[COVID-19: Practice and ethics of videoconsultation assessment of children with autism spectrum disorder]. / COVID-19 : pratique et éthique de l'évaluation par vidéoconsultation des enfants avec trouble du spectre de l'autisme.

OBJECTIVES: The COVID-19 crisis dramatically broke down the administrative, technological and clinical barriers that previously existed in the field of telemedicine. There is an important need to define standards for remote clinical observation, for instance in case of suspected autism spectrum disorder (ASD). Describing tools for the remote assessment of children with ASD and reflecting upon the ethical aspects of this practice will improve the quality of care with telemedicine. METHOD: Since 2013, we have conducted clinical evaluations by means of telemedicine at the center for diagnostic and evaluation of autism of the GHU Paris Psychiatry and Neurosciences which have afforded us opportunities to develop information tools and specific procedures. This clinical procedure is associated with ethical reflections that we included in our procedure. RESULTS: Benefits and risks are presented to families, and informed consent is obtained. The use of validated tools is privileged and their results are analyzed in light of the clinical experience of the professional. Privacy for persons and professionals is preserved, and the patient-doctor relationship is reinforced because of the ability of the patient to make decisions and feel more empowered in the context of the videoconsultation. CONCLUSION: The COVID-19 crisis was the impetus for a dramatic increase in the use of telemedicine with a potential risk because of the broad and blurry framework of its application. Clinical and ethical concerns must be studied. Moving forward, societal reflection about the accessibility of telemedicine will be necessary: telemedicine for all should be a future perspective.

Daratumumab: Therapeutic asset, biological trap!

OBJECTIVES: Recently, daratumumab has been included in the therapeutic strategies for myeloma patients. This molecule is an antibody directed against CD38, strongly expressed on plasma cells. Nevertheless, as CD38 is also present on erythrocyte membrane, daratumumab interferes with immunohaematological tests, complicating the selection of compatible blood. METHODS: A total of 14 patients treated by daratumumab have been followed in our transfusion laboratory. Among them, 11 have been transfused. Dithiotreitol (DTT) has been used to inhibit the daratumumab's interference, in the pre-transfusion tests (irregular antibody screening and cross-match). RESULTS: The red blood cell treatment with DTT has been very efficacious to inhibit the daratumumab's interference in 13 patients out of 14. Some precautionary measures had to be taken into account, especially the pH and the storage conditions. An extended pheno/genotype was an additional security element in the selection of compatible blood. To simplify and to optimize the laboratory practices, a decisional flow chart has been written. CONCLUSION: DTT red blood cell treatment is very useful and efficacious in the pre-transfusion tests of patients treated with daratumumab. It allows to avoid the selection of blood bags only on the basis of an extended pheno/genotype, what is more secure and more ethical with respect to other at higher risk patients. A clear decisional flow chart allows a quality assurance gait. Collaboration with physicians is essential.

[Therapeutic effects of oxytocin in autism: Current status of the research]. / Applications thérapeutiques de l'ocytocine dans l'autisme : premiers résultats et pistes de recherche.

The neuropeptide oxytocin (OT) is an evolutionary highly conserved molecule that plays a part in the regulation of complex social cognition and behaviours. From a pathophysiological point of view, several studies have evidenced dysfunctions of the oxytocinergic system in autism spectrum disorders (ASD): a lowering of plasma OT and genetic or epigenetic anomalies of the OT receptor. Therefore, some authors have hypothesized that an abnormality in the OT neurotransmission may account for several features of autism and that a treatment restoring a normal OT pathway functioning could improve social abilities. OT administration has thus been used in clinical trials, especially in groups of subjects suffering from autism. Some studies found that OT decreased repetitive behaviours, enhanced emotional understanding of speech intonation, improved performance of the Reading the Mind in the Eyes Test and reinforced cooperation. Nevertheless, the findings of the OT administration studies on clinical samples show great diversity. The context, the personality and childhood experiences of the subject could be moderators influencing the effect of exogenous OT. Besides, three mechanisms could play a part in the action of OT on ASD social symptoms: anxiety reduction (with a lowering in the hypothalamic-pituitary-adrenal axis responsiveness and in the amygdale reactivity to social stimuli), increased affiliative motivation (involving the dopaminergic pathway and several regions of the social brain) and enhanced perceptual selectivity and social stimuli salience. To conclude, OT could be a promising molecule used as a treatment to promote social behaviours, helping individuals with ASD to develop new relationships. OT could be administered during a cognitive-behavioural therapy to reinforce the efficacy of such procedures. More studies are needed, on larger samples, to investigate the safety and efficacy of OT administration and to specify optimal dosages and characteristics of patients who may benefit from this treatment.

