Cortical abnormalities in bipolar disorder: an MRI analysis of 6503 individuals from the ENIGMA Bipolar Disorder Working Group.

Despite decades of research, the pathophysiology of bipolar disorder (BD) is still not well understood. Structural brain differences have been associated with BD, but results from neuroimaging studies have been inconsistent. To address this, we performed the largest study to date of cortical gray matter thickness and surface area measures from brain magnetic resonance imaging scans of 6503 individuals including 1837 unrelated adults with BD and 2582 unrelated healthy controls for group differences while also examining the effects of commonly prescribed medications, age of illness onset, history of psychosis, mood state, age and sex differences on cortical regions. In BD, cortical gray matter was thinner in frontal, temporal and parietal regions of both brain hemispheres. BD had the strongest effects on left pars opercularis (Cohen's d=-0.293; P=1.71 × 10-21), left fusiform gyrus (d=-0.288; P=8.25 × 10-21) and left rostral middle frontal cortex (d=-0.276; P=2.99 × 10-19). Longer duration of illness (after accounting for age at the time of scanning) was associated with reduced cortical thickness in frontal, medial parietal and occipital regions. We found that several commonly prescribed medications, including lithium, antiepileptic and antipsychotic treatment showed significant associations with cortical thickness and surface area, even after accounting for patients who received multiple medications. We found evidence of reduced cortical surface area associated with a history of psychosis but no associations with mood state at the time of scanning. Our analysis revealed previously undetected associations and provides an extensive analysis of potential confounding variables in neuroimaging studies of BD.

IVIVC approach based on carbamazepine bioequivalence studies combination.

The aim of the present study was to explore the feasibility of obtaining an IVIVC by combination of data from two bioequivalence (BE) studies of carbamazepine (CBZ) in order to assess if the previously published dissolution media and conditions could be applicable to any other oral immediate release (IR) CBZ products with conventional excipients. Twenty-four healthy male subjects from two BE study received one IR dose of the test (test 1 or 2) or the reference formulation (Tegretol, 400 mg). Dissolution studies of the IR CBZ tablets were performed in two different laboratories. In order to develop IVIVC, individual or average data analysis were considered. A level C, level B and level A correlation have been successfully developed by combining data from different BE studies of CBZ immediate release drug products. A level A IVIVC was developed with all four datasets with a good R2 for all the combinations of in vivo and in vitro data. A dissolution medium containing 1% SLS has demonstrated its suitability as the universal biopredictive dissolution medium, even if different batches and in vivo/in vitro studies were combined.

Assessment of trace element contamination and effects on Paracentrotus lividus using several approaches: Pollution indices, accumulation factors and biochemical tools.

Among the most common contaminants in marine ecosystems, trace elements are recognized as serious pollutants. In Corsica (NW Mediterranean Sea), near the old asbestos mine at Canari, trace elements from the leaching of mine residues have been discharged into the sea for several decades. The aim of this study was to assess the levels of contamination in this area and the potential effects on Paracentrotus lividus (Lamarck, 1816) using pollution indices, accumulation factors and biochemical tools. For this purpose, the concentration of 24 trace elements was measured in sea urchins (gonads and gut content), macroalgae, seawater column and sediment collected at 12 stations nearby the old asbestos mine and at a reference site. The bioaccumulation of trace elements occurs as follows: macroalgae > gut > gonads. TEPI contribute to highlight contamination gradients which are mainly due to the dominant marine currents allowing the migration of mining waste along the coastline. This hypothesis was supported by TESVI, which identified characteristic trace elements in the southern area of the mine. High hydrogen peroxide content, associated with elevated catalase and glutathione-S-transferase enzyme activities, were also identified at these sites and at the reference site. Trace elements contamination as well as several abiotic factors could explain these results (e.g. microbiological contamination, hydrodynamic events, etc.). The results obtained in this study suggest that oxidative stress induced by contamination does not affect the health of Paracentrotus lividus. This work has provided a useful dataset allowing better use of sea urchins and various tools for assessing trace element contamination in coastal ecosystems.

Stress response to trace elements mixture of different embryo-larval stages of Paracentrotus lividus.

