How Physician Self-Perceptions Affect the Impact of Peer Comparison Feedback on Opioid Prescribing.

Peer comparison feedback is a promising strategy for reducing opioid prescribing and opioid-related harms. Such comparisons may be particularly impactful among underestimating clinicians who do not perceive themselves as high prescribers relative to their peers. But peer comparisons could also unintentionally increase prescribing among overestimating clinicians who do not perceive themselves as lower prescribers than peers. The objective of this study was to assess if the impact of peer comparisons varied by clinicians' preexisting opioid prescribing self-perceptions. Subgroup analysis of a randomized trial of peer comparison interventions among emergency department and urgent care clinicians was used. Generalized mixed-effects models were used to assess whether the impact of peer comparisons, alone or combined with individual feedback, varied by underestimating or overestimating prescriber status. Underestimating and overestimating prescribers were defined as those who self-reported relative prescribing amounts that were lower and higher, respectively, than actual relative baseline amounts. The primary outcome was pills per opioid prescription. Among 438 clinicians, 54% (n = 236) provided baseline prescribing self-perceptions and were included in this analysis. Overall, 17% (n = 40) were underestimating prescribers whereas 5% (n = 11) were overestimating prescribers. Underestimating prescribers exhibited a differentially greater decrease in pills per prescription compared to nonunderestimating clinicians when receiving peer comparison feedback (1.7 pills, 95% CI, -3.2 to -0.2 pills) or combined peer and individual feedback (2.8 pills, 95% CI, -4.8 to -0.8 pills). In contrast, there were no differential changes in pills per prescription for overestimating versus nonoverestimating prescribers after receiving peer comparison (1.5 pills, 95% CI, -0.9 to 3.9 pills) or combined peer and individual feedback (3.0 pills, 95% CI, -0.3 to 6.2 pills). Peer comparisons were more impactful among clinicians who underestimated their prescribing compared to peers. By correcting inaccurate self-perceptions, peer comparison feedback can be an effective strategy for influencing opioid prescribing.

Long-term Effect of Machine Learning-Triggered Behavioral Nudges on Serious Illness Conversations and End-of-Life Outcomes Among Patients With Cancer: A Randomized Clinical Trial.

Importance: Serious illness conversations (SICs) between oncology clinicians and patients are associated with improved quality of life and may reduce aggressive end-of-life care. However, most patients with cancer die without a documented SIC. Objective: To test the impact of behavioral nudges to clinicians to prompt SICs on the SIC rate and end-of-life outcomes among patients at high risk of death within 180 days (high-risk patients) as identified by a machine learning algorithm. Design, Setting, and Participants: This prespecified 40-week analysis of a stepped-wedge randomized clinical trial conducted between June 17, 2019, and April 20, 2020 (including 16 weeks of intervention rollout and 24 weeks of follow-up), included 20 506 patients with cancer representing 41 021 encounters at 9 tertiary or community-based medical oncology clinics in a large academic health system. The current analyses were conducted from June 1, 2021, to May 31, 2022. Intervention: High-risk patients were identified using a validated electronic health record machine learning algorithm to predict 6-month mortality. The intervention consisted of (1) weekly emails to clinicians comparing their SIC rates for all patients against peers' rates, (2) weekly lists of high-risk patients, and (3) opt-out text messages to prompt SICs before encounters with high-risk patients. Main Outcomes and Measures: The primary outcome was SIC rates for all and high-risk patient encounters; secondary end-of-life outcomes among decedents included inpatient death, hospice enrollment and length of stay, and intensive care unit admission and systemic therapy close to death. Intention-to-treat analyses were adjusted for clinic and wedge fixed effects and clustered at the oncologist level. Results: The study included 20 506 patients (mean [SD] age, 60.0 [14.0] years) and 41 021 patient encounters: 22 259 (54%) encounters with female patients, 28 907 (70.5%) with non-Hispanic White patients, and 5520 (13.5%) with high-risk patients; 1417 patients (6.9%) died by the end of follow-up. There were no meaningful differences in demographic characteristics in the control and intervention periods. Among high-risk patient encounters, the unadjusted SIC rates were 3.4% (59 of 1754 encounters) in the control period and 13.5% (510 of 3765 encounters) in the intervention period. In adjusted analyses, the intervention was associated with increased SICs for all patients (adjusted odds ratio, 2.09 [95% CI, 1.53-2.87]; P < .001) and decreased end-of-life systemic therapy (7.5% [72 of 957 patients] vs 10.4% [24 of 231 patients]; adjusted odds ratio, 0.25 [95% CI, 0.11-0.57]; P = .001) relative to controls, but there was no effect on hospice enrollment or length of stay, inpatient death, or end-of-life ICU use. Conclusions and Relevance: In this randomized clinical trial, a machine learning-based behavioral intervention and behavioral nudges to clinicans led to an increase in SICs and reduction in end-of-life systemic therapy but no changes in other end-of-life outcomes among outpatients with cancer. These results suggest that machine learning and behavioral nudges can lead to long-lasting improvements in cancer care delivery. Trial Registration: ClinicalTrials.gov Identifier: NCT03984773.

