Radiologists predict differential resource utilization but not clinical outcome in emergency department patients imaged with ultrasound for right upper quadrant pain.

PURPOSE: Radiologists with diverse training, specialization, and habits interpret imaging in the Emergency Department. It is necessary to understand if their variation predicts differential value. The purpose of this study was to determine whether attending radiologist variation predicts major clinical outcomes in adult Emergency Department patients imaged with ultrasound for right upper quadrant pain. METHODS: Consecutive ED patients imaged with ultrasound for RUQ pain from 10/8/2016 to 8/10/2022 were included (N = 7097). The primary outcome was prediction of hospital admission by signing attending radiologist. Secondary outcomes included: ED and hospital length of stay (LOS), 30-day mortality, 30-day re-presentation rate, subspecialty consultation, advanced imaging follow up (HIDA, MRI, CT), and intervention (ERCP, drainage or surgery). Sample size was determined a priori (detectable effect size: w = 0.06). Data were adjusted for demographic data, Elixhauser comorbidities, number of ED visits in prior year, clinical data, and system factors (38 covariates). P-values were corrected for multiple comparisons (false discovery rate-adjusted p-values). RESULTS: The included ultrasounds were read by 35 radiologists (median exams/radiologist: 145 [74.5-241.5]). Signing radiologist did not predict hospitalization (p = 0.85), abdominopelvic surgery or intervention within 30 days, re-presentation to the Emergency Department within 30 days, or subspecialty consultation. Radiologist did predict difference in Emergency Department length of stay (p < 0.001) although this difference was small and imprecise. HIDA was mentioned variably by radiologists (range 0-19%, p < 0.001), and mention of HIDA in the ultrasound report increased 10-fold the odds of HIDA being performed in the next 72 h (odds ratio 10.4 [8.0-13.4], p < 0.001). CONCLUSION: Radiologist variability did not predict meaningful outcome differences for patients with right upper quadrant pain undergoing ultrasound in the Emergency Department, but when radiologists mention HIDA in their reports, it predicts a 10-fold increase in the odds a HIDA is performed. Radiologists are relied on for interpretation that shapes subsequent patient care, and it is important to consider how radiologist variability can influence both outcome and resource utilization.

Long-Term Regret and Satisfaction With Decision Following Gender-Affirming Mastectomy.

Importance: There has been increasing legislative interest in regulating gender-affirming surgery, in part due to the concern about decisional regret. The regret rate following gender-affirming surgery is thought to be approximately 1%; however, previous studies relied heavily on ad hoc instruments. Objective: To evaluate long-term decisional regret and satisfaction with decision using validated instruments following gender-affirming mastectomy. Design, Setting, and Participants: For this cross-sectional study, a survey of patient-reported outcomes was sent between February 1 and July 31, 2022, to patients who had undergone gender-affirming mastectomy at a US tertiary referral center between January 1, 1990, and February 29, 2020. Exposure: Decisional regret and satisfaction with decision to undergo gender-affirming mastectomy. Main Outcomes and Measures: Long-term patient-reported outcomes, including the Holmes-Rovner Satisfaction With Decision scale, the Decision Regret Scale, and demographic characteristics, were collected. Additional information was collected via medical record review. Descriptive statistics and univariable analysis using Fisher exact and Wilcoxon rank sum tests were performed to compare responders and nonresponders. Results: A total of 235 patients were deemed eligible for the study, and 139 responded (59.1% response rate). Median age at the time of surgery was 27.1 (IQR, 23.0-33.4) years for responders and 26.4 (IQR, 23.1-32.7) years for nonresponders. Nonresponders (n = 96) had a longer postoperative follow-up period than responders (median follow-up, 4.6 [IQR, 3.1-8.6] vs 3.6 [IQR, 2.7-5.3] years, respectively; P = .002). Nonresponders vs responders also had lower rates of depression (42 [44%] vs 94 [68%]; P < .001) and anxiety (42 [44%] vs 97 [70%]; P < .001). No responders or nonresponders requested or underwent a reversal procedure. The median Satisfaction With Decision Scale score was 5.0 (IQR, 5.0-5.0) on a 5-point scale, with higher scores noting higher satisfaction. The median Decision Regret Scale score was 0.0 (IQR, 0.0-0.0) on a 100-point scale, with lower scores noting lower levels of regret. A univariable regression analysis could not be performed to identify characteristics associated with low satisfaction with decision or high decisional regret due to the lack of variation in these responses. Conclusions and Relevance: In this cross-sectional survey study, the results of validated survey instruments indicated low rates of decisional regret and high levels of satisfaction with decision following gender-affirming mastectomy. The lack of dissatisfaction and regret impeded the ability to perform a more complex statistical analysis, highlighting the need for condition-specific instruments to assess decisional regret and satisfaction with decision following gender-affirming surgery.

Heart Failure With Recovered Ejection Fraction in Patients With Nonischemic Cardiomyopathy: Characteristics, Outcomes, and Long-term Follow-up.

