Publications by authors named "Andrew Ryan"

288 Publications

Focal low dose-rate brachytherapy for low to intermediate risk prostate cancer: preliminary experience at an Australian institution.

Transl Androl Urol 2021 Sep;10(9):3591-3603

Icon Cancer Centre, Richmond, Australia.

Background: Focal treatment for prostate cancer (PCa) is a hybrid approach combining ablative treatment of the involved prostate gland and continued active surveillance (AS) of the unaffected gland. Low dose-rate (LDR) brachytherapy can be used as a lesion-targeted focal therapy, however, further studies are required to support its use. The aim of this study is to evaluate the dosimetry, toxicity and oncological outcomes of men receiving lesion-targeted focal LDR brachytherapy for low to intermediate risk PCa.

Methods: This is a retrospective cohort study of 26 men with unifocal, low to intermediate grade PCa diagnosed on a combination of multiparametric-magnetic resonance imaging (mp-MRI) and targeted plus template transperineal (TP) biopsy, who received focal LDR brachytherapy at a single institution. Brachytherapy involved a single monotherapy implant using iodine-125 seeds to deliver a prescribed dose of 145 Gy to the index lesion.

Results: The mean focal planning target volume (F-PTV) as a percentage of the prostate volume was 24.5%. The percentage of the focal gross tumour volume (F-GTV) receiving 100% of the prescription dose was 100% for 12 patients and ≥98% for 18 patients. The median follow-up for toxicity and biochemical control outcomes was 23.1 [interquartile range (IQR) 19.1-31.3] and 24.2 (IQR 17.9-30.0) months, respectively. Grade 2 urinary and erectile toxicities were reported by 29.2% and 45.8% of patients, respectively, with resolution of urinary symptoms to baseline by last follow-up. There were no grade ≥3 urinary or erectile toxicities or grade ≥2 rectal toxicity. All 21 patients who underwent a repeat mp-MRI and TP biopsy at 12-24 months post-treatment were negative for clinically significant disease and 25 (96.2%) patients were free from biochemical failure (FFBF).

Conclusions: Focal LDR brachytherapy is associated with a favourable toxicity profile and a high rate of control of significant PCa at 12-18 months post-treatment. We have commenced the LIBERATE prospective registry in focal LDR brachytherapy based on the highly encouraging outcomes of this initial experience.
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http://dx.doi.org/10.21037/tau-21-508DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8511546PMC
September 2021

Evaluation of the efficacy of an intersection conflict warning system at two-way stop-controlled rural intersections: difference-in-differences and triple-difference analytical approaches.

Inj Prev 2021 Oct 29. Epub 2021 Oct 29.

HumanFIRST Laboratory, Department of Mechanical Engineering, University of Minnesota, Minneapolis, Minnesota, USA.

Objective: Intersection conflict warning systems (ICWSs) have been implemented at high-risk two-way stop-controlled intersections to prevent right-angle crashes and associated injuries. This study involved investigation of the impacts of ICWSs on crash reductions.

Methods: The study used a quasi-experimental design to analyse the potential causal relations between Minnesota's ICWSs and various crash rate outcomes (including total, injury, non-injury, targeted right-angle and non-right-angle crashes) in pre-post analyses. A restricted randomisation method enabled identification of three controls to each ICWS treatment intersection, and included as many comparable intersection characteristics as possible. Annual crash rates (per year per intersection) were analysed over the same periods before and after system activation for treatment and control intersections in each matched group. Pre-crash data for 3 years and post-crash data for up to 5 years were included, ranging from 2010 to 2018. Negative binomial regression models with generalised estimating equations were applied to estimate the average, immediate and continuing treatment effects of ICWSs, through the difference-in-differences and difference-in-difference-in-difference approaches, respectively.

Results: The ICWS treatment was significantly associated with a decreasing trend for targeted right-angle crash rates posttreatment. Although not statistically significant, most crash rate outcomes appeared to be elevated immediately after treatment (statistically significant for sideswipe crashes only). Pre-post differences in average crash rates (over entire periods), except for incapacitating injury-related crashes, were not statistically significant between treatment and control intersections.

Conclusions: The study provided important insight into potential causal associations between intersection safety countermeasures and crashes at high-risk rural two-way stop-controlled intersections.
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http://dx.doi.org/10.1136/injuryprev-2021-044321DOI Listing
October 2021

Hospital-specific Template Matching for Benchmarking Performance in a Diverse Multihospital System.

Med Care 2021 Dec;59(12):1090-1098

VA Center for Clinical Management Research, Ann Arbor, MI.

Background: Hospital-specific template matching is a newer method of hospital performance measurement that may be fairer than regression-based benchmarking. However, it has been tested in only limited research settings.

Objective: The objective of this study was to test the feasibility of hospital-specific template matching assessments in the Veterans Affairs (VA) health care system and determine power to detect greater-than-expected 30-day mortality.

Research Design: Observational cohort study with hospital-specific template matching assessment. For each VA hospital, the 30-day mortality of a representative subset of hospitalizations was compared with the pooled mortality from matched hospitalizations at a set of comparison VA hospitals treating sufficiently similar patients. The simulation was used to determine power to detect greater-than-expected mortality.

Subjects: A total of 556,266 hospitalizations at 122 VA hospitals in 2017.

Measures: A number of comparison hospitals identified per hospital; 30-day mortality.

Results: Each hospital had a median of 38 comparison hospitals (interquartile range: 33, 44) identified, and 116 (95.1%) had at least 20 comparison hospitals. In total, 8 hospitals (6.6%) had a significantly lower 30-day mortality than their benchmark, 5 hospitals (4.1%) had a significantly higher 30-day mortality, and the remaining 109 hospitals (89.3%) were similar to their benchmark. Power to detect a standardized mortality ratio of 2.0 ranged from 72.5% to 79.4% for a hospital with the fewest (6) versus most (64) comparison hospitals.

Conclusions: Hospital-specific template matching may be feasible for assessing hospital performance in the diverse VA health care system, but further refinements are needed to optimize the approach before operational use. Our findings are likely applicable to other large and diverse multihospital systems.
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http://dx.doi.org/10.1097/MLR.0000000000001645DOI Listing
December 2021

Comparative Safety of Sleeve Gastrectomy and Gastric Bypass Up to 5 Years After Surgery in Patients With Severe Obesity.

JAMA Surg 2021 Oct 6. Epub 2021 Oct 6.

Department of Surgery, University of Michigan, Ann Arbor.

Importance: Sleeve gastrectomy is the most widely used bariatric operation; however, its long-term safety is largely unknown.

Objective: To compare the risk of mortality, complications, reintervention, and health care use 5 years after sleeve gastrectomy and gastric bypass.

Design, Setting, And Participants: This retrospective cohort study included adult patients in a national Medicare claims database who underwent sleeve gastrectomy or gastric bypass from January 1, 2012, to December 31, 2018. Instrumental variables survival analysis was used to estimate the cumulative incidence of outcomes up to 5 years after surgery.

Exposures: Laparoscopic sleeve gastrectomy and laparoscopic Roux-en-Y gastric bypass.

