Correction: Quantifying the three-dimensional facial morphology of the laboratory rat with a focus on the vibrissae.

[This corrects the article DOI: 10.1371/journal.pone.0194981.].

Characterizing Technology Use and Preferences for Health Communication in South Asian Immigrants With Prediabetes or Diabetes: Cross-Sectional Descriptive Study.

BACKGROUND: Type 2 diabetes disproportionately affects South Asian subgroups. Lifestyle prevention programs help prevent and manage diabetes; however, there is a need to tailor these programs for mobile health (mHealth). OBJECTIVE: This study examined technology access, current use, and preferences for health communication among South Asian immigrants diagnosed with or at risk for diabetes, overall and by sex. We examined factors associated with interest in receiving diabetes information by (1) text message, (2) online (videos, voice notes, online forums), and (3) none or skipped, adjusting for sociodemographic characteristics and technology access. METHODS: We used baseline data collected in 2019-2021 from two clinical trials among South Asian immigrants in New York City (NYC), with one trial focused on diabetes prevention and the other focused on diabetes management. Descriptive statistics were used to examine overall and sex-stratified impacts of sociodemographics on technology use. Overall logistic regression was used to examine the preference for diabetes information by text message, online (videos, voice notes, or forums), and no interest/skipped response. RESULTS: The overall sample (N=816) had a mean age of 51.8 years (SD 11.0), and was mostly female (462/816, 56.6%), married (756/816, 92.6%), with below high school education (476/816, 58.3%) and limited English proficiency (731/816, 89.6%). Most participants had a smartphone (611/816, 74.9%) and reported interest in receiving diabetes information via text message (609/816, 74.6%). Compared to male participants, female participants were significantly less likely to own smartphones (317/462, 68.6% vs 294/354, 83.1%) or use social media apps (Viber: 102/462, 22.1% vs 111/354, 31.4%; WhatsApp: 279/462, 60.4% vs 255/354, 72.0%; Facebook: Messenger 72/462, 15.6% vs 150/354, 42.4%). A preference for receiving diabetes information via text messaging was associated with male sex (adjusted odds ratio [AOR] 1.63, 95% CI 1.01-2.55; P=.04), current unemployment (AOR 1.62, 95% CI 1.03-2.53; P=.04), above high school education (AOR 2.17, 95% CI 1.41-3.32; P<.001), and owning a smart device (AOR 3.35, 95% CI 2.17-5.18; P<.001). A preference for videos, voice notes, or online forums was associated with male sex (AOR 2.38, 95% CI 1.59-3.57; P<.001) and ownership of a smart device (AOR 5.19, 95% CI 2.83-9.51; P<.001). No interest/skipping the question was associated with female sex (AOR 2.66, 95% CI 1.55-4.56; P<.001), high school education or below (AOR 2.02, 95% CI 1.22-3.36; P=.01), not being married (AOR 2.26, 95% CI 1.13-4.52; P=.02), current employment (AOR 1.96, 95% CI 1.18-3.29; P=.01), and not owning a smart device (AOR 2.06, 95% CI 2.06-5.44; P<.001). CONCLUSIONS: Technology access and social media usage were moderately high in primarily low-income South Asian immigrants in NYC with prediabetes or diabetes. Sex, education, marital status, and employment were associated with interest in mHealth interventions. Additional support to South Asian women may be required when designing and developing mHealth interventions. TRIAL REGISTRATION: ClinicalTrials.gov NCT03333044; https://classic.clinicaltrials.gov/ct2/show/NCT03333044, ClinicalTrials.gov NCT03188094; https://classic.clinicaltrials.gov/ct2/show/NCT03188094. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.1186/s13063-019-3711-y.

Spatial arrangement of the whiskers of harbor seals ( Phoca vitulina ) compared to whisker arrangements of mice ( Mus musculus ) and rats ( Rattus norvegicus ).

