Academics are more specific, and practitioners more sensitive, in forecasting interventions to strengthen democratic attitudes.

Concern over democratic erosion has led to a proliferation of proposed interventions to strengthen democratic attitudes in the United States. Resource constraints, however, prevent implementing all proposed interventions. One approach to identify promising interventions entails leveraging domain experts, who have knowledge regarding a given field, to forecast the effectiveness of candidate interventions. We recruit experts who develop general knowledge about a social problem (academics), experts who directly intervene on the problem (practitioners), and nonexperts from the public to forecast the effectiveness of interventions to reduce partisan animosity, support for undemocratic practices, and support for partisan violence. Comparing 14,076 forecasts submitted by 1,181 forecasters against the results of a megaexperiment (n = 32,059) that tested 75 hypothesized effects of interventions, we find that both types of experts outperformed members of the public, though experts differed in how they were accurate. While academics' predictions were more specific (i.e., they identified a larger proportion of ineffective interventions and had fewer false-positive forecasts), practitioners' predictions were more sensitive (i.e., they identified a larger proportion of effective interventions and had fewer false-negative forecasts). Consistent with this, practitioners were better at predicting best-performing interventions, while academics were superior in predicting which interventions performed worst. Our paper highlights the importance of differentiating types of experts and types of accuracy. We conclude by discussing factors that affect whether sensitive or specific forecasters are preferable, such as the relative cost of false positives and negatives and the expected rate of intervention success.

Correcting misperceptions of out-partisans decreases American legislators' support for undemocratic practices.

There is substantial concern about democratic backsliding in the United States. Evidence includes notably high levels of animosity toward out-partisans and support for undemocratic practices (SUP) among the general public. Much less is known, however, about the views of elected officials-even though they influence democratic outcomes more directly. In a survey experiment conducted with state legislators (N = 534), we show that these officials exhibit less animosity toward the other party, less SUP, and less support for partisan violence (SPV) than the general public. However, legislators vastly overestimate the levels of animosity, SUP, and SPV among voters from the other party (though not among voters from their own party). Further, those legislators randomly assigned to receive accurate information about the views of voters from the other party reported significantly lower SUP and marginally significantly lower partisan animosity toward the other party. This suggests that legislators' democratic attitudes are causally linked to their perceptions of other-party voters' democratic attitudes. Our findings highlight the importance of ensuring that office holders have access to reliable information about voters from both parties.

The effects of short messages encouraging prevention behaviors early in the COVID-19 pandemic.

Effectively addressing public health crises like the COVID-19 pandemic requires persuading the mass public to change their behavior in significant ways. Many efforts to encourage behavior change-such as public service announcements, social media posts, and billboards-involve short, persuasive appeals, yet the effectiveness of these messages is unclear. Early in the COVID-19 pandemic, we tested whether short messages could increase intentions to comply with public health guidelines. To identify promising messages, we conducted two pretests (n = 1,596) in which participants rated the persuasiveness of 56 unique messages: 31 based on the persuasion and social influence literatures and 25 drawn from a pool of crowdsourced messages generated by online respondents. The four top-rated messages emphasized: (1) civic responsibility to reciprocate the sacrifices of health care workers, (2) caring for the elderly and vulnerable, (3) a specific, sympathetic victim, and (4) limited health care system capacity. We then conducted three well-powered, pre-registered experiments (total n = 3,719) testing whether these four top-rated messages, and a standard public health message based on language from the CDC, increased intentions to comply with public health guidelines, such as masking in public spaces. In Study 1, we found the four messages and the standard public health message significantly outperformed a null control. In Studies 2 and 3, we compared the effects of persuasive messages to the standard public health message, finding that none consistently out-performed the standard message. This is in line with other research showing minimal persuasive effects of short messages after the very early stages of the pandemic. Across our studies, we found that (1) short messages can increase intentions to comply with public health guidelines, but (2) short messages featuring persuasive techniques from the social science literature did not substantially outperform standard public health messages.

Interventions reducing affective polarization do not necessarily improve anti-democratic attitudes.

