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Idecabtagene vicleucel (ide-cel), a B-cell maturation antigen-directed chimeric antigen receptor T cell therapy, showed deep, durable responses in patients with triple-class exposed, relapsed and refractory multiple myeloma (RRMM) in the phase 2 KarMMa (Efficacy and Safety Study of bb2121 in Subjects With Relapsed and Refractory Multiple Myeloma) trial. We assessed health-related quality of life (HRQoL) among KarMMa patients. The European Organization for Research and Treatment of Cancer Quality of Life C30 Questionnaire and its supplementary 20-item multiple myeloma module, as well as the EuroQol 5-dimension 5-level instrument, were administered at screening, baseline (≤72 hours before or same day as lymphodepletion), day of ide-cel treatment, and after ide-cel treatment. Mean changes from baseline that exceeded the predetermined threshold of minimally important difference were deemed clinically meaningful. The proportions of patients experiencing clinically meaningful changes in HRQoL were assessed using within-patient change thresholds. Time to stable improvement (≥2 consecutive visits with clinically meaningful HRQoL improvements) was analyzed by using the Kaplan-Meier method. A total of 126 (98%) of 128 patients treated with ide-cel were included in the HRQoL analysis. Pretreatment baseline RRMM burden was high and meaningfully worse than that in the age- and sex-weighted general population. Statistically significant and clinically meaningful improvements from baseline were observed by month 1 for pain (-8.9) and disease symptoms (-10.2), and by month 2 for fatigue (-7.2), physical functioning (6.1), cognitive functioning (6.7), and global health status/QoL (8.0). Clinically meaningful improvements in fatigue, pain, and physical functioning were most prominent at months 9, 12, and 18, respectively, and were sustained through 15 to 18 months after ide-cel treatment. For triple-class exposed patients with RRMM with a poor prognosis and few treatment options, a single ide-cel infusion provides early, sustained, statistically significant, and clinically meaningful improvements in HRQoL. This study was registered at Clinicaltrials.gov as #NCT03361748. ispartof: BLOOD ADVANCES vol:6 issue:4 pages:1309-1318 ispartof: location:United States status: published

Lisocabtagene maraleucel (liso-cel) has shown promising efficacy in clinical trials for patients with relapsed/refractory large B-cell lymphoma (LBCL). We present health-related quality of life (HRQOL) results from the TRANSFORM study, the first comparative analysis of liso-cel vs standard of care (SOC) as second-line therapy in this population. Adults with LBCL refractory or relapsed ≤12 months after first-line therapy and eligible for autologous stem cell transplantation were randomized 1:1 to the liso-cel or SOC arms (3 cycles of immunochemotherapy in which responders proceeded to high-dose chemotherapy and autologous stem cell transplantation). HRQOL was assessed by European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire – 30 items and the Functional Assessment of Cancer Therapy-Lymphoma subscale. Patients with baseline and ≥1 postbaseline assessment were analyzed (liso-cel, n = 47; SOC, n = 43). The proportion of patients with meaningful improvement in global health status/quality of life (QOL) was higher, whereas deterioration was lower in the liso-cel arm vs SOC arm from day 126 to month 6. Mean change scores showed meaningful worsening in global health status/QOL at month 6, fatigue at day 29 and month 6, and pain at month 6 with SOC; mean scores for other domains were maintained or improved in both arms. Time to confirmed deterioration favored the liso-cel arm vs SOC arm in global health status/QOL (median: not reached vs 19.0 weeks, respectively; hazard ratio, 0.47; 95% confidence interval, 0.24-0.94). HRQOL was either improved or maintained from baseline in patients with relapsed/refractory LBCL in the liso-cel arm vs SOC arm as second-line treatment. This study is registered at clinicaltrials.gov as #NCT0357531.

