Real-world experience among patients with relapsed/refractory mantle cell lymphoma after Bruton tyrosine kinase inhibitor failure in Europe: The SCHOLAR-2 retrospective chart review study

Mantle cell lymphoma (MCL) after relapse is associated with poor prognosis. No standard of care exists and available evidence for treatments is limited, particularly in patients who fail Bruton tyrosine kinase inhibitor (BTKi) therapy. This multicentre retrospective chart review study, SCHOLAR-2, addresses this knowledge gap and reports on data collected from 240 patients with relapsed/refractory MCL in Europe who were treated with BTKi-based therapy between July 2012 and July 2018, and had experienced disease progression while on BTKi therapy or discontinued BTKi therapy due to intolerance. The median overall survival (OS) from initiation of first BTKi therapy was 14.6 months (95% confidence interval [CI] 11.6–20.0) in the overall cohort, 5.5 months (95% CI 3.9–8.2) in 91 patients without post-BTKi therapy, and 23.8 months (95% CI 18.9–30.1) in 149 patients who received post-BTKi therapy (excluding chimeric antigen receptor T-cell treatment). In the latter group, patients received a median of one (range, one to seven) line of post-BTKi therapy, with lenalidomide-containing regimens and bendamustine plus rituximab being the most frequently administered; the median OS from initiation of first post-BTKi therapy was 9.7 months (95% CI 6.3–12.7). These results provide a benchmark for survival in patients with R/R MCL receiving salvage therapy after BTKi failure

Age-related Differences in Prestimulus Subsequent Memory Effects Assessed with Event-related Potentials

Prestimulus subsequent memory effects (preSMEs)—differences in neural activity elicited by a task cue at encoding that are predictive of later memory performance—are thought to reflect differential engagement of preparatory processes that benefit episodic memory encoding. We investigated age differences in preSMEs indexed by differences in ERP amplitude just before the onset of a study item. Young and older adults incidentally encoded words for a subsequent memory test. Each study word was preceded by a task cue that signaled a judgment to perform on the word. Words were presented for either a short (300 msec) or long (1000 msec) duration with the aim of placing differential benefits on engaging preparatory processes initiated by the task cue. ERPs associated with subsequent successful and unsuccessful recollection, operationalized here by source memory accuracy, were estimated time-locked to the onset of the task cue. In a late time window (1000–2000 msec after onset of the cue), young adults demonstrated frontally distributed preSMEs for both the short and long study durations, albeit with opposite polarities in the two conditions. This finding suggests that preSMEs in young adults are sensitive to perceived task demands. Although older adults showed no evidence of preSMEs in the same late time window, significant preSMEs were observed in an earlier time window (500–1000 msec) that was invariant with study duration. These results are broadly consistent with the proposal that older adults differ from their younger counterparts in how they engage preparatory processes during memory encoding

Alcohol consumption in Estonia and Finland: Finbalt survey 1994-2006

<p>Abstract</p> <p>Background</p> <p>Alcohol consumption has been regarded as an important contributor to the high premature mortality rates. The objective of this paper was to provide an overview and comparison of alcohol consumption and its socio-demographic determinants among adults in Estonia and Finland.</p> <p>Methods</p> <p>The study was based on a 25-64-year-old subsample of nationally representative postal cross-sectional surveys conducted in Estonia (n = 10,340) and Finland (n = 19,672) during 1994-2006. Abstinence, frequency, and the amount of alcohol consumed were examined. Logistic regression models were used to test the socio-demographic differences in alcohol consumption at least once a week. The effect of socio-demographic factors on pure alcohol consumed per week was calculated using linear regression.</p> <p>Results</p> <p>The proportion of abstainers was 1.5 times higher among women than men in both countries. Throughout the study period, the amount of alcohol consumed per week increased for both genders in Estonia and for women in Finland, but was stable for men in Finland. In the final study year, medium risk amount of alcohol consumed per week was nearly 1.5 times higher among men in Estonia than in Finland, but about half that among women in Estonia than in Finland. Compared to ethnic majority in Estonia, alcohol consumption at least once a week was lower among men, but amount of pure alcohol drunk per week was higher among women of ethnic minority. In Finland, alcohol consumption at least once a week was more prevalent among women of ethnic minority, but the amount of pure alcohol drunk per week was lower for both gender groups of ethnic minority. Compared to married/cohabiting respondents, alcohol consumption at least once a week was less pronounced among single respondents in Finland, divorced or separated women in both countries, and widowed respondents in Estonia. Greater amount of alcohol consumed per week was more prevalent among single and divorced or separated respondents in Finland, but only among divorced or separated men in Estonia. Frequency of alcohol consumption was lower among less educated than higher educated respondents in Finland, but not in Estonia. The amount of consumed alcohol per week was higher among less educated men in Estonia, but lower among women with basic education in Finland.</p> <p>Conclusions</p> <p>Alcohol consumption has increased in Estonia and Finland. National alcohol policies should reflect findings of alcohol epidemiology in order to introduce measures that will reduce alcohol related harm in the population effectively.</p