Main Outcomes And Measures: The main outcome was risk of mortality, complications, and reinterventions up to 5 years after surgery. Secondary outcomes were health care use after surgery, including hospitalization, emergency department (ED) use, and total spending.

Results: Of 95 405 patients undergoing bariatric surgery, 57 003 (60%) underwent sleeve gastrectomy (mean [SD] age, 57.1 [11.8] years), of whom 42 299 (74.2%) were women; 124 (0.2%) were Asian; 10 101 (17.7%), Black; 1951 (3.4%), Hispanic; 314 (0.6%), North American Native; 43 194 (75.8%), White; 534 (0.9%), of other race or ethnicity; and 785 (1.4%), of unknown race or ethnicity. A total of 38 402 patients (40%) underwent gastric bypass (mean [SD] age, 55.9 [11.7] years), of whom 29 050 (75.7%) were women; 109 (0.3%), Asian; 6038 (15.7%), Black; 1215 (3.2%), Hispanic; 278 (0.7%), North American Native; 29 986 (78.1%), White; 373 (1.0%), of other race or ethnicity; and 404 (1.1%), of unknown race or ethnicity. Compared with patients undergoing gastric bypass, at 5 years after surgery, patients undergoing sleeve gastrectomy had a lower cumulative incidence of mortality (4.27%; 95% CI, 4.25%-4.30% vs 5.67%; 95% CI, 5.63%-5.69%), complications (22.10%; 95% CI, 22.06%-22.13% vs 29.03%; 95% CI, 28.99%-29.08%), and reintervention (25.23%; 95% CI, 25.19%-25.27% vs 33.57%; 95% CI, 33.52%-33.63%). Conversely, patients undergoing sleeve gastrectomy had a higher cumulative incidence of surgical revision at 5 years (2.91%; 95% CI, 2.90%-2.93% vs 1.46%; 95% CI, 1.45%-1.47%). The adjusted hazard ratio (aHR) of all-cause hospitalization and ED use was lower for patients undergoing sleeve gastrectomy at 1 year (hospitalization, aHR, 0.83; 95% CI, 0.80-0.86; ED use, aHR, 0.87; 95% CI, 0.84-0.90) and 3 years (hospitalization, aHR, 0.94; 95% CI, 0.90-0.98; ED use, aHR, 0.93; 95% CI, 0.90-0.97) after surgery but similar between groups at 5 years (hospitalization, aHR, 0.99; 95% CI, 0.94-1.04; ED use, aHR, 0.97; 95% CI, 0.92-1.01). Total health care spending among patients undergoing sleeve gastrectomy was lower at 1 year after surgery ($28 706; 95% CI, $27 866-$29 545 vs $30 663; 95% CI, $29 739-$31 587), but similar between groups at 3 ($57 411; 95% CI, $55 239-$59 584 vs $58 581; 95% CI, $56 551-$60 611) and 5 years ($86 584; 95% CI, $80 183-$92 984 vs $85 762; 95% CI, $82 600-$88 924).

Conclusions And Relevance: In a large cohort of patients undergoing bariatric surgery, sleeve gastrectomy was associated with a lower long-term risk of mortality, complications, and reinterventions but a higher long-term risk of surgical revision. Understanding the comparative safety of these operations may better inform patients and surgeons in their decision-making.
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http://dx.doi.org/10.1001/jamasurg.2021.4981DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8495604PMC
October 2021

Design and evaluation of a rural intersection conflict warning system and alternative designs among various driver age groups.

Accid Anal Prev 2021 Nov 29;162:106388. Epub 2021 Sep 29.

HumanFIRST Laboratory, Department of Mechanical Engineering, University of Minnesota, Minneapolis, MN, United States.

Advanced Rural Intersection Conflict Warning Systems (RICWS) were deployed as countermeasures to reduce severe right-angle crashes at rural thru-STOP controlled intersections across the United States (U.S.). The simulator study designed and evaluated alternative RICWS designs to existing RICWS interventions, in varying rural driving scenarios, across age groups (N = 40 novice teenage, 40 middle-aged, and 40 older drivers). Each participant was randomly assigned to a RICWS design, either the original or an alternative, and drove through sequences of 17 thru-STOP controlled rural intersections (nine RICWS intervention and eight control intersections). Drivers' gap acceptance performance, intersection driving performance, traffic violation behaviors and self-reported workload were evaluated between intervention and control intersections. Regression models, applying the Generalized Estimating Equation (GEE), enabled efficacy determination of each RICWS design and an aggregated RICWS intervention effect, averaged across all simulated RICWS designs, among different levels of moderating factors. The safety performance and possible risks associated with the use of different RICWS designs were identified. Specifically, the original RICWS design had a significantly greater risk of STOP-sign violations at clear-view intersections with low traffic volumes, compared with control intersections (Risk Ratio = 2.18, 95% CI = 1.03 to 4.64). Except for Alternative RICWS Design 1, the alternative RICWS designs did not appear to outperform the Original RICWS Design. The moderating effects of drivers' ages and intersection types on aggregated RICWS intervention effects were also examined. This study provides important safety implications for development and evaluation of intelligent intersection warning systems, targeted to vulnerable driver populations at high-risk rural intersections.
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http://dx.doi.org/10.1016/j.aap.2021.106388DOI Listing
November 2021

Ga-Prostate-Specific Membrane Antigen Positron Emission Tomography Maximum Standardized Uptake Value as a Predictor of Gleason Pattern 4 and Pathological Upgrading in Intermediate-Risk Prostate Cancer.

J Urol 2021 Sep 21:101097JU0000000000002254. Epub 2021 Sep 21.

Department of Surgery, Monash University, Melbourne, Australia.

Purpose: Accurate risk stratification remains a barrier for the safety of active surveillance in patients with intermediate-risk prostate cancer. [Ga]Ga-PSMA-11 prostate-specific membrane antigen positron emission tomography/computerized tomography (Ga-PSMA PET/CT) and the maximum standardized uptake value (SUVmax) may improve risk stratification within this population.

Materials And Methods: We reviewed men with International Society for Urological Pathology Grade Group (GG) 2-3 disease on transperineal template biopsy undergoing Ga-PSMA PET/CT from November 2015 to January 2021. Primary outcome was the presence of high percentage Gleason pattern 4 (GP4) disease per segment at surgery at 3 thresholds: >/<50% GP4, >/<20% GP4, and >/<10% GP4. SUVmax was compared by GP4, and multivariable logistic regression examined the relationship between SUVmax and GP4. Secondary outcome was association between SUVmax and pathological upgrading (GG 1/2 to GG ≥3 from biopsy to surgery).

Results: Of 220 men who underwent biopsy, 135 men underwent surgery. SUVmax was higher in high GP4 groups: 5.51 (IQR 4.19-8.49) vs 3.31 (2.64-4.41) >/<50% GP4 (p <0.001); 4.77 (3.31-7.00) vs 3.13 (2.64-4.41) >/<20% GP4 (p <0.001); and 4.54 (6.10-3.13) vs 3.03 (2.45-3.70) >/<10% GP4 (p <0.001). SUVmax remained an independent predictor of >50% (OR=1.39 [95%CI 1.18-1.65], p <0.001) and >20% (OR=1.24 [1.04-1.47], p=0.015) GP4 disease per-segment, and of pathological upgrading (OR=1.22 [1.01-1.48], p=0.036). SUVmax threshold 4.5 predicted >20% GP4 with 58% specificity, 85% sensitivity, positive predictive value 75% and negative predictive value 72%. Threshold 5.4 predicted pathological upgrading with 91% specificity and negative predictive value 94%.