The programmed death-1 (PD-1) inhibitor nivolumab prolongs disease-free survival in patients with muscle-invasive urothelial carcinoma (MIUC).To evaluate the effects of nivolumab on health-related quality of life (HRQoL) after radical resection in patients with MIUC.We used data from 709 patients in CheckMate 274 (NCT02632409; 282 with programmed death ligand 1 [PD-L1] expression ≥1%), an ongoing randomized, double-blind, placebo-controlled phase 3 trial of adjuvant nivolumab.Intravenous injection of nivolumab (240 mg) or placebo every 2 wk for ≤1 yr.HRQoL was assessed using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) and the EQ-5D-3L. Linear mixed-effect models for repeated measures were used to compare nivolumab and placebo on changes in HRQoL. Time to confirmed deterioration (TTCD) of HRQoL was analyzed by Cox proportional hazards regression.In the full HRQoL evaluable population, no clinically meaningful deterioration of HRQoL was observed in either treatment arm. Moreover, nivolumab was noninferior to placebo on changes from baseline for all main outcomes. The median TTCD for fatigue was 41.0 wk for nivolumab and 44.3 wk for placebo (hazard ratio [HR]: 1.11, 95% confidence interval [CI], 0.89-1.39). For the visual analog scale, the median TTCD was not reached for nivolumab and it was 57.6 wk for placebo (HR: 0.78, 95% CI, 0.61-1.00). The median TTCD for the other main outcomes was not reached in either treatment arm. The findings were similar for patients with PD-L1 expression ≥1%.These results demonstrate that nivolumab did not compromise the HRQoL of patients with MIUC in CheckMate 274.Nivolumab is being researched as a new treatment for patients with bladder cancer (urothelial carcinoma). We found that nivolumab maintained quality of life while increasing the time until cancer returns in patients whose bladder cancer had spread or grown and who had unsuccessfully tried platinum-containing chemotherapy.

OBJECTIVE: To understand the experience of patients with relapsed and refractory multiple myeloma (RRMM) receiving idecabtagene vicleucel (ide-cel), a B-cell maturation antigen-directed chimeric antigen receptor T cell therapy, in the pivotal, phase 2 KarMMa trial. METHODS: Optional semi-structured interviews before leukapheresis (pre-treatment) captured expectations and after ide-cel infusion (1, 2, and 3 months post-treatment), assessed treatment experience, ide-cel advantages/disadvantages, and health and well-being. In a mixed-method analysis, treatment experiences were categorized by clinical response status, health and well-being, and self-reported recovery after infusion. RESULTS: Pre-treatment interviews indicated unmet treatment needs. In post-treatment interviews, most patients reported the positives of ide-cel outweighed negatives (69%, n = 27/39). Most common advantages of ide-cel were efficacy (18-64%), favorable side-effect profile (46-68%), and recovery time (13-18%); most common disadvantages were related to side effects (13-20%). When analyzed by clinical response, patients most often had stringent complete or very good partial response and improved health and well-being with mild or severe recovery from the infusion (27/58, 47%). Most patients with minimal clinical response reported mild infusion recovery (5/6, 83%). CONCLUSIONS: Patient interviews before ide-cel treatment showed unmet needs in triple-class exposed RRMM. Post-treatment experiences generally favored ide-cel versus previously received treatments. ispartof: LEUKEMIA RESEARCH vol:120 ispartof: location:England status: published

Background: Although the European Organisation for Research and Treatment of Cancer (EORTC) QLQ-PAN26 is widely used to assess health-related quality of life (HRQoL), its group-level minimal important difference (MID) and individual-level responder definition (RD) are not established; we calculated MID and RD using HRQoL data from the APACT trial in patients with surgically resected pancreatic cancer who received adjuvant chemotherapy. Methods: HRQoL was assessed using EORTC QLQ-C30 and QLQ-PAN26 at baseline, during treatment, at end of treatment, and during follow-up. Distribution-based MIDs were estimated using 0.5 × baseline standard deviation (SD) and reliability-based (intraclass correlation) standard error of measurement (SEM). Anchor-based MIDs and RDs (anchor, QLQ-C30 overall health) were estimated using a linear mixed model. Results: Overall, 772 patients completed the baseline assessment. Distribution-based MIDs (0.5 × SD) for QLQ-PAN26 scales ranged from 12 to 13, except hepatic symptoms (≈8), pancreatic pain (≈10), and sexual dysfunction (≈17); those for stand-alone items ranged from 12 to 16. The SEM values were similar. Among scales/items sufficiently correlated (r>0.30) with the anchor, MIDs ranged from 5 to 9. Within-patient QLQ-PAN26 RD estimates varied by direction (deterioration vs. improvement) and scale/item, but all values were lower than the true possible within-patient change (e.g. 16.7 points for a two-item scale) given a one-category change on the raw scale. Conclusions: Compared with distribution-based MIDs, anchor-based MIDs were twice as sensitive in detecting group-level changes in QLQ-PAN26 scales/items. For interpreting clinically meaningful change, RDs cannot be less than the true minimum of the scale. The group-level MID may help clinicians/researchers interpret HRQoL changes. Trial registration: ClinicalTrials.gov NCT01964430; Eudra CT 2013-003398-91.

