The promise and pitfalls of a strength-based approach to child poverty and neurocognitive development: Implications for policy.

There has been significant progress in understanding the effects of childhood poverty on neurocognitive development. This progress has captured the attention of policymakers and promoted progressive policy reform. However, the prevailing emphasis on the harms associated with childhood poverty may have inadvertently perpetuated a deficit-based narrative, focused on the presumed shortcomings of children and families in poverty. This focus can have unintended consequences for policy (e.g., overlooking strengths) as well as public discourse (e.g., focusing on individual rather than systemic factors). Here, we join scientists across disciplines in arguing for a more well-rounded, "strength-based" approach, which incorporates the positive and/or adaptive developmental responses to experiences of social disadvantage. Specifically, we first show the value of this approach in understanding normative brain development across diverse human environments. We then highlight its application to educational and social policy, explore pitfalls and ethical considerations, and offer practical solutions to conducting strength-based research responsibly. Our paper re-ignites old and recent calls for a strength-based paradigm shift, with a focus on its application to developmental cognitive neuroscience. We also offer a unique perspective from a new generation of early-career researchers engaged in this work, several of whom themselves have grown up in conditions of poverty. Ultimately, we argue that a balanced strength-based scientific approach will be essential to building more effective policies.

TENAYA and LUCERNE: Two-Year Results from the Phase 3 Neovascular Age-Related Macular Degeneration Trials of Faricimab with Treat-and-Extend Dosing in Year 2.

PURPOSE: To evaluate 2-year efficacy, durability, and safety of the bispecific antibody faricimab, which inhibits both angiopoietin-2 and VEGF-A. DESIGN: TENAYA (ClinicalTrials.gov identifier, NCT03823287) and LUCERNE (ClinicalTrials.gov identifier, NCT03823300) were identically designed, randomized, double-masked, active comparator-controlled phase 3 noninferiority trials. PARTICIPANTS: Treatment-naive patients with neovascular age-related macular degeneration (nAMD) 50 years of age or older. METHODS: Patients were randomized (1:1) to intravitreal faricimab 6.0 mg up to every 16 weeks (Q16W) or aflibercept 2.0 mg every 8 weeks (Q8W). Faricimab fixed dosing based on protocol-defined disease activity at weeks 20 and 24 up to week 60, followed up to week 108 by a treat-and-extend personalized treatment interval regimen. MAIN OUTCOME MEASURES: Efficacy analyses included change in best-corrected visual acuity (BCVA) from baseline at 2 years (averaged over weeks 104, 108, and 112) and proportion of patients receiving Q16W, every 12 weeks (Q12W), and Q8W dosing at week 112 in the intention-to-treat population. Safety analyses included ocular adverse events (AEs) in the study eye through study end at week 112. RESULTS: Of 1326 patients treated across TENAYA/LUCERNE, 1113 (83.9%) completed treatment (n = 555 faricimab; n = 558 aflibercept). The BCVA change from baseline at 2 years was comparable between faricimab and aflibercept groups in TENAYA (adjusted mean change, +3.7 letters [95% confidence interval (CI), +2.1 to +5.4] and +3.3 letters [95% CI, +1.7 to +4.9], respectively; mean difference, +0.4 letters [95% CI, -1.9 to +2.8]) and LUCERNE (adjusted mean change, +5.0 letters [95% CI, +3.4 to +6.6] and +5.2 letters [95% CI, +3.6 to +6.8], respectively; mean difference, -0.2 letters [95% CI, -2.4 to +2.1]). At week 112 in TENAYA and LUCERNE, 59.0% and 66.9%, respectively, achieved Q16W faricimab dosing, increasing from year 1, and 74.1% and 81.2%, achieved Q12W or longer dosing. Ocular AEs in the study eye were comparable between faricimab and aflibercept groups in TENAYA (55.0% and 56.5% of patients, respectively) and LUCERNE (52.9% and 47.5% of patients, respectively) through week 112. CONCLUSIONS: Treat-and-extend faricimab treatment based on nAMD disease activity maintained vision gains through year 2, with most patients achieving extended dosing intervals. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Faricimab Treat-and-Extend for Diabetic Macular Edema: Two-Year Results from the Randomized Phase 3 YOSEMITE and RHINE Trials.

