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Objective: A wide range in prevalence rates of burnout among general practitioners (GPs) has been reported in various regions, with an increasing trend. This nationwide cross-sectional study aimed to estimate the prevalence and associated determinants of burnout in Czech GPs., Methods: 1000 randomly selected physicians from the Czech Society of General Practitioners (through a pseudorandom number generator) were emailed an online survey based on the Maslach Burnout Inventory - Human Services Survey. Data collection was performed between January and February 2023., Results: 331 questionnaires were obtained (227 females and 104 males, mean age - 49.9 years, the mean number of registered patients - 1951). 21.8 % of GPs scored a high level of burnout in all three of its dimensions and 23.9 % in no dimension at all. The most prevalent dimension was reduced personal accomplishment (PA, 56.2 %) followed by emotional exhaustion (EE, 50.2 %) and depersonalization (DP, 40.5 %). Reaching burnout in all three dimensions was significantly more frequent in males and in GPs registering a number of patients above the median. Increasing age and years of practice were protective factors for DP but risk factors for reduced PA. Employed GPs had lower EE scores than GP practice owners. The respondents' basic characteristics reflected their presence among Czech GPs, which testifies against selection bias., Conclusions: The high rate of burnout (∼22 %) should be addressed by promoting personal resources along with the perception of the importance of GPs in society. A sufficiently dense network of GPs should allow them to register a lower number of patients., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors.)

Normothermic ex vivo liver machine perfusion (NEVLP) has been developed to address the increasing organ shortage in liver transplantation, through optimal preservation, assessment, and conditioning of grafts from extended criteria donors. There remains a need to establish simple and standardized animal models that simulate clinical NEVLP to test novel therapies. Liver grafts from 36 Sprague-Dawley rats were perfused for 6 h in a dual-vessel NEVLP system with a Dulbecco's modified Eagles medium-based perfusate supplemented with rat plasma and erythrocytes. Varying doses of the clinically used vasodilator epoprostenol, Kupffer cell inhibitor glycine, and a Steen™-based perfusate were assessed. Perfusion pressures and bile production were recorded, and perfusate was analyzed for transaminase secretion. Tissue samples were evaluated histologically, and levels of cytokines and 8-Isoprostane were measured. Increasing levels of epoprostenol and the addition of glycine resulted in a stepwise decrease of transaminase secretion and improved bile production. Steen further decreased transaminase release and interleukin 1 beta levels. Liver grafts perfused with the optimized Steen-based protocol exhibited lowest levels of oxidative stress and best-preserved liver integrity. In conclusion, epoprostenol seemed to ameliorate liver function and prevent cellular damage beyond its vasodilatory effect, with glycine acting synergistically. The anti-inflammatory and antioxidative properties of Steen further improved the outcome of perfusion. Our rodent NEVLP system may be used to rapidly test new agents for the pharmacologic conditioning of livers and help translate findings from bench-to-bedside.

Background: When a partial liver graft is unable to meet the demands of the recipient, a clinical phenomenon, small-for-size syndrome (SFSS), may ensue. Clear definition, diagnosis, and management are needed to optimize transplant outcomes., Methods: A Consensus Scientific committee (106 members from 21 countries) performed an extensive literature review on specific aspects of SFSS, recommendations underwent blinded review by an independent panel, and discussion/voting on the recommendations occurred at the Consensus Conference., Results: The ideal graft-to-recipient weight ratio of ≥0.8% (or graft volume standard liver volume ratio of ≥40%) is recommended. It is also recommended to measure portal pressure or portal blood flow during living donor liver transplantation and maintain a postreperfusion portal pressure of <15 mm Hg and/or portal blood flow of <250 mL/min/100 g graft weight to optimize outcomes. The typical time point to diagnose SFSS is the postoperative day 7 to facilitate treatment and intervention. An objective 3-grade stratification of severity for protocolized management of SFSS is proposed., Conclusions: The proposed grading system based on clinical and biochemical factors will help clinicians in the early identification of patients at risk of developing SFSS and institute timely therapeutic measures. The validity of this newly created grading system should be evaluated in future prospective studies., Competing Interests: The authors declare no funding or conflicts of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Biliary atresia (BA) remains the number one indication for paediatric liver transplantation (LT) worldwide but is an uncommon indication for older LT recipients. The impact of recent donor allocation changes, pervasive organ shortage and evolving LT practices on the BA LT population is unknown., Methods: We identified patients who underwent LT between January 2010 and December 2021 using the UNOS database. We compared clinical outcomes between patients with BA and those with non-BA cholestatic liver disease. Groups were stratified by age, <12 years (allocated via PELD system) and ≥12 years (allocated via MELD system). Waitlist outcomes were compared using competing-risk regression analysis, graft survival rates were compared using Kaplan-Meier time-to-event analysis and Cox proportional hazards modelling provided adjusted estimates., Results: There were 2754 BA LT waitlist additions and 2206 BA LTs (1937 <12 years [younger], 269 ≥12 years [older]). There were no differences in waitlist mortality between BA and non-BA cholestatic patients. Among BA LT recipients, there were 441 (20.0%) living-donor liver transplantations (LDLT) and 611 (27.7%) split deceased-donor LTs. Five-year graft survival was significantly higher among BA versus non-BA cholestatic patients in the older group (88.3% vs. 79.5%, p < .01) but not younger group (89.3% vs. 89.5%). Among BA LT recipients, improved graft outcomes were associated with LDLT (vs. split LT: HR: 2, 95% CI: 1.03-3.91) and higher transplant volume (volume >100 vs. <40 BA LTs: HR: 3.41, 95% CI: 1.87-6.2)., Conclusion: Liver transplant outcomes among BA patients are excellent, with LDLT and higher transplant centre volume associated with optimal graft outcomes., (© 2023 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Anti-CD19 chimeric antigen receptor (CAR) T-cell therapy is a highly effective treatment option for patients with relapsed/refractory large B-cell lymphoma. However, widespread use is deterred by the development of clinically significant acute inflammatory toxicities, including cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS), that induce significant morbidity and require close monitoring. Identification of host biochemical signatures that predict the severity and time-to-onset of CRS and ICANS may assist patient stratification to enable timely mitigation strategies. Here, we report pretreatment host metabolites that are associated with CRS and ICANS induced by axicabtagene ciloleucel or tisagenlecleucel therapy. Both untargeted metabolomics analysis and validation using targeted assays revealed a significant association between the abundance of specific pretreatment biochemical entities and an increased risk and/or onset of clinically significant CRS (q < .1) and ICANS (q < .25). Higher pretreatment levels of plasma glucose and lower levels of cholesterol and glutamate were associated with a faster onset of CRS. In contrast, low baseline levels of the amino acids proline and glycine and the secondary bile acid isoursodeoxycholate were significantly correlated with clinically significant CRS. Lower concentration of the amino acid hydroxyproline was associated with higher grade and faster onset of ICANS, whereas low glutamine was negatively correlated with faster development of ICANS. Overall, our data indicate that the pretreatment host metabolome has biomarker potential in determining the risk of clinically significant CRS and ICANS, and may be useful in risk stratification of patients before anti-CD19 CAR T-cell therapy., (© 2023 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)