Conclusions: SUVmax on Ga-PSMA PET/CT is associated with GP4. SUVmax may improve risk stratification for men with intermediate-risk prostate cancer.
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http://dx.doi.org/10.1097/JU.0000000000002254DOI Listing
September 2021

Urologist practice structure and quality of prostate cancer care.

Urol Pract 2020 Sep 1;7(5):419-424. Epub 2020 Sep 1.

Dow Division for Health Services Research, Department of Urology, University of Michigan, Ann Arbor, MI.

Objective: To examine three aspects of urologist practice structure that may affect quality of prostate cancer care: practice size, ownership of an intensity modulated radiation therapy (IMRT) device, participation within a multi-specialty group (MSG). Health care reforms focused on improving quality are particularly relevant for prostate cancer given its prevalence and concerns for overdiagnosis and overtreatment.

Methods: Using data from the Surveillance, Epidemiology and End-Results (SEER)-Medicare linked registry, we examined quality of prostate cancer treatment according to each treating urologist's practice size, type (single-specialty vs. MSG) and ownership of IMRT. Mixed models were used to adjust for patient differences.

Results: We identified 22,412 men with newly diagnosed prostate cancer treated by 2,199 urologists during the study. We observed minimal differences for most quality metrics according to practice size, type, and ownership of IMRT. Adherence to all eligible quality metrics was better among MSGs compared to single specialty groups (20.0% adherence versus 18.2%, p=0.01) whereas there was no significant difference by ownership of IMRT (17.1% adherence in owners versus 18.9% non-owners, p=0.09).

Conclusion: Differences in quality across practice size, type and ownership of IMRT were modest, with substantial room for improvement regardless of practice structure.
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http://dx.doi.org/10.1097/upj.0000000000000123DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8447938PMC
September 2020

Changes in Hospital-acquired Conditions and Mortality Associated With the Hospital-acquired Condition Reduction Program.

Ann Surg 2021 10;274(4):e301-e307

University of Michigan School of Public Health, Ann Arbor, Michigan.

Importance: To improve patient safety, the Centers for Medicare and Medicaid Services announced the Hospital-Acquired Condition Reduction Program (HACRP) in August 2013. The program reduces Medicare payments by 1% for hospitals in the lowest performance quartile related to hospital-acquired conditions. Performance measures are focused on perioperative care.

Objective: To evaluate changes in HACs and 30-day mortality after the announcement of the HACRP.

Design: Interrupted time-series design using Medicare Provider and Analysis Review (MEDPAR) claims data. We estimated models with linear splines to test for changes in HACs and 30-day mortality before the Affordable Care Act (ACA), after the ACA, and after the HACRP.

Setting: Fee-for-service Medicare 2009-2015.

Participants: Medicare beneficiaries undergoing surgery and discharged from an acute care hospital between January 2009 and August 2015 (N = 8,857,877).

Main Outcome And Measure: Changes in HACs and 30-day mortality after the announcement of the HACRP.

Results: Patients experienced HACs at a rate of 13.39 per 1000 discharges [95% confidence interval (CI), 13.10 to 13.68] in the pre-ACA period. This declined after the ACA was passed and declined further after the HACRP announcement [adjusted difference in annual slope, -1.34 (95% CI, -1.64 to -1.04)]. Adjusted 30-day mortality was 3.69 (95% CI, 3.64 to 3.74) in the pre-ACA period among patients receiving surgery. Thirty-day mortality continued to decline after the ACA [adjusted annual slope -0.04 (95% CI, -0.05 to -0.02)] but was flat after the HACRP [adjusted annual slope -0.01 (95% CI, -0.04 to 0.02)].

Conclusions And Relevance: Although hospital-acquired conditions targeted under the HACRP declined at a greater rate after the program was announced, 30-day mortality was unchanged.
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http://dx.doi.org/10.1097/SLA.0000000000003641DOI Listing
October 2021

Medicare Advantage Plan Double Bonuses Drive Racial Disparity In Payments, Yield No Quality Or Enrollment Improvements.

Health Aff (Millwood) 2021 09;40(9):1411-1419

Andrew M. Ryan is the UnitedHealthcare Professor of Health Care Management, Department of Health Management and Policy, University of Michigan School of Public Health, and director of the Center for Evaluating Health Reform, University of Michigan.

Under the Medicare Advantage (MA) quality bonus payment program, initiated in 2012, MA plans with relatively high quality performance that are located in "double bonus"-eligible counties-metropolitan areas with high MA enrollment and low fee-for-service Medicare spending-receive quality bonuses twice as large as those received by equivalently high-quality plans in double-bonus-ineligible counties. Using national data for 2008-18, we found that double bonuses were not associated with either improvements in plan quality or increased MA enrollment. Additionally, because Black beneficiaries were less likely to reside in eligible counties, double bonuses increased payments to plans to care for Black beneficiaries by $60 per year, compared with $91 for White beneficiaries. Our findings suggest that double bonuses not only fail to improve quality and enrollment but also foster a racially inequitable distribution of Medicare funds that disfavors Black beneficiaries. Our study supports eliminating double bonuses, thereby saving Medicare an estimated $1.8 billion per year.
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http://dx.doi.org/10.1377/hlthaff.2021.00349DOI Listing
September 2021

Volume-outcome relationships for Roux-en-Y gastric bypass patients in the sleeve gastrectomy era.

Surg Endosc 2021 Sep 1. Epub 2021 Sep 1.

Center for Healthcare Outcomes and Policy, University of Michigan, Ann Arbor, MI, USA.

Background: Sleeve gastrectomy is now the most common bariatric operation performed. With lower volumes of Roux-en-Y gastric bypass (RYGB), it is unclear whether decreasing surgeon experience has led to worsening outcomes for this procedure.

Methods: We used State Inpatient Databases from Florida, Iowa, New York, and Washington. Bariatric surgeons were designated as those who performed ten or more bariatric procedures yearly. Patients who had RYGB were included in our analysis. Using multi-level logistic regression, we examined whether surgeon average yearly RYGB volume was associated with RYGB patient 30-day complications, reoperations, and readmissions and 1-year revisions and readmissions.

Results: From 2013 to 2017 there were 27,714 patients who underwent laparoscopic RYGB by 311 surgeons. Median surgeon volume was 77 RYGBs per year. The distribution was 10 bypasses yearly at the 5th percentile, 16 bypasses at the 10th percentile, 38 bypasses at the 25th percentile, and 133 bypasses at the 75th percentile. Multi-level regression revealed that patients of surgeons with lower RYGB volumes had small but statistically significant increased risks of 30-day complications and 1-year readmissions. At 30 days, risk for any complication was 6.71%, 6.43%, and 5.55% at 10, 38, and 133 bypasses per year, respectively (p = 0.01). Risk for readmission at 1 year was 13.90%, 13.67%, and 12.90% at 10, 38, and 133 bypasses per year, respectively (p = 0.099). Of note, volume associations with complications and reoperations due to hemorrhage and leak were not statistically significant. There was also no significant association with revisions.

