Targeted prophylactic anticoagulation based on the TRiP(cast) score in patients with lower limb immobilisation: a multicentre, stepped wedge, randomised implementation trial.

BACKGROUND: Prophylactic anticoagulation in emergency department patients with lower limb trauma requiring immobilisation is controversial. The Thrombosis Risk Prediction for Patients with Cast Immobilisation-TRiP(cast)-score could identify a large subgroup of patients at low risk of venous thromboembolism for whom prophylactic anticoagulation can be safely withheld. We aimed to prospectively assess the safety of withholding anticoagulation for patients with lower limb trauma at low risk of venous thromboembolism, defined by a TRiP(cast) score of less than 7. METHODS: CASTING was a stepped-wedge, multicentre, cluster-randomised trial with blinded outcome assessment. 15 emergency departments in France and Belgium were selected and randomly assigned staggered start dates for switching from the control phase (ie, anticoagulation prescription according to the physician's usual practice) to the intervention phase (ie, targeted anticoagulation according to TRiP(cast) score: no prescription if score <7 and anticoagulation if score was ≥7). Patients were included if they presented to a participating emergency department with lower limb trauma requiring immobilisation for at least 7 days and were aged 18 years or older. The primary outcome was the 3-month cumulative rate of symptomatic venous thromboembolism during the intervention phase in patients with a TRiP(cast) score of less than 7. The targeted strategy was considered safe if this rate was less than 1% with an upper 95% CI of less than 2%. The primary analysis was performed in the intention-to-treat population. This study is registered at ClinicalTrials.gov (NCT04064489). FINDINGS: Between June 16, 2020, and Sept 15, 2021, 15 clusters and 2120 patients were included. Of the 1505 patients analysed in the intervention phase, 1159 (77·0%) had a TRiP(cast) score of less than 7 and did not receive anticoagulant treatment. The symptomatic venous thromboembolism rate was 0·7% (95% CI 0·3-1·4, n=8/1159). There was no difference between the control and the intervention phases in the cumulative rate of symptomatic venous thromboembolism or in bleeding rates. INTERPRETATION: Patients with a TRiP(cast) score of less than 7 who are not receiving anticoagulation have a very low risk of venous thromboembolism. A large proportion of patients with lower limb trauma and immobilisation could safely avoid thromboprophylaxis. FUNDING: French Ministry of Health.

Safety of treating acute pulmonary embolism at home: an individual patient data meta-analysis.

BACKGROUND AND AIMS: Home treatment is considered safe in acute pulmonary embolism (PE) patients selected by a validated triage tool (e.g. simplified PE severity index score or Hestia rule), but there is uncertainty regarding the applicability in underrepresented subgroups. The aim was to evaluate the safety of home treatment by performing an individual patient-level data meta-analysis. METHODS: Ten prospective cohort studies or randomized controlled trials were identified in a systematic search, totalling 2694 PE patients treated at home (discharged within 24 h) and identified by a predefined triage tool. The 14- and 30-day incidences of all-cause mortality and adverse events (combined endpoint of recurrent venous thromboembolism, major bleeding, and/or all-cause mortality) were evaluated. The relative risk (RR) for 14- and 30-day mortalities and adverse events is calculated in subgroups using a random effects model. RESULTS: The 14- and 30-day mortalities were 0.11% [95% confidence interval (CI) 0.0-0.24, I2 = 0) and 0.30% (95% CI 0.09-0.51, I2 = 0). The 14- and 30-day incidences of adverse events were 0.56% (95% CI 0.28-0.84, I2 = 0) and 1.2% (95% CI 0.79-1.6, I2 = 0). Cancer was associated with increased 30-day mortality [RR 4.9; 95% prediction interval (PI) 2.7-9.1; I2 = 0]. Pre-existing cardiopulmonary disease, abnormal troponin, and abnormal (N-terminal pro-)B-type natriuretic peptide [(NT-pro)BNP] at presentation were associated with an increased incidence of 14-day adverse events [RR 3.5 (95% PI 1.5-7.9, I2 = 0), 2.5 (95% PI 1.3-4.9, I2 = 0), and 3.9 (95% PI 1.6-9.8, I2 = 0), respectively], but not mortality. At 30 days, cancer, abnormal troponin, and abnormal (NT-pro)BNP were associated with an increased incidence of adverse events [RR 2.7 (95% PI 1.4-5.2, I2 = 0), 2.9 (95% PI 1.5-5.7, I2 = 0), and 3.3 (95% PI 1.6-7.1, I2 = 0), respectively]. CONCLUSIONS: The incidence of adverse events in home-treated PE patients, selected by a validated triage tool, was very low. Patients with cancer had a three- to five-fold higher incidence of adverse events and death. Patients with increased troponin or (NT-pro)BNP had a three-fold higher risk of adverse events, driven by recurrent venous thromboembolism and bleeding.