PURPOSE: To evaluate the 2-year efficacy, durability, and safety of dual angiopoietin-2 and vascular endothelial growth factor (VEGF) A pathway inhibition with intravitreal faricimab according to a personalized treat-and-extend (T&E)-based regimen with up to every-16-week dosing in the YOSEMITE and RHINE (ClinicalTrials.gov identifiers, NCT03622580 and NCT03622593, respectively) phase 3 trials of diabetic macular edema (DME). DESIGN: Randomized, double-masked, noninferiority phase 3 trials. PARTICIPANTS: Adults with visual acuity loss (best-corrected visual acuity [BCVA] of 25-73 letters) due to center-involving DME. METHODS: Patients were randomized 1:1:1 to faricimab 6.0 mg every 8 weeks, faricimab 6.0 mg T&E (previously referred to as personalized treatment interval), or aflibercept 2.0 mg every 8 weeks. The T&E up to every-16-week dosing regimen was based on central subfield thickness (CST) and BCVA change. MAIN OUTCOME MEASURES: Included changes from baseline in BCVA and CST, number of injections, durability, absence of fluid, and safety through week 100. RESULTS: In YOSEMITE and RHINE (n = 940 and 951, respectively), noninferior year 1 visual acuity gains were maintained through year 2; mean BCVA change from baseline at 2 years (weeks 92, 96, and 100 average) with faricimab every 8 weeks (YOSEMITE and RHINE, +10.7 letters and +10.9 letters, respectively) or T&E (+10.7 letters and +10.1 letters, respectively) were comparable with aflibercept every 8 weeks (+11.4 letters and +9.4 letters, respectively). The median number of study drug injections was lower with faricimab T&E (YOSEMITE and RHINE, 10 and 11 injections, respectively) versus faricimab every 8 weeks (15 injections) and aflibercept every 8 weeks (14 injections) across both trials during the entire study. In the faricimab T&E arms, durability was improved further during year 2, with > 60% of patients receiving every-16-week dosing and approximately 80% receiving every-12-week or longer dosing at week 96. Almost 80% of patients who achieved every-16-week dosing at week 52 maintained every-16-week dosing without an interval reduction through week 96. Mean CST reductions were greater (YOSEMITE/RHINE weeks 92/96/100 average: faricimab every 8 weeks -216.0/-202.6 µm, faricimab T&E -204.5/-197.1 µm, aflibercept every 8 weeks -196.3/-185.6 µm), and more patients achieved absence of DME (CST < 325 µm; YOSEMITE/RHINE weeks 92-100: faricimab every 8 weeks 87%-92%/88%-93%, faricimab T&E 78%-86%/85%-88%, aflibercept every 8 weeks 77%-81%/80%-84%) and absence of intraretinal fluid (YOSEMITE/RHINE weeks 92-100: faricimab every 8 weeks 59%-63%/56%-62%, faricimab T&E 43%-48%/45%-52%, aflibercept every 8 weeks 33%-38%/39%-45%) with faricimab every 8 weeks or T&E versus aflibercept every 8 weeks through year 2. Overall, faricimab was well tolerated, with a safety profile comparable with that of aflibercept. CONCLUSIONS: Clinically meaningful visual acuity gains from baseline, anatomic improvements, and extended durability with intravitreal faricimab up to every 16 weeks were maintained through year 2. Faricimab given as a personalized T&E-based dosing regimen supports the role of dual angiopoietin-2 and VEGF-A inhibition to promote vascular stability and to provide durable efficacy for patients with DME. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Efficacy, Durability, and Safety of Faricimab in Patients From Asian Countries With Diabetic Macular Edema: 1-Year Subgroup Analysis of the Phase III YOSEMITE and RHINE Trials.

PURPOSE: To assess the 1-year efficacy, durability, and safety of faricimab in patients with diabetic macular edema from Asian and non-Asian countries. DESIGN: Global, multicenter, randomized, double-masked, active comparator-controlled, phase III trials. METHODS: Subgroup analysis of patients from Asian (N=144) and non-Asian (N=1747) countries randomized to faricimab 6.0 mg every 8 weeks (Q8W), faricimab per personalized treatment interval (PTI), or aflibercept 2.0 mg Q8W in the YOSEMITE/RHINE (NCT03622580/NCT03622593) trials. Primary endpoint: best-corrected visual acuity (BCVA) changes from baseline at 1 year, averaged over weeks 48, 52, and 56. RESULTS: Mean BCVA change from baseline at 1 year in the Asian country subgroup was similar between arms: faricimab Q8W (n=50), +10.9 (95% CI: 8.6-13.2); faricimab PTI (n=48) +10.0 (7.7-12.4) letters; aflibercept Q8W (n=46) +9.0 (6.6-11.4) letters. BCVA gains in the non-Asian country subgroup (n=582, 584, 581) were +11.3 (10.5-12.1), +11.2 (10.5-12.0), and +10.7 (9.9-11.5) letters, respectively. At 1 year, 49% of Asian country patients in the faricimab PTI arm achieved Q16W dosing (vs. 52% non-Asian) and 78% achieved ≥Q12W dosing (vs. 72% non-Asian). Anatomic improvementswere generally greater with faricimab versus aflibercept and similar between the Asian and non-Asian country subgroups. Faricimab was well tolerated, with no new safety signals. CONCLUSIONS: Vision, durability, anatomic, and safety outcomes were generally similar between the Asian and non-Asian country subgroups, suggesting that global YOSEMITE/RHINE results may be generalized to the Asian population. These data support the benefit-risk profile of faricimab for treating Asian patients with diabetic macular edema.