The Effect Of Clinician Feedback Interventions On Opioid Prescribing.

An initial opioid prescription with a greater number of pills is associated with a greater risk for future long-term opioid use, yet few interventions have reliably influenced individual clinicians' prescribing. Our objective was to evaluate the effect of feedback interventions for clinicians in reducing opioid prescribing. The interventions included feedback on a clinician's outlier prescribing (individual audit feedback), peer comparison, and both interventions combined. We conducted a four-arm factorial pragmatic cluster randomized trial at forty-eight emergency department (ED) and urgent care (UC) sites in the western US, including 263 ED and 175 UC clinicians with 294,962 patient encounters. Relative to usual care, there was a significant decrease in pills per prescription both for peer comparison feedback (-0.8) and for the combination of peer comparison and individual audit feedback (-1.2). This decrease was sustained during follow-up. There were no significant changes for individual audit feedback alone, and no interventions changed the proportion of encounters with an opioid prescription.

Effect of a Default Order vs an Alert in the Electronic Health Record on Hepatitis C Virus Screening Among Hospitalized Patients: A Stepped-Wedge Randomized Clinical Trial.

Importance: Hepatitis C virus (HCV) screening has been recommended for patients born between 1945 and 1965, but rates remain low. Objective: To evaluate whether a default order within the admission order set increases HCV screening compared with a preexisting alert within the electronic health record. Design, Setting, and Participants: This stepped-wedge randomized clinical trial was conducted from June 23, 2020, to April 10, 2021, at 2 hospitals within an academic medical center. Hospitalized patients born between 1945 and 1965 with no history of screening were included in the analysis. Interventions: During wedge 1 (a preintervention period), both hospital sites had an electronic alert prompting clinicians to consider HCV screening. During wedge 2, the first intervention wedge, the hospital site randomized to intervention (hospital B) had a default order for HCV screening implemented within the admission order set. During wedge 3, the second intervention wedge, the hospital site randomized to control (hospital A) had the default order set implemented. Main Outcomes and Measures: Percentage of eligible patients who received HCV screening during the hospital stay. Results: The study included 7634 patients (4405 in the control group and 3229 in the intervention group). The mean (SD) age was 65.4 (5.8) years; 4246 patients (55.6%) were men; 2142 (28.1%) were Black and 4625 (60.6%) were White; and 2885 (37.8%) had commercial insurance and 3950 (51.7%) had Medicare. The baseline rate of HCV screening in wedge 1 was 585 of 1560 patients (37.5% [95% CI, 35.1%-40.0%]) in hospital A and 309 of 1003 patients (30.8% [95% CI, 27.9%-33.7%]) in hospital B. The main adjusted model showed an increase of 31.8 (95% CI, 29.7-33.8) percentage points in test completion in the intervention group compared with the control group (P <. 001). Conclusions and Relevance: This stepped-wedge randomized clinical trial found that embedding HCV screening as a default order in the electronic health record substantially increased ordering and completion of testing in the hospital compared with a conventional interruptive alert. Trial Registration: Clinicaltrials.gov: NCT04525690.

Effect of Goal-Setting Approaches Within a Gamification Intervention to Increase Physical Activity Among Economically Disadvantaged Adults at Elevated Risk for Major Adverse Cardiovascular Events: The ENGAGE Randomized Clinical Trial.

Importance: Health promotion efforts commonly communicate goals for healthy behavior, but the best way to design goal setting among high-risk patients has not been well examined. Objective: To test the effectiveness of different ways to set and implement goals within a behaviorally designed gamification intervention to increase physical activity. Design, Setting, and Participants: Evaluation of the Novel Use of Gamification With Alternative Goal-setting Experiences was conducted from January 15, 2019, to June 1, 2020. The 24-week randomized clinical trial included a remotely monitored 8-week introductory intervention period, 8-week maintenance intervention period, and 8-week follow-up period. A total of 500 adults from lower-income neighborhoods in and around Philadelphia, Pennsylvania, who had either an atherosclerotic cardiovascular disease (ASCVD) condition or a 10-year ASCVD risk score greater than or equal to 7.5% were enrolled. Participants were paid for enrolling in and completing the trial. Interventions: All participants used a wearable device to track daily steps, established a baseline level, and were then randomly assigned to an attention control or 1 of 4 gamification interventions that varied only on how daily step goals were set (self-chosen or assigned) and implemented (immediately or gradually). Main Outcome Measures: The primary outcome was change in mean daily steps from baseline to the 8-week maintenance intervention period. Other outcomes included changes in minutes of moderate to vigorous physical activity. All randomly assigned participants were included in the intention-to-treat analysis. Results: Of the 500 participants, 331 individuals (66.2%) were Black, 114 were White (22.8%), and 348 were women (69.6%). Mean (SD) age was 58.5 (10.8) years and body mass index was 33.2 (7.8). A total of 215 participants (43.0%) had an ASCVD condition. Compared with the control arm, participants with self-chosen and immediate goals had significant increases in the number of daily steps during the maintenance intervention period (1384; 95% CI, 805-1963; P < .001) that were sustained during the 8-week follow-up (1391; 95% CI, 785-1998; P < .001). This group also had significant increases in daily minutes of moderate to vigorous physical activity during the maintenance intervention (4.1; 95% CI, 1.8-6.4; P < .001) that were sustained during follow-up (3.5; 95% CI, 1.1-5.8; P = .004). No other gamification arms had consistent increases in physical activity compared with the control arm. No major adverse events were reported. Conclusions and Relevance: In this trial among economically disadvantaged adults at elevated risk for major adverse cardiovascular events, a gamification intervention led to increases in physical activity that were sustained during 8 weeks of follow-up when goals were self-chosen and implemented immediately. Trial Registration: ClinicalTrials.gov Identifier: NCT03749473.

