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Health care education has been widely criticized for not providing training in end-of-life care. Despite calls from various scientific and professional organizations for formal educational improvement, most education in this area is 'on the job.' The current project is a secondary analysis of a surveyed convenience sample (n = 608) of health care providers in Kansas to determine knowledge, background, perceptions, and opinions about pain management and end-of-life care. The sample was primarily nurses (73%), with a small representation of other disciplines. The results of the survey indicate that providers believe they are ill prepared to provide palliative care and want professional education to improve knowledge and skills in this area. In addition, they state a need for increased support from insurers and legal and regulatory agencies to provide an acceptable standard of care. Providers responding to the survey also believe there is a significant need for patient education in this area. [ABSTRACT FROM AUTHOR]

Evidence is steadily mounting that attribute-based models offer a more accurate description of intertemporal choices than traditional alternative-based models. Among the attribute-based models, the tradeoff model offers the broadest coverage of research findings, but at the cost of considerable complexity: There now are various instantiations of the model dealing with partially overlapping universes of choice options and preference patterns. Moreover, there are reports of preference patterns in intertemporal decisions about monetary losses that contradict all attribute-based models proposed so far. Taking stock of these core challenges, and all other evidence, we develop an account of intertemporal choice, the unified tradeoff model, that is simpler, yet more comprehensive, than all currently available versions of the tradeoff model taken together. It borrows extensively from its predecessors, but it introduces a new element, time bias , that enables it to accommodate an extraordinarily broad range of preference patterns, and also generate new predictions that contradict all existing models of intertemporal choice. We report four studies that test and confirm its predictions regarding delay, interval, sign, and magnitude dependence in choices between single-dated outcomes, and a fifth study that tests and confirms its predictions regarding the relation between delay preference in choices that only involve single-dated payments and duration preference in choices that also involve sequences of payments. Having subjected the unified tradeoff model to an elevated risk of disconfirmation, we discuss its parsimony and scope in relation to yet other phenomena, most notably, preference patterns in consumption decisions, the final frontier for attribute-based models. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Importance: Increasing influenza vaccination rates is a public health priority. One method recommended by the US Centers for Disease Control and Prevention and others is for health systems to send reminders nudging patients to be vaccinated., Objective: To evaluate and compare the effect of electronic health record (EHR)-based patient portal reminders vs text message reminders on influenza vaccination rates across a health system., Design, Setting, and Participants: This 3-arm randomized clinical trial was conducted from September 7, 2022, to April 30, 2023, among primary care patients within the University of California, Los Angeles (UCLA) health system., Interventions: Arm 1 received standard of care. The health system sent monthly reminder messages to patients due for an influenza vaccine by portal (arm 2) or text (arm 3). Arm 2 had a 2 × 2 nested design, with fixed vs responsive monthly reminders and preappointment vs no preappointment reminders. Arm 3 had 1 × 2 design, with preappointment vs no preappointment reminders. Preappointment reminders for eligible patients were sent 24 and 48 hours before scheduled primary care visits. Fixed reminders (in October, November, and December) involved identical messages via portal or text. Responsive portal reminders involved a September message asking patients about their plans for vaccination, with a follow-up reminder if the response was affirmative but the patient was not yet vaccinated., Main Outcomes and Measures: The primary outcome was influenza vaccination by April 30, 2023, obtained from the UCLA EHR, including vaccination from pharmacies and other sources., Results: A total of 262 085 patients (mean [SD] age, 45.1 [20.7] years; 237 404 [90.6%] adults; 24 681 [9.4%] children; 149 349 [57.0%] women) in 79 primary care practices were included (87 257 in arm 1, 87 478 in arm 2, and 87 350 in arm 3). At the entire primary care population level, none of the interventions improved influenza vaccination rates. All groups had rates of approximately 47%. There was no statistical or clinically significant improvement following portal vs text, preappointment reminders vs no preappointment reminders (portal and text reminders combined), or responsive vs fixed monthly portal reminders., Conclusions and Relevance: At the population level, neither portal nor text reminders for influenza vaccination were effective. Given that vaccine hesitancy may be a major reason for the lack of impact of portal or text reminders, more intensive interventions by health systems are needed to raise influenza vaccination coverage levels., Trial Registration: ClinicalTrials.gov Identifier: NCT05525494.

Competing Interests: Competing interests: JD receives funding from the National Institutes of Health and Edwards Lifesciences.

Background: Effective strategies are needed to curtail overuse that may lead to harm., Objective: To evaluate the effects of clinician decision support redirecting attention to harms and engaging social and reputational concerns on overuse in older primary care patients., Design: 18-month, single-blind, pragmatic, cluster randomized trial, constrained randomization. (ClinicalTrials.gov: NCT04289753)., Setting: 60 primary care internal medicine, family medicine and geriatrics practices within a health system from 1 September 2020 to 28 February 2022., Participants: 371 primary care clinicians and their older adult patients from participating practices., Intervention: Behavioral science-informed, point-of-care, clinical decision support tools plus brief case-based education addressing the 3 primary clinical outcomes (187 clinicians from 30 clinics) were compared with brief case-based education alone (187 clinicians from 30 clinics). Decision support was designed to increase salience of potential harms, convey social norms, and promote accountability., Measurements: Prostate-specific antigen (PSA) testing in men aged 76 years and older without previous prostate cancer, urine testing for nonspecific reasons in women aged 65 years and older, and overtreatment of diabetes with hypoglycemic agents in patients aged 75 years and older and hemoglobin A 1c (HbA 1c ) less than 7%., Results: At randomization, mean clinic annual PSA testing, unspecified urine testing, and diabetes overtreatment rates were 24.9, 23.9, and 16.8 per 100 patients, respectively. After 18 months of intervention, the intervention group had lower adjusted difference-in-differences in annual rates of PSA testing (-8.7 [95% CI, -10.2 to -7.1]), unspecified urine testing (-5.5 [CI, -7.0 to -3.6]), and diabetes overtreatment (-1.4 [CI, -2.9 to -0.03]) compared with education only. Safety measures did not show increased emergency care related to urinary tract infections or hyperglycemia. An HbA 1c greater than 9.0% was more common with the intervention among previously overtreated diabetes patients (adjusted difference-in-differences, 0.47 per 100 patients [95% CI, 0.04 to 1.20])., Limitation: A single health system limits generalizability; electronic health data limit ability to differentiate between overtesting and underdocumentation., Conclusion: Decision support designed to increase clinicians' attention to possible harms, social norms, and reputational concerns reduced unspecified testing compared with offering traditional case-based education alone. Small decreases in diabetes overtreatment may also result in higher rates of uncontrolled diabetes., Primary Funding Source: National Institute on Aging., Competing Interests: Disclosures: Disclosures can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M23-2183.

Importance: Excess opioid prescribing after surgery can result in prolonged use and diversion. Email feedback based on social norms may reduce the number of pills prescribed., Objective: To assess the effectiveness of 2 social norm-based interventions on reducing guideline-discordant opioid prescribing after surgery., Design, Setting, and Participants: This cluster randomized clinical trial conducted at a large health care delivery system in northern California between October 2021 and October 2022 included general, obstetric/gynecologic, and orthopedic surgeons with patients aged 18 years or older discharged to home with an oral opioid prescription., Interventions: In 19 hospitals, 3 surgical specialties (general, orthopedic, and obstetric/gynecologic) were randomly assigned to a control group or 1 of 2 interventions. The guidelines intervention provided email feedback to surgeons on opioid prescribing relative to institutionally endorsed guidelines; the peer comparison intervention provided email feedback on opioid prescribing relative to that of peer surgeons. Emails were sent to surgeons with at least 2 guideline-discordant prescriptions in the previous month. The control group had no intervention., Main Outcome and Measures: The probability that a discharged patient was prescribed a quantity of opioids above the guideline for the respective procedure during the 12 intervention months., Results: There were 38 235 patients discharged from 640 surgeons during the 12-month intervention period. Control-group surgeons prescribed above guidelines 36.8% of the time during the intervention period compared with 27.5% and 25.4% among surgeons in the peer comparison and guidelines arms, respectively. In adjusted models, the peer comparison intervention reduced guideline-discordant prescribing by 5.8 percentage points (95% CI, -10.5 to -1.1; P = .03) and the guidelines intervention reduced it by 4.7 percentage points (95% CI, -9.4 to -0.1; P = .05). Effects were driven by surgeons who performed more surgeries and had more guideline-discordant prescribing at baseline. There was no significant difference between interventions., Conclusions and Relevance: In this cluster randomized clinical trial, email feedback based on either guidelines or peer comparison reduced opioid prescribing after surgery. Guideline-based feedback was as effective as peer comparison-based feedback. These interventions are simple, low-cost, and scalable, and may reduce downstream opioid misuse., Trial Registration: ClinicalTrials.gov NCT05070338.

