Difficulties of Spanish Primary Health Care nurses to assist emergencies: A cross-sectional study.

BACKGROUND: The competence of a Primary Health Care nurse to handle emergency situations depends largely on prior acquisition of theoretical knowledge to make appropriate decisions, combined with the corresponding practical skills to carry out swift and effective interventions. METHODS: Cross-sectional study conducted in through a survey auto-administered to a simple random sample of 269 nurses (n) with replacement of Asturias, Spain from the total nursing staff of 730 members (N) in Asturias. RESULTS: In rural areas, the most frequently mentioned reasons were the lack of practical skills (18.9%) and the absence of adequate material (14.4 %). In the semi-urban area, the most common reasons were the lack of practical skills (13.2 %) and the lack of theoretical knowledge (10.3 %). Finally, in the urban area, the main reasons were the lack of practical skills (14.4 %) and the absence of adequate material (7.2 %). The differences were significant (p = 0.025). CONCLUSIONS: Despite the requirement that they acquire the necessary theoretical and practical skills, not all PHC nurses perceive themselves to be sufficiently prepared. The degree of self-perceived acquisition of this knowledge and skills, which is so important and necessary, is heterogeneous, with clear differences according to the respective field of work.

A Review of Mpox Outbreak and Public Health Response in Spain.

Objective: In May 2022, an unprecedented Mpox outbreak was reported in several non-endemic countries with unknown epidemiological links. Since May 2022, more than 20,000 cases have been reported in Europe. Spain has been the most affected country in Europe. We aim to describe the Mpox epidemiological profile in Spain, identify its outbreak risks, and describe public health interventions implemented by the Spanish authorities. Methods: A literature review was conducted, using specific selection criteria to obtain relevant publications describing Mpox clinical presentation and risk factors and the public health response in Spain to the ongoing outbreak. Results: 63.1% of the cases presented an anogenital rash, considered a specific and early symptom in this outbreak. Low case fatality rate is observed, mainly in risk groups, such as the immunocompromised population. Patients evolution was generally favorable, although 3-8% required hospitalization and two deaths occurred; 40% of patients were previously diagnosed with HIV infection. Most of the cases were seen among young population and concentrated in men who had sex with other men, mainly with multiple sexual partners, who did not practice safe sex such as using condoms, and those attending mass event parties. Conclusion: To date, the Mpox outbreak is not considered a public health emergency of international concern. The epidemiological trend of the virus in Spain shows that public health response interventions (health education, contact tracing, vaccination, etc.) have adequately controlled the epidemic curve in high-risk populations and avoided spreading the virus to other groups within the community.

Comparative Analysis of META and SALT Disaster Triage in an Adult Trauma Population: A Retrospective Observational Study.

BACKGROUND: Medical professionals can use mass-casualty triage systems to assist them in prioritizing patients from mass-casualty incidents (MCIs). Correct triaging of victims will increase their chances of survival. Determining the triage system that has the best performance has proven to be a difficult question to answer. The Advanced Prehospital Triage Model (Modelo Extrahospitalario de Triaje Avanzado; META) and Sort, Assess, Lifesaving Interventions, Treatment/Transport (SALT) algorithms are the most recent triage techniques to be published. The present study aimed to evaluate the META and SALT algorithms' performance and statistical agreement with various standards. The secondary objective was to determine whether these two MCI triage systems predicted patient outcomes, such as mortality, length-of-stay, and intensive care unit (ICU) admission. METHODS: This retrospective study used patient data from the trauma registry of an American College of Surgeons Level 1 trauma center, from January 1, 2018 through December 31, 2020. The sensitivity, specificity, and statistical agreement of the META and SALT triage systems to various standards (Revised Trauma Score [RTS]/Sort Triage, Injury Severity Score [ISS], and Lerner criteria) when applied using trauma patients. Statistical analysis was used to assess the relationship between each triage category and the secondary outcomes. RESULTS: A total of 3,097 cases were included in the study. Using Sort triage as the standard, SALT and META showed much higher sensitivity and specificity in the Immediate category than for Delayed (Immediate sensitivity META 91.5%, SALT 94.9%; specificity 60.8%, 72.7% versus Delayed sensitivity 28.9%, 1.3%; specificity 42.4%, 28.9%). With the Lerner criteria, in the Immediate category, META had higher sensitivity (77.1%, SALT 68.6%) but lower specificity (61.1%) than SALT (71.8%). For the Delayed category, SALT showed higher sensitivity (META 61.4%, SALT 72.2%), but lower specificity (META 75.1%, SALT 67.2%). Both systems showed a positive, though modest, correlation with ISS. For SALT and META, triaged Immediate patients tended to have higher mortality and longer ICU and hospital lengths-of-stay. CONCLUSION: Both META and SALT triage appear to be more accurate with Immediate category patients, as opposed to Delayed category patients. With both systems, patients triaged as Immediate have higher mortality and longer lengths-of-stay when compared to Delayed patients. Further research can help refine MCI triage systems and improve accuracy.

