Ацетил-L-карнитин при дистимических расстройствах в пожилом возрасте: двойное слепое, мультицентровое, контролируемое рандомизированное исследование в сравнении с флуоксетином

Introduction. L-Acetylcarnitine (LAC), the acetyl ester of carnitine naturally present in the central nervous system and involved in several neural pathways, has been demonstrated to be active in various animal experimental models resembling some features of human depression. The aim of the study is to verify whether LAC can have an antidepressant action in a population of elderly patients with dysthymic disorder in comparison with a traditional antidepressant such as fluoxetine.Methods. Multicentric, double-blind, double-dummy, controlled, randomized study based on a observation period of 7 weeks. 80 patients with DSM-IV diagnosis of dysthymic disorder were enrolled in the study and subdivided into 2 groups. Group A patients received LAC plus placebo; group B patients received fluoxetine 20 mg/die plus placebo. Clinical assessment was performed through several psychometric scales at 6 different moments.Results. Group A patients showed a statistically significant improvement in the following scales: HAM-D, HAM-A, BDI and Touluse–Pieron Test. Comparison between the two groups, A and B, generally showed very similar clinical progression.Discussion. The results obtained with LAC and fluoxetine were equivalent. As the subjects in this study were of senile age, it is possible to hypothesize that the LAC positive effect on mood could be associated with improvement in subjective cognitive symptomatology. The difference in the latency time of clinical response (1 week of LAC treatment, compared with the 2 weeks' latency time with fluoxetine) suggests the existence of different mechanisms of action possibly in relation to the activation of rapid support processes of neuronal activity.Введение. Показано, что ацетил-L-карнитин (АЦ-L-К), ацетиловый эфир карнитина, в норме присутствующий в центральной нервной системе и участвующий в метаболических процессах нервной ткани, обладает активностью в различных экспериментальных моделях животных, напоминающих депрессию у человека. Цель исследования – подтвердить антидепрессивное действие АЦ-L-К у пожилых пациентов с дистимическими расстройствами по сравнению с традиционным антидепрессантом флуоксетином.Материалы и методы. В мультицентровое двойное слепое плацебоконтролируемое рандомизированное исследование продолжительностью 7 нед были включены 80 пациентов с диагнозом дистимического расстройства по DSM-IV. Пациенты были разделены на 2 группы: в группе А получали АЦ-L-К и плацебо; в группе Б получали флуоксетин по 20 мг 2 раза в день и плацебо. Клиническая оценка эффекта проводилась 6 раз по нескольким психометрическим шкалам.Результаты. В группе А отмечено статистически достоверное улучшение по следующим шкалам: HAM-D, HAM-A, BDI и тесту Тулуза–Пьерона. Сопоставление групп А и Б выявило практически одинаковую клиническую динамику.Обсуждение. Получены одинаковые результаты по эффективности приема АЦ-L-К и флуоксетина. В связи с пожилым возрастом пациентов предполагается, что положительное влияние АЦ-L-К на настроение может быть связано с улучшением когнитивных симптомов. Различие во времени наступления клинического эффекта (через 1 нед после начала приема АЦ-L-К и через 2 нед от начала приема флуоксетина) предполагает наличие разных механизмов действия, возможно связанных с быстрой активацией метаболических процессов в нервной ткани

GENERALIZED AND SPECIFIC EMOTION IMPAIRMENTS AS POTENTIAL MARKERS OF SEVERITY IN OBSESSIVECOMPULSIVE DISORDER: A PRELIMINARY STUDY USING FACIAL ACTION CODING SYSTEM (FACS)

Background: The role of emotional deficits in the poor outcomes of patients with Obsessive-Compulsive Disorder (OCD) has been emphasized. Generalized and specific emotional abnormalities have been reported, often related to OCD severity and functional disabilities. The objective of the present study was to assess the abilities of experiencing and displaying emotions in OCD patients in response to specific stimuli in relation with the severity of their clinical condition. Subjects and methods: Thirty-six individuals participated in the study: 10 OCD patients with severe symptoms, 11 with mildmoderate symptoms, and 15 healthy controls. All participants watched emotion-eliciting video clips while their facial activity was videotaped. The congruent/incongruent feeling of emotions and the facial expression in reaction to emotions were evaluated. Results: The two subgroups of OCD patients presented similarly incongruent emotive feelings and facial expressions (significantly worse than healthy participants). Moreover, OCD patients with severe symptoms expressed the emotion of happiness and disgust significantly less appropriately than OCD patients with mild-moderate symptoms. Conclusions: The present data support the hypothesis that impaired emotional processing may: (i) represent a potential contributor to poor outcome in OCD; (ii) constitute a warning sign for clinicians to establish a more comprehensive protocol for more severe cases; (iii) influence therapeutic strategies used to treat this disorder

