Matrix Metalloproteinase Gene Polymorphisms and Bronchopulmonary Dysplasia: Identification of MMP16 as a New Player in Lung Development

International audienceBACKGOUND: Alveolarization requires coordinated extracellular matrix remodeling, a process in which matrix metalloproteinases (MMPs) play an important role. We postulated that polymorphisms in MMP genes might affect MMP function in preterm lungs and thus influence the risk of bronchopulmonary dysplasia (BPD). METHODS AND FINDINGS: Two hundred and eighty-four consecutive neonates with a gestational age of <28 weeks were included in this prospective study. Forty-five neonates developed BPD. Nine single-nucleotide polymorphisms (SNPs) were sought in the MMP2, MMP14 and MMP16 genes. After adjustment for birth weight and ethnic origin, the TT genotype of MMP16 C/T (rs2664352) and the GG genotype of MMP16 A/G (rs2664349) were found to protect from BPD. These genotypes were also associated with a smaller active fraction of MMP2 and with a 3-fold-lower MMP16 protein level in tracheal aspirates collected within 3 days after birth. Further evaluation of MMP16 expression during the course of normal human and rat lung development showed relatively low expression during the canalicular and saccular stages and a clear increase in both mRNA and protein levels during the alveolar stage. In two newborn rat models of arrested alveolarization the lung MMP16 mRNA level was less than 50% of normal. CONCLUSIONS: MMP16 may be involved in the development of lung alveoli. MMP16 polymorphisms appear to influence not only the pulmonary expression and function of MMP16 but also the risk of BPD in premature infants

Supporting women farmers in a changing climate: five policy lessons

Policies, institutions and services to help farmers develop new approaches to deal with climate change will need to produce results for women farmers as well as men. This brief provides five policy lessons to support this process, based on evidence from research in low- and middle- income countries and offers guidelines for crafting gender-responsive climate policies at global and national levels. This research was presented in March 2015 at a seminar in Paris on ‘Closing the gender gap in farming under climate change’, co-organized by the CGIAR Research Program on Climate Change, Agriculture and Food Security (CCAFS), the International Social Science Council (ISSC) and Future Earth

Living with a Crucial Decision: A Qualitative Study of Parental Narratives Three Years after the Loss of Their Newborn in the NICU

BACKGROUND: The importance of involving parents in the end-of-life decision-making-process (EOL DMP) for their child in the neonatal intensive care unit (NICU) is recognised by ethical guidelines in numerous countries. However, studies exploring parents' opinions on the type of involvement report conflicting results. This study sought to explore parents' experience of the EOL DMP for their child in the NICU. METHODS: The study used a retrospective longitudinal design with a qualitative analysis of parental experience 3 years after the death of their child in four NICUs in France. 53 face-to-face interviews and 80 telephone interviews were conducted with 164 individuals. Semi-structured interviews were conducted to explore how parents perceived their role in the decision process, what they valued about physicians' attitudes in this situation and whether their long-term emotional well being varied according to their perceived role in the EOL DMP. FINDINGS: Qualitative analysis identified four types of perceived role in the DMP: shared, medical, informed parental decision, and no decision. Shared DM was the most appreciated by parents. Medical DM was experienced as positive only when it was associated with communication. Informed parental DM was associated with feelings of anxiousness and abandonment. The physicians' attitudes that were perceived as helpful in the long term were explicit sharing of responsibility, clear expression of staff preferences, and respectful care and language toward the child. INTERPRETATION: Parents find it valuable to express their opinion in the EOL DMP of their child. Nonetheless, they do need continuous emotional support and an explicit share of the responsibility for the decision. As involvement preferences and associated feelings can vary, parents should be able to decide what role they want to play. However, our study suggests that fully autonomous decisions should be misadvised in these types of tragic choices

Propos sur le remaniement des tissus parodontaux lors du recul des canines

Le but de cet article est de proposer un protocole opératoire simple, permettant de créer une situation parodontale favorable dans deux situations cliniques classiques : évolution en dehors de la gencive attachée de canines en ectopie vestibulaire, et apparition de « fissures gingivales » lors du recul des canines après extraction des premières prémolaires

Reduced Sufentanil Doses are Effective for Postoperative Analgesia After Ductal Closure in Extremely Premature Infants: A 10 Years Retrospective Cohort Study

