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Background: The Reading the Mind in the Eyes test (RMET) is a 36-item assessment for theory of mind (ToM) performance. While this measure has been shown to be sensitive to age-related ToM difficulties, there are no established cutoffs or guidelines currently available that are specific to older adults. This article seeks to validate a short-form version of the RMET appropriate for use in such populations. Methods: Cross-sectional data from 295 participants (mean age 86 years) from the Sydney Memory and Ageing Study, a longitudinal community observational cohort. Participants underwent an assessment battery that included the RMET. Individuals who scored >1SD below the RMET scores of cognitively normal participants were deemed to have below average RMET scores. Various model-building methods were used to generate short-form solutions of the RMET, which were compared with previously validated versions in their predictive power for below average full RMET performance. Results: Individuals with below average RMET performance tended to be older and have poorer global cognition. Of the eight short-form solutions, the 21-item version generated using genetic algorithm exhibited the best classification performance with an area under the receiver operating curve (AUROC) of 0.98 and had 93.2% accuracy in classifying individuals with below average ToM. A shorter 10-item solution derived by ant colony optimization also had acceptable performance. Conclusion: We recommend the 21-item version of the RMET for use in older adult populations for identifying individuals with impaired ToM. Where an even shorter version is needed with a trade-off of slightly reduced performance, the 10-item version is acceptable.

Dasatinib has shown superiority over imatinib in achieving molecular responses (MRs) in chronic phase chronic myeloid leukemia but with a different toxicity profile, which may impact its overall benefit. Reported toxicities include pleural effusions and pulmonary hypertension, and although the incidence of these events is well described, response to therapy and impact of dose modifications on toxicity has not been comprehensively characterized in a real-world setting. We retrospectively reviewed the incidence of dasatinib adverse events in 212 chronic phase chronic myeloid leukemia patients at 17 Australian institutions. Adverse events were reported in 116 patients (55%), most commonly pleural effusions (53 patients, 25%), which was the predominant cause of permanent drug cessation. Age and dose were risk factors for pleural effusion (P < .01 and .047, respectively). Recurrence rates were higher in those who remained on 100 mg compared with those who dose reduced (P = .041); however, recurrence still occurred at 50 mg. Patients who developed pleural effusions were more likely to have achieved MR4.5 after 6 months of dasatinib than those without effusions (P = .008). Pulmonary hypertension occurred in 5% of patients, frequently in association with pleural effusion, and was reversible upon dasatinib cessation in 6 of 7 patients. Dose reductions and temporary cessations had minimal impact on MR rates. Our observations suggest that by using the lowest effective dose in older patients to minimize the effusion risk, dose modification for cytopenias, and care with concomitant antiplatelet therapy, the necessity for permanent dasatinib cessation due to toxicity is likely to be minimal in immunologically competent patients.

Although second-generation tyrosine kinase inhibitors (TKIs) show superiority in achieving deep molecular responses in chronic myeloid leukemia in chronic phase (CML-CP) compared with imatinib, the differing adverse effect (AE) profiles need consideration when deciding the best drug for individual patients. Long-term data from randomized trials of nilotinib demonstrate an increased risk of vascular AEs (VAEs) compared with other TKIs, although the natural history of these events in response to dose modifications or cessation has not been fully characterized. We retrospectively reviewed the incidence of nilotinib-associated AEs in 220 patients with CML-CP at 17 Australian institutions. Overall, AEs of any grade were reported in 95 patients (43%) and prompted nilotinib cessation in 46 (21%). VAEs occurred in 26 patients (12%), with an incidence of 4.1 events per 100 patient-years. Multivariate analysis identified age (P 5 .022) and dyslipidemia (P 5 .007) as independent variables for their development. There was 1 fatal first VAE, whereas the remaining patients either continued nilotinib (14 patients) or stopped it immediately (11 patients). Recurrent VAEs were associated with ongoing therapy in 7 of 14 who continued (with 2 fatal VAEs) vs 1 of 11 who discontinued (P 5 .04). Nineteen of the 23 evaluable patients surviving a VAE ultimately stopped nilotinib, of whom 14 received an alternative TKI. Dose reduction or cessation because of VAEs did not adversely affect maintenance of major molecular response. These findings demonstrate that in contrast to other AEs, VAEs are ideally managed with nilotinib cessation because of the increased risk of additional events with its ongoing use.Copyright © 2019 by The American Society of Hematology.

Background: Dasatinib (DAS) has shown superiority over imatinib in achieving cytogenetic and molecular responses in chronic phase (CP) CML but with a different toxicity profile, which may impact on its overall benefit. Reported tox- icities from the DASISION trial at 5 years include pleural effusions (PE) (29%), pulmonary hypertension (PHTN) (5%), and low rates of arterial ischemic events. While the literature well describes the incidence of these events, the response to therapy and the impact of subsequent dose modifications on the outcome of the toxicity have generally not been comprehensively characterised. Aim(s): To review the incidence of these side-effects in a snapshot survey of Australian patients (pts) receiving DAS, either as first or subsequent line of therapy for CML-CP, with a focus on risk factors and the response of the toxicity to therapeutic changes. Method(s): Retrospective study of all eligible pts (received DAS for CML-CP and access to sufficient data) at 17 Australian institutions. Each pt's history was tracked in detail to identify any complications potentially attributable to DAS, and the treatment and outcome of these complications in response to cessation or alterations in DAS dose or schedule. Result(s): 221 pts were evaluable, with a median age at DAS commencement of 53 years (range 20 - 86) and median starting dose of 100mg (20-140). 51 (23%) received DAS as 1st line therapy, 133 (60%) 2nd line and 37 (17%) 3rd line. The median follow up from DAS commencement was 27 months (4 -116 months). No side effects were reported in 105 (48%) pts. Of the 116 (52%) pts with side-effects, the most common side effect was PE, observed in 53 (24%) pts with a median age of 65 years (41-86 years) and with median time to onset of 11 months (0.5-59 months). Most (40 pts, 76%) were receiving DAS as 2nd line therapy. DAS dose at PE onset was 100mg in 37 pts (70%), 140mg in 9 pts (17% PEs; notably 38% of pts on this dose developed PE), 70mg in 4 pts, 80mg in 2