Exposure-safety and efficacy response relationships and population pharmacokinetics of eslicarbazepine acetate.

OBJECTIVES: Eslicarbazepine acetate (ESL) is a once-daily (QD) oral antiepileptic drug (AED) for focal-onset seizures (FOS). Pharmacokinetic (PK) and pharmacodynamic (PD) models were developed to assess dose selection, identify significant AED drug interactions, and quantitate relationships between exposure and safety and efficacy outcomes from Phase 3 trials of adjunctive ESL. METHODS: Eslicarbazepine (the primary active metabolite of ESL) population PK was evaluated using data from 1351 subjects enrolled in 14 studies (11 Phase 1 and three Phase 3 studies) after multiple oral doses ranging from 400 to 1200 mg. Population PK and PD models related individual eslicarbazepine exposures to safety outcomes and efficacy responses. RESULTS: Eslicarbazepine PK was described by a one-compartment model with linear absorption and elimination. The probability of a treatment-emergent adverse event (TEAE; dizziness, headache, or somnolence) was higher with an initial dose of ESL 800 mg than with an initial dose of ESL 400 mg QD. Body weight, sex, region, and baseline use of carbamazepine (CBZ) or lamotrigine were also found to influence the probability of TEAEs. Eslicarbazepine exposure influenced serum sodium concentration, standardized seizure frequency, and probability of response; better efficacy outcomes were predicted in patients not from Western Europe (WE; vs WE patients) and those not taking CBZ (vs taking CBZ) at baseline. CONCLUSIONS: Pharmacokinetic and PK/PD modeling were implemented during the development of ESL for adjunctive treatment of FOS in adults. This quantitative approach supported decision-making during the development of ESL, and contributed to dosing recommendations and labeling information related to drug interactions.

A2A adenosine receptor deletion is protective in a mouse model of Tauopathy.

Consumption of caffeine, a non-selective adenosine A2A receptor (A2AR) antagonist, reduces the risk of developing Alzheimer's disease (AD) in humans and mitigates both amyloid and Tau burden in transgenic mouse models. However, the impact of selective A2AR blockade on the progressive development of AD-related lesions and associated memory impairments has not been investigated. In the present study, we removed the gene encoding A2AR from THY-Tau22 mice and analysed the subsequent effects on both pathological (Tau phosphorylation and aggregation, neuro-inflammation) and functional impairments (spatial learning and memory, hippocampal plasticity, neurotransmitter profile). We found that deleting A2ARs protect from Tau pathology-induced deficits in terms of spatial memory and hippocampal long-term depression. These effects were concomitant with a normalization of the hippocampal glutamate/gamma-amino butyric acid ratio, together with a global reduction in neuro-inflammatory markers and a decrease in Tau hyperphosphorylation. Additionally, oral therapy using a specific A2AR antagonist (MSX-3) significantly improved memory and reduced Tau hyperphosphorylation in THY-Tau22 mice. By showing that A2AR genetic or pharmacological blockade improves the pathological phenotype in a Tau transgenic mouse model, the present data highlight A2A receptors as important molecular targets to consider against AD and Tauopathies.

The effect of real-time electronic monitoring of patient-reported symptoms and clinical syndromes in outpatient workflow of medical oncologists: E-MOSAIC, a multicenter cluster-randomized phase III study (SAKK 95/06).