BACKGROUND: Duration of recovery and long-term outcomes have not been well-described in a large cohort of patients with heart failure with recovered ejection fraction (HFrecEF) owing to nonischemic cardiomyopathy. The aim of the study was to characterize the duration of recovery and long-term outcomes of patients with HFrecEF. METHODS AND RESULTS: We performed a retrospective analysis of our institution's databases. Only patients with nonischemic cardiomyopathy, a chronic HF diagnosis, and a previous left ventricular ejection fraction (LVEF) of ≤35% who had a subsequent LVEF of ≥50% were considered to have recovery. Patients with an LVEF of ≤35% who did not recover served as the comparison group. Included were 2319 patients with an LVEF of ≤35%, of whom 465 (20% [18.4%-21.7%]) met the above criteria for recovery (HFrecEF group). Recovery in the HFrecEF group was temporary in most cases, with 50% of patients experiencing a decline in LVEF to <50% within 3.5 [interquartile range 2.4-4.9] years after the day of recovery. Age and sex adjusted death and hospitalization were lower in the HFrecEF group than the HFrEF group (HR 0.29 [interquartile range 0.20-0.41] for death and 0.44 [interquartile range 0.32-0.60] for HF hospitalization, P < .0001 for both). Longer recovery was associated with better survival, with patients spending >5 years in recovery (LVEF of ≥50%) displaying the highest survival rates (83% alive at 10 years after recovery). Survival after recurrence of LV dysfunction was longer for those whose recovery duration was >1 year. CONCLUSIONS: Patients with nonischemic HFrecEF display a unique clinical course. Although recovery is temporary in most cases, patients with HFrecEF display lower mortality and hospitalization rates, with the more durable the recovery of LV systolic function, the longer survival can be anticipated.

Diagnostic Accuracy of Unenhanced Computed Tomography for Evaluation of Acute Abdominal Pain in the Emergency Department.

Importance: Intravenous (IV) contrast medium is sometimes withheld due to risk of complication or lack of availability in patients undergoing computed tomography (CT) for abdominal pain. The risk from withholding contrast medium is understudied. Objective: To determine the diagnostic accuracy of unenhanced abdominopelvic CT using contemporaneous contrast-enhanced CT as the reference standard in emergency department (ED) patients with acute abdominal pain. Design, Setting, and Participants: This was an institutional review board-approved, multicenter retrospective diagnostic accuracy study of 201 consecutive adult ED patients who underwent dual-energy contrast-enhanced CT for the evaluation of acute abdominal pain from April 1, 2017, through April 22, 2017. Three blinded radiologists interpreted these scans to establish the reference standard by majority rule. IV and oral contrast media were then digitally subtracted using dual-energy techniques. Six different blinded radiologists from 3 institutions (3 specialist faculty and 3 residents) interpreted the resulting unenhanced CT examinations. Participants included a consecutive sample of ED patients with abdominal pain who underwent dual-energy CT. Exposure: Contrast-enhanced and virtual unenhanced CT derived from dual-energy CT. Main outcome: Diagnostic accuracy of unenhanced CT for primary (ie, principal cause[s] of pain) and actionable secondary (ie, incidental findings requiring management) diagnoses. The Gwet interrater agreement coefficient was calculated. Results: There were 201 included patients (female, 108; male, 93) with a mean age of 50.1 (SD, 20.9) years and mean BMI of 25.5 (SD, 5.4). Overall accuracy of unenhanced CT was 70% (faculty, 68% to 74%; residents, 69% to 70%). Faculty had higher accuracy than residents for primary diagnoses (82% vs 76%; adjusted odds ratio [OR], 1.83; 95% CI, 1.26-2.67; P = .002) but lower accuracy for actionable secondary diagnoses (87% vs 90%; OR, 0.57; 95% CI, 0.35-0.93; P < .001). This was because faculty made fewer false-negative primary diagnoses (38% vs 62%; OR, 0.23; 95% CI, 0.13-0.41; P < .001) but more false-positive actionable secondary diagnoses (63% vs 37%; OR, 2.11, 95% CI, 1.26-3.54; P = .01). False-negative (19%) and false-positive (14%) results were common. Interrater agreement for overall accuracy was moderate (Gwet agreement coefficient, 0.58). Conclusion: Unenhanced CT was approximately 30% less accurate than contrast-enhanced CT for evaluating abdominal pain in the ED. This should be balanced with the risk of administering contrast material to patients with risk factors for kidney injury or hypersensitivity reaction.

Impact of diabetes on weight loss outcomes after bariatric surgery: Experience from 5-year follow-up of Michigan Bariatric Surgery Cohort.

