Assessment Period Research Articles

The Feasibility of Digital Testing using a Smartphone Application for Precision Brain Health Monitoring in the Framingham Heart Study

AbstractBackgroundEarly detection of cognitive decline is critical to identify effective treatments for Alzheimer’s disease and related dementias. The inherent heterogeneity of behaviors associated with brain health may obscure the signals derived from a typical neuropsychological evaluation, partly because of the limited frequency of assessment with which it can be conducted. This may lead to inaccurate or poor detection sensitivity. Digital health technology using smartphone applications enables frequent assessment and, thereby, more precise monitoring of brain health. The current study sought to examine the feasibility of using smartphone application‐based tasks in community‐based participants from the Framingham Heart Study (FHS).MethodThe smartphone application consists of three blocks of assessments, lasting approximately 15‐20 minutes (Figure 1). Block 1: Participants answer questions to ensure that they can see the stimuli and hear the instructions adequately. Block 2: Participants complete a series of cognitive tasks and respond to open‐ended questions which are voice recorded. Block 3: To ensure that performance is not influenced by external factors, participants respond to questions, for example, about their experiences with using the smartphone application.ResultTo date, 318 FHS participants have been enrolled into the study. Of these, as of 12/09/2022, 168 participants’ first assessment period has been completed within the two week period after being enrolled in the study. Of the 168 participants, a large majority (81%; n = 136) completed all the tasks, while the remaining 32 completed partial assessment. Table 1 reveals that the overall percentage of participants who have been enrolled in the study and the percentage of those who completed their first assessment are highly similar.ConclusionFindings reveal that older adults from a large, community‐based study are able to successfully download and complete the first set of tasks using their smartphone application. As data collection is ongoing, the number of older adults recruited into the study is expected to increase exponentially. These results indicate that it is feasible to monitor brain health on an on‐going basis using self‐administered smartphone applications, potentially creating an effective, lower cost, and scalable approach to detect significant changes in cognitive functions earlier and more accurately in the preclinical neurodegenerative process.

Investigating the social and environmental contexts of habitual walking ACTIVities in older adult DYADs: A mixed methods protocol for the ActivDyad study

AbstractBackgroundMobility‐related ambulatory activity (e.g., walking) is essential to healthy cognitive and functional ageing. Wearable technology (e.g., accelerometers/inertial measurement units; IMUs) allows us to objectively and continuously capture digital mobility outcomes (DMOs), e.g. volume, pattern and variability of walking activities. Continuous digital mobility assessment has been shown as feasible and acceptable to older adults with and without dementia. However, interpretation of DMOs is limited as we do not yet understand the impact of different social and environmental contexts on walking activity. For example, DMOs may be influenced by the volume of walking that one’s partner participates in, or by the walkability of their local area. Understanding the impact of social and environmental contexts on DMOs will support development of socio‐ecological strategies to support mobility in ageing. We aim to conduct a feasibility study in older adults with the following objectives: (1). Objectively assess DMOs in older adult dyads using digital mobility tools (i.e., IMUs/GPS); (2). Identify key social and environmental influences on DMOs through mixed‐methods exploration; (3). Develop a novel analytical approach combining DMOs with GPS data to assess independence/interdependence in dyads’ walking activities.MethodWe will recruit 20 older adult dyads in North‐East England for an observational cross‐sectional study. Walking activities will be recorded continuously for seven days using an IMU attached to participants’ lower backs. DMOs include volume (e.g., daily steps), pattern (e.g. mean bout length) and variability (of bout length) of walking activities. Simultaneously, participants will carry a GPS device (i.e., smartphone) to monitor excursions outside the home. Questionnaires will capture information on cognition, function, falls risk, exercise motivation, wellbeing, relationship mutuality, spatial navigation, and walkability of local area. Participants will complete a “mobility diary” for the assessment period (e.g., daily journeys, motivations/perceptions/familiarity of journeys).ResultPreliminary results will be presented regarding associations between social/environmental contexts with DMOs via flexible Bayesian statistical models and thematic qualitative analysis.ConclusionThis study will assess the feasibility of the protocol and analysis strategies, with intentions of developing further research to examine the impact of social and environmental influences on DMOs in people with dementia and their carers.

Nasopharyngeal Viral Load Is the Major Driver of Incident Antibody Immune Response to SARS-CoV-2 Infection.

Virologic determinants of seroconversion to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection were defined in a post hoc analysis of prospectively studied vaccine- and infection-naïve individuals at high risk for coronavirus disease 2019 (COVID-19). This phase 3 COVID-19 prevention trial (NCT04452318) with casirivimab and imdevimab was conducted in July 2020-February 2021, before widespread vaccine availability. Placebo-treated participants who were uninfected (SARS-CoV-2 quantitative reverse transcription polymerase chain reaction [RT-qPCR] negative) and seronegative were assessed weekly for 28 days (efficacy assessment period [EAP]) for COVID-19 symptoms and SARS-CoV-2 infection by RT-qPCR of nasopharyngeal swab samples and for serostatus by antinucleocapsid immunoglobulin (Ig) G. Regression-based modeling, including causal mediation analysis, estimated the effects of viral load on seroconversion. Of 157/1069 (14.7%) uninfected and seronegative (for antispike IgG, antispike IgA, and antinucleocapsid IgG) participants who became infected during the EAP, 105 (65%) seroconverted. The mean (SD) maximum viral load of seroconverters was 7.23 (1.68) log10 copies/mL vs 4.8 (2.2) log10 copies/mL in those who remained seronegative; viral loads of ∼6.0 log10 copies/mL better predicted seroconversion. The mean of the maximum viral load was 7.11 log10 copies/mL in symptomatic participants vs 5.58 log10 copies/mL in asymptomatic participants. The mean duration of detectable viral load was longer in seroconverted vs seronegative participants: 3.24 vs 1.63 weeks. Maximum SARS-CoV-2 viral load is a major driver of seroconversion and symptomatic COVID-19, with high viral loads (∼6.0 log10 copies/mL) better predicting seroconversion. Serology underestimates infection rates, incidence, and prevalence of SARS-CoV-2 infection.

