Cost-effectiveness analysis of Next generation sequencing tests in critically ill pediatric patients

Rare genetic diseases in the pediatric population constitute an urgent global public health issue; overall, more than 300 million people are affected worldwide. Next Generation Sequencing techniques, as Whole genome sequencing (WGS) and Whole exome sequencing (WES), have proven to be significantly supportive in diagnosing these complex conditions. The aim is to evaluate the cost-effectiveness of WGS versus WES in pediatric patients with suspected genetic disorders. A Bayesian Markov model was calibrated among this target population, comparing WGS to WES. Model parameters were retrieved from the scientific literature. Costs and benefits were discounted at a rate of 3%. A lifetime time horizon and the National Health Service perspective was chosen. The Eurozone threshold, ranging from €30,000 to €50,000, was adopted. Markov Chain Monte Carlo was used as the simulation method for Bayesian inference. Uncertainty was explored through a probabilistic sensitivity analysis (PSA) and a value of information analysis (VOI), illustrated through Cost-Effectiveness Acceptability Curve (CEAC) and Expected Value of Perfect Information (EVPI). Results were reported as Incremental Cost-Effectiveness Ratio (ICER), expressed as euros per additional diagnosis. The base case findings highlighted that WGS was cost-effective with an ICER of €31,973. The CEAC showed that for all thresholds over the ICER, WGS had the highest probability of being cost-effective. The EVPI per patient was estimated to be €6,535 on a threshold of €50,000/diagnosis. In addition to being cost-effective, WGS could allow early genetic diagnosis shortening the diagnostic odyssey. The use of WGS in the diagnostic workup has the potential to revolutionise personalised medicine and to play a significant role in achieving SDG 3 by providing personalised healthcare, identifying genetic risk factors for diseases, and informing public health policies for a target population that represents the human capital of the future

Strengthening and promoting digital health practice: results from a Global Digital Health Partnership’s survey

Background and objectiveThe capacity to promote and disseminate the best evidence-based practices in terms of digital health innovations and technologies represents an important goal for countries and governments. To support the digital health maturity across countries the Global Digital Health Partnership (GDHP) was established in 2019. The mission of the GDHP is to facilitate global collaboration and knowledge-sharing in the design of digital health services, through the administration of surveys and white papers.ObjectiveThe scope of this study is to critically analyze and discuss results from the Evidence and Evaluation GDHP Work Stream’s survey, understand how governments and countries intend to address main obstacles to the digital health implementation, identify their strategies for a communication of effective digital health services, and promote the sharing of international based best practices on digital health.MethodsThis survey followed a cross-sectional study approach. A multiple-choice questionnaire was designed to gather data. Choices were extracted from research publications retrieved through a rapid review.ResultsOut of 29 countries receiving the survey, 10 returned it. On a scale from 1 to 5, eHealth systems/platforms (mean = 3.56) were indicated as the most important tool for centralized infrastructure to collect information on digital health, while primary care (mean = 4.0) represented the most voted item for healthcare services to collect information on digital health. Seven Countries out of 10 identified lack of organization, skepticism of clinicians, and accessibility of the population as a barriers to adopt digital health implementation, resulting to be the most voted items. Finally, the most endorsed priorities in digital health for Countries were the adoption of data-driven approaches (6 Countries), and telehealth (5 Countries).ConclusionThis survey highlighted the main tools and obstacles for countries to promote the implementation of evidence-based digital health innovations. Identifying strategies that would communicate the value of health care information technology to healthcare professionals are particularly imperative. Effective communication programs for clinicians and the general population in addition to improved digital health literacy (both for clinicians and citizens) will be the key for the real implementation of future digital health technologies

Cost-Effectiveness of Whole-Genome vs Whole-Exome Sequencing Among Children With Suspected Genetic Disorders