Derivation and validation of a risk-stratification model for patients with probable or proven COVID-19 in EDs: the revised HOME-CoV score.

BACKGROUND: The HOME-CoV (Hospitalisation or Outpatient ManagEment of patients with SARS-CoV-2 infection) score is a validated list of uniquely clinical criteria indicating which patients with probable or proven COVID-19 can be treated at home. The aim of this study was to optimise the score to improve its ability to discriminate between patients who do and do not need admission. METHODS: A revised HOME-CoV score was derived using data from a previous prospective multicentre study which evaluated the original Home-CoV score. Patients with proven or probable COVID-19 attending 34 EDs in France, Monaco and Belgium between April and May 2020 were included. The population was split into a derivation and validation sample corresponding to the observational and interventional phases of the original study. The main outcome was non-invasive or invasive ventilation or all-cause death within 7 days following inclusion. Two threshold values were defined using a sensitivity of >0.9 and a specificity of >0.9 to identify low-risk and high-risk patients, respectively. The revised HOME-CoV score was then validated by retrospectively applying it to patients in the same EDs with proven or probable COVID-19 during the interventional phase. The revised HOME-CoV score was also tested against original HOME-CoV, qCSI, qSOFA, CRB65 and SMART-COP in this validation cohort. RESULTS: There were 1696 patients in the derivation cohort, of whom 65 (3.8%) required non-invasive ventilation or mechanical ventilation or died within 7 days and 1304 patients in the validation cohort, of whom 22 (1.7%) had a progression of illness. The revised score included seven clinical criteria. The area under the curve (AUC) was 87.6 (95% CI 84.7 to 90.6). The cut-offs to define low-risk and high-risk patients were <2 and >3, respectively. In the validation cohort, the AUC was 85.8 (95% CI 80.6 to 91.0). A score of <2 qualified 73% of patients as low risk with a sensitivity of 0.77 (0.55-0.92) and a negative predictive value of 0.99 (0.99-1.00). CONCLUSION: The revised HOME-CoV score, which does not require laboratory testing, may allow accurate risk stratification and safely qualify a significant proportion of patients with probable or proven COVID-19 for home treatment.

Perceived Hospital Preparedness Is Negatively Associated With Pandemic-Induced Psychological Vulnerability in Primary Care Employees: A Multicentre Cross-Sectional Observational Study.

OBJECTIVE: The COVID-19 pandemic had a profound negative impact on the psychological wellbeing of healthcare providers (HPs), but little is known about the factors that positively predict mental health of primary care staff during these dire situations. METHODS: We conducted an online questionnaire survey among 702 emergency department workers across 10 hospitals in Switzerland and Belgium following the first COVID-19 wave in 2020, to explore their psychological vulnerability, perceived concerns, self-reported impact and level of pandemic workplace preparedness. Participants included physicians, nurses, psychologists and nondirect care employees (administrative staff). We tested for predictors of psychological vulnerability through both an exploratory cross-correlation with rigorous correction for multiple comparisons and model-based path modelling. RESULTS: Findings showed that the self-reported impact of COVID-19 at work, concerns about contracting COVID-19 at work, and a lack of personal protective equipment were strong positive predictors of Depression, Anxiety, and Stress, and low Resilience. Instead, knowledge of the degree of preparedness of the hospital/department, especially in the presence of a predetermined contingency plan for an epidemic and training sessions about protective measures, showed the opposite effect, and were associated with lower psychological vulnerability. All effects were confirmed after accounting for confounding factors related to gender, age, geographical location and the role played by HPs in the hospital/department. CONCLUSIONS: Difficult working conditions during the pandemic had a major impact on the psychological wellbeing of emergency department HPs, but this effect might have been lessened if they had been informed about adequate measures for minimizing the risk of exposure.

