Comparing Patient-reported Functional Outcomes After Radical Prostatectomy in Historical and Contemporary Practice.

PURPOSE: Modifications to surgical technique, particularly the widespread adoption of robotic surgery, have been proposed to improve functional recovery after prostate cancer surgery. However, rigorous comparison of men in historical vs contemporary practice to evaluate the cumulative effect of these changes on urinary and sexual function after radical prostatectomy is lacking. MATERIALS AND METHODS: We compared prospectively collected patient-reported urinary and sexual function from historical (PROSTQA [Prostate Cancer Outcomes and Satisfaction With Treatment Quality Assessment study], n=235) and contemporary (MUSIC-PRO [Michigan Urological Surgery Improvement Collaborative Patient Reported Outcome] registry, n=1,215) cohorts at the University of Michigan to understand whether modern techniques have resulted in functional improvements for men undergoing prostate cancer surgery. RESULTS: We found significant differences in baseline function, with better urinary (median [IQR]; 100 [93.8-100] vs 93.8 [85.5-100], P < .001) and sexual scores (median [IQR]; 83.3 [66.7-100] vs 74.4 [44.2-87.5], P < .001) prior to treatment in PROSTQA compared to MUSIC-PRO patients, respectively. There was no statistically significant difference in the pattern of urinary incontinence recovery after surgery from 6-24 months between groups (P = .14). However, men in the contemporary MUSIC-PRO group did have significantly better recovery of sexual function compared to men in the historical PROSTQA group (P < .0001). Further, we found that contemporary practice consists of men with more unfavorable demographic and clinical characteristics compared to historical practice. CONCLUSIONS: Our results demonstrate that the widespread alterations in prostate cancer surgery over the past 2 decades have yielded improvements in sexual, but not urinary, function recovery.

Intra-practice Urologist-level Variation in Targeted Fusion Biopsy Outcomes.

OBJECTIVE: To examine the extent to which the urologist performing biopsy contributes to variation in prostate cancer detection during fusion-guided prostate biopsy. METHODS: All men in the Michigan Urological Surgery Improvement Collaborative (MUSIC) clinical registry who underwent fusion biopsy at Michigan Medicine from August 2017 to March 2019 were included. The primary outcomes were clinically significant cancer detection rate (defined as Gleason Grade ≥2) in targeted cores and clinically significant cancer detection on targeted cores stratified by PI-RADS score. Bivariate and multivariable logistic regression analyses were performed. RESULTS: A total of 1133 fusion biopsies performed by 5 providers were included. When adjusting for patient age, PSA, race, family history, prostate volume, clinical stage, and PI-RADS score, there was no significant difference in targeted clinically significant cancer detection rates across providers (range = 38.5%-46.9%, adjusted P-value = .575). Clinically significant cancer detection rates ranged from 11.1% to 16.7% in PI-RADS 3 (unadjusted P = .838), from 24.6% to 43.4% in PI-RADS 4 (adjusted P = .003), and from 69.4% to 78.8% in PI-RADS 5 (adjusted P = .766) lesions. CONCLUSION: There was a statistically significant difference in clinically significant prostate cancer detection in PI-RADS 4 lesions across providers. These findings suggest that even among experienced providers, variation at the urologist level may contribute to differences in clinically significant cancer detection rates within PI-RADS 4 lesions. However, the relative impact of biopsy technique, radiologist interpretation, and MR acquisition protocol requires further study.

A study of degradation mechanisms in PVDF-based photovoltaic backsheets.

Commercial backsheets based on polyvinylidene fluoride (PVDF) can experience premature field failures in the form of outer layer cracking. This work seeks to provide a better understanding of the changes in material properties that lead to crack formation and find appropriate accelerated tests to replicate them. The PVDF-based backsheet outer layer can have a different structure and composition, and is often blended with a poly(methyl methacrylate) (PMMA) polymer. We observed depletion of PMMA upon aging with sequential (MAST) and combined (C-AST) accelerated stress testing. In field-aged samples from Arizona and India, where PVDF crystallizes in its predominant α-phase, the degree of crystallinity greatly increased. MAST and C-AST protocols were, to some extent, able to replicate the increase in crystallinity seen in PVDF after ~ 7 years in the field, but no single-stress test condition (UV, damp heat, thermal cycling) resulted in significant changes in the material properties. The MAST regimen used here was too extreme to produce realistic degradation, but the test was useful in discovering weaknesses of the particular PVDF-based outer layer structure studied. No excessive ß-phase formation was observed after aging with any test condition; however, the presence of ß-phase was identified locally by Fourier transform infrared spectroscopy (FTIR). We conclude that both MAST and C-AST are relevant tests for screening outdoor failure mechanisms in PVDF backsheets, as they were successful in producing material degradation that led to cracking.

Combining chemistry and protein engineering for new-to-nature biocatalysis.

Biocatalysis, the application of enzymes to solve synthetic problems of human import, has blossomed into a powerful technology for chemical innovation. In the past decade, a threefold partnership, where nature provides blueprints for enzymatic catalysis, chemists introduce innovative activity modes with abiological substrates, and protein engineers develop new tools and algorithms to tune and improve enzymatic function, has unveiled the frontier of new-to-nature enzyme catalysis. In this perspective, we highlight examples of interdisciplinary studies which have helped to expand the scope of biocatalysis, including concepts of enzymatic versatility explored through the lens of biomimicry, to achieve both activities and selectivities that are not currently possible with chemocatalysis. We indicate how modern tools, such as directed evolution, computational protein design and machine learning-based protein engineering methods, have already impacted and will continue to influence enzyme engineering for new abiological transformations. A sustained collaborative effort across disciplines is anticipated to spur further advances in biocatalysis in the coming years.

Biocatalytic One-Carbon Ring Expansion of Aziridines to Azetidines via a Highly Enantioselective [1,2]-Stevens Rearrangement.

We report enantioselective one-carbon ring expansion of aziridines to make azetidines as a new-to-nature activity of engineered "carbene transferase" enzymes. A laboratory-evolved variant of cytochrome P450BM3, P411-AzetS, not only exerts unparalleled stereocontrol (99:1 er) over a [1,2]-Stevens rearrangement but also overrides the inherent reactivity of aziridinium ylides, cheletropic extrusion of olefins, to perform a [1,2]-Stevens rearrangement. By controlling the fate of the highly reactive aziridinium ylide intermediates, these evolvable biocatalysts promote a transformation which cannot currently be performed using other catalyst classes.

MatOpt: A Python Package for Nanomaterials Design Using Discrete Optimization.

Novel materials are being enabled by advances in synthesis techniques that achieve ever better control over the atomic-scale structure of materials. The pace of materials development has been further increased by high-throughput computational experiments guided by informatics and machine learning. We have previously demonstrated complementary approaches using mathematical optimization models to search through highly combinatorial design spaces of atomic arrangements, guiding the design of nanostructured materials. In this paper, we highlