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Background: Combining anti-VEGF/Ang2 and anti-PD-1 therapy promotes an immunopermissive state, supportive of T-cell-mediated tumour cell destruction. This phase Ib study is assessing BI 836880 plus ezabenlimab in patients (pts) with advanced solid tumours. In Part 1 (dose escalation in pts with advanced NSCLC), the recommended phase 2 dose (RP2D) was determined as BI 836880 720 mg + ezabenlimab 240 mg IV q3w. Here, we report updated results, including data from Part 2 (expansion cohorts). Methods: Part 2 has 7 cohorts: metastatic (m) NSCLC after checkpoint inhibitor (CPI) monotherapy (Cohort A);mNSCLC after chemotherapy (CT) + CPI (Cohort B);mSCLC after CT ± CPI (Cohort C);recurrent GBM (1st and 2nd recurrence;Cohort D);immunotherapy-resistant m-melanoma (Cohort E);HCC after prior sorafenib or lenvatinib (Cohort F);and previously untreated unresectable HCC (Cohort G). Primary endpoint is objective response rate (complete response [CR] + partial response [PR]). Results: As of March 2021, 215 pts have been treated (Part 1: 14, Part 2: 201 [Cohort A, 35;B, 32;C, 19;D, 31;E, 32;F, 29;G, 23];70% male, median age 62 yrs). Any and ≥G3 AEs (any-cause) were reported in 183 (85%) and 72 (33%) pts. 118 (55%) pts had drug-related AEs, most commonly asthenia (13%) and hypertension (12%). 7 pts had G4 AEs (non-related hyperkalaemia + cardiac arrest, laryngospasm, gastrointestinal perforation;drug-related anaphylactic reaction, cholestatic hepatitis, acute pancreatitis, increased transaminases);9 pts had G5 AEs (non-related COVID-19 pneumonia, epilepsy, intracranial haemorrhage, cardio-respiratory arrest, haemoptysis, hepatic failure, general physical health deterioration, Glasgow coma scale abnormal + shortness of breath;drug-related tracheal haemorrhage). 35 (16%) pts had immune-related AEs and 15 (7%) had AEs leading to discontinuation. 179 pts were evaluable for response: 1 had confirmed CR (Cohort F), 22 had PR (Part 1: 2;Part 2: 20 [Cohort A, 4;C, 5;D, 4;E, 3;F, 3;G, 1]) and 110 had stable disease. 106 pts remain on treatment. Conclusions: BI 836880 plus ezabenlimab had a manageable safety profile, with preliminary activity in a range of tumour types. Clinical trial identification: NCT03468426. Editorial acknowledgement: Medical writing support for the development of this manuscript, under the direction of the authors, was provided by Hannah Simmons MSc, of Ashfield MedComms, an Ashfield Health company, and funded by Boehringer Ingelheim. Legal entity responsible for the study: Boehringer Ingelheim. Funding: Boehringer Ingelheim. Disclosure: N. Girard: Financial Interests, Personal, Advisory Role: Roche, Eli Lilly, Boehringer Ingelheim, AstraZeneca, Novartis, Pfizer, BMS, MSD, Takeda, GSK, AbbVie, Pharmamar, Janssen, Sanofi;Financial Interests, Personal, Funding, Travel/accommodation/expenses: Roche, AstraZeneca, BMS MSD Oncology;Financial Interests, Institutional, Research Grant: Roche, AstraZeneca, Boehringer Ingelheim. M. Wermke: Financial Interests, Personal, Advisory Role: MSD, Novartis, Kite, Heidelberg Pharma, Roche, Boehringer Ingelheim;Financial Interests, Personal, Other, Honoraria: BMS, Merck, Roche, Novartis, Kite, Boehringer Ingelheim, AstraZeneca;Financial Interests, Personal, Funding, Travel/Accommodation/Expenses: Glenmark, BMS, AstraZeneca. E. Ledin: Financial Interests, Personal and Institutional, Research Grant: Boehringer Ingelheim. D. Kim: Financial Interests, Personal, Advisory Role: Health Insurance Review & Assessment Service, Korea;Financial Interests, Personal, Invited Speaker: Korean Association for Lung Cancer, Korean Cancer Association, Korean Society of Medical Oncology, Taiwan Lung Cancer Society;Financial Interests, Institutional, Principal Investigator, Clinical Trial Funding: Alpha Biopharma, Amgen, AstraZeneca/Medimmune, Boehringer-Ingelheim, Bridge BioTherapeutics, Chong Keun Dang, Daiich-Sankyo, GSK, Hanmi, Janssen, Merus, MIrati Therapeutics, MSD, Novartis, ONO Pharmaceutical, Pfizer, Roche/Genentech, Takeda, TP Therapeuti;Non-Financial Interests, Person l, Advisory Role: Amgen, AstraZeneca, BMS / ONO Pharmaceuticals, Daiich-Sankyo, GSK, Janssen, Pfizer, SK Biopharm, Takeda, Yuhan;Non-Financial Interests, Personal, Member of the Board of Directors: Asian Thoracic Oncology Research Group, Korean Association for Lung Cancer, Korean Cancer Association, Korean Society of Medical Oncology;Other, Personal, Funding, Travel support for advisory