This study investigated for the first time the oxidative biomarkers responses in all larval stages of sea urchin. The contamination effects were reproduced by using contaminated seawater to concentrations measured in the area adjacent to an old asbestos mine at factors of 5 and 10. The results suggested that the concentrations were not sufficiently high to induce a major oxidative stress. The biometric differences make this method a more sensitive approach for assessing the effects on sea urchin larvae. Measurements of specific activities of antioxidant enzymes at each stage suggested a high capacity of the larvae to respond to oxidative stress. This normal activity of the organism must be considered in future research. This work also highlighted the importance of spawners provenance in ecotoxicological studies. These data are essential to better understand the stress responses of sea urchin larvae and provide baseline information for later environmental assessment research.

Early treatment of obstructive apnoea and stroke outcome: a randomised controlled trial.

The aim of the present study was to assess the impact of nasal continuous positive airway pressure (nCPAP) in ischaemic stroke patients followed for 2 yrs. Stroke patients with an apnoea-hypopnoea index ≥ 20 events·h⁻¹ were randomised to early nCPAP (n = 71; 3-6 days after stroke onset) or conventional treatment (n = 69). The Barthel Index, Canadian Scale, Rankin Scale and Short Form-36 were measured at baseline, and at 1, 3, 12 and 24 months. The percentage of patients with neurological improvement 1 month after stroke was significantly higher in the nCPAP group (Rankin scale 90.9 versus 56.3% (p < 0.01); Canadian scale 88.2 versus 72.7% (p < 0.05)). The mean time until the appearance of cardiovascular events was longer in the nCPAP group (14.9 versus 7.9 months; p = 0.044), although cardiovascular event-free survival after 24 months was similar in both groups. The cardiovascular mortality rate was 0% in the nCPAP group and 4.3% in the control group (p = 0.161). Early use of nCPAP seems to accelerate neurological recovery and to delay the appearance of cardiovascular events, although an improvement in patients' survival or quality of life was not shown.

Addition of clonidine to a continuous patient-controlled epidural infusion of low-concentration levobupivacaine plus sufentanil in primiparous women during labour.

We studied the potentiation of analgesia for labour by the addition of clonidine to epidural low-concentration levobupivacaine with sufentanil in a randomised, double-blinded study. We enrolled primiparous women who were in spontaneous labour. The study solutions, made of 100 ml levobupivacaine 0.0625% plus sufentanil 0.45 µg.ml(-1) and either 150 µg clonidine or no clonidine, were used for induction of analgesia, and for its maintenance with self-administered boluses and a continuous background infusion. The need for additional epidural boluses during labour was lower and analgesia and maternal satisfaction were better in the clonidine (n = 57) than in the control group (n = 58). Blood pressure was lower and the rate of instrumental delivery higher in the clonidine group. Clonidine (1.36 µg.ml(-1)) added to the epidural solution of low-concentration levobupivacaine improves the quality of analgesia. The relevance of the haemodynamic effects should be explored in larger validation studies.

Continuous patient-controlled epidural infusion of levobupivacaine plus sufentanil in labouring primiparous women: effects of concentration.

The effects of two different concentrations of epidural levobupivacaine were compared when used to provide analgesia for labour. Primiparous women in spontaneous uncomplicated labour were enrolled in a prospective, randomised and partially double-blinded study. The study solutions were either 0.568 mg x ml(-1) levobupivacaine (low concentration group) or 1.136 mg x ml(-1) levobupivacaine (high concentration group), with sufentanil 0.45 microg x ml(-1) added to both solutions. Epidural analgesia was initiated with 20 ml of the study solution, followed by a standardised algorithm of top-up bolus injections. Epidural analgesia was then continued by self-administered boluses of 5-ml plus a continuous infusion of 5 ml x h(-1). Analgesia was found to be more efficacious in the high-concentration group. The dose of levobupivacaine administered was higher and sometimes overstepping recommended limits in the high concentration group, but with no observed increase in side-effects. The choice between these two concentrations may still be made according to the patient's and the practitioner's preferences. The effects of an intermediate concentration should be studied in the future.