Most mammals have specialized facial hairs known as vibrissae (whiskers), sensitive tactile structures that subserve both touch and flow sensing. Different animals have different numbers and geometric arrangements of whiskers, and it seems nearly self-evident that these differences would correlate with functional and behavioral use. To date, however, cross-species comparisons of three-dimensional (3D) whisker array geometry have been limited because standard morphometric techniques cannot be applied. Our laboratory recently developed a novel approach to enable quantitative, cross-species vibrissal array comparisons. Here we quantify the 3D morphology of the vibrissal array of the harbor seal ( Phoca vitulina ), construct a CAD model of the array, and compare array morphologies of harbor seals, mice ( Mus musculus ) and rats ( Rattus norvegicus ). In all three species whisker arclength decreases from caudal to rostral, whisker curvature increases from caudal to rostral, and whiskers emerge from the face in smooth orientation gradients. Two aspects of whisker orientation are strikingly consistent across species: the elevation angle is constant within a row, and the twist of the whisker about its own axis varies smoothly in a diagonal gradient across the array. We suggest that invariant whisker elevation within a row may aid localization behaviors, while variable twist-orientation may help the animal sense stimulus direction. We anticipate this work will serve as a starting point for quantitative comparisons of vibrissal arrays across species, help clarify the mechanical basis by which seal vibrissae enable efficient wake detection and following, and enable the creation of whole-body biomechanical models for neuroscience and robotics.

Comparative morphology of the whiskers and faces of mice (Mus musculus) and rats (Rattus norvegicus).

Understanding neural function requires quantification of the sensory signals that an animal's brain evolved to interpret. These signals in turn depend on the morphology and mechanics of the animal's sensory structures. Although the house mouse (Mus musculus) is one of the most common model species used in neuroscience, the spatial arrangement of its facial sensors has not yet been quantified. To address this gap, the present study quantifies the facial morphology of the mouse, with a particular focus on the geometry of its vibrissae (whiskers). The study develops equations that establish relationships between the three-dimensional (3D) locations of whisker basepoints, whisker geometry (arclength, curvature) and the 3D angles at which the whiskers emerge from the face. Additionally, the positions of facial sensory organs are quantified relative to bregma-lambda. Comparisons with the Norway rat (Rattus norvegicus) indicate that when normalized for head size, the whiskers of these two species have similar spacing density. The rostral-caudal distances between facial landmarks of the rat are a factor of ∼2.0 greater than the mouse, while the scale of bilateral distances is larger and more variable. We interpret these data to suggest that the larger size of rats compared with mice is a derived (apomorphic) trait. As rodents are increasingly important models in behavioral neuroscience, the morphological model developed here will help researchers generate naturalistic, multimodal patterns of stimulation for neurophysiological experiments and allow the generation of synthetic datasets and simulations to close the loop between brain, body and environment.

Leveraging Electronic Health Record Technology and Team Care to Address Medication Adherence: Protocol for a Cluster Randomized Controlled Trial.

BACKGROUND: Low medication adherence is a common cause of high blood pressure but is often unrecognized in clinical practice. Electronic data linkages between electronic health records (EHRs) and pharmacies offer the opportunity to identify low medication adherence, which can be used for interventions at the point of care. We developed a multicomponent intervention that uses linked EHR and pharmacy data to automatically identify patients with elevated blood pressure and low medication adherence. The intervention then combines team-based care with EHR-based workflows to address medication nonadherence. OBJECTIVE: This study aims to describe the design of the Leveraging EHR Technology and Team Care to Address Medication Adherence (TEAMLET) trial, which tests the effectiveness of a multicomponent intervention that leverages EHR-based data and team-based care on medication adherence among patients with hypertension. METHODS: TEAMLET is a pragmatic, cluster randomized controlled trial in which 10 primary care practices will be randomized 1:1 to the multicomponent intervention or usual care. We will include all patients with hypertension and low medication adherence who are seen at enrolled practices. The primary outcome is medication adherence, as measured by the proportion of days covered, and the secondary outcome is clinic systolic blood pressure. We will also assess intervention implementation, including adoption, acceptability, fidelity, cost, and sustainability. RESULTS: As of May 2023, we have randomized 10 primary care practices into the study, with 5 practices assigned to each arm of the trial. The enrollment for the study commenced on October 5, 2022, and the trial is currently ongoing. We anticipate patient recruitment to go through the fall of 2023 and the primary outcomes to be assessed in the fall of 2024. CONCLUSIONS: The TEAMLET trial will evaluate the effectiveness of a multicomponent intervention that leverages EHR-based data and team-based care on medication adherence. If successful, the intervention could offer a scalable approach to address inadequate blood pressure control among millions of patients with hypertension. TRIAL REGISTRATION: ClinicalTrials.gov NCT05349422; https://clinicaltrials.gov/ct2/show/NCT05349422. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/47930.