Hiring Frictions and the Promise of Online Job Portals: Evidence from India

Despite the growing prominence of online job portals, firms remain reluctant to hire outside traditional recruitment networks. We find that experimentally providing firms with a combination of advertising and the ability to verify applicant identity increases portal-based hiring by 68 percent and the likelihood of filling a vacancy by 11 percent. Advertising attracts more skilled applicants, while verification enables the screening of unfamiliar applicants. Portal-based hires are retained beyond the standard assessment period, suggesting that they are well suited to the vacancies. Firms assigned only advertising also attract more skilled applicants, but providing neither advertising nor verification alone increases hiring. (JEL D22, J23, J24, J63, M51, O15)

Investigating the social and environmental contexts of habitual walking ACTIVities in older adult DYADs: A mixed methods protocol for the ActivDyad study

AbstractBackgroundMobility‐related ambulatory activity (e.g., walking) is essential to healthy cognitive and functional ageing. Wearable technology (e.g., accelerometers/inertial measurement units; IMUs) allows us to objectively and continuously capture digital mobility outcomes (DMOs), e.g. volume, pattern and variability of walking activities. Continuous digital mobility assessment has been shown as feasible and acceptable to older adults with and without dementia. However, interpretation of DMOs is limited as we do not yet understand the impact of different social and environmental contexts on walking activity. For example, DMOs may be influenced by the volume of walking that one’s partner participates in, or by the walkability of their local area. Understanding the impact of social and environmental contexts on DMOs will support development of socio‐ecological strategies to support mobility in ageing. We aim to conduct a feasibility study in older adults with the following objectives: (1). Objectively assess DMOs in older adult dyads using digital mobility tools (i.e., IMUs/GPS); (2). Identify key social and environmental influences on DMOs through mixed‐methods exploration; (3). Develop a novel analytical approach combining DMOs with GPS data to assess independence/interdependence in dyads’ walking activities.MethodWe will recruit 20 older adult dyads in North‐East England for an observational cross‐sectional study. Walking activities will be recorded continuously for seven days using an IMU attached to participants’ lower backs. DMOs include volume (e.g., daily steps), pattern (e.g. mean bout length) and variability (of bout length) of walking activities. Simultaneously, participants will carry a GPS device (i.e., smartphone) to monitor excursions outside the home. Questionnaires will capture information on cognition, function, falls risk, exercise motivation, wellbeing, relationship mutuality, spatial navigation, and walkability of local area. Participants will complete a “mobility diary” for the assessment period (e.g., daily journeys, motivations/perceptions/familiarity of journeys).ResultPreliminary results will be presented regarding associations between social/environmental contexts with DMOs via flexible Bayesian statistical models and thematic qualitative analysis.ConclusionThis study will assess the feasibility of the protocol and analysis strategies, with intentions of developing further research to examine the impact of social and environmental influences on DMOs in people with dementia and their carers.

Prevalence and Incidence of Primary Autoimmune Hemolytic Anemia and Cold Agglutinin Disease in the United States, 2016-2022: A Retrospective Study in Administrative Claims

Background Autoimmune hemolytic anemia (AIHA) is a decompensated acquired hemolysis caused by autoantibodies that act against red blood cells leading to anemia. Cold agglutinin disease (CAD) is a rare subtype of AIHA mediated by classical complement pathway activation, characterized by chronic hemolysis, severe anemia, fatigue, weakness, dizziness, and circulatory problems. The aim of this study was to update the epidemiology of AIHA and CAD in the United States using administrative claims data that includes commercially insured patients, as well as those with Medicare Advantage, Medicare Fee for Service (FFS) and Managed Medicaid plans. Methods Administrative closed claims from Optum CDM database (commercially insured single-payer and Medicare Advantage), Inovalon MORE 2 Registry (commercially insured multi-payer, Medicare Advantage, and Managed Medicaid), and 100% Medicare FFS (Part A/B services) data were used for this analysis. AIHA cases were defined as patients with at least 2 claims with ICD-9/10 diagnosis codes for AIHA (283.0, D59.1, D59.10, D59.11, D59.12, D59.13, D59.19) at least 30 days apart. CAD cases were defined as patients with at least 2 claims with ICD-10 diagnosis codes for CAD (D59.12) or at least 1 claim with diagnosis code for AIHA followed by 1 claim with diagnosis code for CAD (D59.12) at least 30 days apart. Index date was assigned to the first observed claims with the AIHA/CAD diagnosis. Analyses included patients 18 years of age and above with at least 180 days of continuous enrollment in their health plan prior to index for the assessment of the exclusion criteria. Patients with secondary causes of AIHA/CAD (e.g., lymphoma, leukemia, myeloma, cytomegalovirus, or Epstein-Barr virus) were excluded. US census data from years 2016-2021 was used to standardize the incidence and prevalence estimates by age and sex. Point prevalence was calculated as of January 1 st of each year using an all-data lookback. Period prevalence was calculated using a one calendar year assessment period. Incidence estimated new cases in a given year among patients with no prior evidence of AIHA in all data lookback. For CAD, estimates were presented for years 2022/23 due to the recency of the ICD-10 code specific to CAD (active as of 1 October 2020). Results Age and sex standardized point prevalence of AIHA per 1,000,000 persons was approximately 210 in the Medicare FFS across years 2016-2021, 160 in the Optum claims across years 2016-2022, and 50 in the MORE 2 database across years 2016-2022. One-year prevalence per 1,000,000 persons was approximately 190 in the Medicare FFS, 70 in the Optum claims, and 50 in the MORE 2 database across study years. Incidence per 1,000,000 was 50-60 in the Medicare FFS, 20-30 in the Optum claims, and 15 in the MORE 2 database. While overall standardized estimates differed across databases, incidence and prevalence estimates were similar when stratified by age group, indicating that standardization did not fully account for the underlying differences in the composition and representativeness of the overall US population in the three databases. Incidence and prevalence were higher among females than males and increased with age as expected. Incidence per 1,000,000 for year 2021 ranged from roughly 10-80 among those under the age of 45 years to 30-80 among those over the age of 65 years across the three databases. Point prevalence per 1,000,000 for year 2021 had a broader range from 30 to 220 among those under the age of 45 years and from 120 to 360 among those over the age of 65 years. The standardized point prevalence per 1,000,000 for CAD was 31 in Optum claims (year 2023), 33 in Medicare FFS (year 2021), and 14 in MORE 2 (year 2021). Prevalence of CAD was higher among females and increased with age. Conclusion This multi-database analysis provides updated epidemiology estimates for AIHA and CAD in the US. Age and sex standardized point prevalence for AIHA ranged from 60 to 210 per 1,000,000 across the 3 databases, with higher prevalence in the Medicare FFS database which primarily captures population over the age of 65 and was lower in the two databases that capture younger age groups, such as Managed Medicaid and commercially insured populations. Similarly, incidence of AIHA ranged from 15 to 60 per 1,000,000. Point prevalence of CAD ranged from 14 to 33 per 1,000,000. These estimates are in line with those previously reported for North America and Western Europe.