[Normal childbirth: physiologic labor support and medical procedures. Guidelines of the French National Authority for Health (HAS) with the collaboration of the French College of Gynaecologists and Obstetricians (CNGOF) and the French College of Midwives (CNSF) - Mother's wellbeing and regional or systemic analgesia for labor]. / Accouchement normal : accompagnement de la physiologie et interventions médicales. Recommandations de la Haute Autorité de Santé (HAS) avec la collaboration du Collège National des Gynécologues Obstétriciens Français (CNGOF) et du Collège National des Sages-Femmes de France (CNSF) ­ Bien être maternel et prise en charge médicamenteuse de la douleur.

INTRODUCTION: These guidelines deal with the parturient wellbeing in terms of hydration and regional and systemic pain management during labour. METHOD: Guidelines were established based on literature analysis and experts consensus. RESULTS: Clear liquids consumption is permitted all along labor and postpartum, without volume limitation, in patients at low risk of general anesthesia (grade B). The consumption of solid foods is not recommended during the active stage of labor (consensus agreement). It is recommended to promote on regional analgesia to prevent inhalation (grade A). Pain relief using regional analgesia is a part of normal childbirth. It is recommended to provide regional analgesia to parturient who wish these technics. Regional analgesia is the safest and most effective analgesic method for the mother (grade A) and the child (grade B). It is recommended to inform women on the analgesic technics, to respect their choice and consider the right for a parturient to change her strategy in obstetrical circumstances or in cases of untractable pain (consensus agreement). It is recommended to perform a "low-dose" regional analgesia that respects the experience of childbirth (grade A) and maintain it with a patient controlled epidural analgesia technics (grade A). There is no minimum cervical dilation to allow epidural analgesia (grade A). In cases of rapid labor or after delivery for revision, spinal or combined spinal epidural can be used (grade C). Epidural has not to be ended before birth (consensus agreement). Blood pressure and fetal heart rate must be monitored every 3minutes after induction and/or each 10mL bolus then hourly (consensus agreement). Systematic and preventive fluid loading is not needed if only due to regional analgesia (grade B). Deambulation or postures are allowed in the absence of motor block and must be traced and do not alter the distribution of the regional analgesia (grade C). The postures of childbirth do not alter regional analgesia spread (NP2). There is no effect low dose regional analgesia on the duration of obstetric labor, nor the rate of instrumental births or caesarean section (NP1). Systematic use of oxytocin due to epidural analgesia is neither useful nor recommended (AE). Regional analgesia has no side effect on the fetus or newborn (NP1). If regional analgesia is contraindicated or during the waiting time, alternatives analgesic drugs (entonox, nalbuphine and tramadol or pudendal block) can be used but their analgesic efficiency remains mediocre to moderate and they are associated with adverse maternal and especially neonatal side effects (NP2). Remifentanil, ketamine and volatile anesthetics are excluded from these recommendations. CONCLUSION: The present guidelines were established to update wellbeing of normal parturient during normal labor: hydration is recommended and low dose patient-controlled regional (epidural and spinal) analgesia is the most effective and safest analgesic method.

[Normal childbirth: physiologic labor support and medical procedures. Guidelines of the French National Authority for Health (HAS) with the collaboration of the French College of Gynaecologists and Obstetricians (CNGOF) and the French College of Midwives (CNSF) -- Text of the Guidelines (short text)]. / Accouchement normal : accompagnement de la physiologie et interventions médicales. Recommandations de la Haute Autorité de Santé (HAS) avec la collaboration du Collège National des Gynécologues Obstétriciens Français (CNGOF) et du Collège National des Sages-Femmes de France (CNSF) ­ Texte des recommandations (texte court).

