Integrating a palliative approach into the healthcare provided by the French-African Pediatric Oncology Group's pilot units. Insights from a 3-year training program.

Working alongside local stakeholders, members of the French-African Pediatric Oncology Group developed a 3-year program to train pediatric oncology teams from 15 French-speaking countries in Africa in using analgesics and providing palliative care. This program was rolled out in three phases: initial training, in situ assessment, and advanced training in selected topics. To access this program, multidisciplinary teams had to come up with a project to improve their existing palliative care and pain management practices, and commit themselves to implementing it. All the teams invited agreed to take part in the program, which explicitly broached a subject that is often avoided in oncology teaching. The first phase was rolled out in 2017, with 65 trainees from 19 units attending one of three sessions held in Dakar, Senegal, Abidjan, Côte d'Ivoire, and Rabat, Morocco. The subsequent assessment revealed that only half the teams had started to implement their projects. The advanced training phase was therefore adjusted accordingly. A collective training session held in Marseille was attended by 15 trainees from seven teams whose projects were already underway, while in situ mentoring was provided for six other teams, through French-African twinnings in four cases. The length and openness of the program meant that we were able to identify and share the units' diverse realities, and fine-tune their projects accordingly, as well as plan ways of continuing the training both locally and collectively.

[Reproductive health care for women with spina bifida]. / Suivi gynécologique des patientes atteintes d'un spina bifida.

OBJECTIVES: Few studies have focused on reproductive health care for women with spina bifida. This subject is rarely discussed, whether in patient groups or in the medical community. However, these patients need advice and a care that is appropriate to their condition. METHODS: In association with the spina bifida reference center of the University Hospital of Rennes, we have conducted a four-year retrospective, observational study. Its aim was to analyze the characteristics of the patients' gynecological care and to adapt our practice to their needs. RESULTS: Forty-eight patients were included. We demonstrated an increased risk of precocious puberty, labia minora hypertrophy and genital prolapse. CONCLUSION: Some specific characteristics of the reproductive health care of patients with spina bifida are interesting to know. A study on a larger series of patients is needed to further analyze the obstetric, gynecological and sexological issues of these women.

[Tolerance of copper intrauterine device in nulliparous patients: a single-center prospective study]. / Tolérance du dispositif intra-utérin au cuivre chez les patientes nullipares : étude prospective unicentrique.

INTRODUCTION: The purpose of this work was to study the continuation rate of intrauterine device (IUD) copper in a nulliparous population. PATIENTS AND METHOD: A prospective study in a family planning centre including nulliparous patients between January and December 2012. RESULTS: A total of 83 nulliparous patients had IUD copper insertion and 11 patients were excluded because they were lost to follow-up. Finally, 72 nulliparous patients were included in the study. Continuation rate after one-year follow-up was 90.3% (65/72). Satisfaction rate of patient was high (93.8%). Menstruation amount was increased for 84% (55/65) patients, but 75% (41/55) did not report any inconvenience about this. Dysmenorrhea were increased for 80% (52/65) patients, but 58% (30/52) were not troubled by this. CONCLUSION: Continuation rate of IUD copper was high (90%) after one-year follow-up in nulliparous women. Tolerance was also good for evaluated patients.

Pan-European, open-label dose titration study of fentanyl buccal tablet in patients with breakthrough cancer pain.

BACKGROUND: Fentanyl buccal tablet (FBT), a rapid onset opioid used to treat breakthrough cancer pain, must be titrated to an effective dose that provides adequate analgesia and minimizes undesirable events. This open-label, randomized study compared the percentage of patients achieving an effective dose of FBT when starting titration at 100 or 200 µg. METHODS: Opioid-tolerant patients with chronic cancer-related pain who experienced up to four breakthrough pain episodes daily were randomized to a starting dose of 100 or 200 µg for the titration period. The dose was increased until an effective dose (100, 200, 400, 600 or 800 µg) providing adequate analgesia with acceptable adverse events was achieved. Patients achieving an effective dose entered a treatment period during which they treated up to eight breakthrough pain episodes with their effective dose. RESULTS: A total of 442 patients from 135 sites in seven European countries were screened. Non-inferiority was established with the percentage of patients achieving an effective dose starting titration at 200 µg (81.4%) compared with the 100-µg (75.2%) starting dose. The most common effective doses of FBT were 200 µg (39.6%) and 400 µg (26.9%). No new safety concerns were identified with use of FBT at doses up to 800 µg per episode. CONCLUSIONS: This study involving a real clinical practice setting showed a similar percentage of patients safely achieving an effective dose by titration starting with 100 versus 200 µg of FBT.

