Project description:Definition of preleukemia has evolved. It was first used to describe the myelodysplastic syndrome (MDS) with a propensity to progress to acute myeloid leukemia (AML). Individuals with germline mutations of either RUNX1, CEBPA, or GATA2 can also be called as preleukemic because they have a markedly increased incidence of evolution into AML. Also, alkylating chemotherapy or radiation can cause MDS/preleukemia, which nearly always progress to AML. More recently, investigators noted that AML patients who achieved complete morphological remission after chemotherapy often have clonal hematopoiesis predominantly marked by either DNMT3A, TET2 or IDH1/2 mutations, which were also present at diagnosis of AML. This preleukemic clone represents involvement of an early hematopoietic stem cells, which is resistant to standard therapy. The same clonal hematopoietic mutations have been identified in older 'normal' individuals who have a modest increased risk of developing frank AML. These individuals have occasionally been said, probably inappropriately, to have a preleukemia clone. Our evolving understanding of the term preleukemia has occurred by advancing technology including studies of X chromosome inactivation, cytogenetics and more recently deep nucleotide sequencing.
Project description:The review presents data from the last few years on bioanalytical methods used in therapeutic drug monitoring (TDM) of the 1st-3rd generation and the newest antiepileptic drug (AEDs) cenobamate in patients with various forms of seizures. Chemical classification, structure, mechanism of action, pharmacokinetic data and therapeutic ranges for total and free fractions and interactions were collected. The primary data on bioanalytical methods for AEDs determination included biological matrices, sample preparation, dried blood spot (DBS) analysis, column resolution, detection method, validation parameters, and clinical utility. In conclusion, the most frequently described method used in AED analysis is the LC-based technique (HPLC, UHPLC, USLC) combined with highly sensitive mass detection or fluorescence detection. However, less sensitive UV is also used. Capillary electrophoresis and gas chromatography have been rarely applied. Besides the precipitation of proteins or LLE, an automatic SPE is often a sample preparation method. Derivatization was also indicated to improve sensitivity and automate the analysis. The usefulness of the methods for TDM was also highlighted.
Project description:Semantic verbal fluency (sVF) tasks are commonly used in clinical diagnostic batteries as well as in a research context. When performing sVF tasks to assess executive functions (EFs) the sum of correctly produced words is the main measure. Although previous research indicates potentially better insights into EF performance by the use of finer grained sVF information, this has not yet been objectively evaluated. To investigate the potential of employing a finer grained sVF feature set to predict EF performance, healthy monolingual German speaking participants (n = 230) were tested with a comprehensive EF test battery and sVF tasks, from which features including sum scores, error types, speech breaks and semantic relatedness were extracted. A machine learning method was applied to predict EF scores from sVF features in previously unseen subjects. To investigate the predictive power of the advanced sVF feature set, we compared it to the commonly used sum score analysis. Results revealed that 8 / 14 EF tests were predicted significantly using the comprehensive sVF feature set, which outperformed sum scores particularly in predicting cognitive flexibility and inhibitory processes. These findings highlight the predictive potential of a comprehensive evaluation of sVF tasks which might be used as diagnostic screening of EFs.
Project description:Background: Verbal fluency (VF) has been associated with several cognitive functions, but the cognitive processes underlying verbal fluency deficits in Multiple Sclerosis (MS) are controversial. Further knowledge about VF could be useful in clinical practice, because these tasks are brief, applicable, and reliable in MS patients. In this study, we aimed to evaluate the cognitive processes related to VF and to develop machine-learning algorithms to predict those patients with cognitive deficits using only VF-derived scores. Methods: Two hundred participants with MS were enrolled and examined using a comprehensive neuropsychological battery, including semantic and phonemic fluencies. Automatic linear modeling was used to identify the neuropsychological test predictors of VF scores. Furthermore, machine-learning algorithms (support vector machines, random forest) were developed to predict those patients with cognitive deficits using only VF-derived scores. Results: Neuropsychological tests associated with attention-executive functioning, memory, and language were the main predictors of the different fluency scores. However, the importance of memory was greater in semantic fluency and clustering scores, and executive functioning in phonemic fluency and switching. Machine learning algorithms predicted general cognitive impairment and executive dysfunction, with F1-scores over 67-71%. Conclusions: VF was influenced by many other cognitive processes, mainly including attention-executive functioning, episodic memory, and language. Semantic fluency and clustering were more explained by memory function, while phonemic fluency and switching were more related to executive functioning. Our study supports that the multiple cognitive components underlying VF tasks in MS could serve for screening purposes and the detection of executive dysfunction.
