EVIDENCE trial: design of a phase 2, randomized, controlled, multicenter study comparing flow diversion and traditional endovascular strategy in unruptured saccular wide-necked intracranial aneurysms.

INTRODUCTION: Endovascular treatment of large, wide-necked intracranial aneurysms with coils is associated with low rates of initial angiographic occlusion and high rates of recurrence. The Pipeline™ Embolization Device has shown high rates of complete occlusion in uncontrolled clinical series. METHODS: The study is a prospective, controlled, randomized, multicenter, phase 2 open-label trial. Intention-to-treat population includes age ≥18, unruptured saccular aneurysm located in the intra-dural area, neck diameter ≥4 and ≤10 mm, sac diameter ≥7 mm and ≤20 mm, "dome/neck" ratio is ≥1, diameter of the parent artery ≥2 mm and ≤5 mm, and no prior treatment of the aneurysm. Site can only participate if five patients have been previously treated with the Pipeline device. The primary end point of the study is complete occlusion of the aneurysm on angiogram performed 12 months after the endovascular procedure. Complete aneurysm occlusion is defined as the absence of visible blood flow, grade 1 according to the Raymond scale for the standard procedure group and grade 4 according to the grading scale of Kamran for the flow diverter group. RESULTS: The trial is currently enrolling and results of the data are pending the completion of enrollment and follow-up. CONCLUSION: This paper details the trial design of the French EVIDENCE phase 2 trial, a blinded, controlled randomized trial of wide-neck intra-dural aneurysms amenable to either traditional endovascular strategy or flow diversion with Pipeline device.

Bevacizumab and ranibizumab for neovascular age-related macular degeneration: an updated meta-analysis of randomised clinical trials.

PURPOSE: Neovascular age-related macular degeneration (AMD) is the main cause of central vision loss among individuals aged 50 years or older in developed countries. The aim of this study was to review systematically the effect of bevacizumab compared to ranibizumab in patients with AMD at 1 year. METHODS: A systematic review was performed on Medline, Embase, and the Cochrane Library and Trial registers to October 2013. Eligibility criteria for selecting studies were randomised controlled trials (RCT) comparing bevacizumab with ranibizumab in patients with neovascular AMD. Odds ratio (OR) and mean difference (MD) estimates were synthesized under fixed- and random-effects models. Heterogeneity was assessed using the Q statistic and I(2). RESULTS: Five RCTs were included, representing 2,686 randomised patients. The meta-analysis confirmed the non-inferiority of bevacizumab compared to ranibizumab for change in visual acuity at 1 year (MD 0.57 letters, -1.80 to 0.66, p = 0.37, I(2) = 0 %). Better anatomical results were found for ranibizumab. Bevacizumab was associated with a 34 % increase in the number of patients with at least one serious systemic adverse event (OR 1.34, 1.08 to 1.66, p = 0.01, I(2) = 0 %). CONCLUSIONS: The pooled evidence confirmed that, compared with ranibizumab, bevacizumab was associated with equivalent effects on visual acuity at 1 year and with a higher risk of systemic serious adverse events. The current available data do not show which types of adverse events occur more frequently. In practice, bevacizumab should be used under a risk-management plan until further studies have been carried out to assess accurately the increased risk of systemic adverse events.

[Ethical principles for the design of a clinical trial in oncology]. / Règles éthiques pour la conception d'un essai clinique en oncologie.

Clinical research in the area of cancer is of utmost importance in order to improve patient care, both in terms of overall survival and quality of life. The implementation of clinical trials on medicinal products, now falling under EU Regulation 536/2014, is conditioned on prior scientific authorisation from the French National Agency for the Safety of Medicines and Health Products and a favorable ethical opinion from a Research Ethics Committee (REC). OBJECTIVE: The objective of this work is to report on the main problematic issues identified during the evaluation of oncology dossiers by the REC in order to present the expected elements and thus optimise the evaluation procedures. METHODS: The National Conference of the Research Ethics Committees analysed the questions raised by the REC during their evaluation of clinical trials of oncology drugs submitted to the European information system in 2022. RESULTS: Out of a total of fourteen dossiers, nine were subject to ethical questions on the protocol and all dossiers required modifications to the information documents. DISCUSSION: The heterogeneous quality of the dossiers reminds the need to submit well-argued, methodologically robust protocols with supervised research procedures that are safe for the participants. The drafting of information documents needs to be thoroughly reconsidered in order to present clear, concise, loyal and respectful documents for patients' rights.

