Members of the Plasmodium falciparum Erythrocyte Membrane protein 1 (PfEMP1) family expressed on the surface of malaria-infected erythrocytes mediate binding of the parasite to different receptors on ...the vascular lining. This process drives pathologies, and severe childhood malaria has been associated with the expression of particular subsets of PfEMP1 molecules. PfEMP1 are grouped into subtypes based on upstream sequences and the presence of semi-conserved PfEMP1 domain compositions named domain cassettes (DCs). Earlier studies have indicated that DC5-containing PfEMP1 (DC5-PfEMP1) are more likely to be expressed in children with severe malaria disease than in children with uncomplicated malaria, but these PfEMP1 subtypes only dominate in a relatively small proportion of the children with severe disease. In this study, we have characterised the genomic sequence characteristic for DC5, and show that two genetically different parasite lines expressing DC5-PfEMP1 bind PECAM1, and that anti-DC5-specific antibodies inhibit binding of DC5-PfEMP1-expressing parasites to transformed human bone marrow endothelial cells (TrHBMEC). We also show that antibodies against each of the four domains characteristic for DC5 react with native PfEMP1 expressed on the surface of infected erythrocytes, and that some of these antibodies are cross-reactive between the two DC5-containing PfEMP1 molecules tested. Finally, we confirm that anti-DC5 antibodies are acquired early in life by individuals living in malaria endemic areas, that individuals having high levels of these antibodies are less likely to develop febrile malaria episodes and that the antibody levels correlate positively with hemoglobin levels.
Background
To describe 24‐hour fluid administration in emergency department (ED) patients with suspected infection.
Methods
A prospective, multicenter, observational study conducted in three Danish ...hospitals, January 20 to March 2, 2020. We included consecutive adult ED patients with suspected infection (drawing of blood culture and/or intravenous antibiotic administration within 6 hours of admission). Oral and intravenous fluids were registered for 24 hours. Primary outcome: 24‐hour total fluid volume. We used linear regression to investigate patient and disease characteristics' effect on 24‐hour fluids and to estimate the proportion of the variance in fluid administration explained by potential predictors.
Results
734 patients had 24‐hour fluids available: 387 patients had simple infection, 339 sepsis, eight septic shock. Mean total 24‐hour fluid volumes were 3656 mL (standard deviation SD:1675), 3762 mL (SD: 1839), and 6080 mL (SD: 3978) for the groups, respectively. Fluid volumes varied markedly. Increasing age (mean difference MD: 60‐79 years: −470 mL 95% CI: −789, −150, +80 years; −974 mL 95% CI: −1307, −640), do‐not‐resuscitate orders (MD: −466 mL 95% CI: −797, −135), and preexisting atrial fibrillation (MD: −367 mL 95% CI: −661, −72) were associated with less fluid. Systolic blood pressure < 100 mmHg (MD: 1182 mL 95% CI: 820, 1543), mean arterial pressure < 65 mmHg (MD: 1317 mL 95% CI: 770, 1864), lactate ≥ 2 mmol/L (MD: 655 mL 95% CI: 306, 1005), heart rate > 120 min (MD: 566 95% CI: 169, 962), low (MD: 1963 mL 95% CI: 813, 3112) and high temperature (MD: 489 mL 95% CI: 234, 742), SOFA score > 5 (MD: 1005 mL 95% CI: 501, 510), and new‐onset atrial fibrillation (MD: 498 mL 95% CI: 30, 965) were associated with more fluid. Clinical variables explained 37% of fluid variation among patients.
Conclusions
Patients with simple infection and sepsis received equal fluid volumes. Fluid volumes varied markedly, a variation that was partly explained by clinical characteristics.
Background
Fluid administration and resuscitation of patients with sepsis admitted through emergency departments (ED) remains a challenge, and evidence is sparse especially in sepsis patients without ...shock. We aimed to investigate emergency medicine physicians' and nurses' perceptions, self‐reported decision‐making and daily behavior, and challenges in fluid administration of ED sepsis patients.
Methods
We developed and conducted a multicenter, web‐based, cross‐sectional survey focusing on fluid administration to ED patients with sepsis sent to all nurses and physicians from the five EDs in the Central Denmark Region. The survey consisted of three sections: (1) baseline information; (2) perceptions of fluid administration and daily practice; and (3) clinical scenarios about fluid administration. The survey was performed from February to June, 2021.