There is widespread concern that rising affective polarization-particularly dislike for outpartisans-exacerbates Americans' anti-democratic attitudes. Accordingly, scholars and practitioners alike have invested great effort in developing depolarization interventions that reduce affective polarization. Critically, however, it remains unclear whether these interventions reduce anti-democratic attitudes, or only change sentiments towards outpartisans. Here we address this question with experimental tests (total n = 8,385) of three previously established depolarization interventions: correcting misperceptions of outpartisans, priming inter-partisan friendships and observing warm cross-partisan interactions between political leaders. While these depolarization interventions reliably reduced affective polarization, we do not find compelling evidence that these interventions reduced support for undemocratic candidates, support for partisan violence or prioritizing partisan ends over democratic means. Thus, future efforts to strengthen pro-democratic attitudes may do better if they target these outcomes directly. More broadly, these findings call into question the previously assumed causal effect of affective polarization on anti-democratic attitudes.

Community health workers' critical role in trust building between the medical system and communities of color.

The authors interrogate elements of routine medical practice in New York City to argue for reforms of hospital culture through relational trust-building capabilities of community health workers.

Epigenetic MRI: Noninvasive imaging of DNA methylation in the brain.

Both neuronal and genetic mechanisms regulate brain function. While there are excellent methods to study neuronal activity in vivo, there are no nondestructive methods to measure global gene expression in living brains. Here, we present a method, epigenetic MRI (eMRI), that overcomes this limitation via direct imaging of DNA methylation, a major gene-expression regulator. eMRI exploits the methionine metabolic pathways for DNA methylation to label genomic DNA through 13C-enriched diets. A 13C magnetic resonance spectroscopic imaging method then maps the spatial distribution of labeled DNA. We validated eMRI using pigs, whose brains have stronger similarity to humans in volume and anatomy than rodents, and confirmed efficient 13C-labeling of brain DNA. We also discovered strong regional differences in global DNA methylation. Just as functional MRI measurements of regional neuronal activity have had a transformational effect on neuroscience, we expect that the eMRI signal, both as a measure of regional epigenetic activity and as a possible surrogate for regional gene expression, will enable many new investigations of human brain function, behavior, and disease.

Noninvasive and Spatiotemporal Control of DNAzyme-Based Imaging of Metal Ions In Vivo Using High-Intensity Focused Ultrasound.

Detecting metal ions in vivo with a high spatiotemporal resolution is critical to understanding the roles of the metal ions in both healthy and disease states. Although spatiotemporal controls of metal-ion sensors using light have been demonstrated, the lack of penetration depth in tissue and in vivo has limited their application. To overcome this limitation, we herein report the use of high-intensity focused ultrasound (HIFU) to remotely deliver on-demand, spatiotemporally resolved thermal energy to activate the DNAzyme sensors at the targeted region both in vitro and in vivo. A Zn2+-selective DNAzyme probe is inactivated by a protector strand to block the formation of catalytic enzyme structure, which can then be activated by an HIFU-induced increase in the local temperature. With this design, Zn2+-specific fluorescent resonance energy transfer (FRET) imaging has been demonstrated by the new DNAzyme-HIFU probes in both HeLa cells and mice. The current method can be applied to monitor many other metal ions for in vivo imaging and medical diagnosis using metal-specific DNAzymes that have either been obtained or can be selected using in vitro selection.

Ultrasound controlled mechanophore activation in hydrogels for cancer therapy.