A new prognostic clinicopathological classification of pituitary adenomas: a multicentric case-control study of 410 patients with 8 years post-operative follow-up.

Pituitary adenomas are currently classified by histological, immunocytochemical and numerous ultrastructural characteristics lacking unequivocal prognostic correlations. We investigated the prognostic value of a new clinicopathological classification with grades based on invasion and proliferation. This retrospective multicentric case-control study comprised 410 patients who had surgery for a pituitary tumour with long-term follow-up. Using pituitary magnetic resonance imaging for diagnosis of cavernous or sphenoid sinus invasion, immunocytochemistry, markers of the cell cycle (Ki-67, mitoses) and p53, tumours were classified according to size (micro, macro and giant), type (PRL, GH, FSH/LH, ACTH and TSH) and grade (grade 1a: non-invasive, 1b: non-invasive and proliferative, 2a: invasive, 2b: invasive and proliferative, and 3: metastatic). The association between patient status at 8-year follow-up and age, sex, and classification was evaluated by two multivariate analyses assessing disease- or recurrence/progression-free status. At 8 years after surgery, 195 patients were disease-free (controls) and 215 patients were not (cases). In 125 of the cases the tumours had recurred or progressed. Analyses of disease-free and recurrence/progression-free status revealed the significant prognostic value (p < 0.001; p < 0.05) of age, tumour type, and grade across all tumour types and for each tumour type. Invasive and proliferative tumours (grade 2b) had a poor prognosis with an increased probability of tumour persistence or progression of 25- or 12-fold, respectively, as compared to non-invasive tumours (grade 1a). This new, easy to use clinicopathological classification of pituitary endocrine tumours has demonstrated its prognostic worth by strongly predicting the probability of post-operative complete remission or tumour progression and so could help clinicians choose the best post-operative therapy.

Medical device assessment: scientific evidence examined by the French national agency for health - a descriptive study.

BACKGROUND: Scientific evidence supports decision-making on the use of implantable medical devices (IMDs) in clinical practice, but IMDs are thought to be far less investigated than drugs. In the USA, studies have shown that approval process of high-risk medical devices was often based on insufficiently robust studies, suggesting that evidence prior to marketing may not be adequate. This study aimed to ascertain level of evidence available for IMDs access to reimbursement in France. METHODS: The objective was to examine the scientific evidence used for IMDs assessment by the French National Authority for Health. We collected all public documents summarising supportive clinical data and opinions concerning IMDs issued in 2008. An opinion qualifies the expected benefit (EB) of the IMD assessed as sufficient or insufficient, and if sufficient, the level of improvement of the expected benefit (IEB) on a scale from major (level I) to no improvement (level V). For each opinion, the study with the highest level of evidence of efficacy data, and its design were collected, or, where no studies were available, any other data sources used to establish the opinion. RESULTS: One hundred and two opinions were analysed, with 72 reporting at least one study used for assessment (70.6%). When considering the study with the highest level of evidence: 34 were clinical non-comparative studies (47.2%); 29 were clinical comparative studies of which 25 randomised controlled trials (40.3%); 5 were meta-analyses of randomised controlled trials (6.9%); and 4 were systematic literature reviews (5.6%). The opinions were significantly different according to the study design (p < 0.001). The most frequent design for insufficient EB, IEB level V and IEB level IV was a non-comparative study (10/19, 52.6%; 15/24, 62.5%; and 8/15, 53.3%; respectively). For the 30 opinions with no supporting clinical study, 16 (53.3%) were based on an expert-based process, 9 (30.0%) were based on the conclusions of a previous opinion (all concluding IEB level V), and 5 (16.7%) reported no data (concluding insufficient EB for 4 and IEB level V for 1). CONCLUSIONS: This study confirmed that level of evidence of clinical evaluation of IMDs is low and needs to be improved.

Inadequate dissemination of phase I trials: a retrospective cohort study.

