BACKGROUND: Current guidelines discourage prophylactic plasma use in non-bleeding patients. This study assesses global plasma transfusion practices in the intensive care unit (ICU) and their alignment with current guidelines. STUDY DESIGN AND METHODS: This was a sub-study of an international, prospective, observational cohort. Primary outcomes were in-ICU occurrence rate of plasma transfusion, proportion of plasma events of total blood products events, and number of plasma units per event. Secondary outcomes included transfusion indications, INR/PT, and proportion of events for non-bleeding indications. RESULTS: Of 3643 patients included, 356 patients (10%) experienced 547 plasma transfusion events, accounting for 18% of total transfusion events. A median of 2 (IQR 1, 2) units was given per event excluding massive transfusion protocol (MTP) and 3 (IQR 2, 6) when MTP was activated. MTP accounted for 39 (7%) of events. Indications of non-MTP events included active bleeding (54%), prophylactic (25%), and pre-procedure (12%). Target INR/PT was stated for 43% of transfusion events; pre-transfusion INR/PT or visco-elastic hemostatic assays (VHA) were reported for 73%. Thirty-seven percent of events were administered for non-bleeding indications, 54% with a pre-transfusion INR < 3.0 and 30% with an INR < 1.5. DISCUSSION: Plasma transfusions occurred in 10% of ICU patients. Over a third were given for non-bleeding indications and might have been avoidable. Target INR/PT was not stated in more than half of transfusions, and pre-transfusion INR/PT or VHA was not reported for 27%. Further research and education is needed to optimize guideline implementation and to identify appropriate indications for plasma transfusion.
- MeSH
- Intensive Care Units * MeSH
- Plasma * MeSH
- Hemorrhage therapy etiology prevention & control MeSH
- Middle Aged MeSH
- Humans MeSH
- Blood Component Transfusion * MeSH
- Prospective Studies MeSH
- Aged MeSH
- Practice Guidelines as Topic MeSH
- Check Tag
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Multicenter Study MeSH
- Observational Study MeSH
BACKGROUND: Various explicit screening tools, developed mostly in central Europe and the USA, assist clinicians in optimizing medication use for older adults. The Turkish Inappropriate Medication use in oldEr adults (TIME) criteria set, primarily based on the STOPP/START criteria set, is a current explicit tool originally developed for Eastern Europe and subsequently validated for broader use in Central European settings. Reviewed every three months to align with the latest scientific literature, it is one of the most up-to-date tools available. The tool is accessible via a free mobile app and website platforms, ensuring convenience for clinicians and timely integration of updates as needed. Healthcare providers often prefer to use their native language in medical practice, highlighting the need for prescribing tools to be translated and adapted into multiple languages to promote optimal medication practices. OBJECTIVE: To describe the protocol for cross-cultural and language validation of the TIME criteria in various commonly used languages and to outline its protocol for clinical validation across different healthcare settings. METHODS: The TIME International Study Group comprised 24 geriatric pharmacotherapy experts from 12 countries. In selecting the framework for the study, we reviewed the steps and outcomes from previous research on cross-cultural adaptations and clinical validations of explicit tools. Assessment tools were selected based on both their validity in accurately addressing the relevant issues and their feasibility for practical implementation. The drafted methodology paper was circulated among the study group members for feedback and revisions leading to a final consensus. RESULTS: The research methodology consists of two phases. Cross-cultural adaptation/language validation phase follows the 8-step approach recommended by World Health Organization. This phase allows regions or countries to make modifications to existing criteria or introduce new adjustments based on local prescribing practices and available medications, as long as these adjustments are supported by current scientific evidence. The second phase involves the clinical validation, where participants will be randomized into two groups. The control group will receive standard care, while the intervention group will have their treatment evaluated by clinicians who will review the TIME criteria and consider its recommendations. A variety of patient outcomes (i.e., number of hospital admissions, quality of life, number of regular medications [including over the counter medications], geriatric syndromes and mortality) in different healthcare settings will be investigated. CONCLUSION: The outputs of this methodological report are expected to promote broader adoption of the TIME criteria. Studies building on this work are anticipated to enhance the identification and management of inappropriate medication use and contribute to improved patient outcomes.