[Cognitive remediation therapy for children: literature data and clinical application in a child and adolescent psychiatry department]. / Thérapie par remédiation cognitive chez les enfants : données de la littérature et application clinique dans un service de psychiatrie de l'enfant et de l'adolescent.

The hypothesis of cerebral plasticity in psychiatric disorders has encouraged clinicians to develop cognitive remediation therapy (CRT), a new therapeutic approach based on attention, memory, planning, and mental flexibility tasks. The first cognitive remediation programs were developed and validated for adults with schizophrenia and were shown to have a positive impact on executive functions as well as on quality of life. In children and adolescents, researchers emphasized the existence of executive dysfunction in neurodevelopmental disorders such as autistic spectrum disorder, attention deficit disorder, and eating disorders. For these disorders, neuropsychological studies suggest that memory, planning, attention and mental flexibility are impaired. Despite the paucity of studies on cognitive remediation (CR) in children, preliminary results have suggested, as in adults with schizophrenia, good compliance and optimization of executive functioning. Consequently, programs dedicated to young subjects were developed in English-speaking countries, and the Department of Child and Adolescent Psychiatry of Sainte Anne Hospital (Paris) developed a new CR program for children with attention deficit disorder, academic problems, or eating disorders. These programs complete the field of CRT proposed by Sainte Anne Hospital's Remediation and Psychosocial Rehabilitation Reference Center, initially designed for adults with schizophrenia. Our team used and adapted validated tools such as Delahunty and Wykes's CRT program (translated and validated in French by Amado and Franck) and Lindvall and Lask's CRT Resource Pack. One program was developed for an adolescent with anorexia nervosa and applied to the subject and her family, but the purpose of this paper is to present a CR approach for children with attention deficit disorder or academic disorder, a 6-month program based on paper-pencil tasks and board and card games. The team was trained in different kinds of cognitive remediation, and the program was applied by a clinical nurse with the supervision of a child and adolescent psychiatrist and the department's neuropsychologists. Paper-pencil tasks were adapted from the CRT program for adults; the card and board games used were geometric figures, illusions, Rush Hour(®), Set(®), Jungle Speed(®), Color Addict(®), etc. These games are available in stores and the program can be applied at home, which helps families set aside their preoccupations with their child's academic performance. Diagnostic and neuropsychological evaluations were done before the beginning of the therapy and repeated at the end of the 6-month program. This program does not ignore the metapsychological impact of the therapy, and work on self-esteem is also done. The presence of the therapist is necessary, which seems better than a computer program, which cannot encourage the young subject in the same personalized and empathetic way. We therefore conducted the first clinical feasibility trial of cognitive remediation in young subjects and present a clinical case of a 6-year-old boy with attention deficit disorder and academic disorder. The results of neuropsychological evaluations before and after therapy suggest improvement in executive functions and better self-esteem. Satisfaction for the boy and his family was high. Even if these results need to be replicated, cognitive remediation appears to be a new therapeutic tool, complementary to classical approaches used in childhood psychiatric disorders. The Department of Child and Adolescent Psychiatry will submit this program to a research program conducted by the National Health Department to study the impact of this approach in a controlled study.

[Autism spectrum disorder and suicidality]. / Troubles du spectre autistique et suicidalité.

