[Acute respiratory distress syndrome in childhood: Changing definition and news from the Pediatric Consensus Conference]. / Syndrome de détresse respiratoire aiguë de l'enfant : évolution de la définition et nouveautés de la conférence de consensus pédiatrique.

Acute respiratory distress syndrome (ARDS) is a rapidly progressive hypoxemic respiratory insufficiency induced by alveolar filling mainly caused by alveolocapillary wall disruption, following direct or indirect pulmonary injury. Much less frequent in children than in adults, pediatric intensivists had long applied adult guidelines to their daily practice. In 2015, experts from the Pediatric Acute Lung Injury Consensus Conference (PALICC) published the first international guidelines specifically dedicated to pediatric ARDS. After a short summary of the history of the ARDS definition since its first report in 1967, we describe the main diagnostic and therapeutic guidelines for PALICC.

Effectiveness of venlafaxine in patients hospitalized for major depression and melancholia.

BACKGROUND: This study was undertaken to compare the antidepressant efficacy and short-term safety of venlafaxine with those of placebo in hospitalized patients with major depression and melancholia. METHOD: Ninety-three inpatients with a minimum prestudy Montgomery-Asberg Depression Rating Scale (MADRS) score of 25 were treated for up to 4 weeks with either venlafaxine or placebo. Dosage averaged approximately 350 mg/day during Weeks 2 to 4. Efficacy and safety were assessed throughout the study. Efficacy was evaluated using the MADRS, the 21-item Hamilton Rating Scale for Depression (HAM-D), and the Clinical Global Impressions (CGI) scale. Recorded study events, vital signs and body weight measurements, laboratory determinations, physical examinations, and ECG recordings were used to assess safety. RESULTS: Venlafaxine provided significantly greater improvement in the MADRS scores after 4 days and in the HAM-D scores after 1 week than did placebo. Response rate (based on a 50% decrease in MADRS scores) was 65% (30 of 46 patients) for venlafaxine and 28% (13 of 47 patients) for placebo. Significantly more placebo-treated patients (40%; N = 19) than venlafaxine-treated patients (9%; N = 4) discontinued treatment early because of lack of efficacy. Nausea and sweating were the most common events, occurring at a significantly higher rate in the venlafaxine group. CONCLUSION: Venlafaxine is an effective and well-tolerated antidepressant in hospitalized patients with major depression and melancholia.

Methodological problems in the evaluation of drug induced sexual dysfunction for oral contraceptives.

PIP: Some oral contraceptive (OC) users experience sexual dysfunction. For example, recent studies on sexual dysfunction suggest that 0.5-1% of OC users experience a decreased libido, and 33% of them drop-out of the studies. Even though there are many OC users, researchers have not exerted much energy in studying sex al dysfunction. Sexuality surveys do not tend to yield reliable data. Researchers tend not to consider OCs as normal drugs. Thus, it is difficult to understand the link between adverse effects and OC use. Problems in studies of female sexuality revolve around assessment criteria. Clinical criteria related to female sexuality in the literature are usually decreased libido, vaginal dryness, and lack of orgasm. Yet, the studies rarely scale, standardize, or really validate the severity of these criteria. Various questionnaires used to assess female sexuality in OC users include well-being, sexual interest questionnaire, sex role behavior scale, sexual experience scale, and questions addressing sexual daydreaming and sexual fantasies. They tend to go beyond basic clinical parameters and raise more questions than they provide solid answers. To concretely compare OC users and nonusers, researchers need to obtain a baseline value on sexual activity 1 month before cases begin OC use. No large study with solid assessment criteria has yet included both comparable groups and placebo groups. Thus, both biases and confounding factors render the data unreliable. Perhaps the way to expand knowledge on OCs' relationship with female sexuality is to consider quality of life, i.e., sexuality as a parameter that can be improved or worsened. Standard studies and common methodology do not lend themselves to investigating OC use and female sexuality.^ieng

[Invasive candidiasis in neonatal intensive care units]. / Candidoses invasives en réanimation néonatale.