There is intense interest in developing long-lasting, potent, and broad-spectrum antiviral disinfectants. Ceria nanoparticles (CNPs) can undergo surface redox reactions (Ce 3+ ↔ Ce 4+ ) to generate ROS without requiring an external driving force. Here, we tested the mechanism behind our prior finding of potent inactivation of enveloped and non-enveloped RNA viruses by silver-modified CNPs, AgCNP1 and AgCNP2. Treatment of human respiratory viruses, coronavirus OC43 and parainfluenza virus type 5 (PIV5) with AgCNP1 and 2, respectively, prevented virus interactions with host cell receptors and resulted in virion aggregation. Rhinovirus 14 (RV14) mutants were selected to be resistant to inactivation by AgCNP2. Sequence analysis of the resistant virus genomes predicted two amino acid changes in surface-located residues D91V and F177L within capsid protein VP1. Consistent with the regenerative properties of CNPs, surface-applied AgCNP1 and 2 inactivated a wide range of structurally diverse viruses, including enveloped (OC43, SARS-CoV-2, and PIV5) and non-enveloped RNA viruses (RV14 and feline calicivirus; FCV). Remarkably, a single application of AgCNP1 and 2 potently inactivated up to four sequential rounds of virus challenge. Our results show broad-spectrum and long-lasting anti-viral activity of AgCNP nanoparticles, due to targeting of viral surface proteins to disrupt interactions with cellular receptors.

Importance: Interventions that improve clinician performance through feedback should not contribute to job dissatisfaction or staff turnover. Measurement of job satisfaction may help identify interventions that lead to this undesirable consequence., Objective: To evaluate whether mean job satisfaction was less than the margin of clinical significance among clinicians who received social norm feedback (peer comparison) compared with clinicians who did not., Design, Setting, and Participants: This secondary, preregistered, noninferiority analysis of a cluster randomized trial compared 3 interventions to reduce inappropriate antibiotic prescribing in a 2 × 2 × 2 factorial design from November 1, 2011, to April 1, 2014. A total of 248 clinicians were enrolled from 47 clinics. The sample size for this analysis was determined by the number of nonmissing job satisfaction scores from the original enrolled sample, which was 201 clinicians from 43 clinics. Data analysis was performed from October 12 to April 13, 2022., Interventions: Feedback comparing individual clinician performance to top-performing peers, delivered in monthly emails (peer comparison)., Main Outcomes and Measures: The primary outcome was a response to the following statement: "Overall, I am satisfied with my current job." Responses ranged from 1 (strongly disagree) to 5 (strongly agree)., Results: A total of 201 clinicians (response rate, 81%) from 43 of the 47 clinics (91%) provided a survey response about job satisfaction. Clinicians were primarily female (n = 129 [64%]) and board certified in internal medicine (n = 126 [63%]), with a mean (SD) age of 48 (10) years. The clinic-clustered difference in mean job satisfaction was greater than -0.32 (β = 0.11; 95% CI, -0.19 to 0.42; P = .46). Therefore, the preregistered null hypothesis that peer comparison is inferior by resulting in at least a 1-point decrease in job satisfaction by 1 in 3 clinicians was rejected. The secondary null hypothesis that job satisfaction was similar among clinicians randomized to social norm feedback was not able to be rejected. The effect size did not change when controlling for other trial interventions (t = 0.08; P = .94), and no interaction effects were observed., Conclusions and Relevance: In this secondary analysis of a randomized clinical trial, peer comparison did not lead to lower job satisfaction. Features that may have protected against dissatisfaction include clinicians' agency over the performance measure, privacy of individual performance, and allowing all clinicians to achieve top performance., Trial Registration: ClinicalTrials.gov Identifiers: NCT05575115 and NCT01454947.

Influenza vaccination rates are low. Working with a large US health system, we evaluated three health system-wide interventions using the electronic health record's patient portal to improve influenza vaccination rates. We performed a two-arm RCT with a nested factorial design within the treatment arm, randomizing patients to usual-care control (no portal interventions) or to one or more portal interventions. We included all patients within this health system during the 2020-2021 influenza vaccination season, which overlapped with the COVID-19 pandemic. Through the patient portal, we simultaneously tested: pre-commitment messages (sent September 2020, asking patients to commit to a vaccination); monthly portal reminders (October - December 2020), direct appointment scheduling (patients could self-schedule influenza vaccination at multiple sites); and pre-appointment reminder messages (sent before scheduled primary care appointments, reminding patients about influenza vaccination). The main outcome measure was receipt of influenza vaccine (10/01/2020-03/31/2021). We randomized 213,773 patients (196,070 adults ≥18 years, 17,703 children). Influenza vaccination rates overall were low (39.0%). Vaccination rates for study arms did not differ: Control (38.9%), pre-commitment vs no pre-commitment (39.2%/38.9%), direct appointment scheduling yes/no (39.1%/39.1%), pre-appointment reminders yes/no (39.1%/39.1%); p > 0.017 for all comparisons (p value cut-off adjusted for multiple comparisons). After adjusting for age, gender, insurance, race, ethnicity, and prior influenza vaccination, none of the interventions increased vaccination rates. We conclude that patient portal interventions to remind patients to receive influenza vaccine during the COVID-19 pandemic did not raise influenza immunization rates. More intensive or tailored interventions are needed beyond portal innovations to increase influenza vaccination., Competing Interests: Declaration of Competing Interest Dr. Humiston is a consultant to Sanofi Pasteur. Dr. Humiston's employer gets grant money for her work sponsored by the Pediatric Infectious Diseases Society Foundation, a not-for-profit organization, which is funded for the project through unrestricted joint educational grants from Sanofi Pasteur US, Merck & Co., Inc., Pfizer, Inc., GlaxoSmithKline, and Seqirus USA, Inc. All other authors have no conflicts of interest to report. Trial Registration: This trial was registered with ClinicalTrials.gov (NCT04533685)., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Purpose: To evaluate if nudges delivered by text message prior to an upcoming primary care visit can increase influenza vaccination rates., Design: Randomized, controlled trial., Setting: Two health systems in the Northeastern US between September 2020 and March 2021., Subjects: 74,811 adults., Interventions: Patients in the 19 intervention arms received 1-2 text messages in the 3 days preceding their appointment that varied in their format, interactivity, and content., Measures: Influenza vaccination., Analysis: Intention-to-treat., Results: Participants had a mean (SD) age of 50.7 (16.2) years; 55.8% (41,771) were female, 70.6% (52,826) were White, and 19.0% (14,222) were Black. Among the interventions, 5 of 19 (26.3%) had a significantly greater vaccination rate than control. On average, the 19 interventions increased vaccination relative to control by 1.8 percentage points or 6.1% ( P = .005). The top performing text message described the vaccine to the patient as "reserved for you" and led to a 3.1 percentage point increase (95% CI, 1.3 to 4.9; P < .001) in vaccination relative to control. Three of the top five performing messages described the vaccine as "reserved for you." None of the interventions performed worse than control., Conclusions: Text messages encouraging vaccination and delivered prior to an upcoming appointment significantly increased influenza vaccination rates and could be a scalable approach to increase vaccination more broadly.

Background: Unnecessary testing and treatment of common conditions in older adults can lead to significant morbidity and mortality. The primary objective of this study was to develop and pilot test a set of clinical decision support (CDS) alerts informed by social psychology to address overuse in three areas related to ambulatory care of older adults., Methods: We developed three electronic health record (EHR) CDS alerts to address overuse and pilot tested them from January 17, 2019 to July 17, 2019. We enrolled 14 primary care physicians from three practices within a large health system who cared for adults aged 65 years and older. Three measures of overuse applied to patients meeting the following criteria: ordering of prostate-specific antigen (PSA) for prostate cancer screening in adult men aged 76 years and older, ordering of urinalysis or urine cultures (UA or UC) for non-specific reasons to identify bacteriuria in women aged 65 years and older, and overtreatment of diabetes with insulin or oral hypoglycemic medications in adults aged at 75 years and older (DM). Clinicians received CDS alerts when criteria for any of the three overuse measures were met. We then surveyed clinicians to evaluate their experience with the CDS alerts., Results: The number of clinical encounters that triggered CDS alerts was 19 for PSA, 48 for UA/UC and 128 for DM. For PSA encounters, 4 (21%) orders were not performed after the alert. In the UA/UC encounters 29 (60%) orders were not performed after the alert. For the DM encounters, 21 (34%) had diabetes therapy reduced following the alert. Survey respondents indicated that the alerts were clinically accurate and sometimes led them to change their clinical action., Conclusions: These CDS alerts were feasible to implement and may minimize unnecessary testing and treatment of common conditions in older adults., Competing Interests: Declaration of Competing Interest Dr. Persell receives research support from Omron Healthcare and previously received research support from Pfizer, Inc. He is a consultant QuiO Technologies and the RAND Corporation. After the completion of the research presented in this paper, Dr. Friedberg became a paid employee of Blue Cross Blue Shield of Massachusetts., (Copyright © 2022. Published by Elsevier B.V.)

