Your browser doesn't support javascript.
loading
: 20 | 50 | 100
1 - 20 de 2.999
1.
Am Soc Clin Oncol Educ Book ; 44(3): e100040, 2024 Jun.
Article En | MEDLINE | ID: mdl-38771997

Clinical trials are essential for advancing oncology treatment strategies and have contributed significantly to the decline in cancer mortality rates over the past decades. Traditional explanatory trials, focused on establishing intervention efficacy in ideal settings, often lack generalizability and may not reflect real-world patient care scenarios. Furthermore, increasing complexity in cancer clinical trial design has led to challenges such as protocol deviations, slow enrollment leading to lengthened durations of trial, and escalating costs. By contrast, pragmatic trials aim to assess intervention effectiveness in more representative patient populations under routine clinical conditions. Here, we review the principles, methodologies, challenges, and advantages of incorporating pragmatic features (PFs) into cancer clinical trials. We illustrate the application of pragmatic trial designs in oncology and discuss the QUASAR collaborative, TAPUR study, and the ongoing PRAGMATICA-LUNG trial. Although not all oncology trials may be amenable to adopting fully pragmatic designs, integration of PFs when feasible will enhance trial generalizability and real-world applicability. Project Pragmatica and similar initiatives advocate for the integration of real-world practice with clinical trials, fostering a nuanced approach to oncology research that balances efficacy and effectiveness assessments, ultimately with a goal of improving patient outcomes.


Clinical Trials as Topic , Neoplasms , Humans , Neoplasms/therapy , Research Design , Pragmatic Clinical Trials as Topic/methods , Medical Oncology/methods
3.
Eur J Heart Fail ; 2024 May 13.
Article En | MEDLINE | ID: mdl-38741283

AIMS: We examined the effectiveness of a novel cardiopulmonary management wearable sensor (worn for less than 5 mins) at measuring congestion and correlated the device findings with established clinical measures of congestion. METHODS AND RESULTS: We enrolled three cohorts of patients: (1) patients with heart failure (HF) receiving intravenous diuretics in hospital; (2) patients established on haemodialysis, and (3) HF patients undergoing right heart catheterization (RHC). The primary outcomes in the respective cohorts were a Spearman correlation between (1) change in weight and change in thoracic impedance (TI) (from enrolment, 24 h after admission to discharge) in patients hospitalized for HF; (2) lung ultrasound B-lines and volume removed during dialysis with device measured TI, and (3) pulmonary capillary wedge pressure (PCWP) and sub-acoustic diastolic, third heart sound (S3) in the patients undergoing RHC. A total of 66 patients were enrolled. In HF patients (n = 25), change in weight was correlated with both change in device TI (Spearman correlation [rsp] = -0.64, p = 0.002) and change in device S3 (rsp = -0.53, p = 0.014). In the haemodialysis cohort (n = 21), B-lines and TI were strongly correlated before (rsp = -0.71, p < 0.001) and after (rsp = -0.77, p < 0.001) dialysis. Volume of fluid removed by dialysis was correlated with change in device TI (rsp = 0.49, p = 0.024). In the RHC cohort (n = 20), PCWP measured at one time point and device S3 were not significantly correlated (rsp = 0.230, p = 0.204). There were no device-related adverse events. CONCLUSIONS: A non-invasive device was able to detect changes in congestion in patients with HF receiving decongestion therapy and patients having fluid removed at haemodialysis. The cardiopulmonary management device, which measures multiple parameters, is a potentially useful tool to monitor patients with HF to prevent hospitalizations.

5.
Cell Rep Methods ; 4(4): 100761, 2024 Apr 22.
Article En | MEDLINE | ID: mdl-38653205

The international Synthetic Yeast Project (Sc2.0) aims to construct the first synthetic designer eukaryote genome. Over the past few years, the Sc2.0 consortium has achieved several significant milestones by synthesizing and characterizing all 16 nuclear chromosomes of the yeast Saccharomyces cerevisiae, as well as a 17thde novo neochromosome containing all nuclear tRNA genes. In this commentary, we discuss the recent technological advances achieved in this project and provide a perspective on how they will impact the emerging field of synthetic genomics in the future.


