Dorine Neveu

Dynamics and Clinical Evolution of Bacterial Gut Microflora in Extremely Premature Patients

OBJECTIVE To determine baseline clinical characteristics that influence bacterial gut flora dynamics in very preterm infants and the relationship between gut flora dynamics and clinical evolution. STUDY DESIGN Prospective, monocentric study enrolling 29 consecutive very preterm infants. We collected data about growth, digestive tolerance, nutrition, and antibiotic use. Microflora in stool samples, collected between 3 and 56 days of life, was identified with direct molecular fingerprinting. RESULTS Median (interquartile range) body weight and gestational age at birth were 950 g (760-1060 g) and 27 weeks (27-29 weeks), respectively. The diversity score (number of operational taxonomic units) increased 0.45 units/week (P < .0001), with staphylococci as the major group. Bifidobacterium was poorly represented. Gestational age (≥ 28 weeks) and caesarean delivery independently correlated with better diversity scores during follow-up (P < .05). The 6-week diversity score inversely correlated with the duration of antibiotherapy (P = .0184) and parenteral feeding (P = .013). The microflora dynamics was associated with the digestive tolerance profile. Weight gain increased with increasing diversity score (P = .0428). CONCLUSION Microflora diversity settled progressively in very preterm infants. Staphylococci were the major group, and few infants were colonized with Bifidobacterium spp. Measures that may improve microflora could have beneficial effects on digestive tolerance and growth.

Cumulative Exposure to Cell-Free HIV in Breast Milk, Rather Than Feeding Pattern per se, Identifies Postnatally Infected Infants

In a nested case-control study, postnatal HIV infection was strongly associated with cumulative HIV RNA breastmilk exposure, even after allowing for maternal CD4 and plasma viral load; cases ingested approximately 15 times more HIV-1 RNA particles than controls.

Extended pre-exposure prophylaxis with lopinavir–ritonavir versus lamivudine to prevent HIV-1 transmission through breastfeeding up to 50 weeks in infants in Africa (ANRS 12174): a randomised controlled trial

BACKGROUND Strategies to prevent postnatal mother-to-child transmission of HIV-1 in Africa, including infant prophylaxis, have never been assessed past 6 months of breastfeeding, despite breastfeeding being recommended up to 12 months after birth. We aimed to compare the efficacy and safety of infant prophylaxis with the two drug regimens (lamivudine or lopinavir-ritonavir) to prevent postnatal HIV-1 transmission up to 50 weeks of breastfeeding. METHODS We did a randomised controlled trial in four sites in Burkina Faso, South Africa, Uganda, and Zambia in children born to HIV-1-infected mothers not eligible for antiretroviral therapy (CD4 count >350 cells per μL). An independent researcher electronically generated a randomisation schedule; we then used sequentially numbered envelopes to randomly assign (1:1) HIV-1-uninfected breastfed infants aged 7 days to either lopinavir-ritonavir or lamivudine (paediatric liquid formulations, twice a day) up to 1 week after complete cessation of breastfeeding or at the final visit at week 50. We stratified the randomisation by country and used permuted blocks of four and six. We used a study label on drug bottles to mask participants, study physicians, and assessors to the treatment allocation. The primary outcome was infant HIV-1 infection between age 7 days and 50 weeks, diagnosed every 3 months with HIV-1 DNA PCR, in the modified intention-to-treat population (all who attended at least one follow-up visit). This trial is registered with ClinicalTrials.gov, number NCT00640263. FINDINGS Between Nov 16, 2009, and May 7, 2012, we enrolled and randomised 1273 infants and analysed 1236; 615 assigned to lopinavir-ritonavir or 621 assigned to lamivudine. 17 HIV-1 infections were diagnosed in the study period (eight in the lopinavir-ritonavir group and nine in the lamivudine group), resulting in cumulative HIV-1 infection of 1.4% (95% CI 0.4-2.5) and 1.5% (0.7-2.5), respectively. Infection rates did not differ between the two drug regimens (hazard ratio [HR] of lopinavir-ritonavir versus lamivudine of 0.90, 95% CI 0.35-2.34; p=0.83). Clinical and biological severe adverse events did not differ between groups; 251 (51%) infants had a grade 3-4 event in the lopinavir-ritonavir group compared with 246 (50%) in the lamivudine group. INTERPRETATION Infant HIV-1 prophylaxis with lopinavir-ritonavir was not superior to lamivudine and both drugs led to very low rates of HIV-1 postnatal transmission for up to 50 weeks of breastfeeding. Infant pre-exposure prophylaxis should be extended until the end of HIV-1 exposure and mothers should be informed about the persistent risk of transmission throughout breastfeeding. FUNDING INSERM/National Agency for Research on AIDS and Viral Hepatitis (including funds from the Total Foundation), European Developing Countries Clinical Trials Partnership, Research Council of Norway.

