Is being anti-vegan a distinct dietarian identity? An investigation with omnivores, vegans, and self-identified "anti-vegans".

Adding to research on the form and content of anti-vegan sentiment, recent scholarship has identified a group of individuals who self-subscribe as "anti-vegan". Here, we sought to determine whether anti-veganism might reflect a distinct dietarian identity with its own unique ideological profile. Two-hundred and fourteen vegans, 732 omnivores, and 222 self-identified "anti-vegans" were assessed using a survey methodology that included the Dietarian Identity Questionnaire and ideological markers related to dark humour, social dominance orientation (SDO), speciesism, male-role norms, moral relativism, and attitudes toward science. Our analysis revealed a dietarian identity unique to anti-vegans. The dietary patterns of anti-vegans were more central to their identity than for omnivores, though marginally lower than vegans. Like vegans, anti-vegans scored highly on dietarian measures of private regard and personal dietary motivations, and lower than omnivores on public regard. The diets of anti-vegans were more morally motivated than omnivores. However, anti-vegans scored higher than both omnivores and vegans on a number of ideological measures including dark humour, SDO, speciesism, male-role norms, moral relativism, and distrust of science. Somewhat surprising, anti-vegans held greater trust than omnivores in the science of plant-based nutrition. We discuss the unique dietarian identities of anti-vegans, considering both intra-group differences of omnivores and anti-vegans (e.g., in right-wing ideology), and inter-group similarities of vegans and anti-vegans (e.g., in diet centrality).

Cost-effectiveness of Intervention Implementation Support for Reducing Eating Disorder Symptoms Among College Students.

Implementation support for prevention interventions is receiving increased attention, as many organizations receive training in evidence-based practices but do not deliver the interventions optimally. The Body Project, a four-session program, significantly reduces eating disorder symptoms and future disorder onset among group participants when delivered by peer educators at colleges/universities. Costs and cost-effectiveness of the program were examined using data from a randomized trial that compared three levels of implementation support at 63 colleges: (1) a train-the-trainer (TTT) workshop alone, (2) TTT plus a technical assistance (TA) workshop, or (3) TTT plus TA plus monthly quality assurance (QA) consultations. Effectiveness was measured by the production of reliable change in eating disorder symptoms from pretest to posttest. Costs and cost-effectiveness of two levels of implementation support are reported, comparing TTT-only with TTT + TA + QA (effectiveness of the TTT + TA condition did not differ from TTT-only) and using results from an earlier study as a proxy for a no-treatment control. Two perspectives are considered: a sponsoring organization providing the training at multiple sites and a college delivering the intervention to its eligible students. From the perspective of a sponsoring organization, adding both the TA training and QA support improves the cost-effectiveness per eligible student receiving the intervention. From the perspective of costs for a college to deliver the intervention, receiving TA training and QA support is also more cost-effective than the training workshop alone, whether the peer educators are paid or unpaid and whether costs of group supervision are included or excluded. Results converge with previous research showing that more intensive implementation support can be more cost-effective.

Total serum N-glycans associate with response to immune checkpoint inhibition therapy and survival in patients with advanced melanoma.

BACKGROUND: Immune checkpoint inhibitors (ICIs) have revolutionized the treatment of melanoma and other cancers. However, no reliable biomarker of survival or response has entered the clinic to identify those patients with melanoma who are most likely to benefit from ICIs. Glycosylation affects proteins and lipids' structure and functions. Tumours are characterized by aberrant glycosylation which may contribute to their progression and hinder an effective antitumour immune response. METHODS: We aim at identifying novel glyco-markers of response and survival by leveraging the N-glycome of total serum proteins collected in 88 ICI-naive patients with advanced melanoma from two European countries. Samples were collected before and during ICI treatment. RESULTS: We observe that responders to ICIs present with a pre-treatment N-glycome profile significantly shifted towards higher abundancy of low-branched structures containing lower abundances of antennary fucose, and that this profile is positively associated with survival and a better predictor of response than clinical variables alone. CONCLUSION: While changes in serum protein glycosylation have been previously implicated in a pro-metastatic melanoma behaviour, we show here that they are also associated with response to ICI, opening new avenues for the stratification of patients and the design of adjunct therapies aiming at improving immune response.