Effect of Behaviorally Designed Gamification With Social Incentives on Lifestyle Modification Among Adults With Uncontrolled Diabetes: A Randomized Clinical Trial.

Importance: Gamification is increasingly being used to promote healthy behaviors. However, it has not been well tested among patients with chronic conditions and over longer durations. Objective: To test the effectiveness of behaviorally designed gamification interventions to enhance support, collaboration, or competition to promote physical activity and weight loss among adults with uncontrolled type 2 diabetes. Design, Setting, and Participants: A 4-arm randomized clinical trial with a 1-year intervention was conducted from January 23, 2017, to January 27, 2020, with remotely monitored intervention. Analyses were conducted between February 10 and October 6, 2020. Participants included 361 adults with type 2 diabetes with hemoglobin A1c levels greater than or equal to 8% and body mass index greater than or equal to 25. Interventions: All participants received a wearable device, smart weight scale, and laboratory testing. Participants in the control group received feedback from their devices but no other interventions. Participants in the gamification arms conducted goal setting and were entered into a 1-year game designed using insights from behavioral economics with points and levels for achieving step goals and weight loss targets. The game varied by trial arm to promote either support, collaboration, or competition. Main Outcomes and Measures: Co-primary outcomes included daily step count, weight, and hemoglobin A1c level. Secondary outcome was low-density lipoprotein cholesterol level. Intention-to-treat analysis was used. Results: Participants had a mean (SD) age of 52.5 (10.1) years; hemoglobin A1c level, 9.6% (1.6%); daily steps, 4632 (2523); weight, 107.4 kg (20.8 kg); and body mass index, 37.1 (6.6). Of the 361 participants, 202 (56.0%) were women, 143 (39.6%) were White, and 185 (51.2%) were Black; with 87 (24.1%) randomized to control; 92 (25.4%) randomized to gamification with support and intervention; 95 (26.3%) randomized to gamification with collaboration; and 87 (24.1%) randomized to gamification with competition. Compared with the control group over 1 year, there was a significant increase in mean daily steps from baseline among participants receiving gamification with support (adjusted difference relative to control group, 503 steps; 95% CI, 103 to 903 steps; P = .01) and competition (606 steps; 95% CI, 201 to 1011 steps; P = .003) but not collaboration (280 steps; 95% CI, -115 to 674 steps; P = .16). All trial arms had significant reductions in weight and hemoglobin A1c levels from baseline, but there were no significant differences between any of the intervention arms and the control arm. There was only 1 adverse event reported that may have been related to the trial (arthritic knee pain). Conclusions and Relevance: Among adults with uncontrolled type 2 diabetes, a behaviorally designed gamification intervention in this randomized clinical trial significantly increased physical activity over a 1-year period when designed to enhance either support or competition but not collaboration. No differences between intervention and control groups were found for other outcomes. Trial Registration: ClinicalTrials.gov Identifier: NCT02961192.

Effect of Behaviorally Designed Gamification With a Social Support Partner to Increase Mobility After Hospital Discharge: A Randomized Clinical Trial.