Mechanophores are molecular motifs that respond to mechanical perturbance with targeted chemical reactions toward desirable changes in material properties. A large variety of mechanophores have been investigated, with applications focusing on functional materials, such as strain/stress sensors, nanolithography, and self-healing polymers, among others. The responses of engineered mechanophores, such as light emittance, change in fluorescence, and generation of free radicals (FRs), have potential for bioimaging and therapy. However, the biomedical applications of mechanophores are not well explored. Herein, we report an in vitro demonstration of an FR-generating mechanophore embedded in biocompatible hydrogels for noninvasive cancer therapy. Controlled by high-intensity focused ultrasound (HIFU), a clinically proven therapeutic technique, mechanophores were activated with spatiotemporal precision to generate FRs that converted to reactive oxygen species (ROS) to effectively kill tumor cells. The mechanophore hydrogels exhibited no cytotoxicity under physiological conditions. Upon activation with HIFU sonication, the therapeutic efficacies in killing in vitro murine melanoma and breast cancer tumor cells were comparable with lethal doses of H2O2 This process demonstrated the potential for mechanophore-integrated HIFU combination as a noninvasive cancer treatment platform, named "mechanochemical dynamic therapy" (MDT). MDT has two distinct advantages over other noninvasive cancer treatments, such as photodynamic therapy (PDT) and sonodynamic therapy (SDT). 1) MDT is ultrasound based, with larger penetration depth than PDT. 2) MDT does not rely on sonosensitizers or the acoustic cavitation effect, both of which are necessary for SDT. Taking advantage of the strengths of mechanophores and HIFU, MDT can provide noninvasive treatments for diverse cancer types.

Religious identity cues increase vaccination intentions and trust in medical experts among American Christians.

Containing the COVID-19 pandemic in the United States requires mobilizing a large majority of the mass public to vaccinate, but many Americans are hesitant or opposed to vaccination. A significant predictor of vaccine attitudes in the United States is religiosity, with more-religious individuals expressing more distrust in science and being less likely to get vaccinated. Here, we test whether explicit cues of common religious identity can help medical experts build trust and increase vaccination intentions. In a preregistered survey experiment conducted with a sample of unvaccinated American Christians (n = 1,765), we presented participants with a vaccine endorsement from a prominent medical expert (NIH Director Francis Collins) and a short essay about doctors' and scientists' endorsement of the vaccines. In the common religious identity condition, these materials also highlighted the religious identity of Collins and many medical experts. Unvaccinated Christians in the common identity condition expressed higher trust in medical experts, greater intentions to vaccinate, and greater intentions to promote vaccination to friends and family than those who did not see the common identity cue. These effects were moderated by religiosity, with the strongest effects observed among the most religious participants, and statistically mediated by heightened perceptions of shared values with the medical expert endorsing the vaccine. These findings demonstrate the efficacy of common identity cues for promoting vaccination in a vaccine-hesitant subpopulation. More generally, the results illustrate how trust in science can be built through the invocation of common group identities, even identities often assumed to be in tension with science.

Elite party cues increase vaccination intentions among Republicans.

Overcoming the COVID-19 pandemic requires motivating the vast majority of Americans to get vaccinated. However, vaccination rates have become politically polarized, and a substantial proportion of Republicans have remained vaccine hesitant for months. Here, we explore how endorsements by party elites affect Republicans' COVID-19 vaccination intentions and attitudes. In a preregistered survey experiment (n = 1,480), we varied whether self-identified Republicans saw endorsements of the vaccine from prominent Republicans (including video of a speech by former President Donald Trump), from the Democratic Party (including video of a speech by President Joseph Biden), or a neutral control condition including no endorsements. Unvaccinated Republicans who were exposed to the Republican elite endorsement reported 7.0% higher vaccination intentions than those who viewed the Democratic elite endorsement and 5.7% higher than those in the neutral control condition. These effects were statistically mediated by participants' reports of how much they thought Republican politicians would want them to get vaccinated. We also found evidence of backlash effects against Democratic elites: Republicans who viewed the Democratic elite endorsement reported they would be significantly less likely to encourage others to vaccinate and had more negative attitudes toward the vaccine, compared with those who viewed the Republican elite endorsement or the neutral control. These results demonstrate the relative advantage of cues from Republican elites-and the risks of messaging from Democrats currently in power-for promoting vaccination among the largest vaccine-hesitant subgroup in the United States.

Adverse respiratory outcomes following conventional long-course radiotherapy for non-small-cell lung cancer in patients with pre-existing pulmonary fibrosis: A comparative retrospective study.