International audienceObjectives: The objective of the study was to assess the efficacy of reduced sufentanil doses for postoperative analgesia following surgical ductal closure in extremely premature infants.Methods: This was a retrospective, single-center, cohort study comparing 2 sufentanil dosing regimens used between 2001 and 2010 and included all infants born at <28 weeks of gestation with surgical ductal closure. Sufentanil doses were reduced in 2007 as a standard of care. Time was divided into 3 epochs to distinguish the effects of practice changes over time from the effects of sufentanil dose change: epoch 1 (2001 to 2004), epoch 2 (May 2005 to 2007), and epoch 3 (June 2007 to 2010).Results: A total of 109 of 114 eligible infants were analyzed (mean [±SD], gestational age: 25.1 [±1.1] wk; mean [±SD], birth weight: 756 [±144] g). Median sufentanil doses were significantly higher during epochs 1 and 2 (0.1 to 0.2 µg/kg/h) than during epoch 3 (0.03 to 0.04 µg/kg/h) (P<0.0001). EDIN (Echelle de Douleur et d'Inconfort du Nouveau-né) pain scores were mostly ≤4 throughout the study period and their changes over time were not contemporaneous with the reduction in sufentanil doses; they were lower during epoch 1 versus epochs 2 and 3 (P<0.0001) and comparable between epochs 2 and 3. Midazolam doses and paracetamol use were not higher during epoch 3 as compared with epochs 1 and 2. No difference in opioid-related adverse events was observed between the 3 epochs.Conclusion: Our study supports the use of low continuous intravenous sufentanil doses, consistent with morphine doses currently recommended in this population

Study on preventing adverse events in neonates (SEPREVEN)

International audiencentroduction: Adverse events (AE) in care are recognized as a leading cause of mortality and injury in patients. Improving patients' safety is difficult to achieve. Therefore, innovative research strategies are needed to identify errors in subgroups of patients and related severity of outcomes as well as reliably measured efficiency of reproducible strategies to improve safety. This trial aims to evaluate the impact of a combined multiprofessional education program on the rate of AE in neonatal intensive care units (NICUs).Methods and analysis: This is a stepped-wedge cluster randomised controlled trial with 3 clusters each containing 4 units. The study time period will be 20 months. The education program will be implemented within each cluster following a random sequence with a control period, a 4-month transition period and a post-educational intervention period. Eligibility criteria: for clusters: 6 NICUs from Ile-de-France and 6 NICUs from different regions in France; for patients: in-hospital during the study period (November 23, 2015 and November 2, 2017 [inclusion start dates varying by unit]) in one of the 12 NICUs; corrected gestational age 2 days; and parents informed and not opposed to the use of their newborn's data. A routine occurrence reporting of medical errors and their consequence will take place during the entire study period. The intervention will combine an education to implement a standardized root cause analysis method, creation of bundles (insertion, daily goals, maintenance bundles) to prevent catheter-associated blood-stream infection and a poster to prevent extravasation injuries.Outcome: We hypothesize a reduction from 60 (control) to 50 (intervention) AE/1000 patient-days. The primary outcome will be the rate of AE/1000 patient-days in the NICU

Humidity during high‐frequency oscillatory ventilation compared to intermittent positive pressure ventilation in extremely preterm neonates: An in vitro and in vivo observational study

International audienceBackground: Inappropriate humidification of inspired gas during mechanical ventilation can impair lung development in extremely low birthweight (ELBW) infants. Humidification depends on multiple factors, such as the heater-humidifier device used, type of ventilation, and environmental factors. Few studies have examined inspired gas humidification in these infants, especially during high-frequency oscillatory ventilation (HFOV). Our objective was to compare humidity during HFOV and intermittent positive pressure ventilation (IPPV), in vitro and in vivo.Methods: In vitro and in vivo studies used the same ventilator during both HFOV and IPPV. The bench study used a neonatal test lung and two heater-humidifiers with their specific circuits; the in vivo study prospectively included preterm infants born before 28 weeks of gestation.Results: On bench testing, mean absolute (AH) and relative (RH) humidity values were significantly lower during HFOV than IPPV (RH = 79.4 ± 8.1% vs. 89.0 ± 6.2%, p < 0.001). Regardless of the ventilatory mode, mean RH significantly differed between the two heater-humidifiers (89.6 ± 6.7% vs 78.7 ± 6.8%, p = 0.003). The in vivo study included 10 neonates (mean ± SD gestational age: 25.7 ± 0.9 weeks and birthweight: 624.4 ± 96.1 g). Mean RH during HFOV was significantly lower than during IPPV (74.6 ± 5.7% vs. 83.0 ± 6.7%, p = 0.004).Conclusion: RH was significantly lower during HFOV than IPPV, both in vitro and in vivo. The type of heater-humidifier also influenced humidification. More systematic measurements of humidity of inspired gas, especially during HFOV, should be considered to optimize humidification and consequently lung protection in ELBW infants

