Speech prognosis and need of pharyngeal flap for non syndromic vs syndromic Pierre Robin Sequence

BACKGROUND: The aim of this retrospective study was to evaluate speech outcome and need of a pharyngeal flap in children born with nonsyndromic Pierre Robin Sequence (nsPRS) vs syndromic Pierre Robin Sequence (sPRS). METHODS: Pierre Robin Sequence was diagnosed when the triad microretrognathia, glossoptosis, and cleft palate were present. Children were classified at birth in 3 categories depending on respiratory and feeding problems. The Borel-Maisonny classification was used to score the velopharyngeal insufficiency. RESULTS: The study was based on 38 children followed from 1985 to 2006. For the 25 nsPRS, 9 (36%) pharyngeal flaps were performed with improvements of the phonatory score in the 3 categories. For the 13 sPRS, 3 (23%) pharyngeal flaps were performed with an improvement of the phonatory scores in the 3 children. There was no statistical difference between the nsPRS and sPRS groups (P = .3) even if we compared the children in the 3 categories (P = .2). CONCLUSIONS: Children born with nsPRS did not have a better prognosis of speech outcome than children born with sPRS. Respiratory and feeding problems at birth did not seem to be correlated with speech outcome. This is important when informing parents on the prognosis of long-term therapy

Valved stents for transapical pulmonary valve replacement.

OBJECTIVES: Pulmonary valve insufficiency remains a leading cause for reoperations in congenital cardiac surgery. The current percutaneous approach is limited by the size of the access vessel and variable right ventricular outflow tract morphology. This study assesses the feasibility of transapical pulmonary valve replacement based on a new valved stent construction concept. METHODS: A new valved stent design was implanted off-pump under continuous intracardiac echocardiographic and fluoroscopic guidance into the native right ventricular outflow tract in 8 pigs (48.5 +/- 6.0 kg) through the right ventricular apex, and device function was studied by using invasive and noninvasive measures. RESULTS: Procedural success was 100% at the first attempt. Procedural time was 75 +/- 15 minutes. All devices were delivered at the target site with good acute valve function. No valved stents dislodged. No animal had significant regurgitation or paravalvular leaking on intracardiac echocardiographic analysis. All animals had a competent tricuspid valve and no signs of right ventricular dysfunction. The planimetric valve orifice was 2.85 +/- 0.32 cm(2). No damage to the pulmonary artery or structural defect of the valved stents was found at necropsy. CONCLUSIONS: This study confirms the feasibility of direct access valve replacement through the transapical procedure for replacement of the pulmonary valve, as well as validity of the new valved stent design concept. The transapical procedure is targeting a broader patient pool, including the very young and the adult patient. The device design might not be restricted to failing conduits only and could allow for implantation in a larger patient population, including those with native right ventricular outflow tract configurations.

3

Acute organophosphate (OP) intoxication is associated with many symptoms and clinical signs, including potentially life-threatening seizures and status epilepticus. Instead of being linked to the direct cholinergic toxidrome, OP-related seizures are more probably linked to the interaction of OPs with acetylcholineindependent neuromodulation pathways, such as GABA and NMDA. The importance of preventing, or recognizing and treating OP-related seizures lies in that, the central nervous system (CNS) damage from OP poisoning is thought to be due to the excitotoxicity of the seizure activity itself rather than a direct toxic effect. Muscular weakness and paralysis occurring 1-4 days after the resolution of an acute cholinergic toxidrome, the intermediate syndrome is usually not diagnosed until significant respiratory insufficiency has occurred; it is nevertheless a major cause of OP-induced morbidity and mortality and requires aggressive supportive treatment. The condition usually resolves spontaneously in 1-2 weeks.Treatment of OP intoxication relies on prompt diagnosis, and specific and immediate treatment of the lifethreatening symptoms. Since patients suffering from OP poisoning can secondarily expose care providers via contaminated skin, clothing, hair, or body fluids. EMS and hospital caregivers should be prepared to protect themselves with appropriate protective equipment, isolate such patients, and decontaminate them. After prompt decontamination, the initial priority of patient management is an immediate ABCDE (A : airway, B : breathing, C : circulation, D : dysfunction or disability of the central nervous system, and E : exposure) resuscitation approach, including aggressive respiratory support, since respiratory failure is the usual ultimate cause of death. The subsequent priority is initiating atropine therapy to oppose the muscarinic symptoms and diazepam to prevent or control seizures, with oximes added to enhance acetylcholinesterase (AChE) activity recovery. Large doses of atropine and oximes may be necessary for poisoning due to suicidal ingestions of OP pesticides.

