Impact of multidisciplinary team meetings on the management of venous thromboembolism. A clinical study of 142 cases.

OBJECTIVE: Numerous guidelines have been published on the management of venous thromboembolism (VTE). However, therapeutic decision-making may prove challenging in routine clinical practice. With this in mind, multidisciplinary team (MDT) meetings have been set up in Rennes University Hospital, France. This study sought to describe the situations discussed during MDT meetings and to assess whether the meetings bring about changes in the management of these patients. MATERIALS AND METHODS: A retrospective single-center study conducted at the Rennes University Hospital included cases presented from the beginning of the MDT meetings (February 2015) up to May 2017. RESULTS: In total, 142 cases were presented in 15 MDT meetings, corresponding to a mean of 10±4 cases per meeting. Of these, 129 related to VTE patients: 33 provoked VTEs, 22 unprovoked VTEs, 49 cancer-related VTEs, and 25 unspecified VTEs. MDT meetings led to significant changes in the anticoagulation type (therapeutic, prophylactic, or discontinuation) and duration, but not in the anticoagulant choice (direct oral anticoagulants, vitamin K antagonists, heparins, etc.). CONCLUSION: Requests for MDT meetings are made for all VTE types, and these meetings have an impact on VTE management.

Ecological relevance of the Iowa gambling task in patients with Alzheimer's disease and mild cognitive impairment.

BACKGROUND: In spite of their extensive use, the ecological relevance of tasks dedicated to assessing real-world decision-making in a laboratory setting remains unclear. OBJECTIVES: Our study aimed to evaluate the relationship between decision-making and behavioral competency and awareness of limitations. METHODS: A total of 20 patients with Alzheimer's disease (AD), 20 with amnestic mild cognitive impairment (aMCI) and 20 healthy controls (HC) were assessed for decision-making using the Iowa Gambling Task (IGT). Behavioral competency was evaluated by the Patient Competency Rating Scale (PCRS), which requires each participant and a relative to answer the same 30 questions on participant's competency and to rate each item, while awareness of limitations was evaluated by subtracting the self-rated score from the relative-rated score. RESULTS: Using the median-split approach, the proportion of disadvantageous decision-makers was higher in both the MCI and AD groups than in HC (P=0.02 and P=0.03, respectively), with no differences between clinical groups. The percentage of participants with poorer behavioral competency was also higher in the MCI and AD than in the HC (self-rated: P=0.025 and P=0.01, respectively; relative-rated: P=0.008 and P=0.008, respectively), again with no differences between MCI and AD. All groups were comparable in awareness. For all participants, disadvantageous decision-making was associated with both reduced behavioral competency and poor awareness of limitations (OR: 3.47, P=0.03 and OR: 5.4, P=0.004, respectively). CONCLUSION: Our findings support the ecological relevance of the IGT. Behavioral competency integrity and awareness of limitations are both associated with advantageous decision-making profiles.

Molecular, clinical and neuropsychological study in 31 patients with Kabuki syndrome and KMT2D mutations.

Kabuki syndrome (KS-OMIM 147920) is a rare developmental disease characterized by the association of multiple congenital anomalies and intellectual disability. This study aimed to investigate intellectual performance in children with KS and link the performance to several clinical features and molecular data. We recruited 31 children with KMT2D mutations who were 6 to 16 years old. They all completed the Weschler Intelligence Scale for Children, fourth edition. We calculated all indexes: the Full Scale Intellectual Quotient (FSIQ), Verbal Comprehension Index (VCI), Perceptive Reasoning Index (PRI), Processing Speed Index (PSI), and Working Memory Index (WMI). In addition, molecular data and several clinical symptoms were studied. FSIQ and VCI scores were 10 points lower for patients with a truncating mutation than other types of mutations. In addition, scores for FSIQ, VCI and PRI were lower for children with visual impairment than normal vision. We also identified a discrepancy in indexes characterized by high WMI and VCI and low PRI and PSI. We emphasize the importance of early identification and intensive care of visual disorders in patients with KS and recommend individual assessment of intellectual profile.