BACKGROUND: Patients with advanced, incurable cancer receiving anticancer treatment often experience multidimensional symptoms. We hypothesize that real-time monitoring of both symptoms and clinical syndromes will improve symptom management by oncologists and patient outcomes. PATIENTS AND METHODS: In this prospective multicenter cluster-randomized phase-III trial, patients with incurable, symptomatic, solid tumors, who received new outpatient chemotherapy with palliative intention, were eligible. Immediately before the weekly oncologists' visit, patients completed the palm-based E-MOSAIC assessment (Edmonton-Symptom-Assessment-Scale, ≤3 additional symptoms, estimated nutritional intake, body weight change, Karnofsky Performance Status, medications for pain, fatigue, nutrition). A cumulative, longitudinal monitoring sheet (LoMoS) was printed immediately. Eligible experienced oncologists were defined as one cluster each and randomized to receive the immediate print-out LoMoS (intervention) or not (control). Primary analysis limited to patients having uninterrupted (>4/6 visits with same oncologist) patient-oncologist sequences was a mixed model for the difference in patients global quality of life (G-QoL; items 29/30 of EORTC-QlQ-c30) between baseline (BL) and week 6. Intention-to-treat (ITT) analysis included all eligible patients. RESULTS: In 8 centers, 82 oncologists treated 264 patients (median 66 years; overall survival intervention 6.3, control 5.4 months) with various tumors. The between-arm difference in G-QoL of 102 uninterrupted patients (intervention: 55; control: 47) was 6.8 (P = 0.11) in favor of the intervention; in a sensitivity analysis (oncologists treating ≥2 patients; 50, 39), it was 9.0 (P = 0.07). ITT analysis revealed improvement in symptoms (difference last study visit-BL: intervention -5.4 versus control 2.1, P = 0.003) and favored the intervention for communication and coping. More patients with high symptom load received immediate symptom management (chart review, nurse-patient interview) by oncologists getting the LoMoS. CONCLUSION: Monitoring of patient symptoms, clinical syndromes and their management clearly reduced patients' symptoms, but not QoL. Our results encourage the implementation of real-time monitoring in the routine workflow of oncologist with a computer solution.

Assessment of anticancer-treatment outcome in patients with metastatic castration-resistant prostate cancer-going beyond PSA and imaging, a systematic literature review.

BACKGROUND: In the past years, there has been significant progress in anticancer drug development for patients with metastatic castration-resistant prostate cancer (CRPC). However, the current instruments to assess clinical treatment response have limitations and may not sufficiently reflect patient benefit. Our objective was to systematically identify tools to evaluate both patient benefit and clinical anticancer-treatment response as basis for an international consensus process and development of a specific pragmatic instrument for men with CRPC. METHODS: PubMed, Embase and CINAHL were searched to identify currently available tools to assess anticancer-treatment benefit, other than standard imaging procedures and prostate-specific antigen measurements, namely quality of life (QoL), detailed pain assessment, physical function and objective measures of other complex cancer-related syndromes in patients with CRPC. Additionally, all CRPC phase III trials published in the last 5 years were reviewed as well as studies using physical function tools in a general cancer population. The PRIMSA statement was followed for the systematic review process. RESULTS: The search generated 1096 hits, 185 full-text papers were screened and finally 73 publications were included. Additional 89 publications were included by hand-search. We identified a total of 98 tools used in CRPC trials and grouped these into three categories: 22 tools assessing QoL domains and subgroups, 47 tools for pain assessment and 29 tools for objective measures, mainly physical function and assessment of skeletal disease burden. CONCLUSION: A wide variety of assessment tools and also efforts to standardize and harmonize patient-reported outcomes and pain assessment were identified. However, the specific needs of the increasing CRPC population living longer with their incurable cancer are insufficiently captured and objective physical outcome measures are under-represented. In the age of new anticancer drug targets and principles, new methods to monitor patient relevant outcomes of antineoplastic therapy are of utmost importance.

Validation of the Consensus-Definition for Cancer Cachexia and evaluation of a classification model--a study based on data from an international multicentre project (EPCRC-CSA).