The COVID-19 pandemic marks an inflection point in the perception and treatment of human health. Substantial resources have been reallocated to address the direct medical effects of COVID-19 and to curtail the spread of the virus. Thereby, shortcomings of traditional disinfectants, especially their requirement for regular reapplication and the related complications (e.g., dedicated personnel and short-term activity), have become issues at the forefront of public health concerns. This issue became especially pressing when infection-mitigating supplies dwindled early in the progression of the pandemic. In consideration of the constant threat posed by emerging novel viruses, we report a platform technology for persistent surface disinfection to combat virus transmission through nanomaterial-mediated, localized UV radiation emission. In this work, two formulations of Y 2 SiO 5 -based visible-to-UV upconversion nanomaterials were developed using a facile sol-gel-based synthesis. Our formulations have shown substantial antiviral activities (4 × 10 4 to 0 TCID 50 units in 30 min) toward an enveloped, circulating human coronavirus strain (OC43) under simple white light exposure as an analogue to natural light or common indoor lighting. Additionally, we have shown that our two formulations greatly reduce OC43 RNA recovery from surfaces. Antiviral activities were further demonstrated toward a panel of structurally diverse viruses including enveloped viruses, SARS-CoV-2, vaccinia virus, vesicular stomatitis virus, parainfluenza virus, and Zika virus, as well as nonenveloped viruses, rhinovirus, and calicivirus, as evidence of the technology's broad antiviral activity. Remarkably, one formulation completely inactivated 10 5 infectious units of SARS-CoV-2 in only 45 min. The detailed technology has implications for the design of more potent, long-lived disinfectants and modified/surface-treated personal protective equipment targeting a wide range of viruses.

Zika virus (ZIKV) exhibits distinct selectivity for infection of various cells and tissues, but how host cellular factors modulate varying permissivity remains largely unknown. Previous studies showed that the neuroblastoma cell line SK-N-AS (expressing low levels of cellular protein CD24) was highly restricted for ZIKV infection, and that this restriction was relieved by ectopic expression of CD24. We tested the hypothesis that CD24 expression allowed ZIKV replication by suppression of the antiviral response. SK-N-AS cells expressing an empty vector (termed CD24-low cells) showed elevated basal levels of phosphorylated STAT1, IRF-1, IKKE, and NFκB. In response to exogenously added type I interferon (IFN-I), CD24-low cells had higher-level induction of antiviral genes and activity against two IFN-I-sensitive viruses (VSV and PIV5-P/V) compared to SK-N-AS cells with ectopic CD24 expression (termed CD24-high cells). Media-transfer experiments showed that the inherent antiviral state of CD24-low cells was not dependent on a secreted factor such as IFN-I. Transcriptomics analysis revealed that CD24 expression decreased expression of genes involved in intracellular antiviral pathways, including IFN-I, NFκB, and Ras. Our findings that CD24 expression in neuroblastoma cells represses intracellular antiviral pathways support the proposal that CD24 may represent a novel biomarker in cancer cells for susceptibility to oncolytic viruses.

Background: While cancer outcomes have improved over time, in Northern Ireland they continue to lag behind those of many other developed economies. The role of comorbid conditions has been suggested as a potential contributory factor in this but issues of data comparability across jurisdictions has inhibited efforts to explore relationships. We use data from a single jurisdiction of the UK using data from - the Northern Ireland Cancer Registry (NICR), to examine the association between mortality (all-cause and cancer specific) and pre-existing cardiovascular diseases among patients with cancer., Materials and Methods: All patients diagnosed with cancer (excluding non-melanoma skin cancer) between 2011 and 2014 were identified from Registry records. Those with a pre-existing diagnosis of cardiovascular diseases were identified by record linkage with patient hospital discharge data using ICD10 codes. Survival following diagnosis was examined using descriptive statistics and Cox proportional hazards regression analyses. Analyses examined all-cause mortality and cancer specific mortality for lung, colorectal, breast and prostate cancer. As well as cardiovascular diseases, regression models controlled for age, gender (where appropriate), deprivation (as quintiles), stage at diagnosis and other comorbidities., Results: Almost 35,000 incident cancer cases were diagnosed during the study period of which approximately 23% had a prior heart condition. The pan-cancer hazard ratio for death in the presence of pre-existing cardiovascular diseases was 1.28 (95% CI: 1.18-1.40). All-cause and cancer specific mortality was higher for patients with cardiovascular diseases across lung, female breast, prostate and colorectal cancer groups after controlling for age, gender (where appropriate), deprivation (as quintiles), stage at diagnosis and other comorbidities., Conclusion: Pre-existing morbidity may restrict the treatment of cancer for many patients. In this cohort, cancer patients with pre-existing cardiovascular diseases had poorer outcomes than those without cardiovascular diseases. A high prevalence of cardiovascular diseases may contribute to poorer cancer outcomes at a national level., (© 2022. The Author(s).)

Background: The CDC estimates that over 40% of Urgent Care visits are for acute respiratory infections (ARI), more than half involving inappropriate antibiotic prescriptions. Previous randomized trials in primary care clinics resulted in reductions in inappropriate antibiotic prescribing, but antibiotic stewardship interventions in telehealth have not been systematically assessed. To better understand how best to decrease inappropriate antibiotic prescribing for ARIs in telehealth, we are conducting a large randomized quality improvement trial testing both patient- and physician-facing feedback and behavioral nudges embedded in the electronic health record., Methods: Teladoc® clinicians are assigned to one of 9 arms in a 3 × 3 randomized trial. Each clinician is assigned to one of 3 Commitment groups (Public, Private, Control) and one of 3 Performance Feedback groups (Benchmark Peer Comparison, Trending, Control). After randomly selecting ⅓ of states and associated clinicians required for patient-facing components of the Public Commitment intervention, remaining clinicians are randomized to the Control and Private Commitment arms. Clinicians are randomized to the Performance Feedback conditions. The primary outcome is change from baseline in antibiotic prescribing rate for qualifying ARI visits. Secondary outcomes include changes in inappropriate prescribing and revisit rates. Secondary analyses include investigation of heterogeneity of treatment effects. With 1530 clinicians and an intra-clinician correlation in antibiotic prescribing rate of 0.5, we have >80% power to detect 1-7% absolute differences in antibiotic prescribing among groups., Discussion: Findings from this trial may help inform telehealth stewardship strategies, determine whether significant differences exist between Commitment and Feedback interventions, and provide guidance for clinicians and patients to encourage safe and effective antibiotic use., Clinicaltrials: gov: NCT05138874., (Copyright © 2022. Published by Elsevier Inc.)

Background: Inappropriate polypharmacy, prevalent among older patients, is associated with substantial harms., Objective: To develop measures of high-risk polypharmacy and pilot test novel electronic health record (EHR)-based nudges grounded in behavioral science to promote deprescribing., Design: We developed and validated seven measures, then conducted a three-arm pilot from February to May 2019., Participants: Validation used data from 78,880 patients from a single large health system. Six physicians were pre-pilot test environment users. Sixty-nine physicians participated in the pilot., Main Measures: Rate of high-risk polypharmacy among patients aged 65 years or older. High-risk polypharmacy was defined as being prescribed ≥5 medications and satisfying ≥1 of the following high-risk criteria: drugs that increase fall risk among patients with fall history; drug-drug interactions that increase fall risk; thiazolidinedione, NSAID, or non-dihydropyridine calcium channel blocker in heart failure; and glyburide, glimepiride, or NSAID in chronic kidney disease., Interventions: Physicians received EHR alerts when renewing or prescribing certain high-risk medications when criteria were met. One practice received a "commitment nudge" that offered a chance to commit to addressing high-risk polypharmacy at the next visit. One practice received a "justification nudge" that asked for a reason when high-risk polypharmacy was present. One practice received both., Key Results: Among 55,107 patients 65 and older prescribed 5 or more medications, 6256 (7.9%) had one or more high-risk criteria. During the pilot, the mean (SD) number of nudges per physician per week was 1.7 (0.4) for commitment, 0.8 (0.5) for justification, and 1.9 (0.5) for both interventions. Physicians requested to be reminded to address high-risk polypharmacy for 236/833 (28.3%) of the commitment nudges and acknowledged 441 of 460 (95.9%) of justification nudges, providing a text response for 187 (40.7%)., Conclusions: EHR-based measures and nudges addressing high-risk polypharmacy were feasible to develop and implement, and warrant further testing., (© 2021. The Author(s) under exclusive licence to Society of General Internal Medicine.)