Conclusion: This is the first study to examine the association of surgeon RYGB volume with patient outcomes as the national experience with RYGB diminishes. Overall, surgeon RYGB volume does not appear to have a large effect on patient outcomes. Thus, patients can safely pursue RYGB in this early phase of the sleeve gastrectomy era.
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http://dx.doi.org/10.1007/s00464-021-08705-6DOI Listing
September 2021

Intensity of end-of-life care for dual-eligible beneficiaries with cancer and the impact of delivery system affiliation.

Cancer 2021 Aug 24. Epub 2021 Aug 24.

Department of Urology, University of Michigan, Ann Arbor, Michigan.

Background: Dual-eligible beneficiaries, who qualify for Medicare and Medicaid, are a vulnerable population with much to gain from efforts to improve quality. Integrated delivery networks and cancer centers, with their emphasis on care coordination and communication, may improve quality of care for dual-eligible patients with cancer at the end of life.

Methods: This study used Surveillance, Epidemiology, and End Results registry data linked with Medicare claims to evaluate quality for beneficiaries who died of cancer and were diagnosed from 2009 to 2014. High-intensity care was evaluated with 7 end-of-life quality measures according to dual-eligible status with multivariable logistic regression models. Regression-based techniques were used to assess the effect of delivery system affiliation (ie, cancer center or integrated delivery network vs no affiliation).

Results: Among 100,549 beneficiaries who died during the study interval, 22% were dually eligible. Inferior outcomes were identified for dual-eligible beneficiaries in comparison with nondual beneficiaries across nearly every quality measure assessed, including >1 hospitalization in the last 30 days (12.6% vs 11.3%; P < .001) and a greater proportion of deaths occurring in a hospital setting (30.2% vs 26.2%; P < .001). Receipt of care in an affiliated delivery system was associated with reduced deaths in a hospital setting and increased hospice utilization for dual-eligible beneficiaries.

Conclusions: Dual-eligible status is associated with higher intensity care at the end of life. Delivery system affiliation has a modest impact on quality at the end of life, and this suggests that targeted efforts may be needed to optimize quality for this group of vulnerable patients.
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http://dx.doi.org/10.1002/cncr.33874DOI Listing
August 2021

The MURAL collection of prostate cancer patient-derived xenografts enables discovery through preclinical models of uro-oncology.

Nat Commun 2021 08 19;12(1):5049. Epub 2021 Aug 19.

Sir Peter MacCallum Department of Oncology, The University of Melbourne, Parkville, VIC, Australia.

Preclinical testing is a crucial step in evaluating cancer therapeutics. We aimed to establish a significant resource of patient-derived xenografts (PDXs) of prostate cancer for rapid and systematic evaluation of candidate therapies. The PDX collection comprises 59 tumors collected from 30 patients between 2012-2020, coinciding with availability of abiraterone and enzalutamide. The PDXs represent the clinico-pathological and genomic spectrum of prostate cancer, from treatment-naïve primary tumors to castration-resistant metastases. Inter- and intra-tumor heterogeneity in adenocarcinoma and neuroendocrine phenotypes is evident from bulk and single-cell RNA sequencing data. Organoids can be cultured from PDXs, providing further capabilities for preclinical studies. Using a 1 x 1 x 1 design, we rapidly identify tumors with exceptional responses to combination treatments. To govern the distribution of PDXs, we formed the Melbourne Urological Research Alliance (MURAL). This PDX collection is a substantial resource, expanding the capacity to test and prioritize effective treatments for prospective clinical trials in prostate cancer.
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http://dx.doi.org/10.1038/s41467-021-25175-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8376965PMC
August 2021

Hospital Participation Decisions In Medicare Bundled Payment Program Were Influenced By Third-Party Conveners.

Health Aff (Millwood) 2021 08;40(8):1286-1293

Andrew M. Ryan is the UnitedHealthcare Professor of Health Care Management, Department of Health Management and Policy, University of Michigan School of Public Health, and director of the Center for Evaluating Health Reform, University of Michigan.

The Bundled Payments for Care Improvement initiative Advanced Model (BPCI Advanced) is a voluntary Medicare bundled payment model in which hospitals may participate with third-party conveners-private consulting firms that share in the financial risk built into the program. We found that nonteaching and for-profit status was associated with a higher probability of hospital partnership with third-party conveners in BPCI Advanced. Among hospitals participating in at least one inpatient clinical episode, hospitals that partnered with third-party conveners were more likely to select episodes with higher target prices: A $1,000 increase in episode target price was associated with a 1.66-percentage-point increase in the probability of episode participation in BPCI Advanced compared with a 0.72-percentage-point increase for participating hospitals without third-party conveners. Hospitals with third-party conveners also were more likely than those without them to select inpatient clinical episodes with greater opportunities to reduce spending on postacute care and readmissions. These findings have important implications for understanding the role of private consulting firms in the program and for planning potential program modifications in the future.
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http://dx.doi.org/10.1377/hlthaff.2020.01766DOI Listing
August 2021

Loss of in Prostate Cancer Correlates With Clinical Response to Androgen Deprivation Therapy.

JCO Precis Oncol 2021 Jun 22;5. Epub 2021 Jun 22.

Department of Surgery, University of Melbourne, Parkville, Victoria, Australia.

Purpose: Androgen receptor (AR) signaling is important in prostate cancer progression, and therapies that target this pathway have been the mainstay of treatment for advanced disease for over 70 years. Tumors eventually progress despite castration through a number of well-characterized mechanisms; however, little is known about what determines the magnitude of response to short-term pathway inhibition.

Methods: We evaluated a novel combination of AR-targeting therapies (degarelix, abiraterone, and bicalutamide) and noted that the objective patient response to therapy was highly variable. To investigate what was driving treatment resistance in poorly responding patients, as a secondary outcome we comprehensively characterized pre- and post-treatment samples using both whole-genome and RNA sequencing.

Results: We find that resistance following short-term treatment differs molecularly from typical progressive castration-resistant disease, associated with transcriptional reprogramming, to a transitional epithelial-to-mesenchymal transition (EMT) phenotype rather than an upregulation of AR signaling. Unexpectedly, tolerance to therapy appears to be the default state, with treatment response correlating with the prevalence of tumor cells deficient for , a key regulator of EMT reprogramming.

Conclusion: We show that EMT characterizes acutely resistant prostate tumors and that deletion of , a key transcriptional regulator of EMT, correlates with clinical response.
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http://dx.doi.org/10.1200/PO.20.00337DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8238292PMC
June 2021

The modified International Society of Urological Pathology system improves concordance between biopsy and prostatectomy tumour grade.

BJU Int 2021 Jul 26. Epub 2021 Jul 26.

Department of Urology, Melbourne Health, Royal Melbourne Hospital, Australia.