Evidence that a novel transdiagnostic eating disorder treatment reduces reward region response to the thin beauty ideal and high-calorie binge foods.

BACKGROUND: Findings from brain imaging studies with small samples can show limited reproducibility. Thus, we tested whether the evidence that a transdiagnostic eating disorder treatment reduces responsivity of brain valuation regions to thin models and high-calorie binge foods, the intervention targets, from a smaller earlier trial emerged when we recruited additional participants. METHODS: Women with DSM-5 eating disorders (N = 138) were randomized to the dissonance-based body project treatment (BPT) or a waitlist control condition and completed functional magnetic resonance imaging (fMRI) scans assessing neural response to thin models and high-calorie foods at pretest and posttest. RESULTS: BPT v. control participants showed significantly greater reductions in responsivity of regions implicated in reward valuation (caudate) and attentional motivation (precuneus) to thin v. average-weight models, echoing findings from the smaller sample. Data from this larger sample also provided novel evidence that BPT v. control participants showed greater reductions in responsivity of regions implicated in reward valuation (ventrolateral prefrontal cortex) and food craving (hippocampus) to high-calorie binge foods v. low-calorie foods, as well as significantly greater reductions in eating disorder symptoms, abstinence from binge eating and purging behaviors, palatability ratings for high calorie foods, monetary value for high-calorie binge foods, and significantly greater increases in attractiveness ratings of average weight models. CONCLUSIONS: Results from this larger sample provide evidence that BPT reduces valuation of the thin ideal and high-calorie binge foods, the intervention targets, per objective brain imaging data, and produces clinically meaningful reductions in eating pathology.

Evaluating whether a peer-led dissonance-based eating disorder prevention program prevents onset of each eating disorder type.

BACKGROUND: This study tested whether the dissonance-based Body Project eating disorder prevention program reduced onset of subthreshold/threshold anorexia nervosa (AN), bulimia nervosa (BN), binge eating disorder (BED), and purging disorder (PD) over long-term follow-up. METHODS: Data were combined from three prevention trials that targeted young women at high-risk for eating disorders (N = 1092; M age = 19.3). Participants were randomized to Body Project groups led by peer educators or expressive writing/educational controls and completed masked diagnostic interviews over 2- to 4-year follow-ups. Logistic regressions tested whether onset of each eating disorder over follow-up differed between Body Project and control participants. RESULTS: Peer-led Body Project groups produced a 46% reduction in onset of subthreshold/threshold BN and a 62% reduction in onset of PD relative to controls over follow-up. Rates of onset of subthreshold/threshold AN and BED did not significantly differ between peer-led Body Project participants and control participants. CONCLUSIONS: Results support the dissemination of the peer-led Body Project for reducing future onset of BN and PD. This study and recent research suggest that thin-ideal internalization, the risk factor for eating disorders targeted in the Body Project, may be more relevant for predicting onset of BN and PD compared to AN and BED. Findings support the development of a version of the Body Project aimed to reduce risk factors that have predicted future onset of all four types of eating disorders (e.g. overvaluation of weight/shape, fear of weight gain), which may more effectively prevent all eating disorder types.

Out-of-hours admissions in patients treated with immune checkpoint inhibitors and their primary management with steroids.