Transapical aortic 'valve-in-valve' procedure for degenerated stented bioprosthesis.

Standard surgical aortic valve replacement with a biological prosthesis remains the treatment of choice for low- and mid-risk elderly patients (traditionally >65 years of age) suffering from severe symptomatic aortic valve stenosis or insufficiency, and for young patients with formal contraindications to long-lasting anticoagulation. Unfortunately, despite the fact that several technical improvements have noticeably improved the resistance of pericardial and bovine bioprostheses to leaflet calcifications and ruptures, the risk of early valve failure with rapid degeneration still exists, especially for patients under haemodialysis and for patients <60 years of age at the time of surgery. Until now, redo open heart surgery under cardiopulmonary bypass and on cardioplegic arrest was the only available therapeutic option in case of bioprosthesis degeneration, but it carried a higher surgical risk when elderly patients with severe concomitant comorbidities were concerned. Since a few years, the advent of new transcatheter aortic valve procedures has opened new horizons in cardiac surgery and, in particular, the possibility of implanting stented valves within the degenerated stented bioprosthesis, the so-called 'valve-in-valve' (VinV) concept, has become a clinical practice in experienced cardiac centres. The VinV procedure represents a minimally invasive approach dedicated to high-risk redo patients, and published preliminary reports have shown a success rate of 100% with absence of significant valvular leaks, acceptable transvalvular gradients and low complication rate. However, this procedure is not riskless and the most important concerns are about the size mismatch and the right positioning within the degenerated bioprosthesis. In this article, we review the limited available literature about VinV procedures, underline important technical details for the positioning and provide guidelines to prevent valve-prosthesis mismatch comparing the three sizes of the only commercially available transapical device, the Edwards Sapien, with the inner diameter of three of the most commonly used stented bioprostheses.

Recommandations de vaccination pour les patients atteints de maladie chronique [Immunization guidelines regarding patients with a chronic disease].

Some chronic diseases--like renal failure, liver insufficiency, chronic lung disease, cardiac involvement, diabetes mellitus, asplenia--present limited defects of the immune system and/or a higher risk of infection; therefore, patients with such pathologies should get selective vaccinations. The efficacy of immunization decreases with disease progression; for this reason, these patients should be immunized as soon as possible. At the beginning of their disease, these patients do not need a specialized treatment and are followed by the general practitioner alone who is in charge of immunizing them as well as contact people of any immunocompromised patient. OFSP's regular vaccinations programme is recommended, as well as selective vaccinations against influenza, pneumococci and viral hepatitis, depending on the underlying chronic disease.

Calcifications vasculaires et déficit en vitamine K: un facteur de risque modifiable dans l'insuffisance rénale chronique [Vascular calcifications and vitamin K deficiency: a modifiable risk factor in chronic kidney disease].

The mechanisms of vascular calcifications in chronic renal failure are complex. Apart for clotting factors, vitamin K-dependent proteins include matrix Gla protein. Glutamic acid residues in matrix Gla protein are carboxylated by vitamin K-dependent gamma-carboxylase, which enables it to inhibit calcification. The purpose of this review is to discuss available evidence implicating vitamin K as a modifiable risk factor in the pathogenesis of vascular calcification in renal diseases.