BACKGROUND: Weight loss limits cancer therapy, quality of life and survival. Common diagnostic criteria and a framework for a classification system for cancer cachexia were recently agreed upon by international consensus. Specific assessment domains (stores, intake, catabolism and function) were proposed. The aim of this study is to validate this diagnostic criteria (two groups: model 1) and examine a four-group (model 2) classification system regarding these domains as well as survival. PATIENTS AND METHODS: Data from an international patient sample with advanced cancer (N = 1070) were analysed. In model 1, the diagnostic criteria for cancer cachexia [weight loss/body mass index (BMI)] were used. Model 2 classified patients into four groups 0-III, according to weight loss/BMI as a framework for cachexia stages. The cachexia domains, survival and sociodemographic/medical variables were compared across models. RESULTS: Eight hundred and sixty-one patients were included. Model 1 consisted of 399 cachectic and 462 non-cachectic patients. Cachectic patients had significantly higher levels of inflammation, lower nutritional intake and performance status and shorter survival. In model 2, differences were not consistent; appetite loss did not differ between group III and IV, and performance status not between group 0 and I. Survival was shorter in group II and III compared with other groups. By adding other cachexia domains to the model, survival differences were demonstrated. CONCLUSION: The diagnostic criteria based on weight loss and BMI distinguish between cachectic and non-cachectic patients concerning all domains (intake, catabolism and function) and is associated with survival. In order to guide cachexia treatment a four-group classification model needs additional domains to discriminate between cachexia stages.

Feasibility and acceptance of electronic monitoring of symptoms and syndromes using a handheld computer in patients with advanced cancer in daily oncology practice.

PURPOSE: We investigated the feasibility and acceptance of electronic monitoring of symptoms and syndromes in oncological outpatient clinics using a PALM (handheld computer). METHODS: The assessment of a combination of symptoms and clinical benefit parameters grouped in four pairs was tested in a pilot phase in advanced cancer patients. Based on these experiences, the software E-MOSAIC was developed, consisting of patient-reported symptoms and nutritional intake and objective assessments (weight, weight loss, performance status and medication for pain, fatigue, and cachexia). E-MOSAIC was then tested in four Swiss oncology centers. In order to compare the methods, patients completed the E-MOSAIC as a paper and a PALM version. Preferences of version and completion times were collected. Assessments were compared using Wilcoxon signed-rank tests , and the test-retest reliability was evaluated. RESULTS: The pilot phase was completed by 22 patients. Most patients and physicians perceived the assessment as useful. Sixty-two patients participated in the feasibility study. Twelve patients reported problems (understanding, optical, tactile), and five patients could not complete the assessment. The median time to complete the PALM-based assessment was 3 min. Forty-nine percent of patients preferred the PALM, 23 % preferred a paper version, and 28 % of patients had no preference. Paper vs. PALM revealed no significant differences in symptoms, but in nutritional intake (p = 0.013). Test-retest (1 h, n = 20) reliability was satisfactory (r = 073-98). CONCLUSION: Electronic symptom and clinical benefit monitoring is feasible in oncology outpatient clinics and perceived as useful by patients, oncology nurses, and oncologists. E-MOSAIC is tested in a prospective randomized trial.

Some Additional Data That Might Be Useful for Diastasis Recti Assessment.

Background: Diastasis recti (DR) is characterized by separation of both rectus muscles and protrusion of the median bulging, but besides median bulging DR can also entail global abdominal bulging. On other note, DR classification is based on the width of divarication, but measurement values are different at rest and at effort due to muscle contraction. Aim of the study is to provide additional features concerning the type of bulging and the width of divarication. Methods: Findings were retrospectively drawn from the data prospectively collected in the records of a continuous cohort of 105 patients (89 females, 16 males) referred for diastasis and concomitant ventral hernia repair. Results: There was a median bulging alone in 45 (42.9%) cases, a global bulging alone in 18 (17.1%) cases, both types combined in 37 (35.2%) cases and no bulging in 5 (4.8%). On 55 patients with a global bulging, 51 were females. Tape measurements values of DR width were closer to the values measured on the CT scan at leg raise than at rest. The differences were significant at rest as well as at leg raise. Though the difference at rest was highly significant (p = 0.000), the difference at effort was not far from being not significant (p = 0.049). Conclusion: Besides median bulging, presence or absence of the global bulging should be included in DR assessment. The difference between width of divarication at rest and on exertion raises the question of which value should be used for DR classification. The question is worth being debated.