OBJECTIVE: The objective of these guidelines is to define for women at low obstetric risk modalities that respect the physiology of delivery and guarantee the quality and safety of maternal and newborn care. METHODS: These guidelines were made by a consensus of experts based on an analysis of the scientific literature and the French and international recommendations available on the subject. RESULTS: It is recommended to conduct a complete initial examination of the woman in labor at admission (consensus agreement). The labor will be monitored using a partogram that is a useful traceability tool (consensus agreement). A transvaginal examination may be offered every two to four hours during the first stage of labor and every hour during the second stage of labor or before if the patient requests it, or in case of a warning sign. It is recommended that if anesthesia is required, epidural or spinal anesthesia should be used to prevent bronchial inhalation (grade A). The consumption of clear fluids is permitted throughout labor in patients with a low risk of general anesthesia (grade B). It is recommended to carry out a "low dose" epidural analgesia that respects the experience of delivery (grade A). It is recommended to maintain the epidural analgesia through a woman's self-administration pump (grade A). It is recommended to give the woman the choice of continuous (by cardiotocography) or discontinuous (by cardiotocography or intermittent auscultation) monitoring if the conditions of maternity organization and the permanent availability of staff allow it and, after having informed the woman of the benefits and risks of each technique (consensus agreement). In the active phase of the first stage of labor, the dilation rate is considered abnormal if it is less than 1cm/4h between 5 and 7cm or less than 1cm/2h above 7cm (level of Evidence 2). It is then recommended to propose an amniotomy if the membranes are intact or an oxytocin administration if the membranes are already ruptured, and the uterine contractions considered insufficient (consensus agreement). It is recommended not to start expulsive efforts as soon as complete dilation is identified, but to let the presentation of the fetus drop (grade A). It is recommended to inform the gynecologist-obstetrician in case of nonprogression of the fetus after two hours of complete dilation with sufficient uterine dynamics (consensus agreement). It is recommended not to use abdominal expression (grade B). It is recommended to carry out preventive administration of oxytocin at 5 or 10 IU to prevent PPH after vaginal delivery (grade A). In the case of placental retention, it is recommended to perform a manual removal of the placenta (grade A). In the absence of bleeding, it should be performed 30minutes but not more than 60minutes after delivery (consensus agreement). It is recommended to assess at birth the breathing or screaming, and tone of the newborn to quickly determine if resuscitation is required (consensus agreement). If the parameters are satisfactory (breathing present, screaming frankly, and normal tonicity), it is recommended to propose to the mother that she immediately place the newborn skin-to-skin with her mother if she wishes, with a monitoring protocol (grade B). Delayed cord clamping is recommended beyond the first 30seconds in neonates, not requiring resuscitation (grade C). It is recommended that the first oral dose (2mg) of vitamin K (consensus agreement) be given systematically within two hours of birth. CONCLUSION: These guidelines allow women at low obstetric risk to benefit from a better quality of care and optimal safety conditions while respecting the physiology of delivery.

[Laparoscopy during pregnancy: experience of the French university hospital of Clermont-Ferrand]. / Coelioscopie en cours de grossesse: expérience du centre hospitalier universitaire (CHU) de Clermont-Ferrand.

OBJECTIVE: To describe perioperative management and perinatal outcome for patients undergoing laparoscopy during pregnancy. PATIENTS AND METHODS: We conducted a retrospective study of all cases of laparoscopy during pregnancy performed in our university hospital over a period of six years (from February 2000 to February 2006). RESULTS: We observed 34 cases managed from five to 30 weeks of gestation (11 cases of adnexal torsion, ten adnexal masses, eight appendicitis, one cholecystitis, one sigmoid volvulus, one pelvic peritonitis, two heterotopic pregnancies). Open laparoscopy was used in 12 cases. Conversion was required in two cases mainly due to adherences (one borderline lesion at 16 weeks and one tubal cyst torsion at 24 weeks). No maternal complication was observed. One miscarriage occurred at Day 1 (peritonitis, five weeks of gestation) and one patient opted for abortion. No threatened preterm labour occurred after the perioperative course and no neonate required admission in neonatology unit. DISCUSSION AND CONCLUSION: This study illustrates safety and efficacy of laparoscopy in management of surgical diseases in the gravid patient. Emergent indications are the most common, highlighting the need for all physicians to know specific recommendations related to laparoscopy during pregnancy.

[Autoimmune hepatitis and pregnancy: about a patient's three consecutive pregnancies]. / Hépatite auto-immune et grossesse: à propos de trois grossesses consécutives chez une patiente.

