P3‐209: Impact of Biomarkers On Diagnostic Confidence in Clinical Assessment of Patients with Suspected Alzheimer's Disease and High Diagnostic Uncertainty: An EADC Study

Background: NIA-AA and IWG diagnostic criteria for Alzheimer's Disease (AD) include core structural, functional, and CSF biomarkers. The impact of core biomarkers in clinical settings is still unclear. This study aimed at measuring the impact of core biomarkers on the diagnostic confidence of uncertain AD cases in a routine memory clinic setting. // Methods: 356 patients with mild dementia (MMSE = 20) or Mild Cognitive Impairment possibly due to AD were recruited in 17 European Alzheimer's Disease Consortium (EADC) memory clinics. The following variables were collected: age; sex; MMSE; neuropsychological evaluation including long term memory, executive functions, language and visuospatial abilities. Core biomarkers were collected following local practices: Scheltens’s visual assessment of medial temporal atrophy (MTA) on MR scan; visual assessment of hypometabolism/hypoperfusion on FDG-PET/SPECT brain scan; CSF Aß1-42, tau and phospho-tau levels. At diagnostic workup completion, an estimate of confidence that cognitive complaints were due to AD was elicited from clinicians on a structured scale ranging from 0 to 100. Only cases with uncertain diagnoses (confidence between 15% and 85%) were retained for analysis. Generalized linear models were used to describe the relationship between the collected measures and the diagnostic confidence of AD. // Results: Neuropsychological assessment was carried out in almost all cases (98% of the cases). Medial temporal atrophy ratings were done in 40% of cases, assessment of cortical hypometabolism/hypoperfusion in 34%, and CSF Aß and tau levels in 26%. The markers that better explained the variability of diagnostic confidence were CSF Aß1-42 level (R2=0.46) and hypometabolism/hypoperfusion (R2=0.45), followed by CSF tau level (R2=0.35), MTA assessment (R2=0.32) and. All figures were highly significant, at p<<0.001. The diagnostic confidence variability due to neuropsychological tests for different domains was lower: MMSE (R2=0.29); long term memory (R2=0.23); executive functions (R2=0.05); language (R2=0.02); visuospatial abilities (R2=0.04) even if significant (p<0.01). // Conclusions: The use of core biomarkers in the clinical assessment of subjects with suspected AD and high diagnostic uncertainty is still limited. However, when assessed, these biomarkers show a higher impact on diagnostic confidence of AD than the most widespread clinical measures

Comparison of Two Methods for SARS-CoV-2 Detection in Wastewater: A Case Study from Sofia, Bulgaria

Wastewater surveillance for monitoring the spread of SARS-CoV-2 remains important even in the current endemic stage of the COVID-19 outbreak. This approach has already demonstrated its value by providing early warnings of coronavirus spread in different communities. The aim of the present publication is to share relevant experience from the Center of Competence “Clean&Circle”, obtained in the development of an effective strategy for SARS-CoV-2 detection in the wastewater of Sofia, Bulgaria. Using four different RNA concentration/extraction methods, we revealed that the key hindering factor for successful viral detection was the presence of PCR inhibitors in the wastewater. The most efficient way to overcome their presence turned out to be the application of a specialized polymerase in the RT-PCR detection setup. Our data showed that using such an enzyme increases the detection efficiency from 1.9% to 70.5% in samples with a spiked control virus. We also evaluated the recovery rates of viral particles by using silica columns (71%), PEG precipitation (23%), ultrafiltration (15%), and MCE filtration (10%). These results support the international effort to unify and standardize the various techniques used for SARS-CoV-2 monitoring in wastewater

Human resources in health care - state and trends

Introduction: Human resources are a very important factor for the development of health care. Labour in health care is carried out by people with different occupations and qualifications who perform medical and non-medical activities. However, the imbalance between different types of specialists and their territorial distribution creates a number of difficulties. The aim of the study is to analyse the latest health workforce trends in Bulgaria in a comparative perspective.Materials and methods: The study is based on official reports, analyses, and statistical data by the WHO, European observatory, Organization of Economic Cooperation and Development (OECD), the European Union and Bulgarian sources.Results: The results show the increase in availability of physicians and dentists in Bulgaria between 2000 and 2015. In 2014, the number of physicians and dentists were much higher than the average for the EU 13 and the Region. Although the proportion of physicians is high, only 16.6% of all physicians are general practitioners in 2015, which is much lower than the EU average of 30%. Additionally, in 2015, Bulgaria is one of two countries (together with Cyprus) with the highest densities of practising dentists in the EU. The number of nurses per 1000 population (4.9) is considerably lower than the EU13 average (6.1), EU15 average (9.4) and EU27 average (8.7). Despite a decrease in the number of midwives in the country, their availability is still greater than the average for both the Region and the EU 13.Conclusion: Despite the good availability of doctors in general, the tendency is the reduction in the number of doctors in some specialties. The low availability of health professionals and the unfavourable proportion of nurses and doctors will create even more serious difficulties in providing the necessary health care to the population in the future