OBJECTIVE: For patients with obesity and diabetes, bariatric surgery can lead to the remission of both diseases. However, the possible impact of diabetes on the magnitude of weight loss outcomes after bariatric surgery has not been precisely quantified. RESEARCH DESIGN AND METHODS: Data from Michigan Bariatric Surgery Cohort (MI-BASiC) was extracted to examine the effect of baseline diabetes on weight loss outcomes. Consecutive patients older than 18 years of age undergoing gastric bypass (GB) or sleeve gastrectomy (SG) for obesity at University of Michigan between January 2008 and November 2013 were included. Repeated measures analysis was used to determine if diabetes was a predictor of weight loss outcomes over 5 years postsurgery. RESULTS: Out of the 714 included patients, 380 patients underwent GB [mean BMI 47.3 ± 0.4 kg/m2 , diabetes 149 (39.2%)] and 334 SG [mean BMI 49.9 ± 0.5 kg/m2 , diabetes 108 (32.3%)]. Multivariable repeated measures analysis showed, after adjusting for covariates, that individuals with diabetes had a significantly lower percentage of total (p = .0023) and excess weight loss (p = .0212) compared to individuals without diabetes. CONCLUSIONS: Our data demonstrate that patients with diabetes undergoing bariatric surgery would experience less weight loss than patients without diabetes.

Needles in a Haystack: Finding Qualitative and Quantitative Collaborators in Academic Medical Centers.

Translational research is a data-driven process that involves transforming scientific laboratory- and clinic-based discoveries into products and activities with real-world impact to improve individual and population health. Successful execution of translational research requires collaboration between clinical and translational science researchers, who have expertise in a wide variety of domains across the field of medicine, and qualitative and quantitative scientists, who have specialized methodologic expertise across diverse methodologic domains. While many institutions are working to build networks of these specialists, a formalized process is needed to help researchers navigate the network to find the best match and to track the navigation process to evaluate an institution's unmet collaborative needs. In 2018, a novel analytic resource navigation process was developed at Duke University to connect potential collaborators, leverage resources, and foster a community of researchers and scientists. This analytic resource navigation process can be readily adopted by other academic medical centers. The process relies on navigators with broad qualitative and quantitative methodologic knowledge, strong communication and leadership skills, and extensive collaborative experience. The essential elements of the analytic resource navigation process are as follows: (1) strong institutional knowledge of methodologic expertise and access to analytic resources, (2) deep understanding of research needs and methodologic expertise, (3) education of researchers on the role of qualitative and quantitative scientists in the research project, and (4) ongoing evaluation of the analytic resource navigation process to inform improvements. Navigators help researchers determine the type of expertise needed, search the institution to find potential collaborators with that expertise, and document the process to evaluate unmet needs. Although the navigation process can create a basis for an effective solution, some challenges remain, such as having resources to train navigators, comprehensively identifying all potential collaborators, and keeping updated information about resources as methodologists join and leave the institution.

Racial Inequities in Access to Ventricular Assist Device and Transplant Persist After Consideration for Preferences for Care: A Report From the REVIVAL Study.

BACKGROUND: Racial disparities in access to advanced therapies for heart failure (HF) patients are well documented, although the reasons remain uncertain. We sought to determine the association of race on utilization of ventricular assist device (VAD) and transplant among patients with access to care at VAD centers and if patient preferences impact the effect. METHODS: We performed an observational cohort study of ambulatory chronic systolic HF patients with high-risk features and no contraindication to VAD enrolled at 21 VAD centers and followed for 2 years in the REVIVAL study (Registry Evaluation of Vital Information for VADs in Ambulatory Life). We used competing events cause-specific proportional hazard methodology with multiple imputation for missing data. The primary outcomes were (1) VAD/transplant and (2) death. The exposures of interest included race (Black or White), additional demographics, captured social determinants of health, clinician-assessed HF severity, patient-reported quality of life, preference for VAD, and desire for therapies. RESULTS: The study included 377 participants, of whom 100 (26.5%) identified as Black. VAD or transplant was performed in 11 (11%) Black and 62 (22%) White participants, although death occurred in 18 (18%) Black and 36 (13%) White participants. Black race was associated with reduced utilization of VAD and transplant (adjusted hazard ratio, 0.45 [95% CI, 0.23-0.85]) without an increase in death. Preferences for VAD or life-sustaining therapies were similar by race and did not explain racial disparities. CONCLUSIONS: Among patients receiving care by advanced HF cardiologists at VAD centers, there is less utilization of VAD and transplant for Black patients even after adjusting for HF severity, quality of life, and social determinants of health, despite similar care preferences. This residual inequity may be a consequence of structural racism and discrimination or provider bias impacting decision-making. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT01369407.

Sociodemographic variables associated with risk for diabetic retinopathy.