A straightforward and high yielding synthetic approach is employed to synthesize the novel 1H-1,2,3-triazole tethered pyrazolo[5,1-b]quinazoline hybrids 7(a-t) as new antimicrobial agents with two pharmacophore in the effective two step synthesis. The first step is the four component one-pot synthesis of highly functionalized pyrazolo[5,1-b]quinazolines 5(a-j) catalysed by TBAB, with the advantages of an environmentally benign reaction, high yielding, quick reaction time, and operational simplicity. In the subsequent stage, CuSO 4 /NaAsc system was employed to synthesize the 1H-1,2,3-triazole tethered pyrazolo[1,5-b]quinazoline hybrids as 1H-1,2,3-triazoles are the structures of great diversity and importance in diverse therapeutics containing numerous biological activities. The antimicrobial activity of all the synthesized hybrid compounds have been preliminary tested using the broth dilution technique against two gram-positive and two gram-negative bacterial strains as well as two fungal strains. In comparison to standard drugs, the majority of compounds exhibited good to moderate activity. Among the all the compounds, 7a (MIC 18.54 μM) against Pseudomonas aeruginosa, 7j (MIC 89.76 μM) against Bacillus subtilis as well as Rhizopus oryzae and 7t (MIC 84.88 μM) against Aspergillus parasiticus have remarkable antimicrobial potency as compared to standard drug., (© 2023. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Rationale: Although the mainstay of sepsis treatment is timely initiation of broad-spectrum antimicrobials, treatment delays are common, especially among patients who develop hospital-onset sepsis. The time of day has been associated with suboptimal clinical care in several contexts, but its association with treatment initiation among patients with hospital-onset sepsis is unknown. Objectives: Assess the association of time of day with antimicrobial initiation among ward patients with hospital-onset sepsis. Methods: This retrospective cohort study included ward patients who developed hospital-onset sepsis while admitted to five acute care hospitals in a single health system from July 2017 through December 2019. Hospital-onset sepsis was defined by the Centers for Disease Control and Prevention Adult Sepsis Event criteria. We estimated the association between the hour of day and antimicrobial initiation among patients with hospital-onset sepsis using a discrete-time time-to-event model, accounting for time elapsed from sepsis onset. In a secondary analysis, we fit a quantile regression model to estimate the association between the hour of day of sepsis onset and time to antimicrobial initiation. Results: Among 1,672 patients with hospital-onset sepsis, the probability of antimicrobial initiation at any given hour varied nearly fivefold throughout the day, ranging from 3.0% (95% confidence interval [CI], 1.8-4.1%) at 7 a.m. to 13.9% (95% CI, 11.3-16.5%) at 6 p.m., with nadirs at 7 a.m. and 7 p.m. and progressive decline throughout the night shift (13.4% [95% CI, 10.7-16.0%] at 9 p.m. to 3.2% [95% CI, 2.0-4.0] at 6 a.m.). The standardized predicted median time to antimicrobial initiation was 3.2 hours (interquartile range [IQR], 2.5-3.8 h) for sepsis onset during the day shift (7 a.m.-7 p.m.) and 12.9 hours (IQR, 10.9-14.9 h) during the night shift (7 p.m.-7 a.m.). Conclusions: The probability of antimicrobial initiation among patients with new hospital-onset sepsis declined at shift changes and overnight. Time to antimicrobial initiation for patients with sepsis onset overnight was four times longer than for patients with onset during the day. These findings indicate that time of day is associated with important care processes for ward patients with hospital-onset sepsis. Future work should validate these findings in other settings and elucidate underlying mechanisms to inform quality-enhancing interventions.

Objectives: Racial and ethnic minorities receive opioid prescriptions at lower rates and dosages than White patients. Though opioid stewardship interventions can improve or exacerbate these disparities, there is little evidence about these effects. We conducted a secondary analysis of a cluster-randomized controlled trial conducted among 438 clinicians from 21 emergency departments and 27 urgent care clinics. Our objective was to determine whether randomly allocated opioid stewardship clinician feedback interventions that were designed to reduce opioid prescriptions had unintended effects on disparities in prescribing by patient race and ethnicity., Methods: The primary outcome was likelihood of receiving a low-pill prescription (low ≤10 pills, medium 11-19 pills, high ≥20 pills). Generalized mixed-effects models were used to determine patient characteristics associated with low-pill prescriptions during the baseline period. These models were then used to determine whether receipt of a low-pill prescription varied by patient race or ethnicity during the intervention period between usual care and three opioid stewardship interventions: (1) individual audit feedback, (2) peer comparison feedback, and (3) combined (individual audit + peer comparison) feedback., Results: Compared with White patients, Black patients were more likely to receive a low-pill prescription during the baseline (adjusted odds ratio [OR] 1.18, 95% confidence interval [CI] 1.06-1.31, p = 0.002) and intervention (adjusted OR 1.43, 95% CI 1.07-1.91, p = 0.015). While combined feedback was associated with an overall increase in low-pill prescriptions as intended (adjusted OR 1.89, 95% CI 1.28-2.78, p = 0.001), there were no significant differences in treatment effects of any of the interventions by patient race and ethnicity., Conclusions: Combined individual audit and peer comparison feedback was associated with fewer opioid pills per prescription equally by patient race and ethnicity. However, the intervention did not significantly close the baseline disparity in prescribing by race., (© 2023 Society for Academic Emergency Medicine.)

Introduction: Elderly patients (≥65 years old) are increasingly undergoing liver transplantation and are more likely to be removed from the waitlist. Normothermic machine perfusion (NMP) holds promise in expanding the number of livers available for transplant and improving outcomes for marginal donors and recipients. We aimed to determine the impact of NMP on outcomes in elderly recipients at our institution and nationally using the UNOS database., Methods: The use of NMP on outcomes in elderly recipients was reviewed using both the UNOS/SRTR database (2016-2022) and institutional data (2018-2020). Characteristics and clinical outcomes were compared between the NMP and static cold (control) groups within both populations., Results: Nationally, using the UNOS/SRTR database, we identified 165 elderly recipients from 28 centers who received a liver allograft undergoing NMP and 4270 that underwent traditional cold static storage. NMP donors were older (48.3 vs. 43.4 years, p < 0.01), had similar rates of steatosis (8.5% vs 8.5%, p = 0.58), were more likely to be from a DCD (41.8% vs 12.3%, p < 0.01), and had a higher donor risk index (DRI; 1.70 vs. 1.60, p < 0.02). NMP recipients had similar age but had a lower MELD score at transplant (17.9 vs. 20.7, p = 0.01). Despite increased marginality of the donor graft, NMP recipients had similar allograft survival and decreased length of stay, even after accounting for recipient characteristics including MELD. Institutional data showed that 10 elderly recipients underwent NMP and 68 underwent cold static storage. At our institution, NMP recipients had a similar length of stay, rates of complications, and readmissions., Conclusions: NMP may mitigate donor risk factors that are relative contraindications for transplantation in elderly liver recipients, increasing the donor pool. The application of NMP in older recipients should be considered., (© 2023 The Authors. Artificial Organs published by International Center for Artificial Organ and Transplantation (ICAOT) and Wiley Periodicals LLC.)

