a descriptive analysis of the Eurobact II study

Funding Information: The Eurobact 2 study group, National coordinators, scientific committee and participating intensive care units: East Asia and Pacific: Australia —National Coordinator: A/Prof. Alexis Tabah; Scientific Committee: Prof. Jeffrey Lipman; Participating ICUs: The Prince Charles Hospital, Adult Intensive Care Services: Dr. Mahesh Ramanan. Fiona Stanley Hospital, Intensive Care Unit: Dr. Edward Litton, Ms Anna Maria Palermo, Mr Timothy Yap, Mr Ege Eroglu. Japan —National Coordinator: Dr. Yoshiro Hayashi; Participating ICUs: Hiroshima University Hospital, ICU: Dr. Koji Hosokawa. St. Marianna University School of Medicine Hospital, Mixed ICU: Dr. Hideki Yoshida, Prof. Shigeki Fujitani. Middle East and North Africa: Iran —National Coordinator: Prof. Farid Zand; Participating ICUs: Imam-Reza, General Icu: Prof Ata Mahmoodpoor. Zahedan University of Medical Sciences, Clinical Immunology Research Center: Dr. Seyed Mohammad Nasirodin (S.M.N.) Tabatabaei. Saudi Arabia —Participating ICUs: Prince Sultan Medical Military Center, Intensive Care Unit: Dr. Omar Elrabi, Dr. Ghaleb A Almekhlafi. Latin America and The Caribbean: Argentina —National Coordinator: Dr. Gabriela Vidal; Participating ICUs: Hospital Zatti, Ucia: Dra Marta Aparicio, Microbiologa Irene Alonzo. Mexico —National Coordinator: Dr. Silvio A. Namendys-Silva; Participating ICUs: Centenario Hospital Miguel Hidalgo: Dr. Mariana Hermosillo, Dr. Roberto Alejandro Castillo. Europe And Central Asia: Belgium —National Coordinator: Dr. Liesbet De Bus; Scientific Committee: Jan De Waele; Participating ICUs: A.S.Z., Iz: Dr. Isabelle Hollevoet. Clinique Saint-Pierre, Intensive Care Unit: Dr. Nicolas De Schryver, Dr. Nicolas Serck. Bosnia And Herzegovina —National Coordinator: Dr. Pedja Kovacevic; Participating ICUs: University Clinical Centre of The Republic Of Srpska, Medical Intensive Care Unit: Dr. Pedja Kovacevic, Dr. Biljana Zlojutro. France —National Coordinator: Prof. Marc Leone; Scientific Committee: Prof. Jean-François Timsit, Prof. Etienne Ruppe, Mr. Stephane Ruckly, Prof. Philippe Montravers; Participating ICUs: Centre Hospitalier De Bigorre, Service De Réanimation Polyvalente: Dr. Thierry Dulac, Dr. Jérémy Castanera. Centre Hospitalier De Pau, Réanimation Polyvalente: Dr. Alexandre Massri, Dr. Charlotte Guesdon. Ghef Site De Marne-La-Vallée, Réanimation Polyvalente: Dr. Pierre Garcon, Dr. Matthieu Duprey. Groupe Hospitalier Paris Saint Joseph, Médecine Intensive et Réanimation: Dr. François Philippart, Dr. Marc Tran, Dr. Cédric Bruel. Hôpital De La Source, Centre Hospitalier Régional D'orléans, Médecine Intensive & Réanimation (Medical Icu): Dr. François Barbier. Hôpital Louis Pasteur, Réanimation: Dr. Pierre Kalfon, Mr Gaëtan Badre. Sorbonne Universite Pitie Salpetriere, Médecine Intensive Et Réanimation Neurologique: Dr. Sophie Demeret, Dr. Loïc Le Guennec. Italy —National Coordinator: Prof. Matteo Bassetti and Dr. Daniele Giacobbe; Participating ICUs: Città Della Salute E Della Scienza - Molinette, Anestesia E Rianimazione Universitaria: Dr. Giorgia Montrucchio, Dr. Gabriele Sales. Irccs Sacro Cuore Don Calabria, Terapia Intensiva: Dr. Ivan Daroui, Dr. Giovanni Lodi. Policlino Paolo Giaccone, Università Degli Studi Di Palermo, Terapia Intensiva Polivalente: Dr. Andrea Cortegiani, Dr. Mariachiara Ippolito, Dr. Davide Bellina, Dr. Andrea Di Guardo. Sant'andrea Hospital Sapienza University of Rome, Department of Medical And Surgical Science And Translational Medicine Intensive Care Unit: Dr. Monica Rocco, Dr. Silvia Fiorelli. Poland —National Coordinator: Dr. Adam Mikstacki; Participating ICUs: Wss Im. Wl. Bieganskiego, Oddzial Anestezjologii I Intensywnej Terapii - Osrodek Pozaustrojowych Technik Wspomagania Czynnosci Nerek I Wątroby: Prof Assoc Mariusz Peichota, Dr. Iwona Pietraszek-Grzywaczewska. Portugal —National Coordinator: Prof. José-Artur Paiva; Scientific Committee: Prof. Pedro Póvoa; Participating ICUs: CHUA Faro, Smi-1: Dr. Andriy Krystopchuk, Dr. Ana Teresa. Hospital De Cascais Dr Jose De Almeida, Unidade de Cuidados Intensivos: Dr. António Manuel Pereira de Figueiredo, Dr. Isabel Botelho. Hospital Sao Francisco Xavier, CHLO, Unidade De Cuidados Intensivos Polivalente: Dr. Vasco Costa, Dr. Rui Pedro Cunha. Russian Federation —National Coordinator: Prof Alexey Gritsan; Participating ICUs: Privolzhskiy District Medical Center, Department Anesthesiology and Intensive Care: Dr. Vladislav Belskiy, Dr. Mikhail Furman. Spain —National Coordinator: Dr. Ricard Ferrer; Participating ICUs: Vall D'herbon, Intensive Care Medicine: Dr. Ricard Ferrer, Dr. Maria Martinez, Dr. Vanessa Casares. Hospital Del Mar, Critical Care Unit: Dr. Maria Pilar Gracia Arnillas, Dr. Rosana Munoz Bermudez. Hospital Punta De Europa, Intensive Care Unit: Dr. Alejandro Ubeda, Dra Maria Salgado. Hospital Universitario La Paz, Surgical Critical Care Unit: Dr. Emilio Maseda, Dr. Alejandro Suarez De La Rica. University Hospital Severo Ochoa, Intensive Care Unit: Dr. Miguel Angel Blasco-Navalpotro, Dr. Alberto Orejas Gallego. Switzerland —National Coordinator: Dr. Josef Prazak; Scientific Committee: Dr. Niccolò Buetti; Participating ICUs: Chuv, Service De Médecine Intensive Adulte: Dr. Jl Pagani, Mrs S Abed-Maillard. Turkey —National Coordinator: Prof. Akova Murat, Dr. Abdullah Tarık Aslan; Participating ICUs: Hacettepe University of Faculty of Medicine, Intensive Care Unit(ICU): Dr. Akova Murat, Dr. Abdullah Tarik Aslan, Dr. Arzu Topeli Iskit. Acibadem Kadikoy Hospital, ICU: Dr. Selcuk Mehtap, Dr. Solakoğlu Ceyhun. Ankara Yildirim Beyazit University, Ankara City Hospital, Infectious Diseases and Clinical Microbiology: Dr. Bircan Kayaaslan, Dr. Ayşe Kaya Kalem. Aydin Adnan Menderes University Research Hospital, Anesthesia and Reanimation ICU: Prof. Dr. Ibrahim Kurt, Dr. (Professor) Murat Telli, Dr. (Associate Professor) Barcin Ozturk. Hitit University Erol Olcok Education and Research Hospital, Infectious Diseases and Clinical Microbiology: Prof. Dr. Nurcan (N) Baykam, Assistant Prof. Dr. Özlem (O) Akdoğan. Istanbul University-Cerrahpasa, Cerrahpasa Medical Faculty, Sadi Sun ICU: Prof.Dr. Nese Saltoglu, Ass Prof.Dr. Ridvan Karaali. Karadeniz Technical University Faculty of Medicine, Infectious Disease and Clinical Microbiology: Prof Dr. Iftihar Koksal, Assist. Prof. Firdevs Aksoy. Kartal Dr. Lutfi Kirdar Training and Research Hospital, ICU: Dr. Kemal Tolga Saracoglu, Dr. Yeliz Bilir. Kayseri City Hospital, ICU: Dr. Seda Guzeldag. Mersin University Hospital, Department of Infectious Diseases and Clinical Microbiology: Dr. Gulden Ersoz, Dr. Guliz Evik. School Of Medicine, Medipol Mega University Hospitals Complex, Department of Anesthesiology and Reanimation: Dr. Cem Erdogan. Turgut Ozal Medical Center, Department of Infectious Diseases and Clinical Microbiology: Dr. Yasar Bayindir, Dr. Yasemin Ersoy. The United Kingdom —National Coordinator: Dr. Andrew Conway Morris; Participating ICUs: Addenbrookes Hospital, John V Farman Intensive Care Unit: Dr. Andrew Conway Morris, Dr. Matthew Routledge. Addenbrookes Hospital, Neurocritical Care Unit (NCCU): Dr. Andrew Conway Morris, Dr. Ari Ercole. Croydon University Hospital, Critical Care Unit: Dr. Ashok Raj, Dr. Artemis Zormpa, Dr. George Tinaslanidis, Mrs Reena Khade. Queen Elizabeth Hospital, Lewisham and Greenwich NHS Trust, Critical Care Unit: Dr. Ashraf Roshdy Sandwell And West Birmingham Hospitals NHS Trust, Intensive Care Unit: Dr. Santhana Kannan, Dr. Supriya Antrolikar, Dr. Nicholas Marsden. Warwick Hospital, Intensive Care Unit: Dr. Ben Attwood, Dr. Jamie Patel. South Asia: India —National Coordinator: Prof. Mohan Gurjar; Participating ICUs: St Johns Medical College Hospital, Department of Critical Care Medicine, Micu: Dr. Carol Dsilva, Dr. Jagadish Chandran. Sub-Saharan Africa: Sudan —National Coordinator: Dr. Bashir El Sanousi; Participating