Identifying the psychological mechanisms of utility-value activities to inform educational research and practice.

BACKGROUND: Utility-value interventions have been shown to promote students' achievement and motivation in mathematics through encouraging them to identify connections between course content and their real lives. To extend the benefits of these interventions, additional research is necessary to test their efficacy in diverse high school contexts, as well as investigate the psychological mechanisms through which they benefit students. AIMS: To inform efforts within broader learning contexts to develop activities and messages based on utility-value interventions that effectively target the psychological mechanisms that support student learning. SAMPLES: Study 1 (N = 375) and Study 2 (N = 2894) include racially and socioeconomically diverse samples of students enrolled in mathematics courses across four high schools in the United States. METHODS: We conducted two randomized field experiments to test the effects of brief utility-value activities on students' motivation. Using multi-level path analyses, we then investigated the mechanisms through which utility-value activities bolster students' interest and achievement in mathematics. RESULTS: In pre-registered analyses, we found that the utility-value activities promoted students' perceived value of mathematics, as well as their novel engagement and sense of social identity congruence with mathematics. In turn, these outcomes mediated the indirect effects of the activities on students' grades and interest in mathematics. CONCLUSIONS: Our results underscore the potential of utility-value activities to promote students' success. Based on our mediation findings, we also provide a roadmap for how learning contexts can develop activities and messages that effectively target key processes to advance student success.

Concern about experiencing downward socioeconomic mobility generates precarious types of motivation among students of color.

Students' beliefs about whether they will experience changes in their socioeconomic status influence their academic motivation. We propose that students who are concerned about downward socioeconomic mobility will focus their attention on negative academic outcomes and exhibit motivational goals oriented towards preventing negative possibilities and that this relationship will be particularly pronounced among students of color. Two studies investigated the relationship between college students' concerns about downward socioeconomic mobility and their adoption of academic achievement goals. The more that students of color expressed concerns about experiencing downward socioeconomic mobility, the more they adopted academic mastery-avoidance goals (ß = 0.76), whereas there was no significant relationship between concerns about downward socioeconomic mobility and mastery-avoidance goals among White students (ß = - 0.24; Study 1). Experimentally induced concerns about downward socioeconomic mobility increased academic mastery-avoidance goals among students of color (ß = - 0.58) but decreased mastery-avoidance goals among White students (ß = 0.46; Study 2). Together, results indicate that there is a strong relationship between concerns about downward socioeconomic mobility and mastery-avoidance goals among students of color, highlighting the importance of understating how students of color make sense of their future socioeconomic prospects in order to most effectively support their academic trajectories positively. Supplementary Information: The online version contains supplementary material available at 10.1007/s11218-023-09763-5.

Race, academic achievement and the issue of inequitable motivational payoff.

As racial inequities continue to pervade school systems around the world, further research is necessary to understand the factors undergirding this pressing issue. Here across three studies conducted in the United States (N = 8,293), we provide evidence that race-based differences in student achievement do not stem from a lack of motivation among Black, Latinx and Indigenous (BLI) students, but a lack of equitable motivational payoff. Even when BLI and non-BLI students have the same levels of motivation, BLI students still receive maths grades that are an average of 9% lower than those of their non-BLI peers (95% confidence interval 7 to 11%). This pattern was not explained by differences in students' aptitude, effort or prior achievement but was instead linked to teachers' diminished expectations for their BLI students' academic futures. We conclude by discussing statistical power limitations and the implications of the current findings for how researchers consider the sources of, and solutions for, educational inequity.

The Ongoing Development of Strength-Based Approaches to People Who Hold Systemically Marginalized Identities.