The Prevalence and Correlates of Diabetes Distress among South Asians Living in New York City (NYC): Baseline Results from a Randomized Trial.

Background: Type 2 diabetes (T2D) disproportionately affects South Asians in the United States (US). Living with T2D can be challenging due to the distress it can create for an individual. Distress associated with diabetes, commonly known as diabetes distress (DD), may lead to complications and challenges with the management of diabetes. This study aims to describe the prevalence of DD among a sample of South Asians in New York City (NYC) seeking care in community-based primary care settings and its association with sociodemographic characteristics and clinical measures. Methods: This study utilized baseline data from the Diabetes Research, Education, and Action for Minorities (DREAM) Initiative, an intervention designed to reduce hemoglobin A1C (HbA1c) among South Asians with uncontrolled T2D in NYC. DD was measured using the Diabetes Distress Scale (DDS). First, descriptive statistics were used to analyze sociodemographic variables. Chi-square tests assessed categorical variables and Wilcoxon Rank Sum tests assessed continuous variables using a Type I error rate of 0.05. Logistic regression was performed to determine if HbA1c and mental health, along with other covariates, were associated with dichotomized DDS subscales. Results: Overall, 415 participants completed the DDS at baseline. Median age was 56 years (IQR: 48-62). A total of 25.9% had high emotional burden distress, 6.6% had high physician-related distress, and 22.2% had high regimen-related distress based on subscales. In adjusted analyses, individuals with any days of poor mental health had significantly higher odds of overall distress (OR:3.7, p=0.014), emotional burden distress (OR:4.9, p<0.001), and physician-related distress (OR:5.0, p=0.002) compared to individuals with no days of poor mental health. Individuals with higher HbA1c had significantly higher odds of regimen-related distress (OR:1.31, p=0.007). Conclusions: Findings suggest that DD is prevalent among this sample of South Asians with diagnosed T2D in NYC. Screening for DD in patients with prediabetes/diabetes should be considered by providers to help provide mental and physical health services during primary care visits. Future research can also benefit from a longitudinal analysis of the impact of DD on diabetes self-management, medication adherence, and mental and physical health. Trial registration: This study uses baseline data from "Diabetes Management Intervention For South Asians" (NCT03333044), which was registered with clinicaltrials.gov on 6/11/2017.

Recent innovations in adaptive trial designs: A review of design opportunities in translational research.

Clinical trials are constantly evolving in the context of increasingly complex research questions and potentially limited resources. In this review article, we discuss the emergence of "adaptive" clinical trials that allow for the preplanned modification of an ongoing clinical trial based on the accumulating evidence with application across translational research. These modifications may include terminating a trial before completion due to futility or efficacy, re-estimating the needed sample size to ensure adequate power, enriching the target population enrolled in the study, selecting across multiple treatment arms, revising allocation ratios used for randomization, or selecting the most appropriate endpoint. Emerging topics related to borrowing information from historic or supplemental data sources, sequential multiple assignment randomized trials (SMART), master protocol and seamless designs, and phase I dose-finding studies are also presented. Each design element includes a brief overview with an accompanying case study to illustrate the design method in practice. We close with brief discussions relating to the statistical considerations for these contemporary designs.

Self-reported adherence and reasons for nonadherence among patients with low proportion of days covered for antihypertension medications.

