Is the "in situ" simulation for teaching anesthesia residents a lower cost, feasible and satisfying alternative to simulation center ? A 24 months prospective observational study in a university hospital.

BACKGROUND: The value of simulation in medical education is increasingly obvious. Nevertheless, the high cost of running a simulation center and the time's availability for students to get to simulation center remain a major problem. Technological developments and miniaturization of computer systems now allow handling of simulation manikins. Therefore, "in situ" simulation seems a valuable alternative to center simulation. OBJECTIVE(S): To identify the costs and feasibility of "in situ" simulation. To conduct an evaluation of the sessions by participants in order to adapt the educational objectives. DESIGN: Observational study. SETTING: 118 "in situ" simulation sessions were organized between March 2011 and February 2013 in the university hospital of Université Catholique de Louvain. Sessions took place in OR facilities. At the end of each session, a questionnaire was given to each participant. PARTICIPANTS: 357 of 368 participants completed a questionnaire. For each session, one or two nurses and 2 residents in anesthesia were invited. MAIN OUTCOME MEASURES: Total costs for organizing the sessions. Number of realized sessions. Global satisfaction of participants. RESULTS: Total cost for organizing the sessions is 18 414 Euro. One hundred and one among the 118 scheduled sessions were performed, which corresponds to a rate of 85%. Three hundred and sixty-five people participated in training simulations. During the sessions, 357 questionnaires were completed. The global satisfaction was high with a median Likert scale of 5 (5-5) to the question "I would like to participate in other sessions in the future". CONCLUSION: The "in situ" simulation in anesthesia is feasible in a university hospital using the available facilities of the operating theater during the working hours of both participants and trainers. However, the number of annual sessions may be limited by the availability of the simulation room or staff.

Adjuvant immunotherapy is dependent on inducible nitric oxide synthase.

Rodents immunized with complete Freund's adjuvant (CFA) are resistant to subsequent attempts to induce autoimmune disease, while animals immunized with incomplete Freund's adjuvant (IFA) remain susceptible. Mycobacterial extracts can stimulate inducible nitric oxide synthase (NOS2) gene transcription. Robust expression of NOS2 has been linked to suppression of T cell proliferation and alterations in immune responses. Our studies investigated the hypothesis that the immunoprotective effect of CFA before immunization requires functional NOS2. NOS2 gene expression is chronically elevated in lymph nodes and spleens of CFA-immunized mice. Maximal expression of NOS2 after CFA immunization requires the presence of functional type I tumor necrosis factor alpha receptor (TNFR1) and interferon gamma. Groups of nontreated and CFA-preimmunized male C57BL/6J or C57BL/6NOS2(-/)- mice were immunized with myelin oligodendrocyte glycoprotein (MOG) peptide 35-55 in CFA to induce experimental allergic encephalomyelitis (EAE). Wild-type C57BL/6J mice were protected from the development of symptoms of EAE, while the NOS2(-/)- mice failed to be protected. NOS2-dependent effects of CFA included an augmentation of the MOG-specific IgG1 response, a decrease in interleukin 6 production by MOG-reactive lymphocytes, and a marked decrease in mononuclear cell infiltrates in the central nervous system. These studies support the hypothesis that CFA immunization modulates immune responses through a nitric oxide-dependent mechanism.

Dissociated effects of amphetamine on arousal and cortical blood flow in humans.

The effects of intravenous amphetamine infusion (0.3 mg/kg) on cerebral blood flow (CBF) and measures of autonomic and behavioral arousal were studied in 12 normal male volunteers in a placebo-controlled crossover design. Nonsignificant decreases were seen in CBF (measured by 133Xe inhalation), despite significant increases in autonomic and behavioral arousal. The apparent dissociation of CBF and arousal appears to be compatible with other human experiments suggesting that amphetamine decreases CBF and metabolism, as well as with neurobiological findings on the effects of catecholamines on resting cortical activity and mechanisms of increased attention. The results differ substantially, however, from findings of increased CBF and metabolism in animals. Although the larger doses used in animals most likely explain the discrepancy, technical limitations in human brain imaging cannot be excluded.

