Impact of blood involvement on efficacy and time to response with mogamulizumab in mycosis fungoides and Sézary syndrome.

BACKGROUND: Cutaneous T-cell lymphomas (CTCL) are rare types of non-Hodgkin lymphoma, which present in skin. Mycosis fungoides (MF) and Sézary syndrome (SS) are subtypes which make up two-thirds of all CTCL cases. The phase 3 MAVORIC study (NCT01728805) compared mogamulizumab to vorinostat in MF and SS patients, with post hoc data showing a trend for higher efficacy in mogamulizumab-treated patients as baseline blood tumour burden increases. OBJECTIVES: The aim of this study was to use updated post hoc analyses in order to examine the efficacy of mogamulizumab and vorinostat in MF patients when stratified by baseline blood involvement and to determine what factors affect time-to-global and time-to-skin response to inform clinical follow-up. METHODS: Post hoc analyses were carried out using data from MAVORIC. Overall response rate (ORR), progression-free survival (PFS) and time-to-next-treatment (TTNT) data were used to assess efficacy in patients with MF. Time-to-global response (TTR) was examined by disease subtype, by blood involvement in MF patients, and time-to-skin response was examined by blood involvement in MF patients. RESULTS: Numerically superior results were seen for ORR, PFS and TTNT in mogamulizumab-treated patients with MF compared with vorinostat, with a trend for outcomes improving with increasing baseline blood class. Statistically significant results for mogamulizumab compared with vorinostat were seen for MF B1 pts for PFS (8.43 vs. 2.83 months, p = 0.003) and TTNT (11.9 vs. 3.13 months, p = 0.002), and for MF B2 pts for ORR (46.2 vs. 9.1 months, p = 0.033). CONCLUSIONS: In mogamulizumab-treated MF patients, ORR and PFS were seen to improve with increasing blood involvement, which led to improved TTNT. TTR was more predictable for mogamulizumab-treated MF patients with blood involvement, and skin response may take longer than previously reported in some patients.

Empathy Mediates the Effects of Age and Sex on Altruistic Moral Decision Making.

Moral decision making involves affective and cognitive functions like emotional empathy, reasoning and cognitive empathy/theory of mind (ToM), which are discussed to be subject to age-related alterations. Additionally, sex differences in moral decision making have been reported. However, age-related changes in moral decision making from early to late adulthood and their relation to sex and neuropsychological functions have not been studied yet. One hundred ninety seven participants (122 female), aged 19-86 years, were tested with a moral decision making task comprising forced choice "everyday life" situations in which an altruistic option that favors a socially accepted alternative had to be considered against an egoistic option that favors personal benefit over social interests. The percentage of altruistic decisions was analyzed. A structural equation model (SEM) was calculated to test the hypothesis whether age and sex predict altruistic moral decision, and whether relevant neuropsychological domains mediate these hypothesized relationships. A significant relationship between age and moral decision making was found indicating more frequent altruistic decisions with increasing age. Furthermore, women decided more altruistically than men. The SEM showed that both age and sex are significant predictors of altruistic moral decision making, mediated by emotional empathy but not by reasoning. No cognitive empathy and ToM scores were correlated to age and moral decision making at the same time and thus were not included in the SEM. Our data suggest that increasing age and female sex have an effect on altruistic moral decisions, but that this effect is fully mediated by emotional empathy. The fact that changes of moral decision making with age are mediated by emotional empathy can be interpreted in the light of the so-called "positivity effect" and increasing avoidance of negative affect in aging. The mediated sex effect might represent both biological aspects and socialized sex roles for higher emotional empathy leading to more altruistic decisions.

Cognitive training with and without additional physical activity in healthy older adults: cognitive effects, neurobiological mechanisms, and prediction of training success.

Data is inconsistent concerning the question whether cognitive-physical training (CPT) yields stronger cognitive gains than cognitive training (CT). Effects of additional counseling, neurobiological mechanisms, and predictors have scarcely been studied. Healthy older adults were trained with CT (n = 20), CPT (n = 25), or CPT with counseling (CPT+C; n = 23). Cognition, physical fitness, BDNF, IGF-1, and VEGF were assessed at pre- and post-test. No interaction effects were found except for one effect showing that CPT+C led to stronger gains in verbal fluency than CPT (p = 0.03). However, this superiority could not be assigned to additional physical training gains. Low baseline cognitive performance and BDNF, not carrying apoE4, gains in physical fitness and the moderation of gains in physical fitness × gains in BDNF predicted training success. Although all types of interventions seem successful to enhance cognition, our data do not support the hypotheses that CPT shows superior CT gains compared to CT or that CPT+C adds merit to CPT. However, as CPT leads to additional gains in physical fitness which in turn is known to have positive impact on cognition in the long-term, CPT seems more beneficial. Training success can partly be predicted by neuropsychological, neurobiological, and genetic parameters. Unique Identifier: WHO ICTRP (http://www.who.int/ictrp); ID: DRKS00005194.

Altered moral decision-making in patients with idiopathic Parkinson's disease.

