Cost of exome analysis in patients with intellectual disability: a micro-costing study in a French setting.

BACKGROUND: With the development of next generation sequencing technologies in France, exome sequencing (ES) has recently emerged as an opportunity to improve the diagnosis rate of patients presenting an intellectual disability (ID). To help French policy makers determine an adequate tariff for ES, we aimed to assess the unit cost per ES diagnostic test for ID from the preparation of the pre-analytical step until the report writing step and to identify its main cost drivers. METHODS: A micro-costing bottom-up approach was conducted for the year 2018 in a French setting as part of the DISSEQ study, a cost-effectiveness study funded by the Ministry of Health and performed in collaboration with the GAD (Génétique des Anomalies du Développement), a genetic team from the Dijon University Hospital, and a public sequencing platform, the Centre National de Recherche en Génomique Humaine (CNRGH). The analysis was conducted from the point of view of these two ES stakeholders. All of the resources (labor, equipment, disposables and reagents, reusable material) required to analyze blood samples were identified, collected and valued. Several sensitivity analyses were performed. RESULTS: The unit nominal cost per ES diagnostic test for ID was estimated to be €2,019.39. Labor represented 50.7% of the total cost. The analytical step (from the preparation of libraries to the analysis of sequences) represented 88% of the total cost. Sensitivity analyses suggested that a simultaneous price decrease of 20% for the capture kit and 50% for the sequencing support kit led to an estimation of €1,769 per ES diagnostic test for ID. CONCLUSION: This is the first estimation of ES cost to be done in the French setting of ID diagnosis. The estimation is especially influenced by the price of equipment kits, but more generally by the organization of the centers involved in the different steps of the analysis and the time period in which the study was conducted. This information can now be used to define an adequate tariff and assess the efficiency of ES. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT03287206 on September 19, 2017.

Cost-effectiveness analysis of resorbable biosynthetic mesh in contaminated ventral hernia repair.

BACKGROUND: The aim of this study was to compare, in terms of cost and serious complications, the use of biosynthetic resorbable parietal mesh with biologic mesh in patients undergoing contaminated ventral hernia repair (modified Ventral Hernia Working Group grade 3). Poly-4-hydroxy-butyrate (P4HB) biosynthetic mesh has rarely been the subject of comparative studies in the context of contamination. Data are required to confirm the effects of a transition from biological mesh to biosynthetic resorbable mesh. PATIENTS AND METHODS: A cost-effectiveness analysis was conducted. It was based on a decision analysis model built with clinical and economic data issued from a before-after study that included 94 patients hospitalized for ventral hernia repair at the University Hospital of Strasbourg (France) from June 2011 to February 2018. The effectiveness endpoint was the number of patients presenting with a serious specific complication or a general complication at 6 months. Data for surgical hospitalization stays, home hospitalizations and ambulatory care costs were included. RESULTS: We found fewer serious complications with biosynthetic mesh: 21% versus 33% with biologic mesh. A cost savings of US $5146 was determined. Deterministic sensitivity analyses and a probabilistic analysis confirmed our findings and the robustness of the model. CONCLUSION: P4HB biosynthetic resorbable mesh appeared to be the most effective and the least costly option. Additional data will be needed to confirm the superiority of biosynthetic mesh in terms of the recurrence risk reduction over a longer period.

Incidental findings in a series of 2500 gene panel tests for a genetic predisposition to cancer: Results and impact on patients.

With next generation sequencing, physicians are faced with more complex and uncertain data, particularly incidental findings (IF). Guidelines for the return of IF have been published by learned societies. However, little is known about how patients are affected by these results in a context of oncogenetic testing. Over 4 years, 2500 patients with an indication for genetic testing underwent a gene cancer panel. If an IF was detected, patients were contacted by a physician/genetic counsellor and invited to take part in a semi-structured interview to assess their understanding of the result, the change in medical care, the psychological impact, and the transmission of results to the family. Fourteen patients (0.56%) were delivered an IF in a cancer predisposition gene (RAD51C, PMS2, SDHC, RET, BRCA2, CHEK2, CDKN2A, CDH1, SUFU). Two patients did not collect the results and another two died before the return of results. Within the 10 patients recontacted, most of them reported surprise at the delivery of IF, but not anxiety. The majority felt they had chosen to obtain the result and enough information to understand it. They all initiated the recommended follow-up and did not regret the procedure. Information regarding the IF was transmitted to their offspring but siblings or second-degree relatives were not consistently informed. No major adverse psychological events were found in our experience. IF will be inherent to the development of sequencing, even for restricted gene panels, so it is important to increase our knowledge on the impact of such results in different contexts.