BACKGROUND: Several systemic and sociodemographic factors have been associated with the development and progression of diabetic retinopathy (DR). However, there is limited investigation of the potential role sociodemographic factors may play in augmenting systemic risk factors of DR. We hypothesize that age, sex, race, ethnicity, income, and insurance payor have an impact on hemoglobin A1c (HbA1c), body mass index, and systolic blood pressure, and therefore an upstream effect on the development of DR and vision-threatening forms of DR (VTDR). METHODS: Multivariable analysis of longitudinal electronic health record data at a large academic retina clinic was performed. Sociodemographic factors included race, ethnicity, income, and insurance payor. Systemic risk factors for DR included hemoglobin A1c (HbA1c), systolic blood pressure (SBP), and body mass index (BMI). VTDR was identified from encounter diagnostic codes indicating proliferative retinopathy or diabetic macular edema. Patient-reported primary address zip codes were used to approximate income level, stratified into quartiles. RESULTS: From 2016 to 2018, 3,470 patients with diabetes totaled 11,437 visits were identified. Black patients had higher HbA1c and SBP compared to White patients. White patients had higher BMI and SBP compared to patients of unknown/other race and greater odds of VTDR than the latter. Patients of Hispanic ethnicity had significantly higher SBP than non-Hispanic patients. Low-income patients had higher BMI and SBP than high-income patients and greater odds of VTDR than the latter. Medicaid recipients had greater odds of VTDR than those with Blue Care Network (BCN) and Blue Cross Blue Shield (BCBS) insurance. Medicaid and Medicare recipients had higher SBP compared to BCBS recipients. Finally, both higher HbA1c and SBP had greater odds of VTDR. There were no differences in odds of VTDR between White and Black patients or between Hispanic and non-Hispanic patients. CONCLUSION: Significant associations exist between certain sociodemographic factors and well-known risk factors for DR. Income and payor were associated with increased severity of systemic risk factors and presence of VTDR. These results warrant further investigation of how risk factor optimization and disease prevention may be further improved by targeted intervention of these modifiable sociodemographic factors.

Effect of Prostate MRI Interpretation Experience on PPV Using PI-RADS Version 2: A 6-Year Assessment Among Eight Fellowship-Trained Radiologists.

BACKGROUND. Understanding the effect of specific experience in prostate MRI interpretation on diagnostic performance would help inform the minimum interpretation volume to establish proficiency. OBJECTIVE. The purpose of this article is to assess for an association between increasing experience in prostate MRI interpretation and change in radiologist-level PPVs for PI-RADS version 2 (v2) categories 3, 4, and 5. METHODS. This retrospective study included prostate MRI examinations performed between July 1, 2015, and August 13, 2021, that were assigned a PI-RADS v2 category of 3, 4, or 5 and with an MRI-ultrasound fusion biopsy available as the reference standard. All examinations were among the first 100-200 prostate MRI examinations interpreted using PI-RADS v2 by fellowship-trained abdominal radiologists. Radiologists received feedback through a quality assurance program. Radiologists' experience levels were classified using progressive subsets of 50 interpreted examinations. Change with increasing experience in distribution of individual radiologists' whole-gland PPVs for Gleason sum score 7 or greater prostate cancer, stratified by PI-RADS category, was assessed by hierarchic linear mixed models. RESULTS. The study included 1300 prostate MRI examinations in 1037 patients (mean age, 66 ± 7 [SD] years), interpreted by eight radiologists (median, 13 years of postfellow-ship experience; range, 5-22 years). Aggregate PPVs were 20% (68/340) for PI-RADS category 3, 49% (318/652) for category 4, and 71% (220/308) for category 5. Interquartile ranges (IQRs) of PPVs overlapped for category 4 (51%; IQR, 42-60%) and category 5 (70%; IQR, 54-75%) for radiologists' first 50 examinations. IQRs of PPVs did not overlap between categories of greater experience; for example, at the 101-150 examination level, PPV for category 3 was 24% (IQR, 20-29%), category 4 was 55% (IQR, 54-63%), and category 5 was 81% (IQR, 77-82%). Hierarchic modeling showed no change in radiologists' absolute PPV with increasing experience (category 3, p = .27; category 4, p = .71; category 5, p = .38). CONCLUSION. Absolute PPVs at specific PI-RADS categories did not change during radiologists' first 200 included examinations. However, resolution of initial overlap in IQRs indicates improved precision of PPVs after the first 50 examinations. CLINICAL IMPACT. If implementing a minimum training threshold for fellowship-trained abdominal radiologists, 50 prostate MRI examinations may be sufficient in the context of a quality assurance program with feedback.

An early relook identifies high-risk trajectories in ambulatory advanced heart failure.