BACKGROUND: Drug development is ideally a logical sequence in which information from small early studies (Phase I) is subsequently used to inform and plan larger, more definitive studies (Phases II-IV). Phase I trials are unique because they generally provide the first evaluation of new drugs in humans. The conduct and dissemination of Phase I trials have not previously been empirically evaluated. Our objective was to describe the initiation, completion, and publication of Phase I trials in comparison with Phase II-IV trials. METHODS AND FINDINGS: We reviewed a cohort of all protocols approved by a sample of ethics committees in France from January 1, 1994 to December 31, 1994. The comparison of 140 Phase I trials with 304 Phase II-IV trials, showed that Phase I studies were more likely to be initiated (133/140 [95%] versus 269/304 [88%]), more likely to be completed (127/133 [95%] versus 218/269 [81%]), and more likely to produce confirmatory results (71/83 [86%] versus 125/175 [71%]) than Phase II-IV trials. Publication was less frequent for Phase I studies (21/127 [17%] versus 93/218 [43%]), even if only accounting for studies providing confirmatory results (18/71 [25%] versus 79/125 [63%]). CONCLUSIONS: The initiation, completion, and publications of Phase I trials are different from those of other studies. Moreover, the results of these trials should be published in order to ensure the integrity of the overall body of scientific knowledge, and ultimately the safety of future trial participants and patients.

Heparin-induced thrombocytopenia: an estimate of the average cost in the hospital setting in France.

Heparin-induced thrombocytopenia is a severe drug adverse effect with possible dramatic consequences. The risk is 0.1% to 5%. The costs of heparin-induced thrombocytopenia in France were estimated using the Programme Médicalisé des Systèmes d'Information (PMSI) national discharge database. Hospitalizations with heparin-induced thrombocytopenia were identified using diagnostic codes. Costs were assessed from the perspective of the French Sickness Fund or hospitals. Heparin-induced thrombocytopenia could be the reason of admission or could occur during the stay and lead to a different tariff or to additional costs associated with extra length of stay. Direct costs were also estimated from experts' opinions. A sensitivity analysis was performed from data collected in 1 center. During 2005, 445 hospitalizations with heparin-induced thrombocytopenia codes were identified. For 45 patients, the main diagnosis was heparin-induced thrombocytopenia; for the remaining 400 patients, heparin-induced thrombocytopenia occurred during the hospital stay. Tariffs and extra costs were used to estimate an overall average cost of 3230 for heparin-induced thrombocytopenia. For patients with heparin-induced thrombocytopenia as main diagnosis, the average cost was 3400; for the patients with heparin-induced thrombocytopenia that occurred during the stay, 1910 was due to an increased of the tariff and 3348 to an increased length of stay. Estimated direct costs of an episode were 3350 to 3700. Different methods were used to arrive at an estimated cost of 3500 for a heparin-induced thrombocytopenia episode for inpatients. One limitation of the study is that heparin-induced thrombocytopenia tends to be underreported by physicians during hospitalization.

Growth and bone mineralization in preterm infants fed preterm formula or standard term formula after discharge.

OBJECTIVE: To evaluate growth and bone mineralization in very low birth weight (VLBW) infants fed preterm formula (PF) or term formula (TF). STUDY DESIGN: In a double-blind prospective study, 49 preterm infants of gestational age 33 weeks or less were randomly fed PF or TF for 2 months after discharge, then all of the infants were fed TF for the next 2 months. Anthropometric and dual-energy x-ray absorptiometry data were collected at discharge and at 2 months and 4 months after discharge. Anthropometric data also were collected at 12 months postterm. RESULTS: Four months after discharge, both body weight (6139 +/- 1254 g vs 5540 +/- 863 g; P = .03) and bone mineral content (104.4 +/- 29.2 g vs 87.5 +/- 17.1 g; P = .01) were significantly higher in the PF group compared with the TF group. At 12 months postterm, mean body weight, length, and head circumference remained higher in the PF group than in the TF group, and body mass index was similar and within the normal range in the 2 groups. CONCLUSIONS: At 4 months after discharge, growth and mineralization were better in the VLBW infants who were fed PF during the first 2 months after discharge compared with those who were fed TF, suggesting that PF may be particularly valuable at this early stage of development.

Inflammatory response after ischemic stroke: a USPIO-enhanced MRI study in patients.

BACKGROUND AND PURPOSE: The intensity of the inflammatory response may be related to the volume of acute infarction. Ultra-small superparamagnetic particles of iron oxide (USPIO) may enable assessment of neuroinflammation. We aimed to assess whether the intensity of the inflammatory response might be related to the subacute ischemic lesion volume. METHODS: We enrolled patients who presented with acute anterior circulation stroke. MRI was performed at day 0, day 6, and day 9. The MRI protocol included T1-weighted imaging, gradient-echo T2*-weighted imaging, diffusion-weighted imaging, perfusion-weighted imaging and MR angiography. Blood-brain barrier disruption was defined as post-gadolinium enhancement on T1-weighted images. USPIO was administered after day 6 MRI. USPIO enhancement ratios were defined as the ratio between USPIO-related signal volume on day 9 T1-weighted imaging (respectively T2*-weighted imaging) and day 6 diffusion-weighted imaging infarct volume. The relationship between day 6 infarct volume and the enhancement ratio was assessed using Pearson and Spearman correlation tests. RESULTS: The protocol was completed in 10 patients. Signal alterations after USPIO injection was observed in 9/10 patients on day 9 T1-weighted imaging and in 5/10 patients on day 9 T2*-weighted imaging. USPIO-related MRI enhancement was heterogeneous. Lesion volume on day 6 diffusion-weighted imaging had no impact on USPIO enhancement at day 9 according to the Pearson correlation test (P=0.39) or Spearman test (P=0.25). There was no relationship between blood-brain barrier disruption and USPIO enhancement. CONCLUSIONS: USPIO MRI enhancement is heterogeneous and not clearly related to subacute lesion volume.

Oral presentation bias: a retrospective cohort study.

The aim of this paper was to assess oral presentation bias at a national level. This was a retrospective cohort study with initial characteristics of the approved protocols extracted from the committee's archives, and follow-up characteristics obtained from a questionnaire mailed to the principal investigators. A representative sample of French research ethics committees (25/48), the only committees legally endorsed for ethical authorisation in biomedical research, were studied. All completed research protocols, which had been approved in 1994 by these committees, were included. Initial characteristics (design, study size, investigator) of completed studies and follow-up information (direction of results, rates of publication and rates of oral presentation) were collected. Complete information on results and their dissemination was available for 248 completed non-confidential protocols. Half of these (49%) were declared as orally presented. The observed ranking for strategies to disseminate results was the following: orally presented and published, published only, neither orally presented nor published and orally presented only. Confirmatory results were more often orally presented, with an adjusted OR of 6.4 (95% CI 2.69 to 15.22). Other associated variables are the following: national/international scope of the study, protocol writer's university status, adverse events and interim analysis. There is a trend to submit or accept confirmatory results for oral presentations: meetings are a biased representation of research, and oral presentation bias could even be higher than publication bias.

Microvascular decompression for primary trigeminal neuralgia: long-term effectiveness and prognostic factors in a series of 362 consecutive patients with clear-cut neurovascular conflicts who underwent pure decompression.

OBJECT: The purpose of this study was to evaluate the long-term efficacy of microvascular decompression (MVD) and to identify the factors affecting outcome in patients treated for primary trigeminal neuralgia (TN). Only the cases with a clear-cut neurovascular conflict (vascular contact and/or compression of the root entry zone of the trigeminal nerve) found at surgery and treated with "pure" MVD (decompression of the root without any additional lesioning or cutting of the adjacent rootlets) were retained. METHODS: The study included 362 patients who were followed up over a period of 1 to 18 years (median follow-up 7.2 years). A Kaplan-Meier survival analysis was generated at 1 and 15 years of follow-up for all of the considered factors. According to Kaplan-Meier analysis, the success rate (defined as pain-free patients without any medication) was 91% at 1 year and estimated to be 73.38% after 15 years of follow-up. RESULTS: None of the following patient-related factors played any significant role in prognosis: sex, patient age at surgery, history of systemic hypertension, duration of neuralgia before surgery, or history of failed trigeminal surgery. Patients with atypical neuralgia (a baseline of permanent pain) had the same outcome as those with a typical (purely spasmodic) presentation. In addition, the side and topography of the trigeminal nerve did not play a role, whereas involvement of all three divisions of the nerve had a negative effect on outcome. Concerning anatomical factors, neither the type of the compressive vessel nor its location along or around the root was found to be significant. However, the severity of compression was important-the more severe the degree of compression, the better the outcome (p = 0.002). The authors also found that presence of focal arachnoiditis had a negative influence on outcome (p = 0.002). CONCLUSIONS: Pure MVD can offer patients affected by a primary TN a 73.38% probability of long-term (15 years) cure of neuralgia. The presence of a clear-cut and marked vascular compression at surgery (and possibly-although not yet reliably--on preoperative magnetic resonance imaging) is the guarantee of a higher than 90% success rate.

Subsequent skin cancers in kidney and heart transplant recipients after the first squamous cell carcinoma.

BACKGROUND: The increased incidence of skin cancers in transplant patients is well documented; however, few data exist on the risk of subsequent skin tumors in a given patient after the first skin cancer. The aim of this study was to compare the individual rate of subsequent skin cancers in kidney (KTR) and heart transplant recipients (HTR) after the first squamous cell carcinoma (SCC) and to assess risk factors for tumor multiplicity. METHODS: In all, 188 patients (121 KTR/67 HTR) were studied for up to 5 years. The cumulative number of SCC, basal cell carcinomas, Bowen's diseases, premalignant keratoses, and keratoacanthomas was recorded yearly after the first SCC. RESULTS: Overall, 71% of patients developed 757 new skin tumors. At 5 years, 100% of HTR and 88% of KTR had presented new tumors. However, the mean number of all tumors was significantly higher in KTR (3.4 vs. 2.0, 4.8 vs. 2.6, 6.6 vs. 2.9, 8.5 vs. 3.5, and 9.7 vs. 4.6 at 1, 2, 3, 4, and 5 years, respectively). Transplantation before 1984, multiple tumors at first consultation, eye and hair color, and skin type were predictive of multiple tumors. Early minimization of immunosuppression and of sun exposure tended to be associated with a reduced rate of all tumors and of SCC, respectively. CONCLUSIONS: Although the proportion of HTR developing new tumors is greater as compared with KTR, the mean number of tumors per patient is higher in KTR. This could be due to a longer immunosuppression in patients younger at transplantation.

Reducing contamination when removing and storing corneas: a multidisciplinary, transversal, and environmental approach.

PURPOSE: The combination of a shortage of cornea grafts in France and a national average contamination rate of 9% to 10%, has led us to search for the origins of this contamination. The objective of our study was to reduce the number of unusable grafts resulting from contamination of corneas in organ culture. METHODS: An external audit was carried out by an independent pharmacist on the removal conditions and treatment procedures for corneas. An environmental study was carried out, consisting of microbiological sampling of the corneas of donors who just died (<24 hours) as well as water and air samples in the premises used for removal. The Cornea Bank's procedures were submitted to a microbiological risk analysis using the "failure mode effects and criticity analysis" (FMECA) method. RESULTS: The critical contamination periods were found to be before removal, during mortuary washing and during decontamination of the conjunctival cul-de-sac at the removal stage. The corrective measures taken have reduced contamination rates by half in 1 year. CONCLUSION: Highlighting the sources of contamination has led to the implementation of effective targeted and low-cost measures that have allowed us to reduce significantly the number of cornea graft losses as a result of bacterial and fungal contamination.

Impact of funding on biomedical research: a retrospective cohort study.

BACKGROUND: Public funding is aimed at facilitating the initiation, completion and publication of research study protocols. However, no evaluation is made to investigate the impact of grant success on the conduct of biomedical research. It is therefore of great interest to compare the fate of funded protocols versus not funded: Are they initiated? Are they completed? Did the results confirm the hypothesis? Were they published? The objective was to investigate the fate of protocols submitted for funding, whether they were funded or not. METHODS: Retrospective cohort study of protocols submitted for funding to the Greater Lyon regional scientific committee in 1997. Initial characteristics of protocols (design, study size, investigator status) were abstracted from archives, and follow-up characteristics (initiation, completion and publication) from a mailed questionnaire to the principal investigators. RESULTS: Among the 142 submitted protocols, follow-up information was available for 114 (80%). As a whole, 38% of studies were funded by the Greater Lyon research committee. The rate of initiation varied from 62% for studies with no acknowledged funding to 100% for studies with both committee and other simultaneous funding. When initiated, the rate of completion was 62% for studies with at least one funding and 40% for studies without acknowledged funding. When completed, publication was reached for 77% of studies with either committee or external funding, for 58% of studies without acknowledged funding and for 37% of studies with both committee and external funding. CONCLUSION: Some protocols submitted for funding were initiated and completed without any funding declared. To our understanding this mean that not all protocols submitted really needed funding and also that health care facilities are unaware that they implicitly financially support and pay for biomedical research.