[Pregnancy management among teenagers under 15 years old: a multidisciplinary challenge]. / Prise en charge de la grossesse chez la mineure de moins de 15 ans: un challenge multidisciplinaire.

OBJECTIVE: Pregnancy before 15 years old remains a troublesome issue for medical teams which are not used to working with adolescents. The aim of this work is to study the outcome of the pregnancies among very young adolescents, the psycho-social context, the medical management, the professionals involved in it and the follow-up after pregnancy. MATERIALS AND METHODS: Retrospective analysis from four cases, in the university hospital of Rennes, during the year 2011. RESULTS: All the pregnancies were terminated, half of them on a psychological indication. Three adolescents showed evidence of major psychological distress and two of them had a history of sexual abuse. The medical care was heterogeneous, from the first meet until the follow-up after pregnancy, including the medical abortion. A multidisciplinary teamwork was found in three of the four cases. CONCLUSION: Pregnancy before the age of 15 years old is a rare event and often ends with a medical abortion. The medical management of those vulnerable adolescents is complex and requires a multidisciplinary team approach all along the follow-up. A national evaluation of clinical practice in this area seems to be needed.

[Risk factors and perinatal consequences of short interpregnancy interval: a retrospective case-control study]. / Facteurs de risques et conséquences périnatales des grossesses rapprochées : étude cas-témoin rétrospective.

OBJECTIVES: To study the maternal risk factors and perinatal complications of a short interpregnancy interval. PATIENTS AND METHODS: Retrospective case-control study between 2007 and 2009, comparing a group with a short interpregnancy interval (less than 9 months, n=83), and a control group (interval between two pregnancies between 18 and 24 months, n=166). RESULTS: The main risk factor of short interpregnancy interval is to be unemployed (OR=3.2, P<0.001). There is a significant link between lack of prescription contraceptives in postpartum and a short interval between pregnancies (OR=3.4, P<0.001). We also found a higher rate of anemic women during pregnancy (OR=4.9, P=0.001) and postpartum (OR=2.1, P=0.02) in case of short interpregnancy interval. Short interpregnancy interval increases risk of small for gestational age (OR=2.4, P=0.05) and thermoregulation disorders (OR=3.1, P=0.02). CONCLUSION: A low socioeconomic level is a risk factor of short interpregnancy interval. Short interpregnancy interval is at risk of maternal iron deficiency and neonatal complications like low birth weight and hypothermia.

[Very preterm births (22-26 WG): from the decision to the implement of palliative care in the delivery room. Experience of Rennes University Hospital (France)]. / Naissances très prématurées (22 à 26 SA) : de la décision à la mise en œuvre des soins palliatifs en salle de naissance. Expérience du CHU de Rennes (France).

OBJECTIVES: After the establishment of a palliative care protocol (PC) in the delivery room, study how the postnatal management decision was taken and in particular how PC was developed. MATERIAL AND METHODS: Retrospective analysis of births between 22 and 25+6 WG, in Rennes University Hospital, during 21 months. RESULTS: Twenty-seven women meeting the criteria gave birth to 32 live children. Decision making (intensive care or PC) was fast but shared with the parents, mainly on the criterion of the term. The delivery was vaginal for 24 children. Thirteen children were resuscitated. Nineteen children received comfort care, their life was less than 3 hours, 18/19 were supported by their parents. CONCLUSION: The management of these births is consistent with current recommendations, decisions are individualized but often informally. The secondary prognostic criteria could be better taken into account. Obstetrical and pediatric management is consistent. The PC protocol is fairly well used but the collective decisions should be more formally organized and transcribed more accurately in the records, the requirements for analgesics should be based on clinical assessments.

[Medical abortion from 12 through 14 weeks' gestation: a retrospective study with 126 patients]. / L'interruption volontaire de grossesse médicamenteuse de 12 à 14 semaines d'aménorrhée : étude rétrospective portant sur 126 patientes.

