Intelligence-based medicine

Despite seven hundred thousand new medical references last year, the relationship between a given set of medical features and specific pathophysiology, treatment, and criteria of improvement is often weak. Moreover, the generalization of evidences obtained in specific settings may lead to under-treat or to over-treat a significant proportion of patients. We expose an application of the cybernetic loop, based on traditional medical steps: nosology, semeiology, pathophysiology, therapy and on the four transitions between these steps. This approach leads to formulate eight basic questions evaluating the steps in terms of reproducibility and the transitions in terms of predictivity. We detail two practical applications: 1) the evaluation of a medical decision (implantation of an internal cardioverter-defibrillator) and 2) the evaluation of a specific study (EPHESUS). Using this loop allows to determine clearly when evidence is lacking and/or to which extend an evidence really increases the medical knowledge or just creates a market

Complications of regional citrate anticoagulation: accumulation or overload?

Regional citrate anticoagulation (RCA) is now recommended over systemic heparin for continuous renal replacement therapy in patients without contraindications. Its use is likely to increase throughout the world. However, in the absence of citrate blood level monitoring, the diagnosis of citrate accumulation, the most feared complication of RCA, remains relatively complex. It is therefore commonly mistaken with other conditions. This review aims at providing clarifications on RCA-associated acid-base disturbances and their management at the bedside. In particular, the authors wish to propose a clear distinction between citrate accumulation and net citrate overload

Study protocol: The DOse REsponse Multicentre International collaborative initiative (DO-RE-MI)

INTRODUCTION: Current practices for renal replacement therapy in intensive care units (ICUs) remain poorly defined. The DOse REsponse Multicentre International collaborative initiative (DO-RE-MI) will address the issue of how the different modes of renal replacement therapy are currently chosen and performed. Here, we describe the study protocol, which was approved by the Scientific and Steering Committees. METHODS: DO-RE-MI is an observational, multicentre study conducted in ICUs. The primary end-point will be the delivered dose of dialysis, which will be compared with ICU mortality, 28-day mortality, hospital mortality, ICU length of stay and number of days of mechanical ventilation. The secondary end-point will be the haemodynamic response to renal replacement therapy, expressed as percentage reduction in noradrenaline (norepinephrine) requirement. Based on the the sample analysis calculation, at least 162 patients must be recruited. Anonymized patient data will be entered online in electronic case report forms and uploaded to an internet website. Each participating centre will have 2 months to become acquainted with the electronic case report forms. After this period official recruitment will begin. Patient data belong to the respective centre, which may use the database for its own needs. However, all centres have agreed to participate in a joint effort to achieve the sample size needed for statistical analysis. CONCLUSION: The study will hopefully help to collect useful information on the current practice of renal replacement therapy in ICUs. It will also provide a centre-based collection of data that will be useful for monitoring all aspects of extracorporeal support, such as incidence, frequency, and duration

Clustering ICU patients with sepsis based on the patterns of their circulating biomarkers: A secondary analysis of the CAPTAIN prospective multicenter cohort study.

peer reviewed[en] BACKGROUND: Although sepsis is a life-threatening condition, its heterogeneous presentation likely explains the negative results of most trials on adjunctive therapy. This study in patients with sepsis aimed to identify subgroups with similar immune profiles and their clinical and outcome correlates. METHODS: A secondary analysis used data of a prospective multicenter cohort that included patients with early assessment of sepsis. They were described using Predisposition, Insult, Response, Organ failure sepsis (PIRO) staging system. Thirty-eight circulating biomarkers (27 proteins, 11 mRNAs) were assessed at sepsis diagnosis, and their patterns were determined through principal component analysis (PCA). Hierarchical clustering was used to group the patients and k-means algorithm was applied to assess the internal validity of the clusters. RESULTS: Two hundred and three patients were assessed, of median age 64.5 [52.0-77.0] years and SAPS2 score 55 [49-61] points. Five main patterns of biomarkers and six clusters of patients (including 42%, 21%, 17%, 9%, 5% and 5% of the patients) were evidenced. Clusters were distinguished according to the certainty of the causal infection, inflammation, use of organ support, pro- and anti-inflammatory activity, and adaptive profile markers. CONCLUSIONS: In this cohort of patients with suspected sepsis, we individualized clusters which may be described with criteria used to stage sepsis. As these clusters are based on the patterns of circulating biomarkers, whether they might help to predict treatment responsiveness should be addressed in further studies. TRIAL REGISTRATION: The CAPTAIN study was registered on clinicaltrials.gov on June 22, 2011, # NCT01378169

