Pulmonary arterial hypertension (PAH) has a high morbidity rate and is fatal if left untreated. Increasing evidence supports early intervention, possibly with initial combination therapy. PAH-specific pharmaceuticals, however, are expensive and may have serious adverse effects, particularly when used in combination. The currently dynamic health care economy reinforces the need for a review of early intervention from both outcomes and economic perspectives. We aimed to review the clinical and economic impact of PAH therapy, particularly examining drug cost, hospitalization burden, and health care economics impact, and the effect of early intervention on clinical outcomes. We searched PubMed, Scopus, Ovid, and MEDLINE databases from 2005 to 2017 for studies comparing drug cost, clinical outcomes, and hospitalization burden associated with therapy for PAH. Emerging data indicate that early therapy is effective, but drug therapy is expensive, particularly with combination therapy. Efficacy studies also generally show benefit of combination therapy for patients in World Health Organization functional class II, with a consistent decrease in hospitalization. Pharmacoeconomic studies are limited but indicate that increased pharmacy costs are at least partially offset by decreased health care utilization, particularly inpatient care. Modeling also shows a cost benefit with combination therapy at 2 years. Nonetheless, more rigorously collected health care economic data should be incorporated into future drug efficacy trials to provide a clearer understanding of the impact and the associated cost benefit of early PAH therapy. Increasing evidence in support of early intervention and combination therapy for PAH is associated with rising medication costs that are largely offset by reduced hospitalization, on the basis of the currently available literature. Nonetheless, the studies performed to date have methodologic limitations that highlight the need for prospective studies using more robust economic modeling.

Pulmonary arterial hypertension (PAH) is a devastating disease with significant morbidity and mortality. There are many psychosocial and financial implications of this disease; however, little is known how this affects the treatment of PAH patients. A questionnaire-based prospective cohort study was performed on 106 PAH patients from a Pulmonary Hypertension Center and the Pulmonary Hypertension Association national conference in 2018. The demographic, treatment, psychosocial, employment, financial impact on treatment data was obtained. The majority of patients had cardiopulmonary symptoms despite treatment. The symptoms affected their social and work lives, with about one in three applying for disability because of their PAH. The majority of PAH patients had insurance coverage, but still noted a significant financial burden of the disease, with nearly a half who needed financial assistance to pay for their PAH medications. Thirty (28.3%; 95% CI, 20.6–37.5%) patients mentioned they changed their medication regimen, with some skipping doses outright (28 [26.4%; 95% CI, 19–35.6%]) in order to save money. PAH continues to cause significant psychosocial and financial burden on patients despite advances in medications. This impact ranged from dissatisfaction with quality of life, to unemployment, to altering their medication regimen to save money.

Nanocarriers (NCs) coated with antibodies (Abs) to extracellular epitopes of the transmembrane glycoprotein PECAM (platelet endothelial cell adhesion molecule-1/CD31) enable targeted drug delivery to vascular endothelial cells. Recent studies revealed that paired Abs directed to adjacent, yet distinct epitopes of PECAM stimulate each other's binding to endothelial cells in vitro and in vivo ("collaborative enhancement"). This phenomenon improves targeting of therapeutic fusion proteins, yet its potential role in targeting multivalent NCs has not been addressed. Herein, we studied the effects of Ab-mediated collaborative enhancement on multivalent NC spheres coated with PECAM Abs (Ab/NC, ~180 nm diameter). We found that PECAM Abs do mutually enhance endothelial cell binding of Ab/NC coated by paired, but not "self" Ab. In vitro, collaborative enhancement of endothelial binding of Ab/NC by paired Abs is modulated by Ab/NC avidity,

Abnormalities that characterize pulmonary arterial hypertension (PAH) include impairment in the structure and function of pulmonary vascular endothelial (EC) and smooth muscle cells (SMC). Aldosterone levels are elevated in human PAH and in experimental pulmonary hypertension (PH), while inhibition of the aldosterone-binding mineralocorticoid receptor (MR) attenuates PH in multiple animal models. We explored the role of MR in ECs and SMCs in using cell specific MR knockout mice exposed to sugen/hypoxia-induced PH. MR inhibition with spironolactone significantly reduced right ventricular (RV) systolic pressure. However, this is not reproduced by selective MR deletion in SMCs or ECs. Similarly, MR inhibition attenuated the increase in RV cardiomyocyte area independent of vascular MR with no effect on RV weight or interstitial fibrosis. RV perivascular fibrosis was significantly decreased by spironolactone and this was reproduced by specific deletion of MR from ECs. EC-MR deletion attenuated the sugen/hypoxia-induced increase in the leukocyte-adhesion molecule, E-selectin, and collagen IIIA1 in the RV. Spironolactone also significantly reduced pulmonary arteriolar muscularization, independent of EC-MR or SMC-MR. Finally, the degree of pulmonary perivascular inflammation was attenuated by MR antagonism and was fully reproduced by SMC-specific MR deletion. These studies demonstrate that in the sugen/hypoxia PH model, systemic-MR blockade significantly attenuates the disease and that MR has cell-specific effects, with EC-MR contributing to RV perivascular fibrosis and SMC-MR participating in pulmonary vascular inflammation. As MR antagonists are being investigated to treat PAH, these findings support novel mechanisms and potential MR targets that mediate therapeutic benefits in patients.

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Background: The management of acute gastrointestinal hemorrhage (GIH) is focused on early resuscitation through 2 large-bore intravenous (2LBIV) catheters, although adherence to this recommendation is low. Local Problem: Of 100 patients hospitalized with GIH in 2017, only 14 received 2LBIV access. The goal of this study was to improve this measure. Methods: A multidisciplinary team used the DMAIC (define, measure, analyze, improve, and control) framework to perform a quality improvement initiative. Interventions: The team used quality tools including a stakeholder survey, swimlane diagram, and fishbone diagram. The first intervention involved education of the hospitalists directing admissions, and the second intervention involved education of emergency department (ED) physicians and nurses regarding the importance of 2LBIV placement. Results: Following the second intervention, there was a substantial increase in 2LBIV placement to 37 of 86 (43%). Conclusions: Carefully directed education of ED physicians and nurses with monthly feedback was effective in improving appropriate intravenous placement in patients with GIH.

While the Indian IT/ITeS sector has registered tremendous growth over the last two decades, the viability of the growth models adopted by the IT organisations is now in question. This article, in its first part, assesses the value pyramid of the Indian IT services and in examining the avenues of growth up the value chain, suggests that the industry's involvement in inclusive growth and holistic development of society is imperative in the journey forward. A discussion with industry practitioners in the second part of the article throws light on the strategies and initiatives being taken in the industry to meet the challenges and opportunities going forward.