Impact of Symptom Benefit and Transfusion Response on Survival in Myelofibrosis Patients Treated with Pacritinib: PERSIST-2 Landmark Survival Analysis

Background: Pacritinib is a JAK1-sparing inhibitor of JAK2/IRAK1/ACVR1 that demonstrated symptom benefit measured by TSS (v2.0, excluding tiredness) vs best available therapy (BAT) in PERSIST-2, which enrolled cytopenic myelofibrosis patients with platelets ≤100×10 9/L. Recent datashowed that in patients with cytopenic MF, a ≥10% reduction in spleen volume at 12 weeks is associated with improved survival in patients treated with pacritinib ( Ajufo H, et al., J Clin Oncol;2023:14(16):Suppl). Surprisingly, this association was not confirmed in patients treated with BAT (82% of whom were on ruxolitinib). The association between other important measures of clinical benefit such as symptom burden reduction and anemia improvement on survival in patients treated with pacritinib has not previously been described. Methods: Patients randomized to pacritinib 200 mg BID and to BAT on PERSIST-2 were included if they were alive and on study at the start of the week 12 efficacy assessment period. Survival was assessed by Total Symptom Score (TSS; v2.0 excluding tiredness) reduction at various thresholds (≥50%, ≥20%, ≥10%, >0%) and transfusion independence (TI) response. TI was assessed among patients who required red blood cell (RBC) transfusion at baseline (within 90 days) and was defined, for the purposes of a landmark survival analysis, as the absence of RBC transfusions over any 12-week period from first dose through week 14 (allowing for a ±2-week window around week 12). Overall survival (OS) was estimated via the K-M method following the landmark approach; survival in responders vs non-responders was compared using the log-rank test. Results: Of the 59 patients treated with pacritinib who had a reduction of TSS≥10%, the median age was 67 years, 25% had a baseline high-risk DIPSS, median platelet count was 61 x10 9/L, median hemoglobin was 9.7 g/dL, and baseline TSS was 19.1. Reduction of TSS≥10% was associated with improved OS, with 1 death among 59 responders vs 4 deaths among 30 non-responders (hazard ratio [HR]=0.12, 95% confidence interval [CI]: 0.01, 0.79] P=0.021, Fig 1a). Similar to spleen volume reduction, the association between TSS response and OS weakened at more stringent TSS response thresholds (Fig 1c, e), with the BAT arm not showing an association between TSS response and OS at any threshold. (Fig 1b, d, f). In order to assess the relationship of specific TSS domains and survival , a landmark OS analysis was performed based on ≥20% reduction in physical function scores (sum of ‘tiredness’ and 'inactivity'), spleen-related symptom scores (sum of 'abdominal discomfort', ‘early satiety’, and 'left rib pain'), and cytokine-related symptom scores (sum of 'itching', ‘night sweats’, and ‘bone pain‘). For cytokine-related symptoms, the number of deaths in PAC responders was significantly different compared to non-responders, with 0 deaths among 35 responders vs 2 among 15 non-responders ( P=0.0325). Conversely the deaths among responders (2/22) vs non-responders (2/20) were not significantly different in the BAT arm. For the physical function and spleen-related symptom subscales, no significant differences between PAC responders and non-responders was observed (HR=0.60; 95% CI [0.05, 6.74] P=0.679) and (HR=0.26; 95% CI 0.02, 2.93, P=0.2435) respectively. Among 36 patients on PAC who received RBC transfusions at baseline, 7 achieved TI over at least a 12-week period up to the time of the landmark analysis. There were no deaths among TI responders compared to 2 (6.9%) among TI non-responders. There were too few TI responders on BAT (only 2 out of 38) to assess the impact on survival. Conclusion: In cytopenic myelofibrosis patients enrolled in PERSIST-2, having a reduction of TSS≥10% on full-dose PAC was associated with OS benefit - a finding that has not been noted with other JAK inhibitors to date. By contrast, this association was not found with BAT, (82% of these patients received ruxolitinib). Thus, reductions in TSS in patients treated with PAC were associated with an OS benefit. It is possible that pacritinib, with its distinctive mechanism of action, may offer a unique survival advantage for MF patients with moderate or severe thrombocytopenia, and further studies are required to understand the potential mechanisms of these distinct clinical observations. Study funded by CTI BioPharma Corp., a Sobi company.