Importance: Hospitalization is associated with decreased mobility and functional decline. Behaviorally designed gamification can increase mobility in community settings but has not been tested among patients at risk for functional decline during a high-risk transition period after hospitalization. Objective: To test a behaviorally designed gamification intervention with a social support partner to increase patient mobility after hospital discharge. Design, Setting, and Participants: This study is a randomized clinical trial of a 12-week intervention without follow-up. Enrollment occurred from January 2018 to June 2019 at a referral hospital with a remote at-home monitoring intervention among patients living predominantly in 3 states (Pennsylvania, New Jersey, and Delaware). Participants included adult patients discharged from general medicine and oncology units to home. Data analysis was performed from October 2019 to March 2020. Interventions: All participants received a wearable device to track daily steps. The control group received feedback from the device but no other interventions. The intervention group entered into a 12-week game informed by behavioral economics to assign points and levels for achieving step goals and reinforced by a support partner who received updates on participant progress. Main Outcomes and Measures: The primary outcome was change in mean daily steps from baseline through the 12-week intervention. Secondary measures were change in functional status and urgent care utilization (ie, emergency department visits and hospital readmissions) within this period. Results: A total of 232 participants were enrolled in the study (118 randomized to control and 114 randomized to the intervention). Participants had a mean (SD) age of 40 (14) years, 141 (61%) were female, 101 (43%) were White, and 103 (44%) had an annual household income less than $50 000. Daily step counts increased from 3795 to 4652 steps (difference, 857 steps; 95% CI, 488 to 1224 steps) among intervention participants and increased from 3951 to 4499 steps (difference, 548 steps; 95% CI, 193 to 903 steps) among control participants. The change in mean daily step count from baseline was not significantly different for participants in the intervention group vs the control group (adjusted difference, 270 steps; 95% CI, -214 to 754 steps; P = .27). Among the subgroup of 76 participants with higher levels of social engagement, post hoc exploratory analyses showed a significant increase in mobility for intervention vs control (adjusted difference, 1125 steps; 95% CI, 409 to 1841 steps; P = .002). Fewer participants in this subgroup experienced functional decline (1 of 36 participants [4%] in the intervention group vs 5 of 40 participants [12%] in the control group) and hospital readmission at 30 days (3 of 36 participants [8%] in the intervention group vs 6 of 40 participants [15%] in the control group), but the differences were not statistically significant. There were no significant differences in these secondary outcomes for the overall sample. Conclusions and Relevance: Gamification with social incentives did not affect mobility or functional decline in all participants, but post hoc analysis suggests positive findings for both outcomes for patients with higher social engagement. Trial Registration: ClinicalTrials.gov Identifier: NCT03321279.

Effect of Passive Choice and Active Choice Interventions in the Electronic Health Record to Cardiologists on Statin Prescribing: A Cluster Randomized Clinical Trial.

Importance: Statin therapy is underused for many patients who could benefit. Objective: To evaluate the effect of passive choice and active choice interventions in the electronic health record (EHR) to promote guideline-directed statin therapy. Design, Setting, and Participants: Three-arm randomized clinical trial with a 6-month preintervention period and 6-month intervention. Randomization conducted at the cardiologist level at 16 cardiology practices in Pennsylvania and New Jersey. The study included 82 cardiologists and 11 693 patients. Data were analyzed between May 8, 2019, and January 9, 2020. Interventions: In passive choice, cardiologists had to manually access an alert embedded in the EHR to select options to initiate or increase statin therapy. In active choice, an interruptive EHR alert prompted the cardiologist to accept or decline guideline-directed statin therapy. Cardiologists in the control group were informed of the trial but received no other interventions. Main Outcomes and Measures: Primary outcome was statin therapy at optimal dose based on clinical guidelines. Secondary outcome was statin therapy at any dose. Results: The sample comprised 11 693 patients with a mean (SD) age of 63.8 (9.1) years; 58% were male (n = 6749 of 11 693), 66% were White (n = 7683 of 11 693), and 24% were Black (n = 2824 of 11 693). The mean (SD) 10-year atherosclerotic cardiovascular disease (ASCVD) risk score was 15.4 (10.0); 68% had an ASVCD clinical diagnosis. Baseline statin prescribing rates at the optimal dose were 40.3% in the control arm, 39.1% in the passive choice arm, and 41.2% in the active choice arm. In adjusted analyses, the change in statin prescribing rates at optimal dose over time was not significantly different from control for passive choice (adjusted difference in percentage points, 0.2; 95% CI, -2.9 to 2.8; P = .86) or active choice (adjusted difference in percentage points, 2.4; 95% CI, -0.6 to 5.0; P = .08). In adjusted analyses of the subset of patients with clinical ASCVD, the active choice intervention resulted in a significant increase in statin prescribing at optimal dose relative to control (adjusted difference in percentage points, 3.8; 95% CI, 1.0-6.4; P = .008). No other subset analyses were significant. There were no significant changes in statin prescribing at any dose for either intervention. Conclusions and Relevance: The passive choice and active choice interventions did not change statin prescribing. In the subgroup of patients with clinical ASCVD, the active choice intervention led to a small increase in statin prescribing at the optimal dose, which could inform the design or targeting of future interventions. Trial Registration: ClinicalTrials.gov Identifier: NCT03271931.

Improving the colonization and functions of Wharton's Jelly-derived mesenchymal stem cells by a synergetic combination of porous polyurethane scaffold with an albumin-derived hydrogel.