Lopinavir/Ritonavir versus Lamivudine peri-exposure prophylaxis to prevent HIV-1 transmission by breastfeeding: the PROMISE-PEP trial Protocol ANRS 12174

BackgroundPostnatal transmission of HIV-1 through breast milk remains an unsolved challenge in many resource-poor settings where replacement feeding is not a safe alternative. WHO now recommends breastfeeding of infants born to HIV-infected mothers until 12 months of age, with either maternal highly active antiretroviral therapy (HAART) or peri-exposure prophylaxis (PEP) in infants using nevirapine. As PEP, lamivudine showed a similar efficacy and safety as nevirapine, but with an expected lower rate of resistant HIV strains emerging in infants who fail PEP, and lower restrictions for future HIV treatment. Lopinavir/ritonavir (LPV/r) is an attractive PEP candidate with presumably higher efficacy against HIV than nevirapine or lamivudine, and a higher genetic barrier to resistance selection. It showed an acceptable safety profile for the treatment of very young HIV-infected infants. The ANRS 12174 study aims to compare the risk of HIV-1 transmission during and safety of prolonged infant PEP with LPV/r (40/10 mg twice daily if 2-4 kg and 80/20 mg twice daily if >4 kg) versus Lamivudine (7,5 mg twice daily if 2-4 kg, 25 mg twice daily if 4-8 kg and 50 mg twice daily if >8 kg) from day 7 until one week after cessation of BF (maximum 50 weeks of prophylaxis) to prevent postnatal HIV-1 acquisition between 7 days and 50 weeks of age.MethodsThe ANRS 12174 study is a multinational, randomised controlled clinical trial conducted on 1,500 mother-infant pairs in Burkina Faso, South Africa, Uganda and Zambia. We will recommend exclusive breastfeeding (EBF) until 26th week of life and cessation of breastfeeding at a maximum of 49 weeks in both trial arms.HIV-uninfected infants at day 7 (± 2 days) born to HIV-1 infected mothers not eligible for HAART who choose to breastfeed their infants.The primary endpoint is the acquisition of HIV-1 (as assessed by HIV-1 DNA PCR) between day 7 and 50 weeks of age. Secondary endpoints are safety (including resistance, adverse events and growth) until 50 weeks and HIV-1-free survival until 50 weeks.DiscussionThis study will provide a new evidence-based intervention to support HIV-1-infected women not eligible for HAART to safely breastfeed their babies.Trial registration number ( http://www.clinicaltrials.gov )NCT00640263

Examination of the Hierarchical Structure of the Brief COPE in a French Sample: Empirical and Theoretical Convergences

This study aimed to determine whether the various factors of coping as measured by the Brief COPE could be integrated into a more parsimonious hierarchical structure. To identify a higher structure for the Brief COPE, several measurement models based on prior theoretical and hierarchical conceptions of coping were tested. First, confirmatory factor analysis (CFA) results revealed that the Brief COPEs 14 original factors could be represented more parsimoniously with 5 higher order dimensions: problem-solving, support-seeking, avoidance, cognitive restructuring, and distraction (N = 2,187). Measurement invariance across gender was also shown. Second, results provided strong support for the cross-validation and the concurrent validity of the hierarchical structure of the Brief COPE (N = 584). Results indicated statistically significant correlations between Brief COPE factors and trait anxiety and perceived stress. Limitations and theoretical and methodological implications of these results are discussed.

Mycobacterium bovis in Burkina Faso: Epidemiologic and Genetic Links between Human and Cattle Isolates

Background In sub-Saharan Africa, bovine tuberculosis (bTB) is a potential hazard for animals and humans health. The goal of this study was to improve our understanding of bTB epidemiology in Burkina Faso and especially Mycobacterium bovis transmission within and between the bovine and human populations. Methodology/principal findings Twenty six M. bovis strains were isolated from 101 cattle carcasses with suspected bTB lesions during routine meat inspections at the Bobo Dioulasso and Ouagadougou slaughterhouses. In addition, 7 M. bovis strains were isolated from 576 patients with pulmonary tuberculosis. Spoligotyping, RDAf1 deletion and MIRU-VNTR typing were used for strains genotyping. The isolation of M. bovis strains was confirmed by spoligotyping and 12 spoligotype signatures were detected. Together, the spoligotyping and MIRU-VNTR data allowed grouping the 33 M. bovis isolates in seven clusters including isolates exclusively from cattle (5) or humans (1) or from both (1). Moreover, these data (genetic analyses and phenetic tree) showed that the M. bovis isolates belonged to the African 1 (Af1) clonal complex (81.8%) and the putative African 5 (Af5) clonal complex (18.2%), in agreement with the results of RDAf1 deletion typing. Conclusions/Significance This is the first detailed molecular characterization of M. bovis strains from humans and cattle in Burkina Faso. The distribution of the two Af1 and putative Af5 clonal complexes is comparable to what has been reported in neighbouring countries. Furthermore, the strain genetic profiles suggest that M. bovis circulates across the borders and that the Burkina Faso strains originate from different countries, but have a country-specific evolution. The genetic characterization suggests that, currently, M. bovis transmission occurs mainly between cattle, occasionally between cattle and humans and potentially between humans. This study emphasizes the bTB risk in cattle but also in humans and the difficulty to set up proper disease control strategies in Burkina Faso.