PURPOSE: We set out to develop a publicly available tool that could accurately diagnose spinal muscular atrophy (SMA) in exome, genome, or panel sequencing data sets aligned to a GRCh37, GRCh38, or T2T reference genome. METHODS: The SMA Finder algorithm detects the most common genetic causes of SMA by evaluating reads that overlap the c.840 position of the SMN1 and SMN2 paralogs. It uses these reads to determine whether an individual most likely has 0 functional copies of SMN1. RESULTS: We developed SMA Finder and evaluated it on 16,626 exomes and 3911 genomes from the Broad Institute Center for Mendelian Genomics, 1157 exomes and 8762 panel samples from Tartu University Hospital, and 198,868 exomes and 198,868 genomes from the UK Biobank. SMA Finder's false-positive rate was below 1 in 200,000 samples, its positive predictive value was greater than 96%, and its true-positive rate was 29 out of 29. Most of these SMA diagnoses had initially been clinically misdiagnosed as limb-girdle muscular dystrophy. CONCLUSION: Our extensive evaluation of SMA Finder on exome, genome, and panel sequencing samples found it to have nearly 100% accuracy and demonstrated its ability to reduce diagnostic delays, particularly in individuals with milder subtypes of SMA. Given this accuracy, the common misdiagnoses identified here, the widespread availability of clinical confirmatory testing for SMA, and the existence of treatment options, we propose that it is time to add SMN1 to the American College of Medical Genetics list of genes with reportable secondary findings after genome and exome sequencing.
- MeSH
- Algorithms MeSH
- Exome genetics MeSH
- Genome, Human genetics MeSH
- Genomics methods MeSH
- Humans MeSH
- Survival of Motor Neuron 1 Protein genetics MeSH
- Survival of Motor Neuron 2 Protein genetics MeSH
- Sequence Analysis, DNA methods MeSH
- Exome Sequencing MeSH
- Muscular Atrophy, Spinal * genetics diagnosis MeSH
- High-Throughput Nucleotide Sequencing MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
Fructobacillus, a Gram-positive, non-spore-forming, facultative anaerobic bacterium, belongs to the fructophilic lactic acid bacteria (FLAB) group. The group's name originates from fructose, the favored carbon source for its members. Fructobacillus spp. are noteworthy for their distinctive traits, captivating the interest of scientists. However, there have been relatively few publications regarding the isolation and potential utilization of these microorganisms in the industry. In recent years, F. tropaeoli has garnered interest for its promising role in the food and pharmaceutical sectors, although the availability of isolates is rather limited. A more comprehensive understanding of Fructobacillus is imperative to evaluate their functionality in the industry, given their unique and exceptional properties. Our in vitro study on Fructobacillus tropaeoli KKP 3032 confirmed its fructophilic nature and high osmotolerance. This strain thrives in a 30% sugar concentration, shows resistance to low pH and bile salts, and exhibits robust autoaggregation. Additionally, it displays significant antimicrobial activity against foodborne pathogens. Evaluating its probiotic potential, it aligns with EFSA recommendations in antibiotic resistance, except for kanamycin, to which it is resistant. Further research is necessary, but preliminary analyses confirm the high probiotic potential of F. tropaeoli KKP 3032 and its ability to thrive in the presence of high concentrations of fructose. The results indicate that the isolate F. tropaeoli KKP 3032 could potentially be used in the future as a fructophilic probiotic, protective culture, and/or active ingredient in fructose-rich food.
- MeSH
- Anti-Bacterial Agents pharmacology MeSH
- Fructose metabolism MeSH
- Hydrogen-Ion Concentration MeSH
- Fruit and Vegetable Juices * microbiology MeSH
- Citrus sinensis microbiology chemistry MeSH
- Food Microbiology MeSH
- Probiotics * isolation & purification MeSH
- RNA, Ribosomal, 16S genetics MeSH
- Bile Acids and Salts metabolism MeSH
- Publication type
- Journal Article MeSH
OBJECTIVES: The development of External Quality Assessment Schemes (EQAS) for clinical flow cytometry (FCM) is challenging in the context of rare (immunological) diseases. Here, we introduce a novel EQAS monitoring the primary immunodeficiency Orientation Tube (PIDOT), developed by EuroFlow, in both a 'wet' and 'dry' format. This EQAS provides feedback on the quality of individual laboratories (i.e., accuracy, reproducibility and result interpretation), while eliminating the need for sample distribution. METHODS: In the wet format, marker staining intensities (MedFIs) within landmark cell populations in PIDOT analysis performed on locally collected healthy control (HC) samples, were compared to EQAS targets. In the dry format, participants analyzed centrally distributed PIDOT flow cytometry data (n=10). RESULTS: We report the results of six EQAS rounds across 20 laboratories in 11 countries. The wet format (212 HC samples) demonstrated consistent technical performance among laboratories (median %rCV on MedFIs=34.5 %; average failure rate 17.3 %) and showed improvement upon repeated participation. The dry format demonstrated effective proficiency of participants in cell count enumeration (range %rCVs 3.1-7.1 % for the major lymphoid subsets), and in identifying lymphoid abnormalities (79.3 % alignment with reference). CONCLUSIONS: The PIDOT-EQAS allows laboratories, adhering to the standardized EuroFlow approach, to monitor interlaboratory variations without the need for sample distribution, and provides them educational support to recognize rare clinically relevant immunophenotypic patterns of primary immunodeficiencies (PID). This EQAS contributes to quality improvement of PID diagnostics and can serve as an example for future flow cytometry EQAS in the context of rare diseases.
