemic influenza preparedness. Furthermore, the congruence of our results with the agency and demand theories provides an important test of the validity of using WTP based on CV methods.

Delivery of antisense oligonucleotide to the cornea by iontophoresis.

We wished to evaluate the potential of iontophoresis to promote the delivery of antisense oligonucleotides (ODN) directed at the vascular endothelial growth factor (VEGF)-R2 receptor (KDR/Flk) to the cornea of the rat eye. Fluorescence (CY5)-labeled ODNs in phosphate-buffered saline (PBS) (20 microM) were locally administered to rat eyes, and their fate within the anterior segment was studied. Thirty-four male, 5-week-old Wistar rats were used for all experiments. The rats were divided in four groups. In group I (12 rats, 12 eyes), the ODNs (20 microM) were delivered by iontophoresis (300 microA for 5 minutes) using a specially designed corneal applicator. In group II (12 rats, 12 eyes), the ODNs (20 microM) were delivered using the same applicator, but no electrical current was applied. In group III (6 rats, 6 eyes), a corneal neovascular reaction was induced prior to the application of ODNs (20 microM), and iontophoresis electrical current was delivered as for group I rats. Group IV (4 rats, 4 eyes) received ODN (60 microM) iontophoresis application (300 microA for 5 minutes) and were used for ODN integrity studies. The animals were killed 5 minutes, 90 minutes, and 24 hours after a single ODN application and studied. Topically applied ODNs using the same iontophoresis applicator but without current do not penetrate the cornea and remain confined to the superficial epithelial layer. ODNs delivered with transcorneoscleral iontophoresis penetrate into all corneal layers and are also detected in the iris. In corneas with neovascularization, ODNs were particularly localized within the vascular endothelial cells of the stroma. ODNs extracted from eye tissues 24 hours after iontophoresis remained unaltered. The iontophoresis current did not cause any detectable ocular damage under these conditions. Iontophoresis promotes the delivery of ODNs to the anterior segment of the eye, including all corneal layers. Iontophoresis of ODNs directed at VEGF-R2 may be used for the design of specific antiangiogenic strategy in diseases of the cornea.

Cultural Biases in Public Service Delivery : Evidence from a Regression Discontinuity Approach

What determines the share of public employment, at a given size of the State, in countries of similar levels of economic development? While the theoretical and empirical literature on this issue has mostly considered technical dimensions (efficiency and political considerations), this paper emphasizes the role of culture and quantifies it. We build a representative database for contracting choices of municipalities in Switzerland and exploit the discontinuity at the Swiss language border at identical actual set of policies and institutions to analyze the causal e↵ect of culture on the choice of how public services are provided. We find that French-speaking border municipalities are 50% less likely to contract with the private sector than their German-speaking adjacent municipalities. Technical dimensions are much smaller by comparison. This result points out that culture is a source of a potential bias that distorts the optimal choice for public service delivery. Systematic differences in the level of confidence in public administration and private companies potentially explain this discrepancy in private sector participation in public services provision.

Nanocarriers for DNA Vaccines: Co-Delivery of TLR-9 and NLR-2 Ligands Leads to Synergistic Enhancement of Proinflammatory Cytokine Release

Adjuvants enhance immunogenicity of vaccines through either targeted antigen delivery or stimulation of immune receptors. Three cationic nanoparticle formulations were evaluated for their potential as carriers for a DNA vaccine, and muramyl dipeptide (MDP) as immunostimulatory agent, to induce and increase immunogenicity of Mycobacterium tuberculosis antigen encoding plasmid DNA (pDNA). The formulations included (1) trimethyl chitosan (TMC) nanoparticles, (2) a squalene-in-water nanoemulsion, and (3) a mineral oil-in-water nanoemulsion. The adjuvant effect of the pDNA-nanocomplexes was evaluated by serum antibody analysis in immunized mice. All three carriers display a strong adjuvant effect, however, only TMC nanoparticles were capable to bias immune responses towards Th1. pDNA naturally contains immunostimulatory unmethylated CpG motifs that are recognized by Toll-like receptor 9 (TLR-9). In mechanistic in vitro studies, activation of TLR-9 and the ability to enhance immunogenicity by simultaneously targeting TLR-9 and NOD-like receptor 2 (NLR-2) was determined by proinflammatory cytokine release in RAW264.7 macrophages. pDNA in combination with MDP was shown to significantly increase proinflammatory cytokine release in a synergistic manner, dependent on NLR-2 activation. In summary, novel pDNA-Ag85A loaded nanoparticle formulations, which induce antigen specific immune responses in mice were developed, taking advantage of the synergistic combinations of TLR and NLR agonists to increase the adjuvanticity of the carriers used.

