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1.  Ethical reflections on end-of-life signs and symptoms in the intensive care setting: a place for neuromuscular blockers? 
The death of a loved one is often an ordeal and a tragedy for those who witness it, as death is not merely the end of a life, but also the end of an existence, the loss of a unique individual who is special and irreplaceable. In some situations, end-of-life signs, such as agonal gasps, can be an almost unbearable “sight” because the physical manifestations are hard to watch and can lead to subjective interpretation and irrational fears. Ethical unease arises as the dying patient falls prey to death throes and to the manifestations of ebbing life and the physician can only stand by and watch. From this point on, medicine can put an end to suffering by the use of neuromuscular blockade, but in so doing life ceases at the same time. It is difficult, however, not to respond to the distress of loved ones and caregivers. The ethical problem then becomes the shift from the original ethical concern, i.e. the dying patient, to the patient’s loved ones. Is such a rupture due to a difference in nature or a difference in degree, given that the dying patient remains a person and not a thing as long as the body continues to lead its own life, expressed through movement and sound? Because there cannot be any simple and unequivocal answer to this question, the SRLF Ethics Commission is offering ethical reflections on end-of-life signs and symptoms in the intensive care setting, and on the use of neuromuscular blockade in this context, with presentations on the subject by two philosophers and members of the SRLF Ethics Commission, Ms Lise Haddad and Prof Dominique Folscheid. The SRLF Ethics Commission hopes to provide food for thought for everyone on this topic, which undoubtedly calls for further contributions, the aim being not to provide ready-made solutions or policy, but rather to allow everyone to ponder this question in all conscience.
PMCID: PMC4098689  PMID: 25045580
Ethics; End of life; Critical care; Gasps
2.  Does neonatal pain management in intensive care units differ between night and day? An observational study 
BMJ Open  2014;4(2):e004086.
To determine whether analgesic use for painful procedures performed in neonates in the neonatal intensive care unit (NICU) differs during nights and days and during each of the 6 h period of the day.
Conducted as part of the prospective observational Epidemiology of Painful Procedures in Neonates study which was designed to collect in real time and around-the-clock bedside data on all painful or stressful procedures.
13 NICUs and paediatric intensive care units in the Paris Region, France.
All 430 neonates admitted to the participating units during a 6-week period between September 2005 and January 2006.
Data collection
During the first 14 days of admission, data were collected on all painful procedures and analgesic therapy. The five most frequent procedures representing 38 012 of all 42 413 (90%) painful procedures were analysed.
Observational study.
Main outcome assessment
We compared the use of specific analgesic for procedures performed during each of the 6 h period of a day: morning (7:00 to 12:59), afternoon, early night and late night and during daytime (morning+afternoon) and night-time (early night+late night).
7724 of 38 012 (20.3%) painful procedures were carried out with a specific analgesic treatment. For morning, afternoon, early night and late night, respectively, the use of analgesic was 25.8%, 18.9%, 18.3% and 18%. The relative reduction of analgesia was 18.3%, p<0.01, between daytime and night-time and 28.8%, p<0.001, between morning and the rest of the day. Parental presence, nurses on 8 h shifts and written protocols for analgesia were associated with a decrease in this difference.
The substantial differences in the use of analgesics around-the-clock may be questioned on quality of care grounds.
PMCID: PMC3931991  PMID: 24556241
Pain; Neonate; Neonatology and infant care; After-hours care; painful procedures; pain
3.  The critically-ill pediatric hemato-oncology patient: epidemiology, management, and strategy of transfer to the pediatric intensive care unit 
Cancer is a leading cause of death in children. In the past decades, there has been a marked increase in overall survival of children with cancer. However, children whose treatment includes hematopoietic stem cell transplantation still represent a subpopulation with a higher risk of mortality. These improvements in mortality are accompanied by an increase in complications, such as respiratory and cardiovascular insufficiencies as well as neurological problems that may require an admission to the pediatric intensive care unit where most supportive therapies can be provided. It has been shown that ventilatory and cardiovascular support along with renal replacement therapy can benefit pediatric hemato-oncology patients if promptly established. Even if admissions of these patients are not considered futile anymore, they still raise sensitive questions, including ethical issues. To support the discussion and potentially facilitate the decision-making process, we propose an algorithm that takes into account the reason for admission (surgical versus medical) and the hemato-oncological prognosis. The algorithm then leads to different types of admission: full-support admission, “pediatric intensive care unit trial” admission, intensive care with adapted level of support, and palliative intensive care. Throughout the process, maintaining a dialogue between the treating physicians, the paramedical staff, the child, and his parents is of paramount importance to optimize the care of these children with complex disease and evolving medical status.