Microbial composition of Saharan dust plumes deposited as red rain in Granada (Southern Spain).

During durst storms, also biological material is transported from arid areas such as the Sahara Desert. In the present work, rain samples containing significant amounts of mineral dust have been collected in Granada during different red rain episodes. Biological features (bacteria, biofilm, pollen grain and fungal spore) as well as size-particle distribution and mineralogical composition were studied by SEM. Nanobacteria were observed for the first time in red rain samples. A preliminary metabarcoding analysis was performed on three red rain samples. Here, Bacillota made up 18 % and Pseudomonadota 23 % of the whole prokaryotic community. The fungal community was characterized by a high abundance of Ascomycota and, dependent on the origin, the presence of Chytridiomycota. By means of 16S rRNA sequencing, 18 cultivable microorganisms were identified. In general, members of the phyla Pseudomonadota and Bacillota made up the majority of taxa. Some species, such as Peribacillus frigoritolerans and Bacillus halotolerans were isolated during three different red rain episodes. Generally, red rain carries a wide variety of microorganisms, being their ecosystem and health effects largely unknown.

Prevalence and phenotypic susceptibility to doravirine of the HIV-1 reverse transcriptase V106I polymorphism in B and non-B subtypes.

AIM: To evaluate the prevalence and in vitro susceptibility to doravirine of RT-V106I polymorphism detected in samples collected from drug-naïve subjects. METHODS: Doravirine susceptibility was measured in site-directed mutants (SDMs) containing V106I, V106A, V106 M and Y188L mutations in subtype B (NL4-3, HXB2) and CRF02_AG background and in recombinant viruses with RT harboring V106I alone derived from 50 PLWH. RESULTS: HIV-1 B subtype was detected in 1523/2705 cases. Prevalence of V106I was 3.2% in B and 2.5% in non-B subtypes, and was higher in subtype F (8.1%), and D (14.3%). Fold-changes (FC) in susceptibility for SDMs were below doravirine biological cutoff (3.0) for V106I, but not for V106A, V106 M, and Y188L. Clinically-derived viruses tested included 22 B (median FC 1.2 [IQR 0.9-1.6]) and 28 non-B subtypes (median FC 1.8 [IQR 0.9-3.0]). Nine (18%) viruses showed FC values equal or higher than the doravirine biological FC cutoff. CONCLUSIONS: The prevalence of the HIV-1 RT-V106I polymorphism in MeditRes HIV consortium remains low, but significantly more prevalent in subtypes D and F. V106I minimally decreased the susceptibility to doravirine in SDMs and most clinical isolates. Reduced susceptibility seems to occur at increased frequency in subtype F1, however the clinical impact remains to be investigated.

Factors Associated with the Number of Injured and Fatalities in Motor Vehicle Intentional Mass-Casualty Incidents: A Timely Aid for Scaling the Emergency Response.