Grey and white matter correlates of recent and remote autobiographical memory retrieval:Insights from the dementias

The capacity to remember self-referential past events relies on the integrity of a distributed neural network. Controversy exists, however, regarding the involvement of specific brain structures for the retrieval of recently experienced versus more distant events. Here, we explored how characteristic patterns of atrophy in neurodegenerative disorders differentially disrupt remote versus recent autobiographical memory. Eleven behavioural-variant frontotemporal dementia, 10 semantic dementia, 15 Alzheimer's disease patients and 14 healthy older Controls completed the Autobiographical Interview. All patient groups displayed significant remote memory impairments relative to Controls. Similarly, recent period retrieval was significantly compromised in behavioural-variant frontotemporal dementia and Alzheimer's disease, yet semantic dementia patients scored in line with Controls. Voxel-based morphometry and diffusion tensor imaging analyses, for all participants combined, were conducted to investigate grey and white matter correlates of remote and recent autobiographical memory retrieval. Neural correlates common to both recent and remote time periods were identified, including the hippocampus, medial prefrontal, and frontopolar cortices, and the forceps minor and left hippocampal portion of the cingulum bundle. Regions exclusively implicated in each time period were also identified. The integrity of the anterior temporal cortices was related to the retrieval of remote memories, whereas the posterior cingulate cortex emerged as a structure significantly associated with recent autobiographical memory retrieval. This study represents the first investigation of the grey and white matter correlates of remote and recent autobiographical memory retrieval in neurodegenerative disorders. Our findings demonstrate the importance of core brain structures, including the medial prefrontal cortex and hippocampus, irrespective of time period, and point towards the contribution of discrete regions in mediating successful retrieval of distant versus recently experienced events

Dual task performance in early Alzheimer's disease, amnestic mild cognitive impairment and depression

Background. The dual task paradigm (Baddeley et al. 1986; Della Sala et al. 1995) has been proposed as a sensitive measure of Alzheimer's dementia, early in the disease process. Method. We investigated this claim by administering the modified dual task paradigm (utilising a pencil-and-paper version of a tracking task) to 33 patients with amnestic mild cognitive impairment (aMCI) and 10 with very early Alzheimer's disease, as well as 21 healthy elderly subjects and 17 controls with depressive symptoms. All groups were closely matched for age and pre-morbid intellectual ability. Results. There were no group differences in dual task performance, despite poor performance in episodic memory tests of the aMCI and early Alzheimer's disease groups. In contrast, the Alzheimer patients were specifically impaired in the trail-making test B, another commonly used test of divided attention. Conclusions. The dual task paradigm lacks sensitivity for use in the early differential diagnosis of Alzheimer's disease

Diagnostic and economic evaluation of new biomarkers for Alzheimer's disease: the research protocol of a prospective cohort study

Doc number: 72 Abstract Background: New research criteria for the diagnosis of Alzheimer's disease (AD) have recently been developed to enable an early diagnosis of AD pathophysiology by relying on emerging biomarkers. To enable efficient allocation of health care resources, evidence is needed to support decision makers on the adoption of emerging biomarkers in clinical practice. The research goals are to 1) assess the diagnostic test accuracy of current clinical diagnostic work-up and emerging biomarkers in MRI, PET and CSF, 2) perform a cost-consequence analysis and 3) assess long-term cost-effectiveness by an economic model. Methods/design: In a cohort design 241 consecutive patients suspected of having a primary neurodegenerative disease are approached in four academic memory clinics and followed for two years. Clinical data and data on quality of life, costs and emerging biomarkers are gathered. Diagnostic test accuracy is determined by relating the clinical practice and new research criteria diagnoses to a reference diagnosis. The clinical practice diagnosis at baseline is reflected by a consensus procedure among experts using clinical information only (no biomarkers). The diagnosis based on the new research criteria is reflected by decision rules that combine clinical and biomarker information. The reference diagnosis is determined by a consensus procedure among experts based on clinical information on the course of symptoms over a two-year time period. A decision analytic model is built combining available evidence from different resources among which (accuracy) results from the study, literature and expert opinion to assess long-term cost-effectiveness of the emerging biomarkers. Discussion: Several other multi-centre trials study the relative value of new biomarkers for early evaluation of AD and related disorders. The uniqueness of this study is the assessment of resource utilization and quality of life to enable an economic evaluation. The study results are generalizable to a population of patients who are referred to a memory clinic due to their memory problems. Trial registration: NCT0145089

The application of rules in morphology, syntax and number processing: a case of selective deficit of procedural or executive mechanisms?: Deficit of procedural or executive mechanisms

International audienceDeclarative memory is a long-term store for facts, concepts and words. Procedural memory subserves the learning and control of sensorimotor and cognitive skills, including the mental grammar. In this study, we report a single-case study of a mild aphasic patient who showed procedural deficits in the presence of preserved declarative memory abilities. We administered several experiments to explore rule application in morphology, syntax and number processing. Results partly support the differentiation between declarative and procedural memory. Moreover, the patient's performance varied according to the domain in which rules were to be applied, which underlines the need for more fine-grained distinctions in cognition between procedural rules