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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.

Background: Meropenem dosing for septic critically patients is difficult due to pathophysiological changes associated with sepsis as well as supportive symptomatic therapies. A prospective single-center study assessed whether fluid retention alters meropenem pharmacokinetics and the achievement of the pharmacokinetic/pharmacodynamic (PK/PD) targets for efficacy., Methods: Twenty-five septic ICU patients (19 m, 6f) aged 32-86 years with the mean APACHE II score of 20.2 (range 11-33), suffering mainly from perioperative intra-abdominal or respiratory infections and septic shock (n = 18), were investigated over three days after the start of extended 3-h i.v. infusions of meropenem q8h. Urinary creatinine clearance (CL cr ) and cumulative fluid balance (CFB) were measured daily. Plasma meropenem was measured, and Bayesian estimates of PK parameters were calculated., Results: Eleven patients (9 with peritonitis) were classified as fluid overload (FO) based on a positive day 1 CFB of more than 10% body weight. Compared to NoFO patients (n = 14, 11 with pneumonia), the FO patients had a lower meropenem clearance (CL me 8.5 ± 3.2 vs 11.5 ± 3.5 L/h), higher volume of distribution (V 1 14.9 ± 3.5 vs 13.5 ± 4.1 L) and longer half-life (t 1/2 1.4 ± 0.63 vs 0.92 ± 0.54 h) (p < 0.05). Over three days, the CFB of the FO patients decreased (11.7 ± 3.3 vs 6.7 ± 4.3 L, p < 0.05) and the PK parameters reached the values comparable with NoFO patients (CL me 12.4 ± 3.8 vs 11.5 ± 2.0 L/h, V 1 13.7 ± 2.0 vs 14.0 ± 5.1 L, t 1/2 0.81 ± 0.23 vs 0.87 ± 0.40 h). The CL cr and Cockroft-Gault CL cr were stable in time and comparable. The correlation with CL me was weak to moderate (CL cr , day 3 CGCL cr ) or absent (day 1 and 2 CGCL cr ). Dosing with 2 g meropenem q8h ensured adequate concentrations to treat infections with sensitive pathogens (MIC 2 mg/L). The proportion of pre-dose concentrations exceeding the MIC 8 mg/L and the fraction time with a target-exceeding concentration were higher in the FO group (day 1-3 f C min  > MIC: 67 vs 27%, p < 0.001; day 1%f T > MIC: 79 ± 17 vs 58 ± 17, p < 0.05)., Conclusions: These findings emphasize the importance of TDM and a cautious approach to augmented maintenance dosing of meropenem to patients with FO infected with less susceptible pathogens, if guided by population covariate relationships between CL me and creatinine clearance., (© 2021. The Author(s).)

Introduction: The article contains a summary of the issues of staging and therapy with an emphasis on the neoadjuvant treatment and associated tumor regression grade with the analysis of our own group of patients., Methods: Retrospective analysis of patients with rectal cancer who underwent a surgery at the 1st Department of Surgery - Thoratic, Abdominal and Injury Surgery; First Faculty of Medicine, Charles University in Prague and General University Hospital in Prague, Czech Republic, focusing on those who underwent neoadjuvant chemoradiotherapy and their pathologists evaluated tumor regression grade after the resection., Results: The group consists of 161 patients operated on between 2012 and 2016. 47 patients underwent neoadjuvant oncological treatment with further evaluation of the tumor regression grade by a pathologist, a scoring system according to Ryan was used. A complete pathological response was elicited in 10.4% of patients, no response in 35.4% of patients, and partial tumor regression in 54.2%., Conclusion: Although there is a difference in our results compared to foreign publications, the proportion of patients remains comparable. Studies evaluating the advantages versus disadvantages of neoadjuvant therapy will certainly follow, and the question of the suitability of surgical treatment as the only curative solution is partially raised.

INTRODUCTION AND OBJECTIVE: Cytochrome P450 enzymes are the major drug-metabolizing enzymes in humans and the importance of drug transport proteins, in particular P-glycoprotein, in the variability of drug response has also been highlighted. Activity of cytochrome P450 enzymes and P-glycoprotein can vary widely between individuals and genotyping and/or phenotyping can help assess their activity. Several phenotyping cocktails have been developed. The Geneva cocktail is composed of a specific probe for six different cytochrome P450 enzymes and one for P-glycoprotein and was used in the context of a research aiming at exploring genotypes and phenotypes in distinct human populations (NCT02789527). The aim of the present study is to solely report the safety results of the Geneva cocktail in the healthy volunteers of these populations., Materials and Methods: The Geneva cocktail is composed of caffeine, bupropion, flurbiprofen, omeprazole, dextromethorphan, midazolam, and fexofenadine. The volunteers fasted and avoided drinking caffeine-containing beverages or food and grapefruit juice overnight before receiving the cocktail orally. They provided blood spots for the probes' concentrations at 2, 3, and 6 h after ingestion and were asked about adverse events., Results: A total of 265 healthy adult volunteers were included from Ethiopia, Oman, and the Czech Republic. The mean plasma concentrations at the 2-h sampling time of each probe drug in the total sample were: 1663 ng/mL for caffeine, 8 ng/mL for bupropion, 789 ng/mL for flurbiprofen, 6 ng/mL for dextromethorphan, 2 ng/mL for midazolam, 35 ng/mL for fexofenadine, and 103 ng/mL for omeprazole. Four adverse events were observed representing an occurrence of 1.5%. All these events were categorized as mild to moderate, non-serious, and resolved spontaneously. A causal link with the cocktail cannot be excluded because of the temporal relationship but is at most evaluated as possible according to the World Health Organization-Uppsala Monitoring Centre causal assessment system., Conclusions: In this research, healthy volunteers from three different human populations were phenotyped with the Geneva cocktail. Four adverse events were observed, confirming the safety of this cocktail that is given at lower than clinically relevant doses and therefore results in concentrations lower than those reported to cause adverse events.

