A randomized open-label study of guideline-driven antiemetic therapy versus single agent antiemetic therapy in patients with advanced cancer and nausea not related to anticancer treatment

© 2018 The Author(s). Background: Nausea/vomiting (N/V) not related to anti-cancer treatment is common in patients with advanced cancer. The standard approach to management is to define a dominant cause, and treat with an antiemetic selected through pathophysiologic knowledge of emetic pathways. High rates of N/V control have been reported using both etiology-based guideline-driven antiemetic regimens and an empiric approach using single agents in uncontrolled studies. These different approaches had never been formally compared. Methods: This randomized, prospective, open label, dose-escalating study used readily available antiemetics in accordance with etiology-based guidelines or single agent therapy with haloperidol. Participants had a baseline average nausea score of ≥3/10. Response was defined as a ≥ 2/10 point reduction on a numerical rating scale of average nausea score with a final score < 3/10 at 72 h. Results: Nausea scores and distress from nausea improved over time in the majority of the 185 patients randomized. For those who completed each treatment day, a greater response rate was seen in the guideline arm than the single agent arm at 24 h (49% vs 32%; p = 0.02), but not at 48 or 72 h. Response rates at 72 h in the intention to treat analysis were 49 and 53% respectively, with no significant difference between arms (0.04; 95% CI: -0.11, 0.19; p = 0.59). Over 80% of all participants reported an improved global impression of change. There were few adverse events worse than baseline in either arm. Conclusion: An etiology-based, guideline-directed approach to antiemetic therapy may offer more rapid benefit, but is no better than single agent treatment with haloperidol at 72 h. Clinical trial registration: Australian New Zealand Clinical

A systematic review of the safety of lisdexamfetamine dimesylate

BACKGROUND: Here we review the safety and tolerability profile of lisdexamfetamine dimesylate (LDX), the first long-acting prodrug stimulant for the treatment of attention-deficit/hyperactivity disorder (ADHD). METHODS: A PubMed search was conducted for English-language articles published up to 16 September 2013 using the following search terms: (lisdexamfetamine OR lisdexamphetamine OR SPD489 OR Vyvanse OR Venvanse OR NRP104 NOT review [publication type]). RESULTS: In short-term, parallel-group, placebo-controlled, phase III trials, treatment-emergent adverse events (TEAEs) in children, adolescents, and adults receiving LDX were typical for those reported for stimulants in general. Decreased appetite was reported by 25-39 % of patients and insomnia by 11-19 %. The most frequently reported TEAEs in long-term studies were similar to those reported in the short-term trials. Most TEAEs were mild or moderate in severity. Literature relating to four specific safety concerns associated with stimulant medications was evaluated in detail in patients receiving LDX. Gains in weight, height, and body mass index were smaller in children and adolescents receiving LDX than in placebo controls or untreated norms. Insomnia was a frequently reported TEAE in patients with ADHD of all ages receiving LDX, although the available data indicated no overall worsening of sleep quality in adults. Post-marketing survey data suggest that the rate of non-medical use of LDX was lower than that for short-acting stimulants and lower than or equivalent to long-acting stimulant formulations. Small mean increases were seen in blood pressure and pulse rate in patients receiving LDX. CONCLUSIONS: The safety and tolerability profile of LDX in individuals with ADHD is similar to that of other stimulants

The Diffusion of Inclusion: An Open Polity Model of Ethnic Power Sharing

While there is a growing consensus that ethnic inclusion produces peace, less is known about what causes transitions to power sharing between ethnic groups in central governments in multiethnic states. The few studies that have addressed this question have proposed explanations stressing exclusively domestic factors. Yet, power sharing is spatially clustered, which suggests that diffusion may be at play. Inspired by studies of democratic diffusion, we study the spread of inclusive policies with an “open polity model” that explicitly traces diffusion from inclusion in other states. Our findings indicate that the relevant diffusion processes operate primarily at the level of world regions rather than globally or between territorial neighbors. Thus, the more inclusive the region, the more likely a shift to power sharing becomes. Shifts away from inclusion to dominance are less common since World War II, but they are more likely in regional settings characterized by ethnic exclusion

Cultural Capital and Attitudes Toward Homosexuals: Exploring the Relation Between Lifestyles and Homonegativity

This article explores the potential of cultural capital as explanatory factor in understanding homonegativity. Building on recent findings suggesting the need for a cultural component in understanding homonegativity, this article explores the relation between lifestyles (the measurable expression of cultural capital) and homonegativity. Using the “Social-Cultural Changes in Flanders 2006” survey (a population-wide survey in Flanders, the northern part of Belgium), we observed that homonegativity is lowest in lifestyle clusters where cultural capital is higher. This effect, furthermore, is maintained even after controlling for other homonegativity correlates. These results suggest that cultural capital, expressed by lifestyles, is a valuable addition to the understanding of homonegativity

INTELLANCE 2/EORTC 1410 randomized phase II study of Depatux-M alone and with temozolomide vs temozolomide or lomustine in recurrent EGFR amplified glioblastoma