Patient-Ventilator Synchrony in Extremely Premature Neonates during Non-Invasive Neurally Adjusted Ventilatory Assist or Synchronized Intermittent Positive Airway Pressure: A Randomized Crossover Pilot Trial

International audienceIntroduction: Synchronization of non-invasive ventilation is challenging in extremely premature infants. We compared patient-ventilator synchrony between non-invasive neurally adjusted ventilatory assist (NIV-NAVA) using transdiaphragmatic (Edi) catheter and synchronized intermittent positive airway pressure (SiPAP) using an abdominal trigger. Methods: This study was a monocentric, randomized, crossover trial in premature infants born before 28 weeks of gestation, aged 3 days or more, and below 32 weeks postmenstrual age. NIV-NAVA and SiPAP were applied in a random order for 2 h with analysis of data from the second hour. The primary outcome was the asynchrony index. Results: Fourteen patients were included (median [IQR] gestational age at birth 25.6 (25.3–26.4) weeks, median [IQR] birth weight 755 [680–824] g, median [IQR] postnatal age 26.5 [19.8–33.8] days). The median (IQR) asynchrony index was significantly lower in NIV-NAVA versus SiPAP (49.9% [44.1–52.6] vs. 85.8% [74.2–90.9], p &#x3c; 0.001). Ineffective efforts and auto-triggering were significantly less frequent in NIV-NAVA versus SiPAP (3.0% vs. 32.0% p &#x3c; 0.001 and 10.0% vs. 26.6%, p = 0.004, respectively). Double triggering was significantly less frequent in SiPAP versus NIV-NAVA (0.0% vs. 9.0%, p &#x3c; 0.001). No significant difference was observed for premature cycling and late cycling. Peak Edi and swing Edi were significantly lower in NIV-NAVA as compared to SiPAP (7.7 [6.1–9.9] vs. 11.0 [6.7–14.5] μV, p = 0.006; 5.4 [4.2–7.6] vs. 7.6 [4.3–10.8] μV, p = 0.007, respectively). No significant difference was observed between NIV-NAVA and SiPAP for heart rate, respiratory rate, COMFORTneo scores, apnoea, desaturations, or bradycardias. Discussion/Conclusion: NIV-NAVA markedly improves patient-ventilator synchrony as compared to SiPAP in extremely premature infants

Are cytochrome P450 CYP2C8 and CYP2C9 polymorphisms associated with ibuprofen response in very preterm infants?

BackgroundPatent ductus arteriosus (PDA) in extremely preterm infants remains a challenging condition with conflicting treatment strategies. Ibuprofen is currently used to treat PDA with ductal closure failure rate up to 40%. We test the hypothesis that cytochrome P450 CYP2C8/2C9 polymorphisms may predict ibuprofen response.Methodology/principal findingsWe studied extremely preterm neonates with haemodynamically significant PDA and treated with ibuprofen. One or two variant CYP2C8 and/or 2C9 alleles were found in 17% of the population, most of them were from Caucasian ethnicity (67-74%). Response to ibuprofen and clinical course of infants carrying variants CYP2C8 and CYP2C9 were similar. Comparing infants with wild type or variant CYP2C8 and CYP2C9 genotypes, response rate to ibuprofen was significantly higher in wild type than in mutated carriers in univariate analysis (73% versus 52%, p = 0.04). Comparing responders (ductus closure; n = 75) and non-responders (surgical ligation; n = 36), the only two factors significantly associated with the response to ibuprofen using multivariate analysis were higher gestational age and non Caucasian ethnicity but not CYP2C polymorphism.ConclusionsCYP2C polymorphism was not associated with PDA response to ibuprofen and this factor appears not appropriate to optimize the ductal closure rate by modulating ibuprofen dosing strategy. This study points out the role for ethnicity in the interindividual variability of response to ibuprofen in extremely preterm infants