OBJECTIVE: To assess the efficacy of medical abortion performed according to a single protocol from 12 through 14 weeks. STUDY DESIGN: Retrospective observational study of medical abortions from 12 through 14 weeks performed from January 2007 through March 2009. The protocol combined 600 mg de mifepristone orally, followed 48 h later by 400 µg of misoprostol, administered orally, and repeated after 3h, four times a day (during two days), if patient did not begin to abort. Outcome measures were the abortion rate, the rate of complication, the rate of manual uterine revision or vacuum aspiration, the time of expulsion and the misoprostol dose. RESULTS: The study included 126 medical abortions. The abortion rate was 98% and the secondary manual revision or vacuum aspiration rate was 41%. The mean time to expulsion was 10.4 (±8.8)h, and the mean misoprostol dose 1040 (±420) µg. Higher parity was significantly correlated with shorter time to expulsion (P=0.02). CONCLUSION: Medical abortion was consistently effective from 12 through 14 weeks but with high rate of secondary manual revision or vacuum aspiration.

Diagnosis of fetal urinary tract malformations: prenatal management and postnatal outcome.

OBJECTIVE: To evaluate prenatal management and to define the criteria of gravity for accurate assessment of the renal and overall prognosis of fetuses presenting malformations of the urinary tract. METHODS: We carried out a retrospective study of 127 cases of urinary tract malformation. We carried out descriptive statistical and univariate analyses as a function of severity criteria and the outcome of pregnancy. RESULTS: One-third of fetuses presented associated extrarenal malformations and 10% of the karyotypes were abnormal. There were more abortions in case of decrease in amniotic fluid volume (p < 0.001), extent of renal damage (p < 0.05), presence of associated extrarenal malformations (p < 0.05), early diagnosis of the malformation (p < 0.001) and presence of chromosomal syndrome (p = 0.01). In our study, there was an excellent correlation between prenatal data and pathological findings for the fetus following abortions for medical reasons or obtained during the surveillance of live-born children. Fetal biochemistry made very little contribution. CONCLUSION: In cases of urinary tract malformation, this work confirms the need for regular and frequent ultrasound scans, checking for the echographic factors indicative of gravity and for adapted karyotyping. It also demonstrates that pluridisciplinary management is necessary for the prenatal evaluation of renal and overall fetal prognosis.

[Obstetrical management of women with previous caesarean section]. / Prise en charge de l'accouchement des patientes ayant un antécédent de césarienne.

The authors announce their own experience and data of the literature to clarify their policy in cases of pregnancy after a previous caesarean section. For obstetricians, the question is to accept a trial of labor for vaginal birth or to decide an elective caesarean section. We particularly explain our conclusions in cases of breech deliveries, twin pregnancies, fetal pelvic disproportion, maternal diabetes, and labor inductions. In cases of previous caesarean, a trial of labor can be successfully tempted in numerous situations. Nevertheless, there are some limits not to be crossed.

A comparison of intranasal fentanyl spray with oral transmucosal fentanyl citrate for the treatment of breakthrough cancer pain: an open-label, randomised, crossover trial.

OBJECTIVE: The efficacy of intranasal fentanyl spray (INFS) was compared with that of oral transmucosal fentanyl citrate (OTFC) for the relief of cancer-related breakthrough pain (BTP) in an open-label, crossover trial. METHODS: Adult cancer patients receiving stable background opioid treatment and experiencing BTP episodes were recruited from 44 study centres in seven European countries (Austria, France, Germany, Italy, Poland, Spain and the United Kingdom); of the 196 patients enrolled, 139 were randomised to receive INFS followed by OTFC, or vice versa. Patients were titrated to an effective dose of one agent (50, 100 or 200 microg INFS; 200, 400, 600, 800, 1200 or 1600 microg OTFC) to treat six BTP episodes, then titration and treatment were repeated with the other agent. The primary outcome was patient-recorded time to onset of 'meaningful' pain relief. Secondary outcomes included pain intensity difference (PID) at 10 and 30 minutes (PID(10), PID(30)), sum of PID at 15 and 60 minutes (SPID(0-15), SPID(0-60)), ease of administration, treatment preference and relationship between background opioid dose and effective INFS dose. Additional outcome measures included proportions of episodes with > or =33% and > or =50% pain intensity (PI) reduction, and PID at additional time points. CLINICAL TRIAL REGISTRATION NUMBER: NCT00496392. RESULTS: Among the intention-to-treat population (n = 139), median time to onset of 'meaningful' pain relief was 11 minutes with INFS versus 16 minutes with OTFC; 65.7% of patients attained faster time to 'meaningful' pain-relief onset with INFS (p < 0.001). PID was statistically significantly greater for INFS than OTFC from 5 minutes post-dosing. Significantly more INFS-treated breakthrough pain episodes achieved clinically important pain relief (> or =33% and > or =50% PI reduction) up to 30 minutes post-dosing. The proportions of episodes treated with INFS and OTFC achieving a PI reduction of > or =33% at 5 minutes were 25.3% versus 6.8% (p < 0.001), and at 10 minutes were 51.0% versus 23.6% (p < 0.001), respectively; the proportions of episodes treated with INFS and OTFC achieving a > or =50% PI reduction at 5 minutes were 12.8% versus 2.1% (p < 0.001), and at 10 minutes were 36.9% versus 9.7% (p < 0.001), respectively. Higher SPID(0-15) and SPID(0-60) scores were achieved with INFS (p < 0.001). More patients preferred INFS than OTFC (p < 0.001) and more patients found it very easy/easy to use. Both treatments were well tolerated. In the safety population (n = 139), 56.8% (n = 79) of patients experienced > or =1 AE during the trial. The only AE that occurred in > or =5% of patients in either treatment group was nausea. Among those patients who experienced serious AEs (13.7%, n = 19), none were considered to be related to either study medication. There was a weak correlation between effective INFS doses and background opioid doses. CONCLUSION: In this open-label, randomised, crossover trial, significantly more patients attained faster 'meaningful' pain relief with INFS than OTFC, and more patients preferred INFS to OTFC.