Policymakers and business leaders often use peer comparison information-showing people how their behavior compares to that of their peers-to motivate a range of behaviors. Despite their widespread use, the potential impact of peer comparison interventions on recipients' well-being is largely unknown. We conducted a 5-mo field experiment involving 199 primary care physicians and 46,631 patients to examine the impact of a peer comparison intervention on physicians' job performance, job satisfaction, and burnout. We varied whether physicians received information about their preventive care performance compared to that of other physicians in the same health system. Our analyses reveal that our implementation of peer comparison did not significantly improve physicians' preventive care performance, but it did significantly decrease job satisfaction and increase burnout, with the effect on job satisfaction persisting for at least 4 mo after the intervention had been discontinued. Quantitative and qualitative evidence on the mechanisms underlying these unanticipated negative effects suggest that the intervention inadvertently signaled a lack of support from leadership. Consistent with this account, providing leaders with training on how to support physicians mitigated the negative effects on well-being. Our research uncovers a critical potential downside of peer comparison interventions, highlights the importance of evaluating the psychological costs of behavioral interventions, and points to how a complementary intervention-leadership support training-can mitigate these costs.

The COVID-19 pandemic has underscored the importance of research and development in maintaining public health. Facing unprecedented challenges, the scientific community developed antiviral drugs, virucides, and vaccines to combat the infection within the past two years. However, an ever-increasing list of highly infectious SARS-CoV-2 variants (gamma, delta, omicron, and now ba.2 stealth) has exacerbated the problem: again raising the issues of infection prevention strategies and the efficacy of personal protective equipment (PPE). Against this backdrop, we report an antimicrobial fabric for PPE applications. We have fabricated a nanofibrous silk-PEO material using electrospinning followed by zinc oxide thin film deposition by employing the atomic layer deposition technique. The composite fabric has shown 85% more antibacterial activity than the control fabric and was found to possess substantial superoxide dismutase-mimetic activity. The composite was further subjected to antiviral testing using two different respiratory tract viruses: coronavirus (OC43: enveloped) and rhinovirus (RV14: non-enveloped). We report a 95% reduction in infectious virus for both OC43 and RV14 from an initial load of ∼1 × 10 5 (sample size: 6 mm dia. disk), after 1 h of white light illumination. Furthermore, with 2 h of illumination, ∼99% reduction in viral infectivity was observed for RV14. High activity in a relatively small area of fabric (3.5 × 10 3 viral units per mm 2 ) makes this antiviral fabric ideal for application in masks/PPE, with an enhanced ability to prevent antimicrobial infection overall., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Background: Since the advent of COVID-19, accelerated adoption of systems that reduce face-to-face encounters has outpaced training and best practices. Electronic consultations (eConsults), structured communications between PCPs and specialists regarding a case, have been effective in reducing face-to-face specialist encounters. As the health system rapidly adapts to multiple new practices and communication tools, new mechanisms to measure and improve performance in this context are needed., Objective: To test whether feedback comparing physicians to top performing peers using co-specialists' ratings improves performance., Design: Cluster-randomized controlled trial PARTICIPANTS: Eighty facility-specialty clusters and 214 clinicians INTERVENTION: Providers in the feedback arms were sent messages that announced their membership in an elite group of "Top Performers" or provided actionable recommendations with feedback for providers that were "Not Top Performers.", Main Measures: The primary outcomes were changes in peer ratings in the following performance dimensions after feedback was received: (1) elicitation of information from primary care practitioners; (2) adherence to institutional clinical guidelines; (3) agreement with peer's medical decision-making; (4) educational value; (5) relationship building., Key Results: Specialists showed significant improvements on 3 of the 5 consultation performance dimensions: medical decision-making (odds ratio 1.52, 95% confidence interval 1.08-2.14, p<.05), educational value (1.86, 1.17-2.96) and relationship building (1.63, 1.13-2.35) (both p<.01)., Conclusions: The pandemic has shed light on clinicians' commitment to professionalism and service as we rapidly adapt to changing paradigms. Interventions that appeal to professional norms can help improve the efficacy of new systems of practice. We show that specialists' performance can be measured and improved with feedback using aspirational norms., Trial Registration: clinicaltrials.gov NCT03784950., (© 2021. Society of General Internal Medicine.)

Background: Greater understanding of international cancer survival differences is needed. We aimed to identify predictors and consequences of cancer diagnosis through emergency presentation in different international jurisdictions in six high-income countries., Methods: Using a federated analysis model, in this cross-sectional population-based study, we analysed cancer registration and linked hospital admissions data from 14 jurisdictions in six countries (Australia, Canada, Denmark, New Zealand, Norway, and the UK), including patients with primary diagnosis of invasive oesophageal, stomach, colon, rectal, liver, pancreatic, lung, or ovarian cancer during study periods from Jan 1, 2012, to Dec 31, 2017. Data were collected on cancer site, age group, sex, year of diagnosis, and stage at diagnosis. Emergency presentation was defined as diagnosis of cancer within 30 days after an emergency hospital admission. Using logistic regression, we examined variables associated with emergency presentation and associations between emergency presentation and short-term mortality. We meta-analysed estimates across jurisdictions and explored jurisdiction-level associations between cancer survival and the percentage of patients diagnosed as emergencies., Findings: In 857 068 patients across 14 jurisdictions, considering all of the eight cancer sites together, the percentage of diagnoses through emergency presentation ranged from 24·0% (9165 of 38 212 patients) to 42·5% (12 238 of 28 794 patients). There was consistently large variation in the percentage of emergency presentations by cancer site across jurisdictions. Pancreatic cancer diagnoses had the highest percentage of emergency presentations on average overall (46·1% [30 972 of 67 173 patients]), with the jurisdictional range being 34·1% (1083 of 3172 patients) to 60·4% (1317 of 2182 patients). Rectal cancer had the lowest percentage of emergency presentations on average overall (12·1% [10 051 of 83 325 patients]), with a jurisdictional range of 9·1% (403 of 4438 patients) to 19·8% (643 of 3247 patients). Across the jurisdictions, older age (ie, 75-84 years and 85 years or older, compared with younger patients) and advanced stage at diagnosis compared with non-advanced stage were consistently associated with increased emergency presentation risk, with the percentage of emergency presentations being highest in the oldest age group (85 years or older) for 110 (98%) of 112 jurisdiction-cancer site strata, and in the most advanced (distant spread) stage category for 98 (97%) of 101 jurisdiction-cancer site strata with available information. Across the jurisdictions, and despite heterogeneity in association size (I 2 =93%), emergency presenters consistently had substantially greater risk of 12-month mortality than non-emergency presenters (odds ratio >1·9 for 112 [100%] of 112 jurisdiction-cancer site strata, with the minimum lower bound of the related 95% CIs being 1·26). There were negative associations between jurisdiction-level percentage of emergency presentations and jurisdiction-level 1-year survival for colon, stomach, lung, liver, pancreatic, and ovarian cancer, with a 10% increase in percentage of emergency presentations in a jurisdiction being associated with a decrease in 1-year net survival of between 2·5% (95% CI 0·28-4·7) and 7·0% (1·2-13·0)., Interpretation: Internationally, notable proportions of patients with cancer are diagnosed through emergency presentation. Specific types of cancer, older age, and advanced stage at diagnosis are consistently associated with an increased risk of emergency presentation, which strongly predicts worse prognosis and probably contributes to international differences in cancer survival. Monitoring emergency presentations, and identifying and acting on contributing behavioural and health-care factors, is a global priority for cancer control., Funding: Canadian Partnership Against Cancer; Cancer Council Victoria; Cancer Institute New South Wales; Cancer Research UK; Danish Cancer Society; National Cancer Registry Ireland; The Cancer Society of New Zealand; National Health Service England; Norwegian Cancer Society; Public Health Agency Northern Ireland, on behalf of the Northern Ireland Cancer Registry; the Scottish Government; Western Australia Department of Health; and Wales Cancer Network., Competing Interests: Declarations of interests OB and GM declare salary compensation for analysis of trial data in preparation for review by the Data Safety Monitoring Board for the POWERRANGER trial (NCT01404156), unrelated to this project. BD declares project funding from the Velux Foundation (Velux Fonden) and the Nordic Collaboration Cancer Care Pathways, for the Danish Cancer Society. ATG reports support to her employer (Queen's University Belfast) from the Public Health Agency for Northern Ireland. DWD declares support to his employer (Northern Ireland Cancer Registry) from the Public Health Agency for Northern Ireland. DWH declares project support from Public Health Wales NHS Trust and Macmillan Cancer Support, and personal payment for research consultancy fees from Pfizer for work done by Swansea University concerning value-based health care, unrelated to this work. CGCAJ declares past part-employment by the Cancer Society of New Zealand, who co-sponsors the project. HJ declares research grant funding from the Velux Foundation (Velux Fonden). BM and YN declare research grant funding to the Cancer Registry of Norway from the Norwegian Cancer Society. RST declares project support to Public Health Wales NHS Trust from the NHS Wales Cancer Network and Macmillan Cancer Support. RRW reports research grant funding from the Michael Smith Foundation for Health Research, and the First Nations Health Authority and Canadian Partnership Against Cancer. GL declares research grant funding from the study sponsors to his employer (University College London)., (Copyright © 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

