BRAVE Study Research Articles

Comparing Left Bundle Branch Area vs Right-Ventricular Septal Pacing in High-Degree Conduction Disease After Transcatheter Aortic Valve Replacement: Randomized Trial Study Protocol

Left bundle branch area pacing (LBBAP) is a novel method of conduction-system pacing in the muscular interventricular septum. Although LBBAP has been shown to produce physiologic electrical and mechanical intraventricular synchrony, superiority of LBBAP, compared to right ventricular septal pacing (RVSP) at preserving normal left-ventricular (LV) systolic function after transcatheter aortic valve replacement (TAVR) has not been demonstrated. Left Bundle BRAVE is an investigator-initiated, multicentre, prospective, double-blinded, randomized, crossover study investigating the superiority of LBBAP, compared to RVSP, with respect to preservation of systolic function in patients with high-degree conduction disease after TAVR. Adults with severe aortic stenosis and normal systolic function who sustain high-grade atrioventricular block within 4 weeks of TAVR are eligible. All subjects receive a biventricular pacemaker generator with RVSP, and LBBAP leads. Participants are randomly assigned to 9 months of each pacing mode, in series. The primary endpoint is change in global longitudinal strain, tested in series with change in LV ejection fraction, comparing RVSP to LBBAP. Secondary endpoints include the following: echocardiographic markers of interventricular synchrony and right ventricular performance; heart failure functional status and symptom classification; 6-minute walk test results; pacemaker and lead performance; and brain natriuretic peptide concentration. The Left Bundle BRAVE study is designed to identify an upstream and clinically relevant marker of superiority in LBBAP, compared to RVSP, at preventing deterioration of LV function in patients with a high ventricular pacing burden after TAVR. ClinicalTrials.gov identifierNCT05541679

Brain, behavior, cognition, and physical health in first-onset adolescent anorexia nervosa: The BRAVE Study design and cohort profile

Background Anorexia nervosa is a severe psychiatric disorder with a heterogeneous course with one of the highest rates of morbidity and mortality of all psychiatric disorders. Little is known about factors that predict both course and treatment outcomes of this disorder. The BRAVE Study is a longitudinal first-onset anorexia nervosa cohort study focusing on four topics of interest in girls only: (1) behavior, (2) neurobiology, (3) cognitive functions, and (4) physical health. Objective The goal of this paper is to introduce the BRAVE Study. The primary aim of the BRAVE Study is to identify predictors of treatment response in a large sample of 12-to-22-year-old females with first-onset typical or atypical anorexia nervosa. The second aim is to longitudinally investigate the association between clinically significant changes in eating disorder symptoms with the underlying behavioral, neurobiological, cognitive and physical health changes. The results of this study will allow us to develop more precise treatment strategies in order to provide more optimal treatment. Methods and analysis The BRAVE Study implements a longitudinal case-control design. Study recruitment was designed within a collaborative network of 16 Dutch mental health organizations, each with expertise in the diagnosis and treatment of patients with anorexia nervosa. After obtaining informed consent, assessments were performed at baseline and one-year follow-up. Patients with anorexia nervosa received treatment as usual. The primary outcome measures at one year are restoration of weight and a reduction of eating disorder symptomatology. Predictive measures include neurobiological, cognitive, behavioral and physical health measures. Sample description In the BRAVE Study 79 girls with anorexia nervosa and 75 typically developing girls were included between May 2017 and October 2021. This period of time partially overlapped with the COVID-19 pandemic. 72% of the girls with anorexia nervosa and 88% of the typically developing girls also completed measurements at follow-up. The mean time between data collections points was 13 months. The groups were comparable in education level of their mothers, neurodevelopmental disorders, and ethnical background. The girls with anorexia nervosa were slightly younger than the typically developing girls. Conclusion The BRAVE Study aligns with one of the most important study priorities in the field of anorexia nervosa by examining (i) predictors of treatment response and (ii) investigating how symptoms with eating disorder symptoms track with changes in neurobiological, cognitive, behavorial and physical health functioning. Moreover, the study is innovative by its longitunal case control design, relatively large study sample and broad selection of measures.

Abstract PO3-05-03: Real-World Data on First-line Treatment of Hormone Receptor-positive, HER2-negative, Metastatic Breast Cancer in Brazil (BRAVE study - LACOG 0221)

