Is chemotherapy necessary for premenopausal women with lower-risk node-positive, endocrine responsive breast cancer? 10-year update of International Breast Cancer Study Group Trial 11-93.

INTRODUCTION: International Breast Cancer Study Group (IBCSG) Trial 11-93 is the largest trial evaluating the role of the addition of chemotherapy to ovarian function suppression/ablation (OFS) and tamoxifen in premenopausal patients with endocrine-responsive early breast cancer. METHODS: IBCSG Trial 11-93 is a randomized trial comparing four cycles of adjuvant chemotherapy (AC: doxorubicin or epirubicin, plus cyclophosphamide) added to OFS and 5 years of tamoxifen versus OFS and tamoxifen without chemotherapy in premenopausal patients with node-positive, endocrine-responsive early breast cancer. There were 174 patients randomized from May 1993 to November 1998. The trial was closed before the target accrual was reached due to low accrual rate. RESULTS: Patients randomized tended to have lower risk node-positive disease and the median age was 45. After 10 years median follow up, there remains no difference between the two randomized treatment groups for disease-free (hazard ratio=1.02 (0.57-1.83); P=0.94) or overall survival (hazard ratio=0.97 (0.44-2.16); P=0.94). CONCLUSION: This trial, although small, offers no evidence that AC chemotherapy provides additional disease control for premenopausal patients with lower-risk node-positive endocrine-responsive breast cancer who receive adequate adjuvant endocrine therapy. A large trial is needed to determine whether chemotherapy adds benefit to endocrine therapy for this population.

The costs of disorders of the brain in Switzerland: an update from the European Brain Council Study for 2010.

BACKGROUND: In 2005, findings of the first "cost of disorders of the brain in Europe" study of the European Brain Council (EBC) showed that these costs cause a substantial economic burden to the Swiss society. In 2010 an improved update with a broader range of disorders has been analysed. This report shows the new findings for Switzerland and discusses changes. METHODS: Data are derived from the EBC 2010 census study that estimates 12-month prevalence of 12 groups of disorders of the brain and calculates costs (direct health-care costs, direct non-medical costs and indirect costs) by combining top-down and bottom up cost approaches using existing data. RESULTS: The most frequent disorder was headache (2.3 million). Anxiety disorders were found in 1 million persons and sleep disorders in 700,000 persons. Annual costs for all assessed disorders total to 14.5 billion Euro corresponding to about 1,900 EUR per inhabitant per year. Mood, psychotic disorders and dementias (appr. 2 billion EUR each) were most costly. Costs per person were highest for neurological/neurosurgery-relevant disorders, e.g. neuromuscular disorders, brain tumour and multiple sclerosis (38,000 to 24,000 EUR). CONCLUSION: The estimates of the EBC 2010 study for Switzerland provide a basis for health care planning. Increase in size and costs compared to 2005 are mostly due to the inclusion of new disorders (e.g., sleep disorders), or the re-definition of others (e.g., headache) and to an increase in younger cohorts. We suggest coordinated research and preventive measures coordinated between governmental bodies, private health-care and pharmaceutical companies.

Nouveau spectre des troubles cognitifs liés à l'infection par le VIH à l'ère des trithérapies [New spectrum of HIV-associated cognitive disorders in the HAART era]

Highly active anti-retroviral therapy (HAART) has almost abolished HIV-related mortality and serious opportunistic diseases; among them, AIDS-related dementia. However, minor forms of cognitive dysfunction, have not disappeared, and even increased in frequency. Ageing of HIV+ patients, insufficient penetration of anti-viral drugs into the brain with continuous low-grade viral production and inflammation may play a role. Minor cognitive dysfunction in HIV infection shares some clinical and pathophysiological features with neuro-degenerative diseases, in particular Alzheimers disease. It can thus be postulated that, such in Alzheimer disease, anti-cholinesterase drugs might also be efficacious in AIDS-related minor cognitive dysfunction. This hypothesis has not been tested yet however A clinical trial using ravistigmine is starting this spring in patients with HIV-associated cognitive dysfunction in Geneva and Lausanne.