Infused biologics, such as pegloticase, are a core component of managing uncontrolled gout, which is increasing in prevalence. Pegloticase is often the last line of therapy for patients with uncontrolled gout; therefore, achieving a successful course of treatment is critical. The infusion nurse's role in patient education, serum uric acid monitoring, and patient medication compliance is essential for ensuring patient safety and maximizing the number of patients who benefit from a full treatment course of pegloticase. Infusion nurses are on the front lines with patients and need to be educated on potential negative effects associated with the medications they infuse, such as infusion reactions, as well as risk management methods like patient screening and monitoring. Further, patient education provided by the infusion nurse plays a large role in empowering the patient to become their own advocate during pegloticase treatment. This educational overview includes a model patient case for pegloticase monotherapy, as well as one for pegloticase with immunomodulation and a step-by-step checklist for infusion nurses to refer to throughout the pegloticase infusion process. A video abstract is available for this article at http://links.lww.com/JIN/A105., (Copyright © 2023 The Authors. Published by Wolters Kluwer Health, Inc.)

» Avascular necrosis (AVN) of the humeral head is the result of ischemic injury to the epiphyseal bone leading to humeral head collapse and arthritis.» Common causes include trauma, chronic corticosteroid use, or systemic disease processes, such as sickle cell disease, systemic lupus erythematosus, or alcohol abuse.» Nonoperative treatment consists of risk factor management, physical therapy, anti-inflammatory medications, and activity modification.» Surgical treatment options include arthroscopic debridement, core decompression, vascularized bone grafts, and shoulder arthroplasty., Competing Interests: Disclosure: The Disclosure of Potential Conflicts of Interest forms are provided with the online version of the article (http://links.lww.com/JBJSREV/A977)., (Copyright © 2023 by The Journal of Bone and Joint Surgery, Incorporated.)

Background Globus pallidus interna (GPi) deep brain stimulation (DBS) is an established surgical procedure that confers a benefit in medication refractory dystonia. Patients with generalized dystonia require general anesthesia (GA) for the surgery as their movements may hinder the surgical procedure. General anesthetics tend to dampen the microelectrode recordings (MERs) from the GPi. Methods We describe our experience with a series of consecutive patients with dystonia who underwent bilateral GPi DBS using standard DBS and MER under GA using sevoflurane as the maintenance general anesthetic drug. All patients had Medtronic 3,387 leads implanted and connected to an RC battery. Patients underwent sequential programming of the DBS after the surgery. Results The mean age of the 13 patients who underwent DBS of the GPi for dystonia was 46.5 years with a range from 29 to 71 years. Every patient in our case series received various doses of (1.37% to 2.11%) inhaled sevoflurane for anesthesia maintenance. Sevoflurane provided adequate anesthesia and allowed accurate MERs from the GPi. No adverse effects were encountered. On follow-up and sequential DBS programming, patients had significant improvements in dystonia attesting to the accuracy of the electrode placements. Conclusions We report our experience using sevoflurane for maintenance of GA for bilateral GPi DBS for dystonia. The main benefits identified have been adequate anesthesia and reduction of dystonia-related movements to allow the performance of the DBS surgery. The MER signals from the GPi were not suppressed by sevoflurane. This allowed accurate mapping and placement of the DBS implants in the GPi., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, AlMajali et al.)

After a virtual congress in 2021 and a previous absence in 2020 because of the coronavirus disease 2019 pandemic, the 27th Annual Congress of the International Liver Transplantation Society was held from May 4 to 7, 2022, in a hybrid format in Istanbul, with 1123 (58% on-site) liver transplant professionals from 61 countries attending the meeting. The hybrid format successfully achieved a balance of much yearned-for "in-person interaction" and global online participation. Almost 500 scientific abstracts were presented. In this report, the Vanguard Committee aims to present a summary of key invited lectures and selected abstracts for the liver transplant community., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

An ultrasound-assisted green protocol for one-pot synthesis of a new series of pharmaceutically relevant pyrazolo quinoline derivatives (4a-t) were synthesized, characterized, and evaluated using DFT and biological activities. Pyrazolo quinoline derivatives (4a-t) were synthesized via a three-component tandem reaction of 1,3-dicarbonyl compound (1a-b), substituted aromatic aldehyde (2a-o), and 5-amino indazole (3a) in the presence of 1-butyl-3-methylimidazolium tetrafluoroborate [BMIM]BF 4 ionic liquid in ethanol at ambient conditions. The main purpose of the present work is selective functionalization of pyrazolo quinoline (4a-t) core excluding another potential parallel reaction under environmentally benign reaction conditions. The present protocol shows features such as amphiphilic behavior of ionic liquid during reaction transformation, and reusability of the [BMIM]BF 4 ionic liquid under mild reaction condition. All newly derived compounds were evaluated for their in vitro anti-inflammatory and antioxidant activity. Among them, compound 4c showed encouraging antioxidant activity compared with standard antioxidant ascorbic acid, and compounds 4n and 4r displayed very good anti-inflammatory activity compared with a standard drug. In this study, a theoretical computational density functional study was also executed to perform the geometry optimizations, frontier molecular orbital approach, and molecular electrostatic potential (MESP). The DFT study was carried out with the basis set DFT/B3LYP/6-31+G (d, p) level of theory. The quantum chemical descriptors (QCDS) and MESP diagrams were plotted to examine the biological reactivities of representative pyrazolo quinolines (4a-t)., (© 2022. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Background: Higher levels of physical activity are associated with improvements in cardiovascular health, and consensus guidelines recommend that individuals with or at risk for atherosclerotic cardiovascular disease (ASCVD) participate in regular physical activity. However, most adults do not achieve recommended levels of physical activity. Concepts from behavioral economics have been used to design scalable interventions that increase physical activity over short time periods, but the longer-term efficacy of these strategies is uncertain., Study Design and Objectives: BE ACTIVE (NCT03911141) is a pragmatic, virtual, randomized controlled trial designed to evaluate the effectiveness of 3 strategies informed by behavioral economic concepts to increase daily physical activity in patients with established ASCVD or 10-year ASCVD risk > 7.5% who are seen in primary care and cardiology clinics affiliated with the University of Pennsylvania Health System. Patients are contacted by email or text message, and complete enrollment and informed consent on the Penn Way to Health online platform. Patients are then provided with a wearable fitness tracker, establish a baseline daily step count, set a goal to increase daily step count by 33% to 50%, and are randomized 1:2:2:2 to control, gamification, financial incentives, or both gamification and financial incentives. Interventions continue for 12 months, with follow-up for an additional 6 months to evaluate the durability of behavior change. The trial has met its enrollment goal of 1050 participants, with a primary endpoint of change from baseline in daily steps over the 12-month intervention period. Key secondary endpoints include change from baseline in daily steps over the 6-month post-intervention follow-up period and change in moderate to vigorous physical activity over the intervention and follow-up periods. If the interventions prove effective, their effects on life expectancy will be compared with their costs in cost-effectiveness analysis., Conclusions: BE ACTIVE is a virtual, pragmatic randomized clinical trial powered to demonstrate whether gamification, financial incentives, or both are superior to attention control in increasing physical activity. Its results will have important implications for strategies to promote physical activity in patients with or at risk for ASCVD, as well as for the design and implementation of pragmatic virtual clinical trials within health systems., Competing Interests: Conflict of interest Dr. Fanaroff reports a career development grant from the American Heart Association. Dr. Patel is an employee of Ascension Health. Dr. Volpp is a co-owner of a behavioral economics consulting firm, VAL Health. All other authors report no relevant conflicts of interest., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Hospital readmission prediction models often perform poorly, but most only use information collected until the time of hospital discharge. In this clinical trial, we randomly assigned 500 patients discharged from hospital to home to use either a smartphone or wearable device to collect and transmit remote patient monitoring (RPM) data on activity patterns after hospital discharge. Analyses were conducted at the patient-day level using discrete-time survival analysis. Each arm was split into training and testing folds. The training set used fivefold cross-validation and then final model results are from predictions on the test set. A standard model comprised data collected up to the time of discharge including demographics, comorbidities, hospital length of stay, and vitals prior to discharge. An enhanced model consisted of the standard model plus RPM data. Traditional parametric regression models (logit and lasso) were compared to nonparametric machine learning approaches (random forest, gradient boosting, and ensemble). The main outcome was hospital readmission or death within 30 days of discharge. Prediction of 30-day hospital readmission significantly improved when including remotely-monitored patient data on activity patterns after hospital discharge and using nonparametric machine learning approaches. Wearables slightly outperformed smartphones but both had good prediction of 30-day hospital-readmission., (© 2023. The Author(s).)

