A Randomized Trial of Choice Architecture and Mailed Colorectal Cancer Screening Outreach in a Community Health Setting.

BACKGROUND & AIMS: Mailed outreach for colorectal cancer (CRC) screening increases uptake but it is unclear how to offer the choice of testing. We evaluated if the active choice between colonoscopy and fecal immunochemical test (FIT), or FIT alone, increased response compared with colonoscopy alone. METHODS: This pragmatic, randomized, controlled trial at a community health center included patients between ages 50 and 74 who were not up to date with CRC screening. Patients were randomized 1:1:1 to the following: (1) colonoscopy only, (2) active choice of colonoscopy or FIT, or (3) FIT only. Patients received an outreach letter with instructions for testing (colonoscopy referral and/or an enclosed FIT kit), a reminder letter at 2 months, and another reminder at 3 to 5 months via text message or automated voice recording. The primary outcome was CRC screening completion within 6 months. RESULTS: Among 738 patients in the final analysis, the mean age was 58.7 years (SD, 6.2 y); 48.6% were insured by Medicaid and 24.3% were insured by Medicare; and 71.7% were White, 16.9% were Black, and 7.3% were Hispanic/Latino. At 6 months, 5.6% (95% CI, 2.8-8.5) completed screening in the colonoscopy-only arm, 12.8% (95% CI, 8.6-17.0) in the active-choice arm, and 11.3% (95% CI, 7.4-15.3) in the FIT-only arm. Compared with colonoscopy only, there was a significant increase in screening in active choice (absolute difference, 7.1%; 95% CI, 2.0-12.2; P = .006) and FIT only (absolute difference, 5.7%; 95% CI, 0.8-10.6; P = .02). CONCLUSIONS: Both choice of testing and FIT alone increased response and may align with patient preferences. TRIAL REGISTRATION: clinicaltrials.gov NCT04711473.

Behavioral Interventions to Improve Breast Cancer Screening Outreach: Two Randomized Clinical Trials.

Importance: Despite public health efforts, breast cancer screening rates remain below national goals. Objective: To evaluate whether bulk ordering, text messaging, and clinician endorsement increase breast cancer screening rates. Design, Setting, and Participants: Two concurrent, pragmatic, randomized clinical trials, each with a 2-by-2 factorial design, were conducted between October 25, 2021, and April 25, 2022, in 2 primary care regions of an academic health system. The trials included women aged 40 to 74 years with at least 1 primary care visit in the past 2 years who were eligible for breast cancer screening. Interventions: Patients in trial A were randomized in a 1:1 ratio to receive a signed bulk order for mammogram or no order; in a factorial design, patients were concurrently randomized in a 1:1 ratio to receive or not receive text message reminders. Patients in trial B were randomized in a 1:1 ratio to receive a message signed by their primary care clinician (clinician endorsement) or from the organization (standard messaging); in a factorial design, patients were concurrently randomized in a 1:1 ratio to receive or not receive text message reminders. Main Outcomes and Measures: The primary outcome was the proportion of patients who completed a screening mammogram within 3 months. Results: Among 24 632 patients included, the mean (SD) age was 60.4 (7.5) years. In trial A, at 3 months, 15.4% (95% CI, 14.6%-16.1%) of patients in the bulk order arm and 12.7% (95% CI, 12.1%-13.4%) in the no order arm completed a mammogram, showing a significant increase (absolute difference, 2.7%; 95% CI, 1.6%-3.6%; P < .001). In the text messaging comparison arms, 15.1% (95% CI, 14.3%-15.8%) of patients receiving a text message completed a mammogram compared with 13.0% (95% CI, 12.4%-13.7%) of those in the no text messaging arm, a significant increase (absolute difference of 2.1%; 95% CI, 1.0%-3.0%; P < .001). In trial B, at 3 months, 12.5% (95% CI, 11.3%-13.7%) of patients in the clinician endorsement arm completed a mammogram compared with 11.4% (95% CI, 10.3%-12.5%) of those in the standard messaging arm, which was not significant (absolute difference, 1.1%; 95% CI, -0.5% to 2.7%; P = .18). In the text messaging comparison arms, 13.2% (95% CI, 12.0%-14.4%) of patients receiving a text message completed a mammogram compared with 10.7% (95% CI, 9.7%-11.8%) of those in the no text messaging arm, a significant increase (absolute difference, 2.5%; 95% CI, 0.8%-4.0%; P = .003). Conclusions and Relevance: These findings show that text messaging women after initial breast cancer screening outreach via either electronic portal or mailings, as well as bulk ordering with or without text messaging, can increase mammogram completion rates. Trial Registration: ClinicalTrials.gov Identifier: NCT05089903.