Objectives: To assess the concordance between biopsy and radical prostatectomy (RP) specimens using the 2005 Gleason score (GS) and the International Society of Urological Pathology (ISUP) 2014/World Health Organization 2016 modified system, accounting for the introduction of transperineal biopsy and pre-biopsy multiparametric magnetic resonance imaging (mpMRI).

Patients And Methods: Between 2002 and 2019, we identified 2431 patients with paired biopsy and RP histopathology from a prospectively recorded and maintained prostate cancer database. Biopsy specimens were graded according to the 2005 GS or ISUP 2014 modified system, according to the year of diagnosis. Multivariable logistic regression analysis was conducted to retrospectively assess the impact of prostate-specific antigen (PSA), PSA density, age, pre-biopsy mpMRI, and biopsy method, on the rate of upgraded disease. The kappa coefficient was used to establish the degree of change in concordance between groups.

Results: Overall, 24% of patients had upgraded disease and 8% of patients had downgraded disease when using the modified ISUP 2014 criteria. Agreement in the updated ISUP 2014 cohort was 68%, compared with 55% in the 2005 GS group, which was validated by a kappa coefficient that was good (k = 0.5 ± 0.4) and poor (k = 0.3 ± 0.1), respectively. In multivariable models, a change in grading system independently improved overall disease concordance (P = 0.02), and there were no other co-segregated patient or pathological factors such as PSA, total number of cores, maximum cancer length, biopsy route or the use of mpMRI that impacted this finding.

Conclusion: The 2014 ISUP modifed system improves overall concordance between biopsy and surgical specimens, and thus allows more accurate prognostication and management in high-grade disease, independent of more extensive prostate sampling and the use of mpMRI.
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http://dx.doi.org/10.1111/bju.15556DOI Listing
July 2021

MSH2-deficient prostate tumours have a distinct immune response and clinical outcome compared to MSH2-deficient colorectal or endometrial cancer.

Prostate Cancer Prostatic Dis 2021 Dec 9;24(4):1167-1180. Epub 2021 Jun 9.

Departments of Surgery and Urology, University of Melbourne, Royal Melbourne Hospital, Parkville, VIC, Australia.

Background: Recent publications have shown patients with defects in the DNA mismatch repair (MMR) pathway driven by either MSH2 or MSH6 loss experience a significant increase in the incidence of prostate cancer. Moreover, this increased incidence of prostate cancer is accompanied by rapid disease progression and poor clinical outcomes.

Methods And Results: We show that androgen-receptor activation, a key driver of prostate carcinogenesis, can disrupt the MSH2 gene in prostate cancer. We screened tumours from two cohorts (recurrent/non-recurrent) of prostate cancer patients to confirm the loss of MSH2 protein expression and identified decreased MSH2 expression in recurrent cases. Stratifying the independent TCGA prostate cancer cohort for MSH2/6 expression revealed that patients with lower levels of MSH2/6 had significant worse outcomes, in contrast, endometrial and colorectal cancer patients with lower MSH2/6 levels. MMRd endometrial and colorectal tumours showed the expected increase in mutational burden, microsatellite instability and enhanced immune cell mobilisation but this was not evident in prostate tumours.

Conclusions: We have shown that loss or reduced levels of MSH2/MSH6 protein in prostate cancer is associated with poor outcome. However, our data indicate that this is not associated with a statistically significant increase in mutational burden, microsatellite instability or immune cell mobilisation in a cohort of primary prostate cancers.
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http://dx.doi.org/10.1038/s41391-021-00379-4DOI Listing
December 2021

Improving target price calculations in Medicare bundled payment programs.

Health Serv Res 2021 08 2;56(4):635-642. Epub 2021 Jun 2.

University of Michigan School of Public Health, Ann Arbor, Michigan, USA.

Objective: To compare the predictive accuracy of two approaches to target price calculations under Bundled Payments for Care Improvement-Advanced (BPCI-A): the traditional Centers for Medicare and Medicaid Services (CMS) methodology and an empirical Bayes approach designed to mitigate the effects of regression to the mean.

Data Sources: Medicare fee-for-service claims for beneficiaries discharged from acute care hospitals between 2010 and 2016.

Study Design: We used data from a baseline period (discharges between January 1, 2010 and September 30, 2013) to predict spending in a performance period (discharges between October 1, 2015 and June 30, 2016). For 23 clinical episode types in BPCI-A, we compared the average prediction error across hospitals associated with each statistical approach. We also calculated an average across all clinical episode types and explored differences by hospital size.

Data Collection/extraction Methods: We used a 20% sample of Medicare claims, excluding hospitals and episode types with small numbers of observations.

Principal Findings: The empirical Bayes approach resulted in significantly more accurate episode spending predictions for 19 of 23 clinical episode types. Across all episode types, prediction error averaged $8456 for the CMS approach versus $7521 for the empirical Bayes approach. Greater improvements in accuracy were observed with increasing hospital size.

Conclusions: CMS should consider using empirical Bayes methods to calculate target prices for BPCI-A.
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http://dx.doi.org/10.1111/1475-6773.13675DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8313949PMC
August 2021

Changes in Dialysis Center Quality Associated With the End-Stage Renal Disease Quality Incentive Program : An Observational Study With a Regression Discontinuity Design.

Ann Intern Med 2021 08 1;174(8):1058-1064. Epub 2021 Jun 1.

University of Michigan and Center for Healthcare Outcomes and Policy, Ann Arbor, Michigan (S.A.W.).

Background: In 2012, the Centers for Medicare & Medicaid Services started levying performance-based financial penalties against outpatient dialysis centers under the mandatory End-Stage Renal Disease Quality Incentive Program.

Objective: To determine whether penalization was associated with improvement in dialysis center quality.

Design: Leveraging the threshold for penalization (total performance score < 60), a regression discontinuity design was used to examine the effect of penalization on quality over 2 years. Publicly available Medicare data from 2015-2018 were used. The effect of penalization at dialysis centers with different characteristics (for example, size or chain affiliation) was also examined.

Setting: United States.

Participants: Outpatient dialysis centers ( = 5830).

Measurements: Dialysis center total performance scores (a composite metric ranging from 0 to 100 based on clinical quality and adherence to reporting requirements) and individual measures that contribute to the total performance score.

Results: There were 1109 (19.0%) outpatient dialysis centers that received penalties in 2017 on the basis of performance in 2015. Penalized centers were located in ZIP codes with a higher average proportion of non-White residents (36.4% vs. 31.2%;  < 0.001) and residents with lower median income ($49 290 vs. $51 686;  < 0.001). Penalization was not associated with improvement in total performance scores in 2017 (0.4 point [95% CI, -2.5 to 3.2 points]) or 2018 (0.3 point [CI, -2.8 to 3.4 points]). This was consistent across dialysis centers with different characteristics. There was also no association between penalization and improvement in specific measures.

Limitation: The study could not account for how centers respond to penalization.

Conclusion: Penalization under the End-Stage Renal Disease Quality Incentive Program was not associated with improvement in the quality of outpatient dialysis centers.

Primary Funding Source: None.
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http://dx.doi.org/10.7326/M20-6662DOI Listing
August 2021

Medicare's Hospital Value-Based Purchasing Program Values Quality over QALYs.