Effects of ECT on the TRH stimulation test.

The prognostic value of the TRH stimulation test was evaluated in 23 inpatients with major depressive disorder before and after a trial of ECT. In contrast to previous reports, the peak TSH response to TRH was significantly decreased after treatment compared with before treatment. This effect was consistent across individuals and subgroups (responders/nonresponders; unilateral/bilateral ECT). The particular ECT technique used in the study may account for the discrepancies between these findings and those previously reported by other authors.

The Expert Consensus Guidelines for treating depression in bipolar disorder.

We present expert consensus guideline recommendations for the treatment of bipolar depression. These were arrived at through the statistical aggregation of the survey responses of 61 leading clinical researchers to eight questions about the key decision points in the management of bipolar depression. The experts' first-line recommendation for treating psychotic depression in bipolar disorder is to provide a combination of mood stabilizer, antidepressant, and neuroleptic medication. For severe, but nonpsychotic bipolar depression, the experts recommend the combination of a mood stabilizer and an antidepressant. For milder bipolar depression, a mood stabilizer and an antidepressant together or a mood stabilizer alone would be first line. The experts' antidepressant dose and dosing schedule recommendations are equivalent for unipolar and bipolar depression, but the experts recommend a faster discontinuation of antidepressants during the maintenance phase in bipolar patients--probably to reduce the risk of rapid cycling. Among the antidepressants, the experts prefer bupropion and the serotonin reuptake inhibitors as first line. They also believe that bupropion is least likely among antidepressants to cause switches to mania. Among mood stabilizers, the experts rate lithium as most likely to have a direct antidepressant effect.

The Texas Medication Algorithm Project: report of the Texas Consensus Conference Panel on Medication Treatment of Major Depressive Disorder.

BACKGROUND: This article describes the development of consensus medication algorithms for the treatment of patients with major depressive disorder in the Texas public mental health system. To the best of our knowledge, the Texas Medication Algorithm Project (TMAP) is the first attempt to develop and prospectively evaluate consensus-based medication algorithms for the treatment of individuals with severe and persistent mental illnesses. The goals of the algorithm project are to increase the consistency of appropriate treatment of major depressive disorder and to improve clinical outcomes of patients with the disorder. METHOD: A consensus conference composed of academic clinicians and researchers, practicing clinicians, administrators, consumers, and families was convened to develop evidence-based consensus algorithms for the pharmacotherapy of major depressive disorder in the Texas mental health system. After a series of presentations and panel discussions, the consensus panel met and drafted the algorithms. RESULTS: The panel consensually agreed on algorithms developed for both nonpsychotic and psychotic depression. The algorithms consist of systematic strategies to define appropriate treatment interventions and tactics to assure optimal implementation of the strategies. Subsequent to the consensus process, the algorithms were further modified and expanded iteratively to facilitate implementation on a local basis. CONCLUSION: These algorithms serve as the initial foundation for the development and implementation of medication treatment algorithms for patients treated in public mental health systems. Specific issues related to adaptation, implementation, feasibility testing, and evaluation of outcomes with the pharmacotherapeutic algorithms will be described in future articles.

Bupropion and sertraline combination treatment in refractory depression.

A sizeable minority of depressed patients, estimated at 15-20%, suffer chronic symptoms which often persist despite appropriate treatment. The search for new, more efficacious pharmacotherapies has included testing existing medications for additional therapeutic effects, such as in combination treatment. Four treatment- refractory patients who presented to the authors for clinical care are described, in which the combination of bupropion and sertraline was effective for a major depressive episode. None of the patients experienced adverse effects. Two carried the diagnosis of unipolar depression, and two, bipolar disorder. All had prior adequate, but ineffective, separate trials of buproprion and a selective serotonin re-uptake inhibitor (SSRI), including sertraline. All had chronic depression with multiple failed medication treatments, arguing against the alternative explanation that their improvement represented a placebo response or spontaneous remission. The efficacious combination of sertraline and bupropion may be due to synergism of its two distinct antidepressant mechanisms involving serotonergic, dopaminergic and noradrenergic systems.