Point-of-Care Ultrasound training in undergraduate education in the European Union: current situation and perspectives.

BACKGROUND: Given the widespread use of Point-of-Care UltraSound (PoCUS) in clinical practice, with ultrasound machines becoming more portable and affordable, recommendations and position statements from ultrasound societies now promote teaching PoCUS in the undergraduate curriculum. Nevertheless, surveys about PoCUS teaching in European medical schools are lacking. This survey aims to overview the current and future undergraduate PoCUS courses in the European Union (EU). RESULTS: A questionnaire was sent to medical schools in 26 of the 27 countries of the EU; Luxembourg is the only country without a medical school. The survey was completed by the dean or a member of the medical school with knowledge of the medical curriculum. Of the 58 medical schools from 19 countries that responded to the survey, 18 (31.0%) from 13 (68.4%) EU countries reported the existence of an undergraduate PoCUS curriculum and a further 16 (27.6%) from 12 (41.4%) EU countries intended to offer it in the future. No significant difference was observed between the current and future PoCUS curricula regarding its content and purpose. Less than 40 h of theoretical teaching is provided in all the medical schools and less than 40 h of practical training is provided in 12 (75%) of the 16 medical schools which answered this specific question. Of the 40 (69%) surveyed medical schools that do not currently teach PoCUS, 20 (50%) intend to offer PoCUS courses in the future. CONCLUSION: Although the lack of teaching hours in curricula suggests that most PoCUS courses are introductory in nature and that medical students are possibly not trained to become autonomous in clinical practice, evaluating the feasibility and impact of PoCUS teaching on clinical practice should be promoted. The medical schools that intend to develop this curriculum should be encouraged to implement validated tools to objectively assess their programs and students' performances.

Outpatient management of cancer-associated pulmonary embolism: A post-hoc analysis from the HOME-PE trial.

INTRODUCTION: Cancer-related pulmonary embolism (PE) is associated with poor prognosis. Some decision rules identifying patients eligible for home treatment categorize cancer patients at high risk of complications, precluding home treatment. We sought to assess the effectiveness and the safety of outpatient management of patients with low-risk cancer-associated PE. METHODS: In the HOME-PE trial, hemodynamically stable patients with symptomatic PE were randomized to either triaging with Hestia criteria or sPESI score. We analyzed 3 groups of low-risk PE patients: 47 with active cancer treated at home (group 1), 691 without active cancer treated at home (group 2), and 33 with active cancer as the only sPESI criterion qualifying them for hospitalization (group 3). The main outcome was the composite of recurrent venous thromboembolism, major bleeding, and all-cause death within 30 days after randomization. RESULTS: Patients treated at home had composite outcome rates of 4.3 % (2/47) for those with cancer vs. 1.0 % (7/691) for those without (odds ratio (OR) 4.98, 95%CI 1.15-21.49). Patients with cancer had rates of complications of 4.3 % when treated at home vs. 3.0 % (1/33) when hospitalized (OR 1.19, 95%CI 0.15-9.47). In multivariable analysis, active cancer was associated with an increased risk of complications for patients treated at home (OR 7.95; 95%CI 1.48-42.82). For patients with active cancer, home treatment was not associated with the primary outcome (OR 1.19, 95%CI 0.15-9.74). CONCLUSIONS: Among patients treated at home, active cancer was a risk factor for complications, but among patients with active cancer, home treatment was not associated with adverse outcomes.

