Evaluation of the diagnostic accuracy of laboratory-based screening for hepatitis C in dried blood spot samples: A systematic review and meta-analysis

The dried blood spot (DBS) is increasingly used for the hepatitis C virus (HCV) screening. Our objective was to perform a meta-analysis of the methodology for HCV screening in DBS samples, particularly in the type of diagnostic assay used. We performed a meta-analysis of all eligible studies published to date (March 2018). The literature search revealed 26 studies: 21 for detection of anti-HCV antibodies and 10 for detection of HCV-RNA. Statistical analyses were performed using Meta-DiSc and STATA (MIDAS module). For detection of HCV antibodies, pooled diagnostic accuracy measures were as follows: sensitivity 96.1%, specificity 99.2%, positive likelihood ratio (PLR) 105, negative likelihood ratio (NLR) 0.04, diagnostic odds ratio (DOR) 2692.9, and summary receiver operating characteristic (SROC) 0.997 ± 0.001. For detection of HCV-RNA, the pooled diagnostic accuracy measures were as follows: sensitivity 97.8%, specificity 99.2%, PLR 44.8, NLR 0.04, DOR 1966.9, and SROC 0.996 ± 0.013. Similar values of pooled diagnostic accuracy measures were found according to the type of anti-HCV antibody detection assay (enzyme-linked immunosorbent assay, rapid diagnostic test, and chemiluminescence assays) and HCV-RNA detection assay (real-time polymerase chain reaction and transcription-mediated amplification). The analysis of external validity showed a high negative predicted value (NPV) for both approaches, but a low positive predicted value (PPV) when prevalence was < 10%, particularly in HCV-RNA tests. Finally, this meta-analysis is subject to limitations, especially publication bias and significant heterogeneity between studies. In conclusion, HCV screening in DBS samples has an outstanding diagnostic performance, with no relevant differences between the techniques used. However, external validity may be limited when the HCV prevalence is low.This study was supported by grants from Instituto de Salud Carlos III [grant numbers PI17CIII/00003 and RD16CIII/0002/0002], and a research grant from Merck Sharpe & Dohme (MISP IIS#54846). No funding bodies had any role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.S

Meta-analysis: diagnostic accuracy of hepatitis C core antigen detection during therapy with direct-acting antivirals

Background: Treatment of hepatitis C virus (HCV) infection with direct-acting antivirals (DAAs) is monitored by assessing plasma HCV-RNA load. However, detection of HCV core antigen (HCVcAg) may be an alternative. Aim: To evaluate the diagnostic performance of the HCVcAg assay to monitor the efficacy of DAAs in HCV-infected patients METHODS: We performed searches in multiple electronic databases until 6 July 2022, of studies evaluating the HCVcAg detection in plasma or serum compared with the HCV-RNA test (gold standard). We calculated pooled measurement at 2 and 4 weeks of treatment, and at end-of-treatment (EOT), as well as sustained virological response (SVR; 12 weeks after EOT). Results: We selected 16 studies from 2016 to 2022, with 3237 patients and 8958 samples. Overall, the diagnostic performance and clinical utility of the HCVcAg assay were poor at week 2 (sensitivity = 0.40, specificity = 0.96, positive likelihood ratio (PLR) = 9.16, negative likelihood ratio (NLR) = 0.63, and area under the summary receiver operating curve (SROC) = 0.57), fair at week 4 (sensitivity = 0.30, specificity = 0.90, PLR = 3.18, NLR = 0.77, and AUC = 0.79), acceptable at EOT (sensitivity = 0.40, specificity =0.98, PLR = 16.54, NLR = 0.62, and AUC = 0.97) and excellent for SVR (sensitivity = 0.94, specificity = 0.99, PLR = 107.54, NLR = 0.06, and AUC = 0.99). Conclusions: The HCVcAg assay may be helpful for monitoring the efficacy of HCV treatment with DAAs in HCV-infected patients at EOT and for documenting SVR, but not at weeks 2 and 4 of treatment due to poor diagnostic performance.This study was supported by grants from Instituto de Salud Carlos III (ISCII; grant numbers PI20CIII/00004 to SR, and PI19CIII/00009 and PI22CIII/00019 to IM). This research was also supported by CIBER -Consorcio Centro de Investigación Biomédica en Red- (CB 2021), Instituto de Salud Carlos III, Ministerio de Ciencia e Innovación and Unión Europea – NextGenerationEU (CB21/13/00044). DS-C is a ‘Sara Borrell’ researcher from ISCIII (grant nº CD20CIII/00001). No funding bodies had any role in study design, data collection, analysis, decision to publish, or manuscript preparation.S