INTRODUCTION: There is some evidence to suggest that patients with underlying pulmonary fibrosis (PF) have increased risk of adverse respiratory and survival outcomes, when treated with conventional, long-course radiotherapy (RT) for non-small-cell lung cancer (NSCLC). We performed a retrospective analysis to determine the size of these risks. METHODS: Data from 21 patients with PF (cases) were retrospectively analysed for respiratory toxicity and mortality outcomes, and compared with 84 patients without PF (non-cases). Age and mean lung dose were included as covariates in regression analyses. The additional predictive value of other patient, disease and treatment characteristics on radiation pneumonitis (RP) risk and severity was explored. RESULTS: There was a numerical (though not statistically significant) increase in grade ≥ 2 RP among PF cases (OR 2.74, P = 0.074). Cases were significantly more likely to discontinue radical treatment early (OR 6.10, P = 0.015). There was a significant association between increased RP severity and underlying PF (P = 0.039), with RP strongly implicated in the death in 3 of 21 cases (14.3%) compared to 1 non-case (1.2%). Cases experienced increased grade ≥ 2 respiratory toxicity otherwise (OR 4.35, P = 0.020) and poorer median overall survival (0.6 versus 1.7 years, P < 0.001). Two cases, and no non-cases, died during the proposed RT period. None of the analysed patient, disease or treatment factors, was a significant additional predictor of RP risk/severity. CONCLUSION: Patients with PF are at increased risk of treatment discontinuation, respiratory morbidity and mortality, and poor survival following conventional RT for NSCLC. Caution should be exercised when offering high-dose RT to these patients.

Pragmatic evaluation of a midstream urine collection technique for infants in the emergency department.

OBJECTIVES: Our objective was to examine the performance characteristics of a bladder stimulation technique for urine collection among infants presenting to the emergency department (ED). METHODS: This prospective cohort study enrolled a convenience sample of infants aged ≤ 90 days requiring urine testing in the ED. Infants were excluded if critically ill, moderately to severely dehydrated, or having significant feeding issues. Bladder stimulation consisted of finger tapping on the lower abdomen with or without lower back massage while holding the child upright. The primary outcome was successful midstream urine collection within 5 minutes of stimulation. Secondary outcomes included sample contamination, bladder stimulation time for successful urine collection, and perceived patient distress on a 100-mm visual analog scale (VAS). RESULTS: We enrolled 151 infants and included 147 in the analysis. Median age was 53 days (interquartile range [IQR] 27-68 days). Midstream urine sample collection using bladder stimulation was successful in 78 infants (53.1%; 95% confidence interval [CI] 45-60.9). Thirty-nine samples (50%) were contaminated. Most contaminated samples (n = 31; 79.5%) were reported as "no significant growth" or "growth of 3 or more organisms". Median bladder stimulation time required for midstream urine collection was 45 seconds (IQR 20-120 seconds). Mean VAS for infant distress was 22 mm (standard deviation 23 mm). CONCLUSIONS: The success rate of this bladder stimulation technique was lower than previously reported. The contamination rate was high, however most contaminated specimens were easily identified and had no clinical impact.

Scatter imaging during lung stereotactic body radiation therapy characterized with phantom studies.

By collecting photons scattered out of the therapy beam, scatter imaging creates images of the treated volume. Two phantoms were used to assess the possible application of scatter imaging for markerless tracking of lung tumors during stereotactic body radiation therapy (SBRT) treatment. A scatter-imaging camera was assembled with a CsI flat-panel detector and a 5 mm diameter pinhole collimator. Scatter images were collected during the irradiation of phantoms with megavoltage photons. To assess scatter image quality, spherical phantom lung tumors of 2.1-2.8 cm diameters were placed inside a static, anthropomorphic phantom. To show the efficacy of the technique with a moving target (3 cm diameter), the position of a simulated tumor was tracked in scatter images during sinusoidal motion (15 mm amplitude, 0.25 Hz frequency) in a dynamic lung phantom in open-field, dynamic conformal arc (DCA), and volumetric modulated arc therapy (VMAT) deliveries. Anatomical features are identifiable on static phantom scatter images collected with 10 MU of delivered dose (2.1 cm diameter lung tumor contrast-to-noise ratio of 4.4). The contrast-to-noise ratio increases with tumor size and delivered dose. During dynamic motion, the position of the 3.0 cm diameter lung tumor was identified with a root-mean-square error of 0.8, 1.2, and 2.9 mm for open field (0.3 s frame integration), DCA (0.5 s), and VMAT (0.5 s), respectively. Based on phantom studies, scatter imaging is a potential technique for markerless lung tumor tracking during SBRT without additional imaging dose. Quality scatter images may be collected at low, clinically relevant doses (10 MU). Scatter images are capable of sub-millimeter tracking precision, but modulation decreases accuracy.