Genome, Fungal , Saccharomyces cerevisiae , Genetic Engineering/methods , Genome, Fungal/genetics , Genomics/methods , Saccharomyces cerevisiae/genetics , Synthetic Biology/methods
6.
Brain ; 2024 Apr 04.
Article En | MEDLINE | ID: mdl-38574200

Degeneration of dopaminergic neurons in the substantia nigra and their striatal axon terminals causes cardinal motor symptoms of Parkinson's disease. In idiopathic cases, high levels of mitochondrial DNA alterations leading to mitochondrial dysfunction are a central feature of these vulnerable neurons. Here we present a mouse model expressing the K320E-variant of the mitochondrial helicase Twinkle in dopaminergic neurons, leading to accelerated mitochondrial DNA mutations. These K320E-TwinkleDaN mice showed normal motor function at 20 months of age, although ∼70% of nigral dopaminergic neurons had perished. Remaining neurons still preserved ∼75% of axon terminals in the dorsal striatum and enabled normal dopamine release. Transcriptome analysis and viral tracing confirmed compensatory axonal sprouting of the surviving neurons. We conclude that a small population of substantia nigra dopaminergic neurons is able to adapt to the accumulation of mitochondrial DNA mutations and maintain motor control.

7.
Trends Biotechnol ; 2024 Apr 03.
Article En | MEDLINE | ID: mdl-38575438

Killer yeasts secrete protein toxins that are selectively lethal to other yeast and filamentous fungi. These exhibit exceptional genetic and functional diversity, and have several biotechnological applications. However, despite decades of research, several limitations hinder their widespread adoption. In this perspective we contend that technical advances in synthetic biology present an unprecedented opportunity to unlock the full potential of yeast killer systems across a spectrum of applications. By leveraging these new technologies, engineered killer toxins may emerge as a pivotal new tool to address antifungal resistance and food security. Finally, we speculate on the biotechnological potential of re-engineering host double-stranded (ds) RNA mycoviruses, from which many toxins derive, as a safe and noninfectious system to produce designer RNA.

8.
Microb Genom ; 10(4)2024 Apr.
Article En | MEDLINE | ID: mdl-38625719

Genome sequencing and assembly of the photosynthetic picoeukaryotic Picochlorum sp. SENEW3 revealed a compact genome with a reduced gene set, few repetitive sequences, and an organized Rabl-like chromatin structure. Hi-C chromosome conformation capture revealed evidence of possible chromosomal translocations, as well as putative centromere locations. Maintenance of a relatively few selenoproteins, as compared to similarly sized marine picoprasinophytes Mamiellales, and broad halotolerance compared to others in Trebouxiophyceae, suggests evolutionary adaptation to variable salinity environments. Such adaptation may have driven size and genome minimization and have been enabled by the retention of a high number of membrane transporters. Identification of required pathway genes for both CAM and C4 photosynthetic carbon fixation, known to exist in the marine mamiellale pico-prasinophytes and seaweed Ulva, but few other chlorophyte species, further highlights the unique adaptations of this robust alga. This high-quality assembly provides a significant advance in the resources available for genomic investigations of this and other photosynthetic picoeukaryotes.


Genomics , Photosynthesis , Chromosome Mapping , Photosynthesis/genetics , Chromosomes , Chromatin/genetics
9.
Eur Radiol Exp ; 8(1): 29, 2024 Mar 12.
Article En | MEDLINE | ID: mdl-38467990

Hepatocellular carcinoma (HCC) comprises 75 to 85% of all primary liver cancers. Current guidelines recommend a biannual HCC surveillance using ultrasound (US) for high-risk patients. However, due to its low sensitivity for detection of early-stage HCC lesions, there is an urgency for more sensitive surveillance tools. Here, we describe the potential of a short MRI surveillance (SMS) protocol for HCC, including axial T1-weighted in-out phase, fat-saturated T2-weighted, and diffusion-weighted sequences. In this prospective, multicenter, patient cohort study, patients will be recruited from existing HCC surveillance cohorts of six medical centers in The Netherlands. Surveillance patients who undergo biannual US, will be invited for SMS on the same day for 3 years. In case of a suspicious finding on either US or SMS, patients will be invited for a full MRI liver protocol including gadolinium-based contrast agent intravenous injection within 2 weeks. To our knowledge, this will be the first study to perform a head-to-head comparison with a paired US-MRI design. We hypothesize that the sensitivity of SMS for detection of early-stage HCC will be higher than that of US leading to improved survival of surveillance patients through timely HCC diagnosis. Furthermore, we hypothesize that the SMS-HCC protocol will prove cost-effective.Relevance statement The US sensitivity for detecting early-stage HCC has been reported to be less than 50%. We expect that the proposed SMS will detect at least twice as many early-stage HCC lesions and therefore prove to be cost-effective. Key points • The low sensitivity of US necessitates better imaging tools for HCC screening.• This is the first study with a paired US-MRI design.• This design will allow a head-to-head comparison in both diagnostics and patient-acceptance.• We expect that SMS can contribute to a higher survival rate.