ACADEMIC ABSTRACT: Personality and social psychology have historically viewed individuals' systemically marginalized identities (e.g., as people of color, as coming from a lower-income background) as barriers to their success. Such a deficit-based perspective limits psychological science by overlooking the broader experiences, value, perspectives, and strengths that individuals who face systemic marginalization often bring to their societies. The current article aims to support future research in incorporating a strength-based lens through tracing psychology's journey away from an emphasis on deficits among people who contend with systemic marginalization and toward three distinct strength-based approaches: the universal strengths, difference-as-strength, and identity-specific strengths approaches. Through distinguishing between each approach, we advance scholarship that aims to understand systemically marginalized identities with corresponding implications for addressing inequality. Strength-based approaches guide the field to recognize the imposed limitations of deficit-based ideologies and advance opportunities to engage in research that effectively understands and values systemically marginalized people. PUBLIC ABSTRACT: Inequalities, including those between people from higher- and lower-income backgrounds, are present across society. From schools to workplaces, hospitals to courtrooms, people who come from backgrounds that are marginalized by society often face more negative outcomes than people from more privileged backgrounds. While such inequalities are often blamed on a lack of hard work or other issues within marginalized people themselves, scientific research increasingly demonstrates that this is not the case. Rather, studies consistently find that people's identities as coming from groups that face marginalization in society often serve as a valuable source of unique strengths, not deficiencies, that can help them succeed. Our article reviews these studies to examine how future research in psychology may gain a broader understanding of people who contend with marginalization. In doing so, we outline opportunities for psychological research to effectively support efforts to address persistent inequalities.

Educators' Beliefs About Students' Socioeconomic Backgrounds as a Pathway for Supporting Motivation.

Students' understandings of their socioeconomic status (SES) backgrounds have important implications for their motivation, achievement, and the emergence of SES-based educational disparities. Educators' beliefs about students' backgrounds likely play a meaningful role in shaping these understandings and, thus, may represent an important opportunity to support students from lower-SES backgrounds. We first experimentally demonstrate that educators can be encouraged to adopt background-specific strengths beliefs-which view students' lower-SES backgrounds as potential sources of unique and beneficial strengths (NStudy 1 = 125). Subsequently, we find that exposure to educators who communicate background-specific strengths beliefs positively influences the motivation and academic persistence of students, particularly those from lower-SES backgrounds (NStudy 2 = 256; NStudy 3 = 276). Furthermore, lower-SES students' own beliefs about their backgrounds mediated these effects. Altogether, our work contributes to social-psychological theory and practice regarding how key societal contexts can promote equity through identity-based processes.

Vaccination coverage at seven months of age in Limpopo Province, South Africa: a cross-sectional survey.

Many low- and middle-income countries face challenges in attaining adequate levels of vaccination coverage, and the factors driving this under-coverage have not been completely elucidated. In this cross-sectional study, we investigated factors associated with vaccination coverage in Mopani District, Limpopo Province, South Africa. Between July and October 2017, we surveyed 317 caregivers (83% of whom were mothers) of seven-month-old infants in Mopani District about barriers faced when attaining vaccines and attitudes towards vaccination, and reviewed the infants' documented vaccination history. Caregiver and child demographic data were collected shortly after birth. We described the coverage for vaccines that should be received by age seven months, according to South Africa's Expanded Programme on Immunization schedule, and explored the relationship between coverage and caregiver characteristics, behavioral factors (e.g. attitudes towards vaccination), and structural factors (e.g. vaccination stock-outs at clinics). We found that caregivers reported positive attitudes towards vaccination, based on a seven-question survey of vaccination attitudes. Although coverage was high for most recommended vaccines, it was low for pneumococcal conjugate vaccine (PCV), with just 36% of children having received it by age seven months. This appears to have been due to PCV stock-outs at government clinics. For vaccines other than PCV, children were more likely to be up-to-date on vaccinations if a community health worker (CHW) had visited their home in the past month (adjusted odds ratio (OR) 1.24, confidence interval (CI) (1.10-1.41); p < 0.001) and if the caregiver had more years of schooling (adjusted OR 1.03 (CI 1.01-1.05); p = 0.012). We conclude that addressing PCV stock-outs at government clinics in Mopani District is necessary to ensure coverage reaches adequate levels. Additionally, supporting CHW programs may be a productive avenue for improving vaccination coverage.

Findings From Severe Maternal Morbidity Surveillance and Review in Maryland.