Electronic intracavitary brachytherapy quality management based on risk analysis: The report of AAPM TG 182.

PURPOSE: The purpose of this study was to provide guidance on quality management for electronic brachytherapy. MATERIALS AND METHODS: The task group used the risk-assessment approach of Task Group 100 of the American Association of Physicists in Medicine. Because the quality management program for a device is intimately tied to the procedure in which it is used, the task group first designed quality interventions for intracavitary brachytherapy for both commercial electronic brachytherapy units in the setting of accelerated partial-breast irradiation. To demonstrate the methodology to extend an existing risk analysis for a different application, the task group modified the analysis for the case of post-hysterectomy, vaginal cuff irradiation for one of the devices. RESULTS: The analysis illustrated how the TG-100 methodology can lead to interventions to reduce risks and improve quality for each unit and procedure addressed. CONCLUSION: This report provides a model to guide facilities establishing a quality management program for electronic brachytherapy.

Compton scatter imaging: A promising modality for image guidance in lung stereotactic body radiation therapy.

PURPOSE: Lung stereotactic body radiation therapy (SBRT) requires delivering large radiation doses with millimeter accuracy, making image guidance essential. An approach to forming images of patient anatomy from Compton-scattered photons during lung SBRT is presented. METHODS: To investigate the potential of scatter imaging, a pinhole collimator and flat-panel detector are used for spatial localization and detection of photons scattered during external beam therapy using lung SBRT treatment conditions (6 MV FFF beam). MCNP Monte Carlo software is used to develop a model to simulate scatter images. This model is validated by comparing experimental and simulated phantom images. Patient scatter images are then simulated from 4DCT data. RESULTS: Experimental lung tumor phantom images have sufficient contrast-to-noise to visualize the tumor with as few as 10 MU (0.5 s temporal resolution). The relative signal intensity from objects of different composition as well as lung tumor contrast for simulated phantom images agree quantitatively with experimental images, thus validating the Monte Carlo model. Scatter images are shown to display high contrast between different materials (lung, water, bone). Simulated patient images show superior (~double) tumor contrast compared to MV transmission images. CONCLUSIONS: Compton scatter imaging is a promising modality for directly imaging patient anatomy during treatment without additional radiation, and it has the potential to complement existing technologies and aid tumor tracking and lung SBRT image guidance.

Acoustic-based proton range verification in heterogeneous tissue: simulation studies.

Acoustic-based proton range verification (protoacoustics) is a potential in vivo technique for determining the Bragg peak position. Previous measurements and simulations have been restricted to homogeneous water tanks. Here, a CT-based simulation method is proposed and applied to a liver and prostate case to model the effects of tissue heterogeneity on the protoacoustic amplitude and time-of-flight range verification accuracy. For the liver case, posterior irradiation with a single proton pencil beam was simulated for detectors placed on the skin. In the prostate case, a transrectal probe measured the protoacoustic pressure generated by irradiation with five separate anterior proton beams. After calculating the proton beam dose deposition, each CT voxel's material properties were mapped based on Hounsfield Unit values, and thermoacoustically-generated acoustic wave propagation was simulated with the k-Wave MATLAB toolbox. By comparing the simulation results for the original liver CT to homogenized variants, the effects of heterogeneity were assessed. For the liver case, 1.4 cGy of dose at the Bragg peak generated 50 mPa of pressure (13 cm distal), a 2× lower amplitude than simulated in a homogeneous water tank. Protoacoustic triangulation of the Bragg peak based on multiple detector measurements resulted in 0.4 mm accuracy for a δ-function proton pulse irradiation of the liver. For the prostate case, higher amplitudes are simulated (92-1004 mPa) for closer detectors (<8 cm). For four of the prostate beams, the protoacoustic range triangulation was accurate to ⩽1.6 mm (δ-function proton pulse). Based on the results, application of protoacoustic range verification to heterogeneous tissue will result in decreased signal amplitudes relative to homogeneous water tank measurements, but accurate range verification is still expected to be possible.

