Effect of deferiprone or deferoxamine on right ventricular function in thalassemia major patients with myocardial iron overload

<p>Abstract</p> <p>Background</p> <p>Thalassaemia major (TM) patients need regular blood transfusions that lead to accumulation of iron and death from heart failure. Deferiprone has been reported to be superior to deferoxamine for the removal of cardiac iron and improvement in left ventricular (LV) function but little is known of their relative effects on the right ventricle (RV), which is being increasingly recognised as an important prognostic factor in cardiomyopathy. Therefore data from a prospective randomised controlled trial (RCT) comparing these chelators was retrospectively analysed to assess the RV responses to these drugs.</p> <p>Methods</p> <p>In the RCT, 61 TM patients were randomised to receive either deferiprone or deferoxamine monotherapy, and CMR scans for T2* and cardiac function were obtained. Data were re-analysed for RV volumes and function at baseline, and after 6 and 12 months of treatment.</p> <p>Results</p> <p>From baseline to 12 months, deferiprone reduced RV end systolic volume (ESV) from 37.7 to 34.2 mL (p = 0.008), whilst RV ejection fraction (EF) increased from 69.6 to 72.2% (p = 0.001). This was associated with a 27% increase in T2* (p < 0.001) and 3.1% increase in LVEF (p < 0.001). By contrast, deferoxamine showed no change in RVESV (38.1 to 39.1 mL, p = 0.38), or RVEF (70.0 to 69.9%, p = 0.93) whereas the T2* increased by 13% (p < 0.001), but with no change in LVEF (0.32%; p = 0.66). Analysis of between drugs treatment effects, showed significant improvements favouring deferiprone with a mean effect on RVESV of -1.82 mL (p = 0.014) and 1.16% for RVEF (p = 0.009). Using regression analysis the improvement in RVEF at 12 months was shown to be greater in patients with lower baseline EF values (p < 0.001), with a significant difference in RVEF of 3.5% favouring deferiprone over deferoxamine (p = 0.012).</p> <p>Conclusion</p> <p>In this retrospective analysis of a prospective RCT, deferiprone monotherapy was superior to deferoxamine for improvement in RVEF and end-systolic volume. This improvement in the RV volumes and function may contribute to the improved cardiac outcomes seen with deferiprone.</p

D-Cycloserine-Augmented Behavior Therapy For Body Dysmorphic Disorder: A Preliminary Efficacy Trial

Cognitive behavioral therapy (CBT) is the leading psychotherapeutic treatment for body dysmorphic disorder (BDD), yet not all patients improve. To address the treatment response gap, CBT may be augmented with cognitive enhancers such as d-cycloserine (DCS). DCS-augmented behavior therapy has been tested with mixed results in related disorders. To initially test whether DCS may augment CBT for BDD, we conducted the first preliminary efficacy trial of DCS versus placebo-augmented CBT for BDD, via a randomized, double-blind study. We analyzed data using mixed-effects models in a modified intent-to-treat sample (N = 26). Over 10 weeks of treatment, primary (BDD severity) and secondary (insight, depression) outcomes improved significantly across both conditions, but there were no significant group differences in response. Exploratory analysis revealed that BDD-related distress, specifically, reduced significantly more in the DCS condition compared to placebo. This is the first study testing DCS-augmented CBT for BDD. Implications, limitations, and future directions are discussed. Trial registry: ClinicalTrials.gov Identifier NCT0084230

Self-perceived memory complaints predict progression to Alzheimer disease : the LADIS study

Memory complaints are frequent in the elderly but its implications in cognition over time remain a controversial issue. Our objective was to evaluate the risk of self perceived memory complaints in the evolution for future dementia. The LADIS (Leukoaraiosis and Disability) prospective multinational European study evaluates the impact of white matter changes (WMC) on the transition of independent elderly subjects into disability. Independent elderly were enrolled due to the presence of WMC. Subjects were evaluated yearly during 3 years with a comprehensive clinical protocol and a neuropsychological battery. Dementia and subtypes of dementia were classified. Self perceived memory complaints in independent elderly were collected during the interview. MRI was performed at entry and at the end of the study. 639 subjects were included (74.1 \ub1 5 years old, 55% women, 9.6 \ub1 3.8 years of schooling). At end of follow-up, 90 patients were demented (vascular dementia, 54; Alzheimer's disease (AD) and AD with vascular component, 34; frontotemporal dementia, 2). Using Cox regression analysis, we found that self perceived memory complaints were a strong predictor of AD and AD with vascular component during the follow-up (\u3b2 = 2.7, p = 0.008; HR = 15.5, CI 95% [2.04, 117.6]), independently of other confounders, namely depressive symptoms, WMC severity, medial temporal lobe atrophy, and global cognition status at baseline. Self perceived memory complaints did not predict vascular dementia. In the LADIS study, self perceived memory complaints predicted AD but not vascular dementia in elderly subjects with WMC living independently