Circulating biomarkers may be unable to detect infection at the early phase of sepsis in ICU patients: the CAPTAIN prospective multicenter cohort study.

PURPOSE: Sepsis and non-septic systemic inflammatory response syndrome (SIRS) are the same syndromes, differing by their cause, sepsis being secondary to microbial infection. Microbiological tests are not enough to detect infection early. While more than 50 biomarkers have been proposed to detect infection, none have been repeatedly validated. AIM: To assess the accuracy of circulating biomarkers to discriminate between sepsis and non-septic SIRS. METHODS: The CAPTAIN study was a prospective observational multicenter cohort of 279 ICU patients with hypo- or hyperthermia and criteria of SIRS, included at the time the attending physician considered antimicrobial therapy. Investigators collected blood at inclusion to measure 29 plasma compounds and ten whole blood RNAs, and-for those patients included within working hours-14 leukocyte surface markers. Patients were classified as having sepsis or non-septic SIRS blindly to the biomarkers results. We used the LASSO method as the technique of multivariate analysis, because of the large number of biomarkers. RESULTS: During the study period, 363 patients with SIRS were screened, 84 having exclusion criteria. Ninety-one patients were classified as having non-septic SIRS and 188 as having sepsis. Eight biomarkers had an area under the receiver operating curve (ROC-AUC) over 0.6 with a 95% confidence interval over 0.5. LASSO regression identified CRP and HLA-DRA mRNA as being repeatedly associated with sepsis, and no model performed better than CRP alone (ROC-AUC 0.76 [0.68-0.84]). CONCLUSIONS: The circulating biomarkers tested were found to discriminate poorly between sepsis and non-septic SIRS, and no combination performed better than CRP alone

Les études négatives publiées en anesthésie-réanimation

La médecine factuelle repose sur les études cliniques que les biais éloignent des faits que l on pense interpréter. Les études négatives regroupent un ensemble disparate allant des études de puissance et de méthodologie adéquate démontrant l absence de différence aux études normalement non concluantes car de puissance et/ou de méthodologie insuffisantes. Nous avons étudié les 63 études négatives publiées sur 2 périodes d un an dans les 2 plus prestigieux journaux d anesthésie réanimation, à 10 ans d intervalle. La majorité des études étaient monocentriques, présentaient des critères d inclusion trop larges. La randomisation et l aveugle n étaient corrects que dans 20%, une analyse en intention de traiter n était réalisée que dans 10% des cas. Plus de 80% des études publiées n avaient pas la puissance requise: près de 50% ne mentionnaient pas de calcul a priori de l effectif, 15% n atteignaient pas le nombre de sujets nécessaires, 8% avaient un critère de jugement non pertinent, 8% incluaient une population trop hétérogène et près de 2% avaient surestimé l effet de l intervention. Plus de 50% des auteurs concluaient à l absence de différence, 20% remettaient leurs résultats en question en dépit des faits. Plus de 15% opéraient à une diversion sur des critères de jugement secondaires ou sur un sous-groupe. Près de 8% s attardaient sur des tendances non significatives et 5% concluaient à tort à l équivalence. La diffusion des recommandations CONSORT et la création de registres d études devraient se traduire par une amélioration méthodologique, un recours plus fréquent au calcul a priori de l effectif nécessaire, une remise en question plus fréquente des résultats négatifs.PARIS6-Bibl.Pitié-Salpêtrie (751132101) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF