Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.Peer reviewe

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

Facteurs influençant le délai avant la prise en charge médicale dans les syndromes coronariens aigus ST+ (étude descriptive en Sarthe)

Le temps d'ischémie myocardique dans les syndromes coronariens aigus ST+ est directement corrélée à la mortalité de cette pathologie. L'objectif de cette étude était d'étudier les délais précédant la prise en charge médicale et d'identifier les facteurs influençant ces délais. Il s'agissait d'une étude descriptive, menée dans l'USIC du CH du Mans. 52 patients admis pour syndrome coronarien aigu ST+ ou infarctus du myocarde semi-récent (entre 12 et 72 heures) avec sus-décalage du segment ST ont été inclus. Le délai étudié était celui entre le début de la douleur et l'ECG qualifiant. La filière de prise en charge, ainsi que des données démographiques et médicales étaient enregistrées. Une analyse univariée à été réalisée pour déterminer les facteurs prédictifs de prise en charge tardive et d'appel au 15. Ont été recueillies, par questions ouvertes, les raisons données pour expliquer un délai supérieur à une heure avant un premier contact médical et une absence d'appel au 15.Le délai douleur-ECG qualifiant était significativement plus court chez les patients non retraités (p=0.01), les patients ne vivant pas seuls à domicile (p=0.02), les patients présentant une douleur thoracique révélatrice (p=0.02), les patients ayant appelé le 15 en premier lieu (58%, p=0.0002) et les patients dont le premier intervenant médical était le SMUR (p<0.0001). L existence d antécédents cardio-vasculaires et l utilisation de trinitrine à visée antalgique étaient associés significativement avec l appel au 15 (p=0.03 pour les deux variables).Une éducation des patients à risque est la clef pour réduire le délai précédant la prise en charge dans le SCA ST+.ANGERS-BU Médecine-Pharmacie (490072105) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Prise en charge diagnostique des céphalées aiguës aux urgences

Les céphalées aiguës aux urgences posent le problème des investigations à mettre en œuvre d'autant qu'il n'existe pas de règle décisionnelle claire et validée permettant de stratifier les patients suivants leur risque d'hémorragie méningée. Nous avons réalisé une étude prospective dont l'objectif principal était dévaluer l adéquation aux recommandations d experts actuelles pour les patients présentant une céphalée à risque et également d'évaluer les facteurs cliniques liés à la réalisation d'examens complémentaires et l'apport des différentes stratégies diagnostiques rencontrées dans l'évaluation des céphalées aiguës. 49.5% des patients ont eu un examen complémentaire dont 39.8% un scanner cérébral (rentabilité 28.9%) et 20% une ponction lombaire (rentabilité 34.8%). Dans notre étude, nous avons noté que les recommandations d experts, préconisant un scanner cérébral sans injection, plus ou moins une ponction lombaire devant toute céphalée inhabituelle, ne sont pas appliquées pour tous les patients avec une céphalée à risque d hémorragie méningée: 22% des céphalées à risque n'ont eu aucun examen et 57.1% des céphalées à risque ont eu une ponction lombaire après un scanner cérébral normal. Dans notre population, le facteur le plus lié à la réalisation d examens complémentaires était la probabilité clinique subjective d hémorragie méningée, mesure dont la reproductibilité n a jamais été évaluée pour cette pathologie. Les résultats de notre étude soulignent l'actuel manque de score de probabilité clinique. Ces derniers permettraient de stratifier les patients à risque d'hemorragie méningée et d'orienter les cliniciens sur les investigations complémentaires à engager.ANGERS-BU Médecine-Pharmacie (490072105) / SudocSudocFranceF

Particularités des intoxications médicamenteuses volontaires en fonction de l'âge: Etude épidémiologique.

ANGERS-BU Médecine-Pharmacie (490072105) / SudocSudocFranceF

Reliability and validity of a four-level severity score based triage scale

Abstract Background:Triage scales are essential tools for an early and rapid assessment of patients, by classifying them according to their degree of urgency. The objective of this study was to measure the reliability and validity of a four-level severity score based scale.Methods:To evaluate reliability, 250 triage forms were triaged by 6 triage nurses twice, 15 days apart. Intra and inter-rater reproducibility were measured using a weighted Cohen’s Kappa. For the validity study, 485 charts were evaluated. The relationship between triage level and emergency department resource consumption was measured using Spearman’s correlation coefficient. Prediction of severity was measured by the correlation between triage level and hospitalization in any ward, and between triage level and death in the emergency department or hospitalization in an intensive care or high dependency unit. Areas under the ROC curves were measured for these results.Results:For inter-rater reproducibility, the weighted Kappa was measured at 0.51 (95% CI 0.30 – 0.70), and 0.67 (95% CI 0.42 – 0.91) for intra-rater reproducibility. 474 patients were recruited in the validity study, respectively 26 (5%), 50 (11%), 384 (81%) and 14 (3%) for triage levels 1 through 4. Spearman’s correlation coefficient between triage level and emergency department resource consumption was calculated at R = -0.41 (p&lt;0.001). 111 patients were admitted to the hospital with an area under the ROC curve measured at 0.72. 8 patients were admitted to an intensive care or high dependency unit with an area under the ROC curve measured at 0.73.Conclusions:Our study of a four-level severity score based triage scale finds intermediate results in terms of reliability and validity. Further improvements of the scale have to focus on better discriminating between moderately urgent and non-urgent patients.</jats:p

