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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., Introduction New drugs are developed following a logical, step-by-step procedure in which findings from small early studies are used to inform and design subsequent larger studies [1]. To develop new [...]

Byline: IsmaA< Keywords: Piperacillin/tazobactam; Escherichia coli; Critical care; Infection Abstract: 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. Author Affiliation: (1) Intensive Care Unit, Edouard Herriot Hospital, Claude Bernard University, 69003, Lyon, France (2) Clinical Epidemiology Unit, Edouard Herriot Hospital, Claude Bernard University, Lyon, France Article History: Received Date: 12/07/2002 Accepted Date: 13/03/2003 Online Date: 27/05/2003

Abstract 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 Conclusions This study confirmed that level of evidence of clinical evaluation of IMDs is low and needs to be improved.

Inhaled albuterol is the most frequently used bronchodilator for acute wheezing, and nebulization is the standard mode of delivery in hospital setting. However, recent guidelines consider spacer devices as an easier to use, and cost-saving alternative and recommend the high-dose metered-dose inhaler bronchodilator. Objective. To demonstrate clinical equivalence between a spacer device and a nebulizer for albuterol administration. Design. Randomized, double-blind, parallel group equivalence trial. Setting. Pediatric emergency wards at 2 tertiary teaching hospitals. Patients. Sixty-four 12- to 60-month-old children with acute recurrent wheezing (32 per group). Interventions. Albuterol was administered through the spacer device (50 [micro]g/kg) or through the nebulizer (150 [micro]g/kg) and repeated 3 times at 20-minute intervals. Parents completed a questionnaire. Outcome Measures. Pulmonary index, hospitalization, ease of use, acceptability, and pulse oximetry saturation. Results. The 90% confidence interval of the difference between treatment groups for the median absolute changes in pulmonary index values between T0 and T60 was [-1; +1] and was included in the equivalence interval [-1.5; +1.5]. Clinical improvement increased with time. Less than 10% of the children (3 in each group) required hospitalization (2 in each group attributable to treatment failure). Parents considered administration of albuterol using the spacer device easier (94%) and better accepted by their children (62%). Conclusions. The efficacy of albuterol administered using the spacer device was equivalent to that of the nebulizer. Given its high tolerance, repeated 50 [micro]g/kg doses of albuterol administered through the spacer device should be considered in hospital emergency departments as first-line therapy for wheezing. Pediatrics 2000; 106:311-317; recurrent wheezing, asthma, preschool children, inhaled albuterol, spacer device, metered-dose inhaler, nebulizer, equivalence trial, randomized trial, acceptability., ABBREVIATIONS. ASD, asthma spacer device; MDI, metered-dose inhaler; Sa[O.sub.2], pulse oximetry saturation; I/E ratio, inspiration/expiration ratio. Inhaled albuterol is the most frequently used bronchodilator for acute wheezing, and nebulization is [...]

Conclusions: The database revealed severity factors relating to human papillomavirus (HPV) type and age at diagnosis. While not exhaustive, the database is easy to use and could serve for a European multicentre epidemiological study., Objectives: To propose a database as a starting point for a national registry and to estimate prognostic factors in recurrent respiratory papillomatosis (RRP)., Materials and Methods: This was a retrospective study carried out in a tertiary care teaching hospital. From January 2005 to July 2007, epidemiological, clinical and treatment information on patients undergoing endoscopy for RRP in the department was entered in a database. Data were collected on three forms: the first comprised information about disease history before assessment in the department, the second about the disease and its treatment in the department, and the third about evolution after treatment., Results: Data on 72 patients were entered into an RRP database between January 2005 and July 2007. In all, 82% had already been treated for RRP in a different centre; 24 had juvenile-onset (JORRP) and 48 adult-onset (AORRP) papillomatosis. Cidovir injections had been administered to 91% of the patients. Histology found nine cases of dysplasia, one of carcinoma in situ and one of invasive carcinoma. Subglottic and tracheal locations were significantly more frequent in JORRP than in AORRP, as were the maximum Derkay scores and annual numbers of endoscopies. Patients with type 11 HPV had significantly more endoscopies per year than those with type 6.

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.