Abstract Introduction: Endocrine therapy (ET) plus CDK 4/6 inhibitors is considered the standard of care as first-line therapy in hormone receptor positive (HR+)/HER2 negative (HER2-) metastatic breast cancer (mBC). Nonetheless, the use of chemotherapy (CT) is frequent in clinical practice, and access to CDK 4/6 inhibitors is limited in some countries. We used real-world data to describe treatment patterns, the impact of health insurance type, and outcomes among Brazilian patients with HR+/HER2- mBC treated in the first-line setting. Methods: In this observational retrospective study, female patients ≥ 18 years old diagnosed with de novo or recurrent HR+/HER2- mBC between January 2018 and December 2020 were included. Patients' data were extracted from medical charts or electronic health records (EHR). The primary endpoint was first-line treatment patterns in public and private health system cohorts. Key secondary endpoints were progression-free survival (PFS), defined as time from 1L treatment to progression or death, and overall survival (OS), defined as time from diagnosis of mBC until death or censoring. No formal statistical assumption was performed for sample size, the study recruited 2 cohorts of 150 patients from the public and 150 patients from the private health insurance system. Results: A total of 307 patients were included, 156 from public and 151 from private health insurance system, from 13 sites in Brazil. Median age was 56.8 (range 19.9-94.1), and 32.2% (N=99) had de novo MBC. Treatment patterns are described in Table 1. The most frequent treatment received in 1L was ET alone 42.4%, followed by CT (alone or CT followed by ET +- CDK4/6i) 31.6% and ET + CDK4/6i 25.1%. There was a significant difference between the 1L treatment with ET + CDK4/6i in the private and public systems, 48.3% vs 2.6%, p < .0001, respectively. The most frequently used CDK4/6i in 1L setting was Ribociclib (65.0%), followed by Palbociclib (36.9%) and Abemaciclib (7.1%). There was an increase in the use of CDK4/6i over time, 17% in 2018, 30.0% in 2019, and 27.9% in 2020. With a median follow-up of 32.2 months (95% CI: 29.4 - 34.4), the median 1L PFS was 22.9 months (95% CI: 16.9 - 25.2) in the public and 21.8 months (95% CI: 17.7 - 31.1) in the private health system, p=0.92. Median 1L PFS by treatment received was 13.6 months (95% CI: 6.1-39.0) with CT, 18.4 months (95% CI: 12.1-22.1) with CT followed by ET +-CDK4/6i, 21.9 months (95% CI: 17.3-25.5) with ET and 31.1 months with ET plus CDK 4/6i (95% CI: 15.8-42.8). Overall, median OS was 52.8 months (95%CI 49.4-NR). The 4-year OS rate per 1L treatment received were 50.3% (95% CI: 28.7-68.5) with CT, 39.0% (95% CI: 13.9-63.8) CT followed by ET +- CDK4/6i, 74.4% (95% CI: 58.0-85.1) with ET alone, 71.3% (95% CI: 49.6-85.0) ET + CDK4/6i, 50.3% (95% CI: 28.7-68.5) with CT and 39.0% (95% CI: 13.9-63.8) CT followed by ET +- CDK4/6i. Conclusion: ET is the most commonly used 1L treatment in clinical practice in Brazil, followed by ET + CDK4/6i and CT. A large difference in CDK4/6i use was observed between private and public health systems, reflecting the current limited access to CDK4/6i in Brazil. This study highlights treatment disparities within a nation with a fragmented health insurance system. Table 1. Treatment Patterns in Public and Private Healthcare Systems Citation Format: Gustavo Werutsky, Daniela Rosa, Tomás Reinert, Romualdo Barroso-Sousa, Heloísa Resende, Poliana Signorini, Eduardo Cronenberger, Juliana Góes Martins Fagundes, Jorge Henrique Santos Leal, Marina Dutra Giffoni, Aline Vieira, Luiza Nardin Weis, Jose Marcio Figueiredo, Tatiana Correa, Fernando Castilho Venero, Luisa Mostardeiro Tabajara Franche, Marina Musse Bernardes, Rafaela Jesus, Gustavo Gössling, José Bines. Real-World Data on First-line Treatment of Hormone Receptor-positive, HER2-negative, Metastatic Breast Cancer in Brazil (BRAVE study - LACOG 0221) [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO3-05-03.

Abstract OT3-07-01: Real-World Data on First-line Treatment of HR-positive, HER2-negative, Metastatic Breast Cancer in Brazil (BRAVE Study/LACOG 0221)