Mouvements anormaux et accident vasculaire cérébral [Movement disorders in stroke]

Dyskinesias are infrequent presentations in acute stroke (1%). They can be found more frequently as delayed presentations after a stroke, but the prevalence is not available from the literature. The full spectrum of hyper- and hypo-akinetic syndromes has been described, but three main pictures are rather specific of an acute stroke: limb shaking, hemichorea-hemiballism and unilateral asterixis. Besides limb shaking, that seems to reflect a transient diffuse ischemia of the frontosubcortical motor pathway, lesions are described at all levels of the frontosubcortical motor circuit including the sensorimotor frontoparietal cortex, the striatum, the pallidum, the thalamic nuclei, the subthalamic nucleus, the substantia nigra, the cerebellum, the brainstem and their interconnecting pathways, as ischemic or hemorrhagic strokes. The preferentially late development of dyskinesia could reflect the return to a more ancestral motor control level, the most functional possible with the remaining configuration of structures, elaborated by brain plasticity after stroke.

Diabète de type 2: n'oubliez pas les troubles du comportement alimentaire [Patient with type 2 diabetes: don't forget eating disorders!]

The coexistence of diabetes and eating disorder (ED) is more prevalent than we think; indeed it seems to occur in 10 to 20% of cases. Therefore ED deserve attention to be detected and treated in order to permit a decreased in morbidity and better outcomes in body weight loss. The association of type 2 diabetes and ED is frequently seen in younger, overweighed or obese patients suffering of at least one psychiatric co-morbidities and frequently in a difficult psychosocial setting. To succeed in ED treatment, a multidisciplinary and specialised team in eating disorder is requested, however these patients are highly fragile and complex and therapeutic failure has to be feared.

L'entretien motivationnel, une nouvelle "panacée" dans la prise en charge de patients toxicodépendants ? Une revue de littérature [Motivational interviewing, the new "panacea" for treatment of substance use disorders ? A review of literature]

Cet article aborde l'entretien motivationnel (EM), considéré comme un style thérapeutique centré sur le client et directif, visant à développer la motivation au changement par l'exploration et la résolution de l'ambivalence (Miller, W.R., Rollnick, S., 2002. Motivational interviewing: preparing people for change. The Guilford Press, New York, p. 25). Après une brève présentation théorique de ce style thérapeutique, nous présentons un survol des principaux résultats empiriques relatifs à la question de son efficacité dans la prise en charge des troubles liés à l'utilisation de substances psychoactives. Malgré un corpus important de travaux qui mettent en évidence les effets de l'EM, la question des « ingrédients actifs » reste encore relativement peu explorée. Quelques hypothèses permettant de mieux comprendre le succès de l'EM sont évoquées.

The endocrine disruptor monoethyl-hexyl-phthalate is a selective peroxisome proliferator-activated receptor gamma modulator that promotes adipogenesis.

The ability of pollutants to affect human health is a major concern, justified by the wide demonstration that reproductive functions are altered by endocrine disrupting chemicals. The definition of endocrine disruption is today extended to broader endocrine regulations, and includes activation of metabolic sensors, such as the peroxisome proliferator-activated receptors (PPARs). Toxicology approaches have demonstrated that phthalate plasticizers can directly influence PPAR activity. What is now missing is a detailed molecular understanding of the fundamental basis of endocrine disrupting chemical interference with PPAR signaling. We thus performed structural and functional analyses that demonstrate how monoethyl-hexyl-phthalate (MEHP) directly activates PPARgamma and promotes adipogenesis, albeit to a lower extent than the full agonist rosiglitazone. Importantly, we demonstrate that MEHP induces a selective activation of different PPARgamma target genes. Chromatin immunoprecipitation and fluorescence microscopy in living cells reveal that this selective activity correlates with the recruitment of a specific subset of PPARgamma coregulators that includes Med1 and PGC-1alpha, but not p300 and SRC-1. These results highlight some key mechanisms in metabolic disruption but are also instrumental in the context of selective PPAR modulation, a promising field for new therapeutic development based on PPAR modulation.

The psychosocial difficulties in brain disorders that explain short term changes in health outcomes.

