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Coronavirus disease 2019 (COVID-19) is a pandemic infection caused by the newly discovered severe acute respiratory syndrome coronavirus 2. Remdesivir (RDV) and corticosteroids are used mainly in COVID-19 patients with acute respiratory failure. The main objective of the study was to assess the effectiveness of remdesivir with and without corticosteroids in the treatment of COVID-19 patients. We conducted a prospective observational study, including adult patients consecutively hospitalized with confirmed COVID-19 and acute respiratory failure. Patients were divided according to treatment strategy: RDV alone versus RDV with corticosteroids. The primary outcome was the time to recovery in both treatment groups. We included 374 COVID-19 adult patients, 184 were treated with RDV, and 190 were treated with RDV and corticosteroid. Patients in the RDV group had a shorter time to recovery in comparison with patients in the RDV plus corticosteroids group at 28 days after admission [11 vs. 16 days (95% confidence Interval 9.7–12.8; 14.9–17.1; p  = .016)]. Patients treated with RDV alone had a shorter length of hospital stay. The use of corticosteroids as adjunctive therapy of RDV was not associated with improvement in mortality of COVID-19 patients.

Background: Real-world safety profiles of immune checkpoint inhibitors (ICIs) in older adults remain insufficiently characterized. Although ICIs are widely used across tumor types, older patients, particularly those with frailty, multimorbidity, or polypharmacy, are consistently under-represented in clinical trials, limiting the external validity of trial-derived toxicity estimates. Robust real-world data are therefore essential to clarify the incidence, seriousness, and age-related patterns of immune-related adverse events (irAEs) in routine practice. Methods: This is a nationwide retrospective study of spontaneous ICI-related ADRs reported in INFARMED’s Portal RAM (2011–2024). We evaluated the frequency, seriousness, fatality, and organ-specific patterns of ICI-related adverse drug reactions (ADRs) reported to the Portuguese National Pharmacovigilance System. The analytic unit was the ADR case. Endpoints included seriousness (primary), fatality, hospitalization, time-to-onset, and System Organ Class. Multivariable logistic regression adjusted for age, sex, regimen, tumor type, polypharmacy, and calendar period; sensitivity analyses using first ADR per patient were concordant. Results: We identified 2300 eligible ICI-related ADRs (corresponding to 925 patients). Median age at the time of ADR was 65 years (IQR not reported); 33.7% occurred in adults aged ≥70 years, and 62.8% of reports involved male patients. PD-1 inhibitors accounted for 77.5% of ADRs, and monotherapy for 72.9%. Overall, 85.8% of ADRs were classified as serious; 17.9% led to hospitalization and 19.1% were fatal. Serious-event reporting was similar in older and younger adults (≥70 vs. <70 years: 84.5% vs. 86.5%, p = 0.22), and the proportion explicitly labeled immune-related did not differ (9.3% vs. 8.7%, p = 0.56). In contrast, fatal outcomes were significantly more common in older adults (25.3% vs. 16.0%; p < 0.001). Age was associated with distinct organ-specific patterns. Adults ≥ 70 years had higher odds of nervous system disorders (aOR 1.75, 95% CI 1.23–2.48) and immune system disorders (aOR 1.42, 95% CI 1.02–1.98), but lower odds of hepatobiliary (aOR 0.52, 95% CI 0.36–0.76; p = 0.001) and blood/lymphatic disorders (aOR 0.50, 95% CI 0.32–0.79). In multivariable models, age ≥ 70 years did not predict seriousness (aOR 0.98, 95% CI 0.76–1.27), whereas combination therapy remained independently associated with increased seriousness (aOR 1.57, 95% CI 1.13–2.18). Conversely, age ≥ 70 years independently predicted fatal outcomes (aOR 1.66, 95% CI 1.31–2.09). Later calendar periods (2017–2024) were associated with substantially lower fatality (aOR 0.16; 95% CI 0.10–0.27). CTLA-4-containing regimens demonstrated a tendency toward higher fatality (aOR 1.50; 95% CI 0.94–2.37). Conclusions: Chronological age does not seem to increase the likelihood of reporting a serious ICI-related ADR, but, once toxicity occurs, older adults experience higher fatality rates. Age-related phenotypic differences and regimen-specific risks highlight the need for early recognition systems and tailored toxicity management in older populations.