Importance: In the US, more than 50 000 women experience severe maternal morbidity (SMM) each year, and the SMM rate more than doubled during the past 25 years. In response, professional organizations called for birthing facilities to routinely identify and review SMM events and identify prevention opportunities. Objective: To examine SMM levels, primary causes, and factors associated with the preventability of SMM using Maryland's SMM surveillance and review program. Design, Setting, and Participants: This cross-sectional study included pregnant and postpartum patients at 42 days or less after delivery who were hospitalized at 1 of 6 birthing hospitals in Maryland between August 1, 2020, and November 30, 2021. Hospital-based SMM surveillance was conducted through a detailed review of medical records. Exposures: Hospitalization during pregnancy or within 42 days post partum. Main Outcomes and Measures: The main outcomes were admission to an intensive care unit, having at least 4 U of red blood cells transfused, and/or having COVID-19 infection requiring inpatient hospital care. Results: A total of 192 SMM events were identified and reviewed. Patients with SMM had a mean [SD] age of 31 [6.49] years; 9 [4.7%] were Asian, 27 [14.1%] were Hispanic, 83 [43.2%] were non-Hispanic Black, and 68 [35.4%] were non-Hispanic White. Obstetric hemorrhage was the leading primary cause of SMM (83 [43.2%]), followed by COVID-19 infection (57 [29.7%]) and hypertensive disorders of pregnancy (17 [8.9%]). The SMM rate was highest among Hispanic patients (154.9 per 10 000 deliveries), primarily driven by COVID-19 infection. The rate of SMM among non-Hispanic Black patients was nearly 50% higher than for non-Hispanic White patients (119.9 vs 65.7 per 10 000 deliveries). The SMM outcome assessed could have been prevented in 61 events (31.8%). Clinician-level factors and interventions in the antepartum period were most frequently cited as potentially altering the SMM outcome. Practices that were performed well most often pertained to hospitals' readiness and adequate response to managing pregnancy complications. Recommendations for care improvement focused mainly on timely recognition and rapid response to such. Conclusions and Relevance: The findings of this cross-sectional study, which used hospital-based SMM surveillance and review beyond the mere exploration of administrative data, offers opportunities for identifying valuable quality improvement strategies to reduce SMM. Immediate strategies to reduce SMM in Maryland should target its most common causes and address factors associated with preventability identified at individual hospitals.

YOSEMITE and RHINE: Phase 3 Randomized Clinical Trials of Faricimab for Diabetic Macular Edema: Study Design and Rationale.

Purpose: Faricimab is a novel anti-angiopoietin-2 and anti-vascular endothelial growth factor (VEGF) bispecific antibody with high affinities and specificities for both VEGF and angiopoietin-2. It is postulated that targeting angiogenic factors and inflammatory pathways in addition to the VEGF pathway will increase treatment durability and improve outcomes. The phase 3 YOSEMITE (ClinicalTrials.gov identifier, NCT03622580) and RHINE (ClinicalTrials.gov identifier, NCT03622593) trials are designed to assess efficacy, safety, and durability of faricimab compared with aflibercept in patients with diabetic macular edema (DME). The trials evaluate a personalized treatment interval (PTI) approach to address heterogeneity in treatment response among patients with DME. Design: Two identically designed, global, double-masked, randomized, controlled phase 3 trials (YOSEMITE and RHINE). Participants: Adults with center-involving DME secondary to type 1 or 2 diabetes mellitus. Methods: These studies were designed to evaluate 3 treatment groups: faricimab 6.0 mg dosed either at fixed dosing every 8 weeks after initial treatment with 6 intravitreal doses at 4-week intervals, or faricimab 6.0 mg dosed according to PTI after initial treatment with 4 every-4-week doses, compared with aflibercept 2.0 mg dosed every 8 weeks after 5 initial every-4-week doses. The primary end point of the studies was change from baseline in best-corrected visual acuity at 1 year, averaged over weeks 48, 52, and 56. Secondary end points included anatomic, durability, and patient-reported outcomes. Safety outcomes included incidence and severity of ocular and nonocular adverse events. The PTI is a protocol-defined flexible regimen based on the treat-and-extend concept, which allowed up to every-16-week adjustable dosing based on objective and standardized criteria. The PTI design aimed to maximize therapeutic results while minimizing treatment burden. Main Outcome Measures: We describe the rationale for the study design and the novel PTI (up to every-16-week adjustable dosing) approach for treatment with faricimab. Results: YOSEMITE and RHINE enrolled 940 and 951 patients, respectively. Results from each study will be reported separately. Conclusions: YOSEMITE and RHINE were the first registrational trials in retinal disease to incorporate an objective PTI regimen, allowing for up to every-16-week adjustable dosing with a dual angiopoietin-2 and VEGF-A inhibitor, faricimab 6.0 mg, for treatment of DME.

Efficacy, durability, and safety of intravitreal faricimab up to every 16 weeks for neovascular age-related macular degeneration (TENAYA and LUCERNE): two randomised, double-masked, phase 3, non-inferiority trials.