Biologically-variable rhythmic auditory cues are superior to isochronous cues in fostering natural gait variability in Parkinson's disease.

INTRODUCTION: Rhythmic auditory cueing improves certain gait symptoms of Parkinson's disease (PD). Cues are typically stimuli or beats with a fixed inter-beat interval. We show that isochronous cueing has an unwanted side-effect in that it exacerbates one of the motor symptoms characteristic of advanced PD. Whereas the parameters of the stride cycle of healthy walkers and early patients possess a persistent correlation in time, or long-range correlation (LRC), isochronous cueing renders stride-to-stride variability random. Random stride cycle variability is also associated with reduced gait stability and lack of flexibility. METHOD: To investigate how to prevent patients from acquiring a random stride cycle pattern, we tested rhythmic cueing which mimics the properties of variability found in healthy gait (biological variability). PD patients (n=19) and age-matched healthy participants (n=19) walked with three rhythmic cueing stimuli: isochronous, with random variability, and with biological variability (LRC). Synchronization was not instructed. RESULTS: The persistent correlation in gait was preserved only with stimuli with biological variability, equally for patients and controls (p's<0.05). In contrast, cueing with isochronous or randomly varying inter-stimulus/beat intervals removed the LRC in the stride cycle. Notably, the individual's tendency to synchronize steps with beats determined the amount of negative effects of isochronous and random cues (p's<0.05) but not the positive effect of biological variability. CONCLUSION: Stimulus variability and patients' propensity to synchronize play a critical role in fostering healthier gait dynamics during cueing. The beneficial effects of biological variability provide useful guidelines for improving existing cueing treatments.

A multidimensional approach to impulsivity in Parkinson's disease: measurement and structural invariance of the UPPS Impulsive Behaviour Scale.

BACKGROUND: Poor impulse control is a common feature in patients with Parkinson's disease (PD). However, before testing whether patients with PD and controls differ in impulsivity, one must assess whether impulsivity measures are invariant across groups. Consequently, we examined (a) the measurement and structural invariance of a scale assessing changes in four dimensions of impulsivity (urgency, lack of premeditation, lack of perseverance and sensation seeking) among patients with PD and controls; and (b) whether the four impulsivity traits relate differentially to risky decisions by patients. METHOD: Close relatives of 78 patients with idiopathic PD and 96 control participants were given the short Urgency-Premeditation-Perseverance-Sensation seeking Impulsive Behaviour Scale (UPPS), which assesses changes in four dimensions of impulsivity. Participants also completed the Game of Dice Task (GDT), a laboratory measure of risk taking. RESULTS: Multigroup confirmatory factor analyses supported measurement invariance across groups, whereas structural invariance was not confirmed. Patients with PD showed greater variability and higher impulsivity than controls. Furthermore, patients with impulse control disorders (ICDs) demonstrated even greater levels of sensation seeking than patients without ICDs. Finally, lower premeditation and greater perseverance were significantly associated with greater risk taking in patients with PD, and higher agonist dopaminergic doses with less risky choices on the GDT. CONCLUSIONS: The questionnaire appears to function comparably across patients and controls. Thus, group comparisons on the questionnaire can be considered valid. Mean differences between groups on the dimensions of impulsivity may reflect executive impairments and/or abnormal reward processing in patients with PD, which may lead to risky behaviours.

Restless legs syndrome outside the blood-brain barrier--exacerbation by domperidone in Parkinson's disease.

INTRODUCTION: Models of dopaminergic function in restless legs focus on central dopaminergic neurons. Domperidone, a peripheral dopamine blocker that cannot cross the blood-brain barrier, is commonly used in Parkinson's disease. After encountering a case of restless legs syndrome that dramatically worsened with domperidone, we assessed whether Parkinson's patients may have exacerbation of restless legs with domperidone. METHODS: From two Parkinson's disease cohorts, we assessed restless legs prevalence according to standard criteria, in patients taking vs. not taking domperidone. Regression analysis was performed, adjusting for age, sex, disease duration, UPDRS, dopaminergic medications and other medications. RESULTS: One hundred eighty four patients were assessed, of whom 46 (25%) had restless legs. Thirteen out of twenty seven (48%) patients on domperidone had restless legs compared to 33/157 (21%) without (p = 0.010). Other medications were not associated with restless legs. CONCLUSION: This unexpected finding suggests that dopaminergic neurons outside of the blood-brain barrier may be important in restless legs syndrome pathophysiology.