Universal test and treat in relation to HIV disease progression: results from a stepped-wedge trial in Eswatini.

OBJECTIVES: Universal test and treat (UTT) is recommended for people living with HIV (PLHIV) to reduce morbidity/mortality and minimize transmission. However, concerns exist that this strategy may lead to more crowded hospitals, longer wait times and poorer service, adversely impacting health outcomes for clients with severe disease. We assessed how UTT was related to markers of disease progression in PLHIV overall and specifically among clients with low CD4 count/high World Health Organization (WHO) stage. METHODS: The analysis was conducted using data from a stepped-wedge trial of UTT in 14 government-managed health facilities in Eswatini from 2014 to 2017. Disease progression was defined as CD4 count falling below 200 cells/µL or baseline value, > 10% weight loss, body mass index (BMI) dropping below 18.5, incident tuberculosis (TB) or HIV-related death; these outcomes also were assessed individually. We assessed multivariate Cox proportional hazard models overall and specifically among clients with CD4 count < 350 cells/µL or WHO stage 3-4 at enrolment. RESULTS: Eight hundred and seven of 3176 clients demonstrated at least one marker of disease progression over 2339 person-years of follow-up. Overall, 62.4% of clients were female; 57.2% were < 35 years old. Compared to clients not exposed to UTT, those exposed to UTT had a lower rate of disease progression overall [adjusted hazard ratio (aHR) 0.60; 95% confidence interval (CI) 0.46-0.78] and a lower rate of CD4 decline (aHR 0.40; 95% CI 0.27-0.58). When the analysis was limited to clients with CD4 count < 350 cells/µL or WHO stage 3-4, UTT was not associated with disease progression (aHR 0.92; 95% CI 0.66-1.29). CONCLUSIONS: UTT reduced HIV disease progression overall and was not detrimental for clients with more severe disease.

Mortality under early access to antiretroviral therapy vs. Eswatini's national standard of care: the MaxART clustered randomized stepped-wedge trial.

OBJECTIVES: Current WHO guidelines recommend the treatment of all HIV-infected individuals with antiretroviral therapy (ART) to improve survival and quality of life, and decrease infection of others. MaxART is the first implementation trial of this strategy embedded within a government-managed health system, and assesses mortality as a secondary outcome. Because primary findings strongly supported scale-up of the 'treat all' strategy (hereafter Treat All), this analysis examines mortality as an additional indicator of its impact. METHODS: MaxART was conducted in 14 Eswatinian health clinics through a clinic-based stepped-wedge design, by transitioning clinics from then-national standard of care (SoC) to the Treat All intervention. All-cause, disease-related, and HIV-related mortality were analysed using the Cox proportional hazards model, censoring SoC participants at clinic transition. Median follow-up time among study participants was 292 days. There were 36/2034 deaths in SoC (1.77%) and 49/1371 deaths in Treat All (3.57%). RESULTS: Between September 2014 and August 2017, 3405 participants were enrolled. In SoC and Treat All interventions, respectively, the multivariable-adjusted 12-month all-cause mortality rates were 1.42% [95% confidence interval (CI): 0.66-2.17] and 1.60% (95% CI: 0.78-2.40), disease-related mortality rates were 1.02% (95% CI: 0.40-1.64) and 1.10% (95% CI: 0.46-1.73), and HIV-related mortality rates were 1.03% (95% CI: 0.40-1.65) and 0.99% (95% CI: 0.40-1.58). Treat All had no impact on all-cause [hazard ratio (HR) = 1.12, 95% CI: 0.58-2.18, P = 0.73], disease-related (HR = 1.04, 95% CI: 0.52-2.11, P = 0.90), or HIV-related mortality (HR = 0.93, 95% CI: 0.46-1.87, P = 0.83). CONCLUSION: There was no immediate benefit of the Treat All strategy on mortality, nor evidence of harm. Longer follow-up of participants is needed to establish long-term consequences.

Secondary findings from whole-exome/genome sequencing evaluating stakeholder perspectives. A review of the literature.