Results
In total, 138 of 246 physicians (56%) and 382 of 595 nurses (64%) responded to the survey. Of total, 94% of physicians and 97% of nurses regarded fluid as an important part of sepsis treatment. Of total, 80% of physicians and 61% of nurses faced challenges regarding fluid administration in the ED, and decisions were usually based on clinical judgment. The most common challenge was the lack of guidelines for fluid administration. Of total, 96% agreed that they would like to learn more about fluid administration, and 53% requested research in fluid administration of patients with sepsis. For a normotensive patient with sepsis, 46% of physicians and 44% of nurses administered 1000 ml fluid in the first hour. Of total, 95% of physicians and 89% of nurses preferred to administer ≥1000 ml within an hour if the patients' blood pressure was 95/60 at admission. There was marked variability in responses. Blood pressure was the most commonly used trigger for fluid administration. Respondents preferred to administer less fluid if the patient in the scenario had known renal impairment or heart failure. Normal saline was the preferred fluid.
Conclusion
Fluid administration is regarded as an important but challenging aspect of sepsis management. Responses to scenarios revealed variability in fluid volumes. Blood pressure was the most used trigger. ED nurses and physicians request evidence‐based guidelines to improve fluid administration.
Blaise Pascal (1623-1662) gehört zu den größten Geistern, die je auf Erden gelebt haben. Seine tiefgründigen Gedanken über Recht, Macht und Gerechtigkeit sind von den Juristen eher vereinzelt ...zitiert, nicht immer hinreichend von denen Montaignes abgegrenzt, selten im Zusammenhang durchdrungen und so gut wie nie im Hinblick auf seine großen religionsphilosophischen Gedanken untersucht worden. Der vorliegende Band versucht eine Verbindungslinie zwischen seiner Rechtsphilosophie und seiner Religionsphilosophie herzustellen, indem er Pascals Gedanken über die Gerechtigkeit zu seiner berühmten Lehre von den drei Ordnungen ins Verhältnis setzt.
Despite the widespread implementation of competency-based education, evidence of ensuing enhanced patient care and cost-benefit remains scarce. This narrative review uses the Kirkpatrick/Phillips ...model to investigate the patient-related and organizational effects of graduate competency-based medical education for five basic anesthetic procedures.
The MEDLINE, ERIC, CINAHL, and Embase databases were searched for papers reporting results in Kirkpatrick/Phillips levels 3-5 from graduate competency-based education for five basic anesthetic procedures. A gray literature search was conducted by reference search in Google Scholar.
In all, 38 studies were included, predominantly concerning central venous catheterization. Three studies reported significant cost-effectiveness by reducing infection rates for central venous catheterization. Furthermore, the procedural competency, retention of skills and patient care as evaluated by fewer complications improved in 20 of the reported studies.
Evidence suggests that competency-based education with procedural central venous catheterization courses have positive effects on patient care and are both cost-effective. However, more rigorously controlled and reproducible studies are needed. Specifically, future studies could focus on organizational effects and the possibility of transferability to other medical specialties and the broader healthcare system.
Competency-based education has been shown to enhance clinical skills, improve patient care, and reduce number of complications resulting in a better return on investments. Residents constitute an ...important workforce at many hospitals. Yet, the effect of training on residents' contribution to production in patient care is scarcely studied. This study evaluated the effects of early competency-based procedural training on residents' contribution to patient care in central venous catheterization and spinal and epidural anesthesia.
The design was a non-randomized cohort study of first-year anesthesiology residents. The intervention group received additional early focused skills training while three control groups received traditional competency-based education. The residents' contributions to patient care were compared between the intervention group (n = 20), a historical control group (n = 19), and between a contemporary control group (n = 7) and a historical control group (n = 7) from different departments. The residents' vs specialists' procedural production share was compared between years within each study group. We calculated specialist time saved compared to the time spent providing additional skills training in the intervention group.
We found statistically significant increases in residents' vs specialists' share of total production after the intervention for epidural anesthesia: 2015: 0.51 (0.23, 0.70) to 2017: 0.94 (0.78, 1.05), p = 0.011 and central venous catheterization: 2015: 0.30 (0.23, 0.36) to 2016: 0.46 (0.35, 0.55), p = .008; and to 2017: 0.64 (0.50, 0.79), p = 0.008. Comparison between residents and specialists on production of the three procedures before and after the intervention showed a surplus of 21 h of freed specialist time per year.
Early procedural training results in more productive residents and freed specialist time for additional supervision, other clinical tasks or research. This provides empirical support for a positive correlation between early focused training and increased independent production among residents.
Wild populations of the native European flat oyster (Ostrea edulis) are nowadays rare. Worldwide, flat oyster populations have declined due to overexploitation, diseases and pollution. Yet, in the ...Limfjorden, Denmark, a small but persistent population of wild flat oyster have endured for more than 165 years, which has sustained a unique fishery on wild oyster beds. Over time, fluctuations in the wild population size has had implications for the fishery, alternating between a large population with high yields, and too small to withstand a fishery. The flat oyster fishery has been alleged to cause these unpredictable fluctuations in the population. However, the combined effect of natural variation (e.g. water temperature) and the fishery has not been investigated. Here we indicate that summer water temperature is an important factor causing fluctuations in the flat oyster population, thought to be due to its influence on recruitment success. Whereas the fishery often constitutes a minor part of the net oyster mortality. We found a positive correlation between summer water temperature and increased oyster landings ≥5 years later. Our results demonstrate the importance of adaptive management for the oyster fishery in the Limfjorden, which has ensured the survival of the flat oyster population, even when the oyster population has been low. These results highlight that management based on annual stock assessments, closed areas with brood stock, and dynamic annual total allowable catch, can ensure the persistence of an endangered oyster species and support a sustainable fishery.