BACKGROUND: Moral decision-making essentially contributes to social conduct. Although patients with Parkinson's disease (PD) show deficits in (non-moral) decision making and related neuropsychological functions, i.e. executive functions, theory of mind (ToM), and empathy, moral decision-making has rarely been examined in PD patients. We examined possible alterations of moral decision-making and associated functions in PD. METHODS: Twenty non-demented PD patients and 23 age- and education-matched healthy control participants were examined with tests that assess reasoning, executive functions (set-shifting and planning), ToM and empathy, decision-making under risk, and moral intuitions. Moral decision-making was assessed with a close-to-everyday moral dilemma paradigm that opposes socially oriented "altruistic" choices to self-beneficial "egoistic" choices in 20 moral dilemma short stories (10 high and 10 low emotional). Concurrently, electrodermal activity was recorded. RESULTS: PD patients made more egoistic moral decisions than healthy controls. Remarkably, while reasoning, planning and empathy correlated with moral decision-making in the control group, in the PD group neuropsychological functions and dopaminergic medication did not correlate with moral decisions. No evidence for reduced skin conductance responses in PD patients and no relationships between skin conductance responses and moral decisions were observed. CONCLUSIONS: This study provides evidence for moral decision-making dysfunctions in PD patients who made more egoistic moral decisions. As a possible underlying mechanism, reduced exercise of attentional control due to a dysfunctional interplay between the prefrontal cortex and the basal ganglia is discussed. Future research will have to determine the impact of PD patients' moral decision-making dysfunctions on everyday life and further determine correlates of the deficits.

Sex differences in cognitive training effects of patients with amnestic mild cognitive impairment.

Cognitive training has been shown to be effective in improving cognitive functions in patients with Mild Cognitive Impairment (MCI). However, data on factors that may influence training gains including sociodemographic variables such as sex or age is rare. In this study, the impact of sex on cognitive training effects was examined in N = 32 age- and education-matched female (n = 16) and male (n = 16) amnestic MCI patients (total sample: age M = 74.97, SD = 5.21; education M = 13.50, SD = 3.11). Patients participated in a six-week multidomain cognitive training program including 12 sessions each 90 min twice weekly in mixed groups with both women and men. Various cognitive domains were assessed before and after the intervention. Despite comparable baseline performance in women and men, we found significant interaction effects Time × Sex in immediate (p = .04) and delayed verbal episodic memory (p= .045) as well as in working memory (p = .042) favoring the female MCI patients. In contrast, the overall analyses with the total sample did not reveal any significant within-subject effects Time. In conclusion, our results give preliminary evidence for stronger cognitive training improvements of female compared to male MCI patients. More generally, they emphasize the importance of sex-sensitive evaluations of cognitive training effects. Possible underlying mechanisms of the found sex differences are discussed and directions for future research are given.

Moral decision-making and theory of mind in patients with idiopathic Parkinson's disease.

OBJECTIVE: Cognitive impairments in theory of mind (ToM), executive processing, and decision-making are frequent and highly relevant symptoms in patients with Parkinson's disease (PD). These functions have been related to moral decision-making. Their association to moral decision-making in PD, however, has not been studied yet. It was hypothesized that moral decisions in patients with PD differ from those in healthy control participants, and that more egoistic decisions are related to ToM as well as executive dysfunctions in patients with PD. METHOD: Nineteen patients with PD and 20 healthy control participants were examined with an everyday moral decision-making task, comprised of 10 low and 10 high emotional forced-choice moral dilemma short stories with egoistic and altruistic options. All participants received an elaborate neuropsychological test battery. Electrodermal skin conductance responses were recorded to examine possible unconscious emotional reactions during moral decision-making. RESULTS: The groups performed comparably in total scores of moral decision-making. Although ToM did not differ between groups, it was inversely related to altruistic moral decisions in the healthy control group, but not in patients with PD. Executive functions were not related to moral decision-making. No differences were found for skin conductance responses, yet they differed from zero in both groups. CONCLUSION: Our findings indicate that moral decisions do not differ between patients with PD and healthy control participants. However, different underlying processes in both groups can be presumed. While healthy control participants seem to apply ToM to permit egoistic moral decisions in low emotional dilemmas, patients with PD seem to decide independently from ToM. These mechanisms as well as neuropsychological and neurophysiological correlates are discussed.

The use of a modification of the Patient Enablement Instrument in asthma.

AIM: To ascertain if the Patient Enablement Instrument (PEI) could be adapted for use in asthma management, and to use it to evaluate "enablement" in patients with asthma randomised to either a fixed or adjustable medication dosing regime. METHODS: The original Patient Enablement Instrument was modified by making a minor change to the opening statement. 228 adults with asthma from 72 UK general practices were recruited to the study. The internal and external consistencies of the modified PEI were assessed. Individual scores were compared across treatment groups. RESULTS: The modified PEI had high internal consistency. There was a significant correlation between modified PEI total score and change in Mini Asthma Quality of Life Questionnaire. A significantly greater proportion of patients using adjustable medication dosing had a clinically relevant treatment benefit. CONCLUSIONS: The Patient Enablement Instrument can be used to measure "enablement" in asthma.