ICUs: East Nile Hospital, Intensive Care Unit: Dr. Elfayadh Saidahmed, Dr. Hytham K.S. Hamid. Funding Information: The authors have disclosed that they do not have conflict of interest. Dr. Buetti received a grant from the Swiss National Science Foundation (Grant Number: P4P4PM_194449). Prof. Timsit received fees for lectures to 3M, MSD, Pfizer, and BioMérieux; he received research grants from Astellas, 3M, MSD, and Pfizer; and he participated to advisory boards of 3M, MSD, Bayer Pharma, Nabriva, and Pfizer. Dr. Barbier received consulting and lecture fees from MSD and BioMérieux. Prof. Cortegiani received fees for lectures from Gilead, MSD, Pfizer; and he participated to advisory boards of MSD, Gilead, Pfizer. Dr. Montrucchio received fees for lectures from Gilead, Pfizer, Thermofisher; and she participated to advisory boards of Gilead. Dr. Conway Morris sits on the scientific advisory board of Cambridge Infection Diagnostics. Prof. Akova received grants from Pfizer and Gilead, had lecture fees paid to the institution by Pfizer and Sanofi. Dr. Ramanan acknowledges support from the Metro North Hospital and Health Services Clinician-Researcher Fellowship. Dr. Conway Morris sits on the scientific advisory board of Cambridge Infection Diagnostics. Dr. Conway Morris is supported by a Clinician Scientist Fellowship from the Medical Research Council (MR/V006118/1). Prof. José-Artur Paiva received fees for consulting, advisory boards or lectures from MSD, Pfizer, Astra-Zeneca, Gilead, Jansen, Cepheid, AOP Orphan Pharmaceuticals. Funding Information: Research grants were obtained from the European society of Intensive Care Medicine (ESICM) and the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) study Group for Infections in Critically Ill Patients (ESGCIP), the Norva Dahlia foundation and the Redcliffe Hospital Private Practice Trust Fund. Dr. Buetti received a grant from the Swiss National Science Foundation (Grant Number: P4P4PM_194449). The study was endorsed by the critically ill group of the ESCMID (ESGCIP) and by the infection group of the ESICM with scientific input of the OUTCOMEREA network. Publisher Copyright: © 2022, The Author(s).Background: The study aimed to describe the epidemiology and outcomes of hospital-acquired bloodstream infections (HABSIs) between COVID-19 and non-COVID-19 critically ill patients. Methods: We used data from the Eurobact II study, a prospective observational multicontinental cohort study on HABSI treated in ICU. For the current analysis, we selected centers that included both COVID-19 and non-COVID-19 critically ill patients. We performed descriptive statistics between COVID-19 and non-COVID-19 in terms of patients’ characteristics, source of infection and microorganism distribution. We studied the association between COVID-19 status and mortality using multivariable fragility Cox models. Results: A total of 53 centers from 19 countries over the 5 continents were eligible. Overall, 829 patients (median age 65 years [IQR 55; 74]; male, n = 538 [64.9%]) were treated for a HABSI. Included patients comprised 252 (30.4%) COVID-19 and 577 (69.6%) non-COVID-19 patients. The time interval between hospital admission and HABSI was similar between both groups. Respiratory sources (40.1 vs. 26.0%, p < 0.0001) and primary HABSI (25.4% vs. 17.2%, p = 0.006) were more frequent in COVID-19 patients. COVID-19 patients had more often enterococcal (20.5% vs. 9%) and Acinetobacter spp. (18.8% vs. 13.6%) HABSIs. Bacteremic COVID-19 patients had an increased mortality hazard ratio (HR) versus non-COVID-19 patients (HR 1.91, 95% CI 1.49–2.45). Conclusions: We showed that the epidemiology of HABSI differed between COVID-19 and non-COVID-19 patients. Enterococcal HABSI predominated in COVID-19 patients. COVID-19 patients with HABSI had elevated risk of mortality. Trial registration ClinicalTrials.org number NCT03937245. Registered 3 May 2019.publishersversionpublishe