BACKGROUND: Faricimab is a bispecific antibody that acts through dual inhibition of both angiopoietin-2 and vascular endothelial growth factor A. We report primary results of two phase 3 trials evaluating intravitreal faricimab with extension up to every 16 weeks for neovascular age-related macular degeneration (nAMD). METHODS: TENAYA and LUCERNE were randomised, double-masked, non-inferiority trials across 271 sites worldwide. Treatment-naive patients with nAMD aged 50 years or older were randomly assigned (1:1) to intravitreal faricimab 6·0 mg up to every 16 weeks, based on protocol-defined disease activity assessments at weeks 20 and 24, or aflibercept 2·0 mg every 8 weeks. Randomisation was performed through an interactive voice or web-based response system using a stratified permuted block randomisation method. Patients, investigators, those assessing outcomes, and the funder were masked to group assignments. The primary endpoint was mean change in best-corrected visual acuity (BCVA) from baseline averaged over weeks 40, 44, and 48 (prespecified non-inferiority margin of four letters), in the intention-to-treat population. Safety analyses included patients who received at least one dose of study treatment. These trials are registered with ClinicalTrials.gov (TENAYA NCT03823287 and LUCERNE NCT03823300). FINDINGS: Across the two trials, 1329 patients were randomly assigned between Feb 19 and Nov 19, 2019 (TENAYA n=334 faricimab and n=337 aflibercept), and between March 11 and Nov 1, 2019 (LUCERNE n=331 faricimab and n=327 aflibercept). BCVA change from baseline with faricimab was non-inferior to aflibercept in both TENAYA (adjusted mean change 5·8 letters [95% CI 4·6 to 7·1] and 5·1 letters [3·9 to 6·4]; treatment difference 0·7 letters [-1·1 to 2·5]) and LUCERNE (6·6 letters [5·3 to 7·8] and 6·6 letters [5·3 to 7·8]; treatment difference 0·0 letters [-1·7 to 1·8]). Rates of ocular adverse events were comparable between faricimab and aflibercept (TENAYA n=121 [36·3%] vs n=128 [38·1%], and LUCERNE n=133 [40·2%] vs n=118 [36·2%]). INTERPRETATION: Visual benefits with faricimab given at up to 16-week intervals demonstrates its potential to meaningfully extend the time between treatments with sustained efficacy, thereby reducing treatment burden in patients with nAMD. FUNDING: F Hoffmann-La Roche.

Efficacy, durability, and safety of intravitreal faricimab with extended dosing up to every 16 weeks in patients with diabetic macular oedema (YOSEMITE and RHINE): two randomised, double-masked, phase 3 trials.

BACKGROUND: To reduce treatment burden and optimise patient outcomes in diabetic macular oedema, we present 1-year results from two phase 3 trials of faricimab, a novel angiopoietin-2 and vascular endothelial growth factor-A bispecific antibody. METHODS: YOSEMITE and RHINE were randomised, double-masked, non-inferiority trials across 353 sites worldwide. Adults with vision loss due to centre-involving diabetic macular oedema were randomly assigned (1:1:1) to intravitreal faricimab 6·0 mg every 8 weeks, faricimab 6·0 mg per personalised treatment interval (PTI), or aflibercept 2·0 mg every 8 weeks up to week 100. PTI dosing intervals were extended, maintained, or reduced (every 4 weeks up to every 16 weeks) based on disease activity at active dosing visits. The primary endpoint was mean change in best-corrected visual acuity at 1 year, averaged over weeks 48, 52, and 56. Efficacy analyses included the intention-to-treat population (non-inferiority margin 4 Early Treatment Diabetic Retinopathy Study [ETDRS] letters); safety analyses included patients with at least one dose of study treatment. These trials are registered with ClinicalTrials.gov (YOSEMITE NCT03622580 and RHINE NCT03622593). FINDINGS: 3247 patients were screened for eligibility in YOSEMITE (n=1532) and RHINE (n=1715). After exclusions, 940 patients were enrolled into YOSEMITE between Sept 5, 2018, and Sept 19, 2019, and 951 patients were enrolled into RHINE between Oct 9, 2018, and Sept 20, 2019. These 1891 patients were randomly assigned to faricimab every 8 weeks (YOSEMITE n=315, RHINE n=317), faricimab PTI (n=313, n=319), or aflibercept every 8 weeks (n=312, n=315). Non-inferiority for the primary endpoint was achieved with faricimab every 8 weeks (adjusted mean vs aflibercept every 8 weeks in YOSEMITE 10·7 ETDRS letters [97·52% CI 9·4 to 12·0] vs 10·9 ETDRS letters [9·6 to 12·2], difference -0·2 ETDRS letters [-2·0 to 1·6]; RHINE 11·8 ETDRS letters [10·6 to 13·0] vs 10·3 ETDRS letters [9·1 to 11·4] letters, difference 1·5 ETDRS letters [-0·1 to 3·2]) and faricimab PTI (YOSEMITE 11·6 ETDRS letters [10·3 to 12·9], difference 0·7 ETDRS letters [-1·1 to 2·5]; RHINE 10·8 ETDRS letters [9·6 to 11·9], difference 0·5 ETDRS letters [-1·1 to 2·1]). Incidence of ocular adverse events was comparable between faricimab every 8 weeks (YOSEMITE n=98 [31%], RHINE n=137 [43%]), faricimab PTI (n=106 [34%], n=119 [37%]), and aflibercept every 8 weeks (n=102 [33%], n=113 [36%]). INTERPRETATION: Robust vision gains and anatomical improvements with faricimab were achieved with adjustable dosing up to every 16 weeks, demonstrating the potential for faricimab to extend the durability of treatment for patients with diabetic macular oedema. FUNDING: F Hoffmann-La Roche.

Non-traditional factors affecting referral for coronary angiography following SPECT myocardial perfusion imaging.

BACKGROUND: The use of myocardial perfusion imaging (MPI) in the management of coronary artery disease (CAD) is well established. Although prior studies have shown disparities in the use of invasive angiography in patients with acute MI, data on factors affecting referral to angiography post-MPI are lacking. We sought to evaluate the primary determinants of referral to invasive angiography post-MPI and specifically assess the role of non-traditional non-clinical factors such as race/ethnicity, socioeconomic factors, insurance status, and marital status. METHODS: All patients without known CAD who underwent stress SPECT MPI over 15 years were reviewed and the performance of coronary angiography within 90 days of their MPI was recorded. Multiple factors were analyzed for an association with referral to angiography, including exercise and MPI results, baseline demographics, traditional cardiac risk factors, and non-traditional factors such as ethnicity, insurance, marital and socioeconomic status. In a secondary analysis, these factors were assessed with regard to abnormal MPI results. RESULTS: Out of 27,895 total patients, 2,150 (7.7%) underwent invasive coronary angiography. On multivariate analysis, inpatient location, positive ECG response, and abnormal MPI results were the strongest predictors of angiography. Non-traditional factors such as race/ethnicity and insurance status had a significant association with referral to angiography with Caucasians (OR 1.42, 95% CI 1.18-1.71, P < .0001) and those with private insurance (OR 1.35, 95% CI 1.13-1.62, P = .001) or Medicare (OR 1.30, 95% CI 1.08-1.56, P = .006) having higher rates of angiography despite controlling for traditional risk factors and test results. CONCLUSION: Our study results indicate that non-traditional factors such as race/ethnicity and insurance status influence patient management decisions and impact the performance of downstream cardiac invasive testing after stress MPI. Higher rates of angiography in Caucasians, privately insured and Medicare patients were seen despite controlling for traditional risk factors and abnormal test results. Further research is needed to better understand these disparities, especially in the current healthcare environment.

Postpartum Mental Health in Rural South Africa: Socioeconomic Stressors and Worsening Mental Health.

OBJECTIVES: This study aimed to characterize patterns of worsening mental health during the postpartum period among women in rural areas of Limpopo Province, South Africa, and to identify correlates with household demographic factors. METHODS: We collected data on maternal mental health symptoms shortly after birth and then again 7 months postpartum using the World Health Organization self-reporting questionnaire (SRQ-20) from December 2017 to November 2018. The absolute change in SRQ-20 symptom score was calculated to determine worsening mental health over the postpartum period. Linear regressions were performed to investigate factors associated with mental health symptom scores at varying postpartum time points. RESULTS: We found increased reporting of poor mental health symptoms at 7 months postpartum as compared to shortly after birth (n = 224). Worsening maternal mental health over the postpartum period was associated with higher SRQ-20 symptom score shortly after birth (p < 0.001) and reported food insecurity at 7 months (p < 0.001). SRQ-20 symptom scores in the postpartum period were not associated with breastfeeding in the past 24 h reported at 7 months postpartum (p = 0.08). CONCLUSIONS FOR PRACTICE: Women in rural South Africa, like women in many settings, may be vulnerable to worsening postpartum mental health when they lack sufficient socioeconomic resources and when they have pre-existing depressive/anxiety symptoms.

An experimental demonstration of the positive consequences of guiding students to conceptualize education as connection.

INTRODUCTION: Educators often struggle to sustain students' motivation during adolescence. Students may view school tasks as insignificant because learning, achievement, and success feel detached from valued social connections. Previous findings in the study of development demonstrate that young people derive meaning from key sources of social support and connection. Finding ways to link how students approach their educational goals to meaningful social connections may strengthen responses to daily learning opportunities with positive implications for achievement. METHOD: A randomized-controlled experiment and daily diary survey evaluated the consequences of guiding students to conceptualize educational pursuits as linked to their social connections. A group of ninth-grade students in the United States (N = 39; 58.97 % girls, 30.77 % boys, 2.56 % non-binary, 7.69 % did not disclose) were randomly assigned to one of two brief programs designed to cultivate goals and motivation. RESULTS: Participants randomly assigned to a healthy achievement condition (including an emphasis on the importance of social support and connection as part of achievement and success) reported more productive responses to daily academic difficulty than participants in a standard motivation condition on a daily diary survey over one year after the program. This led to an indirect increase in actual daily support, which was associated with earning higher grades. CONCLUSIONS: The results suggest that a reconceptualization of education as an endeavor grounded in social connection would help keep students engaged in learning.