[Learning potential and cognitive remediation in schizophrenia]. / Potentiel d'apprentissage et revalidation cognitive dans la schizophrénie.

BACKGROUND: Many studies have stressed the importance of neurocognitive deficits in schizophrenia that represent a core feature of the pathology. Cognitive dysfunctions are present in 80% of schizophrenic patients, including deficits in attention, memory, speed processing and executive functioning, with well-known functional consequences on daily life, social functioning and rehabilitation outcome. Recent studies have stressed that cognitive deficits, rather than the positive or negative symptoms of schizophrenia, predict poor performance in basic activities of daily living. If it is possible to reduce psychotic symptoms and to prevent relapses with antipsychotic medication, it is not yet possible to have the same convincing impact on cognitive or functional impairments. Cognitive remediation is a new psychological treatment which has proved its efficacy in reducing cognitive deficits. A growing literature on cognitive rehabilitation suggests possibilities that in schizophrenia, specific techniques are able to enhance an individual's cognitive functioning. LITERATURE FINDINGS: Presently, two distinct and complementary cognitive remediation methods have been developed: the compensatory and the restorative approaches: (A) restorative approaches attempt to improve function by recruiting relatively intact cognitive processes to fill the role of those impaired, or by using prosthetic aids to compensate for the loss of function; (B) in contrast, in the restorative approach cognitive deficits are targeted directly through repeated practice training. However, results concerning cognitive remediation remain inconsistent. It is clear that not all individuals with schizophrenia display cognitive impairment, and even among those who do, the specific pattern of cognitive functioning varies. Moreover, traditional neurocognitive assessment, with a single or static administration of cognitive measures, provides moderately good prediction of skills acquisition in schizophrenia. Among other factors such as motivation, awareness of having a disease and acuteness of symptomatology, some studies have exposed that a cognitive variable, learning potential could mediate in part the effectiveness of cognitive remediation. DISCUSSION: The concept of learning potential is used to explain some of the observed variability in cognitive functioning. Learning potential is the ability to attain and utilize cognitive skills after cognitive training: it is assessed by individual variation in performance across three consecutive administrations of the Wisconsin Card Sorting Test (WCST): a pretest with standard instruction procedures, a training phase with expanded instruction and a post test with only standard instruction. Three learner subtypes can be identified: "learners" who perform poorly at the pretest but improve performance during the post-test, "non-retainers" who perform poorly at pre-test and do not improve at post-testing and "high achievers" who perform well in the initial pretest and maintain their good performance across the other two administrations. The assessment of learning potential could predict, with other psychological measures such as insight and motivation, the most effective neurocognitive rehabilitation program for an individual patient, and could help the clinician to optimize patient outcome through appropriate individual management. CONCLUSION: Indeed, learning potential could represent a good cognitive predictor and indicator for rehabilitation in schizophrenia for clinicians and should be used in cognitive assessment practice. However, the individuals most likely to benefit from cognitive remediation, and whether changes in cognitive function translate into functional improvements, are as yet unclear.

[Lack of insight in schizophrenia: a review]. / La conscience des troubles (insight) dans la schizophrénie : une revue critique Partie II : modèles explicatifs et hypothèses psychopathologiques.