Project description:OBJECTIVES:Describe novel methods for ascertaining verbal fluency in a large national sample of adults, examine demographic factors influencing performance, and compare scores to studies using in-person assessment. METHODS/DESIGN:Participants were from the Reasons for Geographic and Racial Differences in Stroke (REGARDS) study, a national, population-based, longitudinal study of stroke in adults aged 45 years and older. Letter and semantic fluency were gathered, using Letter "F" and Animal Naming, via a telephone-based assessment with computer-assisted scoring of digital recordings. RESULTS:Initial letter and semantic fluency scores were obtained on 18 505 and 18 072 participants, respectively. For both fluency tests, scores were normally distributed. Younger age and more years of education were associated with better performances (p < 0.0001). The mean and standard deviation for matched subgroups, based on age, gender, and education, were quite comparable with scores reported out of samples using an in-person administration format. Telephone-based assessment also allowed for a level of quality control not available via in-person measurement. CONCLUSIONS:Telephone-based assessment of verbal fluency and computer-assisted scoring programs designed for this study facilitated large-scale data acquisition, storage, and scoring of protocols. The resulting scores have similar characteristics to those obtained by traditional methods. These findings extend validation of cognitive assessment methods, using survey research staff and computer-assisted technology for test administration.
Project description:BackgroundContinuous education of clinicians improves quality of care. One Minute Wonder (OMW) summarize best practice knowledge on one page that can be hung on a wall and can be read during waiting times of just one minute. OMW are a fast, efficient and easy-to-adapt educational method and can easily be shared. Since 2018, an interprofessional network has been set up for OMW in German-speaking countries, but the benefits have not been evaluated yet.AimThe primary objective of this evaluation study was to examine whether and to what extent the members of the OMW network used OMW for training in different settings. Secondary objectives were subjective educational gain, OMW as a training method, and OMW-related structures and processes.MethodsAn online survey within the OMW network with 301 members over a period of 3 weeks in 2020 was conducted. Descriptive statistics were used for data analysis.ResultsResponse rate was 62.8% (n = 191). Most participants have used OMW for < 6 months (32.5%, n = 62), developed 1-10 OMW (42.4%, n = 81) by themselves and changed them infrequently (43.5%, n = 74). Topics were most often nursing interventions (79.6%, n = 152), diseases (71.2%, n = 136), drugs (64.4%, n = 123) and others. Participants reported that OMW extended professional knowledge, stimulated them to reflect on their work and are useful for sharing best practice knowledge. Authors of OMW were most often nurses (53.9%, n = 103), who were inspired by the OMW network or by questions of the team.ConclusionParticipants use OMW in practice to share best practice knowledge.