board meeting attendance: Amgen, Daiichi-Sankyo. J. Bennouna: Financial Interests, Personal, Other, Honoraria: Bristol Myers Squibb, MSD, AstraZeneca, Roche, Servier, Bayer, AMGEN;Financial Interests, Personal, Advisory Role: Bristol Myers Squibb, MSD, AstraZeneca, Roche;Financial Interests, Institutional, Research Grant: AstraZeneca. T. Lesimple: Financial Interests, Personal, Advisory Role: MSD, Novartis, BMS, Pierre Fabre;Financial Interests, Personal, Speaker’s Bureau: MSD, Novartis;Financial Interests, Institutional, Research Grant: Roche. E. Felip: Financial Interests, Personal, Advisory Board: Amgen;Financial Interests, Personal, Advisory Board: AstraZeneca;Financial Interests, Personal, Advisory Board: BAYER;Financial Interests, Personal, Advisory Board: Beigene;Financial Interests, Personal, Advisory Board: Boehringer-Ingelheim;Financial Interests, Personal, Advisory Board: Bristol-Myers Squibb;Financial Interests, Personal, Advisory Board: Eli Lilly;Financial Interests, Personal, Advisory Board: F. Hoffman-La Roche;Financial Interests, Personal, Advisory Board: Glaxo Smith Kline;Financial Interests, Personal, Advisory Board: Janssen;Financial Interests, Personal, Advisory Board: Medical Trends;Financial Interests, Personal, Advisory Board: Merck Sharp & Dohme;Financial Interests, Personal, Advisory Board: Merck Serono;Financial Interests, Personal, Advisory Board: Peptomyc;Financial Interests, Personal, Advisory Board: Pfizer;Financial Interests, Personal, Advisory Board: Puma;Financial Interests, Personal, Advisory Board: Regeneron;Financial Interests, Personal, Advisory Board: Sanofi;Financial Interests, Personal, Advisory Board: Syneos Health;Financial Interests, Personal, Advisory Board: Takeda;Financial Interests, Personal, Speaker’s Bureau: Amgen;Financial Interests, Personal, Speaker’s Bureau: AstraZeneca;Financial Interests, Personal, Speaker’s Bureau: Bristol-Myers Squibb;Financial Interests, Personal, Speaker’s Bureau: Eli Lilly;Financial Interests, Personal, Speaker’s Bureau: F. Hoffmann-La Roche;Financial Interests, Personal, Speaker’s Bureau: Janssen;Financial Interests, Personal, Speaker’s Bureau: Medscape;Financial Interests, Personal, Speaker’s Bureau: Merck Sharp & Dohme;Financial Interests, Personal, Speaker’s Bureau: Merck Serono;Financial Interests, Personal, Speaker’s Bureau: Peervoice;Financial Interests, Personal, Speaker’s Bureau: Pfizer;Financial Interests, Personal, Speaker’s Bureau: Springer;Financial Interests, Personal, Speaker’s Bureau: Touch Medical;Financial Interests, Personal, Member, Independent Member of the Board: Grifols. D. Berz: Financial Interests, Personal, Other, Honoraria: Oncocyte;Other, Personal, Other, Honoraria: Sun Pharma;Other, Personal, Other, Honoraria: Caris;Other, Personal, Other, Honoraria: Takeda;Other, Personal, Other, Honoraria: Natera;Other, Personal, Other, Honoraria: Jazz Pharma;Other, Personal, Other, Honoraria: Genentech;Financial Interests, Personal, Advisory Role: Oncocyte;Other, Personal, Advisory Role: Sun Pharma;Other, Personal, Advisory Role: Biocept;Other, Personal, Advisory Role: Prelude;Financial Interests, Personal, Speaker’s Bureau: Oncocyte;Other, Personal, Speaker’s Bureau: Caris;Other, Personal, Speaker’s Bureau: Sun Pharma;Other, Personal, Speaker’s Bureau: AstraZeneca;Other, Personal, Speaker’s Bureau: Takeda;Other, Personal, Speaker’s Bureau: Merck;Other, Personal, Speaker’s Bureau: Natera;Other, Personal, Speaker’s Bureau: Jazz Pharma. C. Mascaux: Financial Interests, Personal, Advisory Role: Roche;Financial Interests, Personal, Advisory Role: Astr Zeneca;Financial Interests, Personal, Advisory Role: Kephren;Financial Interests, Personal, Advisory Role: Bristol-Myers Squibb;Financial Interests, Personal, Advisory Role: MSD;Financial Interests, Personal, Advisory Role: Pfizer;Financial Interests, Personal, Other, Honoraria: Roche;Financial Interests, Personal, Other, Honoraria: AstraZeneca;Financial Interests, Personal, Other, Honoraria: Kephren;Financial Interests, Personal, Other, Honoraria: Bristol-Myers Squibb;Financial Interests, Personal, Other, Honoraria: MSD;Financial Interests, Personal, Other, Honoraria: Pfizer;Financial Interests, Personal, Other, travel, accommodations, expenses: Roche;Financial Interests, Personal, Other, travel, accommodations, expenses: AstraZeneca;Financial Interests, Personal, Other, travel, accommodations, expenses: Boehringer Ingelheim;Financial Interests, Personal, Other, travel, accommodations, expenses: Takeda. M. Voskoboynik: Financial Interests, Personal, Advisory Role: AstraZeneca. H.T. Landsteiner: Financial Interests, Personal, Full or part-time Employment: Boehringer Ingelheim. V. Chen: Financial Interests, Personal, Full or part-time Employment: Boehringer Ingelheim. G. Jayadeva: Financial Interests, Personal, Full or part-time Employment: Boehringer Ingelheim. J. Alt: Financial Interests, Personal, Other, Honoraria: AstraZeneca, Boehringer Ingelheim, BMS, Pfizer, Roche, Takeda;Financial Interests, Personal, Advisory Role: AstraZeneca, Boehringer Ingelheim, BMS, Roche;Financial Interests, Personal, Funding, Travel/accommodation/expenses: AstraZeneca, Boehringer Ingelheim, BMS. B. Hackanson: Financial Interests, Personal, Advisory Role: Boehringer Ingelheim, MSD, AstraZeneca, BMS. All other authors have declared no conflicts of interest.

OBJECTIVES: Current approved health claims in Canada, US and Europe recognize the ability of oat ß-glucan to lower blood cholesterol; however, its ability to improve glycemic control is less certain. We undertook a systematic review and meta-analysis of randomized controlled trials to update the evidence of the effect of oats and oat-fiber on markers of glycemic control in people with and without diabetes. Here we present data for the subgroup with diabetes. METHODS: MEDLINE, EMBASE and the Cochrane Central Register of Controlled Trials were searched through September 23(rd), 2020. We included randomized controlled trials of ≥ 2-weeks of sources of oat ß-glucan and measures of glycemic control in diabetes. Two independent reviewers extracted relevant data and assessed the risk of bias (Cochrane Risk of Bias 2.0 Tool). The outcomes were fasting plasma glucose (FPG), 2h-plasma glucose (2h-PG) from a 75 g-oral glucose tolerance test, HbA1c and fasting plasma insulin (FPI). Data were pooled using the generic inverse variance method. Heterogeneity was assessed (Cochran Q statistic) and quantified (I(2) statistic). Pooled estimates were expressed as mean differences with 95% confidence intervals (CI). GRADE assessed the certainty of the evidence. RESULTS: Eligibility criteria were met by 5 trial comparisons (N = 359) in type 2 diabetes. No trials were identified in type 1 diabetes. Consumption of oat ß-glucan sources reduced FPG (MD = −0.37 mmol/L [95% CI: −0.70, −0.05 mmol/L], P = 0.03, I(2) = 0.00%, P(Q) = 0.76) and 2h-PG (MD = −1.24 mmol/L [95% CI: −1.97, −0.51 mmol/L], P = 0.00, I(2) = 0.00%, P(Q )= 0.56). There were non-significant reductions in HbA1c (MD = −0.12%, [95% CI: −0.26, 0.01%], P = 0.07, I(2) = 0.00%, P(Q) = 1.00) and FPI (MD = −4.59 pmol/L, [95% CI: −14.71, 5.52 pmol/L], P = 0.37, I(2) = 40.84%, P(Q) = 0.19). The certainty of evidence was high for 2h-PG and moderate for FPG, HbA1c and FPI (single downgrades for imprecision in each case). CONCLUSIONS: Current evidence provides a good indication that consumption of oat ß-glucan results in small improvements of glycemic control in type 2 diabetes. More high quality randomized trials are required to improve the precision of the pooled estimates. (ClinicalTrials.gov identifier, NCT04631913) FUNDING SOURCES: Quaker Oats Center of Excellence, Diabetes Canada, Banting & Best Diabetes Centre, Toronto 3D foundation

Category/Date Emerging Knowledge for Clinical Practice Podium Presentations focusing on the Research Agenda Priority of Pediatric Research: Professional Role & Health Promotion and Disease Prevention, Presented at NAPNAP's 40th National Conference on Pediatric Health Care, March 8, 2019, New Orleans, LA. Purpose A recent American Academy of Pediatrics (AAP) survey revealed that more than 80% of clinicians use a screen for autism spectrum disorders (ASD), with 74%, using the Modified Checklist of Autism in Toddlers (MCHAT)/MCHAT-Revised (MCHAT-R). The AAP recommends administering both broad-band (e.g., Parents’ Evaluation of Developmental Status (PEDS) & narrow-band (e.g., MCHAT-R) screens focused on detecting children at-risk for mental health, behavior, & developmental disorder/delay. Yet, use of broad-band mental health, behavior, & developmental disorder/delay screens is less common: only 50% of pediatric providers and fewer family practice providers report use of validated, accurate broad-band screens. Methods Sites were 197 primary care clinics using PEDS Online, a web-based service focused on identifying mental health, behavior, & developmental disorder/delay in children 0 to 8 years of age via: a) two broad-band validated mental health, behavior, & developmental disorder/delay screens– PEDS & PEDS: Developmental Milestones (PEDS:DM); and b) a narrow-band mental health, behavior, & developmental disorder/delay screen focused on ASD – either MCHAT or MCHAT-R. From the 231,789 encounters in 2014 through 2016, we selected only the 16% (N = 37,608) in which children were administered both broad- and narrow-band screens. We defined children at-risk for mental health, behavior, & developmental disorder/delay as children with at-risk screen results on one or more broad-band screens and/or on a narrow-band ASD screen. Results In 197 clinics representing 24 US States, 66% (N=24,992) of screening occurred in pediatric clinics and 34% (N=12,616) in family practices (including public health/community clinics). Compared to US Census Bureau data, the sample resided more in Southern and Northeast States (86% vs 55% nationally) and parents were less likely to be high school graduates (76% vs 87% nationally). Mean age of children was 24 months (SD = 6.02). Of the 37,608 encounters, 12% (N=4572) of children were identified at-risk for mental health, behavior, & developmental disorder/delay. Of the 4572 with probable mental health, behavior, & developmental disorder/delay, broad-band screens identified 73% (N=3332/4572). The MCHAT/MCHAT-R uniquely identified 27% (N= 1240/4572). There was agreement among broad- and narrow-band measures of 22% (N=984/4572). ASD screens, if used alone, identified only 49% of those with probable mental health, behavior, & developmental disorder/delay (N = 2224/4572). Although ASD screens contribute uniquely to early identification, such tools do not seem to adequately detect most children at-risk for mental health, behavior, & developmental disorder/delays. Conclusions Use of an ASD screen alone would miss about 51% of children at-risk for mental health, behavior, & developmental disorder/delay. Mental health, behavior, & developmental disorder/delay screening should embrace both broad-band and narrow-band measures to best identify children at-risk.

Identifying effective literacy instruction programs has been a focal point for governments, educators and parents over the last few decades (Ontario Ministry of Education, 2004, 2006; Council of Ontario Directors of Education, 2011). Given the increasing use of computer technologies in the classroom and in the home, a variety of information communication technology (ICT) interventions for learning have been introduced. Meta-analyses comparing the impact of these programs on learning, however, have yielded inconsistent findings ( Andrews et al., 2007 , Torgerson and Zhu, 2003 , Slavin et al., 2008 , Slavin et al., 2009 ). The present tertiary meta-analytic review re-assesses outcomes presented in three previous meta-analyses. Four moderator variables assessed the impact of the systematic review from which they were retrieved, training and support, implementation fidelity and who delivered the intervention (teacher versus researcher). Significant results were found when training and support was entered as a moderator variable with the small overall effectiveness of the ICTs (ES = 0.18), similar to those found in previous research, increasing significantly (ES = 0.57). These findings indicate the importance of including implementation factors such as training and support, when considering the relative effectiveness of ICT interventions.

This study was undertaken to examine whether marijuana use affects in vitro fertilization and gamete intrafallopian transfer (IVF/GIFT).Prospective study of 221 IVF/GIFT couples.Amount of lifetime heavy marijuana use adversely affected IVF/GIFT. Women smoking more than 90 times in their lifetime had 27% fewer oocytes retrieved (P = .03) and 1 fewer embryo transferred (P.05). Women smoking marijuana more than 10 times in their lifetime had infants 17% (P = .01) smaller at birth. If men smoked marijuana 11 to 90 times in their lifetime, there was a 15% decrease in infant birth weight (P = .03); if this increased to more than 90 times, there was a 23% decrease (P = .01). Timing also played a role. Women smoking marijuana 1 year before IVF/GIFT had 25% fewer oocytes retrieved (P = .03), whereas couples had 28% (P = .04) fewer oocytes fertilized. Women and men who smoked in the past 15 years, had 12% (P = .04) and 16% (P = .03) smaller infants, respectively.Both timing and amount of marijuana use negatively affected IVF/GIFT.