Pulmonary embolism rule-out decision-making tools for patients aged 35 years or younger in hospital emergency departments: a post-hoc analysis of performance in 3 prospective cohorts. / Capacidad de diferentes reglas de decisión clínica para descartar tromboembolismo pulmonar en pacientes de 35 o menos años atendidos en servicios de urgencias: análisis post-hoc de tres cohortes prospectivas.

OBJECTIVES: To assess the performance of the Pulmonary Embolism Rule-out Criteria (PERC) and the age-modified PERC-35 tool in hospital emergency departments (EDs) for evaluating patients aged 35 years or younger. A secondary aim was to assess other decision-making criteria. MATERIAL AND METHODS: Post-hoc analysis of 3 European cohort studies. We included data for patients aged 35 years or younger suspected of PE who were followed for 3 months. The safety and efficacy of applying the PERC and PERC-35 were assessed with the diagnostic error rate (failure to detect PE) and the proportion of patients in whom a diagnosis of PE was ruled out. We also assessed the safety and efficacy of applying the YEARS and PEGeD criteria. RESULTS: Data for 1235 patients aged 35 years or younger were analyzed. Twenty-two (1.8%; 95% CI, 1.2%-2.7%) PE cases were diagnosed at 3 months. Six (1.0%; 95% CI, 0.5%-2.2%) and 5 (0.9%; 95% CI, 0.4%-2.1%) PE cases were not diagnosed by the PERC and PERC-35 tools, respectively. These tools allowed PE to be ruled out in 591 (48.2%; 95% CI, 45.4%-51.0%) and 554 (46.2%; 95% CI, 43.4%-49.0%) cases, respectively. The error rates of the YEARS and PEGeD criteria, respectively, were 0.4% (95% CI, 0.1%-1.1%) and 0.5% (95% CI, 0.2%-1.2%); their efficacy was similar. CONCLUSION: The safety and efficacy profiles of the PERC and PERC-35 algorithms were similar in patients aged 35 years or younger. However, the large confidence intervals we report do not allow us to confirm the safety of using the tools in patients in this age group.

OBJETIVO: Evaluar la capacidad de la regla PERC (Pulmonary Embolism Rule-out Criteria) y la regla modificada por edad (PERC-35) para descartar tromboembolia pulmonar (TEP) en servicios de urgencias hospitalarios (SUH) en pacientes 35 años. El objetivo secundario fue analizar otras reglas de decisión clínica. METODO: Análisis post-hoc de 3 estudios de cohorte europeos (PROPER, PERCEPIC y MODIGLIANI). Se incluyeron pacientes 35 años con sospecha de TEP en SUH y con seguimiento a 3 meses. La seguridad y eficacia de PERC y PERC-35 se evaluaron con su tasa de error -no detectar TEP- y la proporción de pacientes con diagnóstico de TEP descartado. Se evaluó la seguridad y eficacia de las reglas YEARS y PEGeD. RESULTADOS: Se analizaron 1.235 pacientes 35 años. Hubo 22 (1,8%, IC 95%: 1,2-2,7) TEP diagnosticados a los 3 meses. Hubo 6 (1,0%, IC 95%: 0,5-2,2) y 5 (0,9%, IC 95%: 0,4-2,1) TEP no diagnosticados con las reglas PERC y PERC-35 respectivamente. Estas reglas permitieron descartar TEP en 591 (48,2%, IC 95%: 45,4- 51,0) y 554 (46,2%, IC 95%: 43,4- 49,0) respectivamente. La tasa de error de YEARS y PEGeD fue del 0,4% (IC 95%: 0,1- 1,1) y 0,5% (IC 95%: 0,2-1,2), con una eficacia similar. CONCLUSIONES: En pacientes 35 años, las reglas PERC y PERC-35 mostraron perfiles de seguridad y eficacia similares. Sin embargo, el amplio intervalo de confianza comunicado en este estudio no permite confirmar su seguridad.