PCR in Forensic Science: A Critical Review.

The polymerase chain reaction (PCR) has played a fundamental role in our understanding of the world, and has applications across a broad range of disciplines. The introduction of PCR into forensic science marked the beginning of a new era of DNA profiling. This era has pushed PCR to its limits and allowed genetic data to be generated from trace DNA. Trace samples contain very small amounts of degraded DNA associated with inhibitory compounds and ions. Despite significant development in the PCR process since it was first introduced, the challenges of profiling inhibited and degraded samples remain. This review examines the evolution of the PCR from its inception in the 1980s, through to its current application in forensic science. The driving factors behind PCR evolution for DNA profiling are discussed along with a critical comparison of cycling conditions used in commercial PCR kits. Newer PCR methods that are currently used in forensic practice and beyond are examined, and possible future directions of PCR for DNA profiling are evaluated.

Association of Electronic Self-Scheduling and Screening Mammogram Completion.

INTRODUCTION: The purpose of this study was to evaluate if an electronic health record (EHR) self-scheduling function was associated with changes in mammogram completion for primary care patients who were eligible for a screening mammogram using U.S. Preventive Service Task Force recommendations. METHODS: This was a retrospective cohort study (September 1, 2014-August 31, 2019, analyses completed in 2022) using a difference-in-differences design to examine mammogram completion before versus after the implementation of self-scheduling. The difference-in-differences estimate was the interaction between time (pre-versus post-implementation) and group (active EHR patient portal versus inactive EHR patient portal). The primary outcome was mammogram completion among all eligible patients, with completion defined as receiving a mammogram within 6 months post-visit. The secondary outcome was mammogram completion among patients who received a clinician order during their visit. RESULTS: The primary analysis included 35,257 patient visits. The overall mammogram completion rate in the pre-period was 22.2% and 49.7% in the post-period. EHR self-scheduling was significantly associated with increased mammogram completion among those with an active EHR portal, relative to patients with an inactive portal (adjusted difference 13.2 percentage points [95% CI 10.6-15.8]). For patients who received a clinician mammogram order at their eligible visit, self-scheduling was significantly associated with increased mammogram completion among patients with an active EHR portal account (adjusted difference 14.7 percentage points, [95% CI 10.9-18.5]). CONCLUSIONS: EHR-based self-scheduling was associated with a significant increase in mammogram completion among primary care patients. Self-scheduling can be a low-cost, scalable function for increasing preventive cancer screenings.

A randomized trial of mailed outreach with behavioral economic interventions to improve liver cancer surveillance.

BACKGROUND: Surveillance rates for HCC remain limited in patients with cirrhosis. We evaluated whether opt-out mailed outreach increased uptake with or without a $20 unconditional incentive. METHODS: This was a pragmatic randomized controlled trial in an urban academic health system including adult patients with cirrhosis or advanced fibrosis, at least 1 visit to a specialty practice in the past 2 years and no surveillance in the last 7 months. Patients were randomized in a 1:2:2 ratio to (1) usual care, (2) a mailed letter with a signed order for an ultrasound, or (3) a mailed letter with an order and a $20 unconditional incentive. The main outcome was the proportion with completion of ultrasound within 6 months. RESULTS: Among the 562 patients included, the mean age was 62.1 (SD 11.1); 56.8% were male, 51.1% had Medicare, and 40.6% were Black. At 6 months, 27.6% (95% CI: 19.5-35.7) completed ultrasound in the Usual care arm, 54.5% (95% CI: 47.9-61.0) in the Letter + Order arm, and 54.1% (95% CI: 47.5-60.6) in the Letter + Order + Incentive arm. There was a significant increase in the Letter + Order arm compared to Usual care (absolute difference of 26.9%; 95% CI: 16.5-37.3; p<0.001), but no significant increase in the Letter + Order + Incentive arm compared to Letter + Order (absolute difference of -0.4; 95% CI: -9.7 to 8.8; p=0.93). CONCLUSIONS: There was an increase in HCC surveillance from mailed outreach with opt-out framing and a signed order slip, but no increase in response to the financial incentive.

Prediction of Gait Kinematics and Kinetics: A Systematic Review of EMG and EEG Signal Use and Their Contribution to Prediction Accuracy.