398. Increased Risk of Severe COVID-19 Outcomes Across all Groups of Individuals with Hematological Malignancies, Solid Tumors, and Solid Organ Transplants Compared with the General Population: Initial Results from INFORM, a Retrospective Health Database Observational Study in England

Abstract Background Despite COVID-19 vaccination, individuals who are immunocompromised due to underlying conditions, such as cancer and organ transplant, are at a greater risk of severe COVID-19 outcomes compared with the general population that is vaccinated. However, there are limited data quantifying this risk during the omicron-predominant period, particularly for important sub-groups that may have variable risk for severe COVID-19 outcomes. We report initial findings from the INFORM study describing the clinical burden and severe COVID-19 outcomes in patients with immunocompromised conditions (IC) in England, UK in 2022. Methods This retrospective cohort study utilized National Health Service database in England. The study period was from Jan 1–Dec 31, 2022 and the baseline period for assessment of patient characteristics, including IC, was from Jan 1, 2017–Dec 31, 2021. Definitions of IC sub-groups are provided in Table 1. Severe COVID-19 outcomes were defined as COVID-19–related hospitalization, COVID-19–related intensive care unit (ICU) admission, and/or COVID-related death. Results Of the 11,990,730 individuals in the general population sample aged ≥ 12 years, 468,745 (3.9%) were immunocompromised and accounted for approximately one-quarter of severe COVID-19–related outcomes (22% of hospitalizations, 28% of ICU admissions, and 23% of deaths; Table 2). The risk of severe COVID-19 outcomes was higher in well-recognized IC conditions (eg, solid organ transplants, hematological malignancies, and solid tumors) across all the sub-groups compared with the overall population (Table 2). Conclusion There is an increased burden in the prevalence of severe COVID-19 outcomes among all individuals with IC, highlighting the need for additional protection to target this population. Disclosures Richard McNulty, MD, AstraZeneca: Employee Sabada Dube, PhD, AstraZeneca: Employee Yi Lu, PhD, Evidera: Employee Sophie Graham, MSc, Evidera: Employee Sofie Arnetorp, MS, AstraZeneca: Employee Nahila Justo, PhD, MBA, Evidera: Employee|Karolinska Institute: Employee Renata Yokota, PhD, AstraZeneca: Employee Kathryn Evans, MPH, Evidera: Employee Sudhir Venkatesan, MPH, PhD, AstraZeneca: Employee Mark Yates, PhD, Evidera: Employee Sylvia Taylor, PhD, MPH, MBA, AstraZeneca: Stocks/Bonds Jennifer Quint, PhD, AstraZeneca: Grant/Research Support|Evidera: Grant/Research Support|GlaxoSmithKline: Grant/Research Support|Insmed: Grant/Research Support Rachael A. Evans, PhD FRCP, AstraZeneca: Advisor/Consultant|Boehringer: Advisor/Consultant|Evidera: Advisor/Consultant

Effect of probiotic supplementation on cognition and depressive symptoms in patients with depression: A systematic review and meta-analysis.

Depression affects millions globally and often coexists with cognitive deficits. This study explored the potential of probiotics in enhancing cognition and ameliorating depressive symptoms in major depressive disorder patients. Utilizing the Preferred Reporting Items for Systematic Reviews and Meta-Analyses protocol and the Population, Intervention, Comparator, Outcome, and Study design framework, we systematically reviewed randomized controlled trials examining probiotic effects on cognition and depressive symptoms. Searches spanned 7 databases from January 2010 to May 2022. Risk of bias was assessed using Revised Cochrane Risk of Bias 2.0, and meta-analysis was conducted with RevMan 5.4.1. Publication bias was evaluated via Egger test. In a systematic review on the effects of probiotic supplementation on cognition and depressive symptoms in depression patients, 635 records were initially identified, with 4 studies ultimately included. These randomized controlled trials were conducted across diverse regions, primarily involving females, with assessment periods ranging from 1 to 2 months. Concerning cognitive outcomes, a statistically significant moderate improvement was found with probiotic supplementation, based on the mean difference and its 95% confidence interval. However, for depressive symptoms, the overall effect was negligible and not statistically significant. A heterogeneity test indicated consistent findings across studies for both cognitive and depressive outcomes (I² = 0% for both). The potential for publication bias was evaluated using the Egger linear regression test, suggesting no significant bias, though caution is advised due to the limited number of studies. Probiotics may enhance cognitive domains and mitigate depressive symptoms, emphasizing the gut-brain axis role. However, methodological variations and brief intervention durations call for more standardized, extensive research.