BACKGROUND: Relative to other psychiatric disorders, patients with schizophrenia are often unaware of the consequences of their disease and their need for treatment. These deficits in awareness referred in general in the English literature as "poor insight", have been the focus of many clinical studies over recent years. This phenomenon, which is considered as fundamental in clinical evaluations of schizophrenia, should be understood as a multidimensional process rather than a dichotomic phenomenon, as is presently the case. The links between insight deficits and responses to vocational rehabilitation efforts represent a major interest in research, including those related to medication compliance and clinical outcome. To conduct such studies, various evaluation tools have been developed, enabling the assessment of insight, of its time-course and of its components in psychosis and schizophrenia spectrum disorders. LITERATURE FINDINGS: The Scale to Assess Unawareness of illness in Mental Disorders (SUMD) developed by Amador and Strauss appears to be the most frequently used scale for the evaluation of awareness of the disorder in schizophrenia. Although the model proposed by Amador and Strauss is considered as the privileged model in the multidimensional approach of insight, it corresponds only to a phenomenological analysis of this concept. In the second part of this article, we thus review the current models attempting to explain the lack of insight in schizophrenia. Four current explanatory models of lack of insight will be described as follows: resulting either from adaptation or defence mechanisms to environmental stressors, resulting from cognitive bias of data processing, resulting from neuropsychological functional deficits and resulting from metacognitive deficits. DISCUSSION: Several hypotheses concerning these deficits arise from clinical studies. Although coping, and defence mechanisms to the consequences and stigmatization of the disease were hardly studied, the fact that poor insight does not appear related to the severity of symptomatology or to the emotional state of the patients argue against this hypothesis. Conversely, a considerable body of literature emphasized how unawareness may result from cognitive deficits. Research in neuropsychology and cognitive psychology has provided consistent results concerning the link between deficit in executive functions, frontal lobe dysfunction and poor insight. Recent studies on bias in cognitive information treatment and social cognition theories currently open new prospects.

[Lack of insight in schizophrenia: a review. Part I: theoretical concept, clinical aspects and Amador's model]. / La conscience des troubles (insight) dans la schizophrénie : une revue critique. Partie I : insight et schizophrénie, caractéristiques cliniques de l'insight.

INTRODUCTION: Schizophrenia is the psychiatric disorder in which the awareness of pathology (or insight) is most frequently altered. LITERATURE FINDINGS: A review of the literature shows that between 50 and 80% of patients with schizophrenia do not believe they have a disorder. Studies published on this subject over the two last decades stressed the specificity of this phenomenon in schizophrenic patients, taking into account both its prevalence and its clinical consequences comparatively to other mental disorders. If in bipolar disorders a lack of insight is linked with the intensity and acuteness of symptomatology, there is only a limited relationship between these factors in schizophrenia, thus making lack of insight a trait rather than a state-related symptom. DISCUSSION: Though defined for a very long time as a dichotomic phenomenon, the recent interest on insight in psychosis and the development of assessment tools for its evaluation have made it possible to underline its multifactorial and dynamic characteristics. Although lack of insight related to pathologies may vary across time in bipolar disorders, the results of clinical studies suggest that this phenomenon remains stable in schizophrenia. CONCEPTUAL PROPOSALS: In this review, we will reconsider the evolution of this concept in psychiatry and its definition. The clinical characteristics, which are specifically associated with the lack of insight in schizophrenia will be outlined. We will describe more specifically the model of Amador and Strauss and their assessment tool: the Scale to Assess Unawareness of Mental Disorder (SUMD). This model developed since the 1990s takes into account the time-related evolution of insight, and can be applied both to bipolar and psychotic disorders. ASSESSMENT TOOLS: The SUMD has six general items and four subscales. The general items estimate the three most widely used definitions of insight: awareness of having a mental disorder, awareness of the achieved effects of medication and awareness of the social consequences of having a mental disorder, and include assessment of both current and past-time periods. Four other subscales, each composed of 17 items, assess awareness and attribution of specific current and retrospective symptoms as well as deficits associated with severe mental disorders. Insight, thus, appears as a multidimensional and continuous phenomenon, since patients' awareness may apply only to part of their symptoms and vary over time. In this article, we will review existing scales assessing insight in schizophrenia. The deficiency of available scales validated in French limits the number of scientific publications concerning this important aspect of the clinical evaluation of schizophrenic patients. THERAPEUTICAL ASPECTS: Finally, interventions to improve insight in patients with schizophrenia are presented. Recent studies have shown cognitive behavioural therapy (CBT) to be of benefit in the treatment of poor insight in schizophrenia. CONCLUSION: Evidence suggests that early diagnosis and treatment of schizophrenia leads to better prognosis. An important suggestion from theses studies may be that psychosocial therapy needs to focus on explanations that are in tune with the culture, rather than focus on diagnostic labels.