People differ in their lay theories about how and why the financial well-being of individuals changes over time or varies between individuals. We introduce a measure of Causal Attributions of Financial Uncertainty-the CAFU scale-and find that such attributions can be described reliably along three distinct dimensions, respectively capturing the extent to which changes in financial well-being are perceived to be: (a) knowable and within individuals' control due to individual factors such as effort ("Rewarding"); (b) knowable and outside of individuals' control due to factors such as favoritism and discrimination ("Rigged"); and (c) inherently unpredictable and determined by chance events ("Random"). In a sample representative of the U.S. population on various demographic characteristics ( N = 1,102), we find that differences in these beliefs are associated with political ideology, revealing a predicted pattern: conservatives scored higher on the Rewarding subscale and liberals scored higher on the Rigged and Random subscales, even when controlling for key demographics. Moreover, we find that these three dimensions predict responses to different policy messages, even when controlling for political ideology. In three preregistered experiments (combined N = 2,560), we observe increased support for various social welfare policies when we highlighted aspects of these policies that are compatible with people's beliefs about financial well-being. Likewise, we observe increased support for political candidates when they expressed their positions in a way that is compatible with people's beliefs. Thus, this work can help better understand drivers of political attitudes and guide in crafting more persuasive policy messages. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Background: Adult influenza vaccination rates are low. Tailored patient reminders might raise rates., Objective: Evaluate impact of a health system's patient portal reminders: (1) tailored to patient characteristics and (2) incorporating behavioral science strategies, on influenza vaccination rates among adults., Design: Pragmatic 6-arm randomized trial across a health system during the 2019-2020 influenza vaccination season. The setting was one large health system-53 adult primary care practices., Participants: All adult patients who used the patient portal within 12 months, stratified by the following: young adults (18-64 years, without diabetes), older adults (≥65 years, without diabetes), and those with diabetes (≥18 years)., Interventions: Patients were randomized within strata to either (1) pre-commitment reminder alone (1 message, mid-October), (2) pre-commitment + loss frame messages, (3) pre-commitment + gain frame messages, (4) loss frame messages alone, (5) gain frame messages alone, or (6) standard of care control. Patients in the pre-commitment group were sent a message in mid-October, asking if they planned on getting an influenza vaccination. Patients in loss or gain frame groups were sent up to 3 portal reminders (late October, November, and December, if no documented influenza vaccination in the EHR) about importance and safety of influenza vaccine., Main Measures: Receipt of 1 influenza vaccine from 10/01/2019 to 03/31/2020., Key Results: 196,486 patients (145,166 young adults, 29,795 older adults, 21,525 adults with diabetes) were randomized. Influenza vaccination rates were as follows: for young adults 36.8%, for older adults 55.6%, and for diabetics 60.6%. On unadjusted and adjusted (for age, gender, insurance, race, ethnicity, and prior influenza vaccine history) analyses, influenza vaccination rates were not statistically different for any study group versus control., Conclusions: Patient reminders sent by a health system's patient portal that were tailored to patient demographics (young adults, older adults, diabetes) and that incorporated two behavioral economic messaging strategies (pre-commitment and loss/gain framing) were not effective in raising influenza vaccination rates., Trial Registration: This trial was registered with ClinicalTrials.gov (NCT04110314)., (© 2021. The Author(s).)

Background: High levels of opioid prescribing in the United States has resulted in an alarming trend in opioid-related harms. The objective of Trial 2 of the Application of Economics & Social psychology to improve Opioid Prescribing Safety (AESOPS-2) is to dampen the intensity and frequency of opioid prescribing in accordance with the Centers for Disease Control and Prevention recommendation to "go low and slow". We aim to accomplish this by notifying clinicians of harmful patient outcomes, which we expect to increase the mental availability of risks associated with opioid use., Methods: The trial is multi-site. Random assignment determines if prescribers to persons who suffer an opioid overdose (fatal or nonfatal) learn of this event (intervention) or practice usual care (control). Clinicians in the intervention group receive a letter notifying them of their patient's overdose. The primary outcome is the change in clinician weekly milligram morphine equivalent (MME) prescribed in a 6-month period before and after receiving the letter. Additional outcomes are the change in the proportion of patients prescribed at least 50 daily MME and in the proportion of patients referred to medication assisted treatment. Group differences in these outcomes will be compared using an intent-to-treat difference-in-differences framework with a mixed-effects regression model to estimate clinician MME., Discussion: The AESOPS-2 trial will provide new knowledge about whether increasing prescribers' awareness of patients' opioid-related overdoses leads to a reduction in opioid prescribing. Additionally, this trial may better inform how to reduce opioid use disorder and opioid overdoses by lowering population exposure to these drugs., Trial Registration: ClinicalTrials.gov: NCT04758637., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Overtesting and treatment of older patients is common and may lead to harms. The Choosing Wisely campaign has provided recommendations to reduce overtesting and overtreatment of older adults. Behavioral economics-informed interventions embedded within the electronic health record (EHR) have been shown to reduce overuse in several areas. Our objective is to conduct a parallel arm, pragmatic cluster-randomized trial to evaluate the effectiveness of behavioral-economics-informed clinical decision support (CDS) interventions previously piloted in primary care clinics and designed to reduce overtesting and overtreatment in older adults., Methods/design: This trial has two parallel arms: clinician education alone vs. clinician education plus behavioral-economics-informed CDS. There are three co-primary outcomes for this trial: (1) prostate-specific antigen (PSA) screening in older men, (2) urine testing for non-specific reasons in older women, and (3) overtreatment of diabetes in older adults. All eligible primary care clinics from a large regional health system were randomized using a modified constrained randomization process and their attributed clinicians were included. Clinicians were recruited to complete a survey and educational module. We randomized 60 primary care clinics with 374 primary care clinicians and achieved adequate balance between the study arms for prespecified constrained variables. Baseline annual overuse rates for the three co-primary outcomes were 25%, 23%, and 17% for the PSA, urine, and diabetes measures, respectively., Discussion: This trial is evaluating behavioral-economics-informed EHR-embedded interventions to reduce overuse of specific tests and treatments for older adults. The study will evaluate the effectiveness and safety of these interventions., (Copyright © 2021. Published by Elsevier Inc.)

Little is known about the role of complement (C') in infections with highly prevalent circulating human coronaviruses such as OC43, a group of viruses of major public health concern. Treatment of OC43-infected human lung cells with human serum resulted in C3 deposition on their surfaces and generation of C5a, indicating robust C' activation. Real-time cell viability assays showed that in vitro C'-mediated lysis of OC43 infected cells requires C3, C5 and C6 but not C7, and was substantially delayed as compared to rapid C'-mediated killing of parainfluenza virus type 5 (PIV5)-infected cells. In cells co-infected with OC43 and PIV5, C'-mediated lysis was delayed, similar to OC43 infected cells alone, suggesting that OC43 infection induced dominant inhibitory signals. When OC43-infected cells were treated with human serum, their cell surfaces contained both Vitronectin (VN) and Clusterin (CLU), two host cell C' inhibitors that can alter membrane attack complex (MAC) formation and C'-mediated killing. VN and CLU were not bound to OC43-infected cells after treatment with antibody-depleted serum. Reconstitution experiments with purified IgG and VN showed that human antibodies are both necessary and sufficient for VN recruitment to OC43-infected lung cells-novel findings with implications for CoV pathogenesis.

BACKGROUND Cervical cancer is the most common gynecologic malignancy diagnosed in pregnancy. When cervical cancer is diagnosed late in pregnancy, pelvic lymphadenectomy is avoided. Advanced imaging adds an alternative way to assess nodal involvement. The aim of this case report is to demonstrate how magnetic resonance imaging (MRI) can contribute to the clinical staging of cervical cancer and inform treatment decisions when diagnosis is made late in pregnancy. We report the case of a woman in the third trimester who was diagnosed with advanced-stage squamous cell cervical carcinoma by MRI and biopsy. CASE REPORT A 33-year-old woman at 33 weeks of gestation was admitted to our hospital for recurrent vaginal bleeding. Examination revealed a large cervical mass. A gynecologic oncologist was consulted, an examination under anesthesia was performed, and cervical biopsy samples were obtained. Pathology results revealed squamous cell carcinoma of the cervix. A clinical stage of IB3 was assumed. MRI revealed a 5.2×5.8-cm cervical mass and an enlarged left pelvic lymph node. These findings upstaged the patient to IIIC1. Instead of undergoing a radical cesarean hysterectomy, the patient had a cesarean delivery and pelvic lymph node dissection. Four weeks later, she began chemotherapy and pelvic radiation. CONCLUSIONS There is significant value in advanced imaging for cervical cancer staging. This is especially relevant in pregnancy, where the under-staging of disease is a concern. This case report demonstrates the value of MRI in cervical cancer staging, particularly in pregnant women, in whom treatment and the timing of treatment should be individualized.