Diagnostic Performance of the HCV Core Antigen Test To Identify Hepatitis C in HIV-Infected Patients: a Systematic Review and Meta-Analysis

The standard algorithm for diagnosing hepatitis C virus (HCV) infection has two steps, an HCV antibody test for screening and a nucleic acid amplification test (NAAT) for confirmation. However, the HCV core antigen (HCVcAg) detection assay is an alternative for one-step diagnosis. We aimed to evaluate the diagnostic performance of the Abbott ARCHITECT HCV Ag assay to detect active hepatitis C in serum/plasma in people living with HIV/AIDS (PLWHA), through a systematic review and meta-analysis. PubMed, EMBASE, Scopus, Web of Science, and the Cochrane Library were searched until 20 September 2022 (PROSPERO, CRD42022348351). We included studies evaluating Abbott ARCHITECT HCV Ag assay (index assay) versus NAATs (reference test) in PLWHA coinfected with HCV who did not receive antiviral treatment for HCV. Meta-analysis was performed with the MIDAS module using Stata and random-effects models. The QUADAS-2 tool evaluated the risk of bias. The bivariate analysis was conducted on 11 studies with 2,407 samples. Pooled sensitivity was 0.95 (95% CI = 0.92 to 0.97), specificity 0.97 (95% CI = 0.93 to 0.99), positive likelihood ratio 37.76 (95% CI = 12.84 to 111.02), and negative likelihood ratio 0.06 (95% CI = 0.04 to 0.09). The area under the curve was 0.97 (95% CI = 0.20 to 1.00). For low prevalence (≤5%), the posttest probability that an individual with a positive test was a true positive ranged from 4% to 67%, whereas, at high prevalence (≥10%), the posttest probability was between 81% and 87%, indicating that a confirmatory test should be necessary, particularly with prevalence values of ≤1%. Regardless of prevalence, the probability that an individual with a negative test was a false negative was close to zero, indicating that the individual was not infected with HCV. In conclusion, the accuracy of the Abbott ARCHITECT HCV Ag assay was very good for HCV screening in serum/plasma samples from PLWHA. The clinical utility to confirm HCV infection was acceptable in high-prevalence settings (≥10%) but poor in low-prevalence settings (≤1%). Furthermore, it was excellent in excluding active HCV infection.This study was supported by grants from the Instituto de Salud Carlos III (ISCII; grant number PI20CIII/00004 to S.R., and PI19CIII/00009 to I.M.) and Gilead Science (grant number GLD20_0144 to S.R.). This research was also supported by CIBER (Consorcio Centro de Investigación Biomédica en Red) (CB 2021), Instituto de Salud Carlos III, Ministerio de Ciencia e Innovación, and Unión Europea – NextGenerationEU (CB21/13/00044). D.S.-C. is a Sara Borrell researcher from ISCIII (grant no. CD20CIII/00001). A.T.-N. is a PhD student in the Program in Biomedical Sciences and Public Health of the UNED International Doctoral School. No funding bodies had any role in study design, data collection, analysis, decision to publish, or manuscript preparation.S

THE DEVELOPMENT OF AN EDUCATIONAL SYSTEM FOR A LONG TERM TRAINING ON SEISMIC AND VOLCANIC RISK

One of the tasks of the European Project UPStrat-MAFA (Urban Prevention Strategies using MAcroseimic Fields and FAult Sources) is to develop an educational system aimed at long-term training, mainly on seismic hazard and risk. This task will be carried out by sharing the expertise of partners of the project to set different actions, encompassing programs and educational material for students, teachers and general public, and to design an interactive travelling educational path. Starting from the Icelandic educational program tested on schools in the last decade by EERC (Earthquake Engineering Research Centre), the task will develop educational tools especially designed for children, and also new tools using the most spread information channels, in order to outreach information on seismic risk and how to cope with earthquakes. The interactive travelling educational path on earthquakes and volcanoes, aimed at risk-reduction by increasing awareness, is an interactive experience using a multimedia approach, in order to have a very flexible, easy-to-share and appealing set of educational tools (video, simulations, games…) also developed for “edutainment”. The educational path, which is also a travelling exhibition, has to deal with issues related to seismic and volcanoes hazard and risks, especially in urban areas. The whole education-information system developed in the framework of UPStrat-MAFA project is structured to represent both a way to convey project results to the scientific community and to strengthen people’s risk awareness and their training to face up to seismic and/or volcanic events.Co-financed by the EU - Civil Protection Financial Instrument, in the framework the European project ”Urban disaster Prevention Strategies using MAcroseismic Fields and FAult Sources” (UPStrat-MAFA - Num. 230301/2011/613486/SUB/A5), DG ECHO Unit A5. http://ec.europa.eu/echo/funding/cp_projects2011_en.htmUnpublished19-24 August 2012 in Moscow, Russia.5.9. Formazione e informazioneope