Abstract Background: It is estimated that 50 thousand patients live with metastatic breast cancer (MBC) in Brazil. A recent Brazilian registry (LACOG 0312) on MBC demonstrated a median overall survival (OS) by breast subtype of 15 months for triple negative, 23 months for HER2 positive, and 42 months for Luminal tumors, which are very similar to developed countries except the HER2 positive group which have limited access to targeted agents in the public health system. Recently, CDK 4/6 inhibitors were approved for the treatment of HR+ HER2-negative MBC with an improvement in progression-free survival (PFS) and ribociclib and abemaciclib demonstrating benefit in OS over endocrine therapy alone, establishing the standard of care in first-line setting for this BC subtype. In Brazil, disparities exist in the incorporation of novel anticancer agents between public and private health systems limiting treatment options for patients with HR+ HER2- negative MBC in the public system, which covers most of the population. The BRAVE study aims to describe the patient journey and current patterns of care for HR+ HER2-negative MBC to identify possible gaps and how health insurance type influences treatment patterns in Brazil. Trial Design: This is an observational, retrospective cohort study. All patients diagnosed with mBC (either de novo or recurrent) in the period of January 2018 to December 2020 at participating centers will be included. Data will be collected from medical records. No interventions are proposed. Enrollment of a total of 300 patients (150 patients from public health care system and 150 patients from private health care system) is planned. ClinicalTrials.gov identifier: NCT05034393. Eligibility: Inclusion criteria: women ≥18 years old; histologically confirmed HR-positive HER2-negative invasive breast cancer; HR-positive, defined as 1% to 100% of tumor nuclei positive for ER and/or PgR as per ASCO/CAP Guideline 2020 or Allred score of ≥3; HER2-negative, defined as IHC result is 0/1+ or 2+ with ISH negative as per ASCO/CAP Guideline 2018; diagnosed with de novo or recurrent metastatic breast cancer between January 2018 and December 2020. Exclusion criteria: male BC; first-line treatment for mBC received through clinical trial. Specific Aims: Primary objective is to describe the first-line (1L) treatment of HR-positive, HER2-negative mBC in Brazil. Secondary objectives are to describe progression-free survival (PFS) in the 1L setting until month 24; describe and compare the 1L treatment of HR-positive, HER2-negative mBC and PFS until month 24 according to the health care coverage (public vs. private); describe timelines from symptoms, histopathological diagnosis, molecular test, and treatment; describe the mBC pathological characterization; describe frequency of diagnostic tests to define breast cancer molecular subtypes; describe the subsequent line of treatment and corresponding PFS; describe overall survival (OS); evaluate PFS and OS according to visceral vs. non-visceral metastatic disease, primary endocrine resistance vs. acquired endocrine resistance, de novo versus recurrent disease, public vs. private health system and pre vs postmenopausal status. Statistical Methods: No a priori sample size calculation was performed. The expected sample size of 150 patients in each group allows description of the proportion of patients using CDK 4/6 inhibitors with two-sided 90% confidence interval ranging from 53.4% to 66.6% when the expected proportion is 60% in the private health system. Present Accrual and Target Accrual: A total of 12 sites of 14 planned were activated. The first patient was enrolled on February 8, 2022. As of June 24, 2022, a total of 122 patients were enrolled, 86 from public and 36 from private health system. The target accrual of 300 patients is expected to be completed by November 2022. Results are expected to be presented by April 2023. Funding: Novartis. Acknowledgements: SAS. Citation Format: Gustavo Werutsky, Tomás Reinert, Daniela D. Rosa, Romualdo Barroso-Sousa, Heloísa Resende, Poliana A. Signorini, Juliana G. Martins Fagundes, Jose Marcio B. Figueiredo, Eduardo Cronemberger, Aline C. Vieira, Jorge Henrique Santos Leal, Luiza Nardin Weis, Ludmila Thommen, Rafaela G. Jesus, Gustavo Gössling, José Bines. Real-World Data on First-line Treatment of HR-positive, HER2-negative, Metastatic Breast Cancer in Brazil (BRAVE Study/LACOG 0221) [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr OT3-07-01.

The Brave study: promoting active breaks in secondary school from students’ point of view

Abstract Background According to the WHO recommendations, children and adolescents should perform at least 60 minutes per day of moderate to vigorous physical activity (PA). Active Breaks (ABs) interventions, short physical activity breaks of 5-15 minutes during school hours, have been examined in primary school children as a potential strategy to counteract a sedentary lifestyle, with minimal disruption to school learning activities. The aim of the BRAVE STUDY is to investigate the feasibility of ABs in a secondary school setting from the students’ point of view. Methods In December 2020, 10 students (age 12-13, 6 females and 4 males) attending the second and third grade of secondary schools located in Bologna province (Italy) were involved in a focus group (FG). The FG was conducted online because of COVID-19 and the answers transcribed for a later analysis. Students’ opinions were probed on the role of PA in school and possible facilitators/barriers to implementation of ABs in the school. Results Students reported they wanted to be more active as a consequence of time spent in class sitting at a desk. Students also reported that an organized activity like ABs conducted in the classroom setting provides an excellent opportunity to improve social relations with classmates. Students also highlighted the possible psycho-physical well-being benefits arising from PA. Among the potentially negative aspects reported, students underlined the possible confusion that would be created in classroom and the time subtracted from academic learning activities. Conclusions The FG represents an ideal mean to obtain in-depth information on how people feel about a pending program or a change in their routine. The current FG reinforces positive outcomes from exposure to a PA program that can be intertwined with their daily classroom activities. ABs programs can help to reconcile the needs of students that arise during the day with the PA objectives recommended by the WHO. Key messages • ABs can be a zero-cost intervention strategy to achieve WHO recommendations and would create conditions for a greater psycho-physical benefits in classrooms. • A qualitative approach, such as FGs, provides a mean to collect information not obtainable with quantitative methods, that could be useful to co-design interventions for children and adolescents.