Consumers` satisfaction and attitudes to health tourism in the Varna region

Introduction: Modern lifestyle and the increasing number of chronic diseases prompt people to look for new ways for recovery. One of them is health tourism. It helps people to maintain, stabilize and re­store their physical and mental condition. The aim of the research is to study the attitudes of consum­ers towards the health tourism opportunities in the Varna region.Materials and methods: The research is based on a quantitative sociological survey, using a semi-structured questionnaire. The questionnaire consists of 19 questions arranged into two sections, ex­ploring rehabilitation procedures on one hand and opportunities for health tourism on another. The survey was carried out among 119 tourists in the Varna region between 1st and 14th December 2017.Results: Consumers of recreation and rehabilitation health services assess the health tourism services in the Varna region positively in general (`excellent` - 7.6%, `very good` - 28% and `good` - 33.9%). Among the strengths of the Varna region as a health tourism destination, the respondents point out the favourable location (44.8%), high quality and complexity of the tourist products, including an op­portunity to combine health services with other forms of alternative tourism, such as cultural, eco­logical, rural (42.2%). Among the weak points of Varna as a destination are the polluted environment (39%), the outdated facilities (36%), and the lack of modern medical equipment (28%). Users find spe­cific information about the destination mainly on the Internet (75%) and get advice from friends and acquaintances (49.1%).Conclusions: Although the Varna region possesses all required prerequisites to become a preferred destination for health tourism, there is a need to streamline the users` sources of information and to improve the image of the region as a destination for health tourism, together with an improvement of the environment and providers` infrastructure

The impact of automated hippocampal volumetry on diagnostic confidence in patients with suspected Alzheimer's disease: An EADC study

none47Hippocampal volume is a core biomarker of Alzheimer's disease (AD). However, its contribution over the standard diagnostic workup is unclear. Three hundred fifty-six patients, under clinical evaluation for cognitive impairment, with suspected AD and Mini-Mental State Examination ≥20, were recruited across 17 European memory clinics. After the traditional diagnostic workup, diagnostic confidence of AD pathology (DCAD) was estimated by the physicians in charge. The latter were provided with the results of automated hippocampal volumetry in standardized format and DCAD was reassessed. RESULTS: An increment of one interquartile range in hippocampal volume was associated with a mean change of DCAD of -8.0% (95% credible interval: [-11.5, -5.0]). Automated hippocampal volumetry showed a statistically significant impact on DCAD beyond the contributions of neuropsychology, 18F-fluorodeoxyglucose positron emission tomography/single-photon emission computed tomography, and cerebrospinal fluid markers (-8.5, CrI: [-11.5, -5.6]; -14.1, CrI: [-19.3, -8.8]; -10.6, CrI: [-14.6, -6.1], respectively). DISCUSSION: There is a measurable effect of hippocampal volume on DCAD even when used on top of the traditional diagnostic workup.Bosco, Paolo; Redolfi, Alberto; Bocchetta, Martina; Ferrari, Clarissa; Mega, Anna; Galluzzi, Samantha; Austin, Mark; Chincarini, Andrea; Collins, D Louis; Duchesne, Simon; Maréchal, Bénédicte; Roche, Alexis; Sensi, Francesco; Wolz, Robin; Alegret, Montserrat; Assal, Frederic; Balasa, Mircea; Bastin, Christine; Bougea, Anastasia; Emek-Savaş, Derya Durusu; Engelborghs, Sebastiaan; Grimmer, Timo; Grosu, Galina; Kramberger, Milica G; Lawlor, Brian; Mandic Stojmenovic, Gorana; Marinescu, Mihaela; Mecocci, Patrizia; Molinuevo, José Luis; Morais, Ricardo; Niemantsverdriet, Ellis; Nobili, Flavio; Ntovas, Konstantinos; O'Dwyer, Sarah; Paraskevas, George P; Pelini, Luca; Picco, Agnese; Salmon, Eric; Santana, Isabel; Sotolongo-Grau, Oscar; Spiru, Luiza; Stefanova, Elka; Popovic, Katarina Surlan; Tsolaki, Magda; Yener, Görsev G; Zekry, Dina; Frisoni, Giovanni BBosco, Paolo; Redolfi, Alberto; Bocchetta, Martina; Ferrari, Clarissa; Mega, Anna; Galluzzi, Samantha; Austin, Mark; Chincarini, Andrea; Collins, D. Louis; Duchesne, Simon; Maréchal, Bénédicte; Roche, Alexis; Sensi, Francesco; Wolz, Robin; Alegret, Montserrat; Assal, Frederic; Balasa, Mircea; Bastin, Christine; Bougea, Anastasia; Emek Savaş, Derya Durusu; Engelborghs, Sebastiaan; Grimmer, Timo; Grosu, Galina; Kramberger, Milica G; Lawlor, Brian; Mandic Stojmenovic, Gorana; Marinescu, Mihaela; Mecocci, Patrizia; Molinuevo, José Luis; Morais, Ricardo; Niemantsverdriet, Ellis; Nobili, FLAVIO MARIANO; Ntovas, Konstantinos; O'Dwyer, Sarah; Paraskevas, George P; Pelini, Luca; Picco, Agnese; Salmon, Eric; Santana, Isabel; Sotolongo Grau, Oscar; Spiru, Luiza; Stefanova, Elka; Popovic, Katarina Surlan; Tsolaki, Magda; Yener, Görsev G; Zekry, Dina; Frisoni, Giovanni B