How to Preserve Renal Function in Transcatheter Aortic Valve Therapies

Background: Transcatheter aortic valve implantations (TAVI) are indicated in high risk patients requiring aortic valve replacement (AVR). However, CT-scans, coronary angiograms and intraoperative aortographies can induce contrast-related nephro-toxicity with a concrete risk of acute postoperative renal failure, especially in severely diseased patients. To prevent this complication, we routinely perform transapical (TA) TAVI guided by transesophageal echocardiogram and fluoroscopy without angiography. Material and Methods: From November 2008 to December 2009, 31 high-risk patients suffering from severe symptomatic aortic stenosis underwent TA-TAVI in our institution. The preoperative imaging assessment (cardiac CT-scan and coronary angiogram) was performed no less than 10 days before the TA-TAVI in all patients (to recover the renal function) with a low-dose protocol for injected contrast medium (equivalent to the patient's weight for the CT-scan). During the TA-TAVI, the stent-valve positioning was performed without any contrast injection. Results: 32 consecutive stent-valve were successfully positioned in 31 patients (mean age 80.76 8 8.3 years; mean EuroSCORE: 32.2 8 12.9%) through a transapical access (1 patient required 2 valves for valve embolisation). The mean preoperative creatinine and urea blood levels were 102.6 8 67.7 _ g/dl (range 53-339 _ g/dl) and 8.45 8 4.9 mmol/l, respectively. A chronic renal insufficiency affected 12 patients (38.7%) with 1 patient in pre-dialysis. Postoperatively, no patient developed acute myocardial infarction, atrio-ventricular block or acute renal insufficiency (mean creatinine level: 89.7 8 64.55 _ g/dl; urea level: 7.11 8 3.47 mmol/l) and the 30-days mortality was 9.67% (3 patients). Conclusion: Specific preoperative and intraoperative protocols that require lowdoses or absence of contrast medium are useful to preserve the renal function in high risk patients operated for TAVI.

Surviving Sepsis Campaign: international guidelines for management of severe sepsis and septic shock: 2008.

OBJECTIVE: To provide an update to the original Surviving Sepsis Campaign clinical management guidelines, "Surviving Sepsis Campaign guidelines for management of severe sepsis and septic shock," published in 2004. DESIGN: Modified Delphi method with a consensus conference of 55 international experts, several subsequent meetings of subgroups and key individuals, teleconferences, and electronic-based discussion among subgroups and among the entire committee. This process was conducted independently of any industry funding. METHODS: We used the GRADE system to guide assessment of quality of evidence from high (A) to very low (D) and to determine the strength of recommendations. A strong recommendation indicates that an intervention's desirable effects clearly outweigh its undesirable effects (risk, burden, cost), or clearly do not. Weak recommendations indicate that the tradeoff between desirable and undesirable effects is less clear. The grade of strong or weak is considered of greater clinical importance than a difference in letter level of quality of evidence. In areas without complete agreement, a formal process of resolution was developed and applied. Recommendations are grouped into those directly targeting severe sepsis, recommendations targeting general care of the critically ill patient that are considered high priority in severe sepsis, and pediatric considerations. RESULTS: Key recommendations, listed by category, include: early goal-directed resuscitation of the septic patient during the first 6 hrs after recognition (1C); blood cultures prior to antibiotic therapy (1C); imaging studies performed promptly to confirm potential source of infection (1C); administration of broad-spectrum antibiotic therapy within 1 hr of diagnosis of septic shock (1B) and severe sepsis without septic shock (1D); reassessment of antibiotic therapy with microbiology and clinical data to narrow coverage, when appropriate (1C); a usual 7-10 days of antibiotic therapy guided by clinical response (1D); source control with attention to the balance of risks and benefits of the chosen method (1C); administration of either crystalloid or colloid fluid resuscitation (1B); fluid challenge to restore mean circulating filling pressure (1C); reduction in rate of fluid administration with rising filing pressures and no improvement in tissue perfusion (1D); vasopressor preference for norepinephrine or dopamine to maintain an initial target of mean arterial pressure > or = 65 mm Hg (1C); dobutamine inotropic therapy when cardiac output remains low despite fluid resuscitation and combined inotropic/vasopressor therapy (1C); stress-dose steroid therapy given only in septic shock after blood pressure is identified to be poorly responsive to fluid and vasopressor therapy (2C); recombinant activated protein C in patients with severe sepsis and clinical assessment of high risk for death (2B except 2C for post-operative patients). In the absence of tissue hypoperfusion, coronary artery disease, or acute hemorrhage, target a hemoglobin of 7-9 g/dL (1B); a low tidal volume (1B) and limitation of inspiratory plateau pressure strategy (1C) for acute lung injury (ALI)/acute respiratory distress syndrome (ARDS); application of at least a minimal amount of positive end-expiratory pressure in acute lung injury (1C); head of bed elevation in mechanically ventilated patients unless contraindicated (1B); avoiding routine use of pulmonary artery catheters in ALI/ARDS (1A); to decrease days of mechanical ventilation and ICU length of stay, a conservative fluid strategy for patients with established ALI/ARDS who are not in shock (1C); protocols for weaning and sedation/analgesia (1B); using either intermittent bolus sedation or continuous infusion sedation with daily interruptions or lightening (1B); avoidance of neuromuscular blockers, if at all possible (1B); institution of glycemic control (1B) targeting a blood glucose < 150 mg/dL after initial stabilization ( 2C ); equivalency of continuous veno-veno hemofiltration or intermittent hemodialysis (2B); prophylaxis for deep vein thrombosis (1A); use of stress ulcer prophylaxis to prevent upper GI bleeding using H2 blockers (1A) or proton pump inhibitors (1B); and consideration of limitation of support where appropriate (1D). Recommendations specific to pediatric severe sepsis include: greater use of physical examination therapeutic end points (2C); dopamine as the first drug of choice for hypotension (2C); steroids only in children with suspected or proven adrenal insufficiency (2C); a recommendation against the use of recombinant activated protein C in children (1B). CONCLUSION: There was strong agreement among a large cohort of international experts regarding many level 1 recommendations for the best current care of patients with severe sepsis. Evidenced-based recommendations regarding the acute management of sepsis and septic shock are the first step toward improved outcomes for this important group of critically ill patients.