ABSTRACT Objectives: to know the nursing interventions in the identification, prevention and control of sepsis in critical patients. Methods: integrative review of the literature, with two parallel researches using different MesH terms, using the EBSCO database and Google Scholar. Nine studies were included in the sample. Results: nursing interventions are centered on the creation/implementation of protocols for the early recognition of sepsis, the training of teams to ensure a safe and effective approach and the adoption of measures for infection prevention and control as a way to prevent sepsis. Final Considerations: the evidence shows that nurses are fundamental in the early identification, control and prevention of sepsis, preventing disease progression and contributing to decreased morbidity and mortality. RESUMO Objetivos: conhecer as intervenções de enfermagem na identificação, prevenção e controle da sepse no paciente crítico. Métodos: revisão integrativa da literatura, realizadas duas pesquisas paralelas com diferentes descritores MesH, recorrendo à base de dados EBSCO e ao motor de busca Google Acadêmico. Obtiveram-se 9 estudos que integram a amostra. Resultados: as intervenções de enfermagem centram-se na criação/implementação de protocolos que auxiliem o reconhecimento precoce da sepse, na formação das equipes para garantir uma abordagem segura e eficaz e na adoção de medidas que promovam a prevenção e o controle de infeção como forma de prevenir a sepse. Considerações Finais: as evidências demonstraram que o enfermeiro é fundamental na identificação precoce, controle e prevenção da sepse, evitando a progressão da doença e contribuindo para a diminuição da morbilidade e mortalidade. RESUMEN Objetivos: conocer las intervenciones de enfermería en la identificación, prevención y control de la sepsis en el paciente crítico. Métodos: se trata de una revisión integradora de literatura, llevada a cabo mediante dos investigaciones paralelas con diferentes descriptores Me SH, recurriendo a la base de datos EBSCO y motor de búsqueda Google Académico. Se obtuvieron 9 estudios que forman parte de la muestra. Resultados: las intervenciones de enfermería están enfocadas en la creación/implantación de protocolos para el reconocimiento precoz de la sepsis, para la formación de equipos que garanticen un abordaje seguro y eficiente y para la adopción de medidas preventivas y de control de la infección para impedir la sepsis. Consideraciones Finales: las evidencias demostraron que el enfermero es fundamental en la identificación temprana, en el control y prevención de la sepsis, para evitar la progresión de la enfermedad y contribuir en la disminución de la morbilidad y de la mortalidad.

ObjectivesSince the outbreak of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), the pressure to minimise its impact on public health has led to the implementation of different therapeutic strategies, the efficacy of which for the treatment of coronavirus disease 2019 (COVID-19) was unknown at the time. Remdesivir (REM) was granted its first conditional marketing authorisation in the EU in June 2020. The European Medicines Agency (EMA) and local health authorities all across the EU have since strongly recommended the implementation of pharmacovigilance activities aimed at further evaluating the safety of this new drug. The objective of this study was to evaluate adverse drug reactions (ADRs) attributed to either REM or hydroxychloroquine (HCQ) in patients hospitalised for COVID-19 in Centro Hospitalar de Lisboa Ocidental, a Portuguese hospital centre based in Lisbon. We present the preliminary results reporting plausible adverse effects of either HCQ or REM.MethodsAn observational cohort study was carried out between 16 March and 15 August 2020. Participants were divided into two cohorts: those prescribed an HCQ regimen, and those prescribed REM. Suspected ADRs were identified using an active monitoring model and reported to the Portuguese Pharmacovigilance System through its online notification tool. The ADR cumulative incidence was compared between the two cohorts.ResultsThe study included 149 patients, of whom 101 were treated with HCQ and the remaining 48 with REM. The baseline characteristics were similar between the two cohorts. A total of 102 ADRs were identified during the study period, with a greater incidence in the HCQ cohort compared with the REM cohort (47.5% vs 12.5%; p<0.001). Causality was assessed in 81 ADRs, all of which were considered possible.ConclusionsReal-world data are crucial to further establish the safety profile for REM. HCQ is no longer recommended for the treatment of COVID-19.