Virtual Reality Therapy in Palliative Care: A Case Series.

OBJECTIVES: Virtual reality (VR) opens a variety of therapeutic options to improve symptom burden in patients with advanced disease. Until to date, only few studies have evaluated the use of VR therapy in the context of palliative care. This case series aims to evaluate the feasibility and acceptability of VR therapy in a population of palliative care patients. METHODS: In this single-site case series, we report on six palliative care patients undergoing VR therapy. The VR therapy consisted of a one-time session ranging between 20 to 60 minutes depending on the patient's needs and the content chosen for the VR sessions. A semi-structured survey was conducted and the Edmonton Symptom Assessment System (ESAS) and the Distress Thermometer were performed pre- and post-intervention. RESULTS: Overall, VR therapy was well accepted by all patients. Five out of six patients reported having appreciated VR therapy. There were individual differences of perceived effects using VR therapy. The semi-structured survey revealed that some patients felt a temporary detachment from their body and that patients were able to experience the VR session as a break from omnipresent worries and the hospital environment ("I completely forgot where I am"). There was a considerable reduction in the total ESAS score post-treatment (T0 ESASTot = 27.2; T1 ESASTot = 18.8) and a slightly reduction in distress (T0 DTTot = 4.4; T1 DTTot = 3.8). However, two patients were more tired after the intervention.Significance of Results: Our preliminary results demonstrate that VR therapy is acceptable, feasible and safe for use within a palliative care population and appears to be a viable treatment option. Clinical trials are both warranted and necessary to confirm any therapeutic effects of VR therapy, as is the need to tailor VR systems better for use in palliative care settings.

Optimization of a novel class of benzimidazole-based farnesoid X receptor (FXR) agonists to improve physicochemical and ADME properties.

Structure-guided lead optimization of recently described benzimidazolyl acetamides addressed the key liabilities of the previous lead compound 1. These efforts culminated in the discovery of 4-{(S)-2-[2-(4-chloro-phenyl)-5,6-difluoro-benzoimidazol-1-yl]-2-cyclohexyl-acetylamino}-3-fluoro-benzoic acid 7g, a highly potent and selective FXR agonist with excellent physicochemical and ADME properties and potent lipid lowering activity after oral administration to LDL receptor deficient mice.

Patterns of integrating palliative care into standard oncology in an early ESMO designated center: a 10-year experience.

BACKGROUND: Integration of specialist palliative care (PC) into standard oncology care is recommended. This study investigated how integration at the Cantonal Hospital St. Gallen (KSSG) was manifested 10 years after initial accreditation as a European Society for Medical Oncology (ESMO) Designated Center (ESMO-DC) of Integrated Oncology and Palliative Care. METHODS: A chart review covering the years 2006-2009 and 2016 was carried out in patients with an incurable malignancy receiving PC. Visual graphic analysis was utilized to identify patterns of integration of PC into oncology based on the number and nature of medical consultations recorded for both specialties. A follow-up cohort collected 10 years later was analyzed and changes in patterns of integrating specialist PC into oncology were compared. RESULTS: Three hundred and forty-five patients from 2006 to 2009 and 64 patients from 2016 were included into analyses. Four distinct patterns were identified using visual graphic analysis. The 'specialist PC-led pattern' (44.9%) and the 'oncology-led pattern' (20.3%) represent disciplines that took primary responsibility for managing patients, with occasional and limited involvement from other disciplines. Patients in the 'concurrent integrated care pattern' (18.3%) had medical consultations that frequently bounced between specialist PC and oncology. In the 'segmented integrated care pattern' (16.5%), patients had sequences of continuous consultations provided by one discipline before alternating to a stretch of consultations provided by the other specialty. In the 2016 follow-up, while the 'oncology-led pattern' occurred significantly less frequently relative to the 'specialist PC-led pattern' and the 'segmented integrated care pattern', the 'concurrent integrated care pattern' emerged more frequently when compared with the 2006-2009 follow-up. CONCLUSION: The 'specialist PC-led pattern' was the most prominent pattern in this data. The 2016 follow-up showed that a growing number of patients received a collaborative pattern of care, indicating that integration of specialist PC into standard oncology can manifest as either segmented or concurrent care pathways. Our data suggest a closer, more dynamic and flexible collaboration between oncology and specialist PC early in the disease course of patients with advanced cancer and concurrent with active treatment.