Medication treatment of bipolar disorder 2000: a summary of the expert consensus guidelines.

The original Expert Consensus Guidelines on the Treatment of Bipolar Disorder were published in 1996. Since that time, a variety of new treatments for bipolar disorder have been reported; however, evidence for these treatments varies widely, with data especially limited regarding comparisons between treatments and how to sequence them. For this reason, a new survey of expert opinion was undertaken to bridge gaps between the research evidence and key clinical decisions. The results of this new survey, which was completed by 58 experts, are presented in The Expert Consensus Guideline Series: Medication Treatment of Bipolar Disorder 2000, which was published in April 2000 as a Postgraduate Medicine Special Report. In this article, the authors describe the methodology used in the survey and summarize the clinical recommendations given in the resulting guidelines. The expert panel reached consensus on many key strategies, including acute and preventive treatment of mania (euphoric, mixed, and dysphoric subtypes), depression, rapid cycling, and approaches to managing treatment resistance and comorbid psychiatric conditions. Use of a mood stabilizer is recommended in all phases of treatment. Divalproex (especially for mixed or dysphoric subtypes) and lithium are the primary mood stabilizers for both acute and preventive treatment of mania. If monotherapy with these agents fails, the next recommended intervention is to combine them. This combination of lithium and divalproex can then serve as the foundation to which other medications are added if needed. Carbamazepine is the leading alternative mood stabilizer for mania. The experts rated the other new anticonvulsants as second-line options (i.e., their use is recommended if lithium, divalproex, and carbamazepine fail or are contraindicated). For milder depression, a mood stabilizer, especially lithium, may be used as monotherapy. Divalproex and lamotrigine are other first-line choices. For more severe depression, the experts recommend combining a standard antidepressant with lithium or divalproex. Bupropion, selective serotonin reuptake inhibitors (SSRIs), and venlafaxine are preferred antidepressants. The antidepressants should usually be tapered 2-6 months after remission. Monotherapy with divalproex is recommended for the initial treatment of either depression or mania in rapid-cycling bipolar disorder. Antipsychotics are recommended for use in combination with the above regimens for mania or depression with psychosis, and as potential adjuncts in nonpsychotic episodes. Atypical antipsychotics, especially olanzapine and risperidone, were generally preferred over conventional antipsychotics. The guidelines also include recommendations concerning the use of electroconvulsive therapy (ECT), clozapine, thyroid hormone, stimulants, and various novel agents for patients with treatment-refractory bipolar illness. The experts reached high levels of consensus on key steps in treating bipolar disorder despite obvious gaps in high-quality data. To evaluate many of the treatment options in this survey, the experts had to extrapolate beyond controlled data; however, their recommendations are generally conservative. Experts give their strongest support to initial strategies and medications for which high-quality research data or longstanding patterns of clinical usage exist. Within the limits of expert opinion and with the understanding that new research data may take precedence, these guidelines provide clear pathways for addressing common clinical questions and can be used to inform clinicians and educate patients about the relative merits of a variety of interventions.

Treatment of depression in women: a summary of the expert consensus guidelines.