Med Decis Making 2022 Jan 27;42(1):51-59. Epub 2021 May 27.

Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA.

Medicare's Hospital Value-Based Purchasing Program (HVBP) is the first national pay-for-performance program to combine measures of quality of care with a measure of episode spending. We estimated the implicit tradeoffs between mortality reduction and spending reduction. To earn points in HVBP, a hospital can either lower mortality or reduce spending, creating a tradeoff between the 2 measures. We analyzed the quality performance and earned points of 2814 hospitals using publicly available data. We then quantified the tradeoffs between spending and mortality in terms of quality-adjusted life-years (QALYs). If incentives in the program were balanced, then the tradeoff between spending and QALYs should be comparable with those of high-value health interventions, roughly $50,000 to $200,000 per QALY. Instead, the tradeoff in HVBP was about $1.2 million per QALY. HVBP overvalues improvements in quality of care relative to spending reductions. We propose 2 possible policy adjustments that could improve incentives for hospitals to deliver high-value care.
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http://dx.doi.org/10.1177/0272989X211017105DOI Listing
January 2022

Access to Mechanical Thrombectomy for Ischemic Stroke in the United States.

Stroke 2021 Aug 13;52(8):2554-2561. Epub 2021 May 13.

Clinical and Translational Neuroscience Unit, Feil Family Brain and Mind Research Institute and Department of Neurology (H.K., N.S.P., A.C., B.B.N.), Weill Cornell Medicine, New York, NY.

[Figure: see text].
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http://dx.doi.org/10.1161/STROKEAHA.120.033485DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8316281PMC
August 2021

Bundled Payments for Care Improvement (BPCI) Efficacy across Three Common Operations.

Ann Surg 2021 Mar 29. Epub 2021 Mar 29.

*Medical Scientist Training Program, University of Michigan Medical School, Ann Arbor, MI †Department of Economics, University of Michigan, Ann Arbor, MI ‡School of Public Health, University of Michigan, Ann Arbor, MI §National Clinician Scholars Program at the Institute for Healthcare Policy and Innovation, University of Michigan, Ann Arbor, MI ||Department of Surgery, Brigham and Women's Hospital, Boston, MA ¶Department of Surgery, University of Michigan, Ann Arbor, MI.

Objective: To evaluate associations between hospital participation in Bundled Payments for Care Improvement (BPCI) and thirty-day total episode and post-acute care spending for lower extremity joint replacement (LEJR), coronary artery bypass graft (CABG), and colectomy.

Summary Background Data: BPCI has been shown to reduce spending for LEJR episodes only, largely from reductions in post-acute care. However, BPCI efficacy in other common elective procedures, including CABG and colectomy, remains unclear. It is also unknown whether post-acute care spending reductions drive total spending reductions outside of LEJR.

Methods: Retrospective cohort study using 100% Medicare claims data to identify BPCI (312 total) and non-BPCI (1,977 total) acute care hospitals from January 1, 2010 to November 30, 2016 with Medicare-enrolled patient discharges for at least one BPCI episode: LEJR (454,369 episodes), CABG (107,307 episodes), or colectomy (73,717 episodes). Along with difference-in-differences analysis, we constructed generalized synthetic controls in the presence of non-parallel trends to estimate associations between BPCI participation and thirty-day total and post-acute care spending.

Results: Difference-in-differences estimates indicated reduced spending for LEJR (-$541.6 (95% CI: -718.0 to -365.3)) and colectomy (-$582.1 (95% CI: -927.3 to -236.8)) but not CABG (-$268.9 (95% CI: -831.5 to 293.7)). Generalized synthetic control estimates indicated reduced spending for LEJR (-$795.3 (95% CI: -1022.1 to -582.2)) but not colectomy (-$251.3 (95% CI: -997.9 to 335.2)) or CABG (-$257.8 (95% CI: -1024.6 to 414.8)). Post-acute care comprised 42.6% of LEJR spending reductions and 53.0% of colectomy spending reductions.

Conclusions: BPCI participation was associated with significant spending reductions for LEJR and colectomy but not CABG. We conclude that BPCI has episode-dependent efficacy, largely determined by post-acute care.
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http://dx.doi.org/10.1097/SLA.0000000000004869DOI Listing
March 2021

Ribosome quality control activity potentiates vaccinia virus protein synthesis during infection.

J Cell Sci 2021 04 28;134(8). Epub 2021 Apr 28.

Section of Cell and Developmental Biology, University of California, San Diego, La Jolla, CA 92093, USA.

Viral infection both activates stress signaling pathways and redistributes ribosomes away from host mRNAs to translate viral mRNAs. The intricacies of this ribosome shuffle from host to viral mRNAs are poorly understood. Here, we uncover a role for the ribosome-associated quality control (RQC) factor ZNF598 during vaccinia virus mRNA translation. ZNF598 acts on collided ribosomes to ubiquitylate 40S subunit proteins uS10 (RPS20) and eS10 (RPS10), initiating RQC-dependent nascent chain degradation and ribosome recycling. We show that vaccinia infection enhances uS10 ubiquitylation, indicating an increased burden on RQC pathways during viral propagation. Consistent with an increased RQC demand, we demonstrate that vaccinia virus replication is impaired in cells that either lack ZNF598 or express a ubiquitylation-deficient version of uS10. Using SILAC-based proteomics and concurrent RNA-seq analysis, we determine that translation, but not transcription of vaccinia virus mRNAs is compromised in cells with deficient RQC activity. Additionally, vaccinia virus infection reduces cellular RQC activity, suggesting that co-option of ZNF598 by vaccinia virus plays a critical role in translational reprogramming that is needed for optimal viral propagation.
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http://dx.doi.org/10.1242/jcs.257188DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8106952PMC
April 2021

Cystic papillary adenoma of the seminal vesicle.

BMC Urol 2021 Apr 15;21(1):62. Epub 2021 Apr 15.

Austin Health, Melbourne, Australia.

Background: Primary Seminal Vesicle (SV) tumours are a rare entity, with most SV masses representing invasion of the SV by malignancy originating in an adjacent organ, most often the prostate. Previously reported primary SV epithelial tumours have included adenocarcinoma and cystadenoma, with limited prior reports of inracystic papillary structures.

Case Presentation: A 35-year-old male presented with azoospermia, intermittent macroscopic haematuria, and mild right iliac fossa and groin pain. A papillary appearing seminal vesicle mass was found on imaging and seminal vesicoscopy. The mass was robotically excised with diagnosis of benign cystic papillary adenoma made.

Conclusion: In this manuscript we describe a rare case of a benign cystic papillary adenoma of the seminal vesicle, a unique histological entity differentiated from cystadenoma of the Seminal Vesicle by its papillary component.
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http://dx.doi.org/10.1186/s12894-021-00830-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8051035PMC
April 2021

Use of Telehealth by Surgical Specialties During the COVID-19 Pandemic.

JAMA Surg 2021 07;156(7):620-626

Institute for Healthcare Policy and Innovation, University of Michigan, Ann Arbor.

Importance: While telehealth use in surgery has shown to be feasible, telehealth became a major modality of health care delivery during the COVID-19 pandemic.