PURPOSE OF REVIEW: This review explores the design and endpoints of perioperative platforms in clinical trials for muscle-invasive bladder cancer (MIBC). RECENT FINDINGS: The choice of clinical trial design in perioperative platforms for MIBC must align with specific research objectives to ensure robust and meaningful outcomes. Novel designs in perioperative platforms for MIBC integrate bladder-sparing approaches. Primary endpoints such as pathological complete response and disease-free survival are highlighted for their role in expediting trial results in perioperative setting. Incorporating patient-reported outcomes is important to inform healthcare decision makers about the outcomes most meaningful to patients. Given the growing body of evidence, potential biomarkers, predictive and prognostic tools should be considered and implemented when designing trials in perioperative platforms for MIBC. SUMMARY: Effective perioperative platforms for MIBC trials are critical in enhancing patient outcomes. The careful selection and standardization of study designs and endpoints in the perioperative platform are essential for the successful implementation of new therapies and the advancement of personalized treatment approaches in MIBC.
- MeSH
- Cystectomy methods adverse effects MeSH
- Neoplasm Invasiveness * MeSH
- Clinical Trials as Topic MeSH
- Humans MeSH
- Urinary Bladder Neoplasms * surgery pathology therapy mortality MeSH
- Perioperative Care methods standards MeSH
- Endpoint Determination MeSH
- Treatment Outcome MeSH
- Research Design MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Review MeSH
BACKGROUND: Emerging evidence suggests that tumour morphological heterogeneity may influence mutational profiles relevant to therapy response. In this pilot study, we aimed to assess whether mutations identified within specific morphological patterns or at the invasion front correlate with shorter time to progression after anti-EGFR therapy, as compared to whole-tissue analysis. METHODS: We investigated genetic mutations in 142 samples from primary tumours of 39 KRAS wild-type metastatic colorectal cancer (CRC) patients receiving anti-EGFR therapy. Deep next-generation sequencing was performed on whole-tumour sections and six morphology-defined tumour regions. RESULTS: Mutations in genes linked to anti-EGFR therapy response (KRAS, BRAF, NRAS, PTEN and PI3KCA) were found uniquely in the non-responder group, with substantial variability across morphological sub-regions. BRAF mutations were aligned with serrated and mucinous morphologies, while KRAS mutations (p.Lys147Glu and p.Ala146Thr) were associated with mucinous and desmoplastic morphologies. In all cases, the cumulative mutational profile from sub-regions provided more details than that of the whole-tumour profile. CONCLUSION: Our findings highlight that comprehensive analysis, considering morphological heterogeneity, is crucial for personalised CRC treatment strategies.
- MeSH
- Drug Resistance, Neoplasm * genetics MeSH
- Adult MeSH
- ErbB Receptors antagonists & inhibitors MeSH
- PTEN Phosphohydrolase genetics MeSH
- GTP Phosphohydrolases genetics MeSH
- Protein Kinase Inhibitors * therapeutic use MeSH
- Colorectal Neoplasms * genetics drug therapy pathology MeSH
- Middle Aged MeSH
- Humans MeSH
- Mutation * MeSH
- DNA Mutational Analysis MeSH
- Pilot Projects MeSH
- Antineoplastic Agents * therapeutic use MeSH
- Proto-Oncogene Proteins B-raf genetics MeSH
- Proto-Oncogene Proteins p21(ras) genetics MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- High-Throughput Nucleotide Sequencing MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
Celosvetovo patrí obezita k najrozšírenejším chronickým ochoreniam ako v dospelej, tak aj v detskej a adolescentnej populácii. V súčasnosti je jedným z najvýznamnejších problémov verejného zdravia nielen kvôli narastajúcej prevalencii, ale najmä asociácii so širokým spektrom ďalších chronických a život ohrozujúcich ochorení. Na Slovensku sa prevalencia nadhmotnosti pohybuje v rozmedzí okolo 63 %, prevalencia obezity okolo 29 %. V júni 2024 v Nature Medicine publikovala a zaviedla Európska spoločnosť pre štúdium obezity (European Association for the Study of Obesity – EASO) rámec na zosúladenie diagnostiky, hodnotenia závažnosti a liečby obezity so štandardmi iných chronických ochorení. Ciele liečby chronického ochorenia – (pre)obezity by mali byť holistické, mali by ísť „za“ pokles hmotnosti v kilogramoch, čo prináša so sebou dlhodobé prínosy pre zdravie, duševnú pohodu, fyzické fungovanie a zlepšenie kvality života. Holistické ciele môžeme dosiahnuť zmenou životného štýlu (behaviorálne, nutričné a pohybové intervencie). Zhodnotenie závažnosti ochorenia ovplyvňuje individuálnu liečbu (personalizovaná medicína) a v súčasnosti máme možnosť využívať kombináciu zmeny životného štýlu s farmakoterapiou, prípadne aj bariatrickými chirurgickými postupmi. V ostatnom čase nám pribudlo veľa nových informácií, výsledkov zo zaujímavých klinických štúdií týkajúcich sa farmakologického manažmentu založeného na báze inkretínov. V blízkej budúcnosti sa dočkáme aj ďalších noviniek zacielených na chronický manažment obezity.