Project description:Verbal fluency is a cognitive function reflecting executive functions and the ability to retrieve the appropriate information from memory quickly. Previous studies reported conflicting results-impaired and intact verbal fluency-in autism spectrum disorder (ASD). Most studies concentrate on overall word productivity, errors, perseverations, clustering, or switching. We used a comprehensive approach to evaluate the reported discrepancy in the literature and introduced a new angle using the concept of word abstraction and imageability. Moreover, we analyzed the performance in two-time intervals (0-30 s and 31-60 s) to assess the temporal dynamics of verbal fluency and a possible activation or initiation deficit in autism. Sixteen adults with ASD and 16 neurotypical control participants, matched by gender, age, and education level, participated in our study. Contrary to our expectations, we did not find a significant difference between groups in word productivity, the number of errors, clustering, or temporal dynamics, neither in semantic nor in phonemic fluency tasks. Surprisingly, the two study groups' performance did not differ in terms of imageability or concreteness characteristics either. Our results raise the possibility that verbal fluency performance is intact in autism. We also suggest using a comprehensive approach when measuring fluency in autism. LAY SUMMARY: People with autism tend to think and communicate differently. In our study, we tested whether people with autism come up with more concrete or imageable words and whether their performance is better compared with neurotypicals in the beginning or in the later phase of a task measuring how many words they can produce in a minute. We did not detect any difference between the two groups; however, we recommend studying verbal fluency in autism from more and different angles in the future.
Project description:We previously reported that foetal valproate exposure impairs intelligence quotient. In this follow-up investigation, we examined dose-related effects of foetal antiepileptic drug exposure on verbal and non-verbal cognitive measures. This investigation is an ongoing prospective observational multi-centre study in the USA and UK, which has enrolled pregnant females with epilepsy on monotherapy from 1999 to 2004. The study seeks to determine if differential long-term neurodevelopmental effects exist across four commonly used drugs (carbamazepine, lamotrigine, phenytoin and valproate). This report compares verbal versus non-verbal cognitive outcomes in 216 children who completed testing at the age of three years. Verbal and non-verbal index scores were calculated from the Differential Ability Scales, Preschool Language Scale, Peabody Picture Vocabulary Test and Developmental Test of Visual-Motor Integration. Verbal abilities were lower than non-verbal in children exposed in utero to each drug. Preconceptional folate use was associated with higher verbal outcomes. Valproate was associated with poorer cognitive outcomes. Performance was negatively associated with valproate dose for both verbal and non-verbal domains and negatively associated with carbamazepine dose for verbal performance. No dose effects were seen for lamotrigine and phenytoin. Since foetal antiepileptic drug exposure is associated with lower verbal than non-verbal abilities, language may be particularly susceptible to foetal exposure. We hypothesize that foetal drug exposure may alter normal cerebral lateralization. Further, a dose-dependent relationship is present for both lower verbal and non-verbal abilities with valproate and for lower verbal abilities with carbamazepine. Preconceptional folate may improve cognitive outcomes. Additional research is needed to confirm these findings, extend the study to other drugs, define the risks associated with drug treatment for seizures in the neonates, and understand the underlying mechanisms.
Project description:Background:The integrity and connectivity of the frontal lobe, which subserves fluency, may be compromised by both ASD and aging. Alternate networks often integrate to help compensate for compromised functions during aging. We used network analyses to study how compensation may overcome age-related compromised in individuals with ASD. Method:Participants consisted of middle-aged (40-60; n=24) or young (18-25; n=18) right-handed males who have a diagnosis of ASD, and age- and IQ-matched control participants (n=20, 14, respectively). All performed tests of language and executive functioning and a fluency functional MRI task. We first used group individual component analysis (ICA) for each of the 4 groups to determine whether different networks were engaged. An SPM analysis was used to compare activity detected in the network nodes from the ICA analyses. Results:The individuals with ASD performed more slowly on two cognitive tasks (Stroop word reading and Trailmaking Part A). The 4 groups engaged different networks during the fluency fMRI task despite equivalent performance. Comparisons of specific regions within these networks indicated younger individuals had greater engagement of the thalamus and supplementary speech area, while older adults engaged the superior temporal gyrus. Individuals with ASD did not disengage from the Default Mode Network during word generation. Conclusion:Interactions between diagnosis and aging were not found in this study of young and middle-aged men, but evidence for differential engagement of compensatory networks was observed.