Women constitute two-thirds of patients suffering from common depressive disorders, making the treatment of depression in women a substantial public health concern. However, high-quality, empirical data on depressive disorders specific to women are limited, and there are no comprehensive evidence-based practice guidelines on the best treatments for these illnesses. To bridge the gap between research evidence and key clinical decisions, the authors developed a survey of expert opinion concerning treatment of four depressive conditions specific to women: premenstrual dysphoric disorder, depression in pregnancy, postpartum depression in a mother choosing to breast-feed, and depression related to perimenopause/menopause. The survey asked about 858 treatment options in 117 clinical situations and included a broad range of pharmacological, psychosocial, and alternative medicine approaches. The survey was sent to 40 national experts on women's mental health issues, 36 (90%) of whom completed it. The options, scored using a modified version of the RAND Corporation's 9-point scale for rating appropriateness of medical decisions, were assigned one of three categorical rankings-first line/preferred choice, second line/alternate choice, third line/usually inappropriate-based on the 95% confidence interval of each item's mean rating. The expert panel reached consensus (defined as a non-random distribution of scores by chi-square "goodness-of-fit" test) on 76% of the options, with greater consensus in situations involving severe symptoms. Guideline tables indicating preferred treatment strategies were then developed for key clinical situations. The authors summarize the expert consensus methodology they used and then, for each of the four key areas, review the treatment literature and summarize the experts' recommendations and how they relate to the research findings. For women with severe symptoms in each area we asked about, the first-line recommendation was antidepressant medication combined with other modalities (generally psychotherapy). These recommendations parallel existing guidelines for severe depression in general populations. For initial treatment of milder symptoms in each situation, the panel was less uniform in recommending antidepressants, and either gave equal endorsement to other treatment modalities (e.g., nutritional or psychobehavioral approaches in PMDD; hormone replacement in perimenopause) or preferred psychotherapy over medication (during conception, pregnancy, or lactation). In all milder cases, however, antidepressants were recommended as at least second-line options. Among antidepressants, selective serotonin reuptake inhibitors (SSRIs) were recommended as first-line treatment in all situations. The specific SSRIs that were preferred depended on the particular clinical situation. Tricyclic antidepressants were highly rated alternatives to SSRIs in pregnancy and lactation. In evaluating many of the treatment options, the experts had to extrapolate beyond controlled data in comparing treatment options with each other or in combination. Within the limits of expert opinion and with the expectation that future research data will take precedence, these guidelines provide some direction for addressing common clinical dilemmas in women, and can be used to inform clinicians and educate patients regarding the relative merits of a variety of interventions.

The Expert Consensus Guideline Series: Medication Treatment of Bipolar Disorder 2000.

OBJECTIVES: New treatments for bipolar disorder have been reported since we first published survey-based expert consensus guidelines in 1996. The evidence for these treatments varies widely; data are especially limited regarding comparisons between treatments and how to sequence them. We therefore undertook a new survey of expert opinion in order to bridge gaps between the research evidence and key clinical decisions. METHOD: Based on a literature review, a written survey was prepared which asked about 1,276 options for psychopharmacologic interventions in 48 specific clinical situations. Most options were scored using a modified version of the RAND Corporation 9-point scale for rating appropriateness of medical decisions. We contacted 65 national experts, 58 of whom (89%) completed the survey. Consensus on each option was defined as a non-random distribution of scores by chi-square test. We assigned a categorical rank (first-line/preferred choice, second-line/alternate choice, third-line/usually inappropriate) to each option based on the confidence interval of its mean rating. Guideline tables indicating preferred treatment strategies were then developed for key clinical situations. RESULTS: The expert panel reached consensus on many key strategies, including acute and preventive treatment for mania (euphoric, mixed, and dysphoric subtypes), depression, and rapid cycling, and approaches to managing the complications of treatment resistance and comorbidity. Use of a mood stabilizer is recommended in all phases of treatment. Divalproex (especially for mixed or dysphoric subtypes) and lithium are the cornerstone choices among this class for both acute and preventive treatment of mania. Regardless of which is selected first, if monotherapy fails, the next recommended intervention is to use these agents in combination. The combination can then serve as the foundation on which other medications are added, if needed. Carbamazepine is the leading alternative mood stabilizer for mania. Expert opinion regards other new anticonvulsants as second-line options (e.g., if the previously mentioned mood stabilizers fail or are contraindicated). For milder depression, a mood stabilizer, especially lithium, may be used as monotherapy. Divalproex and lamotrigine are other first-line choices. For more severe depression, a standard antidepressant should be combined with lithium or divalproex. Bupropion, selective serotonin reuptake inhibitors (SSRIs), and venlafaxine are preferred antidepressants, and should be tapered 2 to 6 months after remission. Divalproex monotherapy is recommended for initial treatment of either depression or mania with rapid cycling. Antipsychotics are recommended for use with the above regimens for mania or depression with psychosis, and as potential adjuncts in non-psychotic episodes. Atypical antipsychotics, especially olanzapine and risperidone, were generally preferred over conventional antipsychotics. Recommendations are also given concerning the use of electroconvulsive therapy (ECT), clozapine, thyroid hormone, stimulants, and various novel agents for patients with treatment-refractory illness. CONCLUSIONS: The experts reached high levels of consensus on key steps in treating bipolar disorder despite obvious gaps in high-quality data. To evaluate many of the treatment options in this survey, the experts had to extrapolate beyond controlled data; however, their recommendations are generally conservative. Experts reserve strongest support for initial strategies and individual medications for which there are high-quality research data, or for which there are longstanding patterns of clinical usage. Within the limits of expert opinion and with the understanding that new research data may take precedence, these guidelines provide clear pathways for addressing common clinical questions in a manner that can be used to inform clinicians and educate patients regarding the relative merits of a variety of interventions.