BACKGROUND: Depatuxizumab mafodotin (Depatux-M) is a tumor-specific antibody-drug conjugate consisting of an antibody (ABT-806) directed against activated epidermal growth factor receptor (EGFR) and the toxin monomethylauristatin-F. We investigated Depatux-M in combination with temozolomide or as a single agent in a randomized controlled phase II trial in recurrent EGFR amplified glioblastoma. METHODS: Eligible were patients with centrally confirmed EGFR amplified glioblastoma at first recurrence after chemo-irradiation with temozolomide. Patients were randomized to either Depatux-M 1.25 mg/kg every 2 weeks intravenously, or this treatment combined with temozolomide 150-200 mg/m2 day 1-5 every 4 weeks, or either lomustine or temozolomide. The primary endpoint of the study was overall survival. RESULTS: Two hundred sixty patients were randomized. In the primary efficacy analysis with 199 events (median follow-up 15.0 mo), the hazard ratio (HR) for the combination arm compared with the control arm was 0.71 (95% CI = 0.50, 1.02; P = 0.062). The efficacy of Depatux-M monotherapy was comparable to that of the control arm (HR = 1.04, 95% CI = 0.73, 1.48; P = 0.83). The most frequent toxicity in Depatux-M treated patients was a reversible corneal epitheliopathy, occurring as grades 3-4 adverse events in 25-30% of patients. In the long-term follow-up analysis with median follow-up of 28.7 months, the HR for the comparison of the combination arm versus the control arm was 0.66 (95% CI = 0.48, 0.93). CONCLUSION: This trial suggests a possible role for the use of Depatux-M in combination with temozolomide in EGFR amplified recurrent glioblastoma, especially in patients relapsing well after the end of first-line adjuvant temozolomide treatment. (NCT02343406)

Changing deep-rooted implicit evaluation in the blink of an eye: negative verbal information shifts automatic liking of Gandhi

It is often assumed that, once established, spontaneous or implicit evaluations are resistant to immediate change. Recent research contradicts this theoretical stance, showing that a person’s implicit evaluations of an attitude object can be changed rapidly in the face of new counter-attitudinal information. Importantly, it remains unknown whether such changes can also occur for deep-rooted implicit evaluations of well-known attitude objects. We address this question by examining whether the acquisition of negative information changes implicit evaluations of a well-known positive historic figure: Mahatma Gandhi. We report three experiments showing rapid changes in implicit evaluations of Gandhi as measured with an Affect Misattribution Procedure and Evaluative Priming Task but not with an Implicit Association Test (IAT). These findings suggest that implicit evaluations based on deep-rooted representations are subjective to rapid changes in the face of expectancy-violating information, while pointing to limitations of the IAT for assessing such changes

The adaptation of the Affective Norms for English Words (ANEW) for European Portuguese

This study presents the adaptation of the Affective Norms for English Words (ANEW; Bradley & Lang, 1999a) for European Portuguese (EP). The EP adaptation of the ANEW was based on the affective ratings made by 958 college students who were EP native speakers. Participants assessed about 60 words by considering the affective dimensions of valence, arousal, and dominance, using the Self-Assessment Manikin (SAM) in either a paper-and-pencil and a web survey procedures. Results of the adaptation of the ANEW for EP are presented. Furthermore, the differences between EP, American (Bradley & Lang, 1999a), and Spanish (Redondo, Fraga, Padrón, & Comesaña, 2007) standardizations were explored. Results showed that the ANEW words were understood in a similar way by EP, American, and Spanish subjects, although some sex and cross-cultural differences were observed. The EP adaptation of the ANEW is shown to be a valid and useful tool that will allow researchers to control and/or manipulate the affective properties of stimuli as well as to develop cross-linguistic studies. The normative values of EP adaptation of the ANEW can be downloaded at http://brm.psychonomic-journals.org/content/supplemental.COMPETE - Programa Operacional Factores de CompetitividadeFundo Europeu de Desenvolvimento Regional - FEDERQuadro de Referência Estratégico Nacional - QRENFundação para a Ciência e a Tecnologia (FCT) - research project “Procura Palavras (P-Pal ): A software program for deriving objective and subjective psycholinguistic indices for European Portuguese words

Valence-Specific Modulation in the Accumulation of Perceptual Evidence Prior to Visual Scene Recognition

Visual scene recognition is a dynamic process through which incoming sensory information is iteratively compared with predictions regarding the most likely identity of the input stimulus. In this study, we used a novel progressive unfolding task to characterize the accumulation of perceptual evidence prior to scene recognition, and its potential modulation by the emotional valence of these scenes. Our results show that emotional (pleasant and unpleasant) scenes led to slower accumulation of evidence compared to neutral scenes. In addition, when controlling for the potential contribution of non-emotional factors (i.e., familiarity and complexity of the pictures), our results confirm a reliable shift in the accumulation of evidence for pleasant relative to neutral and unpleasant scenes, suggesting a valence-specific effect. These findings indicate that proactive iterations between sensory processing and top-down predictions during scene recognition are reliably influenced by the rapidly extracted (positive) emotional valence of the visual stimuli. We interpret these findings in accordance with the notion of a genuine positivity offset during emotional scene recognition

Soluble HLA in the aqueous humour of uveal melanoma is associated with unfavourable tumour characteristics

A high HLA expression in uveal melanoma (UM) is part of the prognostically unfavorable inflammatory phenotype. We wondered whether the presence of soluble HLA (sHLA) in the aqueous humour is associated with clinical, histopathological or genetic tumour characteristics, and represents tumour HLA expression and intratumoural inflammation. Aqueous humour from 108 UM patients was analysed for the presence of sHLA, using a Luminex assay specific for HLA Class I. Clinical and genetic parameters were compared between sHLA-positive and negative eyes. A qPCR analysis was performed on tumour tissue using a Fluidigm assay. In 19/108 UM-containing eyes, the sHLA level in the aqueous was above the detection limit. Tumours in sHLA-positive eyes were significantly larger, more frequently involved the ciliary body, and more often showed monosomy 3, gain of chromosome 8q and loss of BAP1 staining. Melanoma-related survival was worse in patients with sHLA-positive aqueous humour. sHLA in the aqueous did not represent the tumour's HLA expression and did not relate to immune cell infiltration in the tumour. We conclude that UM-containing eyes may contain sHLA in the aqueous humour, where it is a prognostically-unfavourable sign and may influence local immune responses