Exploring the efficacy of dialectical behaviour therapy and methylphenidate on emotional comorbid symptoms in adults with attention Deficit/Hyperactivity disorder: Results of the COMPAS multicentre randomised controlled trial

This study evaluated the efficacy of dialectical behaviour group therapy (GPT) vs. individual clinical management (CM) and methylphenidate (MPH) vs. placebo (PLB) on emotional symptoms in adults with ADHD. This longitudinal multicentre RCT compared four groups (GPT+MPH, GPT+PLB, CM+MPH, and CM+PLB) over five assessment periods, from baseline to week 130. Emotional symptomatology was assessed using SCL-90-R subscales. Of the 433 randomised participants, 371 remained for final analysis. At week 13, the GPT+MPH group showed smaller reductions in anxiety symptoms than the CM groups, but the differences disappeared at subsequent assessments. Improvements in emotional symptom were significantly predicted by reductions in core ADHD symptoms in all groups except the GPT+MPH group. The unexpected lack of between-group differences may be explained by a "floor effect", different intervention settings (group vs. individual), and psychotherapy type. Multiple regression analyses suggest a more specific effect of combined interventions (GPT+MPH). Implications for clinical practice are discussed.Clinical trial registration: ISRCTN54096201 (Current Controlled Trials).

Abstract 14720: Persistence and Adherence to Proprotein Convertase Subtilisin/Kexin Type 9 Monoclonal Antibodies and Ezetimibe in Real - World Settings

Introduction: Non-statin cholesterol-lowering therapies (proprotein convertase subtilisin/kexin type 9 monoclonal antibodies [PCSK9mAb] and ezetimibe) have been shown to reduce atherosclerotic cardiovascular disease (ASCVD) events in randomized clinical trials of patients treated with statin therapy. Effectiveness in the real world, however, is contingent on treatment persistence and adherence. Aim: To estimate the proportion of patients who were on therapy, persistent and had high adherence at 365 days following the initiation of a PCSK9mAb versus ezetimibe in real-world clinical practice. Methods: We included adults initiating a PCSK9mAb (n= 16,588, 44% ≥ 65 years, 56% male, 78% with ASCVD) or ezetimibe (n=83,086, 35% ≥ 65 years, 51% male, 46% with ASCVD) from Medicare and MarketScan commercial health insurance databases between 7/2015 and 12/2019. We assessed 3 outcomes using pharmacy claims within 365 days following initiation (assessment period): 1) percentage of patients on therapy: percentage of patients with medication supply in the last 60 of 365 days following initiation; 2) persistence: not having a gap of ≥ 60 days between the last day of supply from one pharmacy claim and the next claim; 3) high adherence: having a day of supply for ≥ 80% of the 365 days. Results: Percentage on therapy, persistence, and high adherence were higher among patients on PCSK9mAb versus ezetimibe at 365 days (Table 1). When, restricted to participants who were persistent at 365 days, adherence to both PCSK9mAb and ezetimibe was high. The adjusted multivariable-adjusted risk ratio [95% CI] for percentage on therapy, persistent and having high adherence to PCSK9mAb versus ezetimibe was: 1.20 [1.18, 1.21], 1.22 [1.20, 1.24], and 1.16 [1.14, 1.18]. Conclusions: Patients initiating PCSK9mAb were more likely to be on therapy, persistent and with high adherence at 365 days compared to their counterparts who initiated ezetimibe. Funding: Amgen Inc.

Abstract 13447: Political Orientation of Online Media Sources and Reporting of COVID-19 Vaccine Myocarditis

Background: Political orientation has played a role in patients' perceptions of risk associated with COVID-19 vaccination, including COVID-19 vaccine myocarditis (CVM). We examined the relationship between political orientation of popular online media outlets and reporting of CVM. Methods: Media sites were classified as “left” or “right" biased using the Allsides media bias rating report. For each site “COVID vaccine myocarditis” was searched in articles posted 5/21-12/22. Each search return was reviewed for the following: 1) Did it contain numerical data or reference the source of numerical data regarding CVM risk? 2) Did it report benefits of covid vaccination? 3) Did it mention covid infection -related myocarditis? Monthly reports of vaccine-related adverse events were obtained directly from the Vaccine Adverse Events Reporting System (VAERS). Correlations of reports of left- vs. right-leaning media were performed using Pearson Product Moment Correlation. Results: A total of 520 unique online reports regarding CVM were reviewed. Comparison of report volumes from left vs. right biased media sources by month during the assessment period demonstrated modest correlation (r=0.546, p=0.013), suggesting that monthly reporting volumes were driven by availability of information regarding CVM rather than media political alignment. Peak reporting across both left and right biased media was temporally proximate to peak volume of VAERS reporting. Left biased media sources were significantly more likely to include numerical data and/or links to source data vs. right biased sources (76.6% vs. 24.3%, p<0.001) and likewise were more likely to include data supporting benefits of covid vaccination (85.1% vs. 21.7%. p<0.001). In contrast, there was no difference regarding mention of COVID-19 infection-related myocarditis (24.5% vs. 24.3%, p=0.957). Conclusion: Political orientation of online news sites was not associated with frequency of CVM reports but was significantly related to report content, most notably whether reports included numerical vs verbal representations of CVM risk. These bias-related reporting characteristics may contribute to the relationship between political orientation and patient understanding of risk of CVM.

303 Accuracy of the Smartscale In-Pen Weighing System

Abstract The Beef Improvement Federation recommends repeated body weight (BW) measures in a 70-d test period for accurate assessment of average daily gain (ADG) in growing animals. In-pen automated scale systems enable daily monitoring of BW and ADG without the additional labor, time, and animal stress that is associated with recording static chute BW. The objective of the current study was to determine the utility of partial body weight (pBW) for estimating full BW and average daily gain (ADG) in growing steers. SmartScales (C-Lock Inc.) were positioned in front of water troughs and used to measure front-quarter pBW while animals were drinking. Partial body weight was used to estimate full BW using an internally developed slope-intercept equation. The dataset consisted of pBW, estimated BW, and recorded BW for 300 steers in a 50-d feed performance test. Single-day chute BW were recorded on days 14, 28, 35, and 50. Relationships and errors between estimated BW and recorded BW were evaluated. Individual animal ADG estimates were calculated and compared using estimated and recorded BW measurements. Steers in the study visited the water trough an average of 4.3 ± 2.6 times per day. On average, pBW explained 96.1% variation in recorded BW. Average predicted BW and recorded BW differed by 8.3 ± 6.4 kg, or 0.15 ± 3.0 %-units. Average daily gain calculated from pBW and recorded BW were strongly correlated (r = 0.83). On average, ADG calculated using pBW and recorded BW differed by 0.14 ± 0.12 kg, or 8.8 ± 8.0 %-units. Real-time pBW collected using in-pen weighing systems can be used to accurately estimate full BW and ADG.

A Phase 1 Cohort Dose Escalation and Expansion Trial to Determine the Safety, Tolerance, Maximum Tolerated Dose, and Preliminary Antineoplastic Activity of IKS03 in Patients with Advanced B-Cell Non-Hodgkin Lymphomas (NHL)

Background: IKS03 is an antibody-drug conjugate (ADC) comprising an anti-CD19 antibody conjugated with novel ConjuALL technology to a highly potent proprietary DNA-crosslinking pyrrolobenzodiazepine (PBD) prodrug payload for the treatment of CD19-positive hematologic malignancies. Both the payload and the linker of IKS03 incorporate an innovative tumor-selective chemistry that takes advantage of the overexpression of beta glucuronidase in cancer cells compared to most normal tissues. Payload release and activation require cleavage of glucuronide moieties that are incorporated into the linker payload structure providing improvements in both efficacy and safety compared to traditional ADC formats. This “glucuronide trigger” is stable while in circulation with minimal to no systemic payload release from the ADC. Following binding and internalization of IKS03 into a CD19-positive cancer cell, beta glucuronidase can release the active PBD payload leading to cell death. Normal tissues without CD19 expression and/or with low levels of the beta glucuronidase enzyme have limited ADC uptake, are less able to process IKS03 and are differentially spared. In preclinical studies, IKS03 demonstrated significant in vivo efficacy with complete tumor regressions in CD19-positive diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL), and mantle cell lymphoma (MCL) xenograft models at single doses of 0.1 to 1 mg/kg. IKS03 demonstrated greater activity than the clinical benchmark ADC loncastuximab tesirine. IKS03 is also highly effective in patient-derived xenograft models that contain some of the genetic alterations commonly found in relapsed/refractory NHL patients. Results from toxicology studies in cynomologus monkey suggest a manageable safety profile at single doses, well above those required for in vivo activity. Pharmacokinetics are favorable with a mean total ADC half-life of 8 days and undetectable levels of the active PBD payload in circulation confirming targeted delivery of the payload. Study Design and Methods: This Phase 1 multicenter, open label, non-randomized study of IKS03 will consist of two parts: dose-escalation (Part I) and dose-expansion (Part II) together enrolling approximately 140 adult patients with relapsed or refractory B-cell NHL after at least two prior lines of systemic therapy. Patients will receive repeat doses of study drug by IV infusion on Day 1 of each 21-day cycle, until disease progression, unacceptable toxicity, or another withdrawal criterion is met. Key exclusion criteria include: active central nervous system involvement with NHL; clinically significant cardiovascular, pulmonary or hepatic disease; or receipt of other CD19-directed therapy within 3 months. Part I dose escalation will enroll patients with confirmed CD19-positive, measurable or non-measurable advanced B-cell NHL. Eligible subtypes include DLBCL, MCL, FL, high-grade B-cell, and marginal zone lymphoma as per WHO 2016 classification. Patients with Burkitt's lymphoma, Waldenström macroglobulinemia, and chronic lymphocytic leukemia are excluded. In Part 1, the primary objective is establishment of the recommended Phase 2 dose (RP2D) by evaluation of safety, tolerability and the maximum tolerated dose (MTD) of IKS03. Dose escalation will follow a 3+3 design. A two cycle Dose-Limiting Toxicity (DLT) assessment period will be observed, and dose-escalation decisions will be guided by a study safety committee. Dose escalation increments will be adjusted based on occurrence of protocol-specified DLTs as well as overall tolerability. Secondary objectives include characterization of immunogenicity and pharmacokinetic (PK) profile of IKS03. Exploratory objectives include preliminary antineoplastic activity per Lugano criteria (Cheson et al, JCO 2014) and evaluation of pharmacodynamic markers. Part II will further evaluate the antineoplastic activity of IKS03 at the RP2D in expansion cohorts of patients with selected NHL subtypes and with measurable disease. Sample size will be determined for each subtype using a Simon Two-Stage design. Secondary objectives include further evaluation of safety, tolerability, immunogenicity and PK profile of IKS03 as well as confirmation of the RP2D. Clinical trial information: NCT05365659.