Human-machine interfaces hold promise in enhancing rehabilitation by predicting and responding to subjects' movement intent. In gait rehabilitation, neural network architectures utilize lower-limb muscle and brain activity to predict continuous kinematics and kinetics during stepping and walking. This systematic review, spanning five databases, assessed 16 papers meeting inclusion criteria. Studies predicted lower-limb kinematics and kinetics using electroencephalograms (EEGs), electromyograms (EMGs), or a combination with kinematic data and anthropological parameters. Long short-term memory (LSTM) and convolutional neural network (CNN) tools demonstrated highest accuracies. EEG focused on joint angles, while EMG predicted moments and torque joints. Useful EEG electrode locations included C3, C4, Cz, P3, F4, and F8. Vastus Lateralis, Rectus Femoris, and Gastrocnemius were the most commonly accessed muscles for kinematic and kinetic prediction using EMGs. No studies combining EEGs and EMGs to predict lower-limb kinematics and kinetics during stepping or walking were found, suggesting a potential avenue for future development in this technology.

Stroke survivor perceptions of using an exoskeleton during acute gait rehabilitation.

Robotic-assisted gait training (RAGT) devices allow intensive high repetition of the gait cycle in individuals with locomotor disability, with reduced therapist effort. In addition to usual rehabilitation, RAGT post-stroke improves the likelihood of regaining independent walking, with maximum efficacy identified in the acute and subacute phases of stroke. This study explores the usability and acceptance of RAGT among persons with stroke in an acute hospital setting and examines users' perceptions of two different modes of robotic assistance provided during rehabilitation. A mixed-methods approach comprised semi-structed interviews of end-user perspectives of RAGT in an acute hospital setting following stroke and two 10-point Likert scales rating how comfortable and how natural robotic gait felt using different assistance modes. Content analysis of qualitative data was undertaken with results synthesised by common meaning units. Quantitative data were reported using summary statistics, with Spearmann's correlation co-efficient examining the relationship between Likert scale ratings and measures of participants' stroke related disability. Ten individuals (6 men; 4 women; mean age of 64.5. ± 13 years) were recruited in an acute hospital setting following admission with a stroke diagnosis. Content analysis of interview transcripts identified discussion units centring around positive aspects of how helpful the device was, negative aspects related to set-up time, weight of the device and multiple instructions delivered during use. Initially participants identified that the device could look intimidating, and they feared falling in the device but they subsequently identified the correct mindset for using the device is to trust the technology and not be afraid. Mean ratings for device comfort (7.94 ± 1.4) and how natural walking felt (7.05 ± 1.9) were favourable. Interestingly, a strong relationship was identified, whereby the higher the level of disability, the more natural participants rated walking in the device during maximal assistance mode (rho = 0.62; p = 0.138). This study suggests individuals in the early phases of stroke perceive RAGT to be acceptable and helpful in the main, with some associated negative aspects. Walking in the device was rated as comfortable and natural. Those with greater disability rated the assisted walking as more natural.

Effect of Text Messaging and Behavioral Interventions on COVID-19 Vaccination Uptake: A Randomized Clinical Trial.

