Economic evaluation of pharmacogenomic-guided antiplatelet treatment in Spanish patients suffering from acute coronary syndrome participating in the U-PGx PREPARE study

BackgroundCardiovascular diseases and especially Acute Coronary Syndrome (ACS) constitute a major health issue impacting millions of patients worldwide. Being a leading cause of death and hospital admissions in many European countries including Spain, it accounts for enormous amounts of healthcare expenditures for its management. Clopidogrel is one of the oldest antiplatelet medications used as standard of care in ACS.MethodsIn this study, we performed an economic evaluation study to estimate whether a genome-guided clopidogrel treatment is cost-effective compared to conventional one in a large cohort of 243 individuals of Spanish origin suffering from ACS and treated with clopidogrel. Data were derived from the U-PGx PREPARE clinical trial. Effectiveness was measured as survival of individuals while study data on safety and efficacy, as well as on resource utilization associated with each adverse drug reaction were used to measure costs to treat these adverse drug reactions. A generalized linear regression model was used to estimate cost differences for both study groups.ResultsBased on our findings, PGx-guided treatment group is cost-effective. PGx-guided treatment demonstrated to have 50% less hospital admissions, reduced emergency visits and almost 13% less ADRs compared to the non-PGx approach with mean QALY 1.07 (95% CI, 1.04-1.10) versus 1.06 (95% CI, 1.03-1.09) for the control group, while life years for both groups were 1.24 (95% CI, 1.20-1.26) and 1.23 (95% CI, 1.19-1.26), respectively. The mean total cost of PGx-guided treatment was 50% less expensive than conventional therapy with clopidogrel [euro883 (95% UI, euro316-euro1582), compared to euro1,755 (95% UI, euro765-euro2949)].ConclusionThese findings suggest that PGx-guided clopidogrel treatment represents a cost-effective option for patients suffering from ACS in the Spanish healthcare setting.Personalised Therapeutic

Procalcitonin and Inflammatory Cytokines in Children with Asthma

Asthma is currently defined as a chronic inflammatory disorder of the airway mucosa. The resulting inflammation of the airway mucosa shows signs of an acute as well as a more chronic type of inflammation. Cytokine-mediated interactions among the inflammatory cells may play a role in the pathogenesis of bronchial asthma. The aim of this study is to assess inflammatory agents as markers of chronic inflammation in childhood asthma and as indicators for determining the state of the disease. This study included 3 groups of children. Group A consisted of 35 children with asthma and FEV1<80% of predicted values, 24 boys, 11 girls, aged (mean age ± SE) 9.3 ± 0.4 years, Group B of 70 children with asthma and FEV1≥80% of predicted values, 44 boys, 26 girls, aged 8.65 ± 0.36 years and Group C of 48 healthy children, 33 boys, 15 girls, aged 10.73 ± 0.4 years. In serum, levels of PCT were determined by immunoluminescence, CRP by nephelometry and cytokines IL-1β, IL-6, IL-4 and IL-5 by ELISA. Our results show that the mean concentration of CRP and PCT were not significantly different between groups A, B and C. The mean values of IL-1β were significantly different between groups A, B and C. The mean values of IL-6 were higher in group A than those of Groups B and C, although the difference between the groups was not statistically significant. The mean values of Th2 cytokines IL-4 and IL-5 were significantly different between groups A, B and C. In conclusion, CRP and PCT levels did not play any role in airway allergic inflammation, while strong indications were found that sera levels of inflammatory cytokines associated mainly with Th2 responses play a key role in airway allergic inflammation