The COVID19 pandemic has brought global attention to the threat of emerging viruses and to antiviral therapies, in general. In particular, the high transmissibility and infectivity of respiratory viruses have been brought to the general public's attention, along with the need for highly effective antiviral and disinfectant materials/products. This study has developed two distinct silver-modified formulations of redox-active nanoscale cerium oxide (AgCNP1 and AgCNP2). The formulations show specific antiviral activities toward tested OC43 coronavirus and RV14 rhinovirus pathogens, with materials characterization demonstrating a chemically stable character for silver nanophases on ceria particles and significant differences in Ce 3+ /Ce 4+ redox state ratio (25.8 and 53.7% Ce 3+ for AgCNP1 & 2, respectively). In situ electrochemical studies further highlight differences in formulation-specific viral inactivation and suggest specific modes of action. Altogether, the results from this study support the utility of AgCNP formulations as high stability, high efficacy materials for use against clinically relevant virus species.

Objectives: In a large health system, we evaluated the effectiveness of electronic health record patient portal reminders in increasing pediatric influenza vaccination rates., Methods: We conducted an intention-to-treat randomized clinical trial of 22 046 children from 6 months to <18 years of age in 53 primary care practices. Patients (or parent and/or proxies) who were active portal users were randomly assigned to receive reminder messages framed as gains or losses or no messages. They were separately randomly assigned to receive a precommitment message before the influenza season. The primary outcome was receipt of ≥1 seasonal influenza vaccinations. Additionally, children 6 months to <3 years of age due for a second influenza vaccine were randomly assigned to receive a reminder or no reminder for the second vaccination., Results: First-dose influenza vaccination rates were 56.9% in the control group, 58.0% in the loss-frame reminders group ( P = .07), and 58.0% in the gain-frame group ( P = .47). Rates were 58.3% in the precommitment group versus 57.0% in the control group ( P = .11). Adjusted risk ratios for first vaccination were 1.02 (95% confidence interval [CI]: 1.00-1.04) for loss-frame reminders, 1.01 (95% CI: 0.98-1.05) for gain-frame reminders, and 1.02 (95% CI: 1.00-1.04) for precommitment messages versus controls. Second-dose vaccination rates were 44.1% in the control group and 55.0% in the reminder group, with an adjusted risk ratio of 1.25 (95% CI: 1.07-1.45)., Conclusions: Patient portal reminders for influenza vaccines in children, whether framed as gains or losses, did not increase first-dose influenza vaccination rates but were highly effective for the second dose of the vaccine., Competing Interests: POTENTIAL CONFLICT OF INTEREST: Dr Humiston disclosed the following conflicts of interest: her employer receives grant money for work sponsored by the Pediatric Infectious Diseases Society Foundation, a not-for-profit organization. The Pediatric Infectious Diseases Society is funded for the project through unrestricted joint educational grants from Sanofi Pasteur US, Merck & Co., Inc., Pfizer, Inc., GlaxoSmithKline, and Seqirus USA, Inc. She is a consultant to Sanofi Pasteur, 2 universities with federally funded grants (University of Rochester and University of California, Los Angeles), and several not-for-profit organizations (the American Academy of Pediatrics and its chapters, Immunization Action Coalition, and Immunize Kansas Coalition); the other authors have indicated they have no potential conflicts of interest to disclose., (Copyright © 2021 by the American Academy of Pediatrics.)

Many Americans fail to get life-saving vaccines each year, and the availability of a vaccine for COVID-19 makes the challenge of encouraging vaccination more urgent than ever. We present a large field experiment ( N = 47,306) testing 19 nudges delivered to patients via text message and designed to boost adoption of the influenza vaccine. Our findings suggest that text messages sent prior to a primary care visit can boost vaccination rates by an average of 5%. Overall, interventions performed better when they were 1) framed as reminders to get flu shots that were already reserved for the patient and 2) congruent with the sort of communications patients expected to receive from their healthcare provider (i.e., not surprising, casual, or interactive). The best-performing intervention in our study reminded patients twice to get their flu shot at their upcoming doctor's appointment and indicated it was reserved for them. This successful script could be used as a template for campaigns to encourage the adoption of life-saving vaccines, including against COVID-19., Competing Interests: Competing interest statement: K.G.V. is a part-owner of VAL Health, a behavioral economics consulting firm., (Copyright © 2021 the Author(s). Published by PNAS.)

Background: There is a lack of evidence that long-term opioid use offers benefit for noncancer pain and an abundance of evidence of harm. Despite clinical guidelines and education, prescribing continues at a higher rate than before the opioids crisis. The objective of trial 1 of the Application of Economics & Social psychology to improve Opioid Prescribing Safety (AESOPS-1) is to discourage unnecessary opioid prescribing in primary care by applying "behavioral insights"-empirically-tested social and psychological interventions that affect choice., Methods: AESOPS-1 randomizes primary care clinics in Illinois and California to behavioral intervention or control. Both arms receive opioid guideline education. Clinics randomized to the behavioral intervention arm receive nudges within the electronic health record (EHR) including: 1) an "accountable justification" entered in the chart, 2) a precommitment to address high-risk prescriptions, and 3) a "PainTracker" that broadens discussions about pain. The control arm receives no EHR-based intervention. The primary outcome is the change in weekly milligram morphine equivalents (MME) prescribed. The secondary outcome is the change in the proportion of patients prescribed at least 50 daily MME. To evaluate these outcomes, we will use a difference-in-differences mixed-effects regression model on clinician MME weekly or daily dose. The analysis will be "intent-to-treat." The intervention period is 18-months, with a 6-month follow-up period to measure persistence of effects., Discussion: The AESOPS-1 trial will evaluate the effect of EHR-based interventions in reducing noncancer opioid prescribing in primary care. AESOPS-1 may demonstrate practical and scalable strategies to lower unnecessary population exposure to opioids., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Competing Interests: Competing interests: We have read and understood BMJ policy on declaration of interests and have no relevant interests to declare.

Background: Uncontrolled hypertension contributes to disparities in cardiovascular outcomes. Patient intervention strategies informed by behavioral economics and social psychology could improve blood pressure (BP) control in disadvantaged minority populations., Objective: To assess the impact on BP control of an intervention combining short-term financial incentives with promotion of intrinsic motivation among highly disadvantaged patients., Design: Randomized controlled trial., Participants: Two hundred seven adults (98% African American or Latino) aged 18 or older with uncontrolled hypertension attending Federally Qualified Health Centers., Intervention: Six-month intervention, combining financial incentives for measuring home BP, recording medication use, BP improvement, and achieving target BP values with counseling linking hypertension control efforts to participants' personal reasons to stay healthy., Main Measures: Primary outcomes: percentage achieving systolic BP (SBP) < 140 mmHg, percentage achieving diastolic BP (DBP) < 90 mmHg, and changes in SBP and DBP, all after 6 months. Priority secondary outcomes were SBP < 140 mmHg, DBP < 90 mmHg, and BP change at 12 months, 6 months after the intervention ended., Key Results: After 6 months, rates of achieving target BP values for intervention and control subjects respectively was 57.1% vs. 40.2% for SBP < 140 mmHg (adjusted odds ratio (AOR) 2.53 (1.13-5.70)), 79.8% vs 70.1% for DBP < 90 mmHg (AOR 2.50 (0.84-7.44)), and 53.6% vs 40.2% for achieving both targets (AOR 2.04 (0.92-4.52)). However, at 12 months, the groups did not differ significantly in these 3 measures: 39.5% vs 35.0% for SBP (AOR 1.20 (0.51-2.83)), 68.4% vs 75.0% for DBP (AOR 0.70 (0.24-2.09)), and 35.5% vs 33.8% for both (AOR 1.03 (0.44-2.42)). Change in absolute SBP and DBP did not differ significantly between the groups at 6 or 12 months. Exploratory post hoc analysis revealed intervention benefit only occurred among individuals whose providers intensified their regimens, but not among those with intensification but no intervention., Conclusions: The intervention achieved short-term improvement in SBP control in a highly disadvantaged population. Despite attempts to enhance intrinsic motivation, the effect was not sustained after incentives were withdrawn. Future research should evaluate combined patient/provider strategies to enhance such interventions and sustain their benefit., Trial Registration: NCT01402453; http://clinicaltrials.gov/show/NCT01402453.