BACKGROUND: Incorporation of pharmacy fill data into the electronic health record has enabled calculations of medication adherence, as measured by proportion of days covered (PDC), to be displayed to clinicians. Although PDC values help identify patients who may be nonadherent to their medications, it does not provide information on the reasons for medication-taking behaviors. OBJECTIVE: To characterize self-reported adherence status to antihypertensive medications among patients with low refill medication adherence. Our secondary objective was to identify the most common reasons for nonadherence and examine the patient sociodemographic characteristics associated with these barriers. METHODS: Participants were adult patients seen in primary care clinics of a large, urban health system and on antihypertensive therapy with a PDC of less than 80% based on 6-month linked electronic health record-pharmacy fill data. We administered a validated medication adherence screener and a survey assessing reasons for antihypertensive medication nonadherence. We used descriptive statistics to characterize these data and logistic and Poisson regression models to assess the relationship between sociodemographic characteristics and adherence barriers. RESULTS: The survey was completed by 242 patients (57% female; 61.2% White; 79.8% not Latino/a or Hispanic). Of these patients, 45% reported missing doses of their medications in the last 7 days. In addition, 48% endorsed having at least 1 barrier to adherence and 38.4% endorsed 2 or more barriers. The most common barriers were being busy and having difficulty remembering to take medications. Compared with White participants, Black participants (incident rate ratio = 2.49; 95% CI = 1.93-3.22) and participants of other races (incident rate ratio = 2.16; 95% CI = 1.62-2.89) experienced a greater number of barriers. CONCLUSIONS: Nearly half of patients with low PDC reported nonadherence in the prior week, suggesting PDC can be used as a screening tool. Augmenting PDC with brief self-report tools can provide insights into the reasons for nonadherence. DISCLOSURES: Dr Kharmats, Ms Martinez, Dr Belli, Ms Zhao, Dr Mann, Dr Schoenthaler, and Dr Blecker received grants from the National Institute of Health/National Heart, Lung, Blood Institute. Dr Voils holds a license by Duke University for the DOSE-Nonadherence measure and is a consultant for New York University Grossman School of Medicine. This research was supported by the NIH (R01HL156355). Dr Kharmats received a postdoctoral training grant from the National Institutes of Health (5T32HL129953-04). Dr Voils was supported by a Research Career Scientist award from the Health Services Research & Development Service of the Department of Veterans Affairs (RCS 14-443). The content of this manuscript is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health or the United States Government.

Analyzing User Engagement Within a Patient-Reported Outcomes Texting Tool for Diabetes Management: Engagement Phenotype Study.

BACKGROUND: Patient-reported outcomes (PROs) capture patients' views on their health conditions and its management, and are increasingly used in clinical trials, including those targeting type 2 diabetes (T2D). Mobile health (mHealth) tools offer novel solutions for collecting PRO data in real time. Although patients are at the center of any PRO-based intervention, few studies have examined user engagement with PRO mHealth tools. OBJECTIVE: This study aimed to evaluate user engagement with a PRO mHealth tool for T2D management, identify patterns of user engagement and similarities and differences between the patients, and identify the characteristics of patients who are likely to drop out or be less engaged with a PRO mHealth tool. METHODS: We extracted user engagement data from an ongoing clinical trial that tested the efficacy of a PRO mHealth tool designed to improve hemoglobin A1c levels in patients with uncontrolled T2D. To date, 61 patients have been randomized to the intervention, where they are sent 6 PRO text messages a day that are relevant to T2D self-management (healthy eating and medication adherence) over the 12-month study. To analyze user engagement, we first compared the response rate (RR) and response time between patients who completed the 12-month intervention and those who dropped out early (noncompleters). Next, we leveraged latent class trajectory modeling to classify patients from the completer group into 3 subgroups based on similarity in the longitudinal engagement data. Finally, we investigated the differences between the subgroups of completers from various cross-sections (time of the day and day of the week) and PRO types. We also explored the patient demographics and their distribution among the subgroups. RESULTS: Overall, 19 noncompleters had a lower RR to PRO questions and took longer to respond to PRO questions than 42 completers. Among completers, the longitudinal RRs demonstrated differences in engagement patterns over time. The completers with the lowest engagement showed peak engagement during month 5, almost at the midstage of the program. The remaining subgroups showed peak engagement at the beginning of the intervention, followed by either a steady decline or sustained high engagement. Comparisons of the demographic characteristics showed significant differences between the high engaged and low engaged subgroups. The high engaged completers were predominantly older, of Hispanic descent, bilingual, and had a graduate degree. In comparison, the low engaged subgroup was composed mostly of African American patients who reported the lowest annual income, with one of every 3 patients earning less than US $20,000 annually. CONCLUSIONS: There are discernible engagement phenotypes based on individual PRO responses, and their patterns vary in the timing of peak engagement and demographics. Future studies could use these findings to predict engagement categories and tailor interventions to promote longitudinal engagement. TRIAL REGISTRATION: Clinicaltrials.gov NCT03652389; https://clinicaltrials.gov/ct2/show/NCT03652389. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.2196/18554.