The development of neo-tissues assisted by artificial scaffolds is continually progressing, but the reproduction of the extracellular environment surrounding cells is quite complex. While synthetic scaffolds can support cell growth, they lack biochemical cues that can prompt cell proliferation or differentiation. In this study, Wharton's Jelly-derived mesenchymal stem cells are seeded on a polyurethane (PU) scaffold combined with a hydrogel based on bovine serum albumin (BSA). BSA hydrogel is obtained through thermal treatment. While such treatment leads to partial unfolding of the protein, we show that the extent of denaturation is small enough to maintain its bioactivity, such as protein binding. Therefore, BSA provides a suitable playground for cells inside the scaffold, allowing higher spreading, proliferation and matrix secretions. Furthermore, the poor mechanical properties of the hydrogel are compensated for by the porous PU scaffold, whose architecture is well controlled. We show that even though PU by itself can allow cell adhesion and protein secretion, cell proliferation is 3.5 times higher in the PU + BSA scaffolds as compared to pure PU after 21 d, along with the non-collagenous protein secretions (389 versus 134 µmmg -1). Conversely, the secretion of sulphated glycosaminoglycans is 12.3-fold higher in the scaffold made solely of PU. Thereby, we propose a simple approach to generating a hybrid material composed of a combination of PU and BSA hydrogel as a promising scaffold for tissue regeneration.

Effect of Integrating Machine Learning Mortality Estimates With Behavioral Nudges to Clinicians on Serious Illness Conversations Among Patients With Cancer: A Stepped-Wedge Cluster Randomized Clinical Trial.

IMPORTANCE: Serious illness conversations (SICs) are structured conversations between clinicians and patients about prognosis, treatment goals, and end-of-life preferences. Interventions that increase the rate of SICs between oncology clinicians and patients may improve goal-concordant care and patient outcomes. OBJECTIVE: To determine the effect of a clinician-directed intervention integrating machine learning mortality predictions with behavioral nudges on motivating clinician-patient SICs. DESIGN, SETTING, AND PARTICIPANTS: This stepped-wedge cluster randomized clinical trial was conducted across 20 weeks (from June 17 to November 1, 2019) at 9 medical oncology clinics (8 subspecialty oncology and 1 general oncology clinics) within a large academic health system in Pennsylvania. Clinicians at the 2 smallest subspecialty clinics were grouped together, resulting in 8 clinic groups randomly assigned to the 4 intervention wedge periods. Included participants in the intention-to-treat analyses were 78 oncology clinicians who received SIC training and their patients (N = 14 607) who had an outpatient oncology encounter during the study period. INTERVENTIONS: (1) Weekly emails to oncology clinicians with SIC performance feedback and peer comparisons; (2) a list of up to 6 high-risk patients (≥10% predicted risk of 180-day mortality) scheduled for the next week, estimated using a validated machine learning algorithm; and (3) opt-out text message prompts to clinicians on the patient's appointment day to consider an SIC. Clinicians in the control group received usual care consisting of weekly emails with cumulative SIC performance. MAIN OUTCOMES AND MEASURES: Percentage of patient encounters with an SIC in the intervention group vs the usual care (control) group. RESULTS: The sample consisted of 78 clinicians and 14 607 patients. The mean (SD) age of patients was 61.9 (14.2) years, 53.7% were female, and 70.4% were White. For all encounters, SICs were conducted among 1.3% in the control group and 4.6% in the intervention group, a significant difference (adjusted difference in percentage points, 3.3; 95% CI, 2.3-4.5; P < .001). Among 4124 high-risk patient encounters, SICs were conducted among 3.6% in the control group and 15.2% in the intervention group, a significant difference (adjusted difference in percentage points, 11.6; 95% CI, 8.2-12.5; P < .001). CONCLUSIONS AND RELEVANCE: In this stepped-wedge cluster randomized clinical trial, an intervention that delivered machine learning mortality predictions with behavioral nudges to oncology clinicians significantly increased the rate of SICs among all patients and among patients with high mortality risk who were targeted by the intervention. Behavioral nudges combined with machine learning mortality predictions can positively influence clinician behavior and may be applied more broadly to improve care near the end of life. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03984773.

Association between behavioral phenotypes and response to a physical activity intervention using gamification and social incentives: Secondary analysis of the STEP UP randomized clinical trial.