Although the European Organisation for Research and Treatment of Cancer (EORTC) QLQ-PAN26 is widely used to assess health-related quality of life (HRQoL), its group-level minimal important difference (MID) and individual-level responder definition (RD) are not established; we calculated MID and RD using HRQoL data from the APACT trial in patients with surgically resected pancreatic cancer who received adjuvant chemotherapy.HRQoL was assessed using EORTC QLQ-C30 and QLQ-PAN26 at baseline, during treatment, at end of treatment, and during follow-up. Distribution-based MIDs were estimated using 0.5 × baseline standard deviation (SD) and reliability-based (intraclass correlation) standard error of measurement (SEM). Anchor-based MIDs and RDs (anchor, QLQ-C30 overall health) were estimated using a linear mixed model.Overall, 772 patients completed the baseline assessment. Distribution-based MIDs (0.5 × SD) for QLQ-PAN26 scales ranged from 12 to 13, except hepatic symptoms (≈8), pancreatic pain (≈10), and sexual dysfunction (≈17); those for stand-alone items ranged from 12 to 16. The SEM values were similar. Among scales/items sufficiently correlated (r 0.30) with the anchor, MIDs ranged from 5 to 9. Within-patient QLQ-PAN26 RD estimates varied by direction (deterioration vs. improvement) and scale/item, but all values were lower than the true possible within-patient change (e.g. 16.7 points for a two-item scale) given a one-category change on the raw scale.Compared with distribution-based MIDs, anchor-based MIDs were twice as sensitive in detecting group-level changes in QLQ-PAN26 scales/items. For interpreting clinically meaningful change, RDs cannot be less than the true minimum of the scale. The group-level MID may help clinicians/researchers interpret HRQoL changes.ClinicalTrials.gov NCT01964430; Eudra CT 2013-003398-91.

In order to grasp the difference between “the cat on the mat” and “the mat on the cat,” understanding the words and the grammar is not enough. Rather it is essential to visually synthesize the cat and the mat together in front of the mind’s eye to appreciate their relations. This type of voluntary imagination, which involves juxtaposition of mental objects is conducted by the prefrontal cortex and is therefore called Prefrontal Synthesis (PFS). While PFS is essential for understanding of complex language, its acquisition has a strong experience-dependent critical period putting children with language delay in danger of never acquiring PFS and, consequently, not mastering complex language comprehension. In typical children, the timeline of PFS acquisition correlates with vocabulary expansion. Conversely, atypically developing children may learn hundreds of words but never acquire PFS. In these individuals, common tests of intelligence based on vocabulary assessment may miss the profound deficit in PFS. Accordingly, we developed a 5-minute test specific for PFS – Linguistic Evaluation of Prefrontal Synthesis or LEPS – and administered it to 50 neurotypical children, age 2 to 7 years (4.1±1.3) and to 23 individuals with impairments, age 8-21 years (16.4±3.0). All neurotypical children older than 4 years received the LEPS score 7/10 or greater indicating good PFS ability. Among individuals with impairments only 9 of 23 (39%) received the LEPS score 7/10 or greater. LEPS score was 90% correct in predicting high-functioning vs. low-functioning class assignment in individuals with autism, while full-scale IQ score was only 50% correct.

Background: Although the quality of life (QoL) plays an important role in treatment decision making and clinical management of mycosis fungoides (MF) or Sezary syndrome (SS) subtypes of cutaneous T-cell lymphomas (MF/SS-CTCLs), an MF- or SS-specific measure of QoL does not exist. Objective: The objective of this research was to develop and validate the first QoL instrument for MF/SS-CTCL using a patient-centered approach. Methods: A conceptual framework for the MF/SS-CTCL QoL was developed through a literature review and interviews with key opinion leaders. Concept elicitation with patients was utilized to refine the conceptual model and generate preliminary items. The items were then revised based on qualitative and quantitative feedback obtained through cognitive debriefing surveys and interviews with patients. Next, participants (N=126) completed the preliminary MF/SS-CTCL QoL and a comparator measure of health-related QoL (Skindex-29) through the PatientsLikeMe Open Research Exchange. The MF/SS-CTCL QoL was completed again 5 days later by 66 participants for the purposes of evaluating test-retest reliability. The MF/SS-CTCL QoL was finalized based on results from an empirical evaluation, which included both classical and modern test theory approaches. Specifically, this included evaluation of (1) the optimal item response theory measurement model; (2) item fit; (3) unidimensionality; (4) rating scale performance; (5) reliability; (6) test information (precision); (7) person-to-item map; (8) convergent and discriminant validity; and (9) presence of bias via differential item function. Results: Results from the comprehensive psychometric evaluation utilizing a Rasch-Grouped Rating Scale model yielded a final 12-item instrument. The rating scale functioned as expected, and the instrument exhibited adequate person reliability (.87), good to excellent test-retest reliability (r=.89, P