Background and Aims: Identifying international differences in utilization and outcomes of liver transplantation (LT) after donation after circulatory death (DCD) donation provides a unique opportunity for benchmarking and population-level insight., Methods: Adult (≥18 years) LT data between 2008 and 2018 from the UK and US were used to assess mortality and graft failure after DCD LT. We used time-dependent Cox-regression methods to estimate hazard ratios (HR) for risk-adjusted short-term (0-90 days) and longer-term (90 days-5 years) outcomes., Results: One-thousand five-hundred-and-sixty LT receipts from the UK and 3426 from the US were included. Over the study period, the use of DCD livers increased from 15.7% to 23.9% in the UK compared to 5.1% to 7.6% in the US. In the UK, DCD donors were older (UK:51 vs. US:33 years) with longer cold ischaemia time (UK: 437 vs. US: 333 min). Recipients in the US had higher Model for End-stage Liver Disease (MELD) scores, higher body mass index, higher proportions of ascites, encephalopathy, diabetes and previous abdominal surgeries. No difference in the risk-adjusted short-term mortality or graft failure was observed between the countries. In the longer-term (90 days-5 years), the UK had lower mortality and graft failure (adj.mortality HR:UK: 0.63 (95% CI: 0.49-0.80); graft failure HR: UK: 0.72, 95% CI: 0.58-0.91). The cumulative incidence of retransplantation was higher in the UK (5 years: UK: 11.9% vs. 4.6%; p < .001)., Conclusions: For those receiving a DCD LT, longer-term post-transplant outcomes in the UK are superior to the US, however, significant differences in recipient illness, graft quality and access to retransplantation were seen between the two countries., (© 2023 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

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., (Copyright © 2023 the American College of Medical Quality.)

Background: Given the complexity of managing HCC, professional society guidelines advocate multidisciplinary care (MDC) for patients with HCC. However, implementation of MDC programs requires a significant investment of time and resources. We conducted a systematic review and meta-analysis to enumerate potential benefits of MDC for patients with HCC., Methods: We conducted a search of the PubMed/MEDLINE and EMBASE databases and national conference abstracts to identify studies published after January 2005 that reported early-stage presentation, treatment receipt, or overall survival among patients with HCC, stratified by MDC status. We calculated pooled risk ratios and HRs for clinical outcomes according to MDC receipt using the DerSimonian and Laird method for random effects models., Results: We identified 12 studies (n = 15,365 patients with HCC) with outcomes stratified by MDC status. MDC was associated with improved overall survival (HR = 0.63, 95% CI: 0.45-0.88); however, its association with curative treatment receipt was not statistically significant (risk ratio = 1.60, 95% CI: 0.89-2.89) and pooled estimates were limited by high heterogeneity (I2 > 90% for both). Studies (n = 3) were discordant regarding an association between MDC and time-to-treatment initiation. MDC was associated with early-stage HCC (risk ratio = 1.60, 95% CI: 1.12-2.29), suggesting possible referral bias contributing to improved outcomes. Limitations of studies also included risk of residual confounding, loss to follow-up, and data preceding the availability of immune checkpoint inhibitors., Conclusion: MDC for patients with HCC is associated with improved overall survival, underscoring the likely benefit of managing patients with HCC in a multidisciplinary care setting., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Association for the Study of Liver Diseases.)

The compatibility of drugs with excipients plays a crucial role in the prospective stability of pharmaceutical formulations. Apart from real-time stability studies, conventional analytical tools like DSC, FTIR, NMR, and chromatography help identify the possibilities of drug-excipient interactions. Machine learning can assist in developing a predictive tool for drug-excipient incompatibility. In the present work, PubChem Fingerprint is employed as the descriptor of compounds that thoroughly represents the drug's and excipient's chemistry. The 881-bit binary fingerprints of each drug and excipient make 1762 inputs, and one categorical output makes an instance in the dataset. A dataset of more than 3500 instances of drugs and excipients is carefully selected from peer-reviewed research papers. Rigorous training of the Artificial Neural Network (ANN) model was performed with maximum validation accuracy, minimum validation loss, and maximum validation precision as the checkpoints. The machine learning model (DE-Interact) was trained, achieving training and validation accuracies of 0.9930 and 0.9161, respectively. The performance of the DE-Interact model was evaluated by confirming three incompatible predictions by conventional analytical tools. Paracetamol with vanillin, paracetamol with methylparaben, and brinzolamide with polyethyleneglycol are these instances which are predicted as incompatible by the DE-Interact. DSC, FTIR, HPTLC, and HPLC analysis confirm the prediction. The present work offers a reliable DE-Interact tool for quick referencing while selecting excipients in formulation design., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: Obesity is strongly associated with cardiovascular disease, particularly through its effects on blood pressure. Though maintaining a negative caloric balance leads to weight loss, many patients struggle to adhere to low calorie diets over the long term. Time-restricted eating, a subtype of intermittent fasting (IF), may be an easier dietary pattern for patients to initiate and maintain. We tested the feasibility of a bidirectional texting strategy to help patients with obesity and hypertension initiate and maintain time-restricted eating, and whether a commitment device, a pledge to behave in a certain way in the future while making nonadherence costlier, would increase adherence beyond bidirectional texting., Methods: Patients with obesity and hypertension seen in cardiology clinics were provided education on time-restricted eating and randomized to a commitment device versus attention control. Attention control consisted of daily bidirectional text messages asking whether patients adhered to IF and weekly text messages asking participants to send their weight and blood pressure. The commitment device involved the same text messages as attention control, plus a commitment contract, setting of implementation intentions with respect to details of time-restricted eating, and involvement of a support partner who received weekly updates on the participant's adherence to time-restricted eating. The intervention lasted 12 weeks, followed by a 6-week follow-up period. The primary outcome was days per week adherent to time-restricted eating over the 18-week study period, measured by daily self-report. We also compared change from baseline weight and blood pressure between randomized groups., Results: A total of 37 patients were randomized and started the study-20 to attention control and 17 to the commitment device. Mean age was 60 years old, and mean BMI was 38.4 kg/m 2 . Over the 18-week study period, the mean ± standard deviation (SD) number of days per week adherent to time-restricted eating was 4.7 ± 1.9 in the control arm and 5.4 ± 1.7 in the intervention arm (P = .23). Mean systolic blood pressure declined from 135 to 128 mm Hg among all participants (P = .006) with no difference between groups in change from baseline blood pressure (P = .74). Weight decreased from 229 to 223 pounds among all participants (P = .25) with no significant difference between groups in change from baseline weight (P = .84)., Conclusions: A bidirectional texting strategy was feasible for helping patients with obesity and hypertension initiate and adhere to time-restricted eating. Adding a commitment device to bidirectional texting did not increase adherence to time-restricted eating compared with attention control, nor were there significant between group changes in blood pressure or weight, but these comparisons were underpowered. A larger randomized trial of the effect of this scalable intervention, compared with usual care, on blood pressure and weight among patients with obesity and hypertension is warranted., Clinical Trials Registration: clinicaltrials.gov; unique identifier: NCT04836312., Competing Interests: Disclosures Dr Fanaroff reports research grants from the American Heart Association and National Institutes of Health. Dr Adusumalli reports full-time employment by CVS Health Corporation. Dr Chokshi reports research grants from Independence Blue Cross and National Institutes of Health. Dr Patel reports full-time employment by Ascension Health. All other authors report no relevant disclosures., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Purpose: To evaluate the feasibility, effectiveness, and outcomes of percutaneous cholecystostomy drain internalization in patients with calculous cholecystitis who were not surgical candidates., Materials and Methods: Percutaneous cystic duct interventions were attempted in 17 patients (with the intent to place dual cholecystoduodenal stents) who were deemed unfit for surgery and had previously undergone percutaneous cholecystostomies for acute calculous cholecystitis. Baseline demographics, technical success, time from percutaneous cholecystostomy to internalization (dual cholecystoduodenal stent placement), stent patency duration, and adverse event rates were evaluated., Results: Fifteen (88%) of 17 procedures to cross the cystic duct were technically successful. Of these 17 patients, 13 (76%) underwent successful placement of dual cholecystoduodenal stents. Two of these 13 patients (who had successful dual cholecystoduodenal stent placement) needed repeat percutaneous cholecystostomy drains (1 patient had stent migration leading to recurrent cholecystitis, and the other had a perihepatic biloma). The 1-year patency rate was 77% (95% CI, 47%-100%)., Conclusions: Dual cholecystoduodenal stent placement in nonsurgical patients is a technically feasible treatment option with the goal to remove percutaneous cholecystostomy drains., (Copyright © 2023 SIR. Published by Elsevier Inc. All rights reserved.)