Evaluation of a computerized physician order entry in an Internal Medicine Department, with a unit-dose distribution system. Pharmacy Department, Internal Medicine Department. S. Francisco Xavier Hospital, Lisbon, Portugal. This study was carried out in December 2001 and January 2002. After two years experience of the CPOE system, medication errors were evaluated prospectively, in an internal medical department of a 360-bed academic hospital. Data were collected once a week. Pharmacists reviewed all medical prescriptions as part of their routine work. Medication errors detected were recorded on a data collection form with a design based on the types of errors as defined by the American Society of Hospital Pharmacists (ASHP). Completed forms were reviewed and medication errors were classed according to ASHP guidelines. A total of 2268 orders were monitored (162 patients). In these orders, 73 medication errors (22.4% of the patients) were detected and documented (59 prescribing errors and 14 monitoring errors). The most common prescribing errors were deficiencies related to the right class but wrong drug (28.3%): omeprazole vs. ranitidine/sucralfate in stress ulcer prophylaxis; incorrect dose (30%) and unclear orders (13.3%). Errors related to incorrect frequency of administration (5%); maintenance of IV route (5%); duplicated drug therapy (11.7%); drug interactions (1.7%) and length of therapy (3.3%) were also detected. The 14 monitoring errors detected were failures to review a prescribed regimen for appropriateness and detection of problems. Computerized prescription order entry has demonstrated effectiveness in eliminating medication errors related to transcribing and patient identification. Nevertheless, medication errors related to prescription and monitoring still occur. The use of clinical decision support systems and pharmacist involvement is vital to achieve maximum medication safety and reduce medication error rates.

The human microbiome is an integral component of the human body and a co-determinant of several health conditions 1 , 2 . However, the extent to which interpersonal relations shape the individual genetic makeup of the microbiome and its transmission within and across populations remains largely unknown 3 , 4 . Here, capitalizing on more than 9,700 human metagenomes and computational strain-level profiling, we detected extensive bacterial strain sharing across individuals (more than 10 million instances) with distinct mother-to-infant, intra-household and intra-population transmission patterns. Mother-to-infant gut microbiome transmission was considerable and stable during infancy (around 50% of the same strains among shared species (strain-sharing rate)) and remained detectable at older ages. By contrast, the transmission of the oral microbiome occurred largely horizontally and was enhanced by the duration of cohabitation. There was substantial strain sharing among cohabiting individuals, with 12% and 32% median strain-sharing rates for the gut and oral microbiomes, and time since cohabitation affected strain sharing more than age or genetics did. Bacterial strain sharing additionally recapitulated host population structures better than species-level profiles did. Finally, distinct taxa appeared as efficient spreaders across transmission modes and were associated with different predicted bacterial phenotypes linked with out-of-host survival capabilities. The extent of microorganism transmission that we describe underscores its relevance in human microbiome studies 5 , especially those on non-infectious, microbiome-associated diseases. Data from more than 9,700 human stool and oral metagenomes has been used to decipher the strain transmission patterns of the human microbiome from mother to infant, within households and within populations.

Enough of silos: develop a joint scientific agenda to understand the intertwined global crises of the Earth system. Enough of silos: develop a joint scientific agenda to understand the intertwined global crises of the Earth system.