Solvent-detergent filtered (S/D-F) fresh frozen plasma and cryoprecipitate minipools prepared in a newly designed integral disposable processing bag system.

Solvent-detergent (S/D) viral inactivation was recently adapted to the treatment of single plasma donations and cryoprecipitate minipools. We present here a new process and a new bag system where the S/D reagents are removed by filtration and the final products subjected to bacterial (0.2 microm) filtration. Recovered and apheresis plasma for transfusion (FFP) and cryoprecipitate minipools (400 +/- 20 mL) were subjected to double-stage S/D viral inactivation, followed by one oil extraction and a filtration on a S/D and phthalate [di(2-ethylhexyl) phthalate (DEHP)] adsorption device and a 0.2 microm filter. The initial and the final products were compared for visual appearance, blood cell count and cell markers, proteins functional activity, von Willebrand factor (VWF) multimers and protein profile by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). Tri (n-butyl) phosphate (TnBP) was quantified by gas chromatography and Triton X-45 and DEHP by high-performance-liquid chromatography (HPLC). General safety tests were by 6.5 mL/kg intravenous injection in rats. The treated plasmas and cryoprecipitates were very clear and the protein content and functionality, VWF multimers and SDS-PAGE profiles were well preserved. TnBP and Triton X-45 were < 1 and <25 ppm, respectively, and DEHP (about 5 ppm) was less than it was in the starting materials. Blood cell counts and CD45, CD61 and glycophorin A markers were negative. There was no enhanced toxicity in rats. Thus, plasma and cryoprecipitate can be S/D-treated in this new CE-marked disposable integral processing system under conditions preserving protein function and integrity, removing blood cells, S/D agents and DEHP, and ensuring bacterial sterility. This process may offer one additional option to blood establishments for the production of virally inactivated plasma components.

Transinguinal preperitoneal repair with the Polysoft patch: prospective evaluation of recurrence and chronic pain.

OBJECTIVE: The Polysoft patch was conceived to facilitate performance of the transinguinal preperitoneal patch method and combine the advantages of patch placement in the preperitoneal space and the open inguinal approach. The aim of this prospective study was to evaluate the rate of recurrence and chronic pain at midterm follow-up. METHODS: In a cohort of 200 hernia repairs involved in a prospective evaluation, midterm results of 171 cases operated on from 1 July 2004 to 31 December 2005 were assessed. The anesthesia was spinal in 136 (79.5%) cases, local in 26 (15.2%), and general in nine (5.3%). A questionnaire was sent to patients on 30 November 2006 asking about recurrence, chronic groin pain, and satisfaction. RESULTS: With a median follow-up of 21.9 months (11.6-29.4), 167 (97.7%) patients were evaluated, two were dead, and two were lost to follow-up. There were two (1.2%) recurrences that were reoperated on; both consisted of an indirect sac that protruded between the branches of the split patch. Eleven (6.6%) patients alleged the feeling of a foreign body, and 12 (7.2%) reported pain that occurred occasionally or upon effort but did not prevent activity. In one case, the pain present before operation was unchanged, and in three cases, the pain could clearly be attributed to an origin other than the hernia repair. No case of pain that impaired activity was observed. With regard to results, 98.2% of patients were satisfied and 97.6% declared that they would adopt the same method in case they had to be operated on for another hernia. CONCLUSION: These results suggest that the technique provides a low rate of recurrence and a low percentage of chronic pain that did not impair activity.