2 Infant Imitation: Detecting Risk in the First Year with PediaTrac™

Objective:Imitation has pervasive associations with social and communicative development. However, few methods have been developed to measure this construct in typically developing infants, and even less is available for at-risk populations, such as infants born preterm. Autism spectrum disorder (ASD), a particular risk of premature birth, is associated with atypical imitation and social communication. Although imitation emerges in infancy, most current screening and diagnostic tools for ASD cannot be utilized prior to 12 months. The present study aimed to develop and validate a caregiver-report measure of infant imitation, characterize imitation profiles at 4, 6, and 9 months in term and preterm infants, and explore the relationship between imitation and scores on an ASD screening questionnaire at 18 months.Participants and Methods:Participants (N = 571) were recruited from a larger multi-site study of PediaTrac™ v3.0, a web-based tool for monitoring and tracking infant development, and were surveyed longitudinally at birth, 2, 4, 6, 9, 12, 15, and 18 months. Participants completed the online PediaTrac™ survey and several reliable and validated questionnaires via pen-and-paper format. For the purposes of this study, only the Ages and Stages Questionnaire (3rd ed.; ASQ-3), Communication and Symbolic Behavior Scales-Developmental Profile (CSBS-DP), Brief Infant Sleep Questionnaire (BISQ), and the Modified Checklist for Autism in Toddlers - Revised with Follow-Up (M-CHAT-R/F) were examined. The following hypotheses were tested: (1) proposed imitation items will represent a unitary latent construct, for which convergent and discriminant validity will be demonstrated, (2) there will be measurement invariance between term status groups at each assessment period, (3) preterm infants will obtain lower caregiver-reported imitation scores compared to term infants, and (4) imitation abilities at the assessment period with the most robust imitation factor will predict M-CHAT-R/F scores at 18 months.Results:Distinct imitation factors at 4, 6, and 9 months were modeled with confirmatory and exploratory factor analyses. Relationships between the factors and established measures of infant communication (CSBS; ASQ) and sleep (BISQ) revealed convergent and discriminant validity, respectively. Strict measurement invariance was demonstrated for the 4- and 9-month factors, and metric invariance for the 6-month measure. Full term infants scored higher on imitation at 9 months, though variance in this outcome was related to term status differences in sensorimotor skills. Lastly, the 9-month imitation factor, coupled with 6-month sensorimotor skills, predicted 18-month ASD risk over and above gestational age.Conclusions:This study provides support for the assessment of infant imitation, utilizing imitation to detect risk in preterm infants, and extending the age of identification for ASD risk into the first year. PediaTrac™ imitation, in combination with the PediaTrac™ sensorimotor domain, may be useful in detecting developmental risk, and specifically risk for ASD, within the first year, leading to earlier initiation of intervention. Further, with its minimal completion time and ease of dissemination through digital platforms, this measure can expand access to care and improve long-term outcomes for children and families.

97 Evaluation of Video and Telephone-Based Administration of the Uniform Data Set Version 3 (UDS v3.0) Teleneuropsychological Measures

Objective:Telecommunication-assisted neuropsychological assessment (teleNP) has become more widespread, particularly in response to the COVID-19 pandemic. However, comparatively few studies have evaluated in-home teleNP testing and none, to our knowledge, have evaluated the National Alzheimer’s Coordinating Center’s (NACC) Uniform Data Set version 3 tele-adapted test battery (UDS v3.0 t-cog). The current study compares in-home teleNP administration of the UDS v3.0, acquired while in-person activities were suspended due to COVID-19, with a prior in-person UDS v3.0 evaluation.Participants and Methods:210 participants from the Michigan Alzheimer’s Disease Research Center’s longitudinal study of memory and aging completed both an in-person UDS v3.0 and a subsequent teleNP UDS v3.0 evaluation. The teleNP UDS v3.0 was administered either via video conference (n = 131), telephone (n = 75), or hybrid format (n = 4) with approximately 16 months between evaluations (mean = 484.7 days; SD = 122.4 days; range = 320-986 days). The following clinical phenotypes were represented at the initial assessment period (i.e., the most recent in-person UDS v3.0 evaluation prior to the teleNP UDS v3.0): cognitively healthy (n = 138), mild cognitive impairment (MCI; n = 60), dementia (n = 11), and impaired not MCI (n = 1). Tests included both the in-person and teleNP UDS v3.0 measures, as well as the Hopkins Verbal Learning Test-Revised (HVLT-R) and Letter “C” Fluency.Results:We calculated intraclass correlation coefficients (ICC) with raw scores from each time point for the entire sample. Sub-analyses were conducted for each phenotype among participants with an unchanged consensus research diagnosis: cognitively healthy (n = 122), MCI (n = 47), or cognitively impaired (i.e., MCI, dementia, and impaired not MCI) (n = 66). Test-retest reliability across modalities and clinical phenotypes was, in general, moderate. The poorest agreement was associated with the Trail Making Test (TMT) - A (ICC = 0.00; r = 0.027), TMT - B (ICC = 0.26; r = 0.44), and Number Span Backward (ICC = 0.49). The HVLT-R demonstrated moderate reliability overall (ICC = 0.51-0.68) but had notably weak reliability for cognitively healthy participants (ICC = 0.12-0.36). The most favorable reliability was observed in Craft Story 21 Recall - Delayed (ICC = 0.77), Letter Fluency (C, F, and L) (ICC = 0.74), Multilingual Naming Test (MINT) (ICC = 0.75), and Benson Complex Figure – Delayed (ICC = 0.79).Conclusions:Even after accounting for the inherent limitations of this study (e.g., significant lapse of time between testing intervals), our findings suggest that the UDS v3.0 teleNP battery shows only modest relationships with its in-person counterpart. Particular caution should be used when interpreting measures showing questionable reliability, though we encourage further investigation of remote vs. in-person testing under more controlled conditions.

The lowest carbon HVAC system could be no system: the design and lifecycle comparison of two heating and cooling options for Canada’s first hempcrete institutional building

This paper presents a comparative analysis of lifecycle carbon for two heating and cooling system options: a reversible ductless split ASHP and direct electric baseboards with a radiative cooling paint. It was determined that over a 60-year assessment period including refrigerant leakage, the ASHP contributed between 2 and 7 times the lifecycle carbon of the direct electric, depending on the consideration of the cooling paint. A sensitivity analysis found that the electrical emission factor of the grid and the refrigerant type and leakage reduction measures both had a strong influence on the lifecycle carbon comparison of the two options. The findings of this study are intended to continue advancing the discussion of the true lifecycle carbon impact that mechanical systems contribute to overall building emissions.

