Value co-creation in healthcare: evidence from innovative therapeutic alternatives for hereditary angioedema

Abstract Background Our research focuses on the co-creation of value in healthcare with reference to a case of hereditary angioedema with C1 inhibitor deficiency (C1-INH-HAE). Our work is mainly based on the concept of value co-creation in healthcare. The aim of this study is to assess the impact of an alternative treatment strategy – self-administration – by focusing on treatment outcomes and costs to understand if innovative therapeutic solutions can create value for patients and healthcare systems. Methods This paper compares home-based and hospital-based therapeutic strategies (independent of treatment type) with a cost minimization analysis. It encompasses compliance issues and focuses on both payer and societal perspectives, also benefiting from an operationalization of the service-dominant logic model for healthcare delivery. Data were collected over a 6-month period (August 2014–January 2015) through monthly patient interviews. Archival data were used for variable measurement. Results Thirty-nine out of 62 patients enrolled in the study, experienced at least one HAE attacks, equally distributed between home and hospital-based strategies. No evidence of correlation between therapeutic strategy and disease severity score (p = 0.351), compliance (p = 0.399), and quality of life (p = 0.971), were found. Total direct cost per attack amounts to € 1224 for home-based strategy with respect to € 1454 for hospital-based strategy, with a savings of € 230. The economic advantage of the home-based strategy almost doubles if the societal perspective was considered due to a further savings of €169 (less missed work/school days and no travel expenses). Conclusions Our study suggests that home-based therapies represent a feasible strategy for managing C1-INH-HAE and may result in lower costs and increased value for both patients and the healthcare systems. The findings are relevant to the debate on and extend the extant literature to provide a broader view of value co-creation dynamics for home-based therapies in healthcare and their positive effects. The insights are relevant to practitioners and policy makers

Anti-Inflammatory Effects of Adrenomedullin on Acute Lung Injury Induced by Carrageenan in Mice

Adrenomedullin (AM) is a 52 amino acid peptide that has shown predominant anti-inflammatory activities. In the present study, we evaluated the possible therapeutic effect of this peptide in an experimental model of acute inflammation, the carrageenan- (CAR-) induced pleurisy. Pleurisy was induced by injection of CAR into the pleural cavity of mice. AM (200 ng/kg) was administered by intraperitoneal route 1 h after CAR, and the animals were sacrificed 4 h after that. AM treatment attenuated the recruitment of leucocytes in the lung tissue and the generation and/or the expression of the proinflammatory cytokines as well as the expression of the intercellular cell adhesion molecules. Moreover, AM inhibited the induction of inducible nitric oxide synthase (iNOS), thereby abating the generation of nitric oxide (NO) and prevented the oxidative and nitroxidative lung tissue injury, as shown by the reduction of nitrotyrosine, malondialdehyde (MDA), and poly (ADP-ribose) polymerase (PARP) levels. Finally, we demonstrated that these anti-inflammatory effects of AM were associated with the inhibition of nuclear factor-κB (NF-κB) activation. All these parameters were markedly increased by intrapleural CAR in the absence of any treatment. We report that treatment with AM significantly reduces the development of acute lung injury by downregulating a broad spectrum of inflammatory factors

WY-14643, a Potent Peroxisome Proliferator Activator Receptor-α PPAR-α Agonist Ameliorates the Inflammatory Process Associated to Experimental Periodontitis

We have investigated the effects of WY14643, a potent peroxisome proliferator activator receptor-α (PPAR-α) agonist, in a rat model of ligature-induced periodontitis. Male Sprague-Dawley rats were lightly anaesthetized with pentobarbitone (35 mg/kg). Sterile, 2-0 black braided silk thread was placed around the cervix of the lower left first molar and knotted medially. Animals received WY14643 (1 mg/kg i.p, daily for eight days). Eighths days after placement of the ligature, we evaluated several markers of inflammation such us (1) myeloperoxidase activity, (2) a cytokines and adhesion molecules expression, (3) NF-κB expression, (4) iNOS expression, (5) the nitration of tyrosine residues, (6) activation of the nuclear enzyme poly(ADP-ribose) polymerase, (7) apoptosis, and (8) the degree of gingivomucosal tissues injury. Administration of WY14643 significantly decreased all of the parameters of inflammation as described above. These results demonstrate that WY14643 exerts an anti-inflammatory role during experimental periodontitis and is able to ameliorate the tissue damage

Dietary Regulation of Keap1/Nrf2/ARE Pathway: Focus on Acai Berries and Pistachios and Cashews as Natural Food Sources