Potential association between working memory and physical fitness status: the BRAVE study

Abstract Introduction The World Health Organization launched a global action plan targeted to obtain a 15% relative reduction in the global prevalence of physical inactivity in adolescents by 2030 also promoting school-based PA interventions and programs in school. Active Breaks (ABs) are a school-based intervention consisting of short bursts (5-15 minutes) of Pa led by teachers or peer. Many researches investigated the implementation of ABs into primary school setting as a strategy to reduce sedentary behaviour, improve cognitive and physical function. However, this kind of intervention has not extended to secondary school, especially in Italian context. For this reason we started the BRAVE study to evaluate the potential effect of implementing ABs in secondary school. The study is currently in the administration phase of ABs to adolescents The preliminary analysis aims to underline a potential association between working memory performance (WM) and physical fitness status among secondary school students at baseline. Methods In March 2022 we conducted baseline assessment in a secondary school in Valsamoggia (Bologna, Italy). Working memory was evaluated using backward digit span while physical fitness status was assessed using three different fitness test: standing long-jump (SLJ), six minute Cooper Test (6MCT) and Shuttle run test (SR). Results A total of n = 125 adolescent, mean age 12.79±0.89, were enrolled in the study. After performing a regression analysis we found that WM is significantly associated only with age of student (b = 0.2, 95%CI 0.25, 0.11 p = 0.02). A trend also emerged between WM performance and SLJ but with no statistically significant differences (b = 0.160, 95%CI 0.03, 0.02, p = 0.09). The 6MCT and HT have no relevant associations with WM score. Conclusions These preliminary results suggest that age is associated with cognitive performance but no positive association were found between WM score and physical fitness status excepted for a small trend with SLJ test. Key messages • Age is related to WM in adolescent students. • ABs interventions could represent a valid strategy to encourage movement, improve cognitive and physical fitness performance.

Designing active breaks in secondary school, results from focus group with teachers: the brave study

Abstract Background Many adolescents are unable to accomplish the daily 60 minutes of moderate to vigorous physical activity (PA) recommended by WHO. Secondary school is a critical period for developing healthy habits and PA interventions have the potential to promote healthy development. Active Breaks (ABs) are a school-based intervention consisting of short bursts (5-15 minutes) of PA made part of the academic routine. Primary school has been ABs main setting, while secondary school interventions received less attention. The aim of the BRAVE Study is to investigate teachers’ opinion about the feasibility of ABs in Italian secondary school. Methods In November 2020 20 teachers from two secondary schools located in Bologna province (Italy) were enrolled in two focus groups (FGs). FGs were held online, recorded, and transcribed. Questions were asked about the role of PA in the school routine and related experiences, perceived barriers and facilitators of the intervention, suggestions regarding the intervention design. Final expectations were then discussed. Results Despite limited experience with PA interventions, participants felt ABs would improve psycho-physical well-being for both students and teachers. Lack of time and space and a wary attitude towards ABs were listed as barriers. Program flexibility regarding content, administration time frames and implementation mode was listed as a great facilitator: program should be adaptable to participants’ needs, favoring easy and quick exercises. Overall, expectations emphasized improving classroom behavior and promoting healthy habits. Conclusions Teachers felt that inclusion of ABs in secondary school was promising and could lead to many health benefits. ABs were deemed feasible given their short duration and adaptability, since the program can be implemented with current personnel resources and space configurations. Co-design is essential to overcome personal barriers and create an effective and sustainable intervention. Key messages • According to secondary school teachers, PA interventions have the potential to improve psycho-physical well-being and classroom environment, promoting healthy habits among students. • ABs are deemed as a feasible and sustainable PA intervention thanks to program flexibility regarding contents, administration time frames and implementation mode.

Prognostic value of TARC and quantitative PET parameters in relapsed or refractory Hodgkin lymphoma patients treated with brentuximab vedotin and DHAP.

Risk-stratified treatment strategies have the potential to increase survival and lower toxicity in relapsed/refractory classical Hodgkin lymphoma (R/R cHL) patients. This study investigated the prognostic value of serum (s)TARC, vitamin D and lactate dehydrogenase (LDH), TARC immunohistochemistry and quantitative PET parameters in 65 R/R cHL patients who were treated with brentuximab vedotin (BV) and DHAP followed by autologous stem-cell transplantation (ASCT) within the Transplant BRaVE study (NCT02280993). At a median follow-up of 40 months, the 3-year progression free survival (PFS) was 77% (95% CI: 67-88%) and the overall survival was 95% (90-100%). Significant adverse prognostic markers for progression were weak/negative TARC staining of Hodgkin Reed-Sternberg cells in the baseline biopsy, and a high standard uptake value (SUV)mean or SUVpeak on the baseline PET scan. After one cycle of BV-DHAP, sTARC levels were strongly associated with the risk of progression using a cutoff of 500 pg/ml. On the pre-ASCT PET scan, SUVpeak was highly prognostic for progression post-ASCT. Vitamin D, LDH and metabolic tumor volume had low prognostic value. In conclusion, we established the prognostic impact of sTARC, TARC staining, and quantitative PET parameters for R/R cHL, allowing the use of these parameters in prospective risk-stratified clinical trials. Trial registration: NCT02280993.