In the USA, the incidence of invasive candidiasis in neonates is respectively 0.3% of infants over 2500 g and up to 20% of infants less than 1000 g. Their incidence is increasing. Two populations of newborn infants are particularly vulnerable: the premature infants and newborn infants with severe neonatal digestive diseases. Fifty percent of infants hospitalized in NICU are colonized with Candida at the end of the first week of hospitalization; a direct relationship exists between the importance of colonization and the invasive infection risk. C. albicans is the species most often responsible for invasive candidiasis in the newborn. These infections represent the third cause of related-catheter infection in the USA. Mortality rate in neonates linked to this disease is 20 to 50%; morbidity primarily concerns brain and lungs. Neonatal invasive candidiasis risk factors are known and a primary prevention is possible. The diagnosis of neonatal invasive candidiasis is difficult and often delayed because of a polymorphic clinical expression. Empiric and preemptive treatment are based on the use of amphotericin B. Prophylactic treatment using fluconazole of newborns with birth weight ≤ 1000 grams and/or gestational age ≤ 27 weeks gestation is recommended by the American Academy of Paediatrics and the Infectious Diseases Society of America. A better knowledge of French epidemiological data in this area would improve both the diagnosis and therapeutic management of this disease.

[What non invasive haemodynamic assessment in paediatric intensive care unit in 2009?]. / Quelle évaluation hémodynamique non invasive en réanimation pédiatrique en 2009 ?

The haemodynamic assessment of the patients is a daily activity in paediatric intensive care unit. It completes and is guided by the clinical examination. The will to develop the least invasive possible coverage of the patients is a constant concern. The haemodynamic monitoring, all the more if it is invasive, ceaselessly has to put in balance the profit and the risk of beginning this technique at a fragile patient. In the last three decades, numerous non-invasive haemodynamic tools were developed. The ideal one must be reliable, reproducible, with a time of fast, easily useful answer, with a total harmlessness, cheap and allowing a monitoring continues. Among all the existing tools (oesophageal Doppler ultrasound method, transthoracic echocardiography, NICO, thoracic impedancemetry, plethysmography, sublingual capnography), no one allies all these qualities. We can consider that the transthoracic echocardiography gets closer to most of these objectives. We shall blame it for its cost and for the fact that it is an intermittent monitoring but both in the diagnosis and in the survey, it has no equal among the non-invasive tools of haemodynamic assessment from part the quality and the quantity of the obtained information. The learning of the basic functions (contractility evaluation, cardiac output, cardiac and the vascular filling) useful for the start of a treatment is relatively well-to-do. We shall miss the absence of training in this tool in France in its paediatric and neonatal specificity within the university or interuniversity framework.

A replication-competent adenovirus assay for E1-deleted Ad35 vectors produced in PER.C6 cells.

The presence of replication-competent adenovirus (RCA) is a safety concern for biologics based on recombinant adenoviruses and RCA testing is therefore mandatory for release of clinical material. RCA, which arises from homologous recombination between Ad5 vectors and HEK-293 cells, can be eliminated by the use of PER.C6 cells in combination with a matched vector. However, little is known on RCA formation with vectors based on adenovirus serotypes other than Ad5 and reliable RCA assays to test them are generally lacking. Here we report on the development and qualification of a sensitive RCA assay for Ad35, a promising alternative to Ad5 vectors. The assay is able to detect 1 RCA in 3x10(10) vector particles with 95% confidence, thus meeting current FDA requirements, and can discriminate between RCA and other rare CPE-causing entities, including helper dependent E1 positive particles (HDEP). Using this assay, the first batches of Ad35 vectors produced in PER.C6 cells were analysed and found to be free of RCA and HDEP. Based on the statistical model used, we anticipate that our approach to RCA assay development can be broadly applicable to other adenoviral vectors.

A sensitive cell-based assay for the detection of residual infectious West Nile virus.