Importance: COVID-19 vaccine uptake among urban populations remains low. Objective: To evaluate whether text messaging with outbound or inbound scheduling and behaviorally informed content might increase COVID-19 vaccine uptake. Design, Setting, and Participants: This randomized clinical trial with a factorial design was conducted from April 29 to July 6, 2021, in an urban academic health system. The trial comprised 16 045 patients at least 18 years of age in Philadelphia, Pennsylvania, with at least 1 primary care visit in the past 5 years, or a future scheduled primary care visit within the next 3 months, who were unresponsive to prior outreach. The study was prespecified in the trial protocol, and data were obtained from the intent-to-treat population. Interventions: Eligible patients were randomly assigned in a 1:20:20 ratio to (1) outbound telephone call only by call center, (2) text message and outbound telephone call by call center to those who respond, or (3) text message, with patients instructed to make an inbound telephone call to a hotline. Patients in groups 2 and 3 were concurrently randomly assigned in a 1:1:1:1 ratio to receive different content: standard messaging, clinician endorsement (eg, "Dr. XXX recommends"), scarcity ("limited supply available"), or endowment framing ("We have reserved a COVID-19 vaccine appointment for you"). Main Outcomes and Measures: The primary outcome was the proportion of patients who completed the first dose of the COVID-19 vaccine within 1 month, according to the electronic health record. Secondary outcomes were the completion of the first dose within 2 months and completion of the vaccination series within 2 months of initial outreach. Additional outcomes included the percentage of patients with invalid cell phone numbers (wrong number or nontextable), no response to text messaging, the percentage of patients scheduled for the vaccine, text message responses, and the number of telephone calls made by the access center. Analysis was on an intention-to-treat basis. Results: Among the 16 045 patients included, the mean (SD) age was 36.9 (11.1) years; 9418 (58.7%) were women; 12 869 (80.2%) had commercial insurance, and 2283 (14.2%) were insured by Medicaid; 8345 (52.0%) were White, 4706 (29.3%) were Black, and 967 (6.0%) were Hispanic or Latino. At 1 month, 14 of 390 patients (3.6% [95% CI, 1.7%-5.4%]) in the outbound telephone call-only group completed 1 vaccine dose, as did 243 of 7890 patients (3.1% [95% CI, 2.7%-3.5%]) in the text plus outbound call group (absolute difference, -0.5% [95% CI, -2.4% to 1.4%]; P = .57) and 253 of 7765 patients (3.3% [95% CI, 2.9%-3.7%]) in the text plus inbound call group (absolute difference, -0.3% [95% CI, -2.2% to 1.6%]; P = .72). Among the 15 655 patients receiving text messaging, 118 of 3889 patients (3.0% [95% CI, 2.5%-3.6%]) in the standard messaging group completed 1 vaccine dose, as did 135 of 3920 patients (3.4% [95% CI, 2.9%-4.0%]) in the clinician endorsement group (absolute difference, 0.4% [95% CI, -0.4% to 1.2%]; P = .31), 100 of 3911 patients (2.6% [95% CI, 2.1%-3.1%]) in the scarcity group (absolute difference, -0.5% [95% CI, -1.2% to 0.3%]; P = .20), and 143 of 3935 patients (3.6% [95% CI, 3.0%-4.2%]) in the endowment group (absolute difference, 0.6% [95% CI, -0.2% to 1.4%]; P = .14). Conclusions and Relevance: There was no detectable increase in vaccination uptake among patients receiving text messaging compared with telephone calls only or behaviorally informed message content. Trial Registration: ClinicalTrials.gov Identifier: NCT04834726.

Potential impact of national recommendations to use short course antibiotic therapy on antibiotic use in the emergency department of a UK hospital: retrospective observational study.

BACKGROUND AND IMPORTANCE: The National Institute for Health and Care Excellence (NICE) antimicrobial prescribing guidelines for common infections recommend short course antimicrobial therapy in order to reduce antibiotic associated harm. OBJECTIVE: To quantify the opportunity to reduce antibiotic use in an emergency department (ED) through adoption of these short antibiotic course recommendations. DESIGN, SETTINGS AND PARTICIPANTS: A retrospective observational study in an ED in the UK with 95 000 attendances a year. Patients managed in the ED between 1 December and 31 December 2019 with the following infections were identified: acute otitis media, human and animal bites, pyelonephritis, lower urinary tract infections, cellulitis, cough, infective exacerbation of chronic obstructive pulmonary disease, pneumonia, sore throat, sinusitis, and diverticulitis. OUTCOME MEASURE: Excess antibiotic use due to either a protracted course length, or not meeting criteria for antibiotics. RESULTS: 395 patients (260 adults and 135 children) were identified. Of the 1215 days of antibiotic therapy, 198 (16%) were excess because of protracted course lengths. In terms of antibiotic defined daily doses (DDD), there were 1201.5 antibiotic DDD prescribed, of which 232 (19%) DDD were excess because of protracted course lengths. If both protracted courses and unnecessary antibiotic use were included, then 321 (27%) DDD were excess. Excess antibiotic use and total antibiotic use by infection group were: 123/546 (23%) DDD in lower respiratory tract infection, 46/59 (79%) in upper respiratory tract infection, 44/231 (19%) in upper and lower urinary tract infection, 0/113 (0%) cellulitis, 77/180 (43%) bites, and 30/40 (75%) diverticulitis. Excess antibiotic use, as a proportion of all antibiotic use in the ED, was 321/4291 (7.5%) DDD, and of whole hospital antibiotic use, the ED's excess use was 321/33 566 (0.96%). CONCLUSION: Adoption of NICE antibiotic prescribing guidelines for common infections has the potential to reduce total antibiotic use in the ED by 7.5% and contribute to the hospital-wide antibiotic stewardship programme.

Direct participation of people with communication disabilities in research on poverty and disabilities in low and middle income countries: A critical review.