Objective: To assess patterns of telehealth use across surgical specialties before and during the COVID-19 pandemic.

Design, Setting, And Participants: Insurance claims from a Michigan statewide commercial payer for new patient visits with a surgeon from 1 of 9 surgical specialties during one of the following periods: prior to the COVID-19 pandemic (period 1: January 5 to March 7, 2020), early pandemic (period 2: March 8 to June 6, 2020), and late pandemic (period 3: June 7 to September 5, 2020).

Exposures: Telehealth implementation owing to the COVID-19 pandemic in March 2020.

Main Outcomes And Measures: (1) Conversion rate defined as the rate of weekly new patient telehealth visits divided by mean weekly number of total new patient visits in 2019. This outcome adjusts for a substantial decrease in outpatient care during the pandemic. (2) Weekly number of new patient telehealth visits divided by weekly number of total new patient visits.

Results: Among 4405 surgeons in the cohort, 2588 (58.8%) performed telehealth in any patient care context. Specifically for new patient visits, 1182 surgeons (26.8%) used telehealth. A total of 109 610 surgical new outpatient visits were identified during the pandemic. The median (interquartile range) age of telehealth patients was 46.8 (34.1-58.4) years compared with 52.6 (38.3-62.3) years for patients who received care in-person. Prior to March 2020, less than 1% (8 of 173 939) of new patient visits were conducted through telehealth. Telehealth use peaked in April 2020 (week 14) and facilitated 34.6% (479 of 1383) of all new patient visits during that week. The telehealth conversion rate peaked in April 2020 (week 15) and was equal to 8.2% of the 2019 mean weekly new patient visit volume. During period 2, a mean (SD) of 16.6% (12.0%) of all new patient surgical visits were conducted via telehealth (conversion rate of 5.1% of 2019 mean weekly new patient visit volumes). During period 3, 3.0% (2168 of 71 819) of all new patient surgical visits were conducted via telehealth (conversion rate of 2.5% of 2019 new patient visit volumes). Mean (SD) telehealth conversion rates varied by specialty with urology being the highest (14.3% [7.7%]).

Conclusions And Relevance: Results from this study showed that telehealth use grew across all surgical specialties in Michigan in response to the COVID-19 pandemic. While rates of telehealth use have declined as in-person care has resumed, telehealth use remains substantially higher across all surgical specialties than it was prior to the pandemic.
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http://dx.doi.org/10.1001/jamasurg.2021.0979DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7998347PMC
July 2021

Combined Utility of Ga-Prostate-specific Membrane Antigen Positron Emission Tomography/Computed Tomography and Multiparametric Magnetic Resonance Imaging in Predicting Prostate Biopsy Pathology.

Eur Urol Oncol 2021 Mar 16. Epub 2021 Mar 16.

Department of Surgery, Monash University, Melbourne, Australia; Australian Urology Associates, Malvern, Australia; Cabrini Institute, Cabrini Health, Malvern, Australia.

Background: Gallium-labelled prostate-specific membrane antigen positron emission tomography (Ga-PSMA-11 PET) is a valuable staging tool, but its utility in characterising primary prostate cancer remains unclear. The maximum standardised uptake value (SUVmax) is a quantification measure of highest radiotracer uptake within PET-avid lesions.

Objective: To assess the utility of SUVmax in detecting clinically significant prostate cancer (csPCa) on biopsy alone and in combination with multiparametric magnetic resonance imaging (mpMRI).

Design, Setting, And Participants: This was a retrospective analysis of 200 men who underwent Ga-PSMA-11 PET/CT, mpMRI, and transperineal template prostate biopsy between 2016 and 2018.

Outcome Measurements And Statistical Analysis: The primary and secondary outcomes were detection of grade group (GG) 3-5 and GG 2-5 prostate cancer, respectively. We used the Mann-Whitney U test to compare SUVmax by GG, and calculated sensitivity and specificity for csPCa detection via Ga-PSMA-11 PET/CT, mpMRI, and both. Multivariable logistic regression analyses were used to identify predictors of csPCa on biopsy.

Results And Limitations: The median SUVmax was greater for GG 3-5 tumours (6.40, interquartile range [IQR] 4.47-11.0) than for benign and GG 1-2 tumours (3.14, IQR 2.55-3.91; p <  0.001). The median SUVmax was greater for GG 3 (5.70, IQR 3.68-8.67) than for GG 2 (3.47, IQR 2.70-4.74; p <  0.001). For GG 3-5 disease, sensitivity was 86.5%, 95.9%, and 98.6%, and the negative predictive value (NPV) was 88.4%, 88.5%, and 93.3% using SUVmax ≥4, a Prostate Imaging-Reporting and Data System (PI-RADS) score of 3-5, and both, respectively. This combined model detected more GG 3-5 disease than mpMRI alone (98.6% vs 95.9%; p =  0.04). SUVmax was an independent predictor of csPCa for GG 3-5 disease only (odds ratio 1.27 per unit, 95% confidence interval 1.13-1.45). Our results are limited by the retrospective study design.

Conclusions: Greater SUVmax on Ga-PSMA-11 PET/CT is associated with detection of GG 3-5 cancer on biopsy. The combination of PI-RADS score and SUVmax provides higher sensitivity and NPV than either alone. Ga-PSMA-11 PET/CT may be useful alongside mpMRI in improving risk stratification for localised disease.

Patient Summary: The amount of a radioactive tracer taken up in the prostate during a type of scan called PET (positron emission tomography) can predict whether aggressive prostate cancer is likely to be found on biopsy. This may complement the more usual type of scan, MRI (magnetic resonance imaging), used to detect prostate cancer.
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http://dx.doi.org/10.1016/j.euo.2021.02.006DOI Listing
March 2021

Oxytocin receptor antagonists as a novel pharmacological agent for reducing smooth muscle tone in the human prostate.

Sci Rep 2021 03 18;11(1):6352. Epub 2021 Mar 18.

Drug Discovery Biology, Monash Institute of Pharmaceutical Sciences, Monash University, 381 Royal Parade, Parkville, Melbourne, VIC, 3052, Australia.

Pharmacotherapies for the treatment of Benign Prostatic Hyperplasia (BPH) are targeted at reducing cellular proliferation (static component) or reducing smooth muscle tone (dynamic component), but response is unpredictable and many patients fail to respond. An impediment to identifying novel pharmacotherapies is the incomplete understanding of paracrine signalling. Oxytocin has been highlighted as a potential paracrine mediator of BPH. To better understand oxytocin signalling, we investigated the effects of exogenous oxytocin on both stromal cell proliferation, and inherent spontaneous prostate contractions using primary models derived from human prostate tissue. We show that the Oxytocin Receptor (OXTR) is widely expressed in the human prostate, and co-localises to contractile cells within the prostate stroma. Exogenous oxytocin did not modulate prostatic fibroblast proliferation, but did significantly (p < 0.05) upregulate the frequency of spontaneous contractions in prostate tissue, indicating a role in generating smooth muscle tone. Application of atosiban, an OXTR antagonist, significantly (p < 0.05) reduced spontaneous contractions. Individual tissue responsiveness to both exogenous oxytocin (R = 0.697, p < 0.01) and atosiban (R = 0.472, p < 0.05) was greater in tissue collected from older men. Overall, our data suggest that oxytocin is a key regulator of inherent spontaneous prostate contractions, and targeting of the OXTR and associated downstream signalling is an attractive prospect in the development of novel BPH pharmacotherapies.
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http://dx.doi.org/10.1038/s41598-021-85439-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7973579PMC
March 2021

No More Surprises - New Legislation on Out-of-Network Billing.

