Drug utilization and cost in a Medicaid population: A simulation study of community vs. mail order pharmacy

<p>Abstract</p> <p>Background</p> <p>Outpatient drugs are dispensed through both community and mail order pharmacies. There is no empirical evidence that substitution of community pharmacy with mail order reduces overall drug expenditures. The need for evaluating the potential effects on utilization and costs of the possible extension of mail order services in Medicaid provides the rationale for conducting this study. This study compares drug utilization and drug product cost in community vs. mail order pharmacy dispensing services in a Medicaid population.</p> <p>Methods</p> <p>This study is a retrospective cohort study comparing utilization and cost patterns in community vs. mail order pharmacy. A simulation model was employed to assess drug utilization and cost in mail order pharmacy using community pharmacy claim data. The model assumed that courses of drug therapy (CDT) in mail order pharmacy would have utilization patterns similar to those found in community pharmacy. A 95% confidence interval surrounding changes in average utilization and average cost were estimated using bootstrap analysis. A sensitivity analysis was performed by varying drug selection criteria and supply, fill point, and medication possession ratio (MPR). Sub-analyses were performed to address differences between mail order and community pharmacy related to therapeutic class and dual-eligible patients.</p> <p>Data for the study derived from pharmacy claims database of Ohio Medicaid State program for the period January 2000-September 2004. Drug claims were aggregated to obtain a set of CDTs representing unique patient IDs and unique drug products. Drug product cost estimates excluded dispensing fees and were used to estimate the cost reduction required in mail order to become cost neutral in comparison with community pharmacy.</p> <p>Results</p> <p>The baseline model revealed that the use of mail order vs. community pharmacy would result in a 5.5% increase in drug utilization and a 5.4% cost reduction required in mail order to become cost neutral. Results from Ohio Medicaid drugs for chronic use revealed a 5.1% increase in utilization and a 4.9% cost reduction required to become cost neutral in comparison with community pharmacy.</p> <p>Conclusion</p> <p>The results of the simulation model indicate that mail order pharmacy increases drug utilization and can also increase drug product cost if the cost per unit is not reduced accordingly. Prior consideration should be given to the patient population, day-supply, disease, therapy, and insurance characteristics to ensure the appropriate use of mail order pharmacy services.</p

Successful treatment of Candida parapsilosis mural endocarditis with combined caspofungin and voriconazole

BACKGROUND: Fungal mural endocarditis is a rare entity in which the antemortem diagnosis is seldom made. Seven cases of mural endocarditis caused by Candida spp. have been collected from literature and six of these patients died after treatment with amphotericin B. CASE PRESENTATION: We report a case of mural endocarditis diagnosed by transesophageal echocardiogram and positive blood cultures to Candida parapsilosis. Because blood cultures continued to yield C. parapsilosis despite caspofungin monotherapy, treatment with voriconazole was added. CONCLUSION: This is the first description of successful treatment of C. parapsilosis mural endocarditis with caspofungin and voriconazole

Intradermal Electroporation of Naked Replicon RNA Elicits Strong Immune Responses

RNA-based vaccines represent an interesting immunization modality, but suffer from poor stability and a lack of efficient and clinically feasible delivery technologies. This study evaluates the immunogenic potential of naked in vitro transcribed Semliki Forest virus replicon RNA (RREP) delivered intradermally in combination with electroporation. Replicon-immunized mice showed a strong cellular and humoral response, contrary to mice immunized with regular mRNA. RREP-elicited induction of interferon-γ secreting CD8+ T cells and antibody responses were significantly increased by electroporation. CD8+ T cell responses remained substantial five weeks post vaccination, and antigen-specific CD8+ T cells with phenotypic characteristics of both effector and central memory cells were identified. The immune response during the contraction phase was further increased by a booster immunization, and the proportion of effector memory cells increased significantly. These results demonstrate that naked RREP delivered via intradermal electroporation constitute an immunogenic, safe and attractive alternative immunization strategy to DNA-based vaccines

No effect of synesthetic congruency on temporal ventriloquism

A sound presented in temporal proximity to a light can alter the perceived temporal occurrence of that light (temporal ventriloquism). Recent studies have suggested that pitch–size synesthetic congruency (i.e., a natural association between the relative pitch of a sound and the relative size of a visual stimulus) might affect this phenomenon. To reexamine this, participants made temporal order judgements about small- and large-sized visual stimuli while high- or low-pitched tones were presented before the first and after the second light. We replicated a previous study showing that, at large sound–light intervals, sensitivity for visual temporal order was better for synesthetically congruent than for incongruent pairs. However, this congruency effect could not be attributed to temporal ventriloquism, since it disappeared at short sound–light intervals, if compared with a synchronous audiovisual baseline condition that excluded response biases. In addition, synesthetic congruency did not affect temporal ventriloquism even if participants were made explicitly aware of congruency before testing. Our results thus challenge the view that synesthetic congruency affects temporal ventriloquism

A Novel Modular Antigen Delivery System for Immuno Targeting of Human 6-sulfo LacNAc-Positive Blood Dendritic Cells (SlanDCs)