[Memory symptom exaggeration in a patient with progressive multiple sclerosis outside any medico-legal context]. / Exagération de symptômes mnésiques hors contexte médicolégal chez un patient atteint de sclérose en plaques.

INTRODUCTION: Memory symptom exaggeration or malingering in the forensic neuropsychological evaluation of well-documented brain pathology is seldom described. For some, documented neuropathology and malingering are considered to be mutually exclusive. CASE REPORT: We report an original clinical observation of an amnesic factitious disorder in a patient with progressive multiple sclerosis. This patient, who was seen for a routine comprehensive neuropsychological evaluation, demonstrated a severe memory encoding deficit in a classical standard episodic memory test. This amnesic syndrome was not in agreement with the neurological condition where deficits in retrieval memory processes are essentially observed. Moreover, his performance at two symptom validity tests fell below the admitted cut-off scores. In fact, the patient obtained an accuracy score of 3 (cut-score<10) in the Rey's 15-Items Test, a well known malingered amnesia measure. His performance in the 21-Items Test French adaptation was well below the proposed cut-off score of 15/21 and inferior to the results obtained by an Alzheimer patients group (n=30). A clinical approach of memory symptom exaggeration is described. We discuss the diagnosis of this false disorder. CONCLUSION: This case report demonstrates unequivocally that memory symptom exaggeration or malingering can and does occur in patients seen without litigious contexts and who have a well-documented neurological pathology. Failure to address malingering may compromise neuropsychological clinical findings. Nevertheless, there is a lack of up-to-date standard French-language documentation in this topic.

Air nicotine and saliva cotinine as indicators of workplace passive smoking exposure and risk.

We model nicotine from environmental tobacco smoke (ETS) in office air and salivary cotinine in nonsmoking U.S. workers. We estimate that: an average salivary cotinine level of 0.4 ng/ml corresponds to an increased lifetime mortality risk of 1/1000 for lung cancer, and 1/100 for heart disease; > 95% of ETS-exposed office workers exceed OSHA's significant risk level for heart disease mortality, and 60% exceed significant risk for lung cancer mortality; 4000 heart disease deaths and 400 lung cancer deaths occur annually among office workers from passive smoking in the workplace, at the current 28% prevalence of unrestricted smoking in the office workplace.

Respiratory health effects of exposure to environmental tobacco smoke.

During the last 25 years, several hundred papers have been published on the respiratory health effects of environmental tobacco smoke (ETS). Various independent assessments have concluded that ETS causes lung cancer in adult nonsmokers and increases the risk of various noncancer effects, principally in children. The effects on children include pneumonia, bronchitis and bronchiolitis in young children; chronic middle ear effusion; increased frequency and severity of attacks among asthmatics; possible induction of asthma in previously asymptomatic individuals; small reductions in lung function; and symptoms of upper respiratory tract irritation. In nonsmoking adults, ETS exposure is associated with irritation of the eyes, nose, and throat, and with wheezing, symptoms of bronchitis, shortness of breath, and decreased lung function. The results of recent studies not only confirm and strengthen the above findings but also provide strong suggestive evidence that ETS causes sinonasal cancer and is a risk factor for sudden infant death syndrome. To mitigate such a preventable environmental health impact, public health measures to reduce involuntary ETS exposure are warranted.

Respiratory health effects of passive smoking: EPA's weight-of-evidence analysis.

After an extensive review and assessment of the scientific evidence on the respiratory health effects of passive smoking, the U.S. Environmental Protection Agency has determined that the widespread exposure to environmental tobacco smoke in the United States presents a serious and substantial public health impact. The Environmental Protection Agency concluded that environmental tobacco smoke causes lung cancer in adult nonsmokers and increases the risk for a variety of noncancer respiratory disorders, especially in children. This article reviews evidence presented in the Environmental Protection Agency's 1992 report on the respiratory health effects of passive smoking and responds to critical allegations levied by Gio Gori in his article "Science, policy, and ethics: the case of environmental tobacco smoke", appearing in the same issue of this journal. Several recent studies appearing since the cutoff date for inclusion in the EPA report are also discussed.