A relational analysis of an invisible illness: A meta-ethnography of people with chronic fatigue syndrome/myalgic encephalomyelitis and their support needs

Chronic fatigue syndrome (CFS)/myalgic encephalomyelitis (ME) is indicated by prolonged, medically unexplained fatigue (amongst other symptoms), not alleviated by rest, and causing substantial disability. There are limited treatments on offer, which may not be effective and/or acceptable for all people, and treatment views are polarised. We, thus, aimed to take a step back from this debate, to explore more broadly preferences for formal and informal support among people with CFS/ME. We used a meta-ethnography approach to examine the substantial qualitative literature available. Using the process outlined by Noblit and Hare, and guided by patient involvement throughout, 47 studies were analysed. Our synthesis suggested that to understand people with CFS/ME (such as their invisibility, loss of self, and fraught clinical encounters), it was useful to shift focus to a ‘relational goods’ framework. Emotions and tensions encountered in CFS/ME care and support only emerge via ‘sui generis’ real life interactions, influenced by how social networks and health consultations unfold, and structures like disability support. This relational paradigm reveals the hidden forces at work producing the specific problems of CFS/ME, and offers a ‘no blame’ framework going forward. Chronic fatigue syndrome; myalgic encephalomyelitis; meta-ethnography: qualitative; relational goods; social support; Users' Experience

L acetylcarnitine in dysthymic disorder in elderly patients: a double-blind, multicenter, controlled randomized study vs. fluoxetine

Introduction: L-acetylcarnitine (LAC), the acetyl ester of carnitine naturally present in the central nervous system and involved in several neural pathways, has been demonstrated to be active in various animal experimental models resembling some features of human depression. The aim of the study is to verify whether LAC can have an antidepressant action in a population of elderly patients with Dysthymic Disorder in comparison with a traditional antidepressant such as Fluoxetine. Methods: Multicentric, double-blind, double-dummy, controlled, randomized study based on a observation period of 7 weeks. 80 patients with DSM-IV diagnosis of Dysthymic Disorder were enrolled in the study and subdivided into 2 groups. Group A patients received LAC plus placebo; group B patients received Fluoxetine 20 mg/die plus placebo. Clinical assessment was performed through several psychometric scales at 6 different moments. Results: Group A patients showed a statistically significant improvement in the following scales: HAM-D, HAM-A, BDI and Touluse Pieron Test. Comparison between the two groups, A and B, generally showed very similar clinical progression. Discussion: The results obtained with LAC and Fluoxetine were equivalent. As the subjects in this study were of senile age, it is possible to hypothesize that the LAC positive effect on mood could be associated with improvement in subjective cognitive symptomatology. The difference in the latency time of clinical response (1 week of LAC treatment, compared with the 2 weeks' latency time with Fluoxetine) suggests the existence of different mechanisms of action possibly in relation to the activation of rapid support processes of neuronal activity. (C) 2012 Elsevier B.V. and ECNP. All rights reserved

A complete remission induced by valproic acid in a patient with essential thrombocytemia JAKV617F- positive

