[Innovating in the hospital of tomorrow]. / Innover au sein de l'hôpital de demain.

The hospital of tomorrow must aim not only to be an innovative establishment, but also to become an establishment that innovates. The objective is to bring up initiatives and the expression of needs of the hospital community, to evaluate and prioritize them, and then to implement the selected projects.

Health research and innovation: Can we optimize the interface between startups/pharmaceutical companies and academic health care institutions or not?

Although France has numerous assets in the realm of health care, such as the excellence of its research teams, the reputation of its healthcare system, and the presence of many startups, all of which are necessary to become a leader in innovation, it also has combined cultural and regulatory barriers that limit the flexibility and efficiency of interactions between companies/startups and public health institutions. Therefore, the aim of the roundtable discussion was to optimize the interface between those businesses and institutions. Several institutions have successfully implemented teams and procedures which aim to facilitate this interface, with regard to assessments of technology, services provided, the transfer of biological material, R&D collaboration, and licensing agreements. However, there is still a notable absence of entrepreneurial culture among hospital and academic research practitioners; their training regarding innovation remains insufficient and business-related value-creation is non-existent in their career evolution. Pharmaceutical companies, and particularly startups, often lack knowledge about hospital environments and their constraints. As a result, the recommendations of the roundtable participants are as follows: (1) promote reciprocal acculturation between public health institutions and startups through multidisciplinary training in innovation, promoting project development and staff recognition within the institution, and improving pharmaceutical companies' understanding regarding the health care system; (2) provide those involved with means and resources dedicated to innovation by reserving time for innovation at work, securing the status of the staff involved, and aiding in the search for funding; (3) develop and use standard methodologies and tools; and (4) co-design and co-construct innovative health solutions, encouraging the emergence of participatory and interdisciplinary creative spaces. All of these recommendations should help to make the interface between startups/companies and public health institutions more fluid and attractive for those in the health sector.

[Lab Santé, an innovation accelerator]. / Le Lab Santé, un accélérateur de projets innovants.

Lab Santé is an association created by the Île-de-France regional health agency to accelerate innovative health care solutions. Its expertise, its agility and its network made up of various stakeholders from across the region enable it to successfully carry out the projects it supports and the experiments it conducts.

Using connected objects in clinical research.

Connected objects (CO), whether medical devices or not, are used in clinical research for data collection, a specific activity (communication, diagnosis, effector, etc.), or several functions combined. Their validation should be based on three approaches: technical and clinical reliability, data protection and cybersecurity. Consequently, the round table recommends that the typology of COs, their uses and limitations, be known and shared by all, particularly for implementing precise specifications. COs are used in clinical research during observational studies (assessment of the device itself or data collection), randomized studies, where only one group has a CO (assessment of its impact on patient follow-up or management), or randomized studies where both groups have a CO, which is then used as a tool to help with assessment. The benefits of using COs in clinical research includes: improved collection and quality of data, compliance of patients and pharmacovigilance, easier implementation of e-cohorts and a better representative balance of patients. The societal limits and risks identified relate to the sometimes intrusive nature of certain collected parameters and the possible misuse of data. The round table recommends the following on this last point: anticipation, by securing transmission methods, the qualification of data hosts, and assessment of the object's vulnerability. For this, a risk analysis appears necessary for each project. It is also necessary to accurately document the data flow, in order to inform both patients and healthcare professionals and to ensure adequate security. Anticipating regulatory changes and involving users starting from the study design stage are also recommended.

What strategy should France implement for H2020?

The initiation of Horizon 2020--the European Union's 8th Framework Programme for Research and Innovation, allotted a budget of 79 billion euros--provides an opportunity to review France's participation in previous Framework Programmes. Indeed, French participation does not match either its scientific importance or its financial investment. While France contributed 16.5 to 17% of the EU's 7th Framework Programme research budget, its return through the funding of coordinated projects in which French teams are participating stands at around 12.5 to 13%, a shortfall of 600 million euros. Although the situation depends on the type of activity, French participation in clinical research appears to be smaller than that of its neighbours, with fewer responses to European calls for proposals. While France has many assets, which include the assured funding of clinical research, structured thematic networks and the initiation of major national programmes, it suffers from the dilution of resources due to France's regional development policy, the lack of multidisciplinarity and the ignorance of both the medical and scientific community and the institutions to which they belong as to how Horizon 2020 actually works. We propose three types of strategy to encourage proposals for coordinated clinical research projects or projects involving French teams, and to help in the drawing up of applications: Broaden the vision of our children, students and colleagues, helping them to adapt to the globalisation of knowledge throughout their educational and professional lives. Recognise the value of European actions to influence the European landscape and change mentalities. Help and support project initiators by pooling skills within a limited number of expert centres designed to assist them in their funding application. • Broaden the vision of our children, students and colleagues, helping them to adapt to the globalisation of knowledge throughout their educational and professional lives. • Recognise the value of European actions to influence the European landscape and change mentalities. • Help and support project initiators by pooling skills within a limited number of expert centres designed to assist them in their funding application.

Drotrecogin alfa (activated) in adults with septic shock.

BACKGROUND: There have been conflicting reports on the efficacy of recombinant human activated protein C, or drotrecogin alfa (activated) (DrotAA), for the treatment of patients with septic shock. METHODS: In this randomized, double-blind, placebo-controlled, multicenter trial, we assigned 1697 patients with infection, systemic inflammation, and shock who were receiving fluids and vasopressors above a threshold dose for 4 hours to receive either DrotAA (at a dose of 24 µg per kilogram of body weight per hour) or placebo for 96 hours. The primary outcome was death from any cause 28 days after randomization. RESULTS: At 28 days, 223 of 846 patients (26.4%) in the DrotAA group and 202 of 834 (24.2%) in the placebo group had died (relative risk in the DrotAA group, 1.09; 95% confidence interval [CI], 0.92 to 1.28; P=0.31). At 90 days, 287 of 842 patients (34.1%) in the DrotAA group and 269 of 822 (32.7%) in the placebo group had died (relative risk, 1.04; 95% CI, 0.90 to 1.19; P=0.56). Among patients with severe protein C deficiency at baseline, 98 of 342 (28.7%) in the DrotAA group had died at 28 days, as compared with 102 of 331 (30.8%) in the placebo group (risk ratio, 0.93; 95% CI, 0.74 to 1.17; P=0.54). Similarly, rates of death at 28 and 90 days were not significantly different in other predefined subgroups, including patients at increased risk for death. Serious bleeding during the treatment period occurred in 10 patients in the DrotAA group and 8 in the placebo group (P=0.81). CONCLUSIONS: DrotAA did not significantly reduce mortality at 28 or 90 days, as compared with placebo, in patients with septic shock. (Funded by Eli Lilly; PROWESS-SHOCK ClinicalTrials.gov number, NCT00604214.).

Recombinant tissue factor pathway inhibitor in severe community-acquired pneumonia: a randomized trial.

RATIONALE: Severe community-acquired pneumonia (sCAP) is a leading cause of death worldwide. Adjunctive therapies for sCAP are needed to further improve outcome. A systemic inhibitor of coagulation, tifacogin (recombinant human tissue factor pathway inhibitor) seemed to provide mortality benefit in the sCAP subgroup of a previous sepsis trial. OBJECTIVES: Evaluate the impact of adjunctive tifacogin on mortality in patients with sCAP. METHODS: A multicenter, randomized, placebo-controlled, double-blind, three-arm study was conducted from July 2005 to June 2008 at 188 centers in North and South America, Europe, South Africa, Asia, Australia, and New Zealand. Adults with sCAP were randomized to receive a continuous intravenous infusion of tifacogin 0.025 mg/kg/h, tifacogin 0.075 mg/kg/h, or matching placebo over 96 hours. MEASUREMENTS AND MAIN RESULTS: Severity-adjusted 28-day all-cause mortality. Of 2,138 randomized patients, 946, 238, and 918 received tifacogin 0.025 mg/kg/h, tifacogin 0.075 mg/kg/h, and placebo, respectively. Tifacogin 0.075 mg/kg/h was discontinued after the first interim analysis according to prespecified futility criterion. The 28-day all-cause mortality rates were similar between the 0.025 mg/kg/h (18%) and placebo groups (17.9%) (P = 0.56). Greater reduction in prothrombin fragment 1+2 and thrombin antithrombin complexes levels relative to baseline throughout the first 96 hours was found with tifacogin 0.025 mg/kg/h than with placebo. The incidence of adverse events and serious adverse events were comparable between the tifacogin 0.025 mg/kg/h and placebo groups. CONCLUSIONS: Tifacogin showed no mortality benefit in patients with sCAP despite evidence of biologic activity.

[First steps towards a comparative evaluation of the French medical schools]. / Etude comparative des facultés de médecine en France : premiers résultats.

CONTEXT: AERES has achieved the first comparative study of the French medical schools based on the analysis of both teaching performance and research activity. METHODS: The human resources considered in the evaluation are full-time, tenured, university hospital teaching staff (TUHT), professors or lecturers, and are meaningful only if the number of students is considered. The estimated number of students is based on the Numerus Clausus (NC), number of students allowed each year to enter in the second year of medical studies. Teaching performance of each faculty is based on the success of their students in a national ranking examination (Examen Classant National - ECN), at the end of their second cycle of medical studies which allows them to choose, for their third specialising cycle of medical studies, the specialty and region of practice. Research activity is estimated on the SIGAPS score of the medical school based on the number and impact factor of the scientific papers produced for five years running by the full-time professors and lecturers of each medical school, the number of national clinical research projects (PHRC) they have conducted during the three past years and the number of research units headed by these professors labelled by CNRS and INSERM. RESULTS: French medical school characteristics are markedly different in the number of university-hospital teaching staff, teaching performances and research activities. Numerous teaching staff and labelled research units have a beneficial influence on research activity and teaching results. The impact on teaching results is less statistically significant than that on research activity. A medical school mapping is then outlined. PROSPECT: More precise analysis of the observed differences between medical schools will allow propose recommendations.

Can metabolic abnormalities after a fall predict short term mortality in elderly patients?

Morbidity related is important in older adults who fall and are consequently referred to emergency departments (ED). The aim of this study is to determine 6-month all-causes mortality in patients over 75 years referred to an emergency department after a fall at home, and to define the criteria associated with death. The design was a prospective observational study with a 6-month follow-up in an Emergency Department of a tertiary teaching hospital, Paris, France. We included for a 6-month period patients over 75 years who visited the Emergency Department for a fall that occurred at home and measured the 6-month all-causes mortality. Uni- and multivariate assessment of factors related to mortality were adjusted for the occurrence of trauma. We enrolled 433 patients. Mean age was 86 years and two-thirds were women. The population was in relatively good health and preserved autonomy. The prevailing consequence was trauma and 11% had metabolic disorders. 64 patients (15%) died within 6 months. Factors associated with mortality included decrease in Katz score, male gender, a fall of intrinsic origin and the occurrence of adverse metabolic events. Markers of fragility such as poor previous level of autonomy, clinical disorders and metabolic abnormalities, as cause or consequence, indicate a potentially poor outcome more than the presence of severe trauma. As metabolic abnormalities can be an indirect marker of a long delay before emergency medical care, this study underscored the importance of early warning system for the frailest old individuals in order to prevent such complications.

Role of clinical evaluation committees in sepsis trials: from 'valid cohort' assessment to subgroup analysis.

In this issue of Critical Care, the study from Laterre and colleagues offers suggestions for the role of clinical evaluation committees (CECs) in future sepsis trials. Despite encouraging preliminary results, all randomized controlled trials (RCTs) devoted to potential compounds in severe sepsis have failed to show survival benefit. One of the reasons might be related to RCT-related factors that inevitably occur within a heterogeneous septic patient population. A patient population free from confounding events would seem to provide the most suitable platform upon which to judge therapeutic effect. To solve this issue, CECs have been introduced into RCTs in sepsis to ensure uniform data for analysis and to identify such 'optimal cohorts' for which the therapy was initially designed to treat. More recently, some RCTs have reported positive results in sepsis. The role of CECs has shifted to become a more integral part of the detailed analysis of drug safety and efficacy in large databases, and to identify subgroups of patients in which a therapy might be less or more effective and/or safe. As an example, the retrospective analysis by Laterre and colleagues focuses on patients with severe community-acquired pneumonia (sCAP) within a large, failed RCT (on recombinant tissue factor pathway inhibitor (rTFPI)). However, the results should be interpreted with great caution, and should be viewed as exploratory and a hypothesis-generating activity. This question of potential benefit of rTFPI in patients with sCAP will be definitively answered by the results of the recently completed RCP.

Extended drotrecogin alfa (activated) treatment in patients with prolonged septic shock.

OBJECTIVE: To determine the efficacy and safety of extended drotrecogin alfa (activated) (DAA) therapy. DESIGN: Multicentre, randomised, double-blind, placebo-controlled study. SETTING: Sixty-four intensive care units in nine countries. PATIENTS: Adults with severe sepsis and vasopressor-dependent hypotension after a 96-h infusion of standard DAA. INTERVENTIONS: A total of 193 patients received an intravenous infusion of extended DAA 24 microg/kg/h or sodium chloride placebo for a maximum of 72 h. MEASUREMENTS AND RESULTS: At extended therapy initiation (baseline), DAA-group patients had lower protein C levels (P = 0.23) and higher vasopressor requirements, particularly for the primary vasopressor used, norepinephrine (P = 0.03), compared with placebo-group patients. DAA treatment did not result in a difference in the primary outcome of time to resolution of vasopressor-dependent hypotension versus placebo (P = 0.419). However, few patients reached resolution (DAA 34%, placebo 40%) as most continued to require vasopressor support after 72 additional hours of treatment. Treatment did not reduce 28-day all-cause mortality and in-hospital mortality or improve organ function compared with placebo, although there was a lower percentage change in D-dimers (P < 0.001) and increases in protein C levels were numerically greater on extended infusion. There was no difference in serious adverse events including bleeding events. CONCLUSIONS: Extended DAA treatment did not result in more rapid resolution of vasopressor-dependent hypotension, despite demonstrating anticipated biological effects on D-dimer and protein C levels. A reduced planned sample size combined with baseline imbalances in protein C levels and vasopressor requirements may have limited the ability to demonstrate a clinical benefit.

Do ED staffs have a role to play in the prevention of repeat falls in elderly patients?

BACKGROUND: Fall-related morbidity is a serious public health issue in older adults referred to emergency departments (EDs). Emergency physicians mostly focus on immediate injuries, whereas the specific assessment of functional consequences and opportunities for prevention remain scarce. The aim of this study was to determine the factors influencing 6-month independence. METHODS: We used a prospective observational study at the ED of a tertiary teaching hospital over a 6-month period. Uni- and multivariate assessments of factors related to loss of independence were examined. RESULTS: A total of 367 patients survived to 6 months, mean age was 86 years, and 79% were women. The population was initially healthy and independent. Because this independence reassured the medical staff, more than 42% percent were directly discharged home without any improvement of home facilities; only 63% had recovered their independence at the end of the follow-up. There were 111 patients were hospitalized for 30 days or more. Older patients, initial Katz score, and absence of immediate trauma consequences were associated with an increased risk for loss of independence. CONCLUSIONS: Because prevention is an emerging role of ED, a multidisciplinary team should evaluate fallers and propose medical and environmental changes as required for those discharged after their ED visit.

Appropriateness of diagnosis and orientation of 996 consecutive patients admitted in an emergency department with flow-based organization.

BACKGROUND: Recent data, focused on the inability to transfer emergency patients to inpatient beds, has shown this to be the single most important factor contributing to overcrowding. Our Emergency Department (ED) was reorganized in the year 2000 based on the optimization of patients' flow. In this model, the emergency team had to refer patients to units fitting best to their condition with minimal delays. OBJECTIVES: To evaluate adequacy of both diagnosis between emergency room and hospitalization wards and patients' orientation in the context of an early discharge from the ED. METHODS: We collected data from 996 consecutive nontrauma patients for whom an admission was decided. Duration of stay in the ED and all related parameters were studied. Patients were categorized according to the adequacy of the diagnosis proposed at ED discharge as compared with the final diagnosis at hospital discharge. The patients' orientation appropriateness was also assessed. RESULTS: Despite a median duration of time of 6 h (21 min-54 h) diagnostics made by the emergency physicians and the patients' orientation were considered as adequate in most of the cases (66 and 96%, respectively). Fast track developed with medical intensive care and cardiology intensive care allowed referral of patients requiring these specific units within 2.2 h (27 min-17 h) and 2 h (41 min-8 h), respectively. The ED length of stay was highly influenced by the admission location and by the patient's age. CONCLUSION: A short time of stay in the ED is compatible with both a good diagnosis and a good orientation of ED patients requiring admission for specialized care.