BACKGROUND: This study identifies a set of psychosocial difficulties that are associated with short term changes in health outcomes across a heterogeneous set of brain disorders, neurological and psychiatric. METHODS: Longitudinal observational study over approximately 12 weeks with three time points of assessment and 741 patients with depression, bipolar disorders, multiple sclerosis, parkinson's disease, migraine, traumatic brain injury and stroke. The data on disability was collected with the checklist of the International Classification of Functioning, Disability and Health. The selected health outcomes were the Short Form 36 and the World Health Organization Disability Assessment Schedule. Multilevel models for change were applied controlling for age, gender and disease severity. RESULTS: The psychosocial difficulties that explain the variability and change over time of the selected health outcomes were energy and drive, sleep, and emotional functions, and a broad range of activities and participation domains, such as solving problems, conversation, areas of mobility and self-care, relationships, community life and recreation and leisure. CONCLUSIONS: Our findings are of interest to researchers and clinicians for interventions and health systems planning as they show that in addition to difficulties that are diagnostic criteria of these disorders, there are other difficulties that explain small changes in health outcomes over short periods of time.

Mice transgenic for BAFF develop lymphocytic disorders along with autoimmune manifestations.

The cause of many autoimmune and inflammatory diseases is unresolved, although dysregulated production of tumor necrosis factor (TNF) family members appears to be important in many cases. BAFF, a new member of the TNF family, binds to B cells and costimulates their growth in vitro. Mice transgenic for BAFF have vastly increased numbers of mature B and effector T cells, and develop autoimmune-like manifestations such as the presence of high levels of rheumatoid factors, circulating immune complexes, anti-DNA autoantibodies, and immunoglobulin deposition in the kidneys. This phenotype is reminiscent of certain human autoimmune disorders and suggests that dysregulation of BAFF expression may be a critical element in the chain of events leading to autoimmunity.

Effect of religion on suicide attempts in outpatients with schizophrenia or schizo-affective disorders compared with inpatients with non-psychotic disorders

Little is known of the relations between psychosis, religion and suicide. One hundred and fifteen outpatients with schizophrenia or schizo-affective disorder and 30 inpatients without psychotic symptoms were studied using a semi-structured interview assessing religiousness/spirituality. Their past suicide attempts were examined. Additionally, they were asked about the role (protective or incentive) of religion in their decision to commit suicide. Forty-three percent of the patients with psychosis had previously attempted suicide. Religiousness was not associated with the rate of patients who attempted suicide. Twenty-five percent of all subjects acknowledged a protective role of religion, mostly through ethical condemnation of suicide and religious coping. One out of ten patients reported an incentive role of religion, not only due to negatively connotated issues but also to the hope for something better after death. There were no differences between groups (i.e. psychotic vs. non-psychotic patients). Religion may play a specific role in the decisions patients make about suicide, both in psychotic and non-psychotic patients. This role may be protective, a finding particularly important for patients with psychosis who are known to be at high risk of severe suicide attempts. Interventions aiming to lower the number of suicide attempts in patients with schizophrenia should take these data into account.

Infection of B cells with hepatitis C virus for the development of lymphoproliferative disorders in patients with chronic hepatitis C.

Infection with hepatitis C virus (HCV) is associated with lymphoproliferative disorders, represented by essential mixed cryoglobulinemia and B-cell non-Hodgkin's lymphoma, but the pathogenic mechanism remains obscure. HCV may infect B cells or interact with their cell surface receptors, and induce lymphoproliferation. The influence of HCV infection of B cells on the development of lymphoproliferative disorders was evaluated in 75 patients with persistent HCV infection. HCV infection was more prevalent (63% vs. 16%, 14%, or 17% P < 0.05 for each), and HCV RNA levels were higher (3.35 +/- 3.85 vs. 1.75 +/- 2.52, 2.15 +/- 2.94 or 2.10 +/- 2.90 log copies/100 ng, P < 0.01 for each) in B cells than CD4(+), CD8(+) T cells or other cells. Negative-strand HCV RNA, as a marker of viral replication, was detected in B cells from four of the 75 (5%) patients. Markers for lymphoproliferative disorders were more frequent in the 50 patients with chronic hepatitis C than the 32 with chronic hepatitis B, including cryoglobulinemia (26% vs. 0%, P < 0.001), low CH(50) levels (48% vs. 3%, P = 0.012), and the clonality of B cells (12% vs. 0%, P < 0.01). By multivariate analysis, HCV RNA in B cells was an independent factor associated with the presence of at least one marker for lymphoproliferation (odds ratio: 1.98 [95% confidence interval: 1.36-7.24], P = 0.027). Based on the results obtained, the infection of B cells with HCV would play an important role in the development of lymphoproliferative disorders.