INTRODUCTION: The incidence of immune-related adverse events (irAEs) from immune checkpoint inhibitors (ICI) is well described. However, the impact on emergency care services is not. This study investigated the incidence of irAEs out-of-hours, and the management used to mitigate symptoms and side effects. METHODS: This retrospective cohort study reviewed all emergency presentations triaged by the acute oncology team between December 2021 and June 2022, between 5 pm and 9 am. Patients were identified from triage audit sheets and remaining data points were retrieved from electronic health records. Inclusion criteria included all adult patients admitted on an ICI at one tertiary centre. RESULTS: In 7 months, 970 patients called the acute oncology helpline 11% (n = 109) of patients were on an ICI treatment. After clinical review, 78% (n = 70) resulted in hospital admissions, with length of stay cumulating to 496 bed days. 56% (n = 39) of patients delayed reporting symptoms, ranging between 12 hours and 10 days from symptom onset to seeking support. 49% (n = 34) patients received steroids to manage suspected irAEs. Dexamethasone was the most common steroid used in 71% (n = 24) of patients, and variation was found in prescribed doses. CONCLUSIONS: These results underline the urgent need to address patient and staff education on adverse effects related to ICI. Patients require a comprehensive understanding of the symptoms and importance of prompt reporting. Staff education on recognition and treatment management is needed to reduce variation in practice. Further research is needed to identify barriers in symptom reporting and focus on realtime reporting to reduce the out-of-hours burden on services.

Setting and Provider Predictors of Implementation Success for an Eating Disorder Prevention Program Delivered by College Peer Educators.

INTRODUCTION: College students face increased risk for a variety of mental health problems but experience barriers to treatment access. Prevention programs, including those implemented by peer educators, may decrease treatment needs and increase service access. We examined the implementation of an evidence-based eating disorder prevention program, Body Project, delivered by college peer educators at 63 colleges/universities, comparing three levels of implementation support: (1) Train-the-Trainer (TTT) training; (2) TTT plus a technical assistance workshop (TTT + TA); and (3) TTT + TA with one year of quality assurance calls (TTT + TA + QA). The present study tested the degree to which indicators proposed by the Consolidated Framework for Implementation Research (CFIR) were associated with core implementation outcomes. METHOD: We tested whether indices of CFIR domains (i.e., perceived intervention characteristics, outer and inner setting factors, provider characteristics, and implementation process) were correlated with three implementation outcomes (program reach, fidelity, effectiveness) during a 1-year implementation period. RESULTS: Greater program reach was associated with implementation process, specifically the completion of more implementation activities (ß = 0.46). Greater program fidelity was associated with higher positive (ß = 0.44) and lower negative (ß = - 0.43) perceptions of the Body Project characteristics, and greater reported general support for evidence-based practices (ß = 0.41). Greater effectiveness was associated with lower negative perceptions of Body Project characteristics (d = 0.49). CONCLUSIONS: Several implementation determinants proposed by the CFIR model predicted outcomes, especially intervention fidelity. Across the outcomes of interest, implementation determinants related to peer educator and supervisor perceived characteristics of the specific intervention and general attitudes towards evidence-based practices emerged as robust predictors to inform future work investigating ongoing implementation and sustainability of programs in university settings.

Behavioral Consistency in the Digital Age.

Efforts to infer personality from digital footprints have focused on behavioral stability at the trait level without considering situational dependency. We repeated a classic study of intraindividual consistency with secondary data (five data sets) containing 28,692 days of smartphone usage from 780 people. Using per-app measures of pickup frequency and usage duration, we found that profiles of daily smartphone usage were significantly more consistent when taken from the same user than from different users (d > 1.46). Random-forest models trained on 6 days of behavior identified each of the 780 users in test data with 35.8% accuracy for pickup frequency and 38.5% accuracy for duration frequency. This increased to 73.5% and 75.3%, respectively, when success was taken as the user appearing in the top 10 predictions (i.e., top 1%). Thus, situation-dependent stability in behavior is present in our digital lives, and its uniqueness provides both opportunities and risks to privacy.

Open-source smartphone app and tools for measuring, quantifying, and visualizing technology use.

Psychological science has spent many years attempting to understand the impact of new technology on people and society. However, the frequent use of self-report methods to quantify patterns of usage struggle to capture subtle nuances of human-computer interaction. This has become particularly problematic for devices like smartphones that are used frequently and for a variety of purposes. While commercial apps can provide an element of objectivity, these are 'closed' and cannot be adapted to deliver a researcher-focused 'open' platform that allows for straightforward replication. Therefore, we have developed an Android app that provides accurate, highly detailed, and customizable accounts of smartphone usage without compromising participants' privacy. Further recommendations and code are provided to assist with data analysis. All source code, materials, and data are freely available (see links in supplementary materials section).

Cost-Effectiveness Comparison of Delivery Modalities for a Dissonance-Based Eating Disorder Prevention Program over 4-Year Follow-Up.

The cost-effectiveness of delivery methods for an eating disorder prevention program is reported. In an effectiveness trial (enrollment 2013-2015) comparing three formats (clinician-led, peer-led, and Internet-delivered) for delivering the Body Project eating disorder prevention program to college women versus an educational video control, the peer-led method was more effective than the three alternatives at preventing onset of eating disorders over 4-year follow-up. Eating disorder incidence was 19.3% for clinician-led groups, 8.1% for peer-led groups, 15.5% for Internet-based eBody Project participants, and 17.6% for educational video controls. Delivery costs per person are reported for the Body Project, including participant time, and the cost-effectiveness is calculated for peer-led groups versus the video control. Data analyses were conducted in 2019-2021. Delivery costs per person for the Body Project, including participant time, were approximately $96 for clinician-led groups, $80 for peer-led groups, and $22 for the eBody Project, compared with $9 for the educational video control. For each additional case of eating disorder onset that was prevented by the peer-led groups, compared with the video control, the cost was about $740. There were no differences in health care utilization across condition. Eating disorder prevention costs via the Body Project compare very favorably with the costs for treating an eating disorder, which previously have been estimated to range from approximately $20,300 for cognitive-behavioral therapy for bulimia nervosa to approximately $119,200 for adequate care treatment of anorexia nervosa. These analyses demonstrate the economic value of the Body Project for preventing eating disorders among college-age women when delivered in peer-facilitated groups. ClinicalTrials.gov Identifier: NCT01949649.

Development of an Offline-Friend Addiction Questionnaire (O-FAQ): Are most people really social addicts?

A growing number of self-report measures aim to define interactions with social media in a pathological behavior framework, often using terminology focused on identifying those who are 'addicted' to engaging with others online. Specifically, measures of 'social media addiction' focus on motivations for online social information seeking, which could relate to motivations for offline social information seeking. However, it could be the case that these same measures could reveal a pattern of friend addiction in general. This study develops the Offline-Friend Addiction Questionnaire (O-FAQ) by re-wording items from highly cited pathological social media use scales to reflect "spending time with friends". Our methodology for validation follows the current literature precedent in the development of social media 'addiction' scales. The O-FAQ had a three-factor solution in an exploratory sample of N = 807 and these factors were stable in a 4-week retest (r = .72 to .86) and was validated against personality traits, and risk-taking behavior, in conceptually plausible directions. Using the same polythetic classification techniques as pathological social media use studies, we were able to classify 69% of our sample as addicted to spending time with their friends. The discussion of our satirical research is a critical reflection on the role of measurement and human sociality in social media research. We question the extent to which connecting with others can be considered an 'addiction' and discuss issues concerning the validation of new 'addiction' measures without relevant medical constructs. Readers should approach our measure with a level of skepticism that should be afforded to current social media addiction measures.

Phase 1/2a trial of intravenous BAL101553, a novel controller of the spindle assembly checkpoint, in advanced solid tumours.

BACKGROUND: BAL101553 (lisavanbulin), the lysine prodrug of BAL27862 (avanbulin), exhibits broad anti-proliferative activity in human cancer models refractory to clinically relevant microtubule-targeting agents. METHODS: This two-part, open-label, phase 1/2a study aimed to determine the maximum tolerated dose (MTD) and dose-limiting toxicities (DLTs) of 2-h infusion of BAL101553 in adults with advanced or recurrent solid tumours. The MTD was determined using a modified accelerated titration design in phase I. Patients received BAL101553 at the MTD and at lower doses in the phase 2a expansion to characterise safety and efficacy and to determine the recommended phase 2 dose (RP2D). RESULTS: Seventy-three patients received BAL101553 at doses of 15-80 mg/m2 (phase 1, n = 24; phase 2a, n = 49). The MTD was 60 mg/m2; DLTs observed at doses ≥60 mg/m2 were reversible Grade 2-3 gait disturbance with Grade 2 peripheral sensory neuropathy. In phase 2a, asymptomatic myocardial injury was observed at doses ≥45 mg/m2. The RP2D for 2-h intravenous infusion was 30 mg/m2. The overall disease control rate was 26.3% in the efficacy population. CONCLUSIONS: The RP2D for 2-h infusion of BAL101553 was well tolerated. Dose-limiting neurological and myocardial side effects were consistent with the agent's vascular-disrupting properties. CLINICAL TRIAL REGISTRATION: EudraCT: 2010-024237-23.