Background: The recent trend of organ procurement organizations (OPOs) employing independent surgeons for organ procurement has been developed with the goal of improving the supply of suitable organs for transplantation. We investigated the effects that the addition of an OPO-employed, organ-procurement specialist has on liver allograft discard rate, marginal organ utilization, and graft survival., Methods: Organ Procurement and Transplant Network and OPO data were retrospectively studied between April 1, 2014' and July 31, 2019' within the Southwest Transplant Alliance donor service area. Liver procurements with an OPO-surgeon present (OPO-Present) were compared to those without the involvement of an OPO surgeon (OPO-Absent). Donor and recipient characteristics as well as outcomes were analyzed across groups using propensity score matching., Results: In total 869 OPO-Present liver allografts had similar rates of discard (5.2%) compared to 771 OPO-Absent livers (5.8%). However, after adjusting for donor risk, OPO-Present livers had a lower propensity of discard compared to OPO-Absent (3.4% versus 7.6%, P < 0.05). OPO-Present livers were more likely to be shared nationally (11.0% versus 4.8%, P < 0.001). Outcome analysis showed allograft survival of OPO-Present livers at 5 y was comparable to OPO-Absent livers (79.5% versus 80%, P = 0.34)., Conclusions: The presence of an OPO surgeon was associated with decreased liver allograft discard and increased utilization of marginal donor organs. The OPO surgeon's presence represents a potential strategy to increase organ utilization nationally., Competing Interests: M.M.C. is currently employed by Transmedics Inc. The other authors declare no conflicts of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Pediatric recipients of living donor kidneys have a low rate of delayed graft function (DGF). We examined the incidence, risk factors and outcomes of DGF in pediatric patients who received a living donor allograft., Methods: The STARfile was queried to examine all pediatric patients transplanted with a living donor kidney between 2000 and 2020. Donor and recipient demographic data were examined, as were survival and outcomes. Recipients were stratified into DGF and no DGF groups. DGF was defined as the need for dialysis within the first week after transplant., Results: 6480 pediatric patients received a living donor (LD) kidney transplant during the study period. 269 (4.2%) developed DGF post-transplant. Donors were similar in age, creatinine, and cold ischemia time. Recipients of kidneys with DGF were similar in age, sensitization status and HLA mismatch. Focal segmental glomerulosclerosis (FSGS) was the most common diagnosis in recipients with DGF, and allograft thrombosis was the most common cause of graft loss in this group. Small recipients (weight < 15 kg) were found to have a significantly higher rate of DGF. Length of stay doubled in recipients with DGF, and rejection rates were higher post-transplant. Recipients of LD kidneys who developed DGF had significantly worse 1 year allograft survival (67% vs. 98%, p < .0001)., Conclusions: Pediatric living donor kidney transplant recipients who experience DGF have significantly poorer allograft survival. Optimizing the donor and recipient matching to avoid compounding risks may allow for better outcomes., (© 2022 Wiley Periodicals LLC.)

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.

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.

Increased consumption of dietary pulse protein has been shown to assist in body weight regulation and improve a range of metabolic health outcomes. We investigated if the exchange of casein for yellow pea protein (YPPN) in an obese-inducing maternal diet throughout pregnancy and lactation offered protection against obesity and dyslipidemia in offspring. Sixty female Sprague Dawley rats were fed a low-calorie control diet (CON), a high-caloric obesity-inducing diet (with casein protein (CP), HC-CP), or an isocaloric/macronutrient-matched HC diet supplemented with YPPN isolate (HC-PPN) in pre-pregnancy, gestation, and lactation. Body weight (BW) and metabolic outcomes were assessed in male and female offspring at weaning and in adulthood after consuming the CON diet in the postnatal period. Consumption of the HC-PPN diet did not protect against maternal obesity but did improve reproductive success compared with the HC-CP group (72.7% versus 43.7%) and reduced total energy, fat, and protein in maternal milk. Male, but not female, offspring from mothers fed the HC-CP diet demonstrated hyperphagia, obesity, dyslipidemia, and hepatic triglyceride (TG) accumulation as adults compared with CON offspring. Isocaloric exchange of CP for YPPN in a high-calorie obese-inducing diet did not protect against obesity but did improve several aspects of lipid metabolism in adult male offspring including serum total cholesterol, LDL/VLDL cholesterol, triglycerides (TGs), and hepatic TG concentration. Our results suggest that the exchange of CP for YPPN in a maternal obese-inducing diet selectively protects male offspring from the malprogramming of lipid metabolism in adulthood.

