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.

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.

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.

Ideal vs. real: a systematic review on handling covariates in randomized controlled trials.

BACKGROUND: In theory, efficient design of randomized controlled trials (RCTs) involves randomization algorithms that control baseline variable imbalance efficiently, and corresponding analysis involves pre-specified adjustment for baseline covariates. This review sought to explore techniques for handling potentially influential baseline variables in both the design and analysis phase of RCTs. METHODS: We searched PubMed for articles indexed "randomized controlled trial", published in the NEJM, JAMA, BMJ, or Lancet for two time periods: 2009 and 2014 (before and after updated CONSORT guidelines). Upon screening (343), 298 articles underwent full review and data abstraction. RESULTS: Typical articles reported on superiority (86%), multicenter (92%), two-armed (79%) trials; 81% of trials involved covariates in the allocation and 84% presented adjusted analysis results. The majority reported a stratified block method (69%) of allocation, and of the trials reporting adjusted analyses, 91% were pre-specified. Trials published in 2014 were more likely to report adjusted analyses (87% vs. 79%, p = 0.0100) and more likely to pre-specify adjustment in analyses (95% vs. 85%, p = 0.0045). Studies initiated in later years (2010 or later) were less likely to use an adaptive method of randomization (p = 0.0066; 7% of those beginning in 2010 or later vs. 31% of those starting before 2000) but more likely to report a pre-specified adjusted analysis (p = 0.0029; 97% for those initiated in 2010 or later vs. 69% of those started before 2000). CONCLUSION: While optimal reporting procedures and pre-specification of adjusted analyses for RCTs tend to be progressively more prevalent over time, we see the opposite effect on reported use of covariate-adaptive randomization methods.

Designing for implementation: user-centered development and pilot testing of a behavioral economic-inspired electronic health record clinical decision support module.

BACKGROUND: Current guidelines recommend less aggressive target hemoglobin A1c (HbA1c) levels based on older age and lower life expectancy for older adults with diabetes. The effectiveness of electronic health record (EHR) clinical decision support (CDS) in promoting guideline adherence is undermined by alert fatigue and poor workflow integration. Integrating behavioral economics (BE) and CDS tools is a novel approach to improving adherence to guidelines while minimizing clinician burden. METHODS: We will apply a systematic, user-centered design approach to incorporate BE "nudges" into a CDS module and will perform user testing in two "vanguard" sites. To accomplish this, we will conduct (1) semi-structured interviews with key informants (n = 8), (2) a 2-h, design-thinking workshop to derive and refine initial module ideas, and (3) semi-structured group interviews at each site with clinic leaders and clinicians to elicit feedback on three proposed nudge module components (navigator section, inbasket refill protocol, medication preference list). Detailed field notes will be summarized by module idea and usability theme for rapid iteration. Frequency of firing and user action taken will be assessed in the first month of implementation via EHR reporting to confirm that module components and related reporting are working as expected as well as assess utilization. To assess the utilization and feasibility of the new tools and generate estimates of clinician compliance with the Choosing Wisely guideline for diabetes management in older adults, a 6-month, single-arm pilot study of the BE-EHR module will be conducted in six outpatient primary care clinics. DISCUSSION: We hypothesize that a low burden, user-centered approach to design will yield a BE-driven, CDS module with relatively high utilization by clinicians. The resulting module will establish a platform for exploring the ability of BE concepts embedded within the EHR to affect guideline adherence for other use cases.

Quantification of vibrissal mechanical properties across the rat mystacial pad.

Recent work has quantified the geometric parameters of individual rat vibrissae (whiskers) and developed equations that describe how these parameters vary as a function of row and column position across the array. This characterization included a detailed quantification of whisker base diameter and arc length as well as the geometry of the whisker medulla. The present study now uses these equations for whisker geometry to quantify several properties of the whisker that govern its mechanical behavior. We first show that the average density of a whisker is lower in its proximal region than in its distal region. This density variation appears to be largely attributable to the presence of the whisker cuticle rather than the medulla. The density variation has very little effect on the center of mass of the whisker. We next show that the presence of the medulla decreases the deflection of the whisker under its own weight and also decreases its mass moment of inertia while sacrificing <1% stiffness at the whisker base compared with a solid whisker. Finally, we quantify two dimensionless parameters across the array. First, the deflection-to-length ratio decreases from caudal to rostral: caudal whiskers are longer but deflect more under their own weight. Second, the nondimensionalized radius of gyration is approximately constant across the array, which may simplify control of whisking by the intrinsic muscles. We anticipate that future work will exploit the mechanical properties computed in the present study to improve simulations of the mechanosensory signals associated with vibrissotactile exploratory behavior. NEW & NOTEWORTHY The mechanical signals transmitted by a whisker depend critically on its geometry. We used measurements of whisker geometry and mass to quantify the center of mass, mass moment of inertia, radius of gyration, and deflection under gravity of the whisker. We describe how variations in these quantities across the array could enhance sensing behaviors while reducing energy costs and simplifying whisking control. Most importantly, we provide derivations for these quantities for use in future simulation work.

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

The morphology of an animal's face will have large effects on the sensory information it can acquire. Here we quantify the arrangement of cranial sensory structures of the rat, with special emphasis on the mystacial vibrissae (whiskers). Nearly all mammals have vibrissae, which are generally arranged in rows and columns across the face. The vibrissae serve a wide variety of important behavioral functions, including navigation, climbing, wake following, anemotaxis, and social interactions. To date, however, there are few studies that compare the morphology of vibrissal arrays across species, or that describe the arrangement of the vibrissae relative to other facial sensory structures. The few studies that do exist have exploited the whiskers' grid-like arrangement to quantify array morphology in terms of row and column identity. However, relying on whisker identity poses a challenge for comparative research because different species have different numbers and arrangements of whiskers. The present work introduces an approach to quantify vibrissal array morphology regardless of the number of rows and columns, and to quantify the array's location relative to other sensory structures. We use the three-dimensional locations of the whisker basepoints as fundamental parameters to generate equations describing the length, curvature, and orientation of each whisker. Results show that in the rat, whisker length varies exponentially across the array, and that a hard limit on intrinsic curvature constrains the whisker height-to-length ratio. Whiskers are oriented to "fan out" approximately equally in dorsal-ventral and rostral-caudal directions. Quantifying positions of the other sensory structures relative to the whisker basepoints shows remarkable alignment to the somatosensory cortical homunculus, an alignment that would not occur for other choices of coordinate systems (e.g., centered on the midpoint of the eyes). We anticipate that the quantification of facial sensory structures, including the vibrissae, will ultimately enable cross-species comparisons of multi-modal sensing volumes.