Diagnosis and Decision-Making in Telemedicine

This article provides an analysis of the skills that health professionals and patients employ in reaching diagnosis and decision-making in telemedicine consultations. As governmental priorities continue to emphasize patient involvement in the management of their disease, there is an increasing need to accurately capture the provider–patient interactions in clinical encounters. Drawing on conversation analysis of 10 video-mediated consultations in 3 National Health Service settings in England, this study examines the interaction between patients, General Practitioner (GPs), nurses, and consultants during diagnosis and decision-making, with the aim to identify the range of skills that participants use in the process and capture the interprofessional communication and patient involvement in the diagnosis and decision-making phases of telemedicine consultations. The analysis shows that teleconsultations enhance collaborative working among professionals and enable GPs and nurses to develop their skills and actively participate in diagnosis and decision-making by contributing primary care–specific knowledge to the consultation. However, interprofessional interaction may result in limited patient involvement in decisionmaking. The findings of this study can be used to inform training programs in telemedicine that focus on the development of effective skills for professionals and the provision of information to patients

Determination of the high-pressure crystal structure of BaWO4 and PbWO4

We report the results of both angle-dispersive x-ray diffraction and x-ray absorption near-edge structure studies in BaWO4 and PbWO4 at pressures of up to 56 GPa and 24 GPa, respectively. BaWO4 is found to undergo a pressure-driven phase transition at 7.1 GPa from the tetragonal scheelite structure (which is stable under normal conditions) to the monoclinic fergusonite structure whereas the same transition takes place in PbWO4 at 9 GPa. We observe a second transition to another monoclinic structure which we identify as that of the isostructural phases BaWO4-II and PbWO4-III (space group P21/n). We have also performed ab initio total energy calculations which support the stability of this structure at high pressures in both compounds. The theoretical calculations further find that upon increase of pressure the scheelite phases become locally unstable and transform displacively into the fergusonite structure. The fergusonite structure is however metastable and can only occur if the transition to the P21/n phases were kinetically inhibited. Our experiments in BaWO4 indicate that it becomes amorphous beyond 47 GPa.Comment: 46 pages, 11 figures, 3 table

Unraveling the role of protein dynamics in dihydrofolate reductase catalysis

Protein dynamics have controversially been proposed to be at the heart of enzyme catalysis, but identification and analysis of dynamical effects in enzyme-catalyzed reactions have proved very challenging. Here, we tackle this question by comparing an enzyme with its heavy (15N, 13C, 2H substituted) counterpart, providing a subtle probe of dynamics. The crucial hydride transfer step of the reaction (the chemical step) occurs more slowly in the heavy enzyme. A combination of experimental results, quantum mechanics/molecular mechanics simulations, and theoretical analyses identify the origins of the observed differences in reactivity. The generally slightly slower reaction in the heavy enzyme reflects differences in environmental coupling to the hydride transfer step. Importantly, the barrier and contribution of quantum tunneling are not affected, indicating no significant role for “promoting motions” in driving tunneling or modulating the barrier. The chemical step is slower in the heavy enzyme because protein motions coupled to the reaction coordinate are slower. The fact that the heavy enzyme is only slightly less active than its light counterpart shows that protein dynamics have a small, but measurable, effect on the chemical reaction rate

The Surviving Sepsis Campaign: Basic/Translational Science Research Priorities∗

© 2020 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved. Objectives: Expound upon priorities for basic/translational science identified in a recent paper by a group of experts assigned by the Society of Critical Care Medicine and the European Society of Intensive Care Medicine. Data Sources: Original paper, search of the literature. Study Selection: By several members of the original task force with specific expertise in basic/translational science. Data Extraction: None. Data Synthesis: None. Conclusions: In the first of a series of follow-up reports to the original paper, several members of the original task force with specific expertise provided a more in-depth analysis of the five identified priorities directly related to basic/translational science. This analysis expounds on what is known about the question and what was identified as priorities for ongoing research. It is hoped that this analysis will aid the development of future research initiatives

Catalytic Diastereo- and Enantioselective Vinylogous Mannich Reaction of Alkylidenepyrazolones to Isatin-Derived Ketimines