A Behavioral Economics-Electronic Health Record Module to Promote Appropriate Diabetes Management in Older Adults: Protocol for a Pragmatic Cluster Randomized Controlled Trial.

BACKGROUND: The integration of behavioral economics (BE) principles and electronic health records (EHRs) using clinical decision support (CDS) tools is a novel approach to improving health outcomes. Meanwhile, the American Geriatrics Society has created the Choosing Wisely (CW) initiative to promote less aggressive glycemic targets and reduction in pharmacologic therapy in older adults with type 2 diabetes mellitus. To date, few studies have shown the effectiveness of combined BE and EHR approaches for managing chronic conditions, and none have addressed guideline-driven deprescribing specifically in type 2 diabetes. We previously conducted a pilot study aimed at promoting appropriate CW guideline adherence using BE nudges and EHRs embedded within CDS tools at 5 clinics within the New York University Langone Health (NYULH) system. The BE-EHR module intervention was tested for usability, adoption, and early effectiveness. Preliminary results suggested a modest improvement of 5.1% in CW compliance. OBJECTIVE: This paper presents the protocol for a study that will investigate the effectiveness of a BE-EHR module intervention that leverages BE nudges with EHR technology and CDS tools to reduce overtreatment of type 2 diabetes in adults aged 76 years and older, per the CW guideline. METHODS: A pragmatic, investigator-blind, cluster randomized controlled trial was designed to evaluate the BE-EHR module. A total of 66 NYULH clinics will be randomized 1:1 to receive for 18 months either (1) a 6-component BE-EHR module intervention + standard care within the NYULH EHR, or (2) standard care only. The intervention will be administered to clinicians during any patient encounter (eg, in person, telemedicine, medication refill, etc). The primary outcome will be patient-level CW compliance. Secondary outcomes will measure the frequency of intervention component firings within the NYULH EHR, and provider utilization and interaction with the BE-EHR module components. RESULTS: Study recruitment commenced on December 7, 2020, with the activation of all 6 BE-EHR components in the NYULH EHR. CONCLUSIONS: This study will test the effectiveness of a previously developed, iteratively refined, user-tested, and pilot-tested BE-EHR module aimed at providing appropriate diabetes care to elderly adults, compared to usual care via a cluster randomized controlled trial. This innovative research will be the first pragmatic randomized controlled trial to use BE principles embedded within the EHR and delivered using CDS tools to specifically promote CW guideline adherence in type 2 diabetes. The study will also collect valuable information on clinician workflow and interaction with the BE-EHR module, guiding future research in optimizing the timely delivery of BE nudges within CDS tools. This work will address the effectiveness of BE-inspired interventions in diabetes and chronic disease management. TRIAL REGISTRATION: ClinicalTrials.gov NCT04181307; https://clinicaltrials.gov/ct2/show/NCT04181307. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/28723.

An Integrated Primary Care Initiative for Child Health in Northern Togo.