Carcinoma, Hepatocellular , Liver Neoplasms , Humans , Carcinoma, Hepatocellular/diagnostic imaging , Liver Neoplasms/diagnostic imaging , Prospective Studies , Magnetic Resonance Imaging/methods , Contrast Media , Multicenter Studies as Topic
10.
J Psychol ; : 1-34, 2024 Mar 28.
Article En | MEDLINE | ID: mdl-38546664

How do researchers in psychology view the relation between scientific knowledge, its applicability, and its societal relevance? Most research on psychological science and its benefits to society is discussed from a bird's eye view (a meta-scientific perspective), by identifying general trends such as psychology's dominant focus on lab-based experiments and general descriptive theories. In recent years, several critics have argued that this focus has come at the cost of reduced practical and societal relevance. In this study, we interviewed Dutch psychology professors to gauge their views about the relation between psychological research and its relevance to society. We found that psychology professors engaged in a variety of activities to engage science with society, from work in clinical and applied settings, to consultancy, education, and science communication. However, we found that the role of theory when applying scientific knowledge to practical problems is far from straightforward. While most participants regarded theories as relevant to understanding general contexts of application, psychological theories were seldom directly related to specific applications. We compare and discuss our findings in the light of recent discussions about the lack of applicability and societal relevance of psychological science.

11.
Target Oncol ; 19(2): 131-134, 2024 Mar.
Article En | MEDLINE | ID: mdl-38466534

This is a summary of the original article ?Overall survival with osimertinib in resected EGFR-mutated NSCLC.Ë® Osimertinib blocks the activity of the epidermal growth factor receptor (EGFR) on cancer cells, causing cancer cell death and tumor shrinkage, and is an effective treatment for EGFR-mutated non-small cell lung cancer (NSCLC). The ADAURA study assessed the effects of osimertinib versus placebo in patients with EGFR-mutated (exon 19 deletion or L858R) early stage (IB-IIIA) NSCLC removed by surgery (resected). Previous results from ADAURA demonstrated that patients treated with osimertinib stayed alive and cancer-free (disease-free survival) significantly longer than patients who received placebo. Recent data showed the overall length of time patients were alive after starting treatment (overall survival). In both the primary stage II-IIIA and overall stage IB-IIIA populations, patients in the osimertinib group had a significant 51% reduction in the risk of death compared with the placebo group. The data demonstrated that osimertinib after surgery significantly improved overall survival in patients with resected, EGFR-mutated, stage IB-IIIA NSCLC.


Acrylamides , Carcinoma, Non-Small-Cell Lung , Indoles , Lung Neoplasms , Pyrimidines , Humans , Carcinoma, Non-Small-Cell Lung/drug therapy , Carcinoma, Non-Small-Cell Lung/genetics , Lung Neoplasms/drug therapy , Lung Neoplasms/genetics , Protein Kinase Inhibitors/pharmacology , Protein Kinase Inhibitors/therapeutic use , Mutation , Aniline Compounds/pharmacology , Aniline Compounds/therapeutic use , ErbB Receptors/genetics , ErbB Receptors/therapeutic use
12.
Intensive Care Med ; 50(4): 493-501, 2024 Apr.
Article En | MEDLINE | ID: mdl-38526578

An implantable left ventricular assist device (LVAD) is indicated as a bridge to transplantation or recovery in the United Kingdom (UK). The mechanism of action of the LVAD results in a unique state of haemodynamic stability with diminished arterial pulsatility. The clinical assessment of an LVAD recipient can be challenging because non-invasive blood pressure, pulse and oxygen saturation measurements may be hard to obtain. As a result of this unusual situation and complex interplay between the device and the native circulation, resuscitation of LVAD recipients requires bespoke guidelines. Through collaboration with key UK stakeholders, we assessed the current evidence base and developed guidelines for the recognition of clinical deterioration, inadequate circulation and time-critical interventions. Such guidelines, intended for use in transplant centres, are designed to be deployed by those providing immediate care of LVAD patients under conditions of precipitous clinical deterioration. In summary, the Joint British Societies and Transplant Centres LVAD Working Group present the UK guideline on management of emergencies in implantable LVAD recipients for use in advanced heart failure centres. These recommendations have been made with a UK resuscitation focus but are widely applicable to professionals regularly managing patients with implantable LVADs.