Inflammation is a biological reaction to oxidative stress in which cell starts producing proteins, enzymes, and other substances to restore homeostasis, while oxidative stress could be intrinsically a biochemical imbalance of the physiologically redox status of the intracellular environment. The nuclear factor erythroid 2-related factor 2 (Nrf2)/antioxidant response element (ARE) pathway, which controls the transcription of numerous antioxidant genes that protect cellular homeostasis and detoxification genes that process and eliminate all toxic compounds and substances before they can cause damage. The Nrf2 pathway is the heart of the daily biological response to oxidative stress. Transient activation of Nrf2 by diet can upregulate antioxidant enzymes to protect cells against oxidative stress inducers. In this chapter, we summarize the effects of some novel foods in the regulation of the Nrf2/ARE pathway and its cellular mechanisms

Adrenomedullin in inflammatory process associated with experimental pulmonary fibrosis

<p>Abstract</p> <p>Background</p> <p>Adrenomedullin (AM), a 52-amino acid ringed-structure peptide with C-terminal amidation, was originally isolated from human pheochromocytoma. AM are widely distributed in various tissues and acts as a local vasoactive hormone in various conditions.</p> <p>Methods</p> <p>In the present study, we investigated the efficacy of AM on the animal model of bleomycin (BLM)-induced lung injury. Mice were subjected to intratracheal administration of BLM and were assigned to receive AM daily by an intraperitoneal injection of 200 ngr/kg.</p> <p>Results and Discussion</p> <p>Myeloperoxidase activity, lung histology, immunohistochemical analyses for cytokines and adhesion molecules expression, inducible nitric oxide synthase (iNOS), nitrotyrosine, and poly (ADP-ribose) polymerase (PARP) were performed one week after fibrosis induction. Lung histology and transforming growth factor beta (TGF-β) were performed 14 and 21 days after treatments. After bleomycin administration, AM-treated mice exhibited a reduced degree of lung damage and inflammation compared with BLM-treated mice, as shown by the reduction of (1) myeloperoxidase activity (MPO), (2) cytokines and adhesion molecules expression, (3) nitric oxide synthase expression, (4) the nitration of tyrosine residues, (5) poly (ADP-ribose) (PAR) formation, a product of the nuclear enzyme poly (ADP-ribose) polymerase (PARP) (6) transforming growth factor beta (TGF-β) (7)and the degree of lung injury.</p> <p>Conclusions</p> <p>Our results indicate that AM administration is able to prevent bleomycin induced lung injury through the down regulation of proinflammatory factors.</p

Immunohistochemical evaluation of aquaporin-4 and its correlation with CD68, IBA-1, HIF-1α, GFAP, and CD15 expressions in fatal traumatic brain injury

Traumatic brain injury (TBI) is one of the leading causes of death and disability worldwide. Our understanding of its pathobiology has substantially increased. Following TBI, the following occur, edema formation, brain swelling, increased intracranial pressure, changes in cerebral blood flow, hypoxia, neuroinflammation, oxidative stress, excitotoxicity, and apoptosis. Experimental animal models have been developed. However, the difficulty in mimicking human TBI explains why few neuroprotective strategies, drawn up on the basis of experimental studies, have translated into improved therapeutic strategies for TBI patients. In this study, we retrospectively examined brain samples in 145 cases of death after different survival times following TBI, to investigate aquaporin-4 (AQP4) expression and correlation with hypoxia, and neuroinflammation in human TBI. Antibodies anti-glial fibrillary acid protein (GFAP), aquaporin-4 (AQP4), hypoxia induced factor-1α (HIF-1α), macrophage/phagocytic activation (CD68), ionized calcium-binding adapter molecule-1 (IBA-1), and neutrophils (CD15) were used. AQP4 showed a significant, progressive increase between the control group and groups 2 (one-day survival) and 3 (three-day survival). There were further increases in AQP4 immunopositivity in groups 4 (seven-day survival), 5 (14-dayssurvival), and 6 (30-day survival), suggesting an upregulation of AQP4 at 7 to 30 days compared to group 1. GFAP showed its highest expression in non-acute cases at the astrocytic level compared with the acute TBI group. Data emerging from the HIF-1α reaction showed a progressive, significant increase. Immunohistochemistry with IBA-1 revealed activated microglia starting three days after trauma and progressively increasing in the next 15 to 20 days after the initial trauma. CD68 expression demonstrated basal macrophage and phagocytic activation mostly around blood vessels. Starting from one to three days of survival after TBI, an increase in the number of CD68 cells was progressively observed; at 15 and 30 days of survival, CD68 showed the most abundant immunopositivity inside or around the areas of necrosis. These findings need to be developed further to gain insight into the mechanisms through which brain AQP4 is upregulated. This could be of the utmost clinicopathological importance