Video-assisted right supradiaphragmatic thoracic duct ligation for non traumatic recurrent chylothorax

Introduction : Un chylothorax est une pathologie comprenant des manifestations respiratoires, nutritionnelles et immunologiques. La récidive du chylothorax ou l'échec du traitement conservateur imposent un traitement chirurgical. Ce travail rapporte notre expérience de ligature supra-diaphragmatique, vidéo-assistée du canal thoracique, pour chylothorax récurrent non traumatique. Patients et méthodes : Entre 1999 et 2004, nous avons recensé six observations (quatre du côté droit, un du côté gauche et un bilateral) Le chylothorax s'est développé chez trois patients traités par radio et chimiothérapie pour tumeur (deux lymphomes et une tumeur du sein) un dans le contexte d'une lymphangioléiomatose et un après greffe cardiaque. Résultats : Les patients ont bénéficié sous anesthésie générale, d'une ligature du canal thoracique supra-diaphragmatique, vidéo-assistée. Le temps opératoire moyen a été de 102 minutes. Le chylothorax a régressé chez cinq des six patients en sept jours. Un patient a été repris par thoracotomie droite au huitième jour pour chylothorax persistant. Dans la phase post-opératoire, un patient a développé une détresse respiratoire nécessitant une ventilation mécanique. Un autre patient a présenté un chylopéritoine important traité par un stent de Le Veen®. Le séjour moyen a été de quatorze jours sans mortalité péri-opératoire. Conclusion : Le traitement du chylothorax non traumatique récurrent est, en première intention, un traitement médical. En cas de récidive ou d'échec du traitement conservateur, le traitement chirurgical par ligature du canal thoracique supra- diaphragmatique, vidéo-assistée, permet de traiter avec succès le chylothorax récurrent non traumatique. -- Background: Chylothorax is an uncommon disorder with respiratory, nutritional and immunological manifestations. Surgical management is indicated in case of recurrence or failure after conservative treatment. We report our experience with video-assisted right-sided supradiaphrag¬matic thoracic duct ligation for non-traumatic, non-postoperative persistent or recurrent chylothorax. Patients and methods: The medical records of six patients operated at our institution between 1999 and 2004 were retrospectively reviewed. A right-sided chylothorax was found in four patients, a left-sided in one, and a bilateral in one. Three patients developed chylothorax after chemotherapy and chest irradiation for malignant diseases (lymphoma in two patients and breast cancer in one), one in the context of lymphangioleiomyomatosis, one due to a non-diagnosed lymphoma, and one after heart transplantation. Results: The mean operative time was 102 min, with an average length of hospital stay of 14 days. Persistent cessation of chylous effusion within 7 days after surgery was observed in 5/6 patients without recurrence during a mean follow-up time of 41 months. One patient with undiagnosed mediastinal lymphoma required re-operation and thoracic duct ligation on day 8 by right-sided thoracotomy due to persistent chylothorax. No 30-day mortality was recorded. Two patients presented postoperative complications including respiratory insufficiency requiring mechanical ventilation in one, and chylous ascites development requiring peritoneo-venous LeVeen shunting in one patient. Conclusions: Recurrent or persistent non-traumatic chylothorax may be successfully treated by video-assisted right supradiaphragmatic thoracic duct ligation.