INTRODUCTION: Most studies on suicide exclude subjects with autism spectrum disorders, yet there is a risk group. The purpose of this article is to present the data in the literature regarding the clinical and epidemiological characteristics of suicidality in subjects with autism spectrum disorders and to identify the factors that promote the transition to action. METHODS: This review was carried out using the data set collected in Medline PubMed, items with "autism spectrum disorder", "pervasive developmental disorder", "Asperger's syndrome", "suicide", "suicide attempt", and "suicide behavior". RESULTS: In all subjects from our research on PubMed, 21.3% of subjects with autism spectrum disorder reported suicidal ideation, have attempted suicide or died by suicide (115 out of 539 subjects) and 7.7% of subjects supported for suicidal thoughts or attempted suicide exhibited an autism spectrum disorder (62 out of 806 subjects), all ages combined. Suicidal ideation and morbid preoccupation are particularly common in adolescents and young adults. Suicide attempts are accompanied by a willingness for death and can lead to suicide. They are more common in high-functioning autism and Asperger subjects. The methods used are often violent and potentially lethal or fatal in two cases published. Suicide risk depends on many factors that highlight the vulnerability of these subjects, following autistic and developmental symptoms. Vulnerability complicating the diagnosis of comorbid depressive and anxiety disorders are major factors associated with suicidality. Vulnerability but also directly related to suicidality, since the origin of physical and sexual abuse and victimization by peers assigning them the role of "scapegoat" are both responsible for acting out. CONCLUSION: Given the diversity of factors involved in the risk of suicide in this population, this does not validate "a" program of intervention, but the intervention of "customized programs". Their implementation should be as early as possible in order to treat while the brain has the greatest plasticity. The aim is to provide the necessary access to the greatest possible autonomy. Hence, including working communication skills and interaction, these subject will have independent means of protection, an essential complement to measures to protect vulnerable subjects; the vulnerability of direct and indirect suicidality. Comorbid diagnoses must take into account the specificities of these patients, their difficulties in communicating their mental state, and adapted and innovative therapeutic strategies must be offered and validated.

[Breastfeeding after breast cancer: survey to hospital health professionals in Alsace]. / Allaitement après cancer du sein : enquête auprès des professionnels de santé hospitaliers en Alsace.

OBJECTIVES: For women treated for a breast cancer and wanting childbearing, the issues of breastfeeding and its oncological safety are controversial. Therefore the aim of our study was to establish a state of knowledge of health professionals on this subject. METHODS: Two hundred and fifty questionnaires were distributed to hospital health professionals, in five Units of Obstetrics and Gynecology in Alsace. The results of our study were expressed as the number of responses, and percentage. RESULTS: Analysis of the answers to this questionnaire demonstrated that health professionals have a good theoretical knowledge of the subject and that breastfeeding is not contraindicated. Indeed, in case of breastfeeding, 90% of the hospital health professionals thought that the risk of recurrence was unchanged or decreased and 81% of them answered that the overall survival was unchanged or increased. However, on a practical view, none of these health professionals followed a woman who breastfed after a breast cancer. DISCUSSION AND CONCLUSION: Breastfeeding after breast cancer does not worsen the prognosis and seems even to improve it. Furthermore, women breastfeeding after a breast cancer have an improved life quality and recommend it to other patients. However, few women breastfeed after breast cancer and this is due to often non-justified reasons coming from their health professionals. Their role should be more to pass clear information and bring their support to breastfeeding to help the women to face their fears as well as encountered difficulties which are not specific, but felt in a more intensive way.

[Cognitive remediation therapy for children and adolescents with anorexia nervosa in France: an exploratory study]. / Évaluation d'un programme de remédiation cognitive au sein d'un groupe d'enfants et d'adolescents anorexiques français: étude exploratoire.

OBJECTIVE: Cognitive remediation therapy (CRT) seems to be increasingly interesting in the treatment of anorexia nervosa for adult patients. We attempted to apply this support to a group of young inpatients, initially to assess its feasibility and acceptability, and then to improve its content for therapeutic application and future research. METHODS: Ten 12- to 17-year-old inpatients with primary DSM-IV diagnosis of anorexia nervosa participated in a 10-week intervention program with a one-hour group session of CRT per week. All 10 patients were assessed before the intervention and those who completed the 10 sessions were assessed after. Assessment included a clinical examination by a psychiatrist, a battery of clinical inventories, and set-shifting tests. Moreover, each patient wrote a letter providing feedback on the intervention for subsequent analysis. RESULTS: Only two patients completed all 10 sessions, the other eight who were discharged from the hospital in the meantime could not attend the sessions for practical reasons. After the 10 sessions, an improvement in BMI and in measured levels of some psychopathological symptoms was observed in our two patients. Most neuropsychological task performances were improved after cognitive remediation. Feedback from the 10 patients was generally positive. CONCLUSION AND IMPLICATIONS FOR PRACTICE: This preliminary investigation suggests that cognitive remediation therapy is acceptable and feasible in this population. Replication of these findings requires a larger sample, improvement of the trial design, more sensitive measures, and another training format to avoid loss of so many participants.

[Anorexia nervosa in the light of neurocognitive functioning: New theoretical and therapeutic perspectives]. / L'anorexie mentale à la lumière du fonctionnement neurocognitif : nouvelles perspectives théoriques et thérapeutiques.

INTRODUCTION: Anorexia nervosa is a serious psychiatric disorder, for which very few validated therapeutic strategies exist. The specific sociocognitive style of anorexic patients has already been described in the 1960s: it involves a concrete style with abstraction difficulties. Current neuropsychological tests have contributed to a more precise definition of these difficulties. NEUROPSYCHOLOGICAL DATA: IS THERE A SPECIFIC COGNITIVE PROFILE?: Contrary to common beliefs, these patients' intellectual performances are not superior to those of the general population. However, detailed comparisons of profiles on the Weschler Scales suggest difficulties in synthesizing information and better abilities in concrete problem solving. EXCESSIVE ATTENTION TO DETAILS: The dominant hypothesis concerning the attentional dimension is the existence of a weakness in central coherence, resulting in superior detail processing and a weakness in global integration. This trend appears to be stable even after the normalization of nutritional status. IMPAIRED COGNITIVE FLEXIBILITY: The impairment of set-shifting abilities leads to rigidity, expressed by inflexibility and perseveration, both in reasoning and behaviour. This reduced cognitive flexibility appears to persist after recovery, and may constitute a familial trait. In addition, this likely endophenotype seems to be independent from obsessional traits. CONTROVERSIAL SOCIAL SKILL: Alexithymia is frequently described in anorexic individuals. It is the verbal description of feelings which seems to be particularly impaired. It may explain underlying difficulties in empathy. Indeed, these subjects have lower scores on emotional tests drawn from the theory of mind. These cognitive abnormalities are well documented in pervasive developmental disorders. NEUROANATOMICAL DATA: NEUROIMAGING IN SUPPORT OF LIMBIC AND FRONTO-STRIATAL ABNORMALITIES: Evidence from neuroimaging suggests abnormalities in cortical and subcortical structures, involving the temporal and orbito-frontal lobes. Various functional hypotheses are formulated, involving fronto-striatothalamic circuits, amygdala or insula. IS ANOREXIA NERVOSA A DEVELOPMENTAL DISORDER?: Pervasive developmental disorders are over-represented among anorexic subjects in comparison to the general population. Conversely, restrictive and selective eating disorders are more frequent among individuals presenting an autistic spectrum disorder. THERAPEUTIC IMPLICATIONS AND FUTURE DIRECTIONS: In view of the common cognitive and neuroanatomical data that are found in anorexia nervosa and neurodevelopmental disorders, we adhere to the hypothesis that anorexia nervosa may be similar to a neurodevelopmental disorder. Clinical observations suggest that this hypothesis may be especially relevant in the early forms of anorexia nervosa. These cognitive data confirm the potential relevance of new therapeutic modalities such as cognitive remediation. Initial results from its application to anorexia nervosa seem promising. CONCLUSION: A review of the recent literature highlights the possible existence of a developmental impairment of cortical and subcortical structures, associated with specific abnormalities in cognitive development such as a weakness in central coherence, reduced set-shifting ability and poor social skills. On this basis, cognitive remediation may be a promising therapeutic innovation.

Prospective observational study of treatment pattern, effectiveness and safety of zoledronic acid therapy beyond 24 months in patients with multiple myeloma or bone metastases from solid tumors.

PURPOSE: To study the treatment patterns, effectiveness and safety of zoledronic acid (ZOL) beyond 2 years of therapy, given the paucity of data on long-term treatment in daily clinical practice. METHODS: Patients with multiple myeloma (MM) or solid tumor bone metastases (STM) and at least 24 months of regular q3-4w ZOL therapy were followed prospectively for an additional 18 months beyond the 24 months required for study entry. End-points included ZOL exposure, incidence of skeletal related events (SRE), and safety. RESULTS: In all, 298 evaluable patients were enrolled. The mean continuation rate of ZOL was 90.6%. Exposure to ZOL decreased with time in all patients, but was lower (50.0% vs. 67.6%; p<0.001) and with higher discontinuation rates (incidence rate ratio [IRR]=1.95; p=0.002) in MM compared to the STM group. ZOL suppressed the rate of SREs similarly during the study as compared to before inclusion (0.12 vs. 0.13 events per person-year; p=0.7). At 18 months, 84.5% remained SRE-free. In STM patients, persistent ZOL therapy was associated with lower SRE risk (hazard ratio [HR]=0.42; p=0.01), but not in MM. Renal deterioration occurred in 3.7% and osteonecrosis of the jaw (ONJ) developed in 6.0%, with dental trauma increasing ONJ risk (HR=4.67; p=0.002). CONCLUSIONS: Beyond 2 years of therapy, treatment patterns of ZOL were heterogeneous and SRE rates were low. The safety profile of ZOL was acceptable, and interrupting ZOL in patients with solid tumors was associated with a higher risk of SREs.

Lenalidomide in relapsed refractory myeloma patients: impact of previous response to bortezomib and thalidomide on treatment efficacy. Results of a medical need program in Belgium.

The prognosis of multiple myeloma patients has significantly improved since the introduction of the novel agents thalidomide, bortezomib and lenalidomide. We report the data of a medical need programme with lenalidomide plus dexamethasone, conducted in Belgium between August 2007 and March 2008, and including 98 relapsed refractory multiple myeloma patients. In addition to chemotherapy and steroids, all patients had received prior treatment with bortezomib, and 84% of them had been exposed to thalidomide. In 52 patients response data could be retrieved by post-hoc analysis. A partial remission or better was achieved in 52% (49% partial and 3% complete response) of patients, despite a median of 5 previous anti-myeloma treatment lines. Responses were rapid while the majority of patients received lenalidomide with once weekly (also called low-dose) dexamethasone. Treatment with lenalidomide plus dexamethasone did prolong overall survival by nearly half a year in this population with end-stage myeloma. Overall response and quality of response were independent of previous response to thalidomide and bortezomib, although the time to progression tended to be shorter in thalidomide- and bortezomib-refractory patients. It can be concluded that lenalidomide plus dexamethasone is an effective and safe treatment regimen in highly refractory multiple myeloma patients, and that these responses are irrespective of previous exposure or sensitivity to thalidomide and bortezomib.

Melatonin in children with autistic spectrum disorders: recent and practical data.

Over the last 20 years, melatonin, a pineal hormone synthesized from serotonin, has been implicated in various studies on the autism spectrum disorder (ASD) and altered melatonin levels were detected in subgroups of subjects with ASD. Its effect on sleep disturbances got the attention of clinicians and several investigations were carried out to determine the usefulness and safety of melatonin administration in this disorder. Hypotheses were also raised regarding the possibility that the dysfunctional synthesis and secretion of melatonin detected in subgroups of subjects with ASD may increase the risk as well the severity of ASD. The purpose of this paper is to review our pharmacokinetic knowledge on melatonin and present results from recent studies on sleep disorders in autism, their treatment with melatonin and the impact of melatonin prescription in children with ASD evaluated in a Diagnostic Center for Autism Spectrum Disorder in Paris, France.

The Belgian 2010 consensus recommendations for the treatment of multiple myeloma.

Since the introduction of novel therapeutic agents including thalidomide, lenalidomide and bortezomib, the prognosis of multiple myeloma (MM) has significantly improved. These agents have been incorporated into numerous treatment schedules for newly diagnosed as well as more advanced MM patients. Hence, the therapeutic options for MM have become more complex and subject to rapid changes. The multiple myeloma study group (MMSG) of the Belgian Hematological Society has established recommendations for the treatment of MM as based on an extensive review of the literature which is also summarized in this paper. The recommendations are the result of a consensus opinion between haematologists with experience in the field and representing most haematology centres in Belgium. Where applicable, reimbursement criteria are also taken into account. The consensus recommendations should be a reference for use by clinical haematologists in daily practice.

[Treatment of anorexia nervosa in young patients in a special care unit at Robert-Debré Hospital (Paris): guidelines and practical methods]. / Traitement de l'anorexie mentale du sujet jeune en unité d'hospitalisation spécialisée: recommandations et modalités pratiques.

There are no official guidelines for the treatment of anorexia nervosa in young patients. Some recommendations have been proposed by a group of British experts (N.I.C.E., 2004), based on results from controlled studies. Our inpatient care unit takes into account the different dimensions of anorexia nervosa in this subgroup of young patients and proposes an integrated approach including medical care, nutritional care, and psychological care, as suggested by the N.I.C.E. recommendations. We attempt to take into account variables that are unique to these young patients. More specifically, we insist on weight restoration that will permit adequate growth and we do not systematically separate the patient from his or her family. In addition, family therapy or counseling is systematically provided. The aim of this approach is to support parents, to provide psychoeducational guidance, and to help the family acquire new behaviors and new ways of understanding the eating disorder. Most patients are treated on an outpatient basis, but inpatient care is offered when the patient displays severe medical conditions or a severe comorbid psychiatric illness. Anorexia nervosa is a protracted disorder that requires multidisciplinary outpatient medical follow-up, including the intervention of a general practitioner and a psychiatric team.

[Treatment of a serious autistic disorder in a child with Naltrexone in an oral suspension form]. / Traitement d'un enfant autiste par la naltrexone.

UNLABELLED: CLINICAL BACKGROUND: Autism is a developmental disorder that is usually diagnosed in early childhood. According to ICD-10 criteria, autism can be characterized by delays in language skills, by impaired social interaction, verbal or non-verbal communication and by repetitive, stereotyped or severely restricted activities and interests. The causes of autism are not yet elucidated, but both genetics and environment seem to play a role in 10 to 25% of autism cases. Several biochemical abnormalities, such as impairment of serotoninergic, catecholinergic, dopaminergic, and opioid systems have been reported. Autism therapies are designed to treat symptoms, and medication can be associated with psychoeducational and environmental interventions. Generally, the medications that are currently used are not intended for autism, and must be used with caution and selected according to the type and intensity of symptoms. The most common medication consists of psychotropic therapies by administration of dopaminergic and/or serotoninergic receptor antagonists (haloperidol, risperidone, clomipramine). Several drugs, such as anxiolytics (buspirone), mood stabilisers (lithium, sodium valproate), vitamins (vitamins B6, B12) or opioid antagonists (naltrexone) can be prescribed, in second intention, in cases of severe behavioural disorders. The prescription of opioid antagonists is based on the possible implication of an opioid system disorder observed in some cases. Nevertheless, several clinical studies reveal its variable effectiveness. Naltrexone is a competitive antagonist of opioid receptors OPRM1, OPRD1 and OPRK1. In France, this drug is prescribed for treating opioid and alcohol dependence. Moreover, several studies describe naltrexone as a possible treatment of autistic children in cases of developmental disorder and hyperactivity. CLINICAL CASE: In the Child and Adolescent Psychopathology Department of Sainte-Anne's Hospital, autistic children benefit from a multidisciplinary treatment program that sometimes includes the administration of psychotropic medication. One of these children presented with a severe autistic disorder according to the Childhood Autism Rating Scale (CARS). Considering ICD-10 criteria, he benefited from a multidisciplinary program, associating cognitive psychotherapy, psychomotor rehabilitation, speech therapy and educational intervention. However, persistent sleep disorder and motor instability led to successive prescriptions of several different psychotropic drugs. Initial treatment by thioridazine (10mg per day) followed by propericiazine (2.5mg per day) improved sleep, but was not efficient in reducing self-mutilating behaviour. A new treatment by risperidone (from 0.5mg to 1.5mg per day) was therefore chosen; however it lost its efficacy after five months. Finally, an anxiolytic (cyamemazine) and a thymoregulator (sodium valproate) were successively tried without yielding any clinical improvement. Owing to the persistence of communication difficulties, major instability, self-mutilating behaviour and heteroaggressiveness, treatment with naltrexone was subsequently chosen with parental consent. In France, naltrexone hydrochloride is only available in tablet form (Nalorex 50mg and Revia 50mg), which is not adapted to children at the efficient dose. Consequently, an oral suspension form marketed in Spain (Antaxone 50mg) was imported, having obtained the Afssaps' (the French drug administration) authorisation for its temporary use. The Connors and Nisonger scales were used as outcome measures of behavioural symptom change. The Conners scale is used to assess attention deficit and hyperactivity, whereas the Nisonger scale analyses social skills and behaviour disorders in children and adolescents with mental retardation. The onset of treatment, at a dose of 1mg/kg/day, led to a transitory increase in negative behaviour. However, a dose of 0.75mg/kg per day subsequently led to significant improvements, as shown by outcome measurements. Self-mutilating behaviour disappeared completely. Certain side effects were observed, namely transitory sedation at the beginning of treatment and moderate constipation. CONCLUSION: This clinical case confirms that treatment of a serious autistic disorder in children using Naltrexone in oral suspension form is a potentially interesting therapeutic alternative for treating behavioural symptoms resistant to classical drug therapy.