INTRODUCTION: Intentional mass-casualty incidents (IMCIs) involving motor vehicles (MVs) as weapons represent a growing trend in Western countries. This method has resulted in the highest casualty rates per incident within the field of IMCIs. Consequently, there is an urgent requirement for a timely and accurate casualty estimation in MV-induced IMCIs to scale and adjust the necessary health care resources. STUDY OBJECTIVE: The objective of this study is to identify the factors associated with the number of casualties during the initial phase of MV-IMCIs. METHODS: This is a retrospective, observational, analytical study on MV-IMCIs world-wide, from 2000-2021. Data were obtained from three different sources: Targeted Automobile Ramming Mass-Casualty Attacks (TARMAC) Attack Database, Global Terrorism Database (GTD), and the vehicle-ramming attack page from the Wikipedia website. Jacobs' formula was used to estimate the population density in the vehicle's route. The primary outcome variables were the total number of casualties (injured and fatalities). Associations between variables were analyzed using Spearman's correlation coefficient and simple linear regression. RESULTS: Forty-six MV-IMCIs resulted in 1,636 casualties (1,430 injured and 206 fatalities), most of them caused by cars. The most frequent driving pattern was accelerating whilst approaching the target, with an average speed range between four to 130km/h and a distance traveled between ten to 2,260 meters. The people estimated in the MV-IMCI scenes ranged from 36-245,717. A significant positive association was found of the number affected with the estimated crowd in the scene (R2: 0.64; 95% CI, 0.61-0.67; P <.001) and the average vehicle speed (R2: 0.42; 95% CI, 0.40-0.44; P = .004). CONCLUSION: The estimated number of people in the affected area and vehicle's average speed are the most significant variables associated with the number of casualties in MV-IMCIs, helping to enable a timely estimation of the casualties.

Cost-effectiveness analysis alongside the inter-B-NHL ritux 2010 trial: rituximab in children and adolescents with B cell non-Hodgkin's lymphoma.

OBJECTIVES: The randomized controlled trial Inter-B-NHL ritux 2010 showed overall survival (OS) benefit and event-free survival (EFS) benefit with the addition of rituximab to standard Lymphomes Malins B (LMB) chemotherapy in children and adolescents with high-risk, mature B cell non-Hodgkin's lymphoma. Our aim was to assess the cost-effectiveness of rituximab-chemotherapy versus chemotherapy alone in the French setting. METHODS: We used a decision-analytic semi-Markov model with four health states and 1-month cycles. Resource use was prospectively collected in the Inter-B-NHL ritux 2010 trial (NCT01516580). Transition probabilities were assessed from patient-level data from the trial (n = 328). In the base case analysis, direct medical costs from the French National Insurance Scheme and life-years (LYs) were computed in both arms over a 3-year time horizon. Incremental net monetary benefit and cost-effectiveness acceptability curve were computed through a probabilistic sensitivity analysis. Deterministic sensitivity analysis and several sensitivity analyses on key assumptions were also conducted, including one exploratory analysis with quality-adjusted life years as the health outcome. RESULTS: OS and EFS benefits shown in the Inter-B-NHL ritux 2010 trial translated into the model by rituximab-chemotherapy being the most effective and also the least expensive strategy over the chemotherapy strategy. The mean difference in LYs between arms was 0.13 [95% CI 0.02; 0.25], and the mean cost difference € - 3 710 [95% CI € - 17,877; € 10,525] in favor of rituximab-chemotherapy group. For a € 50,000 per LY willingness-to-pay threshold, the probability of the rituximab-chemotherapy strategy being cost-effective was 91.1%. All sensitivity analyses confirmed these findings. CONCLUSION: Adding rituximab to LMB chemotherapy in children and adolescents with high-risk mature B-cell non-Hodgkin's lymphoma is highly cost-effective in France. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT01516580.

Efficacy and tolerability of add-on stiripentol in real-world clinical practice: An observational study in Dravet syndrome and non-Dravet developmental and epileptic encephalopathies.