OBJECTIVES: To determine if the Integrated Community-Based Health Systems-Strengthening (ICBHSS) initiative was effective in expanding health coverage, improving care quality, and reducing child mortality in Togo. METHODS: Population-representative cross-sectional household surveys adapted from the Demographic Household Survey and Multiple Indicator Cluster Surveys were conducted at baseline (2015) and then annually (2016-2020) in 4 ICBHSS catchment sites in Kara, Togo. The primary outcome was under-5 mortality, with health service coverage and health-seeking behavior as secondary outcomes. Costing analyses were calculated by using "top-down" methodology with audited financial statements and programmatic data. RESULTS: There were 10 022 household surveys completed from 2015 to 2020. At baseline (2015), under-5 mortality was 51.1 per 1000 live births (95% confidence interval [CI]: 35.5-66.8), and at the study end period (2020), under-5 mortality was 35.8 (95% CI: 23.4-48.2). From 2015 to 2020, home-based treatment by a community health worker increased from 24.1% (95% CI: 21.9%-26.4%) to 45.7% (95% CI: 43.3%-48.2%), and respondents reporting prenatal care in the first trimester likewise increased (37.5% to 50.1%). Among respondents who sought care for a child with fever, presenting for care within 1 day increased from 51.9% (95% CI: 47.1%-56.6%) in 2015 to 80.3% (95% CI: 74.6%-85.0%) in 2020. The estimated annual additional intervention cost was $8.84 per person. CONCLUSIONS: Our findings suggest that the ICBHSS initiative, a bundle of evidence-based interventions implemented with a community-based strategy, improves care access and quality and was associated with reduction in child mortality.

The neutralizing antibody, LY-CoV555, protects against SARS-CoV-2 infection in nonhuman primates.

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) poses a public health threat for which preventive and therapeutic agents are urgently needed. Neutralizing antibodies are a key class of therapeutics that may bridge widespread vaccination campaigns and offer a treatment solution in populations less responsive to vaccination. Here, we report that high-throughput microfluidic screening of antigen-specific B cells led to the identification of LY-CoV555 (also known as bamlanivimab), a potent anti-spike neutralizing antibody from a hospitalized, convalescent patient with coronavirus disease 2019 (COVID-19). Biochemical, structural, and functional characterization of LY-CoV555 revealed high-affinity binding to the receptor-binding domain, angiotensin-converting enzyme 2 binding inhibition, and potent neutralizing activity. A pharmacokinetic study of LY-CoV555 conducted in cynomolgus monkeys demonstrated a mean half-life of 13 days and a clearance of 0.22 ml hour-1 kg-1, consistent with a typical human therapeutic antibody. In a rhesus macaque challenge model, prophylactic doses as low as 2.5 mg/kg reduced viral replication in the upper and lower respiratory tract in samples collected through study day 6 after viral inoculation. This antibody has entered clinical testing and is being evaluated across a spectrum of COVID-19 indications, including prevention and treatment.

Effectiveness of an Integrated Engagement Support System to Facilitate Patient Use of Digital Diabetes Prevention Programs: Protocol for a Randomized Controlled Trial.