This study is the first to compare the accuracy of self-reported with actual monetary outcomes of online fixed odds sports betting, live action sports betting, and online casino gambling at the individual level of analysis. Subscribers to bwin.party digital entertainment's online gambling service volunteered to respond to the Brief Bio-Social Gambling Screen and questions about their estimated gambling results on specific games for the last 3 or 12 months. We compared the estimated results of each subscriber with his or her actual betting results data. On average, between 34% and 40% of the participants expressed a favorable distortion of their gambling outcomes (i.e., they underestimated losses or overestimated gains) depending on the time period and game. The size of the discrepancy between actual and self-reported results was consistently associated with the self-reported presence of gambling-related problems. However, the specific direction of the reported discrepancy (i.e., favorable vs. unfavorable bias) was not associated with gambling-related problems.

This study is the first demonstration of the effect of motivational focus (approach vs. avoidance) on the interpretation of graphical view of personal data, specifically, weight loss progress. In two experiments, participants were randomly assigned to see the bogus weight loss data charted against either a goal or a baseline reference line. In the first experiment, we accessed participants' chronic motivational focus. In the second study, we primed motivation by exposing the participants to either a gain- or loss-focused health message. The results demonstrate that participants with either chronic or manipulated approach motivation predicted higher future weight loss in the goal reference line condition than in the baseline reference line condition. The opposite pattern was observed for participants with either chronic or manipulated avoidance motivation. The potential of matching graphical data display to personality characteristics to promote effective health management is discussed. © 2012 Copyright Taylor and Francis Group, LLC.

Background: The goal of this study is to identify betting patterns displayed during the first month of actual Internet gambling on a betting site that can serve as behavioural markers to predict the development of gambling-related problems. Methods: Using longitudinal data, k-means clustering analysis identified a small subgroup of high-risk gamblers. Results: Seventy-three percent of the members of this subgroup eventually closed their account due to gambling-related problems. The characteristics of this high-risk subgroup were as follows: (i) frequent and (ii) intensive betting combined with (iii) high variability across wager amount and (iv) an increasing wager size during the first month of betting. Conclusion: This analysis provides important information that can help to identify potentially problematic gamblers during the early stages of gambling-related problems. Public health workers can use these results to develop early interventions that target high-risk Internet gamblers for prevention efforts. However, one study limitation is that the results distinguish only a small proportion of the total sample; therefore, additional research will be necessary to identify markers that can classify larger segments of high-risk gamblers.

Using actual gambling behavior provides the opportunity to develop behavioral markers that operators can use to predict the development of gambling-related problems among their subscribers. Participants were 4,056 Internet gamblers who subscribed to the Internet betting service provider bwin.party. Half of this sample included multiple platform gamblers who were identified by bwin.party's Responsible Gambling (RG) program; the other half were controls randomly selected from those who had the same first deposit date. Using the daily aggregated Internet betting transactions for gamblers' first 31 calendar days of online betting activities at bwin.party, we employed a 2-step analytic strategy: (a) applying an exploratory chi-squared automatic interaction detection (CHAID) decision tree method to identify characteristics that distinguished a subgroup of high-risk Internet gamblers from the rest of the sample, and (b) conducting a confirmatory analysis of those characteristics among an independent validation sample. This analysis identified two high-risk groups (i.e., groups in which 90% of the members were identified by bwin.party's RG program): Group 1 engaged in three or more gambling activities and evidenced high wager variability on casino-type games; Group 2 engaged in two different gambling activities and evidenced high variability for live action wagers. This analysis advances an ongoing research program to identify potentially problematic Internet gamblers during the earliest stages of their Internet gambling. Gambling providers and public policymakers can use these results to inform early intervention programs that target high-risk Internet gamblers.