[EN] A valuable organocatalytic vinylogous Mannich reaction between alkylidenepyrazolones and isatin-derived ketimines has been successfully established. Squaramide organocatalyst, prepared from quinine, catalyzed the diastereo- and enantioselective vinylogous Mannich addition, affording a range of aminooxindole-pyrazolone adducts (24 examples) with excellent outcomes: up to 98% yield with complete diastereoselectivity and excellent enantioselectivity (up to 99% ee). Additionally, different synthetic transformations were performed with the chiral pyrazolone-oxindole adducts.Financial support from the Agencia Estatal de Investigacion (AEI, Spanish Government) and Fondo Europeo de Desarrollo Regional (FEDER, European Union) (PID2020-116944GB) and from Conselleria d'Innovacio, Universitat, Ciencia i Societat Digital (AICO/2020/68) is acknowledged. L.C.-F. thanks the Universitat de Valencia for a predoctoral grant. C.V. thanks the Spanish Government for a RyC contract (RYC2016-20187). Access to the NMR, MS, and X-ray facilities from the Servei Central de Suport a la Investigacio Experimental (SCSIE)-UV is also acknowledged.Carceller-Ferrer, L.; Vila, C.; Blay, G.; Muñoz Roca, MDC.; Pedro, JR. (2021). Catalytic Diastereo- and Enantioselective Vinylogous Mannich Reaction of Alkylidenepyrazolones to Isatin-Derived Ketimines. Organic Letters. 23(19):7391-7395. https://doi.org/10.1021/acs.orglett.1c0257173917395231

The Surviving Sepsis Campaign: research priorities for the administration, epidemiology, scoring and identification of sepsis

Epidemiologia; Disfunció d'òrgans; SèpsiaEpidemiology; Organ dysfunction; SepsisEpidemiología; Disfunción de órganos; SepsisObjective To identify priorities for administrative, epidemiologic and diagnostic research in sepsis. Design As a follow-up to a previous consensus statement about sepsis research, members of the Surviving Sepsis Campaign Research Committee, representing the European Society of Intensive Care Medicine and the Society of Critical Care Medicine addressed six questions regarding care delivery, epidemiology, organ dysfunction, screening, identification of septic shock, and information that can predict outcomes in sepsis. Methods Six questions from the Scoring/Identification and Administration sections of the original Research Priorities publication were explored in greater detail to better examine the knowledge gaps and rationales for questions that were previously identified through a consensus process. Results The document provides a framework for priorities in research to address the following questions: (1) What is the optimal model of delivering sepsis care?; (2) What is the epidemiology of sepsis susceptibility and response to treatment?; (3) What information identifies organ dysfunction?; (4) How can we screen for sepsis in various settings?; (5) How do we identify septic shock?; and (6) What in-hospital clinical information is associated with important outcomes in patients with sepsis? Conclusions There is substantial knowledge of sepsis epidemiology and ways to identify and treat sepsis patients, but many gaps remain. Areas of uncertainty identified in this manuscript can help prioritize initiatives to improve an understanding of individual patient and demographic heterogeneity with sepsis and septic shock, biomarkers and accurate patient identification, organ dysfunction, and ways to improve sepsis care.The authors volunteered their time to producing this manuscript and no funding was used to produce it

Non‑invasive oxygenation support in acutely hypoxemic COVID‑19 patients admitted to the ICU: a multicenter observational retrospective study

Acute hypoxemic respiratory failure; COVID-19; Intensive careInsuficiència respiratòria hipoxèmica aguda; COVID19; Medicina intensivaInsuficiencia respiratoria hipoxémica aguda; COVID-19; Medicina intensivaBackground: Non-invasive oxygenation strategies have a prominent role in the treatment of acute hypoxemic respiratory failure during the coronavirus disease 2019 (COVID-19). While the efficacy of these therapies has been studied in hospitalized patients with COVID-19, the clinical outcomes associated with oxygen masks, high-flow oxygen therapy by nasal cannula and non-invasive mechanical ventilation in critically ill intensive care unit (ICU) patients remain unclear. Methods: In this retrospective study, we used the best of nine covariate balancing algorithms on all baseline covariates in critically ill COVID-19 patients supported with > 10 L of supplemental oxygen at one of the 26 participating ICUs in Catalonia, Spain, between March 14 and April 15, 2020. Results: Of the 1093 non-invasively oxygenated patients at ICU admission treated with one of the three stand-alone non-invasive oxygenation strategies, 897 (82%) required endotracheal intubation and 310 (28%) died during the ICU stay. High-flow oxygen therapy by nasal cannula (n = 439) and non-invasive mechanical ventilation (n = 101) were associated with a lower rate of endotracheal intubation (70% and 88%, respectively) than oxygen masks (n = 553 and 91% intubated), p < 0.001. Compared to oxygen masks, high-flow oxygen therapy by nasal cannula was associated with lower ICU mortality (hazard ratio 0.75 [95% CI 0.58-0.98), and the hazard ratio for ICU mortality was 1.21 [95% CI 0.80-1.83] for non-invasive mechanical ventilation. Conclusion: In critically ill COVID-19 ICU patients and, in the absence of conclusive data, high-flow oxygen therapy by nasal cannula may be the approach of choice as the primary non-invasive oxygenation support strategy

