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Copyright of Studia Pneumologica et Phthiseologica is the property of TRIOS, spol. sr.o. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background and Objective: In Europe, prostate cancer (PCa) is the most common cancer in men. Screening may therefore be crucial to lower health care costs, morbidity, and mortality. This systematic review aimed to provide a contemporary overview of the costs and benefits of PCa screening programmes., Methods: A peer-reviewed literature search was conducted, using the PICO method. A detailed search strategy was developed in four databases based on the following key search terms: "PCa", "screening", and "cost effectiveness". Any type of economic evaluation was included. The search strategy was restricted to European countries, but no restrictions were set on the year of publication., Key Findings and Limitations: A total of 7484 studies were identified initially. Of these, 19 studies described the cost effectiveness of PCa screening in Europe. Among the studies using an initially healthy study population, most focussed on risk- and/or age- and/or magnetic resonance imaging (MRI)-based screening in addition to prostate-specific antigen (PSA) testing and compared this with no screening. Incremental cost ratios (ICERs) varied from €5872 per quality-adjusted life year (QALY) to €372 948/QALY, with a median of €56 487/QALY. Risk-based screening followed by MRI testing seemed to be a more cost-effective strategy than no screening., Conclusions and Clinical Implications: This systematic review indicates that screening programmes incorporating a risk-based approach and MRI have the potential to be cost effective., Patient Summary: In this review, we looked at the cost effectiveness of prostate cancer screening in Europe. We found that a risk-based approach and incorporation of magnetic resonance imaging has the potential to be cost effective. However, there remains a knowledge gap regarding cost effectiveness of prostate cancer screening. Therefore, determinants of cost effectiveness require further investigation., (Copyright © 2024. Published by Elsevier B.V.)

Background and Objective: While prostate cancer (PCa) incidence and mortality rates continue to rise, early detection of PCa remains highly controversial, and the research landscape is rapidly evolving. Existing systematic reviews (SRs) and meta-analyses (MAs) provide valuable insights, but often focus on single aspects of early detection, hindering a comprehensive understanding of the topic. We aim to fill this gap by providing a comprehensive SR of contemporary SRs covering different aspects of early detection of PCa in the European Union (EU) and the UK., Methods: On June 1, 2023, we searched four databases (Medline ALL via Ovid, Embase, Web of Science, and Cochrane Central Register of Controlled Trials) and Google Scholar. To avoid repetition of previous studies, only SRs (qualitative, quantitative, and/or MAs) were considered eligible. In the data, common themes were identified to present the evidence systematically., Key Findings and Limitations: We identified 1358 citations, resulting in 26 SRs eligible for inclusion. Six themes were identified: (1) invitation: men at general risk should be invited at >50 yr of age, and testing should be discontinued at >70 yr or with <10 yr of life expectancy; (2) decision-making: most health authorities discourage population-based screening and instead recommend a shared decision-making (SDM) approach, but implementation of SDM in clinical practice varies widely; decision aids help men make more informed and value-consistent screening decisions and decrease men's intention to attempt screening, but these do not affect screening uptake; (3) acceptance: facilitators for men considering screening include social prompting by partners and clinician recommendations, while barriers include a lack of knowledge, low-risk perception, and masculinity attributes; (4) screening test and algorithm: prostate-specific antigen-based screening reduces PCa-specific mortality and metastatic disease in men aged 55-69 yr at randomisation if screened at least twice; (5) harms and benefits: these benefits come at the cost of unnecessary biopsies, overdiagnosis, and subsequent overtreatment; and (6) future of screening: risk-adapted screening including (prebiopsy) risk calculators, magnetic resonance imaging, and blood- and urine-based biomarkers could reduce these harms. To enable a comprehensive overview, we focused on SRs. These do not include the most recent prospective studies, which were therefore incorporated in the discussion., Conclusions and Clinical Implications: By identifying consistent and conflicting evidence, this review highlights the evidence-based foundations that can be built upon, as well as areas requiring further research and improvement to reduce the burden of PCa in the EU and UK., Patient Summary: This review of 26 reviews covers various aspects of prostate cancer screening such as invitation, decision-making, screening tests, harms, and benefits. This review provides insights into existing evidence, highlighting the areas of consensus and discrepancies, to guide future research and improve prostate cancer screening strategies in Europe., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