Overexpression of mouse IsK protein fused to green fluorescent protein induces apoptosis of human astroglioma cells.

Intracellular K(+) plays an important role in controlling ion homeostasis for maintaining cell volume and inhibiting activity of pro-apoptotic enzymes. Cytoplasmic K(+) concentration is regulated by K(+) uptake via Na(+) -K(+) -ATPase and K(+) efflux through K(+) channels in the plasma membrane. The IsK (KCNE1) protein is known to co-assemble with KCNQ1 (KvLQT1) protein to form a K(+) channel underlying the slowly activating delayed rectifier K(+) outward current which delays voltage activation. In order to further study the activity and cellular localization of IsK protein, we constructed a C-terminal fusion of IsK with EGFP (enhanced green fluorescent protein). Expression of the fusion protein appeared as clusters located in the plasma membrane and induced degeneration of both transiently or stably transfected cells.

The Polysoft patch: prospective evaluation of feasibility, postoperative pain and recovery.

INTRODUCTION: The Polysoft patch was conceived to associate the advantages of placement of the patch in the preperitoneal space (PPS) and easiness of the inguinal incision. The aim of this study was to evaluate prospectively the feasibility and postoperative outcome of this method. METHODS: Two hundred Polysoft repairs were performed in 191 consecutive patients with Nyhus types III and IV hernias. The anesthesia was spinal in 146 patients (76.4%), local in 36 (18.8%) and general in 9 (4.7%). The patch was placed in the PPS through the hernial orifice in the fascia in direct hernias and through the internal orifice in indirect ones. The technical points and postoperative course data were prospectively recorded and postoperative pain was assessed daily by visual analogue scale (VAS) in 25 patients. RESULTS: The method was achieved in all the cases. The type of the hernias was as follows: 59 direct, 129 indirect (including 28 pantaloon and 16 sliding), 3 inguino-femoral and 9 recurrent. The size of the patch used was medium in 152 cases (76%) and large in 48 (24%). The large patch was used more in pantaloon, sliding and inguino-femoral hernias. In direct hernias the patch was not split; in indirect hernias the patch was split (so the wings recreate a new internal orifice around the spermatic cord) in 79 cases (61.2%) and not split (with the cord parietalized) in 50 cases (38.8%). The length of operation, postoperative hospital stay, return to daily activity, to work and analgesics consumption were [median +/- SD (extremes)]: 35 min +/- 9.1 (20-60), 1 day +/- 0.4 (0-5), 3 days +/- 1.8 (0-8), 15 days +/- 9.7 (1-30) and 3 days +/- 2.3 (0-10), respectively. The median number of analgesics units was 8 +/- 5.9 (0-32). The values of pain assessed daily by VAS (on 100) varied from 20.4 +/- 19.7 (0-60) at day 0, 25.0 +/- 24.5 (0-80) at day 1 to 7.5 +/- 13.7 (0-50) at day 7; the mean value for the week was 16.7 +/- 16.7 (0-57). There were 14 (7%) benign postoperative complications. CONCLUSION: This study permitted the definition of some technical points and showed that the Polysoft patch can be used for all types of hernias with a weak posterior wall, including complex cases (big scrotal, pantaloon, sliding and recurrent), with a low risk of postoperative complications, a low level of postoperative pain and a short recovery time.

[Mechanisms of neuronal death in Huntington's disease. First part: general considerations and histopathological features]. / Mécanismes de mort neuronale dans la maladie de Huntington. Premiere partie: Généralités et aspects histologiques.

Huntington's disease is caused by an abnormal CAG expansion within the gene encoding Huntingtin which induces a major cortico-striatal degeneration as well as motor and cognitive impairments. Since the discovery of the present mutation, a number of experimental data have been collected to uncover the physiopathological consequences of mutated Huntingtin expression. Here, we review the molecular and cellular mechanisms underlying and show how this better knowledge can be translate to clinical trials in patients.