BACKGROUND: Digital diabetes prevention programs (dDPPs) are effective behavior change tools to prevent disease progression in patients at risk for diabetes. At present, these programs are poorly integrated into existing health information technology infrastructure and clinical workflows, resulting in barriers to provider-level knowledge of, interaction with, and support of patients who use dDPPs. Tools that can facilitate patient-provider interaction around dDPPs may contribute to improved patient engagement and adherence to these programs and improved health outcomes. OBJECTIVE: This study aims to use a rigorous, user-centered design (UCD) methodology to develop a theory-driven system that supports patient engagement with dDPPs and their primary care providers with their care. METHODS: This study will be conducted in 3 phases. In phase 1, we will use systematic UCD, Agile software development, and qualitative research methods to identify key user (patients, providers, clinical staff, digital health technologists, and content experts) requirements, constraints, and prioritization of high-impact features to design, develop, and refine a viable intervention prototype for the engagement system. In phase 2, we will conduct a single-arm feasibility pilot of the engagement system among patients with prediabetes and their primary care providers. In phase 3, we will conduct a 2-arm randomized controlled trial using the engagement system. Primary outcomes will be weight, BMI, and A1c at 6 and 12 months. Secondary outcomes will be patient engagement (use and activity) in the dDPP. The mediator variables (self-efficacy, digital health literacy, and patient-provider relationship) will be measured. RESULTS: The project was initiated in 2018 and funded in September 2019. Enrollment and data collection for phase 1 began in September 2019 under an Institutional Review Board quality improvement waiver granted in July 2019. As of December 2020, 27 patients have been enrolled and first results are expected to be submitted for publication in early 2021. The study received Institutional Review Board approval for phases 2 and 3 in December 2020, and phase 2 enrollment is expected to begin in early 2021. CONCLUSIONS: Our findings will provide guidance for the design and development of technology to integrate dDPP platforms into existing clinical workflows. This will facilitate patient engagement in digital behavior change interventions and provider engagement in patients' use of dDPPs. Integrated clinical tools that can facilitate patient-provider interaction around dDPPs may contribute to improved patient adherence to these programs and improved health outcomes by addressing barriers faced by both patients and providers. Further evaluation with pilot testing and a clinical trial will assess the effectiveness and implementation of these tools. TRIAL REGISTRATION: ClinicalTrials.gov NCT04049500; https://clinicaltrials.gov/ct2/show/NCT04049500. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/26750.

A survey of pediatric hematologists/oncologists' perspectives on single patient Expanded Access and Right to Try.

Introduction: Physicians in the United States play an essential role guiding patients through single patient pre-approval access (PAA) to investigational medical products via either the Food and Drug Administration (FDA)'s Expanded Access (EA) or the federal Right To Try (RTT) pathways. In this study, we sought to better understand pediatric hematologist/oncologists' attitudes about seeking PAA, on behalf of single patients, to investigational drugs outside of clinical trials. Methods: A cross-sectional survey was developed and sent to pediatric hematologist/oncologists via St. Baldrick's Foundation's email distribution list. Results: Of 73 respondents (10.1% of those who received the survey), 56 met eligibility criteria and are included in the analysis. Over 80% (n = 46) had prior experience with single patient PAA. Respondents were most concerned about the unknown risks and benefits of investigational drugs and financial implications of PAA for patients. One hundred percent and 91.1% of respondents indicated a willingness to support patients through EA and RTT pathways, respectively. When asked about their most recent experience with PAA, 40 out of 46 indicated that they used the FDA's EA pathway to seek PAA and 4 out of 46 indicated that they used the RTT pathway. Of 44 respondents who had used the EA or RTT pathway, 43 indicated that the biotechnology or pharmaceutical company they solicited granted access to the requested product. Conclusion: Survey results support other findings suggesting a need for additional physician support and education about PAA and that physicians may have unequal access to information about investigational drugs and concerns about financial implications of PAA for their patients.

LY-CoV555, a rapidly isolated potent neutralizing antibody, provides protection in a non-human primate model of SARS-CoV-2 infection.

SARS-CoV-2 poses a public health threat for which therapeutic agents are urgently needed. Herein, we report that high-throughput microfluidic screening of antigen-specific B-cells led to the identification of LY-CoV555, a potent anti-spike neutralizing antibody from a convalescent COVID-19 patient. Biochemical, structural, and functional characterization revealed high-affinity binding to the receptor-binding domain, ACE2 binding inhibition, and potent neutralizing activity. In a rhesus macaque challenge model, prophylaxis doses as low as 2.5 mg/kg reduced viral replication in the upper and lower respiratory tract. These data demonstrate that high-throughput screening can lead to the identification of a potent antiviral antibody that protects against SARS-CoV-2 infection. ONE SENTENCE SUMMARY: LY-CoV555, an anti-spike antibody derived from a convalescent COVID-19 patient, potently neutralizes SARS-CoV-2 and protects the upper and lower airways of non-human primates against SARS-CoV-2 infection.

Implementation of a Behavioral Economics Electronic Health Record (BE-EHR) Module to Reduce Overtreatment of Diabetes in Older Adults.