Effect of deferiprone or deferoxamine on right ventricular function in thalassemia major patients with myocardial iron overload

Background: Thalassaemia major (TM) patients need regular blood transfusions that lead to accumulation of iron and death from heart failure. Deferiprone has been reported to be superior to deferoxamine for the removal of cardiac iron and improvement in left ventricular (LV) function but little is known of their relative effects on the right ventricle (RV), which is being increasingly recognised as an important prognostic factor in cardiomyopathy. Therefore data from a prospective randomised controlled trial (RCT) comparing these chelators was retrospectively analysed to assess the RV responses to these drugs. Methods: In the RCT, 61 TM patients were randomised to receive either deferiprone or deferoxamine monotherapy, and CMR scans for T2* and cardiac function were obtained. Data were re-analysed for RV volumes and function at baseline, and after 6 and 12 months of treatment. Results: From baseline to 12 months, deferiprone reduced RV end systolic volume (ESV) from 37.7 to 34.2 mL (p = 0.014), whilst RV ejection fraction (EF) increased from 69.6 to 72.2% (p = 0.001). This was associated with a 27% increase in T2* (p &lt; 0.001) and 3.1% increase in LVEF (p &lt; 0.001). By contrast, deferoxamine showed no change in RVESV (38.1 to 39.1 mL, p = 0.38), or RVEF (70.0 to 69.9%, p = 0.93) whereas the T2* increased by 13% (p &lt; 0.001), but with no change in LVEF (0.32%; p = 0.66). Analysis of between drugs treatment effects, showed significant improvements favouring deferiprone with a mean effect on RVESV of-1.82 mL (p = 0.013) and 1.16% for RVEF (p = 0.008). Using regression analysis the improvement in RVEF at 12 months was shown to be greater in patients with lower baseline EF values (p &lt; 0.001), with a significant difference in RVEF of 3.5% favouring deferiprone over deferoxamine (p = 0.012). Conclusion: In this retrospective analysis of a prospective RCT, deferiprone monotherapy was superior to deferoxamine for improvement in RVEF and end-systolic volume. This improvement in the RV volumes and function may contribute to the improved cardiac outcomes seen with deferiprone

Mental time travel in mild cognitive impairment

Introduction: Mental Time Travel (MTT) is the people's ability to remember themselves in the past and to imagine themselves in the future, and influence important life domains such as making decisions and planning future actions. It is widely recognized that patients with aMCI have deficits in episodic memory, but they also show impairments in semantic memory. It has been controversial whether MTT tasks are disturbed in aMCI mainly in relation to internal details related to episodic information, or external details, representing semantic and other extraneous information. The present study assessed whether patients with aMCI are affected in MTT regarding generation of internal details and external details, in past and future dimensions. Furthermore, it analyzed production in individual detail categories (internal: event details, thought/emotion, place, time, perceptualexternal: extraneous events, semantic, other, repetitions). Method: Twenty-nine patients with aMCI and 29 healthy controls underwent a MTT task based on an Autobiographical Interview, where they had to generate past and future events in response to cue words. Transcriptions were segmented and classified into internal detail categories and external detail categories, and composite scores were obtained. Results: Patients with aMCI could globally produce significantly less details than controls. Similar to controls, patients with aMCI produced more internal details than external details, had more difficulty in generating details regarding the future as compared to the past, and scored higher in the detail categories event details and thought/emotion which represent internal detail types. Conclusions: Patients with aMCI showed widespread deficits in MTT, presumably reflecting deficiencies in the complex and multiple cognitive abilities required for MTT tasks.Fundacao para a Ciencia e a TecnologiaPortuguese Foundation for Science and Technology [JPND-HC/0003/2012