INTRODUCTION: Polycythemia vera (PV), essential thrombocythemia (ET) and primary myelofibrosis (PMF) are myeloproliferative neoplasms characterized by excessive proliferation of myeloid/erythroid lineage cells and JAK2V617F somatic mutation. Since current treatments of MPNs are unlikely to cure or offer remission to patients, there is a clear necessity of new therapies. Histone Deacetylase inhibitors (HDACi) are a new class of drugs with a potential activity in this group of disease. Among these, valproic acid (VPA) is a well tolerated and long since used drug for the treatment of epilepsy and bipolar disorders. At concentration equivalent to those used by neuro-psychiatrists (> 50 μg/ml), VPA acts as a powerful HDACi, that has been shown to be promising in the treatment of both solid and hematological tumors. Therefore herein we present a 52 years-old woman with JAK2V617F ET who received VPA for a bipolar disorder. METHODS: Diagnosis of ET, was done 2 years before our observation, at the time of an episode of angina pectoris treated with four coronary by-passes. Patient started treatment with antiplatelet drugs and hydrossiurea (HU). However, due to a severe intolerance, HU was intermittently assumed never reaching therapeutic concentration and disease control. During this period, the patient developed heightened mood (either euphoric or irritable), decreased need for sleep and hyperactivity. A psychiatric evaluation allowed to made the diagnosis of bipolar disorder type II. Thus the patient definitively stopped HU and started VPA at increasing doses, reaching a therapeutic serum level of 76 μg/ml after four months with a dosage of 1500 mg/day and achieving the complete remission of her manic phase of the bipolar disorder. RESULTS: As for the clinical course of ET, her hemochromocytometric values before VPA were: Hb 14.3 gr/dl, WBC count 11.3 x 109/L and platelets 793 x 109/L. Two months after reaching the VPA therapeutic level we observed a significant decrease in the values of Hb, WBC and Platelet that resulted 12.9 gr/dl, 6.3 x 109/l and 403 x 109/L, respectively. Since, these values are remained stable after more than one-year of VPA treatment, the patient has been classified in complete remission (CR) of disease (figure 1). Molecular monitoring of disease during VPA treatment was performed by evaluating JAK2 gene dosage and JAK2WT and JAK2V617F transcript levels at diagnosis and after 4, 8 and 12 month from the start of VPA. Although, the JAK2 gene dosage remained constant upon treatment,, JAK2WT and JAK2V617F transcript levels significantly increased at each time points. CONCLUSION: Data herein reported demonstrated, for the first time, the achievement of CR induced by the HDACi VPA in a ET patient intolerant to HU. The findings that JAK2WT and JAK2V617F transcript levels increased, despite the achievement of therapeutic response, support that JAK2 is not fully implicated in the pathogenesis of Ph(-) MPN

Generalized and specific emotion impairments as potential markers of severity in obsessive-compulsive disorder. A preliminary study using Facial Action Coding System (FACS)

BACKGROUND: The role of emotional deficits in the poor outcomes of patients with Obsessive-Compulsive Disorder (OCD) has been emphasized. Generalized and specific emotional abnormalities have been reported, often related to OCD severity and functional disabilities. The objective of the present study was to assess the abilities of experiencing and displaying emotions in OCD patients in response to specific stimuli in relation with the severity of their clinical condition. SUBJECTS AND METHODS: Thirty-six individuals participated in the study: 10 OCD patients with severe symptoms, 11 with mild-moderate symptoms, and 15 healthy controls. All participants watched emotion-eliciting video clips while their facial activity was videotaped. The congruent/incongruent feeling of emotions and the facial expression in reaction to emotions were evaluated. RESULTS: The two subgroups of OCD patients presented similarly incongruent emotive feelings and facial expressions (significantly worse than healthy participants). Moreover, OCD patients with severe symptoms expressed the emotion of happiness and disgust significantly less appropriately than OCD patients with mild-moderate symptoms. CONCLUSIONS: The present data support the hypothesis that impaired emotional processing may: (i) represent a potential contributor to poor outcome in OCD; (ii) constitute a warning sign for clinicians to establish a more comprehensive protocol for more severe cases; (iii) influence therapeutic strategies used to treat this disorder

Efficacy and safety of yttrium-90 ibritumomab tiuxetan in patients with relapsed or refractory diffuse large B-cell lymphoma not appropriate for autologous stem-cell transplantation

A prospective, multicenter, nonrandomized phase 2 trial was conducted to evaluate the efficacy and safety of a single dose of yttrium-90 (90Y) ibritumomab tiuxetan in elderly patients in first relapsed or primary refractory diffuse large B-cell lymphoma (DLBCL) ineligible for stem-cell transplantation. Patients had been previously treated with chemotherapy (group A, n = 76) or chemotherapy plus rituximab (group B, n = 28). Patients in group A were further divided into patients in whom induction therapy had failed (stratum AI, n = 33) and patients who had relapsed after achieving complete response (CR; stratum AII, n = 43). The overall response rate (ORR) was 52% and 53% in strata AI and AII, respectively, and 19% in group B, with CR/CRu rates of 24%, 39.5%, and 12%, respectively. Median progression-free survival was 5.9 months and 3.5 months in strata AI and AII, respectively, and 1.6 months in group B. Median overall survival was 21.4, 22.4, and 4.6 months in stratum AI, stratum AII, and group B, respectively. Two patients died from thrombocytopenic cerebral bleeding following administration of therapy. Nonhematologic adverse events were mild to moderate. 90Y-ibritumomab is active in patients with relapsed and refractory diffuse large B-cell lymphoma (DLBCL) and its further evaluation in phase 3 studies is ongoing. © 2007 by The American Society of Hematology