BackgroundCOVID-19 remains a major infectious disease with substantial implications for individual and public health including the risk of a post-infection syndrome, long COVID. The continuous changes in dominant variants of SARS-CoV-2 necessitate a careful study of the effect of preventative strategies.AimWe aimed to estimate the effectiveness of post-vaccination, post-infection and hybrid immunity against severe cases requiring oxygen support caused by infections with SARS-CoV-2 variants BA1/2 and BA4/5+, and against long COVID in the infected population and their changes over time.MethodsWe used a Cox regression analysis with time-varying covariates and calendar time and logistic regression applied to national-level data from Czechia from December 2021 until August 2023.ResultsRecently boosted vaccination, post-infection and hybrid immunity provide significant protection against a severe course of COVID-19, while unboosted vaccination more than 10 months ago has a negligible protective effect. The post-vaccination immunity against the BA1/2 or BA4/5+ variants, especially based on the original vaccine types, appears to wane rapidly compared with post-infection and hybrid immunity. Once infected, however, previous immunity plays only a small protective role against long COVID.ConclusionVaccination remains an effective preventative measure against a severe course of COVID-19 but its effectiveness wanes over time thus highlighting the importance of booster doses. Once infected, vaccines may have a small protective effect against the development of long COVID.

Background: A population-based cervical cancer screening programme is implemented in the Czech Republic. However, participation is insufficient among women over 50 years. This study aimed to estimate the potential improvement in participation through directly mailed HPV self-sampling kits (HPVssk) compared with standard invitation letters in women aged 50-65 non-participating in screening., Methods: The study recruited 1564 eligible women (no cervical cancer screening in the last 3 years or more, no previous treatment associated with cervical lesions or cervical cancer). Eight hundred women were mailed with an HPVssk (HPVssk group), and 764 women were sent a standard invitation letter (control group) inviting them to a routine screening (Pap test). The primary outcome was a comparison of the overall participation rate between study groups using a binominal regression model., Results: The participation rate in the HPVssk group was 13.4% [95% confidence interval (CI) 11.2-15.9%; 7.4% of women returned the HPVssk and 6.0% attended gynaecological examination] and 5.0% (95% CI 3.6-6.8%) in the control group. Using the binominal regression model, the difference between the groups was estimated as 7.6% (95% CI 5.0-10.2%; P < 0.001). In the HPVssk group, 22% of women who returned HPVssk had a positive result and 70% of them underwent a follow-up examination., Conclusions: Compared with traditional invitation letters, the direct mailing of the HPVssk achieved a significantly higher participation rate, along with a notable HPV positivity rate among HPVssk responders. This approach offers a potentially viable method for engaging women who have not yet attended a cervical screening programme., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Public Health Association.)

Introduction: Most patients with idiopathic pulmonary fibrosis (IPF) treated with antifibrotics (AF) have progressive disease despite treatment. A switch of AF may improve survival, but evidence from randomised controlled trials is missing. We aimed to evaluate the efficacy of an AF switch on survival and FVC decline in patients from the European MultiPartner IPF registry (EMPIRE)., Methods: The study included 612 patients who discontinued the first antifibrotic therapy. Patients were grouped and analysed from two perspectives: (1) whether they had received a second antifibrotic treatment after the discontinuation of the first therapy, and (2) a reason for discontinuation of the first AF - "lack of efficacy" (LE) and "intolerance" (INT)., Results: While 263 (43%) of 612 patients received no second AF ("non-switched"), 349 (57%) patients switched. Overall survival was higher in patients who received a second AF (median 50 vs. 29 months; adjusted HR 0.64, P=0.023). Similarly, the annual FVC decline was significantly reduced in switched patients: -98ml/y in switched and -172ml/y in non-switched patients (P=0.023), respectively. The switched patients had similar risk for mortality in both LE and INT groups (adjusted HR 0.95, P=0.85). The high impact of switching on survival was demonstrated in LE patients (adjusted HR 0.27, P<0.001)., Conclusion: The patients without a second AF had significantly shorter overall survival. Our analysis suggests the importance of switching patients with an ineffective first AF therapy to a second AF therapy., (Copyright © 2023 SEPAR. Published by Elsevier España, S.L.U. All rights reserved.)

Objectives: The acute respiratory syndrome, known as COVID-19, is characterised by high morbidity and increased mortality. Genetic factors may partially explain the differences in susceptibility to and severity of COVID-19., Methods: We have analysed common functional polymorphisms within the OAS1 (rs4767027), TMPRSS6 (rs855791), DPP4 (rs3788979), and ZNF335 (rs3848719) genes in SARS-CoV-2 positive subjects (n = 521, different disease severity) and in population controls (n = 2,559 subjects, COVID-19 status unknown)., Results: Neither DPP4 nor ZNF335 were associated with disease susceptibility or severity in the Czech population in any of the models used for calculation. T allele carriers of the OAS1 polymorphism seem to be protective against symptomatic COVID-19 (p = 0.002 calculated for trend; asymptomatic, symptomatic, hospitalised). Similarly, within the TMPRSS6, minor TT homozygotes associated with lower plasma Fe concentrations were underrepresented in the overall patient group (p = 0.044; OR = 0.77, 95% CI: 0.59-0.99), and the difference was mainly driven by the severe COVID-19 subjects. In general, risky homozygotes of these two polymorphisms were less frequent than expected in the group of hospitalised COVID-19 survivors., Conclusions: Common variants within OAS1 (rs4767027) and TMPRSS6 (rs855791) play some role in COVID-19 pathology in the Czech Caucasian population. Whether the depletion of minor allele carriers of these two variants is associated with increased COVID-19 mortality, needs to be analysed in an external confirmatory study.

We present a novel approach to estimate the time-varying ascertainment rate in almost real-time, based on the surveillance of positively tested infectious and hospital admission data. We also address the age dependence of the estimate. The ascertainment rate estimation is based on the Bayes theorem. It can be easily calculated and used (i) as part of a mechanistic model of the disease spread or (ii) to estimate the unreported infections or changes in their proportion in almost real-time as one of the early-warning signals in case of undetected outbreak emergence. The paper also contains a case study of the COVID-19 epidemic in the Czech Republic. The case study demonstrates the usage of the ascertainment rate estimate in retrospective analysis, epidemic monitoring, explanations of differences between waves, usage in the national Anti-epidemic system, and monitoring of the effectiveness of non-pharmaceutical interventions on Czech nationwide surveillance datasets. The Czech data reveal that the probability of hospitalization due to SARS-CoV-2 infection for the senior population was 12 times higher than for the non-senior population in the monitored period from the beginning of March 2020 to the end of May 2021. In a mechanistic model of COVID-19 spread in the Czech Republic, the ascertainment rate enables us to explain the links between all basic compartments, including new cases, hospitalizations, and deaths., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Přibylová et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

An updated Council of the EU recommendation on cancer screening was adopted in December 2022 during the Czech EU presidency. The recommendation included prostate cancer as a suitable target disease for organised screening, and invited countries to proceed with piloting and further research. To support further discussions and actions to promote early detection of prostate cancer, an international conference in November 2022 (Prostaforum 2022) resulted in a joint declaration. Here we describe the EU policy background, summarise the preparation of the declaration and the key underlying evidence and expert recommendations, and report the text of the declaration. The declaration summarises the striking inequalities in prostate cancer burden in Europe and calls on all stakeholders to consider and support concrete steps for advancement of organised early detection of prostate cancer. Our aim is to request endorsement of the text and potential initiation of practical actions by all stakeholders to support the aims of the declaration., Patient Summary: Prostate cancer is among the most frequent cancers and is one of the most common causes of cancer death among men. The European Union has recommended new pilot programmes for prostate cancer screening. The Prostaforum 2022 declaration invites all stakeholders to support this new recommendation with specific steps., (© 2023 The Author(s).)