Previous results have shown that infection with the cytoplasmic-replicating parainfluenza virus 5 mutant P/V-CPI- sensitizes cells to DNA damaging agents, resulting in the enhanced killing of airway cancer cells. Here, we have tested the hypothesis that histone deacetylase (HDAC) inhibitors can also act with P/V-CPI- infection to enhance cancer cell killing. Using human small cell lung cancer and laryngeal cancer cell lines, 10 HDAC inhibitors were tested for their effect on viability of P/V-CPI- infected cells. HDAC inhibitors such as scriptaid enhanced caspase-3/7, -8 and -9 activity induced by P/V-CPI- and overall cell toxicity. Scriptaid-mediated enhanced killing was eliminated in lung cancer cells that were engineered to express a protein which sequesters double stranded RNA. Scriptaid also enhanced cancer cell killing by two other negative strand RNA viruses - the La Crosse virus and vesicular stomatitis virus. Scriptaid treatment enhanced the spread of the P/V-CPI- virus through a population of cancer cells, and suppressed interferon-beta induction through blocking phosphorylation and nuclear translocation of Interferon Regulatory Factor 3 (IRF-3). Taken together, these data support a role for combinations of a cytoplasmic-replicating RNA virus such as the P/V-CPI- mutant along with chemotherapeutic agents.

A parainfluenza virus 5 (PIV5) with mutations in the P/V gene (P/V-CPI - ) is restricted for spread in normal cells but not in cancer cells in vitro and is effective at reducing tumor burdens in mouse model systems. Here we show that P/V-CPI - infection of HEp-2 human laryngeal cancer cells results in the majority of the cells dying, but unexpectedly, over time, there is an emergence of a population of cells that survive as P/V-CPI - persistently infected (PI) cells. P/V-CPI - PI cells had elevated levels of basal caspase activation, and viability was highly dependent on the activity of cellular inhibitor-of-apoptosis proteins (IAPs) such as Survivin and XIAP. In challenge experiments with external inducers of apoptosis, PI cells were more sensitive to cisplatin-induced DNA damage and cell death. This increased cisplatin sensitivity correlated with defects in DNA damage signaling pathways such as phosphorylation of Chk1 and translocation of damage-specific DNA binding protein 1 (DDB1) to the nucleus. Cisplatin-induced killing of PI cells was sensitive to the inhibition of wild-type (WT) p53-inducible protein 1 (WIP1), a phosphatase which acts to terminate DNA damage signaling pathways. A similar sensitivity to cisplatin was seen with cells during acute infection with P/V-CPI - as well as during acute infections with WT PIV5 and the related virus human parainfluenza virus type 2 (hPIV2). Our results have general implications for the design of safer paramyxovirus-based vectors that cannot establish PI as well as the potential for combining chemotherapy with oncolytic RNA virus vectors. IMPORTANCE There is intense interest in developing oncolytic viral vectors with increased potency against cancer cells, particularly those cancer cells that have gained resistance to chemotherapies. We have found that infection with cytoplasmically replicating parainfluenza virus can result in increases in the killing of cancer cells by agents that induce DNA damage, and this is linked to alterations to DNA damage signaling pathways that balance cell survival versus death. Our results have general implications for the design of safer paramyxovirus-based vectors that cannot establish persistent infection, the repurposing of drugs that target cellular IAPs as antivirals, and the combined use of DNA-damaging chemotherapy agents in conjunction with oncolytic RNA virus vectors., (Copyright © 2018 American Society for Microbiology.)

This article reviews research from several behavioral disciplines to derive strategies for prompting people to perform behaviors that are individually costly and provide negligible individual or social benefits but are meaningful when performed by a large number of individuals. Whereas the term social influence encompasses all the ways in which people influence other people, social mobilization refers specifically to principles that can be used to influence a large number of individuals to participate in such activities. The motivational force of social mobilization is amplified by the fact that others benefit from the encouraged behaviors, and its overall impact is enhanced by the fact that people are embedded within social networks. This article may be useful to those interested in the provision of public goods, collective action, and prosocial behavior, and we give special attention to field experiments on election participation, environmentally sustainable behaviors, and charitable giving.

Objective: The aim of this study was to determine whether exposure to data from a risk calculator influences surgeons' assessments of risk and in turn, their decisions to operate., Background: Little is known about how risk calculators inform clinical judgment and decision-making., Methods: We asked a national sample of surgeons to assess the risks (probability of serious complications or death) and benefits (recovery) of operative and nonoperative management and to rate their likelihood of recommending an operation (5-point scale) for 4 detailed clinical vignettes wherein the best treatment strategy was uncertain. Surgeons were randomized to the clinical vignettes alone (control group; n = 384) or supplemented by data from a risk calculator (risk calculator group; n = 395). We compared surgeons' judgments and decisions between the groups., Results: Surgeons exposed to the risk calculator judged levels of operative risk that more closely approximated the risk calculator value (RCV) compared with surgeons in the control group [mesenteric ischemia: 43.7% vs 64.6%, P < 0.001 (RCV = 25%); gastrointestinal bleed: 47.7% vs 53.4%, P < 0.001 (RCV = 38%); small bowel obstruction: 13.6% vs 17.5%, P < 0.001 (RCV = 14%); appendicitis: 13.4% vs 24.4%, P < 0.001 (RCV = 5%)]. Surgeons exposed to the risk calculator also varied less in their assessment of operative risk (standard deviations: mesenteric ischemia 20.2% vs 23.2%, P = 0.01; gastrointestinal bleed 17.4% vs 24.1%, P < 0.001; small bowel obstruction 10.6% vs 14.9%, P < 0.001; appendicitis 15.2% vs 21.8%, P < 0.001). However, averaged across the 4 vignettes, the 2 groups did not differ in their reported likelihood of recommending an operation (mean 3.7 vs 3.7, P = 0.76)., Conclusions: Exposure to risk calculator data leads to less varied and more accurate judgments of operative risk among surgeons, and thus may help inform discussions of treatment options between surgeons and patients. Interestingly, it did not alter their reported likelihood of recommending an operation.

Objective: To determine how surgeons' perceptions of treatment risks and benefits influence their decisions to operate., Background: Little is known about what makes one surgeon choose to operate on a patient and another chooses not to operate., Methods: Using an online study, we presented a national sample of surgeons (N = 767) with four detailed clinical vignettes (mesenteric ischemia, gastrointestinal bleed, bowel obstruction, appendicitis) where the best treatment option was uncertain and asked them to: (1) judge the risks (probability of serious complications) and benefits (probability of recovery) for operative and nonoperative management and (2) decide whether or not they would recommend an operation., Results: Across all clinical vignettes, surgeons varied markedly in both their assessments of the risks and benefits of operative and nonoperative management (narrowest range 4%-100% for all four predictions across vignettes) and in their decisions to operate (49%-85%). Surgeons were less likely to operate as their perceptions of operative risk increased [absolute difference (AD) = -29.6% from 1.0 standard deviation below to 1.0 standard deviation above mean (95% confidence interval, CI: -31.6, -23.8)] and their perceptions of nonoperative benefit increased [AD = -32.6% (95% CI: -32.8,--28.9)]. Surgeons were more likely to operate as their perceptions of operative benefit increased [AD = 18.7% (95% CI: 12.6, 21.5)] and their perceptions of nonoperative risk increased [AD = 32.7% (95% CI: 28.7, 34.0)]. Differences in risk/benefit perceptions explained 39% of the observed variation in decisions to operate across the four vignettes., Conclusions: Given the same clinical scenarios, surgeons' perceptions of treatment risks and benefits vary and are highly predictive of their decisions to operate.

We argue that people intuitively distinguish epistemic (knowable) uncertainty from aleatory (random) uncertainty and show that the relative salience of these dimensions is reflected in natural language use. We hypothesize that confidence statements (e.g., “I am fairly confident,” “I am 90% sure,” “I am reasonably certain”) communicate a subjective assessment of primarily epistemic uncertainty, whereas likelihood statements (e.g., “I believe it is fairly likely,” “I’d say there is a 90% chance,” “I think there is a high probability”) communicate a subjective assessment of primarily aleatory uncertainty. First, we show that speakers tend to use confidence statements to express epistemic uncertainty and they tend to use likelihood statements to express aleatory uncertainty; we observe this in a 2-year sample of New York Times articles (Study 1), and in participants’ explicit choices of which statements more naturally express different uncertain events (Studies 2A and 2B). Second, we show that when speakers apply confidence versus likelihood statements to the same events, listeners infer different reasoning (Study 3): confidence statements suggest epistemic rationale (singular reasoning, feeling of knowing, internal control), whereas likelihood statements suggest aleatory rationale (distributional reasoning, relative frequency information, external control). Third, we show that confidence versus likelihood statements can differentially prompt epistemic versus aleatory thoughts, respectively, as observed when participants complete sentences that begin with confidence versus likelihood statements (Study 4) and when they quantify these statements based on feeling-of-knowing (epistemic) and frequency (aleatory) information (Study 5)., (PsycINFO Database Record (c) 2016 APA, all rights reserved)