Background: The beginning of the coronavirus disease (COVID-19) epidemic dates back to December 31, 2019, when the first cases were reported in the People's Republic of China. In the Czech Republic, the first three cases of infection with the novel coronavirus were confirmed on March 1, 2020. The joint effort of state authorities and researchers gave rise to a unique team, which combines methodical knowledge of real-world processes with the know-how needed for effective processing, analysis, and online visualization of data., Objective: Due to an urgent need for a tool that presents important reports based on valid data sources, a team of government experts and researchers focused on the design and development of a web app intended to provide a regularly updated overview of COVID-19 epidemiology in the Czech Republic to the general population., Methods: The cross-industry standard process for data mining model was chosen for the complex solution of analytical processing and visualization of data that provides validated information on the COVID-19 epidemic across the Czech Republic. Great emphasis was put on the understanding and a correct implementation of all six steps (business understanding, data understanding, data preparation, modelling, evaluation, and deployment) needed in the process, including the infrastructure of a nationwide information system; the methodological setting of communication channels between all involved stakeholders; and data collection, processing, analysis, validation, and visualization., Results: The web-based overview of the current spread of COVID-19 in the Czech Republic has been developed as an online platform providing a set of outputs in the form of tables, graphs, and maps intended for the general public. On March 12, 2020, the first version of the web portal, containing fourteen overviews divided into five topical sections, was released. The web portal's primary objective is to publish a well-arranged visualization and clear explanation of basic information consisting of the overall numbers of performed tests, confirmed cases of COVID-19, COVID-19-related deaths, the daily and cumulative overviews of people with a positive COVID-19 case, performed tests, location and country of infection of people with a positive COVID-19 case, hospitalizations of patients with COVID-19, and distribution of personal protective equipment., Conclusions: The online interactive overview of the current spread of COVID-19 in the Czech Republic was launched on March 11, 2020, and has immediately become the primary communication channel employed by the health care sector to present the current situation regarding the COVID-19 epidemic. This complex reporting of the COVID-19 epidemic in the Czech Republic also shows an effective way to interconnect knowledge held by various specialists, such as regional and national methodology experts (who report positive cases of the disease on a daily basis), with knowledge held by developers of central registries, analysts, developers of web apps, and leaders in the health care sector., (©Martin Komenda, Vojtěch Bulhart, Matěj Karolyi, Jiří Jarkovský, Jan Mužík, Ondřej Májek, Lenka Šnajdrová, Petra Růžičková, Jarmila Rážová, Roman Prymula, Barbora Macková, Pavel Březovský, Jan Marounek, Vladimír Černý, Ladislav Dušek. Originally published in the Journal of Medical Internet Research (http://www.jmir.org), 27.05.2020.)

Background: Located in the Sudan belt, the Chad Basin forms a remarkable ecosystem, where several unique agricultural and pastoral techniques have been developed. Both from an archaeological and a genetic point of view, this region has been interpreted to be the center of a bidirectional corridor connecting West and East Africa, as well as a meeting point for populations coming from North Africa through the Saharan desert., Methodology/principal Findings: Samples from twelve ethnic groups from the Chad Basin (n = 542) have been high-throughput genotyped for 230 coding region mitochondrial DNA (mtDNA) Single Nucleotide Polymorphisms (mtSNPs) using Matrix-Assisted Laser Desorption/Ionization Time-Of-Flight (MALDI-TOF) mass spectrometry. This set of mtSNPs allowed for much better phylogenetic resolution than previous studies of this geographic region, enabling new insights into its population history. Notable haplogroup (hg) heterogeneity has been observed in the Chad Basin mirroring the different demographic histories of these ethnic groups. As estimated using a Bayesian framework, nomadic populations showed negative growth which was not always correlated to their estimated effective population sizes. Nomads also showed lower diversity values than sedentary groups., Conclusions/significance: Compared to sedentary population, nomads showed signals of stronger genetic drift occurring in their ancestral populations. These populations, however, retained more haplotype diversity in their hypervariable segments I (HVS-I), but not their mtSNPs, suggesting a more ancestral ethnogenesis. Whereas the nomadic population showed a higher Mediterranean influence signaled mainly by sub-lineages of M1, R0, U6, and U5, the other populations showed a more consistent sub-Saharan pattern. Although lifestyle may have an influence on diversity patterns and hg composition, analysis of molecular variance has not identified these differences. The present study indicates that analysis of mtSNPs at high resolution could be a fast and extensive approach for screening variation in population studies where labor-intensive techniques such as entire genome sequencing remain unfeasible.