Optimization and characterization of an engineered human skin equivalent.

Skin equivalents (SEs) have been designed to meet both basic and applied research needs. The successful application of tissue-engineered SEs requires that the reconstituted tissues be endowed with the correct organization and function. A large body of experimental evidence now supports the notion that the inducing effects of mesenchymal tissue on epithelial cell morphogenesis are mediated, at least in part, by extracellular matrix components in addition to cell-cell interactions. A coculture model including both fibroblasts and keratinocytes was used to study the effects of progressive serum reduction on epidermal differentiation, quality of dermal and dermal-epidermal junctions, and expression of extracellular matrix proteins. The cells were successively added to a dermal substrate composed of collagen, glycosaminoglycans, and chitosan. The main aim of this study was to optimize this model for pharmacotoxicological trials. Control skin equivalents were cultured with medium containing 10% serum throughout the production process. Serum content was reduced to 1 and 0% at the air-liquid interface and compared with control skin equivalents. First, we demonstrated that serum deprivation at the air-liquid interface improves keratinocyte terminal differentiation. Second, we showed that, in the absence of serum, the specific characteristics of the SE are maintained, including epidermal and dermal ultrastructure, the expression of major dermal extracellular matrix components (human collagen types I, III, and V, fibronectin, elastin, and fibrillin 1), and the dermal-epidermal junction (laminin, human type IV collagen, alpha6 integrin). Furthermore, our results indicate that coculture models using keratinocytes and fibroblasts have both morphological and functional properties required for biologically useful tissues.

The activity of French research ethics committees and characteristics of biomedical research protocols involving humans: a retrospective cohort study.

BACKGROUND: Clinical trials throughout the world must be evaluated by research ethics committees. No one has yet attempted to clearly quantify at the national level the activity of ethics committees and describe the characteristics of the protocols submitted. The objectives of this study were to describe 1) the workload and the activity of Research Ethics Committees in France, and 2) the characteristics of protocols approved on a nation-wide basis. METHODS: Retrospective cohort of 976 protocols approved by a representative sample of 25/48 of French Research Ethics Committees in 1994. Protocols characteristics (design, study size, investigator), number of revisions requested by the ethics committee before approval, time to approval and number of amendments after approval were collected for each protocol by trained research assistant using the committee's files and archives. RESULTS: Thirty-one percent of protocols were approved with no modifications requested in 16 days (95% CI: 14-17). The number of revisions requested by the committee, and amendments submitted by the investigator was on average respectively 39 (95% CI: 25-53) and 37 (95% CI: 27-46), per committee and per year. When revisions were requested, the main reasons were related to information to the patient (28%) and consent modalities (18%). Drugs were the object of research in 68% of the protocols examined. The majority of the research was national (80%) with a predominance of single-centre studies. Workload per protocol has been estimated at twelve and half hours on average for administrative support and at eleven and half hours for expertise. CONCLUSION: The estimated workload justifies specific and independent administrative and financial support for Research Ethics Committees.

Effect of venous drainage site on insulin action after simultaneous pancreas-kidney transplantation.

BACKGROUND: The aim of the present study was to determine the influence of the venous drainage site on insulin homeostasis in simultaneous pancreas-kidney (SPK) transplant recipients. METHODS: The study included 12 SPK patients with portal venous drainage (P) and 11 SPK patients with systemic venous drainage (S) of pancreas allograft. All of the participants presented similar characteristics. The euglycemic hyperinsulinemic clamp was performed using a 0.4-mU/kg/min insulin infusion. An infusion of [6,6-(2)H2] glucose was used to determine glucose turnover at the basal state and during the clamp to determine liver and peripheral tissue sensitivity to insulin. RESULTS: Minor changes in glycemia and insulinemia were shown: fasting plasma glucose was significantly higher in the SPK-P group and insulinemia was higher in the SPK-S group. Hepatic glucose production was similar in both groups. During the clamp, insulin levels were higher in SPK-S recipients, but hepatic glucose production was suppressed in both groups. Glucose use was lower in SPK-S recipients than in SPK-P recipients, 3.32 +/-1.41 mg/kg/min and 4.70 +/-1.64 mg/kg/min, respectively (P<0.02). Basal and under-clamp free fatty acid levels were similar. In addition, no significant difference in cholesterol and low-density lipoprotein levels was shown, whereas high-density lipoprotein levels were higher in the SPK-S group; triglycerides during fasting and under clamp were significantly higher in the SPK-P group. CONCLUSIONS: In both groups, neither hepatic nor peripheral insulin resistance was detected. In SPK-S recipients, the authors have showed only a lower insulin clearance and a slight decreased peripheral responsiveness to insulin without modifications of lipid status.