With the development of next generation sequencing, beyond identifying the cause of manifestations that justified prescription of the test, other information with potential interest for patients and their families, defined as secondary findings (SF), can be provided once patients have given informed consent, in particular when therapeutic and preventive options are available. The disclosure of such findings has caused much debate. The aim of this work was to summarize all opinion-based studies focusing on SF, so as to shed light on the concerns that this question generate. A review of the literature was performed, focusing on all PubMed articles reporting qualitative, quantitative or mixed studies that interviewed healthcare providers, participants, or society regarding this subject. The methodology was carefully analysed, in particular whether or not studies made the distinction between actionable and non-actionable SF, in a clinical or research context. From 2010 to 2016, 39 articles were compiled. A total of 14,868 people were interviewed (1259 participants, 6104 healthcare providers, 7505 representatives of society). When actionable and non-actionable SF were distinguished (20 articles), 92% of respondents were keen to have results regarding actionable SF (participants: 88%, healthcare providers: 86%, society: 97%), against 70% (participants: 83%, healthcare providers: 62%, society: 73%) for non-actionable SF. These percentages were slightly lower in the specific situation of children probands. For respondents, the notion of the «patient's choice¼ is crucial. For healthcare providers, the importance of defining policies for SF among diagnostic lab, learning societies and/or countries is outlined, in particular regarding the content and extension of the list of actionable genes to propose, the modalities of information, and the access to information about adult-onset diseases in minors. However, the existing literature should be taken with caution, since most articles lack a clear definition of SF and actionability, and referred to hypothetical scenarios with limited information to respondents. Studies conducted by multidisciplinary teams involving patients with access to results are sadly lacking, in particular in the medium term after the results have been given. Such studies would feed the debate and make it possible to measure the impact of such findings and their benefit-risk ratio.

Sinusoidal obstruction syndrome/veno-occlusive disease complication in lymphoma patients treated with oxaliplatin-based regimen: A case series report.

AIM: SOS/VOD is a relevant clinical syndrome that usually appears early after hematopoietic stem cell transplantation. The purpose of this article was to report a case series of SOS/VOD in non-susceptible patients and draw physicians' attention to the plausible relationship between liver injury and oxaliplatin-based chemotherapy, preceding autologous transplantation. METHODS: In this study, we report a case series of SOS/VOD in 4 lymphoma patients following autologous transplantation. The data were collected between July 2013 and November 2015 by analyzing patient's characteristics and outcomes. RESULTS: We noticed 4 severe cases of SOS with unusual presentations in patients who did exhibit few classical risk factors. These patients received R-DHAO before transplantation. CONCLUSIONS: Physicians need to be aware that oxaliplatin-based regimen could contribute to SOS/VOD complications in hematological patients.

[News Skin lesions : a case report of fixed drug eruption]. / Apparition soudaine de lésions cutanées : à propos d'un cas d'érythème pigmenté fixe.

Fixed drug eruption is an erythematous eruption of one or more centimetric rounded or oval lesions well demarcated, recurrent at the same place and leaving a residual purple pigmentation. Diagnosis is clinical. Skin biopsy is not essential except in doubtful cases (eg bullous drug eruption can simulate Lyell Syndrome or mucosal reminiscent of erythema multiforme). The etiology is almost always drug-induced; rare cases of toxic or food issue were reported. Histopathology is immuno-allergic; recurrences correspond to re-exposure to allergen. There is no specific treatment except stopping the causing drug.

L'érythème pigmenté fixe est une éruption érythémateuse d'une ou plusieurs lésions arrondies ou ovalaires centimétriques bien délimitées, récidivant au même endroit et laissant une pigmentation violacée résiduelle. Le diagnostic est clinique. La biopsie cutanée n'est pas indispensable sauf dans les cas douteux (exemple : érythème pigmenté bulleux pouvant simuler un Syndrome de Lyell ou une atteinte des muqueuses faisant penser à un érythème polymorphe). L'étiologie est presque toujours d'origine médicamenteuse; des rares cas de cause alimentaire ou toxique ont été rapportés. L'histopathologie est donc immuno-allergique ; les récidives correspondent à la réexposition à l'allergène. Il n'existe pas de traitement spécifique hormis l'arrêt du médicament incriminé.

[Out of addictions: Alcohol, or alcohol to alcohol]. / Sortir des addictions : à l'alcool, par l'alcool ou vers l'alcool.