Economic evaluation in psychiatric pharmacogenomics: a systematic review

Nowadays, many relevant drug–gene associations have been discovered, but pharmacogenomics (PGx)-guided treatment needs to be cost-effective as well as clinically beneficial to be incorporated into standard health care. To address current challenges, this systematic review provides an update regarding previously published studies, which assessed the cost-effectiveness of PGx testing for the prescription of antidepressants and antipsychotics. From a total of 1159 studies initially identified by literature database querying, and after manual assessment and curation of all of them, a mere 18 studies met our inclusion criteria. Of the 18 studies evaluations, 16 studies (88.89%) drew conclusions in favor of PGx testing, of which 9 (50%) genome-guided interventions were cost-effective and 7 (38.9%) were less costly compared to standard treatment based on cost analysis. More precisely, supportive evidence exists for CYP2D6 and CYP2C19 drug–gene associations and for combinatorial PGx panels, but evidence is limited for many other drug–gene combinations. Amongst the limitations of the field are the unclear explanation of perspective and cost inputs, as well as the underreporting of study design elements, which can influence though the economic evaluation. Overall, the findings of this article demonstrate that although there is growing evidence on the cost-effectiveness of genome-guided interventions in psychiatric diseases, there is still a need for performing additional research on economic evaluations of PGx implementation with an emphasis on psychiatric disorders. © 2021, The Author(s), under exclusive licence to Springer Nature Limited

Beyond the Microbiome: Germ-ganism? An Integrative Idea for Microbial Existence, Organization, Growth, Pathogenicity, and Therapeutics

The advances made by microbiome research call for new vocabulary and expansion of our thinking in microbiology. For example, the life-forms presenting in both unicellular and multicellular formats invite us to rethink microbial existence, organization, growth, pathogenicity, and therapeutics in the 21st century. A view of such populations as parts of single organisms with a loose, distributed multicellular organization, introduced here as a germ-ganism, rather than communities, might open up interesting prospects for diagnostics and therapeutics innovation. This study tested and further contextualized the concept of germ-ganism using solid cultures of bacteria and fungi. Based on our findings and the literature reviewed herein, we propose that germ-ganism has synergy with a systems medicine approach by broadening host-environment interactions from cells and microorganisms to a scale of biological ecosystems. Germ-ganism also brings about the possibility of studying the multilevel impacts of novel therapeutic agents within and across networks of microbial ecosystems. The germ-ganism would lend itself, in the long term, to a veritable biocybernetics system, while in the mid-term, we anticipate it will contribute to new diagnostics and therapeutics. Biosecurity applications would be immensely affected by germ-ganism. Industrial applications of germ-ganism are of interest as a more sustainable alternative to costly solutions such as tampered strains/microorganisms. In conclusion, germ-ganism is informed by lessons from microbiome research and invites rethinking microbial existence, organization, and growth as an organism. Germ-ganism has vast ramifications for understanding pathogenicity, and clinical, biosecurity, and biotechnology applications in the current historical moment of the COVID-19 pandemic and beyond. © Copyright 2022, Mary Ann Liebert, Inc., publishers 2022

Toward High-Throughput Fungal Electroculturomics and New Omics Methodologies in 21st-Century Microbiology and Ecology

Modern microbiology and drug development are in a watershed moment with the advent of electroceuticals. In addition to genomics, electrical impulses in an organism are believed to contribute to tissue and cellular plasticity. Hence, electroceuticals or bioelectronics offers the promise to identify innovative approaches to treat human diseases. However, applications toward electromicrobiology are still limited and rare, despite the high potential to innovate the fields of both microbiology and therapeutics. For example, electric modalities for manipulating microbial growth are highly sustainable; can be combined with biopharmaceuticals, probiotics, and pharmacobiotics; and, thus, are well poised for use in medicine, public health, and ecology and diverse industries. We report here the introduction of a new research framework and technology platform for electroculturomics, by coupling standard solid-state mycological cultures with conductive treatment using a conformité Européene (CE-)-certified medical ionophoresis device. We share our experience with a diverse range of fungi that have been treated with the electroculturomics approach reported herein. We suggest that this line of inquiry can be extended to electrotranscriptomics and electrometabolomics by deploying electroculturomics in tandem with multi-omics approaches in the future. This article makes a specific contribution to fungal microbiology, and a broader contribution to advance the theory and practice of the field of electroculturomics emerging in 21st-century microbiology and ecology research. © Copyright 2020, Mary Ann Liebert, Inc