This article presents findings from the first taxometric study of actual gambling behavior to determine whether we can represent the characteristics of extreme gambling as qualitatively distinct (i.e., taxonic) or as a point along a dimension. We analyzed the bets made during a 24-month study period by the 4,595 most involved gamblers among a cohort of 48,114 people using an Internet service to gamble on sporting events. We applied two taxometric procedures (i.e., MAMBAC and MAXCOV) to three indicators of betting behavior: total money lost, total number of bets, and total money wagered. The results fail to provide support for the view that the most involved Internet sports gamblers include a distinct category of gamblers. More research is necessary to clarify the similar features of recreational and extreme gamblers and the dimensions that scientists can use to measure these behaviors. Finally, we discuss the implications of these findings for clinical, research, and public policy activities.

We developed an educational website for parents of paediatric patients with kidney diseases in Russia. Parents could ask questions regarding their child's illness and submit information, including medical summaries and scanned or electronic images. A US-trained specialist in paediatric nephrology reviewed the information provided and advised about further evaluation or referral, as well as discussing possible treatment plans. In the first nine months, 141 distinct users communicated through the website. Fifty-eight percent of patients were female. An analysis of 70 cases suggested that in 45% there had been overdiagnosis of common paediatric problems, such as urinary tract infection and pyelonephritis. Users completed an anonymous satisfaction survey. The response rate was 84% ( n = 59/70). The majority of respondents found the consultation useful (mean = 4.6 on a 5-point scale). The online consultation answered the questions of most respondents, provided useful information and relieved uncertainty regarding a follow-up. The majority of the respondents (>90%) confirmed that they trusted the online consultation and would recommend the technique to other parents. Online consultation for parents can provide reliable information that results in improved parental satisfaction and education. This approach may be useful in improving care and providing patient education in underserved areas in the USA and elsewhere.

The prevalence, morbidity and mortality of hypertension are strikingly higher for African Americans than for Whites. Poor adherence to the antihypertensive medication regimen is a major cause of inadequate blood pressure control. In this study, we assess the relationship of antihypertensive medication adherence to sociodemographic, clinical and cognitive characteristics of urban African American adults.Data were drawn from a larger randomized controlled trial assessing the effect of a behavioral intervention to improve medication adherence and blood pressure control among hypertensive African American patients followed in an urban primary care network. Medication adherence was assessed at baseline using the Medication Event Monitoring System (MEMS)--a method regarded as the gold standard for assessing medication adherence in clinical research. Information on potential correlates of medication adherence (sociodemographic, clinical and cognitive) was obtained at baseline by computer-assisted interview. We assessed the cross sectional association of these factors to medication adherence in baseline data.Medication adherence was significantly associated with systolic blood pressure (r=.253, P.04) and self-reported medication adherence (r=.285, P.03). The relationship of education to medication adherence varied significantly by sex (P.05 for interaction). Specifically, lower educational attainment was related to higher adherence among men, but lower adherence among women.Identifying correlates of low antihypertensive medication adherence and their interactions, as in this study, will help health providers to better recognize patients at higher risk for worse hypertension-related outcomes. This knowledge can also inform interventions which target a higher-risk subset of hypertensive patients.

The purpose of this research is to explore the effect of mood on the detection of covariation. Predictions were based on an assumption that sad moods facilitate a data-driven information elaboration style and careful data scrutinizing, whereas happy moods predispose individuals toward top-down information processing and decrease the attention given to cognitive tasks. The primary dependent variable involved is the detection of covariation between facial features and personal information and the use of this information for evaluating new target faces. The findings support the view that sad mood facilitates both conscious and unconscious detection of covariation because it increases motivation to engage in the task. Limiting available cognitive resources does not eliminate the effect of mood on the detecting of covariation.

The authors argue that specific emotions can alter the persuasive impact of messages as a function of the emotional framing of persuasive appeals. Because specific emotions inflate expectancies for events possessing matching emotional overtones (D. DeSteno, R. E. Petty, D. T. Wegener, & D. D. Rucker, 2000), the authors predicted that attempts at persuasion would be more successful when messages were framed with emotional overtones matching the emotional state of the receiver and that these changes would be mediated by emotion-induced biases involving expectancies attached to arguments contained in the messages. Two studies manipulating discrete negative emotional states and message frames (i.e., sadness and anger) confirmed these predictions. The functioning of this emotion-matching bias in parallel with emotion-induced processing differences and the limitations of a valence-based approach to the study of attitude change are also considered.