Pathways from alcoholism to recovery are documented; less often are those from drug addiction to alcoholism. Biographical approaches allow analyzing how people change their uses and talk about their trajectories of recovery. METHODS: Three hundred and forty-one people (34% women) in the Paris area were questioned on their trajectories with a biographical questionnaire. Some open questions were aimed to understand the connection they made between events in their lives, how recovered they felt and what they considered strengths or obstacles. All the participants had stopped at least one product. Their mean age was 43, and 26% were over 50. STUDY OBJECTIVES: How can the differences between one substance addicts and dual abusers be explained? Can we hypothesize a better result for the patients with a single dependence to alcohol in their lives for the following two reasons? (1) They could really be taken in charge for their alcoholism whereas the dual abusers mostly receive cared for their illicit drug problems with an under estimation of their problem with alcohol. In this case, they turn to alcohol after weaning themselves from their drug dependence so as to return to a social consumption, especially when they are given an opiate treatment. (2) Conversely could we suggest that the dual substance abusers had different trajectories from their childhood (more adverse events, more social difficulties, mental health problems), and that this accumulation explains their skipping from one substance or behaviour to another without any real recovery for decades? RESULTS: All respondents were polydrug users. Eighty-two had been dependent mainly on alcohol. One hundred and twenty-one people had been drug addicts (mostly heroin), which they had stopped on average ten years before the survey. The last group included 138 persons who had been heroin or cocaine addicts and alcoholics in their lives, a third of whom had been dependent on alcohol before their drug addiction (35%), a tenth on both at the same time (10%) and more than half of the users (55%) had turned from drug addiction to alcoholism. The group concerning alcohol dependence includes the oldest participants, on average 49.7, and 55% of them were abstinent at the survey. Conversely, the group "with no alcohol dependence" had mainly turned to opiate treatments. Their histories in dependence and in various social statuses also showed a longer duration out of employment, in sickness or invalidity, or in prison, for the drug dependents as opposed to the "mainly" alcoholics. The population with dual substance abuse experienced twice as many adverse childhood events as the others (P<0.005): it was the case for 19.5% in "mainly alcohol" dependence compared to 38.4% in dual abuse. The recovery capital gave a mean score of 7.56±2.35 (median 7). A score below 6 was considered low. The score was significantly different according to the dependence groups: while 7.3% of "mainly alcohol" dependents had a score below 6, this was the case for 30.4% of the dual group (with alcohol and drugs), and 19% for the "mainly drug dependence" group. Controlling ages, sexes and groups of dependence in a logistic regression, the risk of having a recovery capital below six was more than four times higher for the dual dependents as opposed to the "mainly alcohol" dependents. CONCLUSION: Some people stay for decades in drug addiction centers switching from one dependence to another. Their alcohol drinking should be addressed earlier to prevent them from turning to drinking excessively in order to wean themselves from their drug addiction.

[Pregnancy and substance use in France: a literature review]. / Grossesse et usage de substances psychoactives en France. Synthèse de la littérature.

OBJECTIVES: Substance use during pregnancy is an important public health issue. It requires identifying at-risk populations and risk perception among women. MATERIALS AND METHODS: A literature review was conducted. It included French studies conducted since 2000 on substance use during pregnancy (tobacco, alcohol, marijuana, psychotropic drugs) and risk perception. RESULTS: In France, in 2010, 24% of pregnant women smoke--17% in the 3rd trimester. Depending on studies, the prevalence of alcohol use ranged from 12 to 63% and binge drinking ranged from 1 to 7%; daily drinking was below 0.5%. Marijuana use ranged from 1 to 3%, and psychotropic drugs ranged from 2 to 4%. Little research has been dedicated to risk perception. Studies show a lack of awareness about the equivalence of risks between fermented and distilled beverages and about the risks of moderate smoking during pregnancy. CONCLUSION: Data is lacking to characterize at-risk populations and mechanisms underlying risky behaviors.

Economic analysis of the costs associated with prematurity from a literature review.

