Decreasing Opioid Addiction and Diversion Using Behavioral Economics Applied Through a Digital Engagement Solution: Protocol for a Randomized Controlled Trial.

BACKGROUND: Despite strong and growing interest in ending the ongoing opioid health crisis, there has been limited success in reducing the prevalence of opioid addiction and the number of deaths associated with opioid overdoses. Further, 1 explanation for this is that existing interventions target those who are opiate-dependent but do not prevent opioid-naïve patients from becoming addicted. OBJECTIVE: Leveraging behavioral economics at the patient level could help patients successfully use, discontinue, and dispose of their opioid medications in an acute pain setting. The primary goal of this project is to evaluate the effect of the 3 versions of the Opioid Management for You (OPY) tool on measures of opioid use relative to the standard of care by leveraging a pragmatic randomized controlled trial (RCT). METHODS: A team of researchers from the Center for Learning Health System Sciences (CLHSS) at the University of Minnesota partnered with M Health Fairview to design, build, and test the 3 versions of the OPY tool: social influence, precommitment, and testimonial version. The tool is being built using the Epic Care Companion (Epic Inc) platform and interacts with the patient through their existing MyChart (Epic Systems Corporation) personal health record account, and Epic patient portal, accessed through a phone app or the MyChart website. We have demonstrated feasibility with pilot data of the social influence version of the OPY app by targeting our pilot to a specific cohort of patients undergoing upper-extremity procedures. This study will use a group sequential RCT design to test the impact of this important health system initiative. Patients who meet OPY inclusion criteria will be stratified into low, intermediate, and high risk of opiate use based on their type of surgery. RESULTS: This study is being funded and supported by the CLHSS Rapid Prospective Evaluation and Digital Technology Innovation Programs, and M Health Fairview. Support and coordination provided by CLHSS include the structure of engagement, survey development, data collection, statistical analysis, and dissemination. The project was initially started in August 2022. The pilot was launched in February 2023 and is still running, with the data last counted in August 2023. The actual RCT is planned to start by early 2024. CONCLUSIONS: Through this RCT, we will test our hypothesis that patient opioid use and diverted prescription opioid availability can both be improved by information delivery applied through a behavioral economics lens via sending nudges directly to the opioid users through their personal health record. TRIAL REGISTRATION: ClinicalTrials.gov NCT06124079; https://clinicaltrials.gov/study/NCT06124079. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/52882.

A nationwide analysis of disparities in guideline-concordant care in American Indians and Alaska Natives with stage I non-small cell lung cancer.

Background: Several studies have shown racial disparities in lung cancer care in the United States in the Black and Hispanic populations but not many have included American Indian/Alaska Native (AI/AN) patients. We retrospectively evaluated the factors associated with receipt of guideline-concordant care in AI/AN and non-Hispanic White (NHW) patients with stage I non-small cell lung cancer (NSCLC) and describe the relationship between guideline-concordant care and survival outcomes in these populations. Methods: Using the National Cancer Database, we identified NHW and AI/AN patients diagnosed with stage I NSCLC between 2004 and 2017. We evaluated the utilization of anatomic resection among both NHW and AI/AN and described the variables associated with anatomic resection. We also evaluated 5-year overall survival (OS) by treatment and race. We used the chi-square test, multivariable analysis, and the Kaplan-Meier method for statistical analysis. Results: We identified 196,349 patients. Of these, 195,736 (99.69%) were NHW and 613 (0.31%) were AI/AN. Relative to NHW, AI/AN were more frequently diagnosed at a younger age (40% vs. 28% diagnosed at 18-64 years of age; P<0.001) and more commonly resided in rural areas (14% vs. 5%; P<0.001). In our multivariable analysis adjusting for all patient factors [age at diagnosis, sex, race, residence location, Charlson Comorbidity Index (CCI), tumor stage, lymph node status, and treatment facility], AI/AN patients were less likely to undergo anatomic resection than NHW patients [odds ratio (OR), 0.74; 95% confidence interval (CI): 0.62-0.89]. In our unadjusted survival analysis, AI/AN patients had lower 5-year OS than NHW (58% vs. 56%; P=0.04). When adjusted for surgery this difference was no longer significant. Conclusions: AI/AN patients with stage I NSCLC undergo anatomic resection less frequently than do NHW, with lower 5-year OS than NHW. However, this survival difference is mitigated when AI/AN undergo anatomic resection.

Retrospective Multicenter Observational Study of Immediate Voiding at End of Urinary Sphincter Surgery (REMOVE).