INTRODUCTION: An estimated 1 billion people with disabilities live in low and middle income countries, a population that includes people with communication disabilities (PwCD). PwCD are a heterogenous group with a wide range of abilities who may be underrepresented in research due to the communication demands involved in research participation. METHODS: A critical analysis of 145 studies from a previously published systematic review was undertaken with the aim of documenting the opportunities for direct participation of PwCD in research on poverty and disability in low- and middle- income countries. RESULTS: The key finding was the high risk of underrepresentation of PwCD in research on poverty and disability in LMICs, despite low rates of explicit exclusion (n = 8; 5.5%). A total of 366 uses of data collection tools were analysed (255 unique tools). The majority of data collection tools had high communication demands (92.9%), including those measuring disability (88.6%) and those assessing poverty (100%). Only 22 studies (15.2%) specifically included PwCD. A subset of these studies (n = 14) presented disaggregated data in a way that allowed for analysis of outcomes for PwCD, suggesting a clear intersection between poverty and communication disability, with findings related to general poverty indicators, reduced access to education, low levels of employment, and additional expenditure. CONCLUSIONS: The findings suggest a systematic underrepresentation of PwCD in research on poverty and disability with substantial implications for future policy and program planning, directly affecting the availability and provision of services and resources for this population. A failure to provide adequate opportunity for participation of PwCD in research risks leaving those with communication disabilities behind in the pursuit of global poverty eradication.

Potential to reduce antibiotic use in secondary care: Single-centre process audit of prescription duration using NICE guidance for common infections.

INTRODUCTION: Antibiotic use drives antibiotic resistance. Reducing antibiotic use through reducing antibiotic course lengths could contribute to the UK national ambition to reduce total antibiotic use. METHODS: Medical notes were reviewed for patients who had received at least 5 days of antibiotic therapy; had been discharged in January 2019; and were from a 750-bed acute secondary care hospital in England. UK national guidelines were used to determine the excess antibiotic use in common medical infections: community-acquired pneumonia (CAP), hospital-acquired pneumonia (HAP), pyelonephritis, cellulitis, infective exacerbation of chronic obstructive pulmonary disease (IECOPD) and cholangitis. RESULTS: Four-hundred and twenty-three patients met the inclusion criteria. Of these, 307 (73%) patient notes were retrieved and reviewed. One-hundred and seventy-three patients met the study case definitions, of which, 137 met short course criteria.Potential antibiotic reductions (measured in defined daily doses) were identified for five of the six infections: 32% in CAP, 20% in HAP, 14% in IECOPD, 11% in cellulitis and 10% in pyelonephritis. These reductions were estimated to reduce total antibiotic use in medical specialties by 12.4%, which equates to 3.6% of the hospital's total antibiotic use. CONCLUSION: Clinical application of the evidence-based guidance for shorter antibiotic course lengths appears to be a valid strategy for reducing total antibiotic consumption.

Effect of Text Messaging on Bowel Preparation and Appointment Attendance for Outpatient Colonoscopy: A Randomized Clinical Trial.

Importance: Outpatient colonoscopy is important for colorectal cancer screening. However, nonadherence and poor bowel preparation are common. Objective: To determine if an automated text messaging intervention with a focus on informational and reminder functions could improve attendance rates and bowel preparation quality for outpatient colonoscopy. Design, Setting, and Participants: This randomized clinical trial was conducted in an endoscopy center at an urban academic medical center. Adult patients scheduled for outpatient colonoscopy between January and September 2019 were enrolled by telephone call (early phase) or by automated text message (late phase). Data were analyzed from October 2019 to January 2020. Interventions: After enrollment, patients were randomized in a 1:1 ratio to usual care (ie, written instructions and nurse telephone call) or to the intervention (ie, usual care plus an automated series of 9 educational or reminder text messages in the week prior to scheduled colonoscopy). Main Outcomes and Measures: The primary outcome was appointment attendance rate with good or excellent bowel preparation. Secondary outcomes included appointment attendance rate, bowel preparation quality (poor or inadequate, fair or adequate, and good or excellent), and cancellation lead time (in days). Results: Among 753 patients included and randomized in the trial (median [interquartile range] age, 56 [49-64] years; 364 [48.3%] men; 429 [57.2%] Black), 367 patients were randomized to the intervention group and 386 patients were randomized to the control group. There was no significant difference in the primary outcome between groups (patients attending appointments with good or excellent bowel preparation: intervention, 195 patients [53.1%]; control, 210 patients [54.4%]; P = .73), including when stratified by early or late phase enrollment groups. Similarly, there were no significant differences in secondary outcomes. Conclusions and Relevance: This randomized clinical trial found no significant difference in appointment attendance or bowel preparation quality with an automated text messaging intervention compared with the usual care control. Future work could optimize the content and delivery of text message interventions or identify patient subgroups that may benefit from this approach. Trial Registration: ClinicalTrials.gov Identifier: NCT03710213.