Participants often vary in their response to behavioral interventions, but methods to identify groups of participants that are more likely to respond are lacking. In this secondary analysis of a randomized clinical trial, we used baseline characteristics to group participants into distinct behavioral phenotypes and evaluated differential responses to a physical activity intervention. Latent class analysis was used to segment participants based on baseline participant data including demographics, validated measures of psychosocial variables, and physical activity behavior. The trial included 602 adults from 40 U.S. states with body mass index ≥25 who were randomized to control or one of three gamification interventions (supportive, collaborative, or competitive) to increase physical activity. Daily step counts were monitored using a wearable device for a 24-week intervention with 12 weeks of follow-up. The model segmented participants into three classes named for key defining traits: Class 1, extroverted and motivated; Class 2, less active and less social; Class 3, less motivated and at-risk. Adjusted regression models were used to test for differences in intervention response relative to control within each behavioral phenotype. In Class 1, only participants in the competitive arm increased their mean daily steps during the intervention (adjusted difference, 945; 95% CI, 352-1537; P = .002), but it was not sustained during follow-up. In Class 2, participants in all three gamification arms significantly increased their mean daily steps compared to control during the intervention (supportive arm adjusted difference 1172; 95% CI, 363-1980; P = .005; collaborative arm adjusted difference 1119; 95% CI, 319-1919; P = .006; competitive arm adjusted difference 1179; 95% CI, 400-1957; P = .003) and all three had sustained impact during follow-up. In Class 3, none of the interventions had a significant effect on physical activity. Three behavioral phenotypes were identified, each with a different response to the interventions. This approach could be used to better target behavioral interventions to participants that are more likely to respond to them.

Intraoperative imaging for remnant viability assessment in bilateral posterior retroperitoneoscopic partial adrenalectomy in an experimental model.

BACKGROUND: A surgical approach preserving functional adrenal tissue allows biochemical cure while avoiding the need for lifelong steroid replacement. The aim of this experimental study was to evaluate the impact of intraoperative imaging during bilateral partial adrenalectomy on remnant perfusion and function. METHODS: Five pigs underwent bilateral posterior retroperitoneoscopic central adrenal gland division (9 divided glands, 1 undivided). Intraoperative perfusion assessment included computer-assisted quantitative fluorescence imaging, contrast-enhanced CT, confocal laser endomicroscopy (CLE) and local lactate sampling. Specimen analysis after completion adrenalectomy (10 adrenal glands) comprised mitochondrial activity and electron microscopy. RESULTS: Fluorescence signal intensity evolution over time was significantly lower in the cranial segment of each adrenal gland (mean(s.d.) 0·052(0·057) versus 0·133(0·057) change in intensity per s for cranial versus caudal parts respectively; P = 0·020). Concordantly, intraoperative CT in the portal phase demonstrated significantly lower contrast uptake in cranial segments (P = 0·031). In CLE, fluorescein contrast was observed in all caudal segments, but in only four of nine cranial segments (P = 0·035). Imaging findings favouring caudal perfusion were congruent, with significantly lower local capillary lactate levels caudally (mean(s.d.) 5·66(5·79) versus 11·58(6·53) mmol/l for caudal versus cranial parts respectively; P = 0·008). Electron microscopy showed more necrotic cells cranially (P = 0·031). There was no disparity in mitochondrial activity (respiratory rates, reactive oxygen species and hydrogen peroxide production) between the different segments. CONCLUSION: In a model of bilateral partial adrenalectomy, three intraoperative imaging modalities consistently discriminated between regular and reduced adrenal remnant perfusion. By avoiding circumferential dissection, mitochondrial function was preserved in each segment of the adrenal glands. Surgical relevance Preservation of adrenal tissue to maintain postoperative function is essential in bilateral and hereditary adrenal pathologies. There is interindividual variation in residual adrenocortical stress capacity, and the minimal functional remnant size is unknown. New intraoperative imaging technologies allow improved remnant size and perfusion assessment. Fluorescence imaging and contrast-enhanced intraoperative CT showed congruent results in evaluation of perfusion. Intraoperative imaging can help to visualize the remnant vascular supply in partial adrenalectomy. Intraoperative assessment of perfusion may foster maximal functional tissue preservation in bilateral adrenal pathologies and procedures.