Importance The diagnosis of rare diseases and other genetic conditions can be daunting due to vague or poorly defined clinical features that are not recognized even by experienced clinicians. Next-generation sequencing technologies, such as whole-genome sequencing (WGS) and whole-exome sequencing (WES), have greatly enhanced the diagnosis of genetic diseases by expanding the ability to sequence a large part of the genome, rendering a cost-effectiveness comparison between them necessary. Objective To assess the cost-effectiveness of WGS compared with WES and conventional testing in children with suspected genetic disorders. Design, Setting, and Participants In this economic evaluation, a bayesian Markov model was implemented from January 1 to June 30, 2023. The model was developed using data from a cohort of 870 pediatric patients with suspected genetic disorders who were enrolled and underwent testing in the Ospedale Pediatrico Bambino Gesu, Rome, Italy, from January 1, 2015, to December 31, 2022. The robustness of the model was assessed through probabilistic sensitivity analysis and value of information analysis. Main Outcomes and Measures Overall costs, number of definitive diagnoses, and incremental cost-effectiveness ratios per diagnosis were measured. The cost-effectiveness analyses involved 4 comparisons: first-tier WGS with standard of care; first-tier WGS with first-tier WES; first-tier WGS with second-tier WES; and first-tier WGS with second-tier WGS. Results The ages of the 870 participants ranged from 0 to 18 years (539 [62%] girls). The results of the analysis suggested that adopting WGS as a first-tier strategy would be cost-effective compared with all other explored options. For all threshold levels above euro29 800 (US $32 408) per diagnosis that were tested up to euro50 000 (US$54 375) per diagnosis, first-line WGS vs second-line WES strategy (ie, 54.6%) had the highest probability of being cost-effective, followed by first-line vs second-line WGS (ie, 54.3%), first-line WGS vs the standard of care alternative (ie, 53.2%), and first-line WGS vs first-line WES (ie, 51.1%). Based on sensitivity analyses, these estimates remained robust to assumptions and parameter uncertainty. Conclusions and Relevance The findings of this economic evaluation encourage the development of policy changes at various levels (ie, macro, meso, and micro) of international health systems to ensure an efficient adoption of WGS in clinical practice and its equitable access

First moves towards photoautotrophic synthetic cells: In vitro study of photosynthetic reaction centre and cytochrome bc1 complex interactions

Following a bottom-up synthetic biology approach it is shown that vesicle-based cell-like systems (shortly â\u80\u9csynthetic cellsâ\u80\u9d) can be designed and assembled to perform specific function (for biotechnological applications) and for studies in the origin-of-life field. We recently focused on the construction of synthetic cells capable to converting light into chemical energy. Here we first present our approach, which has been realized so far by the reconstitution of photosynthetic reaction centre in the membrane of giant lipid vesicles. Next, the details of our ongoing research program are presented. It involves the use of the reaction centre, the coenzyme Qâ\u80\u93cytochrome c oxidoreductase, and the ATP synthase for creating an autonomous synthetic cell. We show experimental results on the chemistry of the first two proteins showing that they can efficiently sustain light-driven chemical oscillations. Moreover, the cyclic pattern has been reproduced in silico by a minimal kinetic model

Organizational Aspects of the Implementation and Use of Whole Genome Sequencing and Whole Exome Sequencing in the Pediatric Population in Italy: Results of a Survey

This study explores the organizational aspects of whole genome sequencing (WGS) implementation for pediatric patients with suspected genetic disorders in Italy, comparing it with whole exome sequencing (WES). Health professionals’ opinions were collected through an internet-based survey and analyzed using a qualitative summative content analysis methodology. Among the 16 respondents, most were clinical geneticists performing only WES, while 5 also used WGS. The key differences identified include higher needs for analyzing genome rearrangements following WES, greater data storage and security requirements for WGS, and WGS only being performed in specific research studies. No difference was detected in centralization and decentralization issues. The main cost factors included genetic consultations, library preparation and sequencing, bioinformatic analysis, interpretation and confirmation, data storage, and complementary diagnostic investigations. Both WES and WGS decreased the need for additional diagnostic analyses when not used as last-resort tests. Organizational aspects were similar for WGS and WES, but economic evidence gaps may exist for WGS in clinical settings. As sequencing costs decline, WGS will likely replace WES and traditional genetic testing. Tailored genomic policies and cost-effectiveness analyses are needed for WGS implementation in health systems. WGS shows promise for enhancing genetics knowledge and expediting diagnoses for pediatric patients with genetic disorders

Community-based participatory research to engage disadvantaged communities: Levels of engagement reached and how to increase it. A systematic review

Community-based participatory research (CBPR) is one of the most used community engagement frameworks to promote health changes in vulnerable populations. The more a community is engaged, the more a program can impact the social determinants of health. The present study aims to measure the level of engagement reached in randomized controlled trials (RCTs) using CBPR in disadvantaged populations, and to find out the CBPR components that better correlate with a higher level of engagement. A systematic review was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Embase, Web of Science, MEDLINE, Cochrane and Scopus databases were queried. Engagement level was assessed using the revised version of IAP2 spectrum, ranging from "inform" to "shared leadership" . Fifty-one RCTs were included, belonging to 36 engagement programs. Fourteen CBPR reached the highest level of engagement. According to the multivariate logistic regression, a pre-existing community intervention was associated with a higher engagement level (OR = 10.08; p<0.05).The variable "institutional funding" was perfectly correlated with a higher level of engagement. No correlation was found with income status or type of preventive programs. A history of collaboration seems to influence the effectiveness in involving communities burdened with social inequities, so starting new partnerships remains a public health priority to invest on. A strong potentiality of CBPR was described in engaging disadvantaged communities, addressing social determinants of health.The key findings described above should be taken into account when planning a community engagement intervention, to build up an effective collaborative field between researchers and population