Background: Coverage by examinations is a crucial indicator of the future impact on the burden of colorectal cancer (CRC). The study aimed to evaluate coverage by examinations associated with CRC screening and early cancer detection of CRC in the Czech Republic. The burden of CRC was also assessed., Methods: The novel nationwide administrative registry with individual data (period 2010-19) was used to evaluate coverage by examinations for screening faecal occult blood test and colonoscopy. In the second step, additional examinations for early CRC detection were included in the coverage calculation (complete coverage). Age-specific trends in CRC incidence (period 1977-2018) were investigated using Joinpoint regression., Results: Coverage by screening examinations within recommended interval was around 30%. Complete coverage reached >37% and >50% at the 3-year interval. The coverage by examinations for the non-screening population aged 40-49 years was almost 4% and 5% (most of them were colonoscopies) at the 3-year interval. In age groups aged ≥50 years, we observed a significant annual decline, especially in the 50-69 age group, with recent annual decreases reaching up to 5-7%. The change in trend and the recent decline were also observed in the age group 40-49., Conclusions: More than half of the target screening population was covered by examinations potentially associated with early detection and subsequent treatment of colorectal neoplasms. The substantial coverage by potentially prophylactic examinations might be an explanation for the considerable decrease in CRC incidence., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Public Health Association.)

A 2021 in silico study highlighted an association between the CD14 polymorphism rs2569190 and increased susceptibility to SARS-CoV-2, which causes coronavirus disease 2019 (COVID-19). The aim of our study was to confirm this finding. We analysed the CD14 polymorphism (C→T; rs2569190) in 516 individuals who tested positive for SARS-CoV-2, with differing disease severity (164 asymptomatic, 245 symptomatic, and 107 hospitalized). We then compared these patients with a sample from the general population consisting of 3,037 individuals using a case-control study design. In comparison with carriers of the C allele, TT homozygotes accounted for 21.7 % of controls and 20.5 % in SARS-CoV-2-positive individuals (P = 0.48; OR; 95 % CI - 0.92; 0.73-1.16). No significant differences in the distribution of genotypes were found when considering co-dominant and recessive genetic models or various between-group comparisons. The CD14 polymorphism is unlikely to be an important predictor of COVID-19 in the Caucasian population in Central Europe.