PMCID: PMC3423066  PMID: 22691690
Oncology; Hematology; Cancer; Stem cell; Transplantation; Graft; Child; Pediatrics; Critical care; Intensive care
4.  Transfer of drug dissolution testing by statistical approaches: Case study 
The analytical transfer is a complete process that consists in transferring an analytical procedure from a sending laboratory to a receiving laboratory. After having experimentally demonstrated that also masters the procedure in order to avoid problems in the future. Method of transfers is now commonplace during the life cycle of analytical method in the pharmaceutical industry. No official guideline exists for a transfer methodology in pharmaceutical analysis and the regulatory word of transfer is more ambiguous than for validation. Therefore, in this study, Gauge repeatability and reproducibility (R&R) studies associated with other multivariate statistics appropriates were successfully applied for the transfer of the dissolution test of diclofenac sodium as a case study from a sending laboratory A (accredited laboratory) to a receiving laboratory B. The HPLC method for the determination of the percent release of diclofenac sodium in solid pharmaceutical forms (one is the discovered product and another generic) was validated using accuracy profile (total error) in the sender laboratory A. The results showed that the receiver laboratory B masters the test dissolution process, using the same HPLC analytical procedure developed in laboratory A. In conclusion, if the sender used the total error to validate its analytical method, dissolution test can be successfully transferred without mastering the analytical method validation by receiving laboratory B and the pharmaceutical analysis method state should be maintained to ensure the same reliable results in the receiving laboratory.
PMCID: PMC3792628  PMID: 24109204
Accuracy profile; Dissolution test; Total error; Transfer; Statistics approach
5.  High Levels and Safety of Oseltamivir Carboxylate Plasma Concentrations after Nasogastric Administration in Critically Ill Children in a Pediatric Intensive Care Unit▿  
During the 2009 H1N1 influenza pandemics, the concentrations of oseltamivir (O) and its active metabolite (oseltamivir carboxylate [OC]) were determined in 11 children (1 month to 16 years of age) admitted to intensive care units for presumed severe H1N1 infection. They received oseltamivir phosphate (OP) nasogastrically at doses between 1.5 and 6.8 mg/kg of body weight. High OC concentrations were found, with a mean level of 678 ± 535 μg/liter. The mean OP concentration was 27 ± 52 μg/liter. No marked side effect was reported.
PMCID: PMC3019675  PMID: 20937783
6.  Congenital Cytomegalovirus Infection Manifesting as Neonatal Persistent Pulmonary Hypertension: Report of Two Cases  
Pulmonary Medicine  2011;2011:293285.
Various neonatal symptoms can lead to a diagnosis of congenital CMV infection. We report two cases of persistent pulmonary hypertension in relation with congenital CMV infection following maternal primary infection and reinfection, respectively. Both infants had severe refractory hypoxemia, requiring high-frequency ventilation, inhaled nitric oxide and inotropic support. One of them required extracorporeal membrane oxygenation for five days. Ganciclovir therapy was attempted in the two cases on day 12 postnatal. One of the infant died on day 15 postnatal. The other survived and is developing uneventfully at 15 months of age. Conclusion: Neonatal persistent pulmonary hypertension can be the consequence of congenital CMV infection. Intensive respiratory support and IV ganciclovir are indicated in case of life-threatening condition.
PMCID: PMC3135121  PMID: 21766016
7.  Daily estimation of the severity of multiple organ dysfunction syndrome in critically ill children 
Daily evaluation of multiple organ dysfunction syndrome has been performed in critically ill adults. We evaluated the clinical course of multiple organ dysfunction over time in critically ill children using the Pediatric Logistic Organ Dysfunction (PELOD) score and determined the optimal days for measuring scores.
We prospectively measured daily PELOD scores and calculated the change in scores over time for 1806 consecutive patients admitted to seven pediatric intensive care units (PICUs) between September 1998 and February 2000. To study the relationship between daily scores and mortality in the PICU, we evaluated changes in daily scores during the first four days; the mean rate of change in scores during the entire PICU stay between survivors and nonsurvivors; and Cox survival analyses using a change in PELOD score as a time-dependent covariate to determine the optimal days for measuring daily scores.
The overall mortality among the 1806 patients was 6.4%. A high PELOD score (≥ 20 points) on day 1 was associated with an odds ratio (OR) for death of 40.7 (95% confidence interval [CI] 20.3–81.4); a medium score (10–19 points) on day 1 was associated with an OR for death of 4.2 (95% CI 2.0–8.7). Mortality was 50% when a high score on day 1 increased on day 2. The course of daily PELOD scores differed between survivors and nonsurvivors. A set of seven days (days 1, 2, 5, 8, 12, 16 and 18) was identified as the optimal period for measurement of daily PELOD scores.
PELOD scores indicating a worsening condition or no improvement over time were indicators of a poor prognosis in the PICU. A set of seven days for measurement of the PELOD score during the PICU stay provided optimal information on the progression of multiple-organ dysfunction syndrome in critically ill children.
PMCID: PMC2917930  PMID: 20547715
8.  Lethal Necrotizing Pneumonia Caused by an ST398 Staphylococcus aureus Strain 
Emerging Infectious Diseases  2010;16(8):1330.
PMCID: PMC3298302  PMID: 20678343
Community-acquired infections; pneumonia; bacteria; Staphylococcus aureus; methicillin-resistant; Panton-Valentine leukocidin; humans; letter

Results 1-8 (8)