Dosimetric effects of saline- versus water-filled balloon applicators for IORT using the model S700 electronic brachytherapy source.

PURPOSE: The Xoft Axxent Electronic Brachytherapy System (Xoft, Inc., San Jose, CA) is a viable option for intraoperative radiation therapy (IORT) treatment of early-stage breast cancer. The low-energy (50-kVp) X-ray source simplifies shielding and increases relative biological effectiveness but increases dose distribution sensitivity to medium composition. Treatment planning systems typically assume homogenous water for brachytherapy dose calculations, including precalculated atlas plans for Xoft IORT. However, Xoft recommends saline for balloon applicator filling. This study investigates dosimetric differences due to increased effective atomic number (Zeff) for saline (Zeff = 7.56) versus water (Zeff = 7.42). METHODS: Balloon applicator diameters range from 3 to 6 cm. Monte Carlo N-Particle software is used to calculate dose at the surface (Ds) of and 1 cm away (D1cm) from the water-/saline-filled balloon applicator using a single dwell at the applicator center as a simple estimation of the dosimetry and multiple dwells simulating the clinical dose distributions for the atlas plans. RESULTS: Single-dwell plans show a 4.4-6.1% decrease in Ds for the 3- to 6-cm diameter applicators due to the saline. Multidwell plans show similar results: 4.9% and 6.4% Ds decrease, for 4-cm and 6-cm diameter applicators, respectively. For the single-dwell plans, D1cm decreases 3.6-5.2% for the 3- to 6-cm diameter applicators. For the multidwell plans, D1cm decreases 3.3% and 5.3% for the 4-cm and 6-cm applicators, respectively. CONCLUSIONS: The dosimetric effect introduced by saline versus water filling for Xoft balloon applicator-based IORT treatments is ∼5%. Users should be aware of this in the context of both treatment planning and patient outcome studies.

Characterization of Compton-scatter imaging with an analytical simulation method.

By collimating the photons scattered when a megavoltage therapy beam interacts with the patient, a Compton-scatter image may be formed without the delivery of an extra dose. To characterize and assess the potential of the technique, an analytical model for simulating scatter images was developed and validated against Monte Carlo (MC). For three phantoms, the scatter images collected during irradiation with a 6 MV flattening-filter-free therapy beam were simulated. Images, profiles, and spectra were compared for different phantoms and different irradiation angles. The proposed analytical method simulates accurate scatter images up to 1000 times faster than MC. Minor differences between MC and analytical simulated images are attributed to limitations in the isotropic superposition/convolution algorithm used to analytically model multiple-order scattering. For a detector placed at 90° relative to the treatment beam, the simulated scattered photon energy spectrum peaks at 140-220 keV, and 40-50% of the photons are the result of multiple scattering. The high energy photons originate at the beam entrance. Increasing the angle between source and detector increases the average energy of the collected photons and decreases the relative contribution of multiple scattered photons. Multiple scattered photons cause blurring in the image. For an ideal 5 mm diameter pinhole collimator placed 18.5 cm from the isocenter, 10 cGy of deposited dose (2 Hz imaging rate for 1200 MU min-1 treatment delivery) is expected to generate an average 1000 photons per mm2 at the detector. For the considered lung tumor CT phantom, the contrast is high enough to clearly identify the lung tumor in the scatter image. Increasing the treatment beam size perpendicular to the detector plane decreases the contrast, although the scatter subject contrast is expected to be greater than the megavoltage transmission image contrast. With the analytical method, real-time tumor tracking may be possible through comparison of simulated and acquired patient images.