Background: The Omicron variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) evades immunity conferred by vaccines and previous infections., Methods: We used a Cox proportional hazards model and a logistic regression on individual-level population-wide data from the Czech Republic to estimate risks of infection and hospitalization, including severe states., Results: A recent (≤2 months) full vaccination reached vaccine effectiveness (VE) of 43% (95% confidence interval [CI], 42%-44%) against infection by Omicron compared to 73% (95% CI, 72%-74%) against Delta. A recent booster increased VE to 56% (95% CI, 55%-56%) against Omicron infection compared to 90% (95% CI, 90%-91%) for Delta. The VE against Omicron hospitalization of a recent full vaccination was 45% (95% 95% CI, 29%-57%), with a recent booster 87% (95% CI, 84%-88%). The VE against the need for oxygen therapy due to Omicron was 57% (95% CI, 32%-72%) for recent vaccination, 90% (95% CI, 87%-92%) for a recent booster. Postinfection protection against Omicron hospitalization declined from 68% (95% CI, 68%-69%) at ≤6 months to 13% (95% CI, 11%-14%) at >6 months after a previous infection. The odds ratios for Omicron relative to Delta were 0.36 (95% CI, .34-.38) for hospitalization, 0.24 (95% CI, .22-.26) for oxygen, and 0.24 (95% CI, .21-.28) for intensive care unit admission., Conclusions: Recent vaccination still brings substantial protection against severe outcome for Omicron., Competing Interests: Potential conflicts of interest. The authors: No reported conflicts of interest. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2022. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Familial hypercholesterolaemia (FH) is the most common inherited metabolic disorder characterized by high cholesterol and if left untreated leads to premature cardiovascular disease, such as heart attacks. Treatment that begins early in life, particularly in childhood, is highly efficacious in preventing cardiovascular disease and cost-effective, thus early detection of FH is crucial. However, in Europe, less than 10% of people living with FH are diagnosed and even less receive life-saving treatment. The Prague Declaration is a call to action for national and European Union policymakers and decision-makers and a result of the Czech EU Presidency meeting on FH Paediatric Screening (early detection of inherited high cholesterol) at the Czech Senate in Prague on 6th September 2022. It builds on a considerable body of evidence which was discussed at the Technical Meeting under the auspices of the Slovenian EU Presidency in October 2021. The Prague meeting addressed the outstanding barriers to the systematic implementation of FH paediatric screening across Europe. In this article, we present the key points from the Prague meeting and concrete actions needed to move forward., Competing Interests: NB is a senior advisor to FH Europe. HB receives research funding from the Instituto de Salud Carlos III, Spain (PIE16/00021 & PI17/01799, PI21/01572), Sociedad Española de Cardiología, AstraZeneca, PhaseBio and Novartis; has received consulting/speaking fees from Astra-Zeneca, Novartis, Novo Nordisk and Organon: and is a scientific advisor for MEDSCAPE-the heart.og. KID reports grants from Pfizer, Amgen, Merck Sharp & Dohme, Sanofi–Aventis, Daiichi Sankyo, and Regeneron, during the conduct of the study; and personal fees from Bayer, outside the submitted work. BAF received grants from Novartis, Amgen, Merck, Esperion Therapeutics, Pfizer; and personal fees for lectures, advisory boards, and/or consulting from Novartis, Amgen, Regeneron, Sanofi, Merck, AstraZeneca, Pfizer, Eli Lilly, Novo Nordisk, The Medicines Co, Mylan, Daiichi Sankyo, Viatris, Ionis Pharmaceuticals, dalCOR, CiVi Pharma, KrKa Phamaceuticals, American College of Cardiology, European Atherosclerosis Society, European Society of Cardiology. TF is supported by the project National Institute for Research of Metabolic and Cardiovascular Diseases (Programme EXCELES, ID Project No. LX22NPO5104) – Funded by the European Union – Next Generation EU. TF received honoraria from Sanofi, Amgen and Novartis in the last 3 years, outside the submitted work. SSG is a consultant at Esperion Therapeutics. UG and part of preparatory work for the Declaration were supported by the Slovenian Research Agency (grants No. J3-2536 and P3-0343). FJP reports grants and modest personal fees from Abbott, AstraZeneca, Boehringer Ingelheim, Bayer, Daiichi Sankyo, Novartis, Pfizer, Philips, Sanofi/Regeneron, Servier, Vifor, outside the submitted work. KKR has received honoraria for consulting, lectures from Kowa, Amgen, Regeneron Pharmaceuticals, Sanofi, Daiichi Sankyo, Pfizer, Viatris, AstraZeneca, Eli Lilly, Esperion, New Amsterdam Pharma, Novartis, Silence Therapeutics, Bayer, Boehringer Ingelheim, Novo Nordisk, SCRIBE, CRISPR, Cargene, Vaxxinity, Abbott, Resverlogix. In addition, he has received research grant support to his institution from Sanofi, Daiichi Sankyo, Amgen, Pfizer and MSD ŽR has received honoraria from Novartis. RDS honoraria related to consulting, research and/or speaker activities from: Abbott, Ache, Amgen, Amryt, Astra Zeneca, Biolab, Esperion, Eli-Lilly, Getz Pharma, Hypera Farma, Kowa, Libbs, Novo-Nordisk, Novartis, Merck, Pfizer, PTC Therapeutics and Sanofi. HS received honoraria and grants from MSD SHARP & DOHME, AMGEN, Bayer Vital GmbH, Boehringer Ingelheim, Daiichi Sankyo, Novartis, Servier, Brahms, Bristol-Myers Squibb, Medtronic, Sanofi Aventis, Synlab, Astra-Zeneca, Pfizer and Vifor. LT received honoraria from the following companies: Abbott, Amgen, Bayer, Daiichi Sankyo, Janssen, Novartis, Novo Nordisk, Sanofi, Pfizer, Recordati. AW reports research support for pharmaceutical trials of lipid-modifying agents from Amgen, Regeneron, Novartis and Silence Therapeutics. Authors declaring no conflicts of interest: MA, BB, MB, RC, ZC, KC, MD, CdB, MG, MH, NJ, TN, OM, AP, NP, BR, JR, JŠ, MS, MV, IGI., (Copyright © 2022 Bedlington et al.)

