Naturally occurring combinations of receptors from single cell transcriptomics in endothelial cells.

VEGF inhibitor drugs are part of standard care in oncology and ophthalmology, but not all patients respond to them. Combinations of drugs are likely to be needed for more effective therapies of angiogenesis-related diseases. In this paper we describe naturally occurring combinations of receptors in endothelial cells that might help to understand how cells communicate and to identify targets for drug combinations. We also develop and share a new software tool called DECNEO to identify them. Single-cell gene expression data are used to identify a set of co-expressed endothelial cell receptors, conserved among species (mice and humans) and enriched, within a network, of connections to up-regulated genes. This set includes several receptors previously shown to play a role in angiogenesis. Multiple statistical tests from large datasets, including an independent validation set, support the reproducibility, evolutionary conservation and role in angiogenesis of these naturally occurring combinations of receptors. We also show tissue-specific combinations and, in the case of choroid endothelial cells, consistency with both well-established and recent experimental findings, presented in a separate paper. The results and methods presented here advance the understanding of signaling to endothelial cells. The methods are generally applicable to the decoding of intercellular combinations of signals.

Cost-Effectiveness of Combined Sexual and Injection Risk Reduction Interventions among Female Sex Workers Who Inject Drugs in Two Very Distinct Mexican Border Cities.

BACKGROUND: We evaluated the cost-effectiveness of combined single session brief behavioral intervention, either didactic or interactive (Mujer Mas Segura, MMS) to promote safer-sex and safer-injection practices among female sex workers who inject drugs (FSW-IDUs) in Tijuana (TJ) and Ciudad-Juarez (CJ) Mexico. Data for this analysis was obtained from a factorial RCT in 2008-2010 coinciding with expansion of needle exchange programs (NEP) in TJ, but not in CJ. METHODS: A Markov model was developed to estimate the incremental cost per quality adjusted life year gained (QALY) over a lifetime time frame among a hypothetical cohort of 1,000 FSW-IDUs comparing a less intensive didactic vs. a more intensive interactive format of the MMS, separately for safer sex and safer injection combined behavioral interventions. The costs for antiretroviral therapy was not included in the model. We applied a societal perspective, a discount rate of 3% per year and currency adjusted to US$2014. A multivariate sensitivity analysis was performed. The combined and individual components of the MMS interactive behavioral intervention were compared with the didactic formats by calculating the incremental cost-effectiveness ratios (ICER), defined as incremental unit of cost per additional health benefit (e.g., HIV/STI cases averted, QALYs) compared to the next least costly strategy. Following guidelines from the World Health Organization, a combined strategy was considered highly cost-effective if the incremental cost per QALY gained fell below the gross domestic product per capita (GDP) in Mexico (equivalent to US$10,300). FINDINGS: For CJ, the mixed intervention approach of interactive safer sex/didactic safer injection had an incremental cost-effectiveness ratio (ICER) of US$4,360 ($310-$7,200) per QALY gained compared with a dually didactic strategy. Using the dually interactive strategy had an ICER of US$5,874 ($310-$7,200) compared with the mixed approach. For TJ, the combination of interactive safer sex/didactic safer injection had an ICER of US$5,921 ($104-$9,500) per QALY compared with dually didactic. Strategies using the interactive safe injection intervention were dominated due to lack of efficacy advantage. The multivariate sensitivity analysis showed a 95% certainty that in both CJ and TJ the ICER for the mixed approach (interactive safer sex didactic safer injection intervention) was less than the GDP per capita for Mexico. The dual interactive approach met this threshold consistently in CJ, but not in TJ. INTERPRETATION: In the absence of an expanded NEP in CJ, the combined-interactive formats of the MMS behavioral intervention is highly cost-effective. In contrast, in TJ where NEP expansion suggests that improved access to sterile syringes significantly reduced injection-related risks, the interactive safer-sex combined didactic safer-injection was highly cost-effective compared with the combined didactic versions of the safer-sex and safer-injection formats of the MMS, with no added benefit from the interactive safer-injection component.

Economic effects of pharmacists on health outcomes in the United States: A systematic review.

PURPOSE: A systematic review examining the economic effects of pharmacist-provided direct patient care on health outcomes in the United States was conducted. METHODS: A comprehensive literature search was conducted using 13 academic and medical databases. Studies were included in the analysis if they described pharmacist-provided direct patient care, used comparison groups, evaluated economic outcomes, and were conducted in the United States. Outcome results were categorized as (1) favorable, indicating significant improvement as a result of pharmacists' interventions or services, (2) not favorable, indicating significant improvement as a result of nonpharmacist care, (3) mixed, having favorable results on one measure of a study variable but not favorable results or no effect on another, (4) having no effect, indicating no significant difference between pharmacists' interventions or services and the comparison, or (5) unclear, indicating the outcome could not be determined based on presented data. RESULTS: Of the 56,573 citations considered, a total of 126 studies met the criteria for inclusion in this systematic review. Results favoring pharmacist-provided care were found in 20 studies (15.9%), mixed results were seen in 53 studies (42.1%), no effect was found in 6 studies (4.8%), and unclear results were found in 47 studies (37.3%). CONCLUSION: A majority of studies examining the economic effects of pharmacist-provided direct patient care in the United States were limited by their partial cost analyses, study design, and other analysis considerations. A majority of the 20 studies that found positive economic benefits examined pharmacists' interventions involving technical methods or multimodal approaches.

Clinical significance of central corneal thickness in the management of glaucoma.

OBJECTIVE: To evaluate the effect of central corneal thickness determination on the clinical management of patients with glaucoma and glaucoma suspect. METHODS: A cross-sectional retrospective study was performed on 188 consecutive patients. Mean ultrasound pachymetry measurements of central corneal thickness and corresponding Goldmann applanation tonometry measurements were obtained. Intraocular pressures (IOPs) were corrected using linear and mathematical (Orssengo-Pye) algorithms. Measurement-significant outcomes were defined as an IOP adjustment of 1.5 mm Hg or greater and outcomes-significant results as an IOP adjustment of 3.0 mm Hg or greater. Changes in therapy such as the use of eyedrops and addition or cancellation of laser therapy or surgery were then noted for those individuals with measurement- or outcomes-significant changes. RESULTS: Using the linear correction scale, 105 (55.9%) of 188 patients had at least a measurement-significant adjustment in their IOP measurements: 67 (35.6%) had adjustments between 1.5 and 3.0 mm Hg, while 38 (20.2%) had an outcomes-significant IOP adjustment (> or =3.0 mm Hg). Among the 188 patients, 16 (8.5%) had a change in eyedrop therapy, 4 (2.1%) had a change regarding laser therapy, and 6 (3.2%) had a change in the decision regarding glaucoma surgery. Using the exponential correction (Orssengo-Pye) scale, similar percentages were obtained. CONCLUSION: Pachymetry-measured central corneal thickness has a significant effect on the clinical management of patients with glaucoma and glaucoma suspect.