The cause of Huntington disease (HD) is a polyglutamine repeat expansion of more than 36 units in the huntingtin protein, which is inversely correlated with the age at onset of the disease. However, ...additional genetic factors are believed to modify the course and the age at onset of HD. Recently, we identified the V471A polymorphism in the autophagy-related gene ATG7, a key component of the autophagy pathway that plays an important role in HD pathogenesis, to be associated with the age at onset in a large group of European Huntington disease patients. To confirm this association in a second independent patient cohort, we analysed the ATG7 V471A polymorphism in additional 1,464 European HD patients of the "REGISTRY" cohort from the European Huntington Disease Network (EHDN). In the entire REGISTRY cohort we could not confirm a modifying effect of the ATG7 V471A polymorphism. However, analysing a modifying effect of ATG7 in these REGISTRY patients and in patients of our previous HD cohort according to their ethnic origin, we identified a significant effect of the ATG7 V471A polymorphism on the HD age at onset only in the Italian population (327 patients). In these Italian patients, the polymorphism is associated with a 6-years earlier disease onset and thus seems to have an aggravating effect. We could specify the role of ATG7 as a genetic modifier for HD particularly in the Italian population. This result affirms the modifying influence of the autophagic pathway on the course of HD, but also suggests population-specific modifying mechanisms in HD pathogenesis.
Since long-term survivorship is now a reality for an increasingly number of people with a history of cancer, understanding their psychological health can inform health care policy as well as help ...supporting individual patients. This study was aimed to describe depression and anxiety (i.e. two of the most common psychological symptoms reported in oncology) in a sample of Italian long-term cancer survivors (LTCSs) defined as people who have been free from cancer and cancer treatments for at least five years. Four hundred and four Italian adult LTCSs completed a battery of questionnaires including the Zung Self-rating Depression Scale and the State Anxiety sub-scale of the State-Trait Anxiety Inventory respectively for depression and anxiety assessment. 16.5% of the sample displayed mild depression, 11.1% moderate depression, and 7.1% severe depression. depression was negatively associated with education (p = .017), perceived social support as provided by the family (p = .028), and perceived social support provided by friends (p = .008), and it was positively associated with occupational status (p = .023), presence of health issues (p = .010), and anxiety (p < .001). 8.7 and 15.8% of the sample were respectively possible and probable cases of anxiety. Anxiety was negatively associated with occupational status (p = .038) and it was positively associated with depression (p < .001). These data support ongoing assessment and monitoring of depression and anxiety in LTCSs, and stimulate the development and testing of psychological interventions for such individuals. In addition, they encourage further study on the psychological health of this specific population.
Purpose
The Impact of Cancer Scale (IOC) is a self-assessment tool designed to capture the unique and multidimensional aspects of the quality of life of long-term cancer survivors. This paper ...describes the adaptation and psychometric evaluation of its Italian version.
Methods
After the adaptation (i.e., removal of nonpertinent items and back-translation procedure), the Italian version of IOC has been administered to a sample of Italian long-term cancer survivors (people free from cancer and its treatments for at least 5 years) together with the Short Form 36 Health Survey Questionnaire, the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30, and the Post-Traumatic Growth Inventory.
Results
Data on 304 participants were analyzed. Exploratory factor analysis revealed a three-factor structure composed of Uncertainty/Worry about Health & Future (13 items), Personal Growth & Altruism (14 items), and Dissatisfaction & Life Interferences (10 items). Internal consistency (Cronbach's alpha, >0.77) and temporal stability (Spearman's rho, >0.70) were good for all three factors. The obtained three factors correlated with the theoretically pertinent subscales of the other administered tools. To facilitate cross-cultural comparisons, reliability and convergent/divergent validity data for the eight-factor IOC structure already described in literature (Impact of Cancer Version 2) have been also provided.
Conclusions
This study supports the use of the IOC in Italy as a trifactorial instrument that is able to isolate aspects characteristic of the condition of long-term cancer survivorship. However, subsequent studies are needed to confirm these findings as well as shed more light on the validity of the IOC construct and its cultural variability.