PURPOSE: Patients may remain catheterized after artificial urinary sphincter surgery to prevent urinary retention, despite a lack of evidence to support this practice. Our study aims to evaluate the feasibility of outpatient, catheter-free continence surgery using a multi-institutional database. We hypothesize that between catheterized controls and patients without a catheter, there would be no difference in the rate of urinary retention or postoperative complications. MATERIALS AND METHODS: We conducted a retrospective review of patients undergoing first-time artificial urinary sphincter placement from 2009-2021. Patients were stratified by postoperative catheter status into either no-catheter (leaving the procedure without a catheter) or catheter (postoperative indwelling catheter for ∼24 hours). The primary outcome, urinary retention, was defined as catheterization due to subjective voiding difficulty or documented postvoid residual over 250 mL. RESULTS: Our study identified 302 catheter and 123 no-catheter patients. Twenty (6.6%) catheter and 9 (7.3%) no-catheter patients developed urinary retention (P = .8). On multivariable analysis, controlling for age, cuff size, radiation history and surgeon, there was no statistically significant association between omitting a catheter and urinary retention (OR: 0.45, 95% CI: 0.13-1.58; P = .2). Furthermore, at 30 months follow-up, Kaplan-Meier survival analysis revealed that device survival was 70% (95% CI: 62%-76%) vs 69% (95% CI: 48%-82%) for the catheter and no-catheter group, respectively. CONCLUSIONS: In our multi-institutional cohort, overall retention rates were low (7%) in groups with a catheter and without. Obviating postoperative catheterization facilitates outpatient incontinence surgery without altering reoperation over medium-term follow-up.

Identification of clinical factors associated with timing and duration of spontaneous regression of retinopathy of prematurity not requiring treatment.

OBJECTIVE: Identify clinical factors that delay or prolong spontaneous regression of retinopathy of prematurity (ROP). STUDY DESIGN: Secondary analysis of three prospective studies with 76 infants with ROP not requiring treatment, born ≤30 weeks postmenstrual age (PMA) and ≤1500 grams. Outcomes were PMA at greatest severity of ROP (PMA MSROP), at which regression began, at time of complete vascularization (PMA CV), and regression duration. Pearson's correlation coefficients, t-tests, or analyses of variance were calculated. RESULTS: Increased positive bacterial cultures, hyperglycemia, transfusion volume of platelets and red blood cells and severity of ROP were associated with later PMA MSROP. Positive bacterial cultures, maternal chorioamnionitis, and less iron deficiency were associated with later PMA CV and prolonged regression duration. Slower length gain was associated with later PMA CV. P < 0.05 for all. CONCLUSIONS: Preterm infants with inflammatory exposures or linear growth impairment may require longer surveillance for ROP resolution and complete vascularization.

Machine Learning Prediction of Objective Hearing Loss With Demographics, Clinical Factors, and Subjective Hearing Status.

OBJECTIVE: Hearing loss (HL) is highly prevalent, yet underrecognized and underdiagnosed. Lack of standardized screening, awareness, cost, and access to hearing testing present barriers to HL identification. To facilitate prescreening and selection of patients who warrant audiometric evaluation, we developed a machine learning (ML) model to predict speech-frequency pure-tone average (PTA). STUDY DESIGN: Cross-sectional study. SETTING: National Health and Nutrition Examination Survey (NHANES). METHODS: The cohort included 8918 adults (≥20 years) who completed audiometric testing with NHANES (2012-2018). The primary outcome measure was the prediction of better hearing ear speech-frequency PTA. Relevant predictors included demographics, medical conditions, and subjective assessment of hearing. Supervised ML with a tree-based architecture was used. Regression performance was determined by the mean absolute error (MAE) with binary classification assessed with area under the receiver operating characteristic curve (AUC). RESULTS: Using the full set of predictors, the test set MAE between the ML-predicted and actual PTA was 5.29 dB HL (95% confidence interval [CI]: 4.97-5.61). The 5 most influential predictors of higher PTA were increased age, worse subjective hearing, male gender, increased body mass index, and history of smoking. The 5-factor abbreviated model performed comparably to the extended feature set with MAE 5.36 (95% CI: 5.03-5.69) and AUC for PTA > 25 dB HL of 0.92 (95% CI: 0.90-0.94). CONCLUSION: The ML model was able to predict PTA with patient demographics, clinical factors, and subjective hearing status. ML-based prediction may be used to identify individuals who could benefit most from audiometric evaluation.

BK DNAemia in pediatric kidney transplant recipients: Predictors and outcomes.