Targeting iron-mediated retinal degeneration by local delivery of transferrin.

Iron is essential for retinal function but contributes to oxidative stress-mediated degeneration. Iron retinal homeostasis is highly regulated and transferrin (Tf), a potent iron chelator, is endogenously secreted by retinal cells. In this study, therapeutic potential of a local Tf delivery was evaluated in animal models of retinal degeneration. After intravitreal injection, Tf spread rapidly within the retina and accumulated in photoreceptors and retinal pigment epithelium, before reaching the blood circulation. Tf injected in the vitreous prior and, to a lesser extent, after light-induced retinal degeneration, efficiently protected the retina histology and function. We found an association between Tf treatment and the modulation of iron homeostasis resulting in a decrease of iron content and oxidative stress marker. The immunomodulation function of Tf could be seen through a reduction in macrophage/microglial activation as well as modulated inflammation responses. In a mouse model of hemochromatosis, Tf had the capacity to clear abnormal iron accumulation from retinas. And in the slow P23H rat model of retinal degeneration, a sustained release of Tf in the vitreous via non-viral gene therapy efficently slowed-down the photoreceptors death and preserved their function. These results clearly demonstrate the synergistic neuroprotective roles of Tf against retinal degeneration and allow identify Tf as an innovative and not toxic therapy for retinal diseases associated with oxidative stress.

Delivery of antigen to nasal-associated lymphoid tissue microfold cells through secretory IgA targeting local dendritic cells confers protective immunity.

BACKGROUND: Transmission of mucosal pathogens relies on their ability to bind to the surfaces of epithelial cells, to cross this thin barrier, and to gain access to target cells and tissues, leading to systemic infection. This implies that pathogen-specific immunity at mucosal sites is critical for the control of infectious agents using these routes to enter the body. Although mucosal delivery would ensure the best onset of protective immunity, most of the candidate vaccines are administered through the parenteral route. OBJECTIVE: The present study evaluates the feasibility of delivering the chemically bound p24gag (referred to as p24 in the text) HIV antigen through secretory IgA (SIgA) in nasal mucosae in mice. RESULTS: We show that SIgA interacts specifically with mucosal microfold cells present in the nasal-associated lymphoid tissue. p24-SIgA complexes are quickly taken up in the nasal cavity and selectively engulfed by mucosal dendritic cell-specific intercellular adhesion molecule 3-grabbing nonintegrin-positive dendritic cells. Nasal immunization with p24-SIgA elicits both a strong humoral and cellular immune response against p24 at the systemic and mucosal levels. This ensures effective protection against intranasal challenge with recombinant vaccinia virus encoding p24. CONCLUSION: This study represents the first example that underscores the remarkable potential of SIgA to serve as a carrier for a protein antigen in a mucosal vaccine approach targeting the nasal environment.

Care delivery value chains for ophthalmic clinics in Switzerland

Perceived patient value is often not aligned with the emerging expenses for health care services. In other words, the costs are often supposed as rising faster than the actual value for the patients. This fact is causing major concerns to governments, health plans, and individuals. Attempts to solve the problem have habitually been on the operational effectiveness side: increasing patient volume, minimizing costs, rationing, or closing hospitals, usually resulting in a zero-sum game. Only few approaches come from the strategic positioning side and "competition" among hospitals is still perceived rather as a danger than as a chance to create a positive-sum game and stimulate patient value. In their 2006 book, "Redefining Health Care", the renowned Harvard strategy professor Michael E. Porter and hospital management expert Professor Elizabeth Olmsted Teisberg approach the challenge from the positive-sum perspective: they propose to form Integrated Practice Units (IPUs) and manage hospitals in a modern, patient value oriented way. They argue that creating value-based competition on results should have the same effect on the health care sector like transparency and competition turned other industries with out-dated management models (like recently the inert telecommunication industry) into highly competitive and customer value creating businesses. The objective of this paper is to elaborate Care Delivery Value Chains for Integrated Practice Units in ophthalmic clinics and gather a first feedback from Swiss hospital managers, ophthalmologists, and patients, if such an approach could be a realistic way to improve health care management. First, Porter's definition of competitiveness (distinction between operational effectiveness and strategic positioning) is explained. Then, the Care Delivery Value Chain is introduced as a key element for understanding value-based management, followed by three practice examples for ophthalmic clinics. Finally, recommendations are given how the Care Delivery Value Chain can be managed efficiently and how the obstacles of becoming a patient-oriented organization can be overcome. The conclusion is that increased transparency and value-based competition on results has the potential to change the mindset of hospital managers-which will align patient value with the emerging health care expenses. Early adapters of this management approach will gain a competitive advantage. [Author, p. 6]