Cytogenetic analyses in Paspalum L. reveal new diploid species and accessions / Análises citogenéticas em Paspalum L. revelam novas espécies e acessos diplóides

Chromosome numbers were counted in 126 new accessions of 50 Paspalum species from Brazil, Argentina, Paraguay and Bolivia. The chromosome numbers 2n=12, 20, 24, 30, 40, 50, 60, 80 were confirmed. Chromosome numbers for P. arenarium (2n=20), P. barretoi (2n=20), P. aff. ceresia (2n=40), P. corcovadense (2n=20), P. crispulum (2n=20), P. flaccidum (2n=40), P. nummularium (2n=20), P. scalare (2n=20), P. vescum (2n=20) and P. rectum (2n=20) and a diploid cytotype of P. malacophyllum are reported for the first time. The predominance of tetraploid accessions (43.6 percent) was confirmed, but an unusually high number of diploid species (44 percent) and accessions (35.7 percent) was found. These results open new perspectives for breeding programs, phylogenetic studies, and for research on apomixis control, since diploids of Paspalum are typically sexual.

O número cromossômico foi determinado para 126 novos acessos de 50 espécies de Paspalum do Brasil, Argentina, Paraguai e Bolívia. Foram verificados os números somáticos 2n=12, 20, 24, 30, 40, 50, 60 e 80. Estas são as primeiras contagens para P. arenarium (2n=20), P. barretoi (2n=20), P. aff. ceresia (2n=40), P. corcovadense (2n=20), P. crispulum (2n=20), P. flaccidum (2n=40), P. nummularium (2n=20), P. scalare (2n=20), P. vescum (2n=20) e P. rectum (2n=20). O nível diplóide (2n=20) é reportado pela primeira vez para P. malacophyllum. Os dados confirmam a predominância de acessos tetraplóides (43,6 por cento) no gênero e mostram um número incomumente elevado de espécies (44 por cento) e acessos diplóides (35,7 por cento). Estes resultados trazem novas perspectivas para programas de melhoramento, para estudos filogenéticos e para pesquisa orientada ao controle da apomixia, já que em Paspalum as plantas diplóides são tipicamente sexuais.

Novos biótipos pentaplóides do grupo Dilatata de Paspalum L. (Gramineae) no Sul do Brasil / New pentaploid biotypes of the Dilatata group of Paspalum L. (Gramineae) from Southern Brazil

Paspalum dilatatum é uma gramínea nativa da América do Sul subtropical, com bom valor forrageiro e ampla variabilidade intraespecífica. Distintos tipos morfológicos, citológicos e reprodutivos têm sido citados para esta espécie. Paspalum dilatatum "Comum" é o biótipo de maior interesse agronômico. A constatação da importância da espécie como componente da produção de forragem de boa qualidade em campos naturais vem resultando em contínuo interesse pela possibilidade de seu melhor aproveitamento em cultivo. Entre o material do grupo Dilatata submetido à análise, seis acessos de classificação taxonômica não definida apresentaram morfologia distinta dos demais. Acredita-se que sejam resultantes de processos de hibridação natural em combinações antes desconhecidas. A análise mitótica evidenciou que todos possuem 2n=50 cromossomos. Três destes acessos mostraram características morfológicas intermediárias entre os biótipos "Virasoro" (4x, sexual) e "Uruguaiana" (6x, apomítico). A confirmação de ocorrência geográfica próxima reforça a hipótese de hibridação e evidencia uma ampliação da área de ocorrência do biótipo sexual envolvido neste cruzamento. Os outros acessos são, provavelmente, híbridos naturais entre P. dilatatum "Torres" e P. urvillei. Tais acessos mostram a inflorescência com eixo mais longo e com mais ramos que as plantas típicas do biótipo "Torres". A caracterização morfológica e citológica do material discrepante poderá levar ao estabelecimento de parâmetros seguros para sua diferenciação, que permitam sua inclusão em categorias taxonômicas adequadas. Sugere-se a origem destes novos biótipos pentaplóides distintos do "Comum", a partir de cruzamentos ocorridos no Sul do Brasil entre outros dois biótipos e espécies do grupo.