Background: There is no clear evidence whether pirfenidone has a benefit in patients with probable or possible UIP, i.e. when idiopathic pulmonary fibrosis (IPF) is diagnosed with a lower degree of diagnostic certainty. We report on outcomes of treatment with pirfenidone in IPF patients diagnosed with various degrees of certainty., Methods and Findings: We followed patients in the multi-national European MultiPartner IPF Registry (EMPIRE) first seen between 2015 and 2018. Patients were assessed with HRCT, histopathology and received a multi-disciplinary team (MDT) IPF diagnosis. Endpoints of interest were overall survival (OS), progression-free survival (PFS) and lung function decline., Results: A total of 1626 patients were analysed, treated with either pirfenidone (N = 808) or receiving no antifibrotic treatment (N = 818). When patients treated with pirfenidone were compared to patients not receiving antifibrotic treatment, OS (one-, two- and three-year probability of survival 0.871 vs 0.798; 0.728 vs 0.632; 0.579 vs 0.556, P = 0.002), and PFS (one-, two- and three-year probability of survival 0.597 vs 0.536; 0.309 vs 0.281; 0.158 vs 0.148, P = 0.043) was higher, and FVC decline smaller (-0.073 l/yr vs -0.169 l/yr, P = 0.017). The benefit of pirfenidone on OS and PFS was also seen in patients with probable or possible IPF., Conclusions: This EMPIRE analysis confirms the favourable outcomes observed for pirfenidone treatment in patients with definitive IPF and indicates benefits also for patients with probable or possible IPF., Competing Interests: Dr. Kirchgässler is an employee of F. Hoffmann-La Roche Ltd. Dr. Lewandowska reports grants, personal fees and non-financial support from F. Hofmann-La Roche, grants, personal fees and non-financial support from Boehringer Ingelheim. Dr. Müller received grants and personal fees from Roche and Boehringer Ingelheim. Dr. Stoeva reports and received fees from Boehringer Ingelheim for participation in advisory boards and from Roche for presentations. Dr. Studnicka reports grants and personal fees from Boehringer-Ingelheim, grants and personal fees from Roche, during the conduct of the study. Dr. Tekavec-Trkanjec reports personal fees from Roche, personal fees and other from Boehringer Ingelheim. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Studies demonstrating the waning of post-vaccination and post-infection immunity against covid-19 generally analyzed a limited range of vaccines or subsets of populations. Using Czech national health data from the beginning of the covid-19 pandemic till November 20, 2021 we estimated the risks of reinfection, breakthrough infection, hospitalization and death by a Cox regression adjusted for sex, age, vaccine type and vaccination status. Vaccine effectiveness against infection declined from 87% at 0-2 months after the second dose to 53% at 7-8 months for BNT162b2 vaccine, from 90% at 0-2 months to 65% at 7-8 months for mRNA-1273, and from 83% at 0-2 months to 55% at 5-6 months for the ChAdOx1-S. Effectiveness against hospitalization and deaths declined by about 15% and 10%, respectively, during the first 6-8 months. Boosters (third dose) returned the protection to the levels observed shortly after dose 2. In unvaccinated, previously infected individuals the protection against infection declined from 97% after 2 months to 72% at 18 months. Our results confirm the waning of vaccination-induced immunity against infection and a smaller decline in the protection against hospitalization and death. Boosting restores the original vaccine effectiveness. Post-infection immunity also decreases over time., Competing Interests: The authors have declared that no competing interests exist.

(1) Background: this prospective study was focused on detailed analysis of the mutation heterogeneity in colorectal lesions removed during baseline (index) colonoscopy to identify patients at high risk of early occurrence of metachronous adenomas. (2) Methods: a total of 120 patients after endoscopic therapy of advanced colorectal neoplasia size ≥10 mm (index lesion) with subsequent surveillance colonoscopy after 10-18 months were included. In total, 143 index lesions and 84 synchronous lesions in paraffin blocks were divided into up to 30 samples. In each of them, the detection of somatic mutations in 11 hot spot gene loci was performed. Statistical analysis to correlate the mutation profiles and the degree of heterogeneity of the lesions with the risk of metachronous adenoma occurrence was undertaken. (3) Results: mutation in exon 7 of the TP53 gene found in the index lesion significantly correlated with the early occurrence of metachronous adenoma (log-rank test p = 0.003, hazard ratio 2.73, 95% confidence interval 1.14-6.56). We did not find an association between the risk of metachronous adenomas and other markers monitored. (4) Conclusions: the findings of this study could lead to an adjustment of existing recommendations for surveillance colonoscopies in a specific group of patients with mutations in exon 7 of the TP53 gene in an index lesion, where a shortening of surveillance interval may be warranted.