INTRODUCTION: Patients with ambulatory advanced heart failure (HF) are increasingly considered for durable mechanical circulatory support (MCS) and heart transplantation and their effective triage requires careful assessment of the clinical trajectory. METHODS: REVIVAL, a prospective, observational study, enrolled 400 ambulatory advanced HF patients from 21 MCS/transplant centers in 2015-2016. Study design included a clinical re-assessment of Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) profile within 120 days after enrollment. The prognostic impact of a worsening INTERMACS Profile assigned by the treating physician was assessed at 1 year after the Early Relook. RESULTS: Early Relook was done in 325 of 400 patients (81%), of whom 24% had a worsened INTERMACS Profile, associated with longer HF history and worse baseline INTERMACS profile, but no difference in baseline LVEF (median 0.20), 6-minute walk, quality of life, or other baseline parameters. Early worsening predicted higher rate of the combined primary endpoint of death, urgent MCS, or urgent transplant by 1 year after Early Relook, (28% vs 15%), with hazard ratio 2.2 (95% CI 1.2- 3.8; p = .006) even after adjusting for baseline INTERMACS Profile and Seattle HF Model score. Deterioration to urgent MCS occurred in 14% vs 5% (p = .006) during the year after Early Relook. CONCLUSIONS: Early Relook identifies worsening of INTERMACS Profile in a significant population of ambulatory advanced HF, who had worse outcomes over the subsequent year. Early reassessment of ambulatory advanced HF patients should be performed to better define the trajectory of illness and inform triage to advanced therapies.

Patient Preferences for Hepatocellular Carcinoma Surveillance Parameters.

BACKGROUND AND AIMS: Professional societies recommend abdominal ultrasound (US) with or without alpha fetoprotein (AFP) for hepatocellular cancer (HCC) surveillance; however, there are several emerging surveillance modalities, including abbreviated MRI and blood-based biomarker panels. Most studies have focused on provider perspectives for surveillance logistics, but few have assessed patient preferences. We aimed to measure preferences among patients with cirrhosis regarding HCC surveillance modalities. METHODS: We conducted a choice-based conjoint survey to patients with cirrhosis at four institutions. Participants were provided 15 scenarios in which they were asked to choose surveillance modalities based on five test attributes: benefits, i.e. sensitivity for early HCC (range: 35-95%), physical harm, i.e. false positives requiring additional testing (range: 10-40%), financial harm, i.e. out-of-pocket costs (range: $10-100), test logistics and convenience, i.e. duration of testing (range: 10-60 min). Hierarchical Bayes discrete choice conjoint analysis was used to derive attribute importance, and preference shares were determined by simulation. RESULTS: In total 91% (182/199) of approached patients consented to participate in the study and 98% (n=179) successfully completed the survey. Surveillance benefits (importance: 51.3%, 95%CI: 49.0-53.4%) were valued more than risk of physical harm (importance: 7.6%, 95%CI 7.0-8.2%), financial harm (importance: 15.2%, 95%CI 14.0-16.3%), convenience (importance: 9.3%, 95%CI 8.5-10.1%) and test logistics (importance: 16.7%, 95%CI 15.4-18.1%). Based on simulations including all possible tests, patients preferred abbreviated MRI (29.0%), MRI (23.3%), or novel blood-based biomarkers (20.9%) to ultrasound alone (3.4%) or with AFP (8.8%). CONCLUSIONS: Patients with cirrhosis prioritize early HCC detection over potential surveillance-related harms or inconvenience.

Frailty Measures of Patient-reported Activity and Fatigue May Predict 1-year Outcomes in Ambulatory Advanced Heart Failure: A Report From the REVIVAL Registry.

BACKGROUND: The Fried Frailty Phenotype predicts adverse outcomes in geriatric populations, but has not been well-studied in advanced heart failure (HF). The Registry Evaluation of Vital Information for Ventricular Assist Devices (VADs) in Ambulatory Life (REVIVAL) study prospectively collected frailty measures in patients with advanced HF to determine relevant assessments and their impact on clinical outcomes. METHODS AND RESULTS: HF-Fried Frailty was defined by 5 baseline components (1 point each): (1) weakness: hand grip strength less than 25% of body weight; (2) slowness based on time to walk 15 feet; (3) weight loss of more than 10 lbs in the past year; (4) inactivity; and (5) exhaustion, both assessed by the Kansas City Cardiomyopathy Questionnaire. A score of 0 or 1 was deemed nonfrail, 2 prefrail, and 3 or greater was considered frail. The primary composite outcome was durable mechanical circulatory support implantation, cardiac transplant or death at 1 year. Event-free survival for each group was determined by the Kaplan-Meier method and the hazard of prefrailty and frailty were compared with nonfrailty with proportional hazards modeling. Among 345 patients with all 5 frailty domains assessed, frailty was present in 17%, prefrailty in 40%, and 43% were nonfrail, with 67% (n = 232) meeting the criteria based on inactivity and 54% (n = 186) for exhaustion. Frail patients had an increased risk of the primary composite outcome (unadjusted hazard ratio [HR] 2.82, 95% confidence interval [CI] 1.52-5.24; adjusted HR 3.41, 95% CI 1.79-6.52), as did prefrail patients (unadjusted HR 1.97, 95% CI 1.14-3.41; adjusted HR 2.11, 95% CI 1.21-3.66) compared with nonfrail patients, however, the predictive value of HF-Fried Frailty criteria was modest (Harrel's C-statistic of 0.603, P = .004). CONCLUSIONS: The HF-Fried Frailty criteria had only modest predictive power in identifying ambulatory patients with advanced HF at high risk for durable mechanical circulatory support, transplant, or death within 1 year, driven primarily by assessments of inactivity and exhaustion. Focus on these patient-reported measures may better inform clinical trajectories in this population.