Disaster prevention strategies, based on an education information system

Earthquake damage includes non-structural failure, failure of utility systems and, infrastructure, loss of function and other non-structural damage. Occupants, building owners, insurance companies, building inspectors and others, through their use of the buildings, systems and content, can affect the risk of such negative events. Thus, a prerequisite for more effective disaster risk reduction is increased risk awareness amongst people and in the community and state development planning process, the educational curriculum, and media. As knowledge is clearly connected with understanding risks, the perception of natural hazards and risks in the local environment should be developed with the help of education. This paper presents a comparative study of the current educational curriculum on natural hazards within the school systems in four European countries: Italy, Portugal, Spain and Iceland. None of the countries provides courses dedicated to this topic but include it within other subjects, most often in the natural sciences

Canopy arthropod declines along a gradient of olive farming intensification

Arthropod declines have been linked to agricultural intensification. However, information about the impacts of intensification is still limited for many crops, as is our understanding of the responses of different arthropod taxa and trophic groups, thus hindering the development of effective mitigation measures. We investigated the impacts of olive farming intensification on canopy-dwelling arthropods in the Mediterranean region. Intensification involves the increased use of agrochemicals, mechanisation and irrigation, but also structural changes from traditional orchards with low densities of large and old trees, to intensive and superintensive orchards with high to very high densities of smaller and younger trees, respectively. Canopy arthropods were vacuum-sampled at 53 sites representing the three orchard intensification levels, in spring, summer and autumn 2017. We evaluated how the arthropod community varied across intensification levels, and in response to orchard structure, management and landscape context. We found no changes in the diversity of arthropod taxa across intensification levels after correcting for sample coverage, but arthropod abundance declined markedly along the intensification gradient. Decreased abundance was associated with changes in orchard structure, lower herbaceous cover, and higher herbicide and insecticide use. The abundance of a specialized olive pest was lower in landscapes with higher woodland cover. The negative effects of intensification were stronger in spring and summer than in autumn, and parasitoids and predators were particularly affected. Overall, results suggest that retaining herbaceous cover, reducing agrochemical inputs and preserving natural woody elements in the landscape, may contribute to mitigate impacts of olive farming intensification on canopy arthropods, particularly on beneficial species

Canopy arthropod declines along a gradient of olive farming intensification

Arthropod declines have been linked to agricultural intensification. However, information about the impacts of intensification is still limited for many crops, as is our understanding of the responses of different arthropod taxa and trophic groups, thus hindering the development of effective mitigation measures. We investigated the impacts of olive farming intensification on canopydwelling arthropods in the Mediterranean region. Intensification involves the increased use of agrochemicals, mechanisation and irrigation, but also structural changes from traditional orchards with low densities of large and old trees, to intensive and superintensive orchards with high to very high densities of smaller and younger trees, respectively. Canopy arthropods were vacuumsampled at 53 sites representing the three orchard intensification levels, in spring, summer and autumn 2017. We evaluated how the arthropod community varied across intensification levels, and in response to orchard structure, management and landscape context. We found no changes in the diversity of arthropod taxa across intensification levels after correcting for sample coverage, but arthropod abundance declined markedly along the intensification gradient. Decreased abundance was associated with changes in orchard structure, lower herbaceous cover, and higher herbicide and insecticide use. The abundance of a specialized olive pest was lower in landscapes with higher woodland cover. The negative effects of intensification were stronger in spring and summer than in autumn, and parasitoids and predators were particularly affected. Overall, results suggest that retaining herbaceous cover, reducing agrochemical inputs and preserving natural woody elements in the landscape, may contribute to mitigate impacts of olive farming intensification on canopy arthropods, particularly on beneficial speciesinfo:eu-repo/semantics/publishedVersio