BACKGROUND: Pediatric data on risk factors and the clinical course of BK DNAemia are limited. We aimed to determine the effects of BK DNAemia on transplant outcomes and delineate the safety and efficacy of various treatment approaches. METHODS: This retrospective-cohort study included 161 transplants (age ≤ 21 years) performed at a single center between 1/1/2012 and 1/1/2020. We used Cox proportional models to evaluate the effects of BK DNAemia on patient survival (PS), graft survival (GS), and acute rejection (AR), using BK as a time-dependent covariate. We also assessed the effects of pharmacological intervention on BK DNAemia duration using intervention as a time-dependent covariate. RESULTS: BK-free survival was 69.1% at 1-year and 54.6% at 3-year posttransplant. After multivariate adjustment, BK DNAemia was associated with young age at transplant (aHR, age 5-<12 vs. ≥12 (years): 2.5 (1.4-4.5); p = .001) and steroid-based immunosuppression (IS) (aHR: 2.2 [1.1-4.5]; p = .03). We found no effect of DNAemia on AR (aHR: 1.25; p = .5), PS (aHR: 2.85; p = .22), and GS (aHR: 0.56; p = .41). Of 70 patients with DNAemia, 22 (31.4%) received no treatment, 20 (28.6%) received IS reduction alone, and 28 patients (40%) received treatment with at least one pharmacological agent (leflunomide, IVIG, ciprofloxacin, cidofovir). Sixty-three patients (90%) cleared DNAemia with median time to resolution of 2.4 months (IQR:1.4-5.6). We found no significant effect of BK-directed pharmacological treatment on time to resolution (aHR: 0.64;p = .13). BK-directed agents were well tolerated. CONCLUSIONS: BK DNAemia is associated with a young age at transplant and steroid-based maintenance IS. We found no effect of BK DNAemia on AR, GS, and PS.

Subxiphoid-subcostal versus transthoracic thoracoscopic thymectomy: A safe and feasible approach.

Objective: Subxiphoid-subcostal thoracoscopic thymectomy (ST) is an emerging alternative to transthoracic thoracoscopic thymectomy. Potential advantages of ST are the avoidance of intercostal incisions and visualization of both phrenic nerves in their entirety. We describe our experience with ST and compare our results to our previous experience with transthoracic thoracoscopic thymectomy. Methods: We conducted an institutional review board-exempt retrospective review of all patients who had a minimally invasive thymectomy from August 2008 to October 2021. We excluded patients with a previous sternotomy or radiological evidence of invasion into major vasculature. The ST approach involved 1 subxiphoid port for initial access, 2 subcostal ports on each side, and carbon dioxide insufflation. We used descriptive and comparative statistics on demographic, operative, and postoperative data. Results: We performed ST in 40 patients and transthoracic thoracoscopic thymectomy in 16 patients. The median age was higher in the ST group (58 years vs 34 years; P = .02). Operative data showed no significant differences in operative times, blood loss, or tumor characteristics. In the ST group, we had 2 emergency conversions for bleeding; 1 ministernotomy, and 1 sternotomy. Postoperative data showed that the ST group had fewer days with a chest tube (1 day vs 2.5 days; P = .02). There were no differences in median length of stay, tumor characteristics, final margins, major complication rate, and opioid requirements between the groups. There has been no incidence of diaphragmatic hernia and no phrenic nerve injuries or mortality in either group. Conclusions: ST is safe and has similar outcomes compared with transthoracic thoracoscopic thymectomy.

Orchialgia After Living Donor Nephrectomy: An Underreported Entity.

Laparoscopic donor nephrectomy (LDN) offers advantages to the donor. The reported incidence of testicular pain after LDN varies in the literature ranging from 3% to 55%. Methods: A survey was sent to 322 male LDN patients who donated from February 5, 2009, to February 5, 2019. The survey assessed if the donor had testicular pain or saw an additional medical professional after donation. Results: Of the 322 surveyed, 147 (46%) responses were received. Of those who had a left nephrectomy, 39% had testicular pain; 23.8% of those patients had testicular swelling in addition. Of those who had pain, laterality of kidney donated did not impact if the patient had pain, pain onset, pain level, or pain duration. Of those who donated their right kidney, 35% had testicular pain, and 16.7% of those patients reported testicular swelling in addition. Twenty-seven symptomatic patients sought additional medical care for the testicular symptoms postdonation. Seven (25%) had hydroceles, 2 (7%) had testicular cysts, 1 had a urinary tract infection, and 16 (59%) had reassurance or no additional procedures provided. Conclusions: Our results suggest that orchialgia is not as uncommon as previously thought and may be one of the most common minor complications experienced by male donors.

Corticosterone Is Essential for Survival Through Frog Metamorphosis.