Interrater Agreement of Bosniak Classification Version 2019 and Version 2005 for Cystic Renal Masses at CT and MRI.

Background The Bosniak classification system for cystic renal masses was updated in 2019 in part to improve agreement compared with the 2005 version. Purpose To compare and investigate interrater agreement of Bosniak version 2019 and Bosniak version 2005 at CT and MRI. Materials and Methods In this retrospective single-center study, a blinded eight-reader assessment was performed in which 195 renal masses prospectively considered Bosniak IIF-IV (95 at CT, 100 at MRI, from 2006 to 2019 with version 2005) were re-evaluated with Bosniak versions 2019 and 2005. Radiologists (four faculty members, four residents) who were blinded to the initial clinical reading and histopathologic findings assessed all feature components and reported the overall Bosniak class for each system independently. Agreement was assessed with Gwet agreement coefficients. Uni- and multivariable linear regression models were developed to identify predictors of dispersion in the final Bosniak class assignment that could inform system refinement. Results A total of 185 patients were included (mean age, 63 years ± 13 [standard deviation]; 118 men). Overall interrater agreement was similar between Bosniak version 2019 and version 2005 (Gwet agreement coefficient: 0.51 [95% CI: 0.45, 0.57] vs 0.46 [95% CI: 0.42, 0.51]). This was true for experts (0.54 vs 0.49) and novices (0.50 vs 0.47) and at CT (0.56 vs 0.51) and MRI (0.52 vs 0.43). Nine percent of masses prospectively considered cystic using Bosniak version 2005 criteria were considered solid using version 2019 criteria. In general, masses were more commonly classified in lower categories when radiologists used Bosniak version 2019 criteria compared with version 2005 criteria. The sole predictor of dispersion in Bosniak version 2019 class assignment was dispersion in septa or wall quality (ie, smooth vs irregular thickening vs nodule; 72% [MRI] and 60% [CT] overall model variance explained; multivariable P < .001). Conclusion Overall interrater agreement was similar between Bosniak version 2019 and version 2005; disagreements in septa or wall quality were common and strongly predictive of variation in Bosniak class assignment. © RSNA, 2021 Online supplemental material is available for this article. See also the editorial by Eberhardt in this issue.

Guidance for biostatisticians on their essential contributions to clinical and translational research protocol review.

Rigorous scientific review of research protocols is critical to making funding decisions, and to the protection of both human and non-human research participants. Given the increasing complexity of research designs and data analysis methods, quantitative experts, such as biostatisticians, play an essential role in evaluating the rigor and reproducibility of proposed methods. However, there is a common misconception that a statistician's input is relevant only to sample size/power and statistical analysis sections of a protocol. The comprehensive nature of a biostatistical review coupled with limited guidance on key components of protocol review motived this work. Members of the Biostatistics, Epidemiology, and Research Design Special Interest Group of the Association for Clinical and Translational Science used a consensus approach to identify the elements of research protocols that a biostatistician should consider in a review, and provide specific guidance on how each element should be reviewed. We present the resulting review framework as an educational tool and guideline for biostatisticians navigating review boards and panels. We briefly describe the approach to developing the framework, and we provide a comprehensive checklist and guidance on review of each protocol element. We posit that the biostatistical reviewer, through their breadth of engagement across multiple disciplines and experience with a range of research designs, can and should contribute significantly beyond review of the statistical analysis plan and sample size justification. Through careful scientific review, we hope to prevent excess resource expenditure and risk to humans and animals on poorly planned studies.

Caregiver Health-Related Quality of Life, Burden, and Patient Outcomes in Ambulatory Advanced Heart Failure: A Report From REVIVAL.