N Engl J Med 2021 Apr 17;384(15):1381-1383. Epub 2021 Mar 17.

From the Department of Surgery, Brigham and Women's Hospital, Boston (K.R.C.), the College of Law, Georgia State University, Atlanta (E.F.B.), and the Center for Evaluating Health Reform and the School of Public Health, University of Michigan, Ann Arbor (A.M.R.).

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http://dx.doi.org/10.1056/NEJMp2035905DOI Listing
April 2021

Predictive Model-Driven Hotspotting to Decrease Emergency Department Visits: a Randomized Controlled Trial.

J Gen Intern Med 2021 09 10;36(9):2563-2570. Epub 2021 Mar 10.

University of Michigan School of Public Health, Ann Arbor, MI, USA.

Background: Emergency department (ED) visits contribute substantially to health care expenditures. Case management has been proposed as a strategy to address the medical and social needs of complex patients. However, strong research designs to evaluate the effectiveness of such interventions are limited.

Objectives: To evaluate whether a community-based case management program was associated with reduced ED utilization among complex patients.

Design: Patients whose risk exceeded a threshold were randomly assigned to a group offered case management or to the control group. Assignment occurred at five intervals between November 2017 and January 2019. Program effectiveness for all assigned patients was assessed using an intention-to-treat effect. Program effectiveness among those who received treatment was assessed using a local average treatment effect, estimated using instrumental variables. Both estimators were adjusted for baseline characteristics using linear models.

Participants: Adults over age 18 with at least one health care encounter with Michigan Medicine or St. Joseph Mercy Health System between June 2, 2016, and November 27, 2018.

Interventions: Intervention arm participants (n = 486) were offered coordinated case management across medical, mental health, and social service organizations. Control arm participants (n = 409) received usual care.

Main Measures: The primary outcome was the number of ED visits in the 6 months following randomization into the study. Secondary outcomes were 6-month counts of inpatient and outpatient visits.

Key Results: Of the 486 patients assigned to the intervention, 131 (27%) consented to receive case management. The intention-to-treat effect on ED visits was + 0.14 (95% CI: - 0.27 to + 0.55). The local average treatment effect among those who consented and received case management was + 0.53 (95% CI: - 1.00 to + 2.05). Intention-to-treat and local average treatment effects were not significant for secondary outcomes.

Conclusions: The community case management intervention targeting ED visits was not associated with reduced utilization. Future case management interventions may benefit from additional patient engagement strategies and longer evaluation time periods.

Trial Registration: Clinicaltrials.gov Identifier: NCT03293160.
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http://dx.doi.org/10.1007/s11606-021-06664-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8390593PMC
September 2021

Ductal variant prostate carcinoma is associated with a significantly shorter metastasis-free survival.

Eur J Cancer 2021 05 5;148:440-450. Epub 2021 Mar 5.

Department of Surgery, University of Melbourne, Parkville, Victoria, Australia; Urology Unit, Royal Melbourne Hospital, Parkville, Victoria, Australia; Victorian Comprehensive Cancer Centre, Melbourne, Victoria, Australia; Department of Urology, Frankston Hospital, Frankston, Victoria, Australia.

Background: Ductal adenocarcinoma is an uncommon prostate cancer variant. Previous studies suggest that ductal variant histology may be associated with worse clinical outcomes, but these are difficult to interpret. To address this, we performed an international, multi-institutional study to describe the characteristics of ductal adenocarcinoma, particularly focussing on the effect of presence of ductal variant cancer on metastasis-free survival.

Methods: Patients with ductal variant histology from two institutional databases who underwent radical prostatectomies were identified and compared with an independent acinar adenocarcinoma cohort. After propensity score matching, the effect of the presence of ductal adenocarcinoma on time to biochemical recurrence, initiation of salvage therapy and the development of metastatic disease was determined. Deep whole-exome sequencing was performed for selected cases (n = 8).

Results: A total of 202 ductal adenocarcinoma and 2037 acinar adenocarcinoma cases were analysed. Survival analysis after matching demonstrated that patients with ductal variant histology had shorter salvage-free survival (8.1 versus 22.0 months, p = 0.03) and metastasis-free survival (6.7 versus 78.6 months, p < 0.0001). Ductal variant histology was consistently associated with RB1 loss, as well as copy number gains in TAP1, SLC4A2 and EHHADH.

Conclusions: The presence of any ductal variant adenocarcinoma at the time of prostatectomy portends a worse clinical outcome than pure acinar cancers, with significantly shorter times to initiation of salvage therapies and the onset of metastatic disease. These features appear to be driven by uncoupling of chromosomal duplication from cell division, resulting in widespread copy number aberration with specific gain of genes implicated in treatment resistance.
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http://dx.doi.org/10.1016/j.ejca.2020.12.030DOI Listing
May 2021

Longitudinal participation in delivery and payment reform programs among US Primary Care Organizations.

Health Serv Res 2021 Feb 28. Epub 2021 Feb 28.

University of Michigan, Ann Arbor, Michigan, USA.

Objective: To assess longitudinal primary care organization participation patterns in large-scale reform programs and identify organizational characteristics associated with multiprogram participation.

Data Sources: Secondary data analysis of national program participation data over an eight-year period (2009-2016).

Study Design: We conducted a retrospective, observational study by creating a unique set of data linkages (including Medicare and Medicaid Meaningful Use and Medicare Shared Savings Program Accountable Care Organization (MSSP ACO) participation from CMS, Patient-Centered Medical Home (PCMH) participation from the National Committee for Quality Assurance, and organizational characteristics) to measure longitudinal participation and identify what types of organizations participate in one or more of these reform programs. We used multivariate models to identify organizational characteristics that differentiate those that participate in none, one, or two-to-three programs.

Data Extraction Methods: We used Medicare claims to identify organizations that delivered primary care services (n = 56 ,287) and then linked organizations to program participation data and characteristics.

Principal Findings: No program achieved more than 50% participation across the 56,287 organizations in a given year, and participation levels flattened or decreased in later years. 36% of organizations did not participate in any program over the eight-year study period; 50% participated in one; 13% in two; and 1% in all three. 14.31% of organizations participated in five or more years of Meaningful Use while 3.84% of organizations participated in five years of the MSSP ACO Program and 0.64% participated in at least five years of PCMH. Larger organizations, those with younger providers, those with more primary care providers, and those with larger Medicare patient panels were more likely to participate in more programs.

Conclusions And Relevance: Primary care transformation via use of voluntary programs, each with their own participation requirements and approach to incentives, has failed to broadly engage primary care organizations. Those that have chosen to participate in multiple programs are likely those already providing high-quality care.
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http://dx.doi.org/10.1111/1475-6773.13646DOI Listing
February 2021
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