Sacubitril/valsartan and the risk of incident dementia in heart failure: a nationwide propensity-matched cohort study.

Sacubitril acts to inhibit neprilysin and as neprilysin is involved in amyloid-beta degradation in the central nervous system, and there is concern that sacubitril/valsartan may increase the risk of dementia. We aimed to compare the risk of incident dementia associated with sacubitril/valsartan and angiotensin II receptor blockers (ARBs). Patients with heart failure with reduced ejection fraction treated with either sacubitril/valsartan or ARB, identified from the Korean National Health Insurance Service database, were matched in a 1:2 ratio using propensity scores (6789 on sacubitril/valsartan and 13,578 on ARBs) and followed up for incident dementia. During a mean follow-up of 2.5years, 526 (2.6%) patients were newly diagnosed with dementia: Alzheimer dementia in 282, vascular dementia in 8, and other dementia in 236. There was no significant difference in the risk of overall dementia (hazard ratio [HR] 0.84, 95% confidence interval [CI] 0.70-1.01), Alzheimer dementia (HR 0.85, 95% CI 0.67-1.10), vascular dementia (HR 0.98, 95% CI 0.23-4.11), and all other dementias (HR 0.81, 95% CI 0.62-1.07) between sacubitril/valsartan users and ARB users. These results were consistent regardless of initial sacubitril/valsartan dose and subgroups including old age, previous mild cognitive impairment, previous stroke, and concomitant antiplatelet or anticoagulation. Sensitivity analysis with a 1-year lag period for dementia assessment confirmed the main analysis. Meanwhile, risk of incident stroke was lower in sacubitril/valsartan users compared to ARBs users. In a nationwide propensity-matched cohort of patients with heart failure, sacubitril/valsartan was not associated with an increased risk of incident dementia compared to ARBs.

Cost-per-responder analysis for eltrombopag and rituximab in the treatment of primary immune thrombocytopenia in Spain

ObjectiveSplenectomy, thrombopoietin receptor agonists and rituximab are the second-line treatments for steroid-resistant adult primary immune thrombocytopenia. The last two are becoming the most widely used treatments to avoid splenectomy adverse effects and inconveniences. However, the choice between rituximab and thrombopoietin receptor agonists is unclear. Therefore, the treatment cost may be of particular interest to prioritize the therapy option. Our aim is to determine the cost per responding-patient after 6 months of use of rituximab compared to thrombopoietin receptor agonists eltrombopag in the treatment of chronic primary immune thrombocytopenia in the Spanish National Health Service. MethodA 26-week decision tree model was developed to assess the cost of treatment response of adult patients with chronic-refractory primary immune thrombocytopenia to eltrombopag and rituximab from the perspective of the Spanish National Health System. Effectiveness was obtained from the literature, and cost was obtained from the official rates. Costs were expressed in € (2018). Due to the short period of assessment, no discount rate was applied. ResultsThe average cost per patient after 6 months of treatment was slightly higher for eltrombopag (€13,089.40) than for rituximab (€11,852.60). However, the greater response rate of eltrombopag decreases the bleeding costs, resulting in a 29% higher cost per responding-patient with rituximab (€18,964.15) than for eltrombopag (€14,732.65). This result is consistent with the results of the 15 sensitivity analyses carried out where eltrombopag always represents a lower cost per responding patient, except in the sensitivity analysis in which treatment with eltrombopag is performed at its maximum dose (75mg). Only in this case, the cost per responder of eltrombopag is €48 more expensive than that of rituximab. Likewise, the greatest difference in favor of eltrombopag occurs in the scenario that uses the minimum dose of this drug —25mg— (eltrombopag €7,622.14 compared to €18,964.15 for rituximab). Thus, the cost per responding patient is lower in eltrombopag even if a second cycle of retreatment with rituximab is not performed (€14,732.65 versus €15,298.61). ConclusionsThe treatment cost of rituximab, including monitoring and bleeding costs, is higher than eltrombopag, favoring the latter over rituximab treatment.

Effects of Salix psammophila on groundwater recharge in a semiarid area of north China

Study regionThe semiarid Mu Us Sandy Land (MUSL) was selected for this study. It is in the farming‐pastoral ecotone of north China and functions as an eco-environmental barrier. Study focusAfforestation can mitigate desertification and soil erosion by improving hydrologic condition, which is particularly true for semiarid and arid regions. However, little is known about the quantitative response of hydrologic improvement to afforestation level that can be measured by leaf area index (LAI). The objective was to setup and use a physically-based model to quantitatively assess the dynamics of water fluxes from Salix psammophila afforestation in the MUSL. New hydrological insights for the regionAcross the assessment period of 28 April to 3 October 2016, the total transpiration was determined to be about 294.4 mm. As LAI increased, while the transpiration tended to increase and the evaporation to decrease, the evapotranspiration tended to increase with increase of LAI until LAI =2.0 and then plateaued for LAI >2.0. On the other hand, the recharge rate tended to decrease with increase of LAI until LAI =2.0 and then plateaued for LAI >2.0. Overall, the impacts of Salix psammophila afforestation on soil-water replenishment and groundwater recharge would plateau for LAI >2.0, mandating a good balance between solving large-scope eco-environmental problems by Salix psammophila afforestation and sustaining water resources in the long run.