Interactions between respiration and systemic hemodynamics. Part II: practical implications in critical care.

In Part I of this review, we have covered basic concepts regarding cardiorespiratory interactions. Here, we put this theoretical framework to practical use. We describe mechanisms underlying Kussmaul's sign and pulsus paradoxus. We review the literature on the use of respiratory variations of blood pressure to evaluate volume status. We show the possibilities of attaining the latter aim by investigating with ultrasonography how the geometry of great veins fluctuates with respiration. We provide a Guytonian analysis of the effects of PEEP on cardiac output. We terminate with some remarks on the potential of positive pressure breathing to induce acute cor pulmonale, and on the cardiovascular mechanisms that at times may underly the failure to wean a patient from the ventilator.

La rate: entre mystères et découvertes [The spleen: between mysteries and discoveries].

Mainly because it is possible to live without it, the spleen has always been considered a secondary and mysterious organ. However, recent observations have revealed new unsuspected functions for this organ whose patho-physiological importance should be reconsidered. Much less known than the hypersplenism, the hyposplenism corresponds historically to the loss or the insufficiency of the two principal functions of spleen: the filtration of faded or senescent elements from the blood and the fight against infections. In this article, after a short recall of the physiological functions of spleen, three innovations relating to hyposplenism will be explored: the vascular complications, the loss of the splenic pool of regenerating monocytes and the loss of the splenic pool of pluripotent mesenchymal stem cell.

Nouveautés en chirurgie vasculaire [New treatments in vascular diseases]

In superficial venous insufficiency, surgery remains the treatment of choice. Endovenous therapies are a minimal invasive alternative, whose long-term results are not demonstrated yet. In the treatment of abdominal aortic aneurysm, endovascular repair (EVAR) and laparoscopic approach are comparatively studied with open repair, to define their precise indications. In occlusive arterial disease, endovascular treatment offers inferior results in term of durability and patency, however with a decrease in morbidity and mortality.

Transcatheter aortic valve implantation in failed bioprosthetic surgical valves.