Record linkage of human biomonitoring (HBM) survey data with administrative register data can be used to enhance available datasets and complement the possible shortcomings of both data sources. Through record linkage, valuable information on medical history (diagnosed diseases, medication use, etc.) and follow-up information on health and vital status for established cohorts can be obtained. In this study, we investigated the availability of health registers in different EU Member States and EEA countries and assessed whether they could be linked to HBM studies. We found that the availability of administrative health registers varied substantially between European countries as well as the availability of unique personal identifiers that would facilitate record linkage. General protocols for record linkage were similar in all countries with ethical and data protections approval, informed consent, approval by administrative register owner, and linkage conducted by the register owner. Record linkage enabled cross-sectional survey data to be used as cohort study data with available follow-up and health endpoints. This can be used for extensive exposure-health effect association analysis. Our study showed that this is possible for many, but not all European countries.

At the time of the COVID-19 pandemic, providing access to data (properly optimised regarding personal data protection) plays a crucial role in providing the general public and media with up-to-date information. Open datasets also represent one of the means for evaluation of the pandemic on a global level. The primary aim of this paper is to describe the methodological and technical framework for publishing datasets describing characteristics related to the COVID-19 epidemic in the Czech Republic (epidemiology, hospital-based care, vaccination), including the use of these datasets in practice. Practical aspects and experience with data sharing are discussed. As a reaction to the epidemic situation, a new portal COVID-19: Current Situation in the Czech Republic (https://onemocneni-aktualne.mzcr.cz/covid-19) was developed and launched in March 2020 to provide a fully-fledged and trustworthy source of information for the public and media. The portal also contains a section for the publication of (i) public open datasets available for download in CSV and JSON formats and (ii) authorised-access-only section where the authorised persons can (through an online generated token) safely visualise or download regional datasets with aggregated data at the level of the individual municipalities and regions. The data are also provided to the local open data catalogue (covering only open data on healthcare, provided by the Ministry of Health) and to the National Catalogue of Open Data (covering all open data sets, provided by various authorities/publishers, and harversting all data from local catalogues). The datasets have been published in various authentication regimes and widely used by general public, scientists, public authorities and decision-makers. The total number of API calls since its launch in March 2020 to 15 December 2020 exceeded 13 million. The datasets have been adopted as an official and guaranteed source for outputs of third parties, including public authorities, non-governmental organisations, scientists and online news portals. Datasets currently published as open data meet the 3-star open data requirements, which makes them machine-readable and facilitates their further usage without restrictions. This is essential for making the data more easily understandable and usable for data consumers. In conjunction with the strategy of the MH in the field of data opening, additional datasets meeting the already implemented standards will be also released, both on COVID-19 related and unrelated topics., Competing Interests: The authors have declared that no competing interests exist.