Age effects in eating disorder baseline risk factors and prevention intervention effects.

OBJECTIVE: Examine the impact of age on baseline eating disorder symptoms/risk factors and on the effects of completing three variants of an eating disorder prevention program. METHOD: Six hundred and eighty women (60% White) were randomized to clinician-led Body Project groups, peer-led Body Project groups, an Internet-based version of the Body Project (eBodyProject), or educational video control condition. Participants, who were on average 22.2 years old (SD = 7.1, range 17-64, median = 19), were assessed at pretest, posttest, and 6-month follow-up. RESULTS: Two of the seven baseline variables were significantly associated with age, indicating that older age was associated with lower reported dieting (r = -.12) and better psychosocial functioning (r = -.13). Interactions indicated that age moderated the intervention effects, such that group-based programs were superior to the Internet-delivered version in terms of eating disorder symptom reductions for women up to age 20, whereas the Internet-delivered program was superior to group-based interventions, particularly in terms of BMI reduction, for women over approximately age 25. None of the four tests examining whether age moderated the effects of delivering Body Project groups by mental health clinicians versus undergraduate peer educators were significant. DISCUSSION: Results suggest that group-based versions of the Body Project should be implemented with young women up to the age of 20, as they produce larger eating disorder symptom reductions, whereas the Internet version of the Body Project should be implemented with women aged 25 or older, as it produces superior weight loss/gain prevention effects.

Cost-effectiveness of achieving clinical improvement with a dissonance-based eating disorder prevention program.

Using data from an effectiveness trial delivered by college clinicians, we examined the cost-effectiveness of the dissonance-based Body Project program for reducing eating disorder symptoms in women with body dissatisfaction. The outcome of interest was individual-level change; 14.9% of Body Project participants attained clinically meaningful improvement vs. 6.7% of controls. Delivering the intervention costs approximately $70 (2012 U.S. dollars) per person. Incremental cost-effectiveness was $838 for each additional at-risk person reducing eating disorder symptomology to a clinically meaningful degree. These analyses demonstrate the economic value of the Body Project for college-age women with symptoms below the eating disorder diagnosis threshold.

Participant feedback from peer-led, clinician-led, and internet-delivered eating disorder prevention interventions.

OBJECTIVE: This article examines qualitative participant feedback to clinician-delivered groups, peer-delivered groups, and an Internet version of a dissonance-based eating disorder prevention program from a controlled trial. These data have not been systematically examined and can inform the refinement and implementation of eating disorder prevention programs. METHOD: Feedback was collected from body dissatisfied young women (N = 680; M age = 22.2, SD = 7.1) randomized to a clinician-led group, peer-led group, Internet version of this prevention program or to an educational video. RESULTS: Clinician and peer-led group participants reported the group setting, feeling that they were not alone, and the letter exercise as most valuable; the most common response of what was less valuable was "none." Many participants of the Internet version suggested increasing community support. CONCLUSIONS: Findings suggest the importance of considering the therapeutic value of group membership, and that online prevention programs could be enhanced by providing a mechanism for community support, such as an online forum. Results also inform selective prevention and suggest that screening potential participants to determine which delivery method best suits them should be considered. © 2016 Wiley Periodicals, Inc. (Int J Eat Disord 2016; 49:1087-1092).

Young woman smokers gain significantly more weight over 2-year follow-up than non-smokers. How Virginia doesn't slim.