the EUROBACT-2 international cohort study

Funding JdW is a senior clinical investigator funded by the Research Foundation Flan ders (FWO, Ref. 1881020N). ACM is supported by a Medical Research Council Clinician Scientist Fellowship (MR/ V006118/1). NB received a fellowship grant (Grant number: P4P4PM_194449) from the Swiss National Science Founda tion. Research grants were obtained from the European Society of Intensive Care Medicine (ESICM), the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) study Group for Infections in Critically Ill Patients (ESGCIP), the Norva Dahlia foundation and the Redclife Hospital Private Practice Trust Fund.PURPOSE: In the critically ill, hospital-acquired bloodstream infections (HA-BSI) are associated with significant mortality. Granular data are required for optimizing management, and developing guidelines and clinical trials. METHODS: We carried out a prospective international cohort study of adult patients (≥ 18 years of age) with HA-BSI treated in intensive care units (ICUs) between June 2019 and February 2021. RESULTS: 2600 patients from 333 ICUs in 52 countries were included. 78% HA-BSI were ICU-acquired. Median Sequential Organ Failure Assessment (SOFA) score was 8 [IQR 5; 11] at HA-BSI diagnosis. Most frequent sources of infection included pneumonia (26.7%) and intravascular catheters (26.4%). Most frequent pathogens were Gram-negative bacteria (59.0%), predominantly Klebsiella spp. (27.9%), Acinetobacter spp. (20.3%), Escherichia coli (15.8%), and Pseudomonas spp. (14.3%). Carbapenem resistance was present in 37.8%, 84.6%, 7.4%, and 33.2%, respectively. Difficult-to-treat resistance (DTR) was present in 23.5% and pan-drug resistance in 1.5%. Antimicrobial therapy was deemed adequate within 24 h for 51.5%. Antimicrobial resistance was associated with longer delays to adequate antimicrobial therapy. Source control was needed in 52.5% but not achieved in 18.2%. Mortality was 37.1%, and only 16.1% had been discharged alive from hospital by day-28. CONCLUSIONS: HA-BSI was frequently caused by Gram-negative, carbapenem-resistant and DTR pathogens. Antimicrobial resistance led to delays in adequate antimicrobial therapy. Mortality was high, and at day-28 only a minority of the patients were discharged alive from the hospital. Prevention of antimicrobial resistance and focusing on adequate antimicrobial therapy and source control are important to optimize patient management and outcomes.publishersversionpublishe

Acceptability to patients, carers and clinicians of an mHealth platform for the management of Parkinson's disease (PD_Manager): study protocol for a pilot randomised controlled trial.

BACKGROUND: Parkinson's disease is a degenerative neurological condition causing multiple motor and non-motor symptoms that have a serious adverse effect on quality of life. Management is problematic due to the variable and fluctuating nature of symptoms, often hourly and daily. The PD_Manager mHealth platform aims to provide a continuous feed of data on symptoms to improve clinical understanding of the status of any individual patient and inform care planning. The objectives of this trial are to (1) assess patient (and family carer) perspectives of PD_Manager regarding comfort, acceptability and ease of use; (2) assess clinician views about the utility of the data generated by PD_Manager for clinical decision making and the acceptability of the system in clinical practice. METHODS/DESIGN: This trial is an unblinded, parallel, two-group, randomised controlled pilot study. A total of 200 persons with Parkinson's disease (Hoehn and Yahr stage 3, experiencing motor fluctuations at least 2 h per day), with primary family carers, in three countries (110 Rome, 50 Venice, Italy; 20 each in Ioannina, Greece and Surrey, England) will be recruited. Following informed consent, baseline information will be gathered, including the following: age, gender, education, attitudes to technology (patient and carer); time since Parkinson's diagnosis, symptom status and comorbidities (patient only). Randomisation will assign participants (1:1 in each country), to PD_Manager vs control, stratifying by age (1 ≤ 70 : 1 > 70) and gender (60% M: 40% F). The PD_Manager system captures continuous data on motor symptoms, sleep, activity, speech quality and emotional state using wearable devices (wristband, insoles) and a smartphone (with apps) for storing and transmitting the information. Control group participants will be asked to keep a symptom diary covering the same elements as PD_Manager records. After a minimum of two weeks, each participant will attend a consultation with a specialist doctor for review of the data gathered (by either means), and changes to management will be initiated as indicated. Patients, carers and clinicians will be asked for feedback on the acceptability and utility of the data collection methods. The PD_Manager intervention, compared to a symptom diary, will be evaluated in a cost-consequences framework. DISCUSSION: Information gathered will inform further development of the PD_Manager system and a larger effectiveness trial. TRIAL REGISTRATION: ISRCTN Registry, ISRCTN17396879 . Registered on 15 March 2017