Personalized Care and the Role of Insulin as a Vehicle to Optimizing Treatments in Diabetes Care.

BACKGROUND: In patients with type 2 diabetes (T2D) with poor glycemic control, there is an unmet need for treatment optimization involving the initiation and/or intensification of insulin therapy, which is often delayed because of clinical inertia. Educational initiatives that target patients and physicians might be one way to address this need. OBJECTIVE: To evaluate the effectiveness of educational materials mailed to physicians and their patients in affecting initiation of insulin therapy and other health care outcomes. METHODS: This study, named PIVOTs (Personalized care and the role of Insulin as a Vehicle to Optimizing Treatments), used integrated medical and pharmacy claims data from the U.S.-based HealthCore Integrated Research Database between January 1, 2006, and April 4, 2014, to identify patients who were potential candidates for insulin therapy. Eligible patients were aged 18-75 years, currently enrolled in a commercial or Medicare Advantage health plan, with T2D diagnosis codes. Patients selected for insulin treatment education had glycated hemoglobin A1c (A1c) > 10%, irrespective of the number of noninsulin antihyperglycemic drugs used, or A1c > 8.0% and ≤ 10% while receiving ≥ 2 noninsulin antihyperglycemic drugs. For each identified patient, a corresponding treating physician was identified on a hierarchical basis. Physician-level randomization was conducted to assign physicians and their linked patients to the following 4 cohorts: (1) a cross-sectional cohort in which educational materials were sent to patients and physicians on a single outreach date; (2) a longitudinal cohort in which educational materials were sent to patients and physicians on 2 occasions, 3 months apart; (3) an enhanced cohort in which patients and physicians received the same mailings as the longitudinal cohort, plus physicians were invited to attend a 1:1 video conference academic detailing session; and (4) a control cohort in which patients and physicians did not receive any educational materials. Insulin initiation rates, A1c levels, and medical and pharmacy costs were assessed from claims over 6 and 12 months follow-up within each cohort. RESULTS: Mean insulin initiation rates at 12 months ranged from 9.2%-10.3% (all patients) to 12.3%-14.9% (subset with baseline A1c ≥ 9.0%), with similar rates across the intervention and control cohorts. Reductions in A1c from baseline were also similar across cohorts for all patients (0.1%-0.6%), as well as for those with a baseline A1c ≥ 9.0% (0.9%-1.6%). Approximately 14%-20% of patients achieved A1c < 7.0%, with no differences across cohorts. Changes in mean total all-cause and diabetes-related health care costs were also similar across cohorts. CONCLUSIONS: The findings of this real-world, randomized intervention call into question the value of educational mailings as a means to overcoming clinical inertia and improving health outcomes in patients with T2D, at least in the context of insulin initiation. DISCLOSURES: This study was funded by Sanofi US. Bieszk and Wei are employees of Sanofi US. Grabner, Barron, and Quimbo are employees of HealthCore, which was under contract with Sanofi US for the conduct of this study. Yan is an employee of PHAR, LLC and was employed by HealthCore at the time this study was conducted and completed. Biel is an employee of Anthem. Chu is a consultant for Sanofi US; a member of the lecture bureaus for AstraZeneca, Eli Lilly, and Sanofi US; and has received research funding from Novo Nordisk. Study concept and design were contributed by Bieszk, Grabner, Wei, Quimbo, and Barron. Yan, Barron, Quimbo, and Grabner collected the data, which were interpreted by Biel, Chu, Bieszk, and Wei, with assistance from the other authors. The manuscript was written by Bieszk, with assistance from the other authors, and revised by Bieszk, Grabner, Biel, and Chu, along with the other authors. Part of this work was presented in poster format at the 76th Scientific Sessions of the American Diabetes Association; June 10-14, 2016; New Orleans, Louisiana.