OBJECTIVES: To analyse published cost-of-illness studies that had assessed the cost of prematurity according to gestational age at birth. METHODS: A review of the literature was carried out in March 2011 using the following databases: Medline, ScienceDirect, The Cochrane Library, Econlit and Business Source Premier, and a French Public-Health database. Key-word sequences related to 'prematurity' and 'costs' were considered. Studies that assessed costs according to the gestational age (GA) at the premature birth (<37 weeks of gestation) in industrialized countries and during the last two decades were included. Variations in the reported costs were analysed using a check-list, which allowed the studies to be described according to several methodological and contextual criteria. RESULTS: A total of 18 studies published since 1990 were included. According to these studies, costs were assessed for different follow-up periods (short, medium or long-term), and for different degrees of prematurity (extreme, early, moderate and late). Results showed that whatever the follow-up period, costs correlated inversely with GA. They also showed considerable variability in costs within the same GA group. Differences between studies could be explained by the choices made, concerning i/the study populations, ii/contextual information, iii/and various economic criteria. Despite these variations, a global trend of costs was estimated in the short-term period using mean costs from four American studies that presented similar methodologies. Costs stand at over US$ 100,000 for extreme prematurity, between US$ 40,000 and US$ 100,000 for early prematurity, between US$ 10,000 and US$ 30,000 for moderate prematurity and below US$ 4500 for late prematurity. CONCLUSION: This review underlined not only the clear inverse relationship between costs and GA at birth, but also the difficulty to transfer the results to the French context. It suggests that studies specific to the French health system need to be carried out.

Diagnostic yield of a one sample immunochemical test at different cut-off values in an organised screening programme for colorectal cancer.

BACKGROUND: Quantitative immunochemical faecal occult blood tests have become the recommended tests for colorectal cancer screening. The aim of this study was to complete our knowledge on the performance of one of the quantitative immunochemical tests available, FOB-Gold, and to propose a possible strategy for an organised screening programme. PATIENTS AND METHODS: Within the French organised screening programme, 23,231 average-risk individuals, aged 50-74 performed both a 3-day Hemoccult test and a 1-day FOB-Gold test. Performances of the immunochemical test were evaluated at different cut-off levels. RESULTS: The positivity rate for the Hemoccult was 2.1% and for the FOB-Gold varied between 4.6% (cut-off value of 100 ng/mL, the lowest studied cut-off) and 2.1% (cut-off value of 352 ng/mL). The number of colonoscopies decreased with increasing cut-off values by 21.5% (150 ng/mL), 35.4% (200 ng/mL) and 53.3% (352 ng/mL). The corresponding miss rate for CRC was respectively 6.4%, 11.1% and 22.2%, and for advanced adenoma respectively 16.3%, 29.2% and 43.6%. Compared with the reference cut-off for the FOB-Gold (100 ng/mL) the miss rate for Hemoccult was 53% for CRC and 77% for advanced adenoma. CONCLUSION: The study suggests that in countries with colonoscopy facilities compatible with a screening test positivity rate of up to 5%, use of a 1-day test with a cut-off value between 100 and 150 ng/mL could be the recommended strategy. Further increasing the cut-off value up to the same positivity rate as Hemoccult could be used in areas with limited access to colonoscopy.

[Retrospective analysis of neonatal data in a monocentric cohort of 170 newborns of polydrug-using mothers, Île-de-France, 1999-2008]. / Analyse rétrospective des données de 170 nouveau-nés de mères consommatrices de substances psychoactives.