Bilateral verses bilateral with tri-segmental endoscopic drainage using metal stents for high-grade malignant hilar biliary obstructions: A multicenter, randomized controlled trial: BRAVE study (BRAVE study).

Introduction:Bilateral endoscopic drainage with self-expanding metallic stent (SEMS) can be used to manage hilar malignant biliary obstruction (HMBO) more effectively in comparison to unilateral drainage. An increased drainage area is predicted to prolong stent patency and patient survival. However, few reports have described the utility of trisegmental drainage and the benefits of using trisegmental drainage remain unknown. Thus, we launched a randomized clinical trial (RCT) to compare the clinical outcomes between bilateral and trisegmental drainage using SEMSs in patients with high-grade HMBO.Methods and analysis:This study was conducted as a multicenter randomized control trial (RCT) in 8 high-volume medical centers in Japan, and will prove the non-inferiority of bilateral drainage to trisegmental drainage. Patients with unresectable HMBO with Bismuth type IIIa or IV who pass the inclusion and exclusion criteria will be randomized to receive bilateral or trisegmental drainage at a 1:1 ratio. At each center, the on-site study investigators will obtain informed consent from the candidates, and will use an electronic data capture system (REDCap) to input necessary information, and register candidates with the registration secretariat. The primary endpoint is the rate of non-recurrent biliary obstruction (RBO) at 180 days after SEMSs placement. A −10% non-inferiority margin is assumed in the statistical analysis of the primary endpoint. Secondary endpoints include the rate of technical and clinical success, time to recurrent biliary obstruction (TRBO), causes of RBO, procedure-related adverse events (AEs), procedure time, TRBO with or without endoscopic sphincterotomy, overall survival, and the technical and clinical success rates at reintervention.Discussion:If the non-inferiority of bilateral drainage is demonstrated, it is predicted that the procedure time will be shortened and the medical cost will be reduced, which will be beneficial to the patient and the medical economy.Trial registration:Registered in Japan Registry of Clinical Trial-Registration (trial number. jRCTs062220038). This version number 1. Protocol dated Jun 23, 2022.

POSITIVE ENVISIA GENOMIC CLASSIFIER RESULT PREDICTS CLINICAL PROGRESSION IN FIBROTIC INTERSTITIAL LUNG DISEASE

POSITIVE ENVISIA GENOMIC CLASSIFIER RESULT PREDICTS CLINICAL PROGRESSION IN FIBROTIC INTERSTITIAL LUNG DISEASE

Brentuximab Vedotin versus checkpoint inhibitors: Which one? When? Why should be preferred?

About 15% of classical Hodgkin lymphoma (cHL) patients remain refractory to first-line therapy and about one third of the responding patients relapse1. The standard of care for relapsed or refractory (R/R) cHL is salvage chemotherapy followed by high-dose chemotherapy (HDCT) and autologous stem cell transplantation (ASCT)2. Three novel agents effective in R/R cHL were introduced; brentuximab-vedotin (BV), anti-CD30 antibody-drug conjugate3 and the programmed-death-1 (PD-1) blocking antibodies, nivolumab and pembrolizumab4, 5 has been approved. The optimal line to incorporate these agents is an actual dilemma. BV and PD1-blockers are effective in R/R cHL after ASCT. KEYNOTE-204 study reported that pembrolizumab treatment was associated with significantly longer PFS compared with BV (median:13.2 vs 8.3 months)6. In case of durable responses with PD1-blockers, cessation of the treatment may be an individualized decision and high response rates to re-treatment with PD1-blockers is an important advantage7. There is not obvious differences in the efficacy and toxicity of nivolumab and pembrolizumab8. We can conclude that PD1-blockers could be preferred over BV in patients who relapse following ASCT and who are naïve to BV and PD-1 blockade. For patients relapsing after ASCT with prior BV or PD1-blocker exposure, selection of the agent that has not been used previously could be recommended8. BV and PD1-blockers are incorporated into the pre-ASCT salvage regimens in clinical trials. In the phase II BRaVE study, BV added to DHAP provided a complete metabolic response rate of 81% before ASCT, with a 2-year PFS and OS rates of 74% and 95%, respectively9. Similarly, pembrolizumab in combination with GVD provided an overall response rate (ORR) of 100%10. BV and nivolumab combination resulted in an ORR of 85%. The 3-year PFS rate for ASCT group was 91%11. Regarding these data, the need for ASCT will be an important point of debate in the next years. In case of primary refractory disease, chemotherapy-based salvage regimens remain the standard. Combination treatment with BV and nivolumab resulted in a 21-month PFS of 65% in this group11, which may be a satisfactory option in the future. Post-ASCT consolidation with BV is now standard of care in patients with risk factors defined by AETHERA trial12, which is supported by real-world data including pre-treated with and responsive to BV patients13. Novel agents are not recommended in the front-line management of early-stage disease. ECHELON-1 study performed on treatment-naïve stage III/IV cHL patients reported 6-year PFS, and OS ratio were 82.3% and 93.9% for BV-AVD cohort versus 74.5% and 89.4% for ABVD cohort14. Beside advanced stage cases, BV-based therapies should be considered for elderly, unfit patients who cannot tolerate combination chemotherapies, as they are associated with longer duration of response compared to BV monotherapy8. Giving decision about novel therapies, major adverse events, such as neuropathy for BV and immune related events for PD1-blockers. Optimal timing of BV and PD1-blockers and treatment strategies in case of resistance to novel agents are critical questions for the future of cHL management, which hopefully will be answered by the results of clinical trials and real-world data.

Differences in Barriers to Healthcare and Discrimination in Healthcare Settings Among Undocumented Immigrants by Deferred Action for Childhood Arrivals (DACA) Status

Undocumented immigrants face barriers to and discrimination in healthcare, but those with Deferred Action for Childhood Arrivals (DACA) status may fare better. This analysis uses the cross-sectional BRAVE Study of young undocumented Latinx and Asian immigrants to examine differences in barriers to and discrimination in healthcare by DACA status. A majority of respondents experienced financial, language, and cultural barriers, and up to half experienced documentation status barriers, discrimination when seeking healthcare or by a health provider, and negative experiences related to documentation status. In multivariable analyses, DACA recipients have over 90% lower odds of language and cultural barriers, approximately 80% lower odds of discrimination when seeking healthcare and by a health provider, and approximately 70% lower odds of documentation status barriers and negative experience related to documentation status compared to nonrecipients. These findings indicate that DACA recipients experience fewer barriers to healthcare and discrimination in healthcare compared to nonrecipients.

Text Messaging Intervention for Mental Wellness in American Indian and Alaska Native Teens and Young Adults (BRAVE Study): Analysis of User Engagement Patterns.

BackgroundMany American Indian and Alaska Native (AI/AN or Native) communities express concern about high rates of suicide and poor mental health. Technology-based health interventions that nurture resilience, coping skills, connectedness, and help-seeking skills may be an effective strategy for promoting health and wellbeing among AI/AN youth. The Northwest Portland Area Indian Health Board designed the BRAVE intervention for AI/AN youth. BRAVE is delivered via SMS text messaging and includes role model videos, mental wellness strategies, links to culturally relevant resources, and social support from family and friends.ObjectiveThe aim of this study is to explore system data from the BRAVE intervention to determine patterns of user engagement and differences in psychosocial outcomes based on the number of clicks on BRAVE content.MethodsThe BRAVE study included 1030 AI/AN teens and young adults nationwide (15 to 24 years old). The message series in the BRAVE and STEM study arms included 3 to 5 SMS text messages per week, featuring 1 role model video and 1 image per week. Messages were sent out via Mobile Commons (Upland Software Inc), a mobile messaging provider that supports text, picture, and video SMS.ResultsOf the 509 participants in the original BRAVE analysis, 270 had sufficient data to analyze user engagement, with at least 1 trackable click on a study SMS text message. Of the 270, 184 (68.1%) were female, 50 (18.5%) were male, and 36 (13.3%) selected another gender category. The average participant was 20.6 years old, with a minimum and maximum age of 15 and 26 years. Most participants had relatively low engagement measured by the number of clicks (median 2; mean 3.4), although others clicked message content as many as 49 times. Users engaged most frequently with the YouTube-based content (viewing 1 of 7 role model videos), with 64.8% (175/270) of total clicks coming from the role model videos, and earlier episodes receiving the highest number of clicks. Most baseline psychosocial measures were not significantly associated with the number of links clicked. However, help-seeking behavior was highly significant (P<.001), with a rate ratio of 0.82 (0.73, 0.92), indicating that each 1-unit increase in help-seeking score at baseline was associated with an 18% decrease in the expected number of study content clicks.ConclusionsThis is the first study to set initial standards for assessing user engagement in an mHealth intervention. Our work underscores the feasibility of exploring the impact of engagement on intended outcomes, allowing for more precise exploration of the dose-response relationship that may be realized through these low-touch interventions that offer promising potential for reaching high numbers of program participants.Trial RegistrationClinicalTrials.gov NCT04979481; https://clinicaltrials.gov/ct2/show/NCT04979481

Radiofrequency ablation in Brugada syndrome.