In the Czech Republic, the strategic data-based and organizational support for individual regions and for providers of acute care at the nationwide level is coordinated by the Ministry of Health. At the beginning of the COVID-19 pandemic, the country needed to very quickly implement a system for the monitoring, reporting, and overall management of hospital capacities. The aim of this viewpoint is to describe the purpose and basic functions of a web-based application named "Control Centre for Intensive Care," which was developed and made available to meet the needs of systematic online technical support for the management of intensive inpatient care across the Czech Republic during the first wave of the pandemic in spring 2020. Two tools of key importance are described in the context of national methodology: one module for regular online updates and overall monitoring of currently free capacities of intensive care in real time, and a second module for online entering and overall record-keeping of requirements on medications for COVID-19 patients. A total of 134 intensive care providers and 927 users from hospitals across all 14 regions of the Czech Republic were registered in the central Control Centre for Intensive Care database as of March 31, 2021. This web-based application enabled continuous monitoring and decision-making during the mass surge of critical care from autumn 2020 to spring 2021. The Control Center for Intensive Care has become an indispensable part of a set of online tools that are employed on a regular basis for crisis management at the time of the COVID-19 pandemic., (©Martin Komenda, Vladimír Černý, Petr Šnajdárek, Matěj Karolyi, Miloš Hejný, Petr Panoška, Jiří Jarkovský, Jakub Gregor, Vojtěch Bulhart, Lenka Šnajdrová, Ondřej Májek, Tomáš Vymazal, Jan Blatný, Ladislav Dušek. Originally published in the Journal of Medical Internet Research (https://www.jmir.org), 16.02.2022.)

Background: The capacity to use data linkage and artificial intelligence to estimate and predict health indicators varies across European countries. However, the estimation of health indicators from linked administrative data is challenging due to several reasons such as variability in data sources and data collection methods resulting in reduced interoperability at various levels and timeliness, availability of a large number of variables, lack of skills and capacity to link and analyze big data. The main objective of this study is to develop the methodological guidelines calculating population-based health indicators to guide European countries using linked data and/or machine learning (ML) techniques with new methods., Method: We have performed the following step-wise approach systematically to develop the methodological guidelines: i. Scientific literature review, ii. Identification of inspiring examples from European countries, and iii. Developing the checklist of guidelines contents., Results: We have developed the methodological guidelines, which provide a systematic approach for studies using linked data and/or ML-techniques to produce population-based health indicators. These guidelines include a detailed checklist of the following items: rationale and objective of the study (i.e., research question), study design, linked data sources, study population/sample size, study outcomes, data preparation, data analysis (i.e., statistical techniques, sensitivity analysis and potential issues during data analysis) and study limitations., Conclusions: This is the first study to develop the methodological guidelines for studies focused on population health using linked data and/or machine learning techniques. These guidelines would support researchers to adopt and develop a systematic approach for high-quality research methods. There is a need for high-quality research methodologies using more linked data and ML-techniques to develop a structured cross-disciplinary approach for improving the population health information and thereby the population health., (© 2021. The Author(s).)

The fusion genes containing neuregulin-1 (NRG1) are newly described potentially actionable oncogenic drivers. Initial clinical trials have shown a positive response to targeted treatment in some cases of NRG1 rearranged lung adenocarcinoma, cholangiocarcinoma, and pancreatic carcinoma. The cost-effective large scale identification of NRG1 rearranged tumors is an open question. We have tested a data-drilling approach by performing a retrospective assessment of a de-identified molecular profiling database of 3263 tumors submitted for fusion testing. Gene fusion detection was performed by RNA-based targeted next-generation sequencing using the Archer Fusion Plex kits for Illumina (ArcherDX Inc., Boulder, CO). Novel fusion transcripts were confirmed by a custom-designed RT-PCR. Also, the aberrant expression of CK20 was studied immunohistochemically. The frequency of NRG1 rearranged tumors was 0.2% (7/3263). The most common histologic type was lung adenocarcinoma (n = 5). Also, renal carcinoma (n = 1) and prostatic adenocarcinoma (n = 1) were found. Identified fusion partners were of a wide range (CD74, SDC4, TNC, VAMP2, UNC5D), with CD74, SDC4 being found twice. The UNC5D is a novel fusion partner identified in prostate adenocarcinoma. There was no co-occurrence with the other tested fusions nor KRAS, BRAF, and the other gene mutations specified in the applied gene panels. Immunohistochemically, the focal expression of CK20 was present in 2 lung adenocarcinomas. We believe it should be considered as an incidental finding. In conclusion, the overall frequency of tumors with NRG1 fusion was 0.2%. All tumors were carcinomas. We confirm (invasive mucinous) lung adenocarcinoma as being the most frequent tumor presenting NRG1 fusion. Herein novel putative pathogenic gene fusion UNC5D-NRG1 is described. The potential role of immunohistochemistry in tumor identification should be further addressed., (© 2021 Wiley Periodicals LLC.)