La legislación panameña en relación con la epidemiología del Síndrome de InmunoDeficiencia Adquirida (SIDA) / The panamanian law and its relation to the epidemiology of the Acquired ImmunoDeficiency Syndrome (AIDS)

Con la introducción del Síndrome de InmunoDeficiencia Adquirida (SIDA), la más reciente de las enfermedades de transmisión sexual, la legislación panameña vigente, en vez de estigmatizar al enfermo o infectado, al tipificar la transmisión sexual como un delito a la salud pública, debería orientarse a garantizar para el paciente, el pleno derecho a una vida social y económicamente productiva. Esto permitiría respetar la condición humana y evitar prácticas descriminatorias y alienantes

Cancer risk assessment of 1,3-butadiene.

This paper discusses the Environmental Protection Agency's (EPA) risk assessment of 1,3-butadiene. The assessment focuses on estimation of increased cancer risk to populations living near industrial sources of 1,3-butadiene emissions rather than occupationally exposed populations. Incremental cancer risk estimates based on extrapolation from laboratory animal data are presented. Pharmacokinetic data published since the EPA's 1985 assessment are incorporated, which somewhat alters the earlier assessment of cancer risk. Characterization of emission sources, estimates of ambient air concentrations, and population exposure are also discussed. The estimate presented in this paper of excess cancer cases resulting from point source exposure to 1,3-butadiene is decreased to approximately 40% of the estimate published in 1985 from 6.4 in 10 to 2.5 chances in 10 for a lifetime exposure to 1 ppm. The current estimate is no more than eight additional cancer incidences in the general population. Increased risk to the most exposed individuals is not anticipated to be greater than 1 in 10. This reduction in the risk estimate is due to a change in the estimate of 1,3-butadiene potency (i.e., incremental unit risk estimate) based on incorporation of new pharmacokinetic data.

Detergent toxicity survey.

A survey of over 249 detergent products involving biological testing, chemical analyses, and product label reviews has been conducted from 1971-1976 for determining compliance with the Federal Hazardous Substances Act. Test results for 145 detergent products having both chemical and biological data were examined. All of the tested detergents were rabbit eye irritants. Forty-seven per cent were also either rabbit primary skin irritants or corrosives. Eighty-one per cent were either rabbit esophageal test irritants or corrosives, and 80 per cent had rat oral toxicities 5g/kg or less.

Appraisal of existing methodology in aspiration toxicity testing.

New methods or modifications of currently used methods in aspiration toxicology must be capable of accurately assessing the hazard and toxicity potentials of those products which are capable of being aspirated. The methods evaluated in the rat were intratracheal injections,intravenous injections, and modifications of the Gerarde technique. A product containing petroleum distillates and a standard viscosity petroleum distillate sample were administered to Osborne-Mendel rats, rabbits, and guinea pigs in ml/kg doses. The utility of the methods was determined by comparing lung weight increases, lung-body weight ratios, gross pathological lung changes, and mortality. The modified Gerarde technique showed the best potential for predicting aspiration hazard and toxicity based on the severity of the reactions which, using a radiolabeled oil, was shown to be a function of the amount of product which enters and reacts with the lungs. The influence of preventing the swallowing reflex to assure aspiration of the oil was assessed in the rat. The results show that less than 10% of the dose is aspirated when the swallowing reflex occurs. Methods of sacrifice were investigated for an effect on rat lung weight. No tested method except stunning with cervical dislocation produced an effect. Tests were conducted on rats and rabbits to determine differences in lung reactivity to the influence of inhalation anesthetics, pentothal sodium, or no anesthesia in response to petroleum distillate administration and to determine which test species is the better animal model. The resuls indicate that the rat is the better test model because of degree of lung reaction, size, and economy, and that inhalation anesthesia with ether is preferable over the other choices.