Relationship of TRIM5 and TRIM22 polymorphisms with liver disease and HCV clearance after antiviral therapy in HIV/HCV coinfected patients

BACKGROUND AND AIMS: TRIM5 and TRIM22 are restriction factors involved in innate immune response and exhibit anti-viral activity. Single nucleotide polymorphisms (SNPs) at TRIM5 and TRIM22 genes have shown to influence several viral infections such as human immunodeficiency virus (HIV), hepatitis B, as well as measles and rubella vaccination. The aim of this study is to analyze whether TRIM5 and TRIM22 polymorphisms are associated with liver fibrosis inflammation-related biomarkers and response to pegylated-interferon-alpha plus ribavirin (pegIFNα/RBV) therapy in HIV/hepatitis C virus (HCV) coinfected patients. METHODS: A retrospective study was performed in 319 patients who started pegIFNα/RBV therapy. Liver fibrosis stage was characterized in 288 patients. TRIM5 rs3824949 and TRIM22 polymorphisms (rs1063303, rs7935564, and rs7113258) were genotyped using the GoldenGate assay. The primary outcomes were: a) significant liver fibrosis (≥F2) evaluated by liver biopsy or transient elastography (liver stiffness values ≥7.1 Kpa); b) sustained virological response (SVR) defined as no detectable HCV viral load (<10 IU/mL) at week 24 after the end of the treatment. The secondary outcome variable was plasma chemokine levels. RESULTS: Patients with TRIM5 rs3824949 GG genotype had higher SVR rate than patients with TRIM5 rs3824949 CC/CG genotypes (p = 0.013), and they had increased odds of achieving SVR (adjusted odds ratio (aOR = 2.58; p = 0.012). Patients with TRIM22 rs1063303 GG genotype had higher proportion of significant liver fibrosis than patients with rs1063303 CC/CG genotypes (p = 0.021), and they had increased odds of having significant hepatic fibrosis (aOR = 2.19; p = 0.034). Patients with TRIM22 rs7113258 AT/AA genotype had higher SVR rate than patients with rs7113258 TT genotypes (p = 0.013), and they had increased odds of achieving SVR (aOR = 1.88; p = 0.041). The TRIM22 haplotype conformed by rs1063303_C and rs7113258_A was more frequent in patients with SVR (p = 0.018) and was significantly associated with achieving SVR (aOR = 2.80; p = 0.013). The TRIM5 rs3824949 GG genotype was significantly associated with higher levels of GRO-α (adjusted arithmetic mean ratio ((aAMR) = 1.40; p = 0.011) and MCP-1 (aAMR = 1.61; p = 0.003). CONCLUSIONS: TRIM5 and TRIM22 SNPs are associated to increased odds of significant liver fibrosis and SVR after pegIFNα/RBV therapy in HIV/HCV coinfected patients. Besides, TRIM5 SNP was associated to higher baseline levels of circulating biomarkers GRO and MCP-1.The authors wish to thank the Spanish National Genotyping Center (CeGen) for providing the genotyping services (http://www.cegen.org). We also acknowledge the patients in this study for their participation.S

THE DEVELOPMENT OF AN EDUCATIONAL SYSTEM FOR A LONG TERM TRAINING ON SEISMIC AND VOLCANIC RISK

One of the tasks of the European Project UPStrat-MAFA (Urban Prevention Strategies using MAcroseimic Fields and FAult Sources) is to develop an educational system aimed at long-term training, mainly on seismic hazard and risk. This task will be carried out by sharing the expertise of partners of the project to set different actions, encompassing programs and educational material for students, teachers and general public, and to design an interactive travelling educational path. Starting from the Icelandic educational program tested on schools in the last decade by EERC (Earthquake Engineering Research Centre), the task will develop educational tools especially designed for children, and also new tools using the most spread information channels, in order to outreach information on seismic risk and how to cope with earthquakes. The interactive travelling educational path on earthquakes and volcanoes, aimed at risk-reduction by increasing awareness, is an interactive experience using a multimedia approach, in order to have a very flexible, easy-to-share and appealing set of educational tools (video, simulations, games…) also developed for “edutainment”. The educational path, which is also a travelling exhibition, has to deal with issues related to seismic and volcanoes hazard and risks, especially in urban areas. The whole education-information system developed in the framework of UPStrat-MAFA project is structured to represent both a way to convey project results to the scientific community and to strengthen people’s risk awareness and their training to face up to seismic and/or volcanic events