The Expert Consensus Guideline Series. Treatment of depression in women.

OBJECTIVES: Women constitute two-thirds of patients suffering from common depressive disorders. The treatment of depression in women is therefore a substantial public health concern. High-quality, empirical data on depressive disorders specific to women are limited. As a result, there are no comprehensive evidence-based practice guidelines on the best treatment approaches for these illnesses. We conducted a consensus survey of expert opinion on the treatment of 4 depressive conditions specific to women: premenstrual dysphoric disorder (PMDD), depression in pregnancy, postpartum depression in a mother choosing to breast-feed, and depression related to perimenopause/menopause. METHOD: After reviewing the literature and convening a work group of leading experts, we prepared a written survey covering a total of 858 treatment options in 117 specific clinical situations. Depression severity (mild to severe) was specified for most clinical situations. Treatment options included a broad range of pharmacological, psychosocial, and alternative medicine approaches. Most options were scored using a modified version of the RAND 9-point scale for rating appropriateness of medical decisions. We identified 40 national experts, 36 (90%) of whom completed the survey. Consensus on each option was defined as a non-random distribution of scores by chi-square "goodness-of-fit" test. We assigned a categorical rank (first line/preferred choice, second line/alternate choice, third line/usually inappropriate) to each option based on the 95% confidence interval around the mean rating. Guideline tables indicating preferred treatment strategies were then developed for key clinical situations. RESULTS: The expert panel reached consensus on 76% of the options, with greater consensus in situations involving severe symptoms. For women with severe symptoms in each of the 4 central disorder areas we asked about, the first-line recommendation was for antidepressant medication combined with other modalities (generally psychotherapy), paralleling existing guidelines for severe depression in general populations. For milder symptoms in each situation, the panel was less uniform in recommending antidepressants. For the initial treatment of milder symptoms, the panel either gave equal endorsement to other treatment modalities (e.g., nutritional or psychobehavioral approaches in PMDD; hormone replacement in perimenopause) or preferred psychotherapy over medication (in conception, pregnancy, or lactation). In all milder cases, however, antidepressants were recommended as at least second-line options. Among antidepressants, selective serotonin reuptake inhibitors (SSRIs) as a class were recommended as first-line treatment in all situations. The specific SSRIs that were preferred depended on the particular clinical situation. Tricyclic antidepressants were highly rated alternatives to SSRIs in pregnancy and lactation. CONCLUSIONS: The experts reached a high level of consensus on the appropriateness of including both antidepressant medication, specifically SSRIs, and nonpharmacological modalities in treatment plans for severe depression in 4 key clinical situations unique to women. To evaluate many of the treatment options in this survey, the experts had to extrapolate beyond controlled data in comparing modalities with each other or in combination. Within the limits of expert opinion and with the expectation that future research data will take precedence, these guidelines provide some direction for addressing common clinical dilemmas in women. They can be used to inform clinicians and educate patients regarding the relative merits of a variety of interventions.