Worldwide, obesity is one of the most widespread chronic diseases in the adult, child and adolescent population. It is currently one of the most significant public health problems not only due to its increasing prevalence, but especially due to its association with a wide range of other chronic and life-threatening diseases. In Slovakia, the prevalence of overweight is around 63 %, and the prevalence of obesity is around 29 %. In June 2024, the European Association for the Study of Obesity (EASO) published and introduced a framework to align the diagnosis, assessment of severity and treatment of obesity with the standards of other chronic diseases. The goals of treatment of chronic disease – (pre)obesity should be holistic, they should go “beyond” weight loss in kilograms, which brings with it long-term benefits for health, mental well-being, physical functioning and improved quality of life. Holistic goals can be achieved by changing lifestyle (behavioral, nutritional and exercise interventions). The assessment of the severity of the disease influences individual treatment (personalized medicine) and currently we have the opportunity to use a combination of lifestyle changes with pharmacotherapy, or even bariatric surgical procedures. Recently, we have received a lot of new information, results from interesting clinical studies related to pharmacological management based on incretins. In the near future we will also see other news aimed at chronic management of obesity.
- MeSH
- Glucagon-Like Peptide-1 Receptor Agonists pharmacology therapeutic use MeSH
- Anti-Obesity Agents pharmacology therapeutic use MeSH
- Obesity Management methods MeSH
- Humans MeSH
- Obesity * drug therapy MeSH
- Tirzepatide pharmacology therapeutic use MeSH
- Check Tag
- Humans MeSH
- Publication type
- Review MeSH
BACKGROUND: The education of healthcare professionals, including nurses, represents a critical intersection with health systems science (HSS), which is often considered the third pillar of healthcare education alongside basic and clinical sciences. Despite the amount of research on nursing education during the COVID-19 pandemic, there remains a gap in analysis from an HSS perspective. METHODS: A Comparative Education Approach involving undergraduate nursing programs (UNPs) across Europe, with longitudinal data collection from 2002 to 2023. The aim of the study was threefold: (a) to summarize the overall changes in UNPs during the COVID-19 pandemic; (b) to identify the changes retained in the post-pandemic era; and (c) to identify the impact of the pandemic on nursing education as perceived by nurse educators across nine European countries. RESULTS: This study compares the changes in nursing education in European countries during and after the COVID-19 pandemic using a qualitative approach with data from nine universities. The COVID-19 pandemic had a significant impact on education provision. During the first wave, government restrictions forced a complete shift to online learning for theory classes, clinical training and laboratories. In subsequent waves, a hybrid format was chosen that combined online and face-to-face sessions. A major challenge was the placement of nursing students alongside general university students. This approach neglected their need for practical clinical training, which is crucial for their future careers. To compensate for the lack of clinical hours, various alternative teaching methods were introduced. Students were also offered the opportunity to volunteer in large-scale public health initiatives such as vaccination and testing campaigns, although bedside care for COVID-19 patients remained limited. The pandemic has also left its mark in the post-pandemic period. Some UNPs have retained elements of online education, notably lectures, research seminars, meetings, consultations and even online exams. Interestingly, an initial increase in applicant numbers was observed at six of the nine participating UNPs. CONCLUSIONS: The COVID-19 pandemic has widened the gap between university-educated nurses and the clinical setting, i.e. between theory and practise, underlining the importance of HSS in nursing education. Rebuilding strong partnerships is crucial, but simply returning to the pre-pandemic model is not enough. To ensure uninterrupted education during future crises, proactive planning, including the creation of predefined protocols for collaboration, is essential. The pandemic underscores the need for closer alignment between the two sectors, which would better equip future nurses with the skills they need to thrive in the nursing workforce and ensure they are prepared for the challenges of the 21st century.
- MeSH
- COVID-19 * epidemiology MeSH
- Education, Distance trends MeSH
- Curriculum MeSH
- Humans MeSH
- Longitudinal Studies MeSH
- Pandemics MeSH
- SARS-CoV-2 MeSH
- Education, Nursing, Baccalaureate * trends organization & administration MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Comparative Study MeSH
- Geographicals
- Europe MeSH