IMPORTANCE: Owing to a considerable shift toward bioprosthesis implantation rather than mechanical valves, it is expected that patients will increasingly present with degenerated bioprostheses in the next few years. Transcatheter aortic valve-in-valve implantation is a less invasive approach for patients with structural valve deterioration; however, a comprehensive evaluation of survival after the procedure has not yet been performed. OBJECTIVE: To determine the survival of patients after transcatheter valve-in-valve implantation inside failed surgical bioprosthetic valves. DESIGN, SETTING, AND PARTICIPANTS: Correlates for survival were evaluated using a multinational valve-in-valve registry that included 459 patients with degenerated bioprosthetic valves undergoing valve-in-valve implantation between 2007 and May 2013 in 55 centers (mean age, 77.6 [SD, 9.8] years; 56% men; median Society of Thoracic Surgeons mortality prediction score, 9.8% [interquartile range, 7.7%-16%]). Surgical valves were classified as small (≤21 mm; 29.7%), intermediate (>21 and <25 mm; 39.3%), and large (≥25 mm; 31%). Implanted devices included both balloon- and self-expandable valves. MAIN OUTCOMES AND MEASURES: Survival, stroke, and New York Heart Association functional class. RESULTS: Modes of bioprosthesis failure were stenosis (n = 181 [39.4%]), regurgitation (n = 139 [30.3%]), and combined (n = 139 [30.3%]). The stenosis group had a higher percentage of small valves (37% vs 20.9% and 26.6% in the regurgitation and combined groups, respectively; P = .005). Within 1 month following valve-in-valve implantation, 35 (7.6%) patients died, 8 (1.7%) had major stroke, and 313 (92.6%) of surviving patients had good functional status (New York Heart Association class I/II). The overall 1-year Kaplan-Meier survival rate was 83.2% (95% CI, 80.8%-84.7%; 62 death events; 228 survivors). Patients in the stenosis group had worse 1-year survival (76.6%; 95% CI, 68.9%-83.1%; 34 deaths; 86 survivors) in comparison with the regurgitation group (91.2%; 95% CI, 85.7%-96.7%; 10 deaths; 76 survivors) and the combined group (83.9%; 95% CI, 76.8%-91%; 18 deaths; 66 survivors) (P = .01). Similarly, patients with small valves had worse 1-year survival (74.8% [95% CI, 66.2%-83.4%]; 27 deaths; 57 survivors) vs with intermediate-sized valves (81.8%; 95% CI, 75.3%-88.3%; 26 deaths; 92 survivors) and with large valves (93.3%; 95% CI, 85.7%-96.7%; 7 deaths; 73 survivors) (P = .001). Factors associated with mortality within 1 year included having small surgical bioprosthesis (≤21 mm; hazard ratio, 2.04; 95% CI, 1.14-3.67; P = .02) and baseline stenosis (vs regurgitation; hazard ratio, 3.07; 95% CI, 1.33-7.08; P = .008). CONCLUSIONS AND RELEVANCE: In this registry of patients who underwent transcatheter valve-in-valve implantation for degenerated bioprosthetic aortic valves, overall 1-year survival was 83.2%. Survival was lower among patients with small bioprostheses and those with predominant surgical valve stenosis.

Factors associated with elevated pulmonary arterial pressure levels on the echocardiographic assessment in patients with prior pulmonary embolism.

BACKGROUND: Factors associated with the detection of raised systolic pulmonary artery pressure (sPAP) levels in patients with a prior episode of pulmonary embolism (PE) are not well known. METHODS: We used the RIETE Registry database to identify factors associated with the finding of sPAP levels ≥50 mm Hg on trans-thoracic echocardiography, in 557 patients with a prior episode of acute, symptomatic PE. RESULTS: Sixty-two patients (11.1%; 95% CI: 8.72-14.1) had sPAP levels ≥50 mm Hg. These patients were more likely women, older, and more likely had chronic lung disease, heart failure, renal insufficiency or leg varicosities than those with PAP levels <50mm Hg. During the index PE event, they more likely had recent immobility, and more likely presented with hypoxemia, increased sPAP levels, atrial fibrillation, or right bundle branch block. On multivariate analysis, women aged ≥70 years (hazard ratio [HR]: 2.0; 95% CI: 1.0-3.7), chronic heart or chronic lung disease (HR: 2.4; 95% CI: 1.3-4.4), atrial fibrillation at PE presentation (HR: 2.8; 95% CI: 1.3-6.1) or varicose veins (HR: 1.8; 95% CI: 1.0-3.3) were all associated with an increased risk to have raised sPAP levels. Chronic heart disease, varicose veins, and atrial fibrillation were independent predictors in women, while chronic heart disease, atrial fibrillation, a right bundle branch block or an S1Q3T3 pattern on the electrocardiogram were independent predictors in men. CONCLUSIONS: Women aged ≥70 years more likely had raised sPAP levels than men after a PE episode. Additional variables influencing this risk seem to differ according to gender.