[Acute pancreatitis induced by major hypertriglyceridemia during pregnancy. A case report]. / Pancréatite aiguë secondaire à une hypertriglycéridémie majeure au cours de la grossesse. A propos d'un cas.

A parturient in the 37th week of gestation is referred to the obstetrical emergency ward for an acute abdominal pain with vomiting and fever. Few hours after her admission, a caesarean section is performed for acute fetal distress. It gave birth to a 3940 g healthy newborn. An abundant and milky peritoneal fluid is noted during the C-section related to a major hypertriglyceridemia (84,47 g/L) which induced an acute pancreatitis explaining the early symptoms. The patient is then hospitalized in surgical reanimation: heparin and a low fat diet led to a quick decrease of triglyceridemia and the healing of the acute pancreatitis. We review the most recent literature about acute pancreatitis during pregnancy, especially induced by hypertriglyceridemia, and the different management option: heparin, parenteral nutrition or plasmapheresis.

[Length of pushing efforts: pushing is not playing. Reply to the article of C. Le Ray and F. Audibert]. / Durée des efforts expulsifs : pousser n'est pas jouer. Réponse à l'article de C. Le Ray et F. Audibert.

The aim of this work is to answer constructively to C. Le Ray and F. Audibert who were surprised that the French guidelines recommended an assisted delivery after 30 min pushing, even if the fetal heart rate is reassuring. We first resumed the definition of "second stage of labor", this word including the first phase with no pushing efforts and the second phase with active pushing of the mother. With that definition, the length of the second stage is around 60 min for the primipara and 20 min for the multipara, this length being modified by the use of peridural. We then specified the physiological mechanisms influencing the acidobasic equilibrium during the pushing time. Those mechanisms are difficult to consider because foetal heart rate monitoring is often "lost" during that phase. Altogether, these factors bring incertitude about progressive foetal acidosis and incapacity to diagnose it. Finally, the literature analysis teaches us that increasing the second stage of labor (inactive plus active phases) during the normal pregnancy seems to be at low risk for the foetus within the primiparas, but display a risk for the mother and so might be limited. Comparing the delayed pushing with the immediate pushing only lead us to conclude that delayed pushing is dangerous, as is prolonged second stage. In conclusion, we think that prolonging the second stage of labor is possible but must be by increasing the inactive first phase of the second stage, especially as long as we will not get a noninvasive and reliable method allowing assessing the well-being of the foetus.

Insights on protein-DNA recognition by coarse grain modelling.

Coarse grain modelling of macromolecules is a new approach, potentially well adapted to answer numerous issues, ranging from physics to biology. We propose here an original DNA coarse grain model specifically dedicated to protein-DNA docking, a crucial, but still largely unresolved, question in molecular biology. Using a representative set of protein-DNA complexes, we first show that our model is able to predict the interaction surface between the macromolecular partners taken in their bound form. In a second part, the impact of the DNA sequence and electrostatics, together with the DNA and protein conformations on docking is investigated. Our results strongly suggest that the overall DNA structure mainly contributes in discriminating the interaction site on cognate proteins. Direct electrostatic interactions between phosphate groups and amino acid side chains strengthen the binding. Overall, this work demonstrates that coarse grain modeling can reveal itself a precious auxiliary for a general and complete description and understanding of protein-DNA association mechanisms.