Previously, we identified a major myeloid-derived proinflammatory subpopulation of human blood dendritic cells which we termed slanDCs (e.g. Schäkel et al. (2006) Immunity 24, 767-777). The slan epitope is an O-linked sugar modification (6-sulfo LacNAc, slan) of P-selectin glycoprotein ligand-1 (PSGL-1). As slanDCs can induce neoantigen-specific CD4+ T cells and tumor-reactive CD8+ cytotoxic T cells, they appear as promising targets for an in vivo delivery of antigens for vaccination. However, tools for delivery of antigens to slanDCs were not available until now. Moreover, it is unknown whether or not antigens delivered via the slan epitope can be taken up, properly processed and presented by slanDCs to T cells.Single chain fragment variables were prepared from presently available decavalent monoclonal anti-slan IgM antibodies but failed to bind to slanDCs. Therefore, a novel multivalent anti-slanDC scaffold was developed which consists of two components: (i) a single chain bispecific recombinant diabody (scBsDb) that is directed on the one hand to the slan epitope and on the other hand to a novel peptide epitope tag, and (ii) modular (antigen-containing) linker peptides that are flanked at both their termini with at least one peptide epitope tag. Delivery of a Tetanus Toxin-derived antigen to slanDCs via such a scBsDb/antigen scaffold allowed us to recall autologous Tetanus-specific memory T cells.In summary our data show that (i) the slan epitope can be used for delivery of antigens to this class of human-specific DCs, and (ii) antigens bound to the slan epitope can be taken up by slanDCs, processed and presented to T cells. Consequently, our novel modular scaffold system may be useful for the development of human vaccines

Inter-organizational governance and trilateral trust building: a case study of crowdsourcing-based open innovation in China

In a case study of a Chinese crowdsourcing intermediary, we explore the impact of inter-organizational governance on trilateral trust-building. We show that formal control and relational governance mechanisms are essential for swift and knowledge-based trust in R&D crowdsourcing. The case also indicates that Chinese businesses continue to use guanxi (informal personal connections) as a relational and contingent mechanism to maintain affect-based trust, but guanxi is shown to inhibit the growth of Internet-based crowdsourcing for open innovation in China

Characterization of global transcription profile of normal and HPV-immortalized keratinocytes and their response to TNF treatment

<p>Abstract</p> <p>Background</p> <p>Persistent infection by high risk HPV types (e.g. HPV-16, -18, -31, and -45) is the main risk factor for development of cervical intraepithelial neoplasia and cervical cancer. Tumor necrosis factor (TNF) is a key mediator of epithelial cell inflammatory response and exerts a potent cytostatic effect on normal or HPV16, but not on HPV18 immortalized keratinocytes. Moreover, several cervical carcinoma-derived cell lines are resistant to TNF anti-proliferative effect suggesting that the acquisition of TNF-resistance may constitute an important step in HPV-mediated carcinogenesis. In the present study, we compared the gene expression profiles of normal and HPV16 or 18 immortalized human keratinocytes before and after treatment with TNF for 3 or 60 hours.</p> <p>Methods</p> <p>In this study, we determined the transcriptional changes 3 and 60 hours after TNF treatment of normal, HPV16 and HPV18 immortalized keratinocytes by microarray analysis. The expression pattern of two genes observed by microarray was confirmed by Northern Blot. NF-κB activation was also determined by electrophoretic mobility shift assay (EMSA) using specific oligonucleotides and nuclear protein extracts.</p> <p>Results</p> <p>We observed the differential expression of a common set of genes in two TNF-sensitive cell lines that differs from those modulated in TNF-resistant ones. This information was used to define genes whose differential expression could be associated with the differential response to TNF, such as: <it>KLK7 </it>(<it>kallikrein 7</it>), <it>SOD2 </it>(<it>superoxide dismutase 2</it>), <it>100P </it>(<it>S100 calcium binding protein P</it>), <it>PI3 </it>(<it>protease inhibitor 3, skin-derived</it>), <it>CSTA </it>(<it>cystatin A</it>), <it>RARRES1 </it>(<it>retinoic acid receptor responder 1</it>), and <it>LXN </it>(<it>latexin</it>). The differential expression of the <it>KLK7 </it>and <it>SOD2 </it>transcripts was confirmed by Northern blot. Moreover, we observed that <it>SOD2 </it>expression correlates with the differential NF-κB activation exhibited by TNF-sensitive and TNF-resistant cells.</p> <p>Conclusion</p> <p>This is the first in depth analysis of the differential effect of TNF on normal and HPV16 or HPV18 immortalized keratinocytes. Our findings may be useful for the identification of genes involved in TNF resistance acquisition and candidate genes which deregulated expression may be associated with cervical disease establishment and/or progression.</p

Molecular Characterization of the Ro/SS-A Autoantigens

AbstractMolecular techniques have recently revealed that there are several immunologically distinct Ro/SS-A antigens. Three genes encoding putative Ro/SS-A protein antigens with calculated masses of 46, 52, and 60 kD have been isolated. The encoded amino acid sequence of each is quite dissimilar. The 46-kD antigen is calreticulin (CR), a highly conserved calcium-binding protein that resides predominately in the endoplasmic reticulum where it may be involved in protein assembly. Although CR has recently been confirmed to be a new human rheumatic disease-associated autoantigen, its relationship to the other components of the Ro/SS-A ribonucleoprotein has become somewhat controversial owing predominately to the fact that recombinant forms of calreticulin have not displayed the same pattern of autoantibody reactivity possesse by the native form of this protein.The 52-kD antigen most likely resides in the nucleus and may be involved in the regulation of gene expression. The cellular location and function of the 60-kD antigen is uncertain but studies indicate that it is a RNA-binding protein.The 46- and 60-kD antigens share homology with foreign polypeptides, suggesting that an immune response initially directed against a foreign protein may give rise to the autoimmune response directed at cross-reacting self proteins

ICAR: endoscopic skull‐base surgery

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