ANTECEDENTES: Un abordaje quirúrgico que preserve la función del tejido suprarrenal permite lograr la curación bioquímica, a la vez que evita la necesidad de tratamiento sustitutivo con corticoides de por vida. El objetivo de este estudio experimental fue evaluar el impacto de las técnicas de imagen intraoperatorias en la suprarrenalectomía parcial (partial adrenalectomy, AE) bilateral sobre la perfusión y función del remanente glandular. MÉTODOS: Cinco cerdos fueron sometidos a una división bilateral central de la glándula suprarrenal por retroperitoneoscopia posterior (n = 9, 1 sin dividir). Durante la intervención, la evaluación de la perfusión incluyó la fluorescencia con cuantificación asistida por ordenador (Realidad Aumentada basada en la Fluorescencia, FLuorescence-based Enhanced Reality, FLER), tomografía computarizada (computed tomography, CT), endomicroscopia con laser confocal (confocal laser endomicroscopy, CLE) y un muestreo local de lactato. El análisis de la pieza quirúrgica tras completar la AE (n = 10) incluyó actividad mitocondrial y microscopia electrónica. RESULTADOS: La evolución de la intensidad de la señal de fluorescencia a lo largo del tiempo (ΔI/s) fue significativamente más baja en el segmento craneal de cada una de las glándulas (0,052 ± 0,057 craneal versus 0,133 ± 0,057 caudal, P = 0,02). De forma concordante, la CT intraoperatoria en la fase portal demostró una captación de contraste significativamente más baja en los segmentos craneales (P = 0,03). En la CLE, el contraste de fluoresceína se observó en todos los segmentos caudales, pero solo en el 44% de los segmentos craneales (P = 0,04). Los hallazgos obtenidos en las pruebas de imagen favorables a la perfusión caudal fueron congruentes con niveles significativamente más bajos de lactato capilar a nivel local (11,58 ± 6,53 mmol/L craneal versus 5,66 ± 5,79 mmol/L caudal, P = 0,008). A nivel craneal, la microscopia electrónica mostró más células necróticas (P = 0,03). La actividad mitocondrial (tasas de respiración, especies reactivas de oxígeno y producción de H2 O2 ) no mostraron disparidad entre los diferentes segmentos. CONCLUSIÓN: En un modelo de AE parcial bilateral, las tres modalidades de pruebas de imagen intraoperatorias podrían discriminar de forma consistente una perfusión regular y reducida del remanente suprarrenal. Al evitar una disección circunferencial, se preservó la función mitocondrial en cada segmento de las glándulas suprarrenales.

Phenotyping physician practice patterns and associations with response to a nudge in the electronic health record for influenza vaccination: A quasi-experimental study.

BACKGROUND: Health systems routinely implement changes to the design of electronic health records (EHRs). Physician behavior may vary in response and methods to identify this variation could help to inform future interventions. The objective of this study was to phenotype primary care physician practice patterns and evaluate associations with response to an EHR nudge for influenza vaccination. METHODS AND FINDINGS: During the 2016-2017 influenza season, 3 primary care practices at Penn Medicine implemented an active choice intervention in the EHR that prompted medical assistants to template influenza vaccination orders for physicians to review during the visit. We used latent class analysis to identify physician phenotypes based on 9 demographic, training, and practice pattern variables, which were obtained from the EHR and publicly available sources. A quasi-experimental approach was used to evaluate response to the intervention relative to control practices over time in each of the physician phenotype groups. For each physician latent class, a generalized linear model with logit link was fit to the binary outcome of influenza vaccination at the patient visit level. The sample comprised 45,410 patients with a mean (SD) age of 58.7 (16.3) years, 67.1% were white, and 22.1% were black. The sample comprised 56 physicians with mean (SD) of 24.6 (10.2) years of experience and 53.6% were male. The model segmented physicians into groups that had higher (n = 41) and lower (n = 15) clinical workloads. Physicians in the higher clinical workload group had a mean (SD) of 818.8 (429.1) patient encounters, 11.6 (4.7) patient appointments per day, and 4.0 (1.1) days per week in clinic. Physicians in the lower clinical workload group had a mean (SD) of 343.7 (129.0) patient encounters, 8.0 (2.8) patient appointments per day, and 3.1 (1.2) days per week in clinic. Among the higher clinical workload group, the EHR nudge was associated with a significant increase in influenza vaccination (adjusted difference-in-difference in percentage points, 7.9; 95% CI, 0.4-9.0; P = .01). Among the lower clinical workload group, the EHR nudge was not associated with a significant difference in influenza vaccination rates (adjusted difference-in-difference in percentage points, -1.0; 95% CI, -5.3-5.8; P = .90). CONCLUSIONS: A model-based approach categorized physician practice patterns into higher and lower clinical workload groups. The higher clinical workload group was associated with a significant response to an EHR nudge for influenza vaccination.

Integrating machine-generated mortality estimates and behavioral nudges to promote serious illness conversations for cancer patients: Design and methods for a stepped-wedge cluster randomized controlled trial.

INTRODUCTION: Patients with cancer often receive care that is not aligned with their personal values and goals. Serious illness conversations (SICs) between clinicians and patients can help increase a patient's understanding of their prognosis, goals and values. METHODS AND ANALYSIS: In this study, we describe the design of a stepped-wedge cluster randomized trial to evaluate the impact of an intervention that employs machine learning-based prognostic algorithms and behavioral nudges to prompt oncologists to have SICs with patients at high risk of short-term mortality. Data are collected on documented SICs, documented advance care planning discussions, and end-of-life care utilization (emergency room and inpatient admissions, chemotherapy and hospice utilization) for patients of all enrolled clinicians. CONCLUSION: This trial represents a novel application of machine-generated mortality predictions combined with behavioral nudges in the routine care of outpatients with cancer. Findings from the trial may inform strategies to encourage early serious illness conversations and the application of mortality risk predictions in clinical settings. TRIAL REGISTRATION: Clinicaltrials.gov Identifier: NCT03984773.