OBJECTIVES: To analyze neonatal morbidity in a single-center retrospective cohort (1999-2008) according to the mothers' polydrug use and to the social and demographic context. MATERIAL AND METHODS: One hundred and seventy newborns were identified whose mothers used two or more substances (such as heroin, cocaine, opioid maintenance treatment, tobacco, alcohol, hashish, amphetamines, benzodiazepines, or other psychotropics) at the beginning of their pregnancies. The database included 168 sociodemographic variables describing mothers' living conditions and their drug-abuse characteristics; perinatal variables such as gestational age, weight, neonatal abstinence syndrome, and modalities of discharge; and correlations with the main neonatal morbidities. RESULTS: The mothers' mean age at delivery was 31.6yrs. It was the first pregnancy for 35.2% of the mothers but the mean number of previous abortions was 1.14 and 16.3% already had previous children in foster care. At delivery only 8.2% used only one product, 52.9% 2 or 3 products, and 37.6% four or more substances. All sociodemographic variables, the deprivation score, the number of previous abortions and miscarriages, and poor prenatal monitoring were significantly different for the mothers using four products or more. The uses changed along the years of study: fewer mothers used heroin but more used hashish, combined with other substances. The medical care also changed: greater participation on the part of mothers in neonatal care, more frequent breastfeeding, less medication for neonatal abstinence syndrome with the same severity score: i.e., 45.5% of infants with a Lipsitz score between 8 and 12 received a morphine treatment in 1999-2000 versus only 5.5% in 2005-2006 and none in 2007-2008. The mean gestational age was 38.1weeks. Preterm births (22.2%) and intrauterine growth restriction (18% with birth weight <10th percentile) were mainly correlated with the number of substances at delivery (17.3% preterm if three substances or less and 31.3% if four substances or more; p<0.001), social deprivation, poor prenatal care, and mothers having gained less than 5kg in weight during pregnancy (57.1% of intrauterine growth restriction versus 14.5%). Birth weight, height, and head circumference were significantly different for mothers having drunken alcohol. Among the newborns, seven showed complete fetal alcohol syndrome. The neonatal abstinence syndrome severity (23% with a Lipsitz score>9, one-quarter of whom were medicated with morphine) was correlated with an in-utero exposure to opiates, mainly in combination with benzodiazepines, and with the use of four or more substances. The mean age of infants at discharge was 18.1days (SD 3.39): 21.1% stayed 30 days or more in the hospital, mainly because of prematurity or intrauterine growth restriction, a high neonatal abstinence syndrome score, maternal polydrug use, psychosocial deprivation, or foster care placement decisions. Decisions for foster care placement (15%) applied to polydrug users, with social deprivation, undermonitored pregnancies, or bonding difficulties. CONCLUSION: The main factors correlated with poor neonatal results were polydrug use, maternal psychiatric pathologies, and social deprivation. Overall, prenatal and postnatal care such as rooming-in improved the results.

[Maternal and obstetrical data in a retrospective cohort of 170 newborns from polydrug using mothers, in the Paris area, 1999-2008]. / Analyse des données maternelles et obstétricales dans une cohorte rétrospective de 170 nouveau-nés de mères polyconsommatrices, Île-de-France, 1999-2008.

OBJECTIVES: Polydrug use in pregnancy is harmful. This survey aimed to explore the issue of the associations of substances during pregnancy and to determine the consumer profiles. PATIENTS AND METHODS: One hundred and seventy newborns whose mothers were psychoactive substances users were identified over the period 1999 to 2008. The data relating to maternal consumption, their reproductive history, and their living environment were collated. RESULTS: At the end of their pregnancy, the mothers reported using on average 3.14 substances. Three profiles were determined: 65 women were heroin users or had consumed it in their lifetime and were currently on substitution treatment, and had a very unfavourable social living environment; 30 women were mainly consumers of alcohol, with or without benzodiazepines or other psychotropic drugs, and had a history of abortions; 75 women were mainly tobacco and cannabis smokers, with or without substitution treatment, had good social living conditions and had wanted the pregnancy. CONCLUSION: Polydrug use increases the risk for the women to avoid prenatal care and is often linked with a history of abortions.

[Consequences for the newborn of alcohol consumption during pregnancy]. / Conséquences, pour l'enfant à naître, du maintien de la consommation d'alcool pendant la grossesse.

BACKGROUND: This paper aims at showing the immediate and long-term consequences affecting newborns whose mothers did not reduce or stop their consumption of alcohol when they were pregnant; these women were chosen among women who also used psychoactive substances. METHODS: A retrospective cohort was constituted of babies who were found to have been exposed in utero to one or more legal or illegal psychoactive substance(s) and who were born or hospitalized between 1999 and 2008 in a hospital near Paris. Among the cohort of 170 babies, 56 had mothers who had not modified their alcohol consumption when they were pregnant, 30 had mothers who had reduced their alcohol consumption, and 84 had mothers who declared having been abstinent. RESULTS: The babies born to mothers who did not modify their alcohol consumption when pregnant were more likely to be premature (30%) and hospitalized in the neonatology hospital unit (60.7%). They needed specific care for durations significantly longer than the babies exposed in utero to other psychoactive substances (P<0.005). They were more often diagnosed with fetal alcohol spectrum disorders (18%) and placed in a foster family (18%). CONCLUSION: Given the negative consequences on the babies born to mothers who do not modify their alcohol consumption when pregnant, these mothers should be identified and provided with better care. The successful strategies for early therapeutic interventions used in other countries should be studied as examples. This would make it possible to reduce the enormous financial, material and human costs that are a direct consequence of alcohol consumption during pregnancy.