Weld kinematics of synrift salt during basement-involved extension and subsequent inversion: Results from analog models

Scaled analog models based on extensional basins with synrift salt show how basement topography exerts a control factor on weld kinematics during the extension and inversion phases. In the case of basement-involved extension, syn-rift salt thickness differences may lead to variable degrees of extensional decoupling between basement topography and overburden, which in turn have a strong impact on the development of salt structures. With ongoing extension and after welding, the basin kinematics evolves toward a coupled deformation style. The basin architecture of our experimental results record the halokinetic activity related to growing diapirs and the timing of weld formation during extension. Moreover, the structures that result from any subsequent inversion of these basins strongly depends on the inherited welds and salt structures. While those basins are uplifted, the main contractional deformation during inversion is absorbed by the pre-existing salt structures, whose are squeezed developing secondary welds that often evolve into thrust welds. The analysis of our analog models shows that shortening of diapirs is favored by: 1) basement topography changes that induce reactivation of primary welds as thrust welds; 2) reactivation of the salt unit as a contractional detachment; and 3) synkinematic sedimentation during basin inversion. Finally in this article we also compare two natural examples from the southern North Sea that highlight deformation patterns very similar to those observed in our analog models

Why Are Outcomes Different for Registry Patients Enrolled Prospectively and Retrospectively? Insights from the Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF).

Background: Retrospective and prospective observational studies are designed to reflect real-world evidence on clinical practice, but can yield conflicting results. The GARFIELD-AF Registry includes both methods of enrolment and allows analysis of differences in patient characteristics and outcomes that may result. Methods and Results: Patients with atrial fibrillation (AF) and ≥1 risk factor for stroke at diagnosis of AF were recruited either retrospectively (n = 5069) or prospectively (n = 5501) from 19 countries and then followed prospectively. The retrospectively enrolled cohort comprised patients with established AF (for a least 6, and up to 24 months before enrolment), who were identified retrospectively (and baseline and partial follow-up data were collected from the emedical records) and then followed prospectively between 0-18 months (such that the total time of follow-up was 24 months; data collection Dec-2009 and Oct-2010). In the prospectively enrolled cohort, patients with newly diagnosed AF (≤6 weeks after diagnosis) were recruited between Mar-2010 and Oct-2011 and were followed for 24 months after enrolment. Differences between the cohorts were observed in clinical characteristics, including type of AF, stroke prevention strategies, and event rates. More patients in the retrospectively identified cohort received vitamin K antagonists (62.1% vs. 53.2%) and fewer received non-vitamin K oral anticoagulants (1.8% vs . 4.2%). All-cause mortality rates per 100 person-years during the prospective follow-up (starting the first study visit up to 1 year) were significantly lower in the retrospective than prospectively identified cohort (3.04 [95% CI 2.51 to 3.67] vs . 4.05 [95% CI 3.53 to 4.63]; p = 0.016). Conclusions: Interpretations of data from registries that aim to evaluate the characteristics and outcomes of patients with AF must take account of differences in registry design and the impact of recall bias and survivorship bias that is incurred with retrospective enrolment. Clinical Trial Registration: - URL: http://www.clinicaltrials.gov . Unique identifier for GARFIELD-AF (NCT01090362)

A new approach to obtain pure and active proteins from Lactococcus lactis protein aggregates

The production of pure and soluble proteins is a complex, protein-dependent and time-consuming process, in particular for those prone-to-aggregate and/or difficult-to-purify. Although Escherichia coli is widely used for protein production, recombinant products must be co-purified through costly processes to remove lipopolysaccharide (LPS) and minimize adverse effects in the target organism. Interestingly, Lactococcus lactis, which does not contain LPS, could be a promising alternative for the production of relevant proteins. However, to date, there is no universal strategy to produce and purify any recombinant protein, being still a protein-specific process. In this context and considering that L. lactis is also able to form functional protein aggregates under overproduction conditions, we explored the use of these aggregates as an alternative source of soluble proteins. In this study, we developed a widely applicable and economically affordable protocol to extract functional proteins from these nanoclusters. For that, two model proteins were used: mammary serum amyloid A3 (M-SAA3) and metalloproteinase 9 (MMP-9), a difficult-to-purify and a prone-to-aggregate protein, respectively. The results show that it is possible to obtain highly pure, soluble, LPS-free and active recombinant proteins from L. lactis aggregates through a cost-effective and simple protocol with special relevance for difficult-to-purify or highly aggregated proteins