Spontaneous evolution of autoimmune hepatitis during pregnancy is not well known, nor are its consequences on pregnancy evolution. Immunosuppressive treatment during pregnancy is sometimes necessary but the long- and short-term consequences are unrecognized. We relate a patient's disease with autoimmune hepatitis and cirrhosis and three consecutive pregnancies with different obstetrical and medical complications.

External rotation of the femoral component increases asymmetry of the posterior condyles.

AIMS: The morphometry of the distal femur was largely studied to improve bone-implant fit in total knee arthroplasty (TKA), but little is known about the asymmetry of the posterior condyles. This study aimed to investigate the dimensions of the posterior condyles and the influence of externally rotating the femoral component on potential prosthetic overhang or under-coverage. PATIENTS AND METHODS: We analysed the shape of 110 arthritic knees at the time of primary TKA using pre-operative CT scans. The height and width of each condyle were measured at the posterior femoral cut in neutral position, and in 3º and 5º of external rotation, using both central and medial referencing systems. We compared the morphological characteristics with those of 14 TKA models. RESULTS: In the neutral position, the dimensions of the condyles were nearly equal. Externally rotating the femoral cut by 3º and 5º with 'central referencing' induced width asymmetry > 3 mm in 23 (21%) and 33 (30%) knees respectively, while with 'medial referencing' it induced width asymmetry > 3 mm in 43 (39%) and 75 (68%) knees respectively. The asymmetries induced by rotations were not associated with gender, aetiology or varus-valgus alignment. CONCLUSION: External rotation may amplify the asymmetry between the medial and lateral condyles, and exacerbate prosthetic overhang, particularly in the superolateral zone. 'Central referencing' guides result in less potential prosthetic overhang than 'medial referencing' guides. Cite this article: Bone Joint J 2017;99-B:894-903.

Hemoperitoneum in peripartum: A case-series.

Hemorrhages are the first cause of perinatal deaths in French women. Thirteen percent of these deaths are not linked to obstetrical problems but rather to hemoperitoneum. These incidents are under-diagnosed and as a result, treatment is delayed and fetal and maternal mortality increases. We report three cases of patients, all White female in their last trimester of a non-problematic pregnancy presenting with hemoperitoneum and resulting in different outcomes. The analysis of published materials and of our cases leads us to infer that a diagnosis of hemoperitoneum must be considered in pregnant women when abdominal pain, symptoms of shock and a decrease in hemoglobin are associated. An immediate response and intensive care followed by hemostatic surgery give these patients the best chance to survive.

Quality of life following lower third molar removal.

The objective of this study was to evaluate the quality of life (QoL) and degree of satisfaction among adult outpatients after surgical extraction of a lower third molar under local anaesthesia, and to assess the impact of thorough explanation of the anticipated postoperative course on their pain and daily activities. Ninety-two patients filled a questionnaire assessing social isolation, working isolation, eating ability, speaking ability, sleep impairment, physical appearance, discomfort at suture removal and overall satisfaction on days 4 and 7 after surgery. A 100-mm visual analogue scale (VAS) of pain was scored by the patients every day after extraction until day 7. Before extraction, patients were randomly allocated to one of two groups: the test group received detailed verbal instructions from a surgeon about the postoperative course after extraction of the third molars, together with a written text containing postoperative instructions. One day after extraction, they were asked by telephone about their status. The control group only received the written text with postoperative instructions, with a few basic oral explanations. Ninety-one patients (53 of them female) completed the questionnaires. The decrease in pain was linear over time. Men referred significantly less pain than women, but there were no statistically significant differences between the test and control groups. The test group was characterized by a significantly greater inability to work. Lower third molar surgery significantly affects patient quality of life and environment, particularly during the first 3 days after extraction.

[Laparoscopic management of ovarian cysts during pregnancy]. / Traitement coelioscopique des kystes de l'ovaire au cours de la grossesse.