Annotated corpora and tools of the PARSEME Shared Task on Automatic Identification of Verbal Multiword Expressions (edition 1.0)

The PARSEME shared task aims at identifying verbal MWEs in running texts. Verbal MWEs include idioms (let the cat out of the bag), light verb constructions (make a decision), verb-particle constructions (give up), and inherently reflexive verbs (se suicider 'to suicide' in French). VMWEs were annotated according to the universal guidelines in 18 languages. The corpora are provided in the parsemetsv format, inspired by the CONLL-U format. For most languages, paired files in the CONLL-U format - not necessarily using UD tagsets - containing parts of speech, lemmas, morphological features and/or syntactic dependencies are also provided. Depending on the language, the information comes from treebanks (e.g., Universal Dependencies) or from automatic parsers trained on treebanks (e.g., UDPipe). This item contains training and test data, tools and the universal guidelines file

Safety and immunogenicity of the ChAdOx1 nCoV-19 vaccine against SARS-CoV-2: a preliminary report of a phase 1/2, single-blind, randomised controlled trial.

BACKGROUND: The pandemic of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) might be curtailed by vaccination. We assessed the safety, reactogenicity, and immunogenicity of a viral vectored coronavirus vaccine that expresses the spike protein of SARS-CoV-2. METHODS: We did a phase 1/2, single-blind, randomised controlled trial in five trial sites in the UK of a chimpanzee adenovirus-vectored vaccine (ChAdOx1 nCoV-19) expressing the SARS-CoV-2 spike protein compared with a meningococcal conjugate vaccine (MenACWY) as control. Healthy adults aged 18-55 years with no history of laboratory confirmed SARS-CoV-2 infection or of COVID-19-like symptoms were randomly assigned (1:1) to receive ChAdOx1 nCoV-19 at a dose of 5 × 1010 viral particles or MenACWY as a single intramuscular injection. A protocol amendment in two of the five sites allowed prophylactic paracetamol to be administered before vaccination. Ten participants assigned to a non-randomised, unblinded ChAdOx1 nCoV-19 prime-boost group received a two-dose schedule, with the booster vaccine administered 28 days after the first dose. Humoral responses at baseline and following vaccination were assessed using a standardised total IgG ELISA against trimeric SARS-CoV-2 spike protein, a muliplexed immunoassay, three live SARS-CoV-2 neutralisation assays (a 50% plaque reduction neutralisation assay [PRNT50]; a microneutralisation assay [MNA50, MNA80, and MNA90]; and Marburg VN), and a pseudovirus neutralisation assay. Cellular responses were assessed using an ex-vivo interferon-γ enzyme-linked immunospot assay. The co-primary outcomes are to assess efficacy, as measured by cases of symptomatic virologically confirmed COVID-19, and safety, as measured by the occurrence of serious adverse events. Analyses were done by group allocation in participants who received the vaccine. Safety was assessed over 28 days after vaccination. Here, we report the preliminary findings on safety, reactogenicity, and cellular and humoral immune responses. The study is ongoing, and was registered at ISRCTN, 15281137, and ClinicalTrials.gov, NCT04324606. FINDINGS: Between April 23 and May 21, 2020, 1077 participants were enrolled and assigned to receive either ChAdOx1 nCoV-19 (n=543) or MenACWY (n=534), ten of whom were enrolled in the non-randomised ChAdOx1 nCoV-19 prime-boost group. Local and systemic reactions were more common in the ChAdOx1 nCoV-19 group and many were reduced by use of prophylactic paracetamol, including pain, feeling feverish, chills, muscle ache, headache, and malaise (all p<0·05). There were no serious adverse events related to ChAdOx1 nCoV-19. In the ChAdOx1 nCoV-19 group, spike-specific T-cell responses peaked on day 