OBJECTIVE: Although young women often report smoking for weight control purposes, no prospective study has tested whether smokers subsequently gain less weight over time than non-smokers. As this is an important lacuna because smoking results in greater mortality than obesity, the present study addresses this question. METHOD: Female college students (N = 398; M age = 18.4, SD =0.6; M BMI = 23.7, SD =4.3) recruited for a body acceptance intervention trial provided data on smoking behavior and had their body mass measured at baseline and at 1-mo, 6-mo, 1-yr, and 2-yr follow-ups. RESULTS: Counter to the belief that smoking is an effective weight control strategy, baseline smokers (n = 29) gained significantly more weight (r = .29) than baseline non-smokers (n = 304), controlling for baseline BMI, parental obesity status, socio-economic status, and intervention condition; over 2-yr follow-up smokers gained 2.9 kg versus 0.9 kg for non-smokers. Descriptive data indicated that weight gain was greater for young women who quit smoking during follow-up (n = 13; M = 4.8 kg) than for persistent smokers (n = 16; M = 1.4 kg), though both groups gained more weight than non-smokers. CONCLUSIONS: RESULTS challenge the widely held belief that smoking is an effective weight control strategy, ironically suggesting that smokers gain more weight than non-smokers during young adulthood, though non-experimental prospective studies do not establish causal relations and future research with larger representative samples is needed.

Dissonance-based prevention of eating disorder risk factors in middle school girls: results from two pilot trials.

OBJECTIVE: Although several eating disorder prevention programs reduce eating disorder risk factors and symptoms for female high school and college students, few efficacious prevention programs exist for female middle school students, despite the fact that body image and eating disturbances often emerge then. Two pilot trials evaluated a new dissonance-based eating disorder prevention program for middle school girls with body image concerns. METHOD: Female middle school students with body dissatisfaction from two sites [Study 1: N = 81, M age = 12.1, standard deviation (SD) = 0.9; Study 2: N = 52, M age = 12.5, SD = 0.8] were randomized to a dissonance intervention (MS Body Project) or educational brochure control; Study 2 included a 3-month follow-up. RESULTS: Intervention participants showed significant post-test reductions in only one of the six variables with both Studies 1 and 2 (i.e., pressure to be thin and negative affect, respectively), though post-test effect sizes suggested medium reductions in eating disorder risk factors and symptoms (Study 1: M d = .40; Study 2: M d = .65); reductions at 3-month follow-up in Study 2 were not evident (M d = .19). CONCLUSIONS: Results suggest that this new middle school version of the Body Project is producing medium magnitude reductions in eating disorder risk factors at post-test but that effects are showing limited persistence. Continued refinement and evaluation of this intervention appears warranted to develop more effective prevention programs for this age group.

Predictors of the sustainability for an evidence-based eating disorder prevention program delivered by college peer educators.

BACKGROUND: Despite ongoing efforts to introduce evidence-based interventions (EBIs) into mental health care settings, little research has focused on the sustainability of EBIs in these settings. College campuses are a natural place to intervene with young adults who are at high risk for mental health disorders, including eating disorders. The current study tested the effect of three levels of implementation support on the sustainability of an evidence-based group eating disorder prevention program, the Body Project, delivered by peer educators. We also tested whether intervention, contextual, or implementation process factors predicted sustainability. METHODS: We recruited 63 colleges with peer educator programs and randomly assigned them to (a) receive a 2-day Train-the-Trainer (TTT) training in which peer educators were trained to implement the Body Project and supervisors were taught how to train future peer educators (TTT), (b) TTT training plus a technical assistance (TA) workshop (TTT + TA), or (c) TTT plus the TA workshop and quality assurance (QA) consultations over 1-year (TTT + TA + QA). We tested whether implementation support strategies, perceived characteristics of the intervention and attitudes towards evidence-based interventions at baseline and the proportion of completed implementation activities during the implementation year predicted three school-level dichotomous sustainability outcomes (offering Body Project groups, training peer educators, training supervisors) over the subsequent two-year sustainability period using logistic regression models. RESULTS: Implementation support strategies did not significantly predict any sustainability outcomes, although a trend suggested that colleges randomized to the TTT + TA + QA strategy were more likely to train new supervisors (OR = 5.46, 95% CI [0.89-33.38]). Colleges that completed a greater proportion of implementation activities were more likely to offer Body Project groups (OR = 1.53, 95% CI [1.19-1.98]) and train new peer educators during the sustainability phase (OR = 1.39, 95% CI [1.10-1.74]). Perceived positive characteristics of the Body Project predicted training new peer educators (OR = 18.42, 95% CI [1.48-299.66]), which may be critical for sustainability in routine settings with high provider turnover. CONCLUSIONS: Helping schools complete more implementation activities and increasing the perceived positive characteristics of a prevention program may result in greater sustainment of prevention program implementation. TRIAL REGISTRATION: This study was preregistered on 12/07/17 with ClinicalTrials.gov, ID NCT03409809, https://clinicaltrials.gov/ct2/show/NCT03409809 .