OBJECTIVE: To evaluate the results of laparoscopic surgery in the management of ovarian cysts in pregnant patients. PATIENTS AND METHODS: Retrospective study including 26 pregnant patients who underwent the laparoscopic management of ovarian cysts. The indications for surgery were persistent adnexal mass, abnormal ovarian cysts revealed by ultrasound examination, suspicion of cyst complications. The technique used, the immediate postoperative results and obstetrical outcomes were studied. RESULTS: Twelve patients were operated during the first trimester of pregnancy, 13 in the second, and one in the third trimester. A 12 mmHg CO2 pneumoperitoneum was created, using a Veress needle in 22 cases, and an open technique in 4 cases. Trocar sites were decided according to the uterine size and to the cyst situation. A cystectomy was performed in 11 cases, an adnexectomy in 7 cases, an oophorectomy in one case, a cyst aspiration with a biopsy of the cyst wall in 6 cases and an ovarian torsion removal in one case. A conversion to laparotomy was necessary in 3 cases. There were no immediate postoperative complications and obstetrical outcomes were good in all cases. DISCUSSION AND CONCLUSION: In pregnant patients, laparoscopic management of adnexal masses appears to be safe for both mother and child.

[Pelvic pain by acute symphysis pubis separation after vaginal delivery]. / Douleur pelvienne par disjonction pubienne après accouchement par voie basse.

Pelvic pain during pregnancy and postpartum period is common. Pubic separation is a physiologic phenomenon caused by pregnancy and delivery. It's an aetiology of pregnancy and postpartum pain requiring a specialized management in case of severe pain. We report the case of a 34-year-old multiparous woman suffering from severe pubic symphysis pain after twin delivery by vaginal approach, with extraction support, under epidural analgesia. Pubic symphysis separation was diagnosed according both to the clinical symptoms and to the radiology. A local anesthetic infiltration was performed twice to substantially relieve the patient.

[Pregnant woman anaesthetic management in gynaecologic laparoscopic surgery at the maternity hospital of Clermont-Ferrand]. / Prise en charge anesthésique de la femme enceinte pour coeliochirurgie gynécologique non obstétricale à la maternité de Clermont-Ferrand.

OBJECTIVE: To evaluate the anaesthetic management intended for pregnant women in the field of non obstetric and gynaecologic laparoscopic surgery. STUDY DESIGN: Retrospective and monocentric investigation. PATIENTS AND METHODS: Analysis of the anaesthetic and obstetric files from 27 pregnant women operated on in the establishment, between January 2001 and July 2004. RESULTS: 27 female patients involved in the study. The mean pregnancy term was 15 weeks when laparoscopic surgery was performed, though a single patient was at 30 weeks. The average duration of the surgery was 61 minutes, of which 28 minutes were dedicated to pneumoperitoneum. Twenty-four patients underwent general anaesthesia, the three others underwent locoregional anaesthesia. During the perioperative period no surgical, anaesthetic or obstetric complications were observed. CONCLUSION: Laparoscopic surgery during pregnancy requires double skilled management, both in anaesthesiology and obstetrics. On haemodynamics and breathing, pneumoperitoneum does not induce any additional effects when compared to operations without pregnancy. Except with delivery cases, anaesthetic support in laparoscopic surgery intended for pregnant women eventually does not generate any specific problems, but requires the same rigorous management as the one usually following surgery for pregnant patients.

Extensor tendon ruptures after total knee arthroplasty.

Extensor tendon rupture is a rare but serious complication after total knee arthroplasty (TKA) that impairs active knee extension, thereby severely affecting knee function. Surgery is usually required. Surgical options range from simple suturing to allograft reconstruction of the entire extensor mechanism and include intermediate methods such as reconstruction using neighbouring tendons or muscles, synthetic ligament implantation, and partial allograft repair. Simple suturing carries a high failure rate and should therefore be routinely combined with tissue augmentation using a neighbouring tendon or a synthetic ligament. After allograft reconstruction, outcomes are variable and long-term complications common. Salvage procedures for managing the most severe cases after allograft failure involve reconstruction using gastrocnemius or vastus flaps. Regardless of the technique used, suturing must be performed under tension, with the knee fully extended, and rehabilitation must be conducted with great caution. Weaknesses of available case-series studies include small sample sizes, heterogeneity, and inadequate follow-up duration. All treatment options are associated with substantial failure rates. The patient should be informed of this fact and plans made for a salvage option. Here, the main techniques and their outcomes are discussed, and a therapeutic strategy is suggested.