BACKGROUND Latrepirdine is an orally administered experimental small molecule that was initially developed as an antihistamine and subsequently was shown to stabilize mitochondrial membranes and ...function, which might be impaired in Huntington disease. OBJECTIVE To determine the effect of latrepirdine on cognition and global function in patients with mild to moderate Huntington disease. DESIGN Randomized, double-blind, placebo-controlled study. SETTING Sixty-four research centers in Australia, Europe, and North America. PATIENTS Four hundred three patients with mild to moderate Huntington disease and baseline cognitive impairment (Mini-Mental State Examination score, 10-26). INTERVENTION Latrepirdine (20 mg) vs matching placebo administered orally 3 times daily for 26 weeks. MAIN OUTCOME MEASURES The co-primary outcome measures were cognition as measured by the change in Mini-Mental State Examination score from baseline to week 26 and global function at week 26 as measured by the Clinician Interview-Based Impression of Change, plus carer interview, which ranges from 1 (marked improvement) to 7 (marked worsening). Secondary efficacy outcome measures included behavior, daily function, motor function, and safety. RESULTS The mean change in Mini-Mental State Examination score among participants randomized to latrepirdine (1.5-point improvement) did not differ significantly from that among participants randomized to placebo (1.3-point improvement) (P=.39). Similarly, the distribution of the Clinician Interview-Based Impression of Change, plus carer interview did not differ significantly among those randomized to latrepirdine compared with placebo (P=.84). No significant treatment effects were detected on the secondary efficacy outcome measures. The incidence of adverse events was similar between those randomized to latrepirdine (68.5%) and placebo (68.0%). CONCLUSION In patients with mild to moderate Huntington disease and cognitive impairment, treatment with latrepirdine for 6 months was safe and well tolerated but did not improve cognition or global function relative to placebo. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00920946.
Huntington's disease results from a CAG repeat expansion within the Huntingtin gene; this is measured routinely in diagnostic laboratories. The European Huntington's Disease Network REGISTRY project ...centrally measures CAG repeat lengths on fresh samples; these were compared with the original results from 121 laboratories across 15 countries. We report on 1326 duplicate results; a discrepancy in reporting the upper allele occurred in 51% of cases, this reduced to 13.3% and 9.7% when we applied acceptable measurement errors proposed by the American College of Medical Genetics and the Draft European Best Practice Guidelines, respectively. Duplicate results were available for 1250 lower alleles; discrepancies occurred in 40% of cases. Clinically significant discrepancies occurred in 4.0% of cases with a potential unexplained misdiagnosis rate of 0.3%. There was considerable variation in the discrepancy rate among 10 of the countries participating in this study. Out of 1326 samples, 348 were re-analysed by an accredited diagnostic laboratory, based in Germany, with concordance rates of 93% and 94% for the upper and lower alleles, respectively. This became 100% if the acceptable measurement errors were applied. The central laboratory correctly reported allele sizes for six standard reference samples, blind to the known result. Our study differs from external quality assessment (EQA) schemes in that these are duplicate results obtained from a large sample of patients across the whole diagnostic range. We strongly recommend that laboratories state an error rate for their measurement on the report, participate in EQA schemes and use reference materials regularly to adjust their own internal standards.
Efficacy of levetiracetam in Huntington disease de Tommaso, Marina; Di Fruscolo, Olimpia; Sciruicchio, Vittorio ...
Clinical neuropharmacology,
11/2005, Letnik:
28, Številka:
6
Journal Article
Recenzirano
Levetiracetam (LEV) is a novel antiepileptic drug characterized by a wide spectrum of action; no pharmacologic interaction and poor adverse events are reported. In animal models, effects of LEV are ...observed in basal ganglia. The aim of this study was to evaluate the efficacy of LEV in reducing involuntary movements in subjects affected by Huntington disease (HD).
This was a single-center, short-term, open-label, controlled study. Patients had LEV as add-on therapy for 6 months. In the first visit patients were rated according to the Unified Huntington Disease Rating Scale. Every 2 months they were submitted to all these tests. LEV was added at the dose of 500 mg twice daily for the first 2 months and then the dosage was increased until 1000 mg twice daily for the next 4 more months. The authors enrolled 22 patients: 15 were assigned to the LEV group and 7 were enrolled as control subjects.
No serious adverse events were experienced by the treated patients. After 6 months of treatment patients on LEV showed a significant reduction of involuntary movements, with a slight improvement of functional capacity compared with the control group.
Results of this short-term, prospective, controlled study indicates that in HD patients, LEV is effective in reducing involuntary movements, thus improving the quality of life.
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