OBJECTIVE: To assess efficacy and tolerability of stiripentol (STP) as adjunctive treatment in Dravet syndrome and non-Dravet refractory developmental and epileptic encephalopathies (DREEs). METHODS: Retrospective observational study of all children and adults with DREE and prescribed adjunctive STP at Hospital Ruber Internacional from January 2000 to February 2023. Outcomes were retention rate, responder rate (proportion of patients with ≥50% reduction in total seizure frequency relative to baseline), seizure freedom rate, responder rate for status epilepticus, rate of adverse event and individual adverse events, reported at 3, 6, and 12 months and at final visit. Seizure outcomes are reported overall, and for Dravet and non-Dravet subgroups. RESULTS: A total of 82 patients (55 Dravet syndrome and 27 non-Dravet DREE) were included. Median age was 5 years (range 1-59 years), and median age of epilepsy onset was younger in the Dravet group (4.9 [3.6-6] months) than non-Dravet (17.9 [6-42.3], P < 0.001). Median follow-up time STP was 24.1 months (2 years; range 0.3-164 months) and was longer in the Dravet group (35.9 months; range 0.8-164) than non-Dravet (17 months range 0.3-62.3, P < 0.001). At 12 months, retention rate, responder rate and seizure free rate was 68.3% (56/82), 65% [48-77%] and 18% [5.7-29%], respectively. There were no statistically significant differences between groups on these seizure outcomes. Adverse events were reported in 46.3% of patients (38/82), without differences between groups. SIGNIFICANCE: In this population of patients with epileptic and developmental encephalopathies, outcomes with adjunctive STP were similar in patients with non-Dravet DREE to patients with Dravet syndrome.

C60-based Multivalent Glycoporphyrins Inhibit SARS-CoV-2 Specific Interaction with the DC-SIGN Transmembrane Receptor.

Since WHO has declared the COVID-19 outbreak a global pandemic, nearly seven million deaths have been reported. This efficient spread of Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) is facilitated by the ability of the spike glycoprotein to bind multiple cell membrane receptors. Although ACE2 is identified as the main receptor for SARS-CoV-2, other receptors could play a role in viral entry. Among others, C-type lectins such as DC-SIGN are identified as efficient trans-receptor for SARS-CoV-2 infection, so the use of glycomimetics to inhibit the infection through the DC-SIGN blockade is an encouraging approach. In this regard, multivalent nanostructures based on glycosylated [60]fullerenes linked to a central porphyrin scaffold have been designed and tested against DC-SIGN-mediated SARS-CoV-2 infection. First results show an outstanding inhibition of the trans-infection up to 90%. In addition, a deeper understanding of nanostructure-receptor binding is achieved through microscopy techniques, high-resolution NMR experiments, Quartz Crystal Microbalance experiments, and molecular dynamic simulations.

Preclinical immune efficacy against SARS-CoV-2 beta B.1.351 variant by MVA-based vaccine candidates.

The constant appearance of new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern (VoCs) has jeopardized the protective capacity of approved vaccines against coronavirus disease-19 (COVID-19). For this reason, the generation of new vaccine candidates adapted to the emerging VoCs is of special importance. Here, we developed an optimized COVID-19 vaccine candidate using the modified vaccinia virus Ankara (MVA) vector to express a full-length prefusion-stabilized SARS-CoV-2 spike (S) protein, containing 3 proline (3P) substitutions in the S protein derived from the beta (B.1.351) variant, termed MVA-S(3Pbeta). Preclinical evaluation of MVA-S(3Pbeta) in head-to-head comparison to the previously generated MVA-S(3P) vaccine candidate, expressing a full-length prefusion-stabilized Wuhan S protein (with also 3P substitutions), demonstrated that two intramuscular doses of both vaccine candidates fully protected transgenic K18-hACE2 mice from a lethal challenge with SARS-CoV-2 beta variant, reducing mRNA and infectious viral loads in the lungs and in bronchoalveolar lavages, decreasing lung histopathological lesions and levels of proinflammatory cytokines in the lungs. Vaccination also elicited high titers of anti-S Th1-biased IgGs and neutralizing antibodies against ancestral SARS-CoV-2 Wuhan strain and VoCs alpha, beta, gamma, delta, and omicron. In addition, similar systemic and local SARS-CoV-2 S-specific CD4+ and CD8+ T-cell immune responses were elicited by both vaccine candidates after a single intranasal immunization in C57BL/6 mice. These preclinical data support clinical evaluation of MVA-S(3Pbeta) and MVA-S(3P), to explore whether they can diversify and potentially increase recognition and protection of SARS-CoV-2 VoCs.