Clinical Deterioration , Heart Failure , Heart Transplantation , Heart-Assist Devices , Humans , Emergencies , Heart Failure/therapy
13.
Front Oncol ; 14: 1328512, 2024.
Article En | MEDLINE | ID: mdl-38444675

Background: While many molecular assays can detect mutations at low tumor purity and variant allele frequencies, complex biomarkers such as tumor mutational burden (TMB), microsatellite instability (MSI), and genomic loss of heterozygosity (gLOH) require higher tumor purity for accurate measurement. Scalable, quality-controlled, tissue-conserving methods to increase tumor nuclei percentage (TN%) from tumor specimens are needed for complex biomarkers and hence necessary to maximize patient matching to approved therapies or clinical trial enrollment. We evaluated the clinical utility and performance of precision needle-punch enrichment (NPE) compared with traditional razor blade macroenrichment of tumor specimens on molecular testing success. Methods: Pathologist-directed NPE was performed manually on formalin-fixed, paraffin embedded (FFPE) blocks. Quality control of target capture region and quantity of residual tumor in each tissue block was determined via a post-enrichment histologic slide recut. Resultant tumor purity and biomarker status were determined by the computational analysis pipeline component of the FDA-approved next-generation sequencing (NGS) assay, FoundationOne®CDx. Following NPE implementation for real-world clinical samples, assay performance and biomarker (MSI, TMB, gLOH) detection were analyzed. Results: In real-world clinical samples, enrichment rate via NPE was increased to ~50% over a 2.5-year period, exceeding the prior use of razor blade macro-enrichment (<30% of cases) prior to NPE implementation due to proven efficacy in generating high quality molecular results from marginal samples and the ease of use for both pathologist and histotechnologists. NPE was associated with lower test failures, higher computational tumor purity, and higher rates of successful TMB, MSI and gLOH determination when stratified by pre-enriched (incipient) tumor nuclei percentage. In addition, challenging cases in which tumor content was initially insufficient for testing were salvaged for analysis of biomarker status, gene amplification/deletion, and confident mutant or wild-type gene status determination. Conclusions: Pathologist-directed precision enrichment from tissue blocks (aka NPE) increases tumor purity, and consequently, yields a greater number of successful tests and complex biomarker determinations. Moreover, this process is rapid, safe, inexpensive, scalable, and conserves patient surgical pathology material. NPE may constitute best practice with respect to enriching tumor cells from low-purity specimens for biomarker detection in molecular laboratories.

14.
Behav Brain Sci ; 47: e48, 2024 Feb 05.
Article En | MEDLINE | ID: mdl-38311450

We disagree with Almaatouq et al. that no realistic alternative exists to the "one-at-a-time" paradigm. Seventy years ago, Egon Brunswik introduced representative design, which offers a clear path to commensurability and generality. Almaatouq et al.'s integrative design cannot guarantee the external validity and generalizability of results which is sorely needed, while representative design tackles the problem head on.

16.
Behav Res Methods ; 56(4): 3280-3299, 2024 Apr.
Article En | MEDLINE | ID: mdl-38424292

Blinks, the closing and opening of the eyelids, are used in a wide array of fields where human function and behavior are studied. In data from video-based eye trackers, blink rate and duration are often estimated from the pupil-size signal. However, blinks and their parameters can be estimated only indirectly from this signal, since it does not explicitly contain information about the eyelid position. We ask whether blinks detected from an eye openness signal that estimates the distance between the eyelids (EO blinks) are comparable to blinks detected with a traditional algorithm using the pupil-size signal (PS blinks) and how robust blink detection is when data quality is low. In terms of rate, there was an almost-perfect overlap between EO and PS blink (F1 score: 0.98) when the head was in the center of the eye tracker's tracking range where data quality was high and a high overlap (F1 score 0.94) when the head was at the edge of the tracking range where data quality was worse. When there was a difference in blink rate between EO and PS blinks, it was mainly due to data loss in the pupil-size signal. Blink durations were about 60 ms longer in EO blinks compared to PS blinks. Moreover, the dynamics of EO blinks was similar to results from previous literature. We conclude that the eye openness signal together with our proposed blink detection algorithm provides an advantageous method to detect and describe blinks in greater detail.