[Mechanisms of neuronal death in Huntington's disease. Second part: therapeutic challenges]. / Mécanismes de mort neuronale dans la maladie de Huntington. Seconde partie: aspects thérapeutiques.

Huntington's disease is caused by an abnormal CAG expansion within the gene encoding Huntingtin which induces a major cortico-striatal degeneration as well as motor and cognitive impairments. Since the discovery of the present mutation, a number of experimental data have been collected to uncover the physiopathological consequences of mutated Huntingtin expression. Here, we review the therapeutic challenges of Huntington's disease.

Molecular pathways involved in the neurotoxicity of 6-OHDA, dopamine and MPTP: contribution to the apoptotic theory in Parkinson's disease.

Parkinson's disease (PD) is a neurodegenerative disorder characterized by a preferential loss of the dopaminergic neurons of the substantia nigra pars compacta. Although the etiology of PD is unknown, major biochemical processes such as oxidative stress and mitochondrial inhibition are largely described. However, despite these findings, the actual therapeutics are essentially symptomatical and are not able to block the degenerative process. Recent histological studies performed on brains from PD patients suggest that nigral cell death could be apoptotic. However, since post-mortem studies do not allow precise determination of the sequence of events leading to this apoptotic cell death, the molecular pathways involved in this process have been essentially studied on experimental models reproducing the human disease. These latter are created by using neurotoxic compounds such as 6-hydroxydopamine (6-OHDA), 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) or dopamine (DA). Extensive study of these models have shown that they mimick, in vitro and in vivo, the histological and/or the biochemical characteristics of PD and thus help to define important cellular actors of cell death presumably critical for the nigral degeneration. This review reports recent data concerning the biochemical and molecular apoptotic mechanisms underlying the experimental models of PD and correlates them to the phenomena occurring in human disease.

[The pain of the newborn: between reality and perception]. / La douleur des nouveau-nés: entre réalité et perception.

UNLABELLED: A newborn hospitalized in neonatology suffers a lot of painful and fully perceived procedures. However this pain is not enough taken into consideration. There are various reasons for this failure. The objective of our study was to analyze the perception of 3 groups of participants (parents, nurses and doctors) about newborns'pain. We wanted to compare these perceptions with pain scales (EDIN and BBdol scale) and to study their connection with newborn illness severity and mortality risk scores (SNAP and CRIB). POPULATION AND METHOD: We have led a prospective study involving 80 newborns. Questionnaires assessing, with the help of a visual analogic scale, the pains' perception and the efficiency of the treatment of this pain were given to the 3 groups of participants. RESULTS: Parents assessed that their newborn feels an important pain (median: 5/10), that was not correlated with pain scales. Nurses and doctors assessed a lower level of pain (median: 2/10), greatly correlated with the pain scales. Parents assessed that the treatment of pain was better when the newborn was severely ill. The nurses, and even more the doctors, assessed the opposite effect. The nurses appeared to hold an intermediate position between parents and doctors. Nurses underlined moreover some lack of communication of the doctors about the newborns' pain. This communication problem is a major hindrance to the adequate treatment of pain.

Lower-limb hypoplasia due to intrauterine infection with herpes simplex virus type 2: possible confusion with intrauterine varicella-zoster syndrome.

A neonate with lower-limb hypoplasia, cutaneous scars, bilateral chorioretinitis, and multiple brain abnormalities is presented. Intrauterine herpes simplex virus type 2 (HSV-2) infection was established on the basis of serological testing of the mother and viral cultures of the child's cutaneous lesions, obtained soon after birth. This is, to the best of our knowledge, the first case of a patient with in utero-acquired HSV-2 infection presenting with a limb hypoplasia. It illustrates that, in addition to congenital varicella-zoster syndrome, HSV-2 infection should also be considered in patients presenting with limb hypoplasia.