Effect of Remote Monitoring on Discharge to Home, Return to Activity, and Rehospitalization After Hip and Knee Arthroplasty: A Randomized Clinical Trial.

Importance: Hip and knee arthroplasty are the most common inpatient surgical procedures for Medicare beneficiaries in the US, with substantial variation in cost and quality. Whether remote monitoring incorporating insights from behavioral science might help improve outcomes and increase value of care remains unknown. Objective: To evaluate the effect of activity monitoring and bidirectional text messaging on the rate of discharge to home and clinical outcomes in patients receiving hip or knee arthroplasty. Design, Setting, and Participants: Randomized clinical trial conducted between February 7, 2018, and April 15, 2019. The setting was 2 urban hospitals at an academic health system. Participants were patients aged 18 to 85 years scheduled to undergo hip or knee arthroplasty with a Risk Assessment and Prediction Tool score of 6 to 8. Interventions: Eligible patients were randomized evenly to receive usual care (n = 153) or remote monitoring (n = 147). Those in the intervention arm who agreed received a wearable activity monitor to track step count, messaging about postoperative goals and milestones, pain score tracking, and connection to clinicians as needed. Patients assigned to receive monitoring were further randomized evenly to remote monitoring alone or remote monitoring with gamification and social support. Remote monitoring was offered before surgery, began at hospital discharge, and continued for 45 days postdischarge. Main Outcomes and Measures: The primary outcome was discharge status (home vs skilled nursing facility or inpatient rehabilitation). Prespecified secondary outcomes included change in average daily step count and rehospitalizations. Results: A total of 242 patients were analyzed (124 usual care, 118 intervention); median age was 66 years (interquartile range, 58-73 years); 78.1% were women, 45.5% were White, 43.4% were Black; and 81.4% in the intervention arm agreed to receive monitoring. There was no significant difference in the rate of discharge to home between the usual care arm (57.3%; 95% CI, 48.5%-65.9%) and the intervention arm (56.8%; 95% CI, 47.9%-65.7%) and no significant increase in step count in those receiving remote monitoring plus gamification and social support compared with remote monitoring alone. There was a statistically significant reduction in rehospitalization rate in the intervention arm (3.4%; 95% CI, 0.1%-6.7%) compared with the usual care arm (12.2%; 95% CI, 6.4%-18.0%) (P = .01). Conclusions and Relevance: In this study, the remote monitoring program did not increase rate of discharge to home after hip or knee arthroplasty, and gamification and social support did not increase activity levels. There was a significant reduction in rehospitalizations among those receiving the intervention, which may have resulted from goal setting and connection to the care team. Trial Registration: ClinicalTrials.gov Identifier: NCT03435549.

Applying Behavioral Economics to Enhance Safe Firearm Storage.

Behavioral economics applies key principles from psychology and economics to address obstacles to behavior change. The important topic of pediatric firearm injuries has not yet been explored through a behavioral economic lens. Pediatric firearm-related injuries are a significant public health problem in the United States. Despite American Academy of Pediatrics guidelines advising that firearms be stored unloaded, in a locked box or with a locking device, and separate from ammunition, estimates suggest that ∼4.6 million children live in homes with at least 1 loaded and unlocked firearm. In this article, we use behavioral economic theory to identify specific cognitive biases (ie, present bias; in-group, out-group bias; and the availability heuristic) that may influence parental decision-making around firearm storage. We illustrate situations in which these biases may occur and highlight implementation prompts, in-group messengers, and increased salience as behaviorally informed strategies that may counter these biases and subsequently enhance safe firearm storage. We also describe other opportunities to leverage the behavioral economic tool kit. By better understanding the individual behavioral levers that may impact decision-making around firearm storage, behavioral scientists, pediatric providers, and public health practitioners can partner to design and test tailored interventions aimed at decreasing pediatric firearm injuries. Further empirical study is warranted to identify the presence of specific biases and heuristics and determine the most effective behavior change strategies for different subpopulations.

Changes in Cardiovascular Biomarkers With Breast Cancer Therapy and Associations With Cardiac Dysfunction.