Preference for Safe Over Risky Options in Binge Eating

Binge eating has been usually viewed as a loss of control and an impulsive behavior. But, little is known about the actual behavior of binging patients (prevalently women) in terms of basic decision-making under risk or under uncertainty. In healthy women, stressful cues bias behavior for safer options, raising the question of whether food cues that are perceived as threatening by binging patients may modulate patients’ behaviors towards safer options. A cross-sectional study was conducted with binging patients (20 bulimia nervosa (BN) and 23 anorexia nervosa binging (ANB) patients) and two control groups (22 non-binging restrictive (ANR) anorexia nervosa patients and 20 healthy participants), without any concomitant impulsive disorder. We assessed decisions under risk with a gambling task with known probabilities and decisions under uncertainty with the balloon analog risk taking task (BART) with unknown probabilities of winning, in three cued-conditions including neutral, binge food and stressful cues. In the gambling task, binging and ANR patients adopted similar safer attitudes and coherently elicited a higher aversion to losses when primed by food as compared to neutral cues. This held true for BN and ANR patients in the BART. After controlling for anxiety level, these safer attitudes in the food condition were similar to the ones under stress. In the BART, ANB patients exhibited a higher variability in their choices in the food compared to neutral condition. This higher variability was associated with higher difficulties to discard irrelevant information. All these results suggest that decision-making under risk and under uncertainty is not fundamentally altered in all these patients.

Improved planning abilities in binge eating.

Objective The role of planning in binge eating episodes is unknown. We investigated the characteristics of planning associated with food cues in binging patients. We studied planning based on backward reasoning, reasoning that determines a sequence of actions back to front from the final outcome. Method A cross-sectional study was conducted with 20 healthy participants, 20 bulimia nervosa (BN), 22 restrictive (ANR) and 23 binging anorexia nervosa (ANB), without any concomitant impulsive disorder. In neutral/relaxing, binge food and stressful conditions, backward reasoning was assessed with the Race game, promotion of delayed large rewards with an intertemporal discounting task, attention with the Simon task, and repeating a dominant behavior with the Go/No-go task. Results BN and to a lower extent ANB patients succeeded more at the Race game in food than in neutral condition. This difference discriminated binging from non-binging participants. Backward reasoning in the food condition was associated with lower approach behavior toward food in BN patients, and higher food avoidance in ANB patients. Enhanced backward reasoning in the food condition related to preferences for delayed large rewards in BN patients. In BN and ANB patients the enhanced success rate at the Race game in the food condition was associated with higher attention paid to binge food. Conclusion These findings introduce a novel process underlying binges: planning based on backward reasoning is associated with binges. It likely aims to reduce craving for binge foods and extend binge refractory period in BN patients, and avoid binging in ANB patients. Shifts between these goals might explain shifts between eating disorder subtypes.

Association between breast milk fatty acids and HIV-1 transmission through breastfeeding

A residual mother-to-child transmission of HIV through breastfeeding persists despite prophylaxis. We identified breast milk fatty acids (FA) associated with postnatal HIV transmission through breastfeeding in a case-control study. Cases (n=23) were HIV-infected women with an infant who acquired HIV after 6 weeks of age. Controls (n=23) were matched on infant׳s age at sample collection. Adjusting for maternal antenatal plasma CD4 T cell count, cis-vaccenic acid (18:1n-7) and eicosatrienoic acid (20:3n-3) were associated with HIV transmission in opposite dose-response manner: OR (tertile 3 versus tertile 1): 10.8 and 0.16, p for trend=0.02 and 0.03, respectively. These fatty acids correlated with HIV RNA load, T helper-1 related cytokines, IL15, IP10, and β2 microglobulin, positively for cis-vaccenic acid, negatively for eicosatrienoic acid. These results suggested a change in FA synthesis by mammary gland cells leading to increased cis-vaccenic acid in milk of mothers who transmitted HIV to their infant during breastfeeding.

The Sequential Binge, a New Therapeutic Approach for Binge Eating: A Pilot Study.

Background and Objectives A sizeable proportion of patients experiencing binge eating do not respond to cognitive behavioral therapy (CBT). We present the sequential binge (SB), a new behavioral intervention that complements CBT, and preliminary results of its effects. SB breaks up the binge into repeated identical sequences of eating separated by incremental pauses. This pattern of ingestion aims at facilitating boredom toward the ingested foods and at turning cognitive control away from binge food restriction. SB is hypothesized to reduce food intake during the binge and the number of daily binges. Methods Prospective pilot study. Fifteen binging patients with previous unsuccessful intensive CBT were given SB as an adjunct to their treatment and were followed up for 16 weeks from admission. All patients were reassessed 47 weeks on average after discharge. Results SB was associated with a 44% relative reduction in the planned food intake (p<0.001), a longer consecutive binge refractory period compared to regular binges (median: 48 hours versus 4 hours, p = 0.002) and an average relative reduction by 26% of binge number the day after each SB (p = 0.004). 47% of patients reached binge abstinence for four consecutive weeks 16 weeks after the first SB. Conclusion This case series shows promising evidence for the use of SB in patients with refractory binge eating. Further evaluation in a prospective randomized controlled trial would be justified.