Cell type dependent stability and virulence of a recombinant SARS-CoV-2, and engineering of a propagation deficient RNA replicon to analyze virus RNA synthesis.

Engineering of reverse genetics systems for newly emerged viruses allows viral genome manipulation, being an essential tool for the study of virus life cycle, virus-host interactions and pathogenesis, as well as for the development of effective antiviral strategies. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an emergent human coronavirus that has caused the coronavirus disease (COVID-19) pandemic. The engineering of a full-length infectious cDNA clone and a fluorescent replicon of SARS-CoV-2 Wuhan-Hu-1, using a bacterial artificial chromosome, is reported. Viral growth and genetic stability in eleven cell lines were analyzed, showing that both VeroE6 cells overexpressing transmembrane serin protease 2 (TMPRSS2) and human lung derived cells resulted in the optimization of a cell system to preserve SARS-CoV-2 genetic stability. The recombinant SARS-CoV-2 virus and a point mutant expressing the D614G spike protein variant were virulent in a mouse model. The RNA replicon was propagation-defective, allowing its use in BSL-2 conditions to analyze viral RNA synthesis. The SARS-CoV-2 reverse genetics systems developed constitute a useful tool for studying the molecular biology of the virus, the development of genetically defined vaccines and to establish systems for antiviral compounds screening.

MAFB shapes human monocyte-derived macrophage response to SARS-CoV-2 and controls severe COVID-19 biomarker expression.

Monocyte-derived macrophages, the major source of pathogenic macrophages in COVID-19, are oppositely instructed by macrophage CSF (M-CSF) or granulocyte macrophage CSF (GM-CSF), which promote the generation of antiinflammatory/immunosuppressive MAFB+ (M-MØ) or proinflammatory macrophages (GM-MØ), respectively. The transcriptional profile of prevailing macrophage subsets in severe COVID-19 led us to hypothesize that MAFB shapes the transcriptome of pulmonary macrophages driving severe COVID-19 pathogenesis. We have now assessed the role of MAFB in the response of monocyte-derived macrophages to SARS-CoV-2 through genetic and pharmacological approaches, and we demonstrate that MAFB regulated the expression of the genes that define pulmonary pathogenic macrophages in severe COVID-19. Indeed, SARS-CoV-2 potentiated the expression of MAFB and MAFB-regulated genes in M-MØ and GM-MØ, where MAFB upregulated the expression of profibrotic and neutrophil-attracting factors. Thus, MAFB determines the transcriptome and functions of the monocyte-derived macrophage subsets that underlie pulmonary pathogenesis in severe COVID-19 and controls the expression of potentially useful biomarkers for COVID-19 severity.

Optimized vaccine candidate MVA-S(3P) fully protects against SARS-CoV-2 infection in hamsters.

The development of novel optimized vaccines against coronavirus disease 2019 (COVID-19) that are capable of controlling the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic and the appearance of different variants of concern (VoC) is needed to fully prevent the transmission of the virus. In the present study, we describe the enhanced immunogenicity and efficacy elicited in hamsters by a modified vaccinia virus Ankara (MVA) vector expressing a full-length prefusion-stabilized SARS-CoV-2 spike (S) protein [termed MVA-S(3P)]. Hamsters vaccinated with one or two doses of MVA-S(3P) developed high titers of S-binding IgG antibodies and neutralizing antibodies against the ancestral Wuhan SARS-CoV-2 virus and VoC beta, gamma, and delta, as well as against omicron, although with a somewhat lower neutralization activity. After SARS-CoV-2 challenge, vaccinated hamsters did not lose body weight as compared to matched placebo (MVA-WT) controls. Consistently, vaccinated hamsters exhibited significantly reduced viral RNA in the lungs and nasal washes, and no infectious virus was detected in the lungs in comparison to controls. Furthermore, almost no lung histopathology was detected in MVA-S(3P)-vaccinated hamsters, which also showed significantly reduced levels of proinflammatory cytokines in the lungs compared to unvaccinated hamsters. These results reinforce the use of MVA-S(3P) as a vaccine candidate against COVID-19 in clinical trials.