Background: Despite most liver transplants in North America being from deceased donors, the number of living donor liver transplants has increased over the last decade. Although outcomes of liver retransplantation after deceased donor liver transplantation have been widely published, outcomes of retransplant after living donor liver transplant need to be further elucidated., Method: We aimed to compare waitlist outcomes and survival post-retransplant in recipients of initial living or deceased donor grafts. Adult liver recipients relisted at University Health Network between April 2000 and October 2020 were retrospectively identified and grouped according to their initial graft: living donor liver transplants or deceased donor liver transplant. A competing risk multivariable model evaluated the association between graft type at first transplant and outcomes after relisting. Survival after retransplant waitlisting (intention-to-treat) and after retransplant (per protocol) were also assessed. Multivariable Cox regression evaluated the effect of initial graft type on survival after retransplant., Results: A total of 201 recipients were relisted (living donor liver transplants, n = 67; donor liver transplants, n = 134) and 114 underwent retransplant (living donor liver transplants, n = 48; deceased donor liver transplants, n = 66). The waitlist mortality with an initial living donor liver transplant was not significantly different (hazard ratio = 0.51; 95% confidence interval, 0.23-1.10; P = .08). Both unadjusted and adjusted graft loss risks were similar post-retransplant. The risk-adjusted overall intention-to-treat survival after relisting (hazard ratio = 0.76; 95% confidence interval, 0.44-1.32; P = .30) and per protocol survival after retransplant (hazard ratio:1.51; 95% confidence interval, 0.54-4.19; P = .40) were equivalent in those who initially received a living donor liver transplant., Conclusion: Patients requiring relisting and retransplant after either living donor liver transplants or deceased donor liver transplantation experience similar waitlist and survival outcomes., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Genomic medicine, an emerging medical discipline, applies the principles of evolution, developmental biology, functional genomics, and structural genomics within clinical care. Enabling widespread adoption and integration of genomic medicine into clinical practice is key to achieving precision medicine. We delineate a biological framework defining diagnostic utility of genomic testing and map the process of genomic medicine to inform integration into clinical practice. This process leverages collaboration and collective cognition of patients, principal care providers, clinical genomic specialists, laboratory geneticists, and payers. We detail considerations for referral, triage, patient intake, phenotyping, testing eligibility, variant analysis and interpretation, counseling, and management within the utilitarian limitations of health care systems. To reduce barriers for clinician engagement in genomic medicine, we provide several decision-making frameworks and tools and describe the implementation of the proposed workflow in a prototyped electronic platform that facilitates genomic care. Finally, we discuss a vision for the future of genomic medicine and comment on areas for continued efforts., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Handra, Elbert, Gazzaz, Moller-Hansen, Hyunh, Lee, Boerkoel, Alderman, Anderson, Clarke, Hamilton, Hamman, Hughes, Ip, Langlois, Lee, Li, Mackenzie, Patel, Prentice, Sangha, Sato, Seath, Seppelt, Swenerton, Warnock, Zambonin, Boerkoel, Chin and Armstrong.)

Many countries curate national registries of liver transplant (LT) data. These registries are often used to generate predictive models; however, potential performance and transferability of these models remain unclear. We used data from 3 national registries and developed machine learning algorithm (MLA)-based models to predict 90-day post-LT mortality within and across countries. Predictive performance and external validity of each model were assessed. Prospectively collected data of adult patients (aged ≥18 years) who underwent primary LTs between January 2008 and December 2018 from the Canadian Organ Replacement Registry (Canada), National Health Service Blood and Transplantation (United Kingdom), and United Network for Organ Sharing (United States) were used to develop MLA models to predict 90-day post-LT mortality. Models were developed using each registry individually (based on variables inherent to the individual databases) and using all 3 registries combined (variables in common between the registries [harmonized]). The model performance was evaluated using area under the receiver operating characteristic (AUROC) curve. The number of patients included was as follows: Canada, n = 1214; the United Kingdom, n = 5287; and the United States, n = 59,558. The best performing MLA-based model was ridge regression across both individual registries and harmonized data sets. Model performance diminished from individualized to the harmonized registries, especially in Canada (individualized ridge: AUROC, 0.74; range, 0.73-0.74; harmonized: AUROC, 0.68; range, 0.50-0.73) and US (individualized ridge: AUROC, 0.71; range, 0.70-0.71; harmonized: AUROC, 0.66; range, 0.66-0.66) data sets. External model performance across countries was poor overall. MLA-based models yield a fair discriminatory potential when used within individual databases. However, the external validity of these models is poor when applied across countries. Standardization of registry-based variables could facilitate the added value of MLA-based models in informing decision making in future LTs., (Copyright © 2022 American Society of Transplantation & American Society of Transplant Surgeons. Published by Elsevier Inc. All rights reserved.)

Opioid misuse represents a major public health issue in the United States. One driver is overprescription for acute pain, with the size of initial prescription associated with subsequent long-term use. However, little work has been done to elicit clinician feedback about interventions to reduce opioid prescribing. To address this knowledge gap, qualitative analyses were conducted with clinicians who participated in a randomized controlled trial in which clinicians received monthly emailed feedback notifications about their opioid prescribing behaviors. Semistructured telephone interviews were conducted (N = 12) with urgent care (N = 7) and emergency department (N = 5) clinicians who participated in the trial between November 2020 and April 2021. Clinicians appreciated feedback about their prescribing behavior and found comparative data with peer clinicians to be most useful. Sharing opioid prescribing feedback data with clinicians can be an acceptable way to address opioid prescribing among emergency and urgent care clinicians., (Copyright © 2023 the American College of Medical Quality.)

Objectives: Accurate analysis of preoperative shoulder pain and function is important for understanding treatment efficacy and producing high-quality research. Oftentimes, preoperative patient-reported outcomes (PROs) are missing. Therefore the accuracy of recalled preoperative PROs may be important. We investigate the ability of patients who underwent rotator cuff repair (RCR) or shoulder arthroplasty (TSA) to recall their preoperative PROs., Methods: We identified 145 patients who underwent either RCR or TSA and had preoperative PROs. All patients completed the ASES, SANE, SST, and VAS surveys within 3 months prior to surgery. Patients were contacted between one and four years after surgery and asked to recall their baseline pain and shoulder function prior to surgery. The mean difference was calculated by determining the difference between the mean recalled score and the mean actual score. Intraobserver reliability analysis was performed, comparing recall and actual score for each using the 2-way mixed-effects intraclass correlation coefficient (ICC) model. The ICC values > 0.75 were considered excellent, values between 0.4 and 0.75 were considered moderate, and values of < 0.4 demonstrated a weak agreement., Results: For patients who underwent RCR, the mean differences between actual and recalled ASES, SANE, SST and VAS pain were 6.3 ( P=0.004 ), 2.0 ( P=0.155 ), -0.04 ( P=0.625 ) and - 1.0 ( P<0.001 ), respectively. In patients who underwent TSA, the mean differences between actual and recalled ASES, SANE, SST and VAS pain were 4.5 ( P =0.038 ), -3.9 ( P=0.262 ), -1.2 ( P=0.001 ) and -1.5 ( P<0.001 ), respectively. ASES, SST, and VAS show moderate reliability, and SANE reliability was weak in both RCR and TSA populations. Patients had a tendency to recall higher pain scores than actual preoperative pain scores., Conclusion: In patients who underwent RCR or TSA, there was too much variability between individual patient's ability to accurately recall preoperative pain and function to reliably use recall data for research purposes.