Background Heart failure (HF) imposes significant burden on patients and caregivers. Longitudinal data on caregiver health-related quality of life (HRQOL) and burden in ambulatory advanced HF are limited. Methods and Results Ambulatory patients with advanced HF (n=400) and their participating caregivers (n=95) enrolled in REVIVAL (Registry Evaluation of Vital Information for VADs [Ventricular Assist Devices] in Ambulatory Life) were followed up for 24 months, or until patient death, left ventricular assist device implantation, heart transplantation, or loss to follow-up. Caregiver HRQOL (EuroQol Visual Analog Scale) and burden (Oberst Caregiving Burden Scale) did not change significantly from baseline to follow-up. At time of caregiver enrollment, better patient HRQOL by Kansas City Cardiomyopathy Questionnaire was associated with better caregiver HRQOL (P=0.007) and less burden by both time spent (P<0.0001) and difficulty (P=0.0007) of caregiving tasks. On longitudinal analyses adjusted for baseline values, better patient HRQOL (P=0.034) and being a married caregiver (P=0.016) were independently associated with better caregiver HRQOL. Patients with participating caregivers (versus without) were more likely to prefer left ventricular assist device therapy over time (odds ratio, 1.43; 95% CI, 1.03-1.99; P=0.034). Among patients with participating caregivers, those with nonmarried (versus married) caregivers were at higher composite risk of HF hospitalization, death, heart transplantation or left ventricular assist device implantation (hazard ratio, 2.99; 95% CI, 1.29-6.96; P=0.011). Conclusions Patient and caregiver characteristics may impact their HRQOL and other health outcomes over time. Understanding the patient-caregiver relationship may better inform medical decision making and outcomes in ambulatory advanced HF.

Prospective multicenter assessment of patient preferences for properties of gadolinium-based contrast media and their potential socioeconomic impact in a screening breast MRI setting.

OBJECTIVE: It is unknown how patients prioritize gadolinium-based contrast media (GBCM) benefits (detection sensitivity) and risks (reactions, gadolinium retention, cost). The purpose of this study is to measure preferences for properties of GBCM in women at intermediate or high risk of breast cancer undergoing annual screening MRI. METHODS: An institutional reviewed board-approved prospective discrete choice conjoint survey was administered to patients at intermediate or high risk for breast cancer undergoing screening MRI at 4 institutions (July 2018-March 2020). Participants were given 15 tasks and asked to choose which of two hypothetical GBCM they would prefer. GBCMs varied by the following attributes: sensitivity for cancer detection (80-95%), intracranial gadolinium retention (1-100 molecules per 100 million administered), severe allergic-like reaction rate (1-19 per 100,000 administrations), mild allergic-like reaction rate (10-1000 per 100,000 administrations), out-of-pocket cost ($25-$100). Attribute levels were based on published values of existing GBCMs. Hierarchical Bayesian analysis was used to derive attribute "importance." Preference shares were determined by simulation. RESULTS: Response (87% [247/284]) and completion (96% [236/247]) rates were excellent. Sensitivity (importance = 44.3%, 95% confidence interval = 42.0-46.7%) was valued more than GBCM-related risks (mild allergic-like reaction risk (19.5%, 17.9-21.1%), severe allergic-like reaction risk (17.0%, 15.8-18.1%), intracranial gadolinium retention (11.6%, 10.5-12.7%), out-of-pocket expense (7.5%, 6.8-8.3%)). Lower income participants placed more importance on cost and less on sensitivity (p < 0.01). A simulator is provided that models GBCM preference shares by GBCM attributes and competition. CONCLUSIONS: Patients at intermediate or high risk for breast cancer undergoing MRI screening prioritize cancer detection over GBCM-related risks, and prioritize reaction risks over gadolinium retention. KEY POINTS: • Among women undergoing annual breast MRI screening, cancer detection sensitivity (attribute "importance," 44.3%) was valued more than GBCM-related risks (mild allergic reaction risk 19.5%, severe allergic reaction risk 17.0%, intracranial gadolinium retention 11.6%, out-of-pocket expense 7.5%). • Prospective four-center patient preference data have been incorporated into a GBCM choice simulator that allows users to input GBCM properties and calculate patient preference shares for competitor GBCMs. • Lower-income women placed more importance on out-of-pocket cost and less importance on cancer detection (p < 0.01) when prioritizing GBCM properties.

Predictive Value of Cardiopulmonary Exercise Testing Parameters in Ambulatory Advanced Heart Failure.

OBJECTIVES: This study sought to determine cardiopulmonary exercise (CPX) predictors of the combined outcome of durable mechanical circulatory support (MCS), transplantation, or death at 1 year among patients with ambulatory advanced heart failure (HF). BACKGROUND: Optimal CPX predictors of outcomes in contemporary ambulatory advanced HF patients are unclear. METHODS: REVIVAL (Registry Evaluation of Vital Information for ventricular assist devices [VADs] in Ambulatory Life) enrolled 400 systolic HF patients, INTERMACS (Interagency Registry for Mechanically Assisted Circulatory Support) profiles 4-7. CPX was performed by 273 subjects 2 ± 1 months after study enrollment. Discriminative power of maximal (peak oxygen consumption [peak VO2]; VO2 pulse, circulatory power [CP]; peak systolic blood pressure â€¢ peak VO2], peak end-tidal pressure CO2 [PEtCO2], and peak Borg scale score) and submaximal CPX parameters (ventilatory efficiency [VE/VCO2 slope]; VO2 at anaerobic threshold [VO2AT]; and oxygen uptake efficiency slope [OUES]) to predict the composite outcome were assessed by univariate and multivariate Cox regression and Harrell's concordance statistic. RESULTS: At 1 year, there were 39 events (6 transplants, 15 deaths, 18 MCS implantations). Peak VO2, VO2AT, OUES, peak PEtCO2, and CP were higher in the no-event group (all p < 0.001), whereas VE/VCO2 slope was lower (p < 0.0001); respiratory exchange ratio was not different. CP (hazard ratio [HR]: 0.89; p = 0.001), VE/VCO2 slope (HR: 1.05; p = 0.001), and peak Borg scale score (HR: 1.20; p = 0.005) were significant predictors on multivariate analysis (model C-statistic: 0.80). CONCLUSIONS: Among patients with ambulatory advanced HF, the strongest maximal and submaximal CPX predictor of MCS implantation, transplantation, or death at 1 year were CP and VE/VCO2, respectively. The patient-reported measure of exercise effort (Borg scale score) contributed substantially to the prediction of outcomes, a surprising and novel finding that warrants further investigation. (Registry Evaluation of Vital Information for VADs in Ambulatory Life [REVIVAL]; NCT01369407).