BackgroundHuntington's disease (HD) is a rare, progressive neurodegenerative disease. Currently, there is no cure for the disease, but treatment may alleviate HD symptoms. In recent years, several ...exercise training interventions have been conducted in HD patients. In the current article, we review previous studies investigating targeted exercise training interventions in HD patients. MethodsWe performed a literature search using the PubMed, Scopus, Web of Science, and Google Scholar databases on exercise training interventions in HD patients. Six publications fulfilled the criteria and were included in the review. ResultsExercise training resulted in beneficial effects on cardiovascular and mitochondrial function. Training effects on cognition, motor function, and body composition were less congruent, but a positive effect seems likely. Health-related quality of life during the training interventions was stable. Most studies reported no related adverse events in response to training. DiscussionExercise training seems to be safe and feasible in HD patients. However, current knowledge is mainly based on short, small-scale studies and it cannot be transferred to all HD patients. Therefore, longer-term interventions with larger HD patient cohorts are necessary to draw firm conclusions about the potentially positive effects of exercise training in HD patients.
To expand upon the limited knowledge of the long-term effects of prolonged-release (PR) fampridine in patients with multiple sclerosis (PwMS) regarding safety, walking improvements, and changes in ...drug responsiveness.
Fifty-three PwMS who completed the FAMPKIN core study were included in this extension trial. Drug efficacy was assessed in an open-label and randomized double-blind, placebo-controlled study design with regular baseline assessments over a period of 2 years using the Timed 25-Foot Walk (T25FW), 6-Minute Walk Test (6MWT), and 12-item MS Walking Scale (MSWS-12) as outcome measures.
The data showed good tolerability and persisting efficacy of PR fampridine during long-term treatment in PwMS. Significant improvements in walking speed, endurance, and self-perceived ambulatory function were observed during open-label (T25FW: +11.5%; 6MWT: 10.7%; MSWS-12: 6.1 points) and double-blind controlled treatment with PR fampridine (T25FW: +13.1%; 6MWT: 11.9%; MSWS-12: 7.4 points). Several patients showed changes in drug responsiveness over time, resulting in an increased proportion of patients exceeding 10% or 20% improvements in walking measures after long-term treatment.
Efficacy and tolerability data confirmed PR fampridine as a valuable long-term treatment for improving ambulatory function in gait-impaired PwMS. Similar results in open-label and double-blind phases reveal that the walking tests used are objective and reliable. The considerable proportion of patients in whom responsiveness to PR fampridine changed over time emphasizes the importance of regular reassessment of drug efficacy in clinical practice to optimize treatment. Such reassessments seem to be particularly important in patients with poor initial drug responses, as this group demonstrated enhanced responsiveness after long-term treatment.
NCT01576354.
This study provides Class II evidence that PR fampridine significantly improved gait compared to placebo in a 2-week study in PwMS who had been using PR fampridine for 2 years.
Radiation oncology, a major treatment modality in the care of patients with malignant disease, is a technology‐ and computer‐intensive medical specialty. As such, it should lend itself ideally to ...data science methods, where computer science, statistics, and clinical knowledge are combined to advance state‐of‐the‐art care. Nevertheless, data science methods in radiation oncology research are still in their infancy and successful applications leading to improved patient care remain scarce. Here, we discuss data interoperability issues within and across organizational boundaries that hamper the introduction of big data and data science techniques in radiation oncology. At the semantic level, creating common underlying models and codification of the data, including the use of data elements with standardized definitions, an ontology, remains a work in progress. Methodological issues in data science and in the use of large population‐based health data registries are identified. We show that data science methods and big data cannot replace randomized clinical trials in comparative effectiveness research by reviewing a series of instances where the outcomes of big data analyses and randomized trials are at odds. We also discuss the modern wave of machine learning and artificial intelligence as represented by deep learning and convolutional neural networks. Finally, we identify promising research avenues and remain optimistic that the data sources in radiation oncology can be linked to yield important insights in the near future. We argue that data science will be a valuable complement to, but not a replacement of, the traditional hypothesis‐driven translational research chain and the randomized clinical trials that form the backbone of evidence‐based medicine.
Data science has an important role to play in the technology and computer‐intensive field of radiation oncology, but requires multidisciplanry teams and domain knowledge to be successful. We argue that data science will be a valuable complement to, but not a replacement of, the traditional hypothesis‐driven translational research chain and the randomized clinical trials.
PDF