Background: Clinicians frequently prescribe antibiotics inappropriately for acute respiratory infections (ARIs). Our objective was to test information technology-enabled behavioral interventions to reduce inappropriate antibiotic prescribing for ARIs in a randomized controlled pilot test trial., Methods: Primary care clinicians were randomized in a 2 × 2 × 2 factorial experiment with 3 interventions: 1) Accountable Justifications; 2) Suggested Alternatives; and 3) Peer Comparison. Beforehand, participants completed an educational module. Measures included: rates of antibiotic prescribing for: non-antibiotic-appropriate ARI diagnoses, acute sinusitis/pharyngitis, all other diagnoses/symptoms of respiratory infection, and all three ARI categories combined., Results: We examined 3,276 visits in the pre-intervention year and 3,099 in the intervention year. The antibiotic prescribing rate fell for non-antibiotic-appropriate ARIs (24.7 % in the pre-intervention year to 5.2 % in the intervention year); sinusitis/pharyngitis (50.3 to 44.7 %); all other diagnoses/symptoms of respiratory infection (40.2 to 25.3 %); and all categories combined (38.7 to 24.2 %; all p < 0.001). There were no significant relationships between any intervention and antibiotic prescribing for non-antibiotic-appropriate ARI diagnoses or sinusitis/pharyngitis. Suggested Alternatives was associated with reduced antibiotic prescribing for other diagnoses or symptoms of respiratory infection (odds ratio [OR], 0.62; 95 % confidence interval [CI], 0.44-0.89) and for all ARI categories combined (OR, 0.72; 95 % CI, 0.54-0.96). Peer Comparison was associated with reduced prescribing for all ARI categories combined (OR, 0.73; 95 % CI, 0.53-0.995)., Conclusions: We observed large reductions in antibiotic prescribing regardless of whether or not study participants received an intervention, suggesting an overriding Hawthorne effect or possibly clinician-to-clinician contamination. Low baseline inappropriate prescribing may have led to floor effects., Trial Registration: ClinicalTrials.gov: NCT01454960 .

Importance: Interventions based on behavioral science might reduce inappropriate antibiotic prescribing., Objective: To assess effects of behavioral interventions and rates of inappropriate (not guideline-concordant) antibiotic prescribing during ambulatory visits for acute respiratory tract infections., Design, Setting, and Participants: Cluster randomized clinical trial conducted among 47 primary care practices in Boston and Los Angeles. Participants were 248 enrolled clinicians randomized to receive 0, 1, 2, or 3 interventions for 18 months. All clinicians received education on antibiotic prescribing guidelines on enrollment. Interventions began between November 1, 2011, and October 1, 2012. Follow-up for the latest-starting sites ended on April 1, 2014. Adult patients with comorbidities and concomitant infections were excluded., Interventions: Three behavioral interventions, implemented alone or in combination: suggested alternatives presented electronic order sets suggesting nonantibiotic treatments; accountable justification prompted clinicians to enter free-text justifications for prescribing antibiotics into patients' electronic health records; peer comparison sent emails to clinicians that compared their antibiotic prescribing rates with those of "top performers" (those with the lowest inappropriate prescribing rates)., Main Outcomes and Measures: Antibiotic prescribing rates for visits with antibiotic-inappropriate diagnoses (nonspecific upper respiratory tract infections, acute bronchitis, and influenza) from 18 months preintervention to 18 months afterward, adjusting each intervention's effects for co-occurring interventions and preintervention trends, with random effects for practices and clinicians., Results: There were 14,753 visits (mean patient age, 47 years; 69% women) for antibiotic-inappropriate acute respiratory tract infections during the baseline period and 16,959 visits (mean patient age, 48 years; 67% women) during the intervention period. Mean antibiotic prescribing rates decreased from 24.1% at intervention start to 13.1% at intervention month 18 (absolute difference, -11.0%) for control practices; from 22.1% to 6.1% (absolute difference, -16.0%) for suggested alternatives (difference in differences, -5.0% [95% CI, -7.8% to 0.1%]; P = .66 for differences in trajectories); from 23.2% to 5.2% (absolute difference, -18.1%) for accountable justification (difference in differences, -7.0% [95% CI, -9.1% to -2.9%]; P < .001); and from 19.9% to 3.7% (absolute difference, -16.3%) for peer comparison (difference in differences, -5.2% [95% CI, -6.9% to -1.6%]; P < .001). There were no statistically significant interactions (neither synergy nor interference) between interventions., Conclusions and Relevance: Among primary care practices, the use of accountable justification and peer comparison as behavioral interventions resulted in lower rates of inappropriate antibiotic prescribing for acute respiratory tract infections., Trial Registration: clinicaltrials.gov Identifier: NCT01454947.

Background & Aims: Ubiquitination is a reversible protein modification involved in the major cellular processes that define cell phenotype and behaviour. Ubiquitin modifications are removed by a large family of proteases named deubiquitinases. The role of deubiquitinases in hepatic stellate cell (HSC) activation and their contribution to fibrogenesis are poorly defined. We have identified that the deubiquitinase ubiquitin C-terminal hydrolase 1 (UCHL1) is highly induced following HSC activation, determined its function in activated HSC and its potential as a therapeutic target for fibrosis., Methods: Deubiquitinase expression was determined in day 0 and day 10 HSC. Increased UCHL1 expression was confirmed in human HSC and in an alcoholic liver disease (ALD) patient liver. The importance of UCHL1 in hepatic fibrosis was investigated in CCl4 and bile duct ligation injured mice using a pharmacological inhibitor (LDN 57444). The effects of UCHL1 inhibition on HSC proliferation were confirmed by Western blot and 3H thymidine incorporation., Results: Here we report that pharmacological inhibition of UCHL1 blocks progression of established fibrosis in CCl4 injured mice. UCHL1 siRNA knockdown, LDN 57444 treatment, or HSC isolated from UCHL1(-/-) mice show attenuated proliferation in response to the mitogen, platelet-derived growth factor. Additionally, we observed changes in the phosphorylation of the cell cycle regulator retinoblastoma protein (Rb) in the absence of UCHL1 highlighting a potential mechanism for the reduced proliferative response., Conclusions: UCHL1 expression is highly upregulated upon HSC activation and is involved in the regulation of HSC proliferation. This study highlights therapeutic opportunities for pharmacological targeting of UCHL1 in chronic liver disease., (Copyright © 2015 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)

Background: It has been suggested that inaccuracies in cancer registries are distorting UK survival statistics. This study compared the Northern Ireland Cancer Registry (NICR) database of living patients, with independent data held by Northern Ireland's General Practitioners (GPs) to compare and validate the recorded diagnoses and dates held by the registry., Methods: All 387 GP practice managers were invited to participate. 100 practices (25.84%) responded. Comparisons were made for 17,102 patients, equivalent to 29.08% of the living patients (58,798) extracted from the NICR between 1993 and 2010., Results: There were no significant differences (p>0.05) between the responding and nonresponding GP patient profiles for age, marital status or deprivation score. However, the responding GPs included more female patients (p=0.02). NICR data accuracy was high, 0.08% of GP cancer patients (n=15) were not included in registry records and 0.02% (n=2) had a diagnosis date which varied more than 2 weeks from GP records (3 weeks and 5 months). The NICR had recorded two different tumour types and three different tumour statuses (benign vs. malignant) to the GPs., Conclusion: This comparison demonstrates a high level of accuracy within the NICR and that the survival statistics based on this data can be relied upon., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Background: Healthcare professionals are rapidly adopting electronic health records (EHRs). Within EHRs, seemingly innocuous menu design configurations can influence provider decisions for better or worse., Objective: The purpose of this study was to examine whether the grouping of menu items systematically affects prescribing practices among primary care providers., Participants: We surveyed 166 primary care providers in a research network of practices in the greater Chicago area, of whom 84 responded (51% response rate). Respondents and non-respondents were similar on all observable dimensions except that respondents were more likely to work in an academic setting., Design: The questionnaire consisted of seven clinical vignettes. Each vignette described typical signs and symptoms for acute respiratory infections, and providers chose treatments from a menu of options. For each vignette, providers were randomly assigned to one of two menu partitions. For antibiotic-inappropriate vignettes, the treatment menu either listed over-the-counter (OTC) medications individually while grouping prescriptions together, or displayed the reverse partition. For antibiotic-appropriate vignettes, the treatment menu either listed narrow-spectrum antibiotics individually while grouping broad-spectrum antibiotics, or displayed the reverse partition., Main Measures: The main outcome was provider treatment choice. For antibiotic-inappropriate vignettes, we categorized responses as prescription drugs or OTC-only options. For antibiotic-appropriate vignettes, we categorized responses as broad- or narrow-spectrum antibiotics., Key Results: Across vignettes, there was an 11.5 percentage point reduction in choosing aggressive treatment options (e.g., broad-spectrum antibiotics) when aggressive options were grouped compared to when those same options were listed individually (95% CI: 2.9 to 20.1%; p = .008)., Conclusions: Provider treatment choice appears to be influenced by the grouping of menu options, suggesting that the layout of EHR order sets is not an arbitrary exercise. The careful crafting of EHR order sets can serve as an important opportunity to improve patient care without constraining physicians' ability to prescribe what they believe is best for their patients.