Comorbid Conditions and Health-Related Quality of Life in Ambulatory Heart Failure Patients: REVIVAL (Registry Evaluation of Vital Information for VADs in Ambulatory Life REVIVAL).

BACKGROUND: Patients with heart failure (HF) often have multiple chronic conditions that may impact health-related quality of life (HRQOL) despite HF therapy. We sought to determine the association between noncardiac comorbidities and HRQOL in ambulatory patients with advanced HF. METHODS: Baseline data from 373 subjects in REVIVAL (Registry Evaluation of Vital Information for Ventricular Assist Devices in Ambulatory Life) were analyzed using multivariable general linear models to evaluate the relationship between comorbidities and HRQOL (EuroQol Visual Analogue Scale, EQ-5D-3L Index Score, and Kansas City Cardiomyopathy Questionnaire). The primary independent variables were a comorbidity index (sum of 14 noncardiac conditions), a residual comorbidity index (without depression), and depression alone. The median (25th to 75th percentile) number of comorbidities was 3 (2-4). RESULTS: Increasing comorbidity burden was associated with a reduction in generic (EQ-5D Index, P=0.005) and HF-specific (Kansas City Cardiomyopathy Questionnaire, P=0.001) HRQOL. The residual comorbidity index was not associated with HRQOL when depression included in the model independently, while depression was associated with HRQOL across all measures. Participants with depression (versus without) scored on average 13 points (95% CI, 8-17) lower on the EuroQol Visual Analogue Scale, 0.15 points (95% CI, 0.12-0.18) lower on the EQ-5D Index, and 24.9 points (95% CI, 21.2-28.5) lower on the Kansas City Cardiomyopathy Questionnaire overall summary score. CONCLUSIONS: While noncardiac comorbidities were prevalent in ambulatory advanced HF patients, only depression was associated with decreased generic and HF-specific HRQOL. Other than depression, the presence of noncardiac comorbidities should not impact expected gains in HRQOL following ventricular assist device implantation, provided the conditions are not a contraindication to implant. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01369407.

Prospective Imaging Trial Assessing Gadoteridol Retention in the Deep Brain Nuclei of Women Undergoing Breast MRI.

RATIONALE AND OBJECTIVES: To assess for indirect evidence of gadoteridol retention in the deep brain nuclei of women undergoing serial screening breast MRI. METHODS: This HIPAA-compliant prospective observational noninferiority imaging trial was approved by the IRB. From December 2016 to March 2018, 12 consented subjects previously exposed to 0-1 doses of gadoteridol (group 1) and 7 consented subjects previously exposed to ≥4 doses of gadoteridol (group 2) prospectively underwent research-specific unenhanced brain MRI including T1w spin echo imaging and T1 mapping. Inclusion criteria were: (1) planned breast MRI with gadoteridol, (2) no gadolinium exposure other than gadoteridol, (3) able to undergo MRI, (4) no neurological illness, (5) no metastatic disease, (6) no chemotherapy. Regions of interest were manually drawn in the globus pallidus, thalamus, dentate nucleus, and pons. Globus pallidus/thalamus and dentate nucleus/pons signal intensities and T1-time ratios were calculated using established methods and correlated with cumulative gadoteridol dose (mL). RESULTS: All subjects were female (mean age: 50 ± 12 years) and previously had received an average of 0.5 ± 0.5 (group 1) and 5.9 ± 2.1 (group 2) doses of gadoteridol (cumulative dose: 8 ± 8 and 82 ± 31 mL, respectively), with the last dose an average of 492 ± 299 days prior to scanning. There was no significant correlation between cumulative gadoteridol dose (mL) and deep brain nuclei signal intensity at T1w spin echo imaging (p = 0.365-0.512) or T1 mapping (p = 0.197-0.965). CONCLUSION: We observed no indirect evidence of gadolinium retention in the deep brain nuclei of women undergoing screening breast MRI with gadoteridol.