Background We examined the longitudinal associations between changes in cardiovascular biomarkers and cancer therapy-related cardiac dysfunction (CTRCD) in patients with breast cancer treated with cardotoxic cancer therapy. Methods and Results Repeated measures of high-sensitivity cardiac troponin T (hs-cTnT), NT-proBNP (N-terminal pro-B-type natriuretic peptide), myeloperoxidase, placental growth factor, and growth differentiation factor 15 were assessed longitudinally in a prospective cohort of 323 patients treated with anthracyclines and/or trastuzumab followed over a maximum of 3.7 years with serial echocardiograms. CTRCD was defined as a ≥10% decline in left ventricular ejection fraction to a value <50%. Associations between changes in biomarkers and left ventricular ejection fraction were evaluated in repeated-measures linear regression models. Cox regression models assessed the associations between biomarkers and CTRCD. Early increases in all biomarkers occurred with anthracycline-based regimens. hs-cTnT levels >14 ng/L at anthracycline completion were associated with a 2-fold increased CTRCD risk (hazard ratio, 2.01; 95% CI, 1.00-4.06). There was a modest association between changes in NT-proBNP and left ventricular ejection fraction in the overall cohort; this was most pronounced with sequential anthracycline and trastuzumab (1.1% left ventricular ejection fraction decline [95% CI, -1.8 to -0.4] with each NT-proBNP doubling). Increases in NT-proBNP were also associated with CTRCD (hazard ratio per doubling, 1.56; 95% CI, 1.32-1.84). Increases in myeloperoxidase were associated with CTRCD in patients who received sequential anthracycline and trastuzumab (hazard ratio per doubling, 1.28; 95% CI, 1.04-1.58). Conclusions Cardiovascular biomarkers may play an important role in CTRCD risk prediction in patients with breast cancer who receive cardiotoxic cancer therapy, particularly in those treated with sequential anthracycline and trastuzumab therapy. Clinical Trial Registration URL: https://www.clinicaltrials.gov/. Unique identifier: NCT01173341.

Colorectal Cancer Screening Among Patients who Receive Medical and Dental Care at an Urban Community Health Center.

Colorectal cancer (CRC) screening rates remain subpar, particularly among underserved populations. As the role of health care providers evolves, it has been suggested that dentists could play a larger role in preventive health. Building on this concept, dental visits could serve as an additional touchpoint for CRC screening outreach. The primary goal of this study was to compare CRC screening rates among patients who receive both dental and medical care to those who only receive medical care at an urban community health center in order to inform future CRC screening intervention development. We conducted a retrospective medical and dental record data abstraction of all patients meeting the criteria for CRC screening who had a medical and/or dental appointment within the last 2 years. A total of 1081 eligible patients were identified-250 in the dental and medical group and 831 in the medical only group. The patient population was largely black, female, and publicly insured. Among the dental and medical group patients, 36% were up to date on CRC screening compared to 22% among the medical only group (p < 0.001). In addition, the medical and dental group patients had higher screening rates in all other preventive health measures analyzed (p < 0.001). Despite higher screening rates among patients who received both dental and medical care, overall rates were very low. Further screening outreach is needed in this population, and engaging patients at dental visits may be one approach.

Detailed phenotyping reveals distinct trajectories of cardiovascular function and symptoms with exposure to modern breast cancer therapy.

BACKGROUND: Breast cancer therapies are associated with a risk of cardiac dysfunction, most commonly defined by changes in left ventricular ejection fraction (LVEF). Recently, the authors identified 3 classes of LVEF change after exposure to anthracyclines and/or trastuzumab using latent class growth modeling. The objective of the current study was to characterize the clinical, biochemical, and functional profiles associated with LVEF trajectory class membership. METHODS: Transthoracic echocardiography and biomarker assessments were performed and questionnaires were administered at standardized intervals in a longitudinal cohort of 314 patients with breast cancer who were treated with anthracyclines and/or trastuzumab. Univariable and multivariable multinomial regression analyses evaluated associations between baseline variables and LVEF trajectory class membership. Generalized estimating equations were used to define mean changes in cardiovascular measures over time within each class. RESULTS: Among the 3 distinct subgroups of LVEF changes identified (stable [class 1]; modest, persistent decline [class 2]; and significant early decline followed by partial recovery [class 3]), higher baseline LVEF, radiotherapy, and sequential therapy with anthracyclines and/or trastuzumab were associated with class 2 or 3 membership. Sustained abnormalities in longitudinal strain and N-terminal pro-B-type natriuretic peptide (NT-proBNP) were observed in patients in class 2, as were heart failure symptoms. Similar abnormalities were observed in patients in class 3, but there was a trend toward recovery, particularly for longitudinal strain. CONCLUSIONS: Patients with modest, persistent LVEF declines experienced sustained abnormalities in imaging and biochemical markers of cardiac function and heart failure symptoms. Further investigation is needed to characterize the long-term risk of heart failure, particularly in those with modest LVEF declines.