A three-arm randomised phase II study of the MEK inhibitor selumetinib alone or in combination with paclitaxel in metastatic uveal melanoma.

AIMS: The MAPK pathway is constitutively activated in uveal melanoma (UM). Selumetinib (AZD6244, ARRY-142886), a MEK inhibitor, has shown limited activity as monotherapy in metastatic UM. Pre-clinical studies support synergistic cytotoxic activity for MEK inhibitors combined with taxanes, and here we sought to assess the clinical efficacy of combining selumetinib and paclitaxel. PATIENTS AND METHODS: Seventy-seven patients with metastatic UM who had not received prior chemotherapy were randomised to selumetinib alone, or combined with paclitaxel with or without interruption in selumetinib two days before paclitaxel. The primary endpoint was progression free survival (PFS). After amendment, the combination arms were combined for analysis and the sample size adjusted to detect a hazard ratio (HR): 0.55, 80% power at 1-sided 5% significance level. RESULTS: The median PFS in the combination arms was 4.8 months (95% CI: 3.8 - 5.6) compared with 3.4 months (2.0 - 3.9) in the selumetinib arm (HR 0.62 [90% CI 0.41 - 0.92], 1-sided p-value = 0.022). ORR was 14% and 4% in the combination and monotherapy arms respectively. Median OS was 9 months for the combination and was not significantly different from selumetinib alone (10 months) with HR of 0.98 [90% CI 0.58 - 1.66], 1-sided p-value = 0.469. Toxicity was in keeping with the known profiles of the agents involved. CONCLUSIONS: SelPac met its primary endpoint, demonstrating an improvement in PFS for combination selumetinib and paclitaxel. No improvement in OS was observed, and the modest improvement in PFS is not practice changing.

Longitudinal gut microbiome changes in immune checkpoint blockade-treated advanced melanoma.

Multiple clinical trials targeting the gut microbiome are being conducted to optimize treatment outcomes for immune checkpoint blockade (ICB). To improve the success of these interventions, understanding gut microbiome changes during ICB is urgently needed. Here through longitudinal microbiome profiling of 175 patients treated with ICB for advanced melanoma, we show that several microbial species-level genome bins (SGBs) and pathways exhibit distinct patterns from baseline in patients achieving progression-free survival (PFS) of 12 months or longer (PFS ≥12) versus patients with PFS shorter than 12 months (PFS <12). Out of 99 SGBs that could discriminate between these two groups, 20 were differentially abundant only at baseline, while 42 were differentially abundant only after treatment initiation. We identify five and four SGBs that had consistently higher abundances in patients with PFS ≥12 and <12 months, respectively. Constructing a log ratio of these SGBs, we find an association with overall survival. Finally, we find different microbial dynamics in different clinical contexts including the type of ICB regimen, development of immune-related adverse events and concomitant medication use. Insights into the longitudinal dynamics of the gut microbiome in association with host factors and treatment regimens will be critical for guiding rational microbiome-targeted therapies aimed at enhancing ICB efficacy.