Influenza burden in children newborn to eleven months of age in a pediatric emergency department during the peak of an influenza epidemic.

BACKGROUND: The aim of this study was to determine the burden of influenza-related diseases in children 0 to 11 months of age during the peak of the 2001 to 2002 influenza epidemic. METHODS: This was a prospective study at the Pediatric Emergency Department of Edouard Herriot tertiary teaching hospital in Lyon, France. The study included 304 infants 0 to 11 months of age. Consecutive patients were systematically enrolled during the 4 weeks of the influenza epidemic peak (Weeks 3 to 6, 2002). Influenza viruses were detected by antigen detection and virus culture from nasal swabs. Structured telephone interviews were conducted on Days 8 and 15 after virus detection. There was also a 6-month survey into the medicoadministrative database to detect late complications that required delayed hospitalization of influenza-positive children. RESULTS: Influenza virus was detected in 99 (33%) of 304 patients (A/H3N2 in 30% and B in 3%). Nonrespiratory symptoms were the dominant clinical manifestations in 30% of influenza-positive children. One child with influenza presented with febrile seizures. Twenty (20%) children with influenza were hospitalized. Parents reported recovery from the illness in 63 and 94% of children on Days 8 and 15, respectively. The median length of an influenza episode was 8 days. CONCLUSIONS: Our results confirm the high prevalence of influenza-related morbidity in infants during the epidemic peak. One child in three consulting to the pediatric emergency room had a virologically confirmed influenza infection regardless of the body temperature. Every fifth child with influenza was admitted to hospital, which corresponds to an admission rate of 237 per 100 000 children 0 to 11 months of age.

Risk factors for piperacillin/tazobactam-resistant Escherichia coli in ICU patients: a clinical study.

OBJECTIVE: To determine risk factors of infections with piperacillin/tazobactam-resistant Escherichia coli in critical care patients. DESIGN: Prospective, consecutive sample survey study. SETTING: Surgical intensive care unit (ICU) in a university hospital. PATIENTS: A consecutive series of 133 patients from whom culture results were positive for E. coli during their ICU stay. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Multivariate logistic regression analysis identified the following significant independent factors associated with the emergence of a piperacillin/tazobactam-resistant Escherichia coli: prior use of amoxicillin (odds ratio, 4.15) and amoxicillin/clavulanate (odds ratio, 3.25). CONCLUSIONS: Treatment with amoxicillin or amoxicillin/clavulanate is a major risk factor for the detection of piperacillin/tazobactam-resistant E. coli in ICU patients.

[The interest of a short-lived orientation unit in a department of internal medicine]. / Intérêt d'un secteur d'orientation courte dans un service de médecine interne.

OBJECTIVE: To assess the activity of a short-lived orientation unit (SLO) with 9 beds that only receives patients from the emergency department in whom diagnosis and/or specific treatment must be set-up while awaiting a vacant bed in the appropriate medical department. METHODS: During the 29 months after the creation of the SLO (Feb. 2001 to June 2003), we analysed the parameters supplied every month by the medical computer department: number of patients hospitalized in the SLO, age, gender, principle diagnosis according to the PMSI coded data, duration of hospitalisation, number of deaths, number of releases direct to home, number of transfers to a specialized unit and qualification of the referral units. RESULTS: 1840 patients (mean age: 73 years) were hospitalized in this unit. The most frequent diseases were bronchopneumonia (16%), syncope episode (14%), cerebral stroke (12%), thromboembolic diseases (11%) and heart failure (10%). The mean duration of hospitalization was 3.7 days (less than 48 hours in 46% of cases). In 40% of cases, patients were able to return directly to their homes. In 62% of cases, the patients were referred to a specialised unit within 48 hours. The functioning of the SLO has various specificities (repeated personalised telephone contacts, letters for rapid transfer, difficult co-operation with certain departments...). CONCLUSION: The SLO is useful for patients since it accelerates their adapted management and allows quick transfer to the unit adapted to their pathology, permitting correct adequation between the pathologies of the patients and the competence of the specialised medical unit.