Advantages and disadvantages of combination treatment with antipsychotics ECNP Consensus Meeting, March 2008, Nice.

TERMINOLOGY AND PRINCIPLES OF COMBINING ANTIPSYCHOTICS WITH A SECOND MEDICATION: The term "combination" includes virtually all the ways in which one medication may be added to another. The other commonly used terms are "augmentation" which implies an additive effect from adding a second medicine to that obtained from prescribing a first, an "add on" which implies adding on to existing, possibly effective treatment which, for one reason or another, cannot or should not be stopped. The issues that arise in all potential indications are: a) how long it is reasonable to wait to prove insufficiency of response to monotherapy; b) by what criteria that response should be defined; c) how optimal is the dose of the first monotherapy and, therefore, how confident can one be that its lack of effect is due to a truly inadequate response? Before one considers combination treatment, one or more of the following criteria should be met; a) monotherapy has been only partially effective on core symptoms; b) monotherapy has been effective on some concurrent symptoms but not others, for which a further medicine is believed to be required; c) a particular combination might be indicated de novo in some indications; d) The combination could improve tolerability because two compounds may be employed below their individual dose thresholds for side effects. Regulators have been concerned primarily with a and, in principle at least, c above. In clinical practice, the use of combination treatment reflects the often unsatisfactory outcome of treatment with single agents. ANTIPSYCHOTICS IN MANIA: There is good evidence that most antipsychotics tested show efficacy in acute mania when added to lithium or valproate for patients showing no or a partial response to lithium or valproate alone. Conventional 2-armed trial designs could benefit from a third antipsychotic monotherapy arm. In the long term treatment of bipolar disorder, in patients responding acutely to the addition of quetiapine to lithium or valproate, this combination reduces the subsequent risk of relapse to depression, mania or mixed states compared to monotherapy with lithium or valproate. Comparable data is not available for combination with other antipsychotics. ANTIPSYCHOTICS IN MAJOR DEPRESSION: Some atypical antipsychotics have been shown to induce remission when added to an antidepressant (usually a SSRI or SNRI) in unipolar patients in a major depressive episode unresponsive to the antidepressant monotherapy. Refractoriness is defined as at least 6 weeks without meeting an adequate pre-defined treatment response. Long term data is not yet available to support continuing efficacy. SCHIZOPHRENIA: There is only limited evidence to support the combination of two or more antipsychotics in schizophrenia. Any monotherapy should be given at the maximal tolerated dose and at least two antipsychotics of different action/tolerability and clozapine should be given as a monotherapy before a combination is considered. The addition of a high potency D2/3 antagonist to a low potency antagonist like clozapine or quetiapine is the logical combination to treat positive symptoms, although further evidence from well conducted clinical trials is needed. Other mechanisms of action than D2/3 blockade, and hence other combinations might be more relevant for negative, cognitive or affective symptoms. OBSESSIVE-COMPULSIVE DISORDER: SSRI monotherapy has moderate overall average benefit in OCD and can take as long as 3 months for benefit to be decided. Antipsychotic addition may be considered in OCD with tic disorder and in refractory OCD. For OCD with poor insight (OCD with "psychotic features"), treatment of choice should be medium to high dose of SSRI, and only in refractory cases, augmentation with antipsychotics might be considered. Augmentation with haloperidol and risperidone was found to be effective (symptom reduction of more than 35%) for patients with tics. For refractory OCD, there is data suggesting a specific role for haloperidol and risperidone as well, and some data with regard to potential therapeutic benefit with olanzapine and quetiapine. ANTIPSYCHOTICS AND ADVERSE EFFECTS IN SEVERE MENTAL ILLNESS: Cardio-metabolic risk in patients with severe mental illness and especially when treated with antipsychotic agents are now much better recognized and efforts to ensure improved physical health screening and prevention are becoming established.