[Substitutive and dietetic approaches in childhood autistic disorder: interests and limits]. / Approches substitutive et diététique du trouble autistique de l'enfant : intérêts ou limites ?

INTRODUCTION: Autism is a developmental disorder that requires specialized therapeutic approaches. Influenced by various theoretical hypotheses, therapeutic programs are typically structured on a psychodynamic, biological or educative basis. Presently, educational strategies are recommended in the treatment of autism, without excluding other approaches when they are necessary. Some authors recommend dietetic or complementary approaches to the treatment of autism, which often stimulates great interest in the parents but also provokes controversy for professionals. Nevertheless, professionals must be informed about this approach because parents are actively in demand of it. LITERATURE FINDINGS: First of all, enzymatic disorders and metabolic errors are those most frequently evoked in the literature. The well-known phenylalanine hydroxylase deficit responsible for phenylketonuria has been described as being associated with autism. In this case, adapted diet prevents mental retardation and autistic symptoms. Some enzymatic errors are also corrected by supplementation with uridine or ribose for example, but these supplementations are the responsibility of specialized medical teams in the domain of neurology and cannot be applied by parents alone. Secondly, increased opoid activity due to an excess of peptides is also supposed to be at the origin of some autistic symptoms. Gluten-free or casein-free diets have thus been tested in controlled studies, with contradictory results. With such diets, some studies show symptom regression but others report negative side effects, essentially protein malnutrition. Methodological bias, small sample sizes, the use of various diagnostic criteria or heterogeneity of evaluation interfere with data analysis and interpretation, which prompted professionals to be cautious with such diets. The third hypothesis emphasized in the literature is the amino acid domain. Some autistic children lack some amino acids such as glutamic or aspartic acids for example and this deficiency would create autistic symptoms. However, for some authors, these deficits are attributed to nutritional deficits caused by the food selectivity of children. A fourth hypothesis concerning metabolic implication in autism is the suspicion that a food allergy phenomenon could interfere with development, and it has been observed that Ig levels are higher in autistic children than in control children. Autistic children with a positive reaction to food Ig would have a more favourable outcome with diet excluding some kinds of food; but most of those diets are drastic and ethically debatable. Fifth, glucidic catabolism could be deleterious with an excess of ketonic products that will initiate comitial seizures. Few studies with ketogenic diet have been conducted but, as it has been described with epileptic subjects, those diets would diminish autistic symptoms. Not enough studies have been conducted that would allow one to draw any firm conclusions. The sixth hypothesis is linked with vitamin deficiencies that are a notably important area of research in the treatment of autism. Vitamin B12 or B6 deficiencies have been studied in several articles, and many of them were controlled studies. French teams also emphasize an interest in supplementation with B12 or B6. The two last hypotheses concern auto-immune patterns and the toxic effects of heavy metals like mercury. There is a paucity of methodologically satisfying studies that support these two hypotheses and diet recommendations. Following these assumptions, some dietetic approaches have been recommended, even though the methodological aspects of supporting studies are poor. The most famous diet is the gluten-free and/or casein-free diet. Only two controlled studies attracted our attention. Even if for