Mapping the human genetic architecture of COVID-19

The genetic make-up of an individual contributes to the susceptibility and response to viral infection. Although environmental, clinical and social factors have a role in the chance of exposure to SARS-CoV-2 and the severity of COVID-19(1,2), host genetics may also be important. Identifying host-specific genetic factors may reveal biological mechanisms of therapeutic relevance and clarify causal relationships of modifiable environmental risk factors for SARS-CoV-2 infection and outcomes. We formed a global network of researchers to investigate the role of human genetics in SARS-CoV-2 infection and COVID-19 severity. Here we describe the results of three genome-wide association meta-analyses that consist of up to 49,562 patients with COVID-19 from 46 studies across19 countries. We report 13 genome-wide significant loci that are associated with SARS-CoV-2 infection or severe manifestations of COVID-19. Several of these loci correspond to previously documented associations to lung or autoimmune and inflammatory diseases(3-7). They also represent potentially actionable mechanisms in response to infection. Mendelian randomization analyses support a causal role for smoking and body-mass index for severe COVID-19 although not for type II diabetes. The identification of novel host genetic factors associated with COVID-19 was made possible by the community of human genetics researchers coming together to prioritize the sharing of data, results, resources and analytical frameworks. This working model of international collaboration underscores what is possible for future genetic discoveries in emerging pandemics, or indeed for any complex human disease.Peer reviewe

The use of discharge haemoglobin and NT-proBNP to improve short and long-term outcome prediction in patients with acute heart failure

AIMS: To examine the prognostic value of admission (A) and discharge (D) haemoglobin (Hb) and its relationship with N-terminal pro-hormone B-type natriuretic peptide (NT-proBNP) in patients hospitalised for acute heart failure (AHF). The outcomes of interests were rehospitalisation or death after one, six or twelve months after discharge. METHODS: 317 hospitalised AHF patients (74.7±9.4 years) were enrolled in two academic centres in Belgrade and Rome. Laboratory analyses, including NT-proBNP were assessed at admission, and Hb also at discharge. Patients were divided into two groups according to the presence of anaemia. Follow-up contact was made by telephone. Statistical analyses were performed using SPSS software version 21.0. RESULTS: According to A and DHb levels (&lt;120 g/l for women and &lt;130 g/l for men), anaemia was present in 55% and 62% of patients, respectively ( P=0.497). Lower DHb was associated with the rehospitalisation risk after one (OR=0.96, P=0.004), six (OR=0.97, P&lt;0.001) and 12 months (OR=0.97, P&lt;0.001). For every g/l decrease of DHb, the risk of rehospitalisation after one year was increased by 3.3%. In the first six months, DHb contributed to increased risk of death (OR=0.97, P=0.005), but NT-proBNP showed greater power (OR=2.1, P&lt;0.001). CONCLUSIONS: In AHF patients discharge anaemia is a strong predictor for short and long-term rehospitalisation, while NT-proBNP seems to be a better predictor for mortality. Discharge Hb and NT-proBNP should be assessed together in order to detect the patients with higher risk of future death and rehospitalisation

IMPACT OF EXTRACTION PROCEDURE ON CHEMICAL PROFILE AND ANTIOXIDANT EFFECT OF VERONICA OFFICINALIS EXTRACT

Veronica officinalis is plant species used in traditional medicine worldwide, but its effects have not been investigated so far. Consequently, the aim of this research was to identify dominant compound in V. officinalis extracts and to determine the effect of ultrasound and extraction temperature on the content of that compound and total phenolic content. Moreover we investigated the correlation between the concentration of dominant compound and antiradical activity of tested extracts. The main compound in extracts was acteoside. Higher amount of total phenolics and acteoside were obtained using ultrasound-assisted extraction technique and higher temperatures. DPPH assay, which is used for measuring antiradical potential, showed that concentration of acteoside, as well as concentration of polyphenolic compounds, is directly correlated with antioxidative potentiality tested extracts