[Fetal assessment of the labor admission in low risk pregnancies]. / Evaluation du foetus à l'admission des grossesses "a priori" à bas risque.

The assessment of fetal well-being at the beginning of labor must lead to an appropriate monitoring, adapted to the present risks. Even if some medical events are unforeseeable, three ways of reflexions get clear: abnormal maternofetal signs at the admission indicate the need for an increased monitoring (NP5); the reading of the medical file could reveal a high-risk pregnancy; at least, the realization of electronic fetal heart rate monitoring for any woman at the beginning of the labor is recommended: in case of normality, it remains a good criterion of a fetal good health. In this context of admission, there is no evidence supporting that other techniques (amnioscopy, acoustic test, echography, Doppler, etc.) could be beneficial in low-risk women and be recommended (NP5). Research is to be continued in this field.

Embryology of neural tube defects: information provided by associated malformations.

OBJECTIVES: To get information about embryologic mechanisms of neural tube defects (NTD), by studying the associated malformations. METHODS: Eighty three cases of NTD, seen at the prenatal diagnosis unit of Rennes University Hospital (France) between May 1999 and December 2002, were retrospectively studied. Cases with chromosomal anomalies (5/83), cases without available karyotype or pathologic examination were excluded. 24 spina bifida, and 27 cephalic forms (anencephalies, exencephalies, and encephaloceles) were thus analyzed. RESULTS: Only 22/51 cases (43%) were strictly isolated NTD. Anomalies of tissues arising from neural crests were noted in 8/51 fetuses (16%), midline or lateralization anomalies in 12/51 (24%), and anomalies of mesoblastic tissues in 17/51 (33%). An already known syndrome was found in 4/51 cases (8%). CONCLUSION: NDT are more extensive congenital damages that would suggest the restrictive terminology. That prompts to assess cautiously prenatal diagnosis of NTD, and to get detailed pathological examination after termination of pregnancy.

Performances of Wang-Landau algorithms for continuous systems.

The relative performances of different implementations of the Wang-Landau method are assessed on two classes of systems with continuous degrees of freedom, namely, two polypeptides and two atomic Lennard-Jones clusters. Parallel tempering Monte Carlo simulations serve as a reference, and we pay particular attention to the variations of the multiplicative factor f during the course of the simulation. For the systems studied, the Wang-Landau method is found to be of comparable accuracy as parallel tempering, but has significant difficulties in reproducing low-temperature transitions exhibited by the Lennard-Jones clusters at low temperature. Using a complementary order parameter and calculating a two-dimensional joint density of states significantly improves the situation, especially for the notoriously difficult LJ(38) system. However, while parallel tempering easily converges for LJ(31), we have not been able to get data of comparable accuracy with Wang-Landau multicanonical sampling.

Comparison of the fragmentation pattern induced by collisions, laser excitation and electron capture. Influence of the initial excitation.

Collision-induced dissociation, laser-induced dissociation and electron-capture dissociation are compared on a singly and doubly protonated pentapeptide. The dissociation spectrum depends on the excitation mechanism and on the charge state of the peptide. The comparison of these results with the conformations obtained from Monte Carlo simulations suggests that the de-excitation mechanism following a laser or an electron-capture excitation is related to the initial geometry of the peptide.

[Prenatal diagnosis of sirenomelia]. / Diagnostic anténatal d'une sirénomélie.

Sirenomelia sequence associates a fusion of inferior legs with renal anomalies until bilateral agenesis. It is a rare and lethal polymalformation. The purpose of the ultrasonographic study is to identify the sirenomelia as early as possible during pregnancy and to differentiate it from caudal regression syndrome. A case of sirenomelia diagnosed early is reported together with a review of the literature. The ultrasonographic diagnosis, associated defects, the interest of color Doppler study of abdominal vasculature are discussed. Antenatal ultrasonographic diagnosis should be obtained as early as possible, before 20th gestational week at the latest. Color Doppler is helpful to confirm the diagnosis in case of bilateral renal agenesis. The main differences between sirenomelia and caudal regression syndrome (which requires a very different genetic counselling) are summarized in a table.