Prognostic accuracy of using lactate in addition to the quick Sequential Organ Failure Assessment score and the National Early Warning Score for emergency department patients with suspected infection

BackgroundThe aim of this study was to determine whether: (1) the quick Sequential (Sepsis-related) Organ Failure Assessment (qSOFA) and National Early Warning Score (NEWS) clinical prediction tools alone, (2) modified versions of these prediction tools that integrate lactate into their scores, or (3) use of the two tools in tandem with lactate better predicts in-hospital 28-day mortality among adult EDpatients with suspected infection.MethodsFrom 1 January through 31 December 2018, this retrospective cohort study enrolled consecutive adult patients with suspected infection evaluated at two EDs in France. Patients were included if blood cultures were obtained and non-prophylactic antibiotics were administered in the ED. qSOFA, NEWS criteria and lactate measurements were recorded when patients were clinically suspected of having an infection. Two composite scores (lactate qSOFA (LqSOFA) and lactate NEWS (LNEWS)) integrating lactate were created. Diagnostic test performances for predicting in-hospital mortality within 28days were assessed for qSOFA≥2, LqSOFA≥2, qSOFA≥2 or lactate≥2 mmol/L, and for NEWS≥7, LNEWS≥7, and NEWS≥7 or lactate≥2 mmol/L.Results1003 patients were included, 130 (13%) of whom had died by day 28. Sensitivities for 28-day mortality were 50% (95%CI41% to 59%) for qSOFA≥2,69% (95% CI60% to 77%) for LqSOFA≥2,77% (95% CI69% to 84%) for qSOFA or lactate≥2 mmol/L; and 69% (95% CI60% to 77%) for NEWS≥7, 80% (95% CI72% to 86%) for LNEWS≥7, 87% (95% CI80% to 92%) for NEWS≥7 or lactate≥2 mmol/L.ConclusionLactate used in tandem with qSOFA or NEWS yielded higher sensitivities in predicting in-hospital 28-day mortality, as compared with integration of lactate into these prediction tools or usage of the tools independently.</jats:sec

Impact of daily cyclic enteral nutrition versus standard continuous enteral nutrition in critically ill patients: a study protocol for a randomised controlled trial in three intensive care units in France (DC-SCENIC)

Introduction Current guidelines on clinical nutrition of ventilated patients in the intensive care unit (ICU) recommend initiating continuous enteral nutrition within 48 hours of ICU admission when feasible. However, discontinuous feeding regimens, alternating feeding and fasting intervals, may have an impact on clinical and patient centred outcomes. The ongoing Impact of daily cyclic enteral nutrition versus standard continuous enteral nutrition in critically ill patients (DC-SCENIC) trial aims to compare standard continuous enteral feeding with daily cyclic enteral feeding over 10 hours to evaluate if implementing a fasting-mimicking diet can decrease organ failure in ventilated patients during the acute phase of ICU management.Methods and analysis DC-SCENIC is a randomised, controlled, multicentre, open-label trial comparing two parallel groups of patients 18 years of age or older receiving invasive mechanical ventilation and having an indication for enteral nutrition through a gastric tube. Enteral feeding is continuous in the control group and administered over 10 hours daily in the intervention group. Both groups receive isocaloric nutrition with 4 g of protein per 100 mL, and have the same 20 kcal/kg/day caloric target. The primary endpoint is the change in the Sequential Organ Failure Assessment score at 7 days compared with the day of inclusion in the study. Secondary outcomes include daily caloric and protein delivery, digestive, respiratory and metabolic tolerance as well as 28-day mortality, duration of mechanical ventilation and ventilator-free days. Outcomes will be analysed on an intention-to-treat basis. Recruitment started in June 2023 in 3 French ICU’s and a sample size of 318 patients is expected by February 2026.Ethics and dissemination This study received approval from the national ethics review board on 8 November 2022 (Comité de Protection des Personnes Sud-Est VI, registration number 2022-A00827-36). Patients are included after informed consent. Results will be submitted for publication in peer-reviewed journals.Trial registration number NCT05627167