Association of an Active Choice Intervention in the Electronic Health Record Directed to Medical Assistants With Clinician Ordering and Patient Completion of Breast and Colorectal Cancer Screening Tests.

Importance: Early cancer detection can lead to improved outcomes, but cancer screening tests are often underused. Objective: To evaluate the association of an active choice intervention in the electronic health record directed to medical assistants with changes in clinician ordering and patient completion of breast and colorectal cancer screening tests. Design, Setting, and Participants: A retrospective quality improvement study was conducted among 69 916 patients eligible for breast or colorectal cancer screening at 25 primary care practices at the University of Pennsylvania Health System between September 1, 2014, and August 31, 2017. Data analysis was conducted from January 21 to July 8, 2019. Interventions: From 2016 to 2017, 3 primary care practices at the University of Pennsylvania Health System implemented an active choice intervention in the electronic health record that prompted medical assistants to inform patients about cancer screening during check-in and template orders for clinicians to review during the visit. Main Outcomes and Measures: The primary outcome was clinician ordering of cancer screening tests. The secondary outcome was patient completion of cancer screening tests within 1 year of the primary care visit. Results: The sample eligible for breast cancer screening comprised 26 269 women with a mean (SD) age of 60.4 (6.9) years; 15 873 (60.4%) were white and 7715 (29.4%) were black. The sample eligible for colorectal cancer screening comprised 43 647 patients with a mean (SD) age of 59.4 (7.5) years; 24 416 (55.9%) were women, 19 231 (44.1%) were men, 29 029 (66.5%) were white, and 9589 (22.0%) were black. For breast cancer screening, the intervention was associated with a significant increase in clinician ordering of tests (22.2 percentage points; 95% CI, 17.2-27.6 percentage points; P < .001) but no change in patient completion (0.1 percentage points; 95% CI, -4.0 to 4.3 percentage points; P = .45). For colorectal cancer screening, the intervention was associated with a significant increase in clinician ordering of tests (13.7 percentage points; 95% CI, 8.0-18.9 percentage points; P < .001) but no change in patient completion (1.0 percentage points; 95% CI, -3.2 to 4.6 percentage points; P = .36). Conclusions and Relevance: An active choice intervention in the electronic health record directed to medical assistants was associated with a significant increase in clinician ordering of breast and colorectal cancer screening tests. However, it was not associated with a significant change in patient completion of either cancer screening test during a 1-year follow-up.

Effectiveness of Behaviorally Designed Gamification Interventions With Social Incentives for Increasing Physical Activity Among Overweight and Obese Adults Across the United States: The STEP UP Randomized Clinical Trial.

Importance: Gamification, the use of game design elements in nongame contexts, is increasingly being used in workplace wellness programs and digital health applications. However, the best way to design social incentives in gamification interventions has not been well examined. Objective: To assess the effectiveness of support, collaboration, and competition within a behaviorally designed gamification intervention to increase physical activity among overweight and obese adults. Design, Setting, and Participants: This 36-week randomized clinical trial with a 24-week intervention and 12-week follow-up assessed 602 adults from 40 states with body mass indexes (calculated as weight in kilograms divided by height in meters squared) of 25 or higher from February 12, 2018, to March 17, 2019. Interventions: Participants used a wearable device to track daily steps, established a baseline, selected a step goal increase, were randomly assigned to a control (n = 151) or to 1 of 3 gamification interventions (support [n = 151], collaboration [n = 150], and competition [n = 150]), and were remotely monitored. The control group received feedback from the wearable device but no other interventions for 36 weeks. The gamification arms were entered into a 24-week game designed using insights from behavioral economics with points and levels for achieving step goals. No gamification interventions occurred during follow-up. Main Outcomes and Measures: The primary outcome was change in mean daily steps from baseline through the 24-week intervention period. Results: A total of 602 participants (mean [SD] age, 39 [10] years; mean [SD] body mass index, 30 [5]; 427 [70.9%] male) were included in the study. Compared with controls, participants had a significantly greater increase in mean daily steps from baseline during the intervention in the competition arm (adjusted difference, 920; 95% CI, 513-1328; P < .001), support arm (adjusted difference, 689; 95% CI, 267-977; P < .001), and collaboration arm (adjusted difference, 637; 95% CI, 258-1017; P = .001). During follow-up, physical activity remained significantly greater in the competition arm than in the control arm (adjusted difference, 569; 95% CI, 142-996; P = .009) but was not significantly greater in the support (adjusted difference, 428; 95% CI, 19-837; P = .04) and collaboration (adjusted difference, 126; 95% CI, -248 to 468; P = .49) arms than in the control arm. Conclusions and Relevance: All 3 gamification interventions significantly increased physical activity during the 24-week intervention, and competition was the most effective. Physical activity was lower in all arms during follow-up and only remained significantly greater in the competition arm than in the control arm. Trial Registration: ClinicalTrials.gov identifier: NCT03311230.