Ensuring complete viral inactivation is critical for the safety of vaccines based on an inactivated virus. Detection of residual infectious virus is dependent on sensitivity of the assay, sample volume analyzed and the absence of interference with viral infection. Here we describe the development and qualification of a sensitive cell-based assay for the detection of residual infectious West Nile Virus (WNV). The results of the assay are in good agreement with the assumption that at low concentrations the number of infectious units in relatively small samples follows a Poisson distribution. The assay can detect 1 infectious unit with a confidence of 99%, provides statistical controls for interference and can easily be scaled up to test large amounts of vaccine material. Furthermore, we show equivalence in sensitivity between the cell-based assay and an in vivo assay for detection of infectious WNV. Finally, the assay has been used for successful release testing of clinical lots of inactivated WNV vaccine. Given the principle and generic setup of the method we envision broad applicability to the detection of very low concentrations of infectious virus.

The significance of circulating antiethinyl-estradiol antibodies (AEEA) in the occurrence of thrombosis in women while taking the pill.

The aim of the study was to investigate the hypothesis that oral contraceptives (OC) lead to antiethinyl-estradiol antibody (AEEA) synthesis which might in turn be responsible for the thrombo-embolic complications observed in women users. The trial included 428 women divided into a) 204 healthy female volunteers as the control group (CONT), b) 139 women who had suffered thrombo-embolic accidents (THR), c) 85 women suffering from recurrent fetal loss (RFL). In each of these three categories, 50% were pill users (OC+) and 50% were not (OC-). Specific immune markers of systemic autoimmunity and anticardiolipin antibodies were looked for, as they are thought to be present in increased amounts in thrombosis or recurrent fetal loss. The AEEA prevalence differed significantly (p less than 0.05) between the CONT OC+ (32%) and the CONT OC- (13%) women. It also differed (p less than 10(-5)) between the RFL OC+ (60%) and the RFL OC- (12%) women. It did not differ between THR OC+ (36%) and THR OC- (39%) women. Within the OC+ women, the difference between the THR and the CONT groups was not found to be significant, whereas it was found to differ significantly between the RFL and the CONT groups (odds-ratio RFL/CONT estimated at 3.20, confidence interval 1.53, 6.69). Within the OC-women, the AEEA prevalence was found to differ significantly between the THR (39%) and the CONT (13%) groups (odds-ratio THR/CONT estimated at 4.40, confidence interval 2.07, 9.38%) but not between the RFL and the CONT groups.(ABSTRACT TRUNCATED AT 250 WORDS)

A double-blind, placebo-controlled evaluation of the effects of orally administered venlafaxine on sleep in inpatients with major depression.

Venlafaxine, a member of a novel chemical class, phenethylamines, is a new antidepressant that inhibits neuronal uptake of serotonin, norepinephrine, and dopamine (in decreasing order of potency) at doses of 75 to 375 mg per day. Depression and antidepressant drugs are known to modify human sleep patterns. Our objective in this double-blind, placebo-controlled study was to assess the effects of venlafaxine on polysomnographic variables by comparing the effects of venlafaxine and placebo on sleep (hypnographic and all-night electroencephalographic [EEG] spectral analysis) and clinical measures (Hamilton Rating Scale for Depression [HAM-D], Montgomery-Asberg Depression Rating Scale [MADRS], and Clinical Global Impressions [CGI]) in inpatients with major depression (DSM-III-R). Following a 7- to 13-day placebo washout period, patients were randomly assigned to receive either placebo or venlafaxine (maximum dose 225 mg/day) for up to 29 days. Sleep evaluations took place at baseline (3 nights immediately before entering the double-blind phase), after 1 week of treatment, and after 1 month of treatment. Sleep stage parameters and all-night spectral parameters were first tested by analysis of variance for repeated measures and then, if indicated, by two-tailed Student t-test. The results on psychiatric rating scales showed improvement from baseline in both treatment groups at all time points, with improvement tending to be greater in the venlafaxine group. Venlafaxine induced a decrease of sleep continuity (decreased total sleep time and increased wake time), an important increase in the onset latency of rapid eye movement (REM) sleep, and a decrease in total REM sleep duration. All-night sleep EEG frequency structure was not modified significantly by venlafaxine treatment as compared with placebo. In conclusion, venlafaxine, despite its novel chemical structure, shows a sleep profile comparable with that of most classical antidepressants.