Radiofrequency ablation in Brugada syndrome.

Comment on "Combining brentuximab vedotin with dexamethasone, high-dose cytarabine and cisplatin as salvage treatment in relapsed or refractory Hodgkin lymphoma: the phase II HOVON/LLPC Transplant BRaVE study."

Comment on "Combining brentuximab vedotin with dexamethasone, high-dose cytarabine and cisplatin as salvage treatment in relapsed or refractory Hodgkin lymphoma: the phase II HOVON/LLPC Transplant BRaVE study."

The BRAVE Study: Formative Research to Design a Multimedia Intervention for American Indian and Alaska Native Young Adults.

American Indian and Alaska Native (AI/AN) young adults are strong and resilient. Interventions designed to improve their mental health and help-seeking skills are especially needed, particularly those that include culturally relevant resources and relatable role models. This paper presents formative research from the BRAVE study, a five-year community based participatory research project led by the Northwest Portland Area Indian Health Board. Formative research included three phases and more than 38 AI/AN young adults and content experts from across the United States. Results indicate that behavioral interventions can be feasibly delivered via text message to AI/AN young adults and that including Native youth in the formative research is critical to designing a comprehensive, culturally-responsive intervention. Lessons learned from this five-year process may help other youth-serving organizations, prevention programs, policymakers, researchers, and educators as they support the next generation of AI/AN leaders.

Recruiting and Engaging American Indian and Alaska Native Teens and Young Adults in a SMS Help-Seeking Intervention: Lessons Learned from the BRAVE Study.

This paper shares lessons learned recruiting and engaging participants in the BRAVE study, a randomized controlled trial carried out by the Northwest Portland Area Indian Health Board and the mHealth Impact Lab. The team recruited 2330 American Indian/Alaska Native (AI/AN) teens and young adults nationwide (15–24 years old) via social media channels and text message and enrolled 1030 to participate in the 9 month study. Teens and young adults who enrolled in this study received either: 8 weeks of BRAVE text messages designed to improve mental health, help-seeking skills, and promote cultural pride and resilience; or 8 weeks of Science Technology Engineering and Math (STEM) text messages, designed to elevate and re-affirm Native voices in science, technology, engineering, math and medicine; and then received the other set of messages. Results indicate that social media channels like Facebook and Instagram can be used to recruit AI/AN teens and young adults. Retention in this study was high, with 87% of participants completing both the BRAVE and STEM intervention arms. Lessons learned from this process may help teen and young adult-serving organizations, prevention programs, policy makers, researchers, and educators as they support the next generation of AI/AN change makers.

The effects of brain-friendly diet on cognitive performance (Brave study)

AbstractIntroduction:Cognitive performance is related to lipid and glucose metabolism and metabolic activation that are regulated by diet. The Brave study has shown beneficial effects of brain-friendly diet (Brainfood) on metabolic health in office workers with elevated metabolic risk. We further examined the effects of Brainfood on cognitive performance.Materials and methods:We conducted a diet-switch, 4-week intervention study on 84 volunteers with elevated plasma LDL levels in pre-screening. During the control period participants continued their habitual eating pattern and were offered an optional lunch following western-type diet, and they did not receive nutritional guidance. In Brainfood period, lunch, snack and breakfast offering was optimised for the quality of carbohydrates and fat and the intake of salt and protein. Educated nutritionist instructed the participants to follow the Brainfood diet and regular meal pattern.Participants kept a 3-day food record at the end of control and Brainfood periods. For each participant, we calculated the Brainfood ratio comparing the total frequencies of consumption of brain-friendly and brain-unfriendly foods. We ranked the subjects also according to the change in brain-friendly nutrient intake (saturated fat, polyunsaturated fat, fibre, sugar and salt) from control to Brainfood period.Cognitive performance (cognitive control and flexibility, attention, inhibition, learning, and memory) were measured with a combination of traditional standardized neuropsychological tests (Bourdon-Wiersma double task, Stroop Colour and Word Test, WMS-III: Letter-Number Sequencing, Rey Auditory Verbal Learning Test) and modern computer and mobile tests (Flexible Attention Test FAT, N-Back task and Task-switching task) before and after the Brainfood diet. In addition, participants evaluated their vigilance, task load and performance after each test with the Karolinska Sleepiness Scale (KSS) and NASA Task Load Index (NASA-TLX).We compared the change in cognitive performance before and after Brainfood diet between the subgroups with the highest and lowest Brainfood ratio and the highest and lowest brain-friendly nutrient intake using repeated measures analysis of variance.Results:Brainfood diet reduced intakes of saturated fat and salt, and increased intakes of polyunsaturated fat, fibre, vitamin C and D, iron and magnesium (p &lt; 0,03). Participants with the highest Brainfood ratio improved reaction time (FAT; p-value for interaction 0,01, multiple comparison correction not applied), switch cost (Task-switching; p = 0,02) and inhibition tendency (Stroop; p = 0,047). Better dietary fat quality decreased self-reported physical strain (NASA-TLX; p-values &lt; 0,007), and higher fibre intake decreased self-reported sleepiness (KSS; p = 0,033).Discussion:Brainfood diet may positively affect cognitive performance in office workers with elevated metabolic risk.