BACKGROUND: Intensive glycemic control is of unclear benefit and carries increased risk for older adults with diabetes. The American Geriatrics Society's (AGS) Choosing Wisely (CW) guideline promotes less aggressive glycemic targets and reduction in pharmacologic therapy for older adults with type II diabetes. Meanwhile, behavioral economic (BE) approaches offer promise in influencing hard-to-change behavior, and previous studies have shown the benefits of using electronic health record (EHR) technology to encourage guideline adherence. OBJECTIVE: This study aimed to develop and pilot test an intervention that leverages BE with EHR technology to promote appropriate diabetes management in older adults. DESIGN: A pilot study within the New York University Langone Health (NYULH) EHR and Epic system to deliver BE-inspired nudges at five NYULH clinics at varying time points from July 12, 2018, through October 31, 2019. PARTICIPANTS: Clinicians across five practices in the NYULH system whose patients were older adults (age 76 and older) with type II diabetes. INTERVENTIONS: A BE-EHR module comprising six nudges was developed through a series of design workshops, interviews, user-testing sessions, and clinic visits. BE principles utilized in the nudges include framing, social norming, accountable justification, defaults, affirmation, and gamification. MAIN MEASURES: Patient-level CW compliance. KEY RESULTS: CW compliance increased 5.1% from a 16-week interval at baseline to a 16-week interval post intervention. From February 14 to June 5, 2018 (prior to the first nudge launch in Vanguard clinics), CW compliance for 1278 patients was mean (95% CI)-16.1% (14.1%, 18.1%). From July 3 to October 22, 2019 (after BE-EHR module launch at all five clinics), CW compliance for 680 patients was 21.2% (18.1%, 24.3%). CONCLUSIONS: The BE-EHR module shows promise for promoting the AGS CW guideline and improving diabetes management in older adults. A randomized controlled trial will commence to test the effectiveness of the intervention across 66 NYULH clinics. NIH TRIAL REGISTRY NUMBER: NCT03409523.

Implementing an integrated community based health systems strengthening approach to improve HIV survival in Northern Togo.

To disseminate lessons learned from the implementation experience of a public-private sector partnership, we describe a comprehensive HIV/AIDS program including 5-year survival outcomes for individuals who initiated antiretroviral therapy (ART) treatment in Togo from 2010 to 2015. A retrospective case study analysis was conducted from a cohort of patients receiving ART at an HIV/AIDS care clinic in Kara Region, Togo. Kaplan-Meier curves with Log rank tests were used to compare estimated survival curves by demographic and clinical characteristics. Associations were described between survival probability and age, gender, World Health Organization (WHO) disease stage, and timing of ART initiation. Cox proportional hazard model was used to determine predictors of mortality. After approximately five-years since ART initiation (1780 days), there were 114 deaths, with a survival probability of 75.3% (95% CI: 70.3-80.6%). Participants with advanced WHO disease stage were more likely at risk of death relative to patients categorized as WHO Stage 1, with Stage 4 approximately 9 times more likely (aHR 9.22, 95% CI 4.29-19.84). Our study suggests that delivering comprehensive HIV care through a private-public partnership may serve as a model to expand and improve HIV/AIDS care as well as high quality primary care.

User-Centered Development of a Behavioral Economics Inspired Electronic Health Record Clinical Decision Support Module.

Changing physician behaviors is difficult. Electronic health record (EHR) clinical decision support (CDS) offers an opportunity to promote guideline adherence. Behavioral economics (BE) has shown success as an approach to supporting evidence-based decision-making with little additional cognitive burden. We applied a user-centered approach to incorporate BE "nudges" into a CDS module in two "vanguard" sites utilizing: (1) semi-structured interviews with key informants (n = 8); (2) a design thinking workshop; and (3) semi-structured group interviews with clinicians. In the 133 day development phase at two clinics, the navigator section fired 299 times for 27 unique clinicians. The inbasket refill alert fired 124 times for 22 clinicians. Fifteen prescriptions for metformin were written by 11 clinicians. Our user-centered approach yielded a BE-driven CDS module with relatively high utilization by clinicians. Next steps include the addition of two modules and continued tracking of utilization, and assessment of clinical impact of the module.