Importance: Statins reduce the risk of major adverse cardiovascular events, but less than one-half of individuals in America who meet guideline criteria for a statin are actively prescribed this medication., Objective: To evaluate whether nudges to clinicians, patients, or both increase initiation of statin prescribing during primary care visits., Design, Setting, and Participants: This cluster randomized clinical trial evaluated statin prescribing of 158 clinicians from 28 primary care practices including 4131 patients. The design included a 12-month preintervention period and a 6-month intervention period between October 19, 2019, and April 18, 2021., Interventions: The usual care group received no interventions. The clinician nudge combined an active choice prompt in the electronic health record during the patient visit and monthly feedback on prescribing patterns compared with peers. The patient nudge was an interactive text message delivered 4 days before the visit. The combined nudge included the clinician and patient nudges., Main Outcomes and Measures: The primary outcome was initiation of a statin prescription during the visit., Results: The sample comprised 4131 patients with a mean (SD) age of 65.5 (10.5) years; 2120 (51.3%) were male; 1210 (29.3%) were Black, 106 (2.6%) were Hispanic, 2732 (66.1%) were White, and 83 (2.0%) were of other race or ethnicity, and 933 (22.6%) had atherosclerotic cardiovascular disease. In unadjusted analyses during the preintervention period, statins were prescribed to 5.6% of patients (105 of 1876) in the usual care group, 4.8% (97 of 2022) in the patient nudge group, 6.0% (104 of 1723) in the clinician nudge group, and 4.7% (82 of 1752) in the combined group. During the intervention, statins were prescribed to 7.3% of patients (75 of 1032) in the usual care group, 8.5% (100 of 1181) in the patient nudge group, 13.0% (128 of 981) in the clinician nudge arm, and 15.5% (145 of 937) in the combined group. In the main adjusted analyses relative to usual care, the clinician nudge significantly increased statin prescribing alone (5.5 percentage points; 95% CI, 3.4 to 7.8 percentage points; P = .01) and when combined with the patient nudge (7.2 percentage points; 95% CI, 5.1 to 9.1 percentage points; P = .001). The patient nudge alone did not change statin prescribing relative to usual care (0.9 percentage points; 95% CI, -0.8 to 2.5 percentage points; P = .32)., Conclusions and Relevance: Nudges to clinicians with and without a patient nudge significantly increased initiation of a statin prescription during primary care visits. The patient nudge alone was not effective., Trial Registration: ClinicalTrials.gov Identifier: NCT04307472.

Objective: The objective of this pilot study was to examine the feasibility of a remote physical activity monitoring program, quantify baseline activity levels, and examine predictors of activity among rurally residing adults with Parkinson disease (PD) or stroke., Design: Thirty-day observational study. Participants completed standardized assessments, connected a wearable device, and synced daily step counts via a remote monitoring platform., Setting: Community-based remote monitoring., Participants: Rurally residing adults with PD or stroke enrolled in the Veterans Health Administration., Intervention: N/A., Main Outcome Measures: Feasibility was evaluated using recruitment data (response rates), study completion (completed assessments and connected the wearable device), and device adherence (days recording ≥100 steps). Daily step counts were examined descriptively. Predictors of daily steps were explored across the full sample, then by diagnosis, using linear mixed-effects regression analyses., Results: Forty participants (n=20 PD; n=20 stroke) were included in the analysis with a mean (SD) age of 72.9 (7.6) years. Participants resided 252.6 (105.6) miles from the coordinating site. Recruitment response rates were 11% (PD) and 6% (stroke). Study completion rates were 71% (PD) and 80% (stroke). Device adherence rates were 97.0% (PD) and 95.2% (stroke). Participants with PD achieved a median [interquartile range] of 2618 [3896] steps per day and participants with stroke achieved 4832 [7383] steps. Age was the only significant predictor of daily steps for the full sample (-265 steps, 95% confidence interval [-407, -123]) and by diagnosis (PD, -175 steps, [-335, -15]; stroke, -357 steps [-603, -112])., Conclusions: A remote physical activity monitoring program for rurally residing individuals with PD or stroke was feasible. This study establishes a model for a scalable physical activity program for rural, older populations with neurologic conditions from a central coordinating site.

Background & Aims: Adult-to-adult living donor liver transplantation (LDLT) offers an opportunity to decrease the liver transplant waitlist and reduce waitlist mortality. We sought to compare donor and recipient characteristics and post-transplant outcomes after LDLT in the US, the UK, and Canada., Methods: This is a retrospective multicenter cohort-study of adults (≥18-years) who underwent primary LDLT between Jan-2008 and Dec-2018 from three national liver transplantation registries: United Network for Organ Sharing (US), National Health Service Blood and Transplantation (UK), and the Canadian Organ Replacement Registry (Canada). Patients undergoing retransplantation or multi-organ transplantation were excluded. Post-transplant survival was evaluated using the Kaplan-Meier method, and multivariable adjustments were performed using Cox proportional-hazards models with mixed-effect modeling., Results: A total of 2,954 living donor liver transplants were performed (US: n = 2,328; Canada: n = 529; UK: n = 97). Canada has maintained the highest proportion of LDLT utilization over time (proportion of LDLT in 2008 - US: 3.3%; Canada: 19.5%; UK: 1.7%; p <0.001 - in 2018 - US: 5.0%; Canada: 13.6%; UK: 0.4%; p <0.001). The 1-, 5-, and 10-year patient survival was 92.6%, 82.8%, and 70.0% in the US vs. 96.1%, 89.9%, and 82.2% in Canada vs. 91.4%, 85.4%, and 66.7% in the UK. After adjustment for characteristics of donors, recipients, transplant year, and treating transplant center as a random effect, all countries had a non-statistically significantly different mortality hazard post-LDLT (Ref US: Canada hazard ratio 0.53, 95% CI 0.28-1.01, p = 0.05; UK hazard ratio 1.09, 95% CI 0.59-2.02, p = 0.78)., Conclusions: The use of LDLT has remained low in the US, the UK and Canada. Despite this, long-term survival is excellent. Continued efforts to increase LDLT utilization in these countries may be warranted due to the growing waitlist and differences in allocation that may disadvantage patients currently awaiting liver transplantation., Lay Summary: This multicenter international comparative analysis of living donor liver transplantation in the United States, the United Kingdom, and Canada demonstrates that despite low use of the procedure, the long-term outcomes are excellent. In addition, the mortality risk is not statistically significantly different between the evaluated countries. However, the incidence and risk of retransplantation differs between the countries, being the highest in the United Kingdom and lowest in the United States., Competing Interests: Conflict of interest Gonzalo Sapisochin discloses consultancy for Astra-Zeneca, Roche, Novartis, and Integra. Gonzalo Sapisochin has received financial compensation for talks for Roche, Astra-Zeneca, Chiesi, and Integra. Gonzalo Sapisochin has received a grant from Roche. None of the other authors have any conflicts of interest to declare. Please refer to the accompanying ICMJE disclosure forms for further details., (Copyright © 2022 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)

Objective: To evaluate the impact of implementing commercial whole exome sequencing (WES) and targeted gene panel testing in pregnancies with fetal anomalies., Methods: A retrospective chart review of 124 patients with sequencing performed by commercial laboratories., Results: The diagnostic yield of WES and panel testing was 21.5% and 26%, respectively, based on likely pathogenic (LP) or pathogenic (P) variants. Forty-two percent of exomes and 32% of panels analysed had one or more variants of uncertain significance (VUS) reported. A multidisciplinary in-depth review of the fetal phenotype, disease phenotype, variant data, and, in some patients, additional prenatal or postnatal investigations increased the diagnostic yield by 5% for exome analysis and 6% for panel analysis., Conclusions: The diagnostic yield of WES and panel testing combined was 23% based on LP and P variants. Although the reporting of VUS contributed to a 5% increase in diagnostic yield for WES and 6% for panels, the large number of VUS reported by commercial laboratories has significant resource implications. Our results support the need for greater adherence to the recommendations on the prenatal reporting of VUS and the importance of a multidisciplinary approach that brings together clinical and laboratory expertise in prenatal genetics and genomics., (© 2022 John Wiley & Sons Ltd.)