Medication consultation and split treatment during psychotherapy.

In split treatment a patient simultaneously sees both a psychotherapist and a pharmacotherapist. Research indicates that medication and psychotherapy have additive value when used together in the treatment of depression and probably in other disorders as well. However, little is known about the presumably common technique of separate therapists administering these treatments. Complex interpersonal issues arise, reflecting both ideological and transferential attitudes toward medication as well as the intricacies of triangular relationships. Establishing a three-way therapeutic alliance, awareness of competitive countertransference feelings, and recognition of covert issues other than medication in the request for consultation are examples of areas where special attention can help the treatment succeed.

Anti-apoptotic effect of hyperglycemia can allow survival of potentially autoreactive T cells.

Thymocyte development is a tightly controlled multi-step process involving selective elimination of self-reactive and non-functional T cells by apoptosis. This developmental process depends on signaling by Notch, IL-7 and active glucose metabolism. In this study, we explored the requirement of glucose for thymocyte survival and found that in addition to metabolic regulation, glucose leads to the expression of anti-apoptotic genes. Under hyperglycemic conditions, both mouse and human thymocytes demonstrate enhanced survival. We show that glucose-induced anti-apoptotic genes are dependent on NF-κB p65 because high glucose is unable to attenuate normal ongoing apoptosis of thymocytes isolated from p65 knockout mice. Furthermore, we demonstrate that in vivo hyperglycemia decreases apoptosis of thymocytes allowing for survival of potentially self-reactive thymocytes. These results imply that hyperglycemic conditions could contribute to the development of autoimmunity through dysregulated thymic selection.

Absence of functional inducible NO synthase enhances the efficacy of tolerance induced by high dose antigen feeding.

Recent studies have suggested that IL-12 and IFN-gamma may impair the ability of fed Ag to induce systemic tolerance. Because both of these cytokines can function to directly or indirectly induce inducible NO synthase (iNOS) expression, we have investigated whether the functional expression of iNOS regulates oral tolerance. C57BL/6J wild-type or C57BL/6J NOS2(-/-) mice were gavaged with a single dose of 20 mg of keyhole limpet hemocyanin (KLH), followed by s.c. immunization with KLH/CFA. In the absence of feeding Ag, several parameters of the immune response were more robust in C57BL/6J NOS2(-/-) mice following KLH/CFA immunization, including the magnitude of the delayed-type hypersensitivity response, the proliferative response, and the production of IFN-gamma and IL-2 by Ag-activated draining lymph node cells. These heightened responses in the C57BL/6J NOS2(-/-) mice are still effectively inhibited by feeding KLH. Feeding KLH to the C57BL/6J NOS2(-/-) mice elicited heightened TGF-ss1 production by Ag-activated lymphocytes, as well as augmented total IgG, IgG1, and IgG2a responses to KLH/CFA compared with that seen in Ag-fed wild-type mice. Feeding Ag to the NOS2(-/-) mice suppressed proliferative responses and IFN-gamma production, while increasing IL-4 production and the IgG1/IgG2a ratio even following a booster immunization of KLH/CFA. Administrating L-N:(6)-(1-iminoethyl)-lysine. 2HCl to wild-type mice during the period of Ag feeding reproduced the high TGF-ss1 production seen in Ag-activated lymphocytes from Ag-fed NOS2(-/-) mice. Feeding KLH is followed by transient up-regulation of NOS2 mRNA expression in the Peyer's patches of wild-type mice. Selective inhibition of NOS2 may be a simple way to augment tolerogenic mucosal immune responses.