some autistic children such a diet was positive, for others, gluten-free or casein-free diets were poorly tolerated and, for some authors, not without considerable side effects, the more prejudicial of which was the Kwashiorkor risk. Ketogenic diets have been studied in one non controlled study, but even if positive results have been noted by the authors, the ketogenic diet is very restricting and the long term effects have not been evaluated. Vitamin supplementation is the one and only diet domain where there have been many repeated and placebo-controlled studies. Side effects are rare and mild even if high doses of vitamin B6 are advocated in these studies. In total, as evoked by Rimland, 11 controlled placebo-blind studies have been conducted and 50% of autistic children with this supplementation had improved autistic signs. However, these results still remain debated. Finally, more rarely, enzymatic abnormalities need specific diets which have some positive consequences, but such diets could not be applied by parents alone and are the responsibility of specialized teams. For discussion purposes we can emphasize that, in spite of the amount of studies concerning the effects of specialized diets, few are methodologically satisfying. We can not ignore that some side effects are possible with such approaches and parents need to be informed of them. Some are even potentially serious, such as diets with metal chelators. In spite of those results, vitamin supplementation seems to be the only one that some specialized teams in autism could apply, always with parent agreement. In conclusion, within this scientific field, studies on eating habits of autistic children should be conducted because of their food selectivity or avoidance.

Family therapy in the treatment of adolescent anorexia nervosa: current research evidence and its therapeutic implications.

From the outset, the systemic and family movement has expressed an interest in eating disorders, more specifically anorexia nervosa, establishing causal links between family functioning and aetiology and advocating family therapy as the treatment of choice for this disorder. Because of high consistency between its explanatory and therapeutic dimensions, this model continues to dominate our conceptualizations and clinical practice, in spite of a lack of empirical support. This article summarizes present empirical evidence concerning both family functioning (explanatory dimension) and the effectiveness of family therapy (therapeutic dimension) in anorexia nervosa, and describes resulting changes in theoretical and clinical perspectives. A model of evidence-based family therapy is presented and several unresolved issues are raised. Overall, this overview of the literature supports the use of therapeutic models that are more flexible and normative, less guilt-inducing, more diversified (eclectic and integrative), and more rooted in the empirical literature.

Heterogeneity of t(4;14) in multiple myeloma. Long-term follow-up of 100 cases treated with tandem transplantation in IFM99 trials.

One hundred de novo multiple myeloma patients with t(4;14) treated with double intensive therapy according to IFM99 protocols were retrospectively analyzed. The median overall survival (OS) and event-free survival (EFS) were 41.4 and 21 months, respectively, as compared to 65 and 37 for patients included in the IFM99 trials without t(4;14) (P<10(-7)). We identified a subgroup of patients presenting at diagnosis with both low beta(2)-microglobulin <4 mg/l and high hemoglobin (Hb) >/=10 g/l (46% of the cases) with a median OS of 54.6 months and a median EFS of 26 months, respectively, which benefits from high-dose therapy (HDT); conversely patients with one or both adverse prognostic factor (high beta(2)-microglobulin and/or low Hb) had a poor outcome. The achievement of either complete response or very good partial response after HDT was also a powerful independent prognostic factor for both OS and EFS.