Pharmacological prevention of sevoflurane- and desflurane-related emergence agitation in children: a meta-analysis of published studies.

BACKGROUND: Emergence agitation (EA) in children is increased after sevoflurane anaesthesia. The efficacy of prophylactic treatment is controversial. The aim of this study was to provide a meta-analysis of the studies of the pharmacological prevention of EA in children. METHODS: A comprehensive literature search was conducted to identify clinical trials that focused on the prevention of EA in children anaesthetized with sevoflurane, desflurane, or both. The data from each trial were combined using the Mantel-Haenszel model to calculate the pooled odds ratio (OR) and 95% confidence interval. I(2) statistics were used to assess statistics heterogeneity and the funnel plot and the Begg-Mazumdar test to assess bias. RESULTS: Thirty-seven articles were found which included a total of 1695 patients in the intervention groups and 1477 in the control ones. Midazolam and 5HT(3) inhibitors were not found to have a protective effect against EA [OR=0.88 (0.44, 1.76); OR=0.39 (0.12, 1.31), respectively], whereas propofol [OR=0.21 (0.16, 0.28)], ketamine [OR=0.28 (0.13, 0.60)], alpha(2)-adrenoceptors [OR=0.23 (0.17, 0.33)], fentanyl [OR=0.31 (0.18, 0.56)], and peroperative analgesia [OR=0.15 (0.07, 0.34)] were all found to have a preventive effect. Subgroup analysis according to the peroperative analgesia given does not affect the results. CONCLUSIONS: This meta-analysis found that propofol, ketamine, fentanyl, and preoperative analgesia had a prophylactic effect in preventing EA. The analgesic properties of these drugs do not seem to have a role in this effect.

[Interest of immunohistochemic markers (Ki67, HMB45, p53) in risk analysis of congenital naevi of little and middle size]. / Intérêt des marqueurs immunohistochimiques (Ki67, HMB45, p53) dans l'analyse de risque des naevi congénitaux de petite et moyenne taille.

The risk to develop melanoma from small or medium size congenital naevus remain controversial. The main goal of the present study was to determine the interest of three immunohistochemical markers (Ki67, HMB45 and p53) in predicting malignant transformation of these congenital naevi and to see if a specific immunohistochemical profile of such transformed naevi can be identified. The markers (Ki67, HMB45 and p53) have been used retrospectively on sections of small or medium size congenital naevi (group NC, n = 15), of melanoma developed on small or medium size congenital naevi (group MNC, n = 15) and of melanoma developed on acquired naevi (group MNA, n = 15). The labelled cells have been counted in different cutaneous layers: junction, superficial dermal layer and deep dermal layer. No reactivity was observed for the three markers in group NC. The percentage of labelled cells was significantly different for the three markers between the group NC and the groups MNC and MNA. There was no difference between the groups MNC and MNA. In the groups MNC and MNA, a gradient in the percentage of labelled cells was observed between superficial and deep layers. These three markers do not differentiate melanoma developed from congenital naevi of small or medium size and melanoma developed from acquired naevi. Moreover, the results suggest that these three markers are useless in predicting the risk of malignant transformation of small or medium size congenital naevi.

[Obstetrical and pediatric impact of in utero cocaine exposure]. / Conséquences obstétricales et pédiatriques de la consommation de cocaïne pendant la grossesse.

Review of recent publications about perinatal consequences of cocaine use during pregnancy points out that: - dramatic obstetrical, neonatal and developmental abnormalities, reported during 1980-90', are less frequent in recent cohort studies; - pregnant women who use cocaine or crack, also consume other psychoactive drugs (alcohol, tobacco, benzodiazepines, cannabis, opiates, ...) and have a very chaotic life-style; so, it is difficult to distinguish abnormalities caused by cocaine per se, even with numerous cohorts, control groups and multivariate analysis.

[Alcohol and pregnancy]. / Alcool et grossesse.

Alcohol consumption during pregnancy is a major cause of mental retardation in Western countries. Fetal alcohol syndrome (FAS) is mainly characterized by pre- and postnatal stunted growth, neurocognitive disorders, and facial dysmorphism. It compromises the intellectual and behavioral prognosis of the child. Prevention tools exist, through better information of health professionals, for optimal care of high-risk women before, during, and after pregnancy, which would decrease the incidence of SAF in the future.