Structural and Morphological Study of a Poly(3-hexylthiophene)/Streptavidin Multilayer Structure Serving as Active Layer in Ultra-Sensitive OFET Biosensors

Organic field-effect transistors including a functional bio-recognition interlayer, sandwiched between the dielectric and the organic semiconductor layers, have been recently proposed as ultrasensitive label-free biosensors capable to detect target molecule in the low pM concentration range. The morphology and the structure of the stacked bilayer formed by the protein bio-interlayer and the overlying organic semiconductor is here investigated for different protein deposition methods. X-ray scattering techniques and scanning electron microscopy allow to gather key relevant information on the interface structure and to assess target analyte molecules capability to percolate through the semiconducting layer reaching the protein deposit lying underneath. Correlations between the structural and morphological data and the device analytical performances are established allowing to gather relevant details on the sensing mechanism and further improving sensor performances, in particular in terms of sensitivity and selectivity

Whole genome sequencing diagnostic yield for paediatric patients with suspected genetic disorders: systematic review, meta-analysis, and GRADE assessment

Abstract Background About 80% of the roughly 7,000 known rare diseases are single gene disorders, about 85% of which are ultra-rare, affecting less than one in one million individuals. NGS technologies, in particular whole genome sequencing (WGS) in paediatric patients suffering from severe disorders of likely genetic origin improve the diagnostic yield allowing targeted, effective care and management. The aim of this study is to perform a systematic review and meta-analysis to assess the effectiveness of WGS, with respect to whole exome sequencing (WES) and/or usual care, for the diagnosis of suspected genetic disorders among the paediatric population. Methods A systematic review of the literature was conducted querying relevant electronic databases, including MEDLINE, EMBASE, ISI Web of Science, and Scopus from January 2010 to June 2022. A random-effect meta-analysis was run to inspect the diagnostic yield of different techniques. A network meta-analysis was also performed to directly assess the comparison between WGS and WES. Results Of the 4,927 initially retrieved articles, thirty-nine met the inclusion criteria. Overall results highlighted a significantly higher pooled diagnostic yield for WGS, 38.6% (95% CI: [32.6 – 45.0]), in respect to WES, 37.8% (95% CI: [32.9 – 42.9]) and usual care, 7.8% (95% CI: [4.4 – 13.2]). The meta-regression output suggested a higher diagnostic yield of the WGS compared to WES after controlling for the type of disease (monogenic vs non-monogenic), with a tendency to better diagnostic performances for Mendelian diseases. The network meta-analysis showed a higher diagnostic yield for WGS compared to WES (OR = 1.54, 95%CI: [1.11 – 2.12]). Conclusions Although whole genome sequencing for the paediatric population with suspected genetic disorders provided an accurate and early genetic diagnosis in a high proportion of cases, further research is needed for evaluating costs, effectiveness, and cost-effectiveness of WGS and achieving an informed decision-making process. Trial Registration This systematic review has not been registered

Organizational Aspects of the Implementation and Use of Whole Genome Sequencing and Whole Exome Sequencing in the Pediatric Population in Italy: Results of a Survey

This study explores the organizational aspects of whole genome sequencing (WGS) implementation for pediatric patients with suspected genetic disorders in Italy, comparing it with whole exome sequencing (WES). Health professionals' opinions were collected through an internet-based survey and analyzed using a qualitative summative content analysis methodology. Among the 16 respondents, most were clinical geneticists performing only WES, while 5 also used WGS. The key differences identified include higher needs for analyzing genome rearrangements following WES, greater data storage and security requirements for WGS, and WGS only being performed in specific research studies. No difference was detected in centralization and decentralization issues. The main cost factors included genetic consultations, library preparation and sequencing, bioinformatic analysis, interpretation and confirmation, data storage, and complementary diagnostic investigations. Both WES and WGS decreased the need for additional diagnostic analyses when not used as last-resort tests. Organizational aspects were similar for WGS and WES, but economic evidence gaps may exist for WGS in clinical settings. As sequencing costs decline, WGS will likely replace WES and traditional genetic testing. Tailored genomic policies and cost-effectiveness analyses are needed for WGS implementation in health systems. WGS shows promise for enhancing genetics knowledge and expediting diagnoses for pediatric patients with genetic disorders