Early Changes in Cardiovascular Biomarkers with Contemporary Thoracic Radiation Therapy for Breast Cancer, Lung Cancer, and Lymphoma.

PURPOSE: We characterized the early changes in cardiovascular biomarkers with contemporary thoracic radiation therapy (RT) and evaluated their associations with radiation dose-volume metrics including mean heart dose (MHD), V5, and V30. METHODS AND MATERIALS: In a prospective longitudinal study of 87 patients with breast cancer, lung cancer, or mediastinal lymphoma treated with photon or proton thoracic RT, blood samples were obtained pre-RT and after completion of RT (median, 20 days; interquartile range [IQR], 1-35). High-sensitivity cardiac troponin T, N-terminal pro-B-type natriuretic peptide, placental growth factor (PIGF), and growth differentiation factor 15 (GDF-15) were measured. Associations between MHD, V5 and V30, and biomarker levels and associations between echocardiography-derived measures of cardiac function and biomarker levels were assessed in multivariable linear regression models. Analyses were performed according to the following subgroups: (1) breast cancer alone and (2) lung cancer and lymphoma combined. RESULTS: The median (IQR) estimates of MHD ranged from 1.3 Gy (0.9-2.4) in breast cancer (n = 60) to 6.8 Gy (5.4-10.2) in mediastinal lymphoma (n = 14) and 8.4 Gy (6.7-16.1) in lung cancer (n = 13) patients (P < .001). There were no significant increases in biomarker levels from pre-RT to post-RT in breast cancer. In lung cancer/lymphoma, PIGF increased from a median (IQR) of 20 ng/L (16-26) to 22 ng/L (16-30) (P = .005), and GDF-15 increased from 1171 ng/L (755-2493) to 1887 ng/L (903-3763) (P = .006). MHD, V5, and V30 were significantly associated with post-RT PIGF and GDF-15 levels in multivariable models. Changes in biomarkers were not significantly associated with changes in echocardiography-derived measures of cardiac function. CONCLUSION: Contemporary thoracic RT induces acute abnormalities in vascular and inflammatory biomarkers that are associated with radiation dose-volume metrics, particularly in lung cancer and mediastinal lymphoma. Long-term follow-up studies are needed to determine the impact of these changes on the development of overt cardiac disease.

Genomic integration of ERRγ-HNF1ß regulates renal bioenergetics and prevents chronic kidney disease.

Mitochondrial dysfunction is increasingly recognized as a critical determinant of both hereditary and acquired kidney diseases. However, it remains poorly understood how mitochondrial metabolism is regulated to support normal kidney function and how its dysregulation contributes to kidney disease. Here, we show that the nuclear receptor estrogen-related receptor gamma (ERRγ) and hepatocyte nuclear factor 1 beta (HNF1ß) link renal mitochondrial and reabsorptive functions through coordinated epigenomic programs. ERRγ directly regulates mitochondrial metabolism but cooperatively controls renal reabsorption via convergent binding with HNF1ß. Deletion of ERRγ in renal epithelial cells (RECs), in which it is highly and specifically expressed, results in severe renal energetic and reabsorptive dysfunction and progressive renal failure that recapitulates phenotypes of animals and patients with HNF1ß loss-of-function gene mutations. Moreover, ERRγ expression positively correlates with renal function and is decreased in patients with chronic kidney disease (CKD). REC-ERRγ KO mice share highly overlapping renal transcriptional signatures with human patients with CKD. Together these findings reveal a role for ERRγ in directing independent and HNF1ß-integrated programs for energy production and use essential for normal renal function and the prevention of kidney disease.

GDF15 is a heart-derived hormone that regulates body growth.

The endocrine system is crucial for maintaining whole-body homeostasis. Little is known regarding endocrine hormones secreted by the heart other than atrial/brain natriuretic peptides discovered over 30 years ago. Here, we identify growth differentiation factor 15 (GDF15) as a heart-derived hormone that regulates body growth. We show that pediatric heart disease induces GDF15 synthesis and secretion by cardiomyocytes. Circulating GDF15 in turn acts on the liver to inhibit growth hormone (GH) signaling and body growth. We demonstrate that blocking cardiomyocyte production of GDF15 normalizes circulating GDF15 level and restores liver GH signaling, establishing GDF15 as a bona fide heart-derived hormone that regulates pediatric body growth. Importantly, plasma GDF15 is further increased in children with concomitant heart disease and failure to thrive (FTT). Together these studies reveal a new endocrine mechanism by which the heart coordinates cardiac function and body growth. Our results also provide a potential mechanism for the well-established clinical observation that children with heart diseases often develop FTT.