TENAYA and LUCERNE: Rationale and Design for the Phase 3 Clinical Trials of Faricimab for Neovascular Age-Related Macular Degeneration.

Purpose: To describe the design and rationale of the phase 3 TENAYA (ClinicalTrials.gov identifier, NCT03823287) and LUCERNE (ClinicalTrials.gov identifier, NCT03823300) trials that aimed to assess efficacy, safety, and durability of faricimab, the first bispecific antibody for intraocular use, which independently binds and neutralizes both angiopoietin-2 and vascular endothelial growth factor-A (VEGF-A) versus aflibercept in patients with neovascular age-related macular degeneration (nAMD). Design: Identical, global, double-masked, randomized, controlled, phase 3 clinical trials. Participants: Adults with treatment-naïve nAMD. Methods: These trials were designed to evaluate patients randomized to receive faricimab 6.0 mg up to every 16 weeks after 4 initial every-4-week doses or aflibercept 2.0 mg every 8 weeks after 3 initial every-4-week doses. The initial doses in the faricimab arm were followed by individualized fixed treatment intervals up to week 60, based on disease activity assessment at weeks 20 and 24, guided by central subfield thickness, best-corrected visual acuity (BCVA), and investigator assessment. The primary efficacy end point was BCVA change from baseline averaged over weeks 40, 44, and 48. Secondary end points included the proportion of patients receiving every-8-week, every-12-week, and every-16-week faricimab and anatomic outcomes. Safety outcomes included incidence and severity of ocular and nonocular adverse events. From week 60, faricimab-treated patients followed a personalized treatment interval (PTI), a novel protocol-driven treat-and-extend regimen with interval adjustment from every 8 weeks to every 16 weeks based on individualized treatment response measured by anatomic criteria, functional criteria, and investigator assessment of patients' disease activity. Main Outcome Measures: Rationale for trial design and PTI approach. Results: The TENAYA and LUCERNE trials were the first registrational trials in nAMD to test fixed dosing regimens up to every 16 weeks based on patients' disease activity in year 1 and incorporate a PTI paradigm during year 2. The PTI approach was designed to tailor treatment intervals to individual patient needs, to reflect clinical practice treatment practice, and to reduce treatment burden. Conclusions: The innovative trial design rationale for the TENAYA and LUCERNE trials included maximizing the benefits of angiopoietin-2 blockade through dosing up to every 16 weeks and PTI regimens based on patients' disease activity while fulfilling health authority requirements for potential registrational efforts.

Tablet-Based Limited Echocardiography to Reduce Sonographer Scan and Decontamination Time during the COVID-19 Pandemic.

BACKGROUND: Limited assessments with handheld ultrasound have found meaningful clinical use in the care of acutely ill patients. However, there are limited data on incorporating handheld-based limited echocardiography into the echocardiography laboratory. The purpose of this study was to assess the efficacy of limited handheld tablet echocardiography as an alternative to traditional echocardiography during the coronavirus disease 2019 (COVID-19) pandemic as a means to limit exposure while providing essential clinical information. METHODS: Ninety consecutive inpatients with known or suspected COVID-19 were scanned according to laboratory COVID-19 guidelines using a limited 11- to 20-clip protocol on a tablet sonograph. The primary assessment was length of study time. Comparison data were drawn from comprehensive echocardiographic examinations ordered on intensive care patients not under COVID-19 precautions. RESULTS: Over a 36-day time period, a total of 91 requests were deemed to be appropriate for echocardiography on patients with suspected or confirmed COVID-19 (average age, 67 years; 64% men; mean body mass index, 32 kg/m2). Of these, 90 (99%) examinations were performed using a handheld device, and all were deemed diagnostic and provided sufficient information for the clinical care team. Sonographer scan time decreased from an average of 24 ± 6.8 min on a traditional platform to 5.4 ± 1.9 min on a tablet. CONCLUSIONS: Limited handheld echocardiography can be successfully implemented in the echocardiography laboratory for screening of COVID-19-related cardiac conditions. The protocol performed with handheld tablet ultrasound provides adequate diagnostic information of major cardiac complications of COVID-19 while decreasing sonographer contact and simplifying decontamination.