The remain well clear (RWC) function of a detect-and-avoid (DAA) system provides guidance to a remote pilot (RP) of a remotely piloted aircraft to prevent a conflict from developing into a collision hazard. The ACAS Xu standard is a decision support system that uses RWC bands to advise a RP which headings to avoid. A recent A* DAA system is a resolution support system that advises a RP which route to take. The objective of this study is to achieve structured feedback by professional RPs on the horizontal RWC guidance of both systems. Nine RPs participated in on-line experiments, where they were shown videos of DAA displays of encounter scenarios between two aircraft. At various stages the RPs were asked for their opinion about transparency, pilot manoeuvring, situation awareness, display orientation, risk perception, competence, trust, and overall system preference. The results show that the scores for competence, trust and pilot manoeuvring were significantly higher, and the score for perceived risk was significant lower for the RWC route guidance. Overall, 89% of the RPs preferred the RWC route guidance, while one RP had no preference. An implication of the uncertainty in pilot behaviour is that ACAS Xu model-based optimisation may provide suboptimal RWC guidance strategies, while the A* DAA optimisation can be managed effectively.

While numerous studies report shifts in vegetation phenology, in this regard eddy covariance (EC) data, despite its continuous high-frequency observations, still requires further exploration. Furthermore, there is no general consensus on optimal methodologies for data smoothing and extracting phenological transition dates (PTDs). Here, we revisit existing methodologies and present new prospects to investigate phenological changes in gross primary productivity (GPP) from EC measurements. First, we present a smoothing technique of GPP time series through the derivative of its smoothed annual cumulative sum. Second, we calculate PTDs and their trends from a commonly used threshold method that identifies days with a fixed percentage of the annual maximum GPP. A systematic analysis is performed for various thresholds ranging from 0.1 to 0.7. Lastly, we examine the relation of PTDs trends to trends in GPP across the years on a weekly basis. Results from 47 EC sites with long time series (> 10 years) show that advancing trends in start of season (SOS) are strongest at lower thresholds but for the end of season (EOS) at higher thresholds. Moreover, the trends are variable at different thresholds for individual vegetation types and individual sites, outlining reasonable concerns on using a single threshold value. Relationship of trends in PTDs and weekly GPP reveal association of advanced SOS and delayed EOS to increase in immediate primary productivity, but not to the trends in overall seasonal productivity. Drawing on these analyses, we emphasise on abstaining from subjective choices and investigating relationship of PTDs trend to finer temporal trends of GPP. Our study examines existing methodological challenges and presents approaches that optimize the use of EC data in identifying vegetation phenological changes and their relation to carbon uptake.

PB1-F2 is a 90 amino acid protein that is expressed from the +1 open reading frame in the PB1 gene of some influenza A viruses and has been shown to contribute to viral pathogenicity. Notably, a serine at position 66 (66S) in PB1-F2 is known to increase virulence compared to an isogenic virus with an asparagine (66N) at this position. Recently, we found that an influenza virus expressing PB1-F2 N66S suppresses interferon (IFN)-stimulated genes in mice. To characterize this phenomenon, we employed several in vitro assays. Overexpression of the A/Puerto Rico/8/1934 (PR8) PB1-F2 protein in 293T cells decreased RIG-I mediated activation of an IFN-β reporter and secretion of IFN as determined by bioassay. Of note, the PB1-F2 N66S protein showed enhanced IFN antagonism activity compared to PB1-F2 wildtype. Similar observations were found in the context of viral infection with a PR8 PB1-F2 N66S virus. To understand the relationship between NS1, a previously described influenza virus protein involved in suppression of IFN synthesis, and PB1-F2, we investigated the induction of IFN when NS1 and PB1-F2 were co-expressed in an in vitro transfection system. In this assay we found that PB1-F2 N66S further reduced IFN induction in the presence of NS1. By inducing the IFN-β reporter at different levels in the signaling cascade, we found that PB1-F2 inhibited IFN production at the level of the mitochondrial antiviral signaling protein (MAVS). Furthermore, immunofluorescence studies revealed that PB1-F2 co-localizes with MAVS. In summary, we have characterized the anti-interferon function of PB1-F2 and we suggest that this activity contributes to the enhanced pathogenicity seen with PB1-F2 N66S- expressing influenza viruses.