Algorithms , Blinking , Eye-Tracking Technology , Humans , Blinking/physiology , Pupil/physiology , Eyelids/physiology , Male , Adult , Female , Eye Movements/physiology
17.
Behav Res Methods ; 2024 Jan 10.
Article En | MEDLINE | ID: mdl-38200239

We built a novel setup to record large gaze shifts (up to 140[Formula: see text]). The setup consists of a wearable eye tracker and a high-speed camera with fiducial marker technology to track the head. We tested our setup by replicating findings from the classic eye-head gaze shift literature. We conclude that our new inexpensive setup is good enough to investigate the dynamics of large eye-head gaze shifts. This novel setup could be used for future research on large eye-head gaze shifts, but also for research on gaze during e.g., human interaction. We further discuss reference frames and terminology in head-free eye tracking. Despite a transition from head-fixed eye tracking to head-free gaze tracking, researchers still use head-fixed eye movement terminology when discussing world-fixed gaze phenomena. We propose to use more specific terminology for world-fixed phenomena, including gaze fixation, gaze pursuit, and gaze saccade.

18.
Mymensingh Med J ; 33(1): 9-15, 2024 Jan.
Article En | MEDLINE | ID: mdl-38163767

Magnesium (Mg) has important effects on vascular system and deficiency of this cation is thought to be a risk factor for cerebrovascular atherosclerosis and complications. The study was planned to find out the association of serum magnesium level with severity of neurological disability in patient with acute ischemic stroke. This cross-sectional descriptive study was conducted in the department of Neurology and Medicine at Mymensingh Medical College & Hospital, Mymensingh from June, 2018 to October, 2019. Patients with acute ischemic stroke were evaluated following informed written consent. Diagnosis was confirmed by neuroimaging of brain. Moreover, serum magnesium assay was done for each patient. Data were collected by interview, clinical examination and laboratory investigations of patients using a case record form and analysis was carried out by using the SPSS 22.0 (IBM Inc., Armonk, NY, USA). Mean age of acute ischemic stroke patients was 63.94±13.93 years with male predominance (58.30%). Majority of the respondents (70.2%) had NIH Stroke Scale (NIHSS) score 5-15 (moderate stroke), 13.1% had score 1-5 (minor stroke), 13.1% had score15-20 (Moderate to severe stroke) and 3.6% had score 21-42 (severe stroke). Mean serum magnesium level was 1.83±0.283mg/dl. Hypomagnesaemia was present in 28(33.3%) patients and it was related with higher NIHSS scoring (p<0.05). Multiple regression showed that among the risk factors, serum magnesium level was independently associated with severity of neurological disability of the acute ischemic stroke (p<0.001). In this study, the correlation coefficient between serum magnesium level and NIHSS score was found as r= - 0.667 which showed negative relationship between serum magnesium and NIHSS score. Lower serum magnesium level is associated with the severity of neurological disability of acute ischemic stroke patient. Further case-control studies are required to validate this finding.


Brain Ischemia , Ischemic Stroke , Stroke , Humans , Male , Middle Aged , Aged , Female , Brain Ischemia/complications , Magnesium , Cross-Sectional Studies
19.
Mymensingh Med J ; 33(1): 49-61, 2024 Jan.
Article En | MEDLINE | ID: mdl-38163773