Background: Early serious illness conversations (SICs) about goals of care and prognosis improve mood, quality of life, and end-of-life care quality. Algorithm-based behavioral nudges to oncologists increase the frequency and timeliness of such conversations. However, clinicians' perspectives on such nudges are unknown. Design: Qualitative study consisting of semistructured interviews among medical oncology clinicians who participated in a stepped-wedge cluster randomized trial of Conversation Connect, an algorithm-based intervention consisting of behavioral nudges to promote early SICs in the outpatient oncology setting. Results: Of 79 eligible oncology clinicians, 56 (71%) were approached to participate in interviews and 25 (45%) accepted. Key facilitators to algorithm-based nudges included prompting documentation of conversations, peer comparisons, performance reports, and validating norms around early conversations. Barriers included cancer-specific heterogeneity in algorithm performance and the frequency and tone of text messages. Areas of improvement included utilizing different information channels, identifying patients earlier in the disease trajectory, and incorporating patient-targeted messaging that emphasizes the value of early conversations. Conclusions: Oncology clinicians identified key facilitators and barriers to Conversation Connect. These insights inform future algorithm-based supportive care interventions in oncology. Controlled trial (NCT03984773).

Background and Aims: Following liver resection (LR) for HCC, the likelihood of survival is dynamic, in that multiple recurrences and/or metastases are possible, each having variable impacts on outcomes. We sought to evaluate the natural progression, pattern, and timing of various disease states after LR for HCC using multistate modeling and to create a practical calculator to provide prognostic information for patients and clinicians., Approach and Results: Adult patients undergoing LR for HCC between January 2000 and December 2018 were retrospectively identified at a single center. Multistate analysis modeled post-LR tumor progression by describing transitions between distinct disease states. In this model, the states included surgery, intrahepatic recurrence (first, second, third, fourth, fifth), distant metastasis with or without intrahepatic recurrence, and death. Of the 486 patients included, 169 (34.8%) remained recurrence-free, 205 (42.2%) developed intrahepatic recurrence, 80 (16.5%) developed distant metastasis, and 32 (7%) died. For an average patient having undergone LR, there was a 33.1% chance of remaining disease-free, a 31.0% chance of at least one intrahepatic recurrence, a 16.3% chance of distant metastasis, and a 19.8% chance of death within the first 60 months post-LR. The transition probability from surgery to first intrahepatic recurrence, without a subsequent state transition, increased from 3% (3 months) to 17.4% (30 months) and 17.2% (60 months). Factors that could modify these probabilities included tumor size, satellite lesions, and microvascular invasion. The online multistate model calculator can be found on https://multistatehcc.shinyapps.io/home/., Conclusions: In contrast to standard single time-to-event estimates, multistate modeling provides more realistic prognostication of outcomes after LR for HCC by taking into account many postoperative disease states and transitions between them. Our multistate modeling calculator can provide meaningful data to guide the management of patients undergoing postoperative surveillance and therapy., (© 2022 American Association for the Study of Liver Diseases.)

Objectives: This investigation was aimed at designing an effective mucoadhesive microemulsion system to accomplish higher brain uptake of curcumin through intranasal route., Materials and Methods: Mucoadhesive microemulsion of curcumin (MMEC) was developed using screened oil, surfactant, and co-surfactant by Box-Behnken design and was evaluated for mucoadhesion, stability, and naso-ciliotoxicity study. Comparative brain uptake of curcumin after nasal administration of MMEC and polycarbophil curcumin gel and intravenous administration of plain curcumin solution was studied by performing bio-distribution study in Swiss albino rats., Results: The results showed that all formulation variables i.e., the amount of capmul MCM (X1), S mix (accenon CC: transcutol P) (X2) and percentage of aqueous. Polycarbophil (X3) had a significant effect (p<0.05) on the responses. The developed MMEC was stable and non-ciliotoxic with 66.74 ± 3.46 nm and 98.58% ± 1.21 as average globule size and drug content, respectively. Polydispersibility index (0.133 ± 0.17) data and transmission electron microscopy study depicted the narrow size distribution of MMEC. Furthermore, following a comparative investigation of the brain uptake of curcumin among MMEC, plain drug gel and intravenous administration at 2.86 mg/kg, more brain uptake of curcumin was demonstrated for MMEC over intravenous application. Moreover, curcumin uptake in olfactory bulb after nasal administration of MMEC (31.11 ± 1.6) was than 9.44 times higher than intravenous injection of curcumin solution (3.25 ± 1.01). Area under curve represents the ratio of 2.86 mg/kg in brain tissue to plasma acquired afterward(s) the intranasal injection of MMEC (and it) was essentially greater than after the intravenous administration of curcumin solution., Conclusion: Findings of the investigation revealed that optimal MMEC and intranasal route may be considered to be promising and an alternative approach for brain targeting of curcumin., Competing Interests: Conflict of Interest: No conflict of interest was declared by the authors., (©Turk J Pharm Sci, Published by Galenos Publishing House.)

The discovery of humans with monogenic disorders has a rich history of generating new insights into biology. Here we report the first human identified with complete deficiency of nuclear factor of activated T cells 1 (NFAT1). NFAT1, encoded by NFATC2, mediates calcium-calcineurin signals that drive cell activation, proliferation, and survival. The patient is homozygous for a damaging germline NFATC2 variant (c.2023&#95;2026delTACC; p.Tyr675Thrfs∗18) and presented with joint contractures, osteochondromas, and recurrent B-cell lymphoma. Absence of NFAT1 protein in chondrocytes caused enrichment in prosurvival and inflammatory genes. Systematic single-cell-omic analyses in PBMCs revealed an environment that promotes lymphomagenesis with accumulation of naïve B cells (enriched for oncogenic signatures MYC and JAK1), exhausted CD4+ T cells, impaired T follicular helper cells, and aberrant CD8+ T cells. This work highlights the pleiotropic role of human NFAT1, will empower the diagnosis of additional patients with NFAT1 deficiency, and further defines the detrimental effects associated with long-term use of calcineurin inhibitors., (© 2022 by The American Society of Hematology.)

Secondhand smoke (SHS), composed of mainstream and sidestream smoke, is a known human carcinogen. It contains a variety of harmful substances at even higher concentrations than mainstream smoke itself, which is inhaled during firsthand smoking. Exposure to SHS, affecting more than a third of the worldwide population, increases the likelihood of lung cancer by roughly 30%, with specific contributions depending on the histological type of cancer. This study aimed to present the harmful potential of SHS through case reports and describe the burden of SHS via a literature review. From a collection of lung cancer case reports occurring in never smokers from the Olomouc district over the last 10 years, 2 cases with no risk factors for lung cancer except for significant exposure to SHS were identified. Both cases were of young women who lived in households where their parents smoked during childhood. They suffered from rarer histological types of lung cancer in which the association with SHS has not yet been analyzed. As the literature confirms, SHS has the most adverse effects in individuals exposed during childhood. It is necessary to both take measures to reduce the prevalence of SHS, especially among children in households and pay due attention to the smoking history of patients, including current and previous exposure to SHS, when obtaining anamnestic data. Furthermore, the effect of SHS on rarer histological types of lung cancer should be studied.