Thyroid hormone (TH) is required for frog metamorphosis, and corticosterone (CORT) increases TH signaling to accelerate metamorphic progression. However, a requirement for CORT in metamorphosis has been difficult to assess prior to the recent development of gene-editing technologies. We addressed this long-standing question using transcription activator-like effector nuclease (TALEN) gene disruption to knock out proopiomelanocortin (pomc) and disrupt CORT production in Xenopus tropicalis. As expected, mutant tadpoles had a reduced peak of plasma CORT at metamorphosis with correspondingly reduced expression of the CORT-response gene Usher syndrome type-1G (ush1g). Mutants had reduced rates of growth and development and exhibited lower expression levels of 2 TH response genes, Krüppel-like factor 9 (klf9) and TH receptor ß (thrb). In response to exogenous TH, mutants had reduced TH response gene induction and slower morphological change. Importantly, death invariably occurred during tail resorption, unless rescued by exogenous CORT and, remarkably, by exogenous TH. The ability of exogenous TH by itself to overcome death in pomc mutants indicates that the CORT-dependent increase in TH signaling may ensure functional organ transformation required for survival through metamorphosis and/or may shorten the nonfeeding metamorphic transition to avoid lethal inanition.

Intravitreal Delivery of VEGF-A165-loaded PLGA Microparticles Reduces Retinal Vaso-Obliteration in an In Vivo Mouse Model of Retinopathy of Prematurity.

PURPOSE: Retinopathy of prematurity (ROP) is a condition of abnormal retinal vascularization with reduced levels of vascular endothelial growth factor (VEGF) causing vaso-obliteration (Phase I), followed by abnormal neovascularization from increased VEGF (Phase II). We hypothesized that intravitreal pro-angiogenic VEGF-A in microparticle form would promote earlier retinal revascularization in an oxygen-induced ischemic retinopathy (OIR) mouse model. MATERIALS AND METHODS: Wildtype mice (39) were exposed to 77% oxygen from postnatal day 7 (P7) to P12. VEGF-A165-loaded poly(lactic-co-glycolic acid) (PLGA) (n = 15) or empty PLGA (n = 14) microparticles were fabricated using a water-in-oil-in-water double emulsion method, and injected intravitreally at P13 into mice right eyes (RE). Left eyes (LE) were untreated. At P20, after retinal fluorescein angiography, vascular parameters were quantified. Retinal VEGF levels at P13 and flatmounts at P20 were performed separately. RESULTS: VEGF-A165-loaded microparticles had a mean diameter of 4.2 µm. with a loading level of 8.6 weight.%. Retinal avascular area was reduced in VEGF-treated RE (39.5 ± 9.0%) compared to untreated LE (52.6 ± 6.1%, p < 0.0001) or empty microparticle-treated RE (p < 0.001) and untreated LEs (p = 0.001). Retinal arteries in VEGF-treated RE were less tortuous than untreated LE (1.08 ± 0.05 vs. 1.18 ± 0.08, p < 0.001) or empty-microparticles-treated RE (p = 0.02). Retinal arterial tortuosity was similar in the LE of VEGF and empty microparticle-treated mice (P > 0.05). Retinal vein width was similar in VEGF-treated and empty microparticle-treated RE (P > 0.9), which were each less dilated than their contralateral LE (p < 0.01). VEGF levels were higher in P13 OIR mice than RA mice (p < 0.0001). Retinal flatmounts showed vaso-obliteration and neovascularization. CONCLUSIONS: Endogenous retinal VEGF is suppressed in OIR mice. Exogenous intravitreal VEGF-A165-loaded microparticles in OIR mice reduced retinal vaso-obliteration and accelerated recovery from vein dilation and arterial tortuosity. This may be beneficial in preventing Phase II ROP without systemic effects.

Simultaneous Fluorescein Angiography and Spectral Domain Optical Coherence Tomography Correlate Retinal Thickness Changes to Vascular Abnormalities in an In Vivo Mouse Model of Retinopathy of Prematurity.

BACKGROUND: Retinopathy of prematurity (ROP) is a condition of abnormal retinal vascular development (RVD) in premature infants. Fluorescein angiography (FA) has depicted phases (early, mid, late, and mature) of RVD in oxygen-induced retinopathy (OIR) mice. We sought to establish the relationship between retinal structural and vascular changes using simultaneous FA and spectral domain optical coherence tomography (SD-OCT). METHOD: 63 mice were exposed to 77% oxygen at postnatal day 7 (P7) for 5 days, while 63 mice remained in room air (RA). Total retinal thickness (TRT), inner retinal thickness (IRT), and outer retinal thickness (ORT) were calculated at early (P19), mid (P24), late (P32), and mature (P47) phases of RVD. RESULTS: TRT was reduced in OIR (162.66 ± 17.75 µm, n = 13) compared to RA mice at P19 (197.57 ± 3.49 µm, n = 14), P24, P32, and P49 (P < 0.0001). ORT was similar in RA and OIR mice at all ages (P > 0.05). IRT was reduced in OIR (71.60 ± 17.14 µm) compared to RA (103.07 ± 3.47 µm) mice at P19 and all ages (P < 0.0001). CONCLUSION: We have shown the spatial and temporal relationship between retinal structure and vascular development in OIR. Significant inner retinal thinning in OIR mice persisted despite revascularization of the capillary network; further studies will elucidate its functional implications in ROP.