Superior neutralizing response after first versus second SARS-CoV-2 infection in fully vaccinated individuals.

Currently, the majority of the population has been vaccinated against COVID-19 and/or has experienced SARS-CoV-2 infection either before or after vaccination. The immunological response to repeated episodes of infections is not completely clear. We measured SARS-CoV-2 specific neutralization titers by a pseudovirus assay after BA.1 infection and RBD-specific immunoglobulin G (IgG), immunoglobulin A (IgA), and immunoglobulin M (IgM) in a cohort of COVID-19 uninfected and triple vaccinated individuals (breakthrough infection group, BTI) as compared with those previously infected by SARS-CoV-2 (reinfection group, REI) who underwent identical vaccination schedule. SARS-CoV-2 specific neutralizing response after BA.1 infection was significantly higher in the BTI group as compared with the REI. Furthermore, neutralization titers in REI were not significant different from convalescent non reinfected controls. RBD-specific IgG and IgA, but not IgM, were also significantly higher in BTI as compared with REI. Our results show that the first episode of SARS-CoV-2 infection induces a significant increase in neutralizing titers in triple vaccinated individuals and that previous SARS-CoV-2 infection compromise significantly the neutralization response induced by reinfection, even by divergent SARS-CoV-2 variants and at least up to 2 years postinfection, suggesting a fundamental limitation in inducing effective booster through the intranasal route in previously infected individuals.

The role of DC-SIGN as a trans-receptor in infection by MERS-CoV.

DC-SIGN is a C-type lectin expressed in myeloid cells such as immature dendritic cells and macrophages. Through glycan recognition in viral envelope glycoproteins, DC-SIGN has been shown to act as a receptor for a number of viral agents such as HIV, Ebola virus, SARS-CoV, and SARS-CoV-2. Using a system of Vesicular Stomatitis Virus pseudotyped with MERS-CoV spike protein, here, we show that DC-SIGN is partially responsible for MERS-CoV infection of dendritic cells and that DC-SIGN efficiently mediates trans-infection of MERS-CoV from dendritic cells to susceptible cells, indicating a potential role of DC-SIGN in MERS-CoV dissemination and pathogenesis.

Dendritic Cell-Mediated Cross-Priming by a Bispecific Neutralizing Antibody Boosts Cytotoxic T Cell Responses and Protects Mice against SARS-CoV-2.

Administration of neutralizing antibodies (nAbs) has proved to be effective by providing immediate protection against SARS-CoV-2. However, dual strategies combining virus neutralization and immune response stimulation to enhance specific cytotoxic T cell responses, such as dendritic cell (DC) cross-priming, represent a promising field but have not yet been explored. Here, a broadly nAb, TNT , are first generated by grafting an anti-RBD biparatopic tandem nanobody onto a trimerbody scaffold. Cryo-EM data show that the TNT structure allows simultaneous binding to all six RBD epitopes, demonstrating a high-avidity neutralizing interaction. Then, by C-terminal fusion of an anti-DNGR-1 scFv to TNT , the bispecific trimerbody TNT DNGR-1 is generated to target neutralized virions to type 1 conventional DCs (cDC1s) and promote T cell cross-priming. Therapeutic administration of TNT DNGR-1, but not TNT , protects K18-hACE2 mice from a lethal SARS-CoV-2 infection, boosting virus-specific humoral responses and CD8+ T cell responses. These results further strengthen the central role of interactions with immune cells in the virus-neutralizing antibody activity and demonstrate the therapeutic potential of the Fc-free strategy that can be used advantageously to provide both immediate and long-term protection against SARS-CoV-2 and other viral infections.