Implication of chromosome 13 on hypertension and associated disorders in Lyon hypertensive rats.

BACKGROUND: Hypertension and associated disorders are major risk factors for cardiovascular disease. The Lyon hypertensive rat (LH) is a genetically hypertensive strain that exhibits spontaneous and salt-sensitive hypertension, exaggerated proteinuria, high body weight, hyperlipidemia, and elevated insulin-to-glucose ratio. Previous genetic mapping identified quantitative trait loci (QTLs) influencing blood pressure (BP) on rat chromosome 13 (RNO13) in several models of hypertension. METHODS: To study the effects of a single chromosome on the mapped traits, we generated consomic strains by substituting LH RNO13 with that of the normotensive Brown Norway (BN) strain (LH-13BN) and reciprocal consomics by substituting a BN RNO13 with that of LH (BN-13LH). These reciprocal consomic strains, as well as the two parental strains were characterized for BP, metabolic and morphological parameters. RESULTS: Compared with LH parents, LH-13BN rats showed decreased mean BP (up to -24 mmHg on 2% NaCl in the drinking water), urine proteins and lipids, and increased body weight. Differences between BN-13LH and BN rats were much smaller than those observed between LH-13BN and LH rats, demonstrating the effects of the highly resistant BN genome background. Plasma renin activity was not affected by the substitution of RNO13, despite the significant BP differences. CONCLUSION: The present work demonstrates that RNO13 is a determinant of BP, proteinuria, and plasma lipids in the LH rat. The distinct phenotypic differences between the consomic LH-13BN and the LH make it a powerful model to determine genes and pathways leading to these risk factors for cardiovascular and renal disease.

Experience and endocrine stress responses in neonatal and pediatric critical care nurses and physicians.

OBJECTIVE: Critical care is a working environment with frequent exposure to stressful events. High levels of psychological stress have been associated with increased prevalence of burnout. Psychological distress acts as a potent trigger of cortisol secretions. We attempted to objectify endocrine stress reactivity. DESIGN: Observational cohort study during two 12-day periods in successive years. SETTING: A tertiary multidisciplinary neonatal and pediatric intensive care unit (33 beds). SUBJECTS: One hundred and twelve nurses and 27 physicians (94% accrual rate). INTERVENTIONS AND MEASUREMENTS: Cortisol determined from salivary samples collected every 2 hrs and after stressful events. Participants recorded the subjective perception of stress with every sample. Endocrine reactions were defined as transient surges in cortisol of &gt;50% and 2.5 nmol/L over the baseline. MAIN RESULTS: During 7,145 working hours, we observed 474 (12.5%) endocrine reactions from 3,781 samples. The mean cortisol increase amounted to 10.6 nmol/L (219%). The mean occurrence rate of endocrine reactions per subject and sample was 0.159 (range, 0-0.43). Although the mean raw cortisol levels were lower in experienced team members (&gt;3 yrs of intensive care vs. &lt;3 yrs, 4.1 vs. 4.95 nmol/L, p &lt; .001), professional experience failed to attenuate the frequency and magnitude of endocrine reactions, except for the subgroup of nurses and physicians with &gt;8 yrs of intensive care experience. A high proportion (71.3%) of endocrine reactions occurred without conscious perception of stress. Unawareness of stress was higher in intensive care nurses (75.1%) than in intermediate care nurses (51.8%, p &lt; .01). CONCLUSIONS: Stress-related cortisol surges occur frequently in neonatal and pediatric critical care staff. Cortisol increases are independent of subjective stress perception. Professional experience does not abate the endocrine stress reactivity.