Sepsis is a serious, life-threatening condition, occurring when an infectious agent invades the body, resulting in systemic inflammatory response syndrome (SIRS). Neonates and children are among the most vulnerable population groups of developing sepsis because of their weak immune barrier. Despite major advances in prevention, diagnosis and treatment of bacterial infections, invasive infections followed by sepsis remain one of the leading causes of childhood mortality. The aim of this study was to identify bacterial agents and antimicrobial resistance patterns of aerobic bacteria among children suspected of having sepsis. This cross-sectional descriptive type of observational study was conducted in the Department of Microbiology, Mymensingh Medical College, Bangladesh from March 2021 to February 2022. Blood samples were collected from pediatric patients, suspected of having sepsis referred from inpatient facility of department of Neonatology and Pediatrics, Mymensingh Medical College Hospital (MMCH). Blood samples were inoculated into BacT/ALERT PF Plus bottles followed by sub-culture of positive samples in blood agar, MacConkey agar and chocolate agar plates. Isolated bacteria were identified by routine biochemical tests. Antimicrobial resistance pattern of all isolated bacteria was seen by disk diffusion method. MIC of vancomycin by agar dilution method was determined for isolated S. aureus and Coagulase negative Staphylococci (CoNS). The prevalence of pediatric sepsis was 31.82% with highest isolation rate 35.55% among neonates. The isolation rate of gram-positive bacteria was 62.50% where S. aureus was the most common isolate 32.15% followed by CoNS 30.36%. Out of 21 gram-negative bacteria, Pseudomonas spp. was the most frequent isolate 7(33.33%), all of which were resistant to cefuroxime, ceftriaxone and ceftazidime along with all klebsiella and Acinetobacter isolates. Out of 18 S. aureus isolates, 94.44%, 88.89% and 66.67% were resistant to Azithromycin, Penicillin-G and Ciprofloxacin respectively. The MIC of Vancomycin by agar dilution method was observed <2µg/ml against all isolated S. aureus and CoNS. All the Gram-positive isolates were sensitive to Linezolid and Vancomycin. Early detection of bacteria followed by antimicrobial susceptibility test can help by selection of appropriate antibiotic and prevent spread of infection.


Sepsis , Vancomycin , Infant, Newborn , Humans , Child , Staphylococcus aureus , Blood Culture , Bangladesh/epidemiology , Tertiary Care Centers , Cross-Sectional Studies , Agar , Microbial Sensitivity Tests , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/therapeutic use , Sepsis/diagnosis , Sepsis/drug therapy , Sepsis/microbiology , Bacteria
20.
Eur J Heart Fail ; 26(1): 5-17, 2024 Jan.
Article En | MEDLINE | ID: mdl-38169072

Document Reviewers: Rudolf A. de Boer (CPG Review Co-ordinator) (Netherlands), P. Christian Schulze (CPG Review Co-ordinator) (Germany), Elena Arbelo (Spain), Jozef Bartunek (Belgium), Johann Bauersachs (Germany), Michael A. Borger (Germany), Sergio Buccheri (Sweden), Elisabetta Cerbai (Italy), Erwan Donal (France), Frank Edelmann (Germany), Gloria Färber (Germany), Bettina Heidecker (Germany), Borja Ibanez (Spain), Stefan James (Sweden), Lars Køber (Denmark), Konstantinos C. Koskinas (Switzerland), Josep Masip (Spain), John William McEvoy (Ireland), Robert Mentz (United States of America), Borislava Mihaylova (United Kingdom), Jacob Eifer Møller (Denmark), Wilfried Mullens (Belgium), Lis Neubeck (United Kingdom), Jens Cosedis Nielsen (Denmark), Agnes A. Pasquet (Belgium), Piotr Ponikowski (Poland), Eva Prescott (Denmark), Amina Rakisheva (Kazakhstan), Bianca Rocca (Italy), Xavier Rossello (Spain), Leyla Elif Sade (United States of America/Türkiye), Hannah Schaubroeck (Belgium), Elena Tessitore (Switzerland), Mariya Tokmakova (Bulgaria), Peter van der Meer (Netherlands), Isabelle C. Van Gelder (Netherlands), Mattias Van Heetvelde (Belgium), Christiaan Vrints (Belgium), Matthias Wilhelm (Switzerland), Adam Witkowski (Poland), and Katja Zeppenfeld (Netherlands) All experts involved in the development of this Focused Update have submitted declarations of interest. These have been compiled in a report and simultaneously published in a supplementary document to the Focused Update. The report is also available on the ESC website www.escardio.org/guidelines See the European Heart Journal online for supplementary documents that include evidence tables.


Cardiology , Heart Failure , Humans , Heart Failure/diagnosis , Heart Failure/therapy , Poland , United Kingdom , Spain
...