14 (median 856 spot-forming cells per million peripheral blood mononuclear cells, IQR 493-1802; n=43). Anti-spike IgG responses rose by day 28 (median 157 ELISA units [EU], 96-317; n=127), and were boosted following a second dose (639 EU, 360-792; n=10). Neutralising antibody responses against SARS-CoV-2 were detected in 32 (91%) of 35 participants after a single dose when measured in MNA80 and in 35 (100%) participants when measured in PRNT50. After a booster dose, all participants had neutralising activity (nine of nine in MNA80 at day 42 and ten of ten in Marburg VN on day 56). Neutralising antibody responses correlated strongly with antibody levels measured by ELISA (R2=0·67 by Marburg VN; p<0·001). INTERPRETATION: ChAdOx1 nCoV-19 showed an acceptable safety profile, and homologous boosting increased antibody responses. These results, together with the induction of both humoral and cellular immune responses, support large-scale evaluation of this candidate vaccine in an ongoing phase 3 programme. FUNDING: UK Research and Innovation, Coalition for Epidemic Preparedness Innovations, National Institute for Health Research (NIHR), NIHR Oxford Biomedical Research Centre, Thames Valley and South Midland's NIHR Clinical Research Network, and the German Center for Infection Research (DZIF), Partner site Gießen-Marburg-Langen

Annotated corpora and tools of the PARSEME Shared Task on Automatic Identification of Verbal Multiword Expressions (edition 1.1)

This multilingual resource contains corpora in which verbal MWEs have been manually annotated. VMWEs include idioms (let the cat out of the bag), light-verb constructions (make a decision), verb-particle constructions (give up), inherently reflexive verbs (help oneself), and multi-verb constructions (make do). VMWEs were annotated according to the universal guidelines in 19 languages. The corpora are provided in the cupt format, inspired by the CONLL-U format. The corpora were used in the 1.1 edition of the PARSEME Shared Task (2018). For most languages, morphological and syntactic information ­­­­– not necessarily using UD tagsets – including parts of speech, lemmas, morphological features and/or syntactic dependencies are also provided. Depending on the language, the information comes from treebanks (e.g., Universal Dependencies) or from automatic parsers trained on treebanks (e.g., UDPipe). This item contains training, development and test data, as well as the evaluation tools used in the PARSEME Shared Task 1.1 (2018). The annotation guidelines are available online: http://parsemefr.lif.univ-mrs.fr/parseme-st-guidelines/1.

Annotated corpora and tools of the PARSEME Shared Task on Automatic Identification of Verbal Multiword Expressions (edition 1.1)

This multilingual resource contains corpora in which verbal MWEs have been manually annotated. VMWEs include idioms (let the cat out of the bag), light-verb constructions (make a decision), verb-particle constructions (give up), inherently reflexive verbs (help oneself), and multi-verb constructions (make do). VMWEs were annotated according to the universal guidelines in 19 languages. The corpora are provided in the cupt format, inspired by the CONLL-U format. The corpora were used in the 1.1 edition of the PARSEME Shared Task (2018). For most languages, morphological and syntactic information ­­­­– not necessarily using UD tagsets – including parts of speech, lemmas, morphological features and/or syntactic dependencies are also provided. Depending on the language, the information comes from treebanks (e.g., Universal Dependencies) or from automatic parsers trained on treebanks (e.g., UDPipe). This item contains training, development and test data, as well as the evaluation tools used in the PARSEME Shared Task 1.1 (2018). The annotation guidelines are available online: http://parsemefr.lif.univ-mrs.fr/parseme-st-guidelines/1.