The effects of a brain-friendly diet on metabolic and physiological parameters and cognitive performance (Brave study)

AbstractCognitive performance is related to lipid and glucose metabolism and metabolic activation that are regulated by diet. Further, there is good evidence to support that change in lifestyle, for instance in diet, may promote cognitive health. However, vast majority of the existing studies have focused on children or older adults. We studied the effects of a brain-friendly diet (Brainfood) on metabolic and physiological parameters and cognitive performance in office workers at assumed metabolic risk. We conducted a diet-switch, 4-week intervention study on 84 volunteers with elevated plasma LDL levels in pre-screening. The brainfood diet was planned to be optimal for metabolism and cognitive function; special attention was paid for regular meal frequency, a well-balanced light lunch at work and optimised recipes ensuring quality of carbohydrates and fat, and sufficient protein amount. The control diet was a typical western diet. Breakfast supplies, lunch and afternoon snacks were provided to participants, and they received nutritional counselling. Participants' sociodemographic characteristics, such as age and sex, were queried in the beginning of the intervention. Plasma samples were collected at the end of the 2-week lead-in period, and control and intervention periods. The samples were analysed using high-throughput nuclear magnetic resonance (NMR) spectrometry for quantification of lipoprotein subclasses and particle sizes, cholesterol, glycerides, phospholipids, apolipoproteins, fatty acids, amino acids, ketone bodies, fluid balance, glycolysis and inflammation markers. Participants completed a 3-day food diary at the end of the 2-week lead-in period, and control and intervention periods. Anthropometric measurements (height and weight) were measured at the same timepoints by a study nurse. Physical activity was instructed to be maintained at the pre-study level during the whole study period and it was monitored by using a 3-axial accelerometer (Active style Pro HJA, Omron, Japan). Cognition was measured with standardized neuropsychological tests (Bourdon-Wiersma, FAT, N-Back, NASA-TLX, KSS, RAVLT, Stroop, WMS-III, task-switching) under a psychologist's supervision and as tablet, PC or online tests. Brainfood reduced saturated fat and salt intakes and increased polyunsaturated fat, fibre, vitamin C and D, iron and magnesium intakes. Favourable effects were seen in the atherogenic lipid measurements, such as fatty acids, LDL, IDL and small VLDL, as well as fatty acids, phospholipids and glutamine. Intervention did not affect the physiological or cognitive parameters except for a decrease in inaccuracy of visual attention (p = 0.027). In conclusion, the Brainfood diet could be recommended for office workers as a healthy diet following Nordic nutrition recommendations.

Biomarker testing for personalized, first-line therapy in advanced nonsquamous non-small cell lung cancer patients in the real world setting in Japan: a retrospective, multicenter, observational study (the BRAVE study).

Background:Molecular diagnostic testing is necessary to guide optimal first-line treatment. The number of patients who receive first-line treatment based on biomarker analysis in Japan is unknown. We aimed to determine the proportion of nonsquamous non-small cell lung cancer (NSCLC) patients for whom first-line treatment was selected based on biomarker testing.Methods:This retrospective, multicenter, observational study registered patients aged ⩾20 years with locally advanced or metastatic nonsquamous NSCLC who started first-line treatment between August and December 2017 in Japan. Data were collected from medical records between January and May 2018. The primary endpoint was the proportion of patients with confirmed biomarker status for first-line treatment decision.Results:Among 202 patients enrolled from 11 centers, 161 (79.7%; 95% confidence interval, 74.2–85.2%) had confirmed biomarker status. The testing rate was highest for epidermal growth factor receptor (EGFR; 97.5%), followed by anaplastic lymphoma kinase (ALK; 88.1%), programmed death ligand-1 (PD-L1; 87.1%), and ROS1 (67.3%). For first-line treatment, 70/75 patients with EGFR-positive tumors were administered an EGFR-TKI; 14/15 patients with ALK-positive tumors received an ALK inhibitor; 2/2 patients with ROS1-positive tumors received a ROS1 inhibitor; and 29/36 driver mutation-negative patients with a PD-L1 tumor proportion score ⩾50% were administered an anti-PD-1 monoclonal antibody. Median times from confirmed diagnosis date to first-line treatment initiation, and from first biomarker test order to last biomarker test result were 19 and 11 days, respectively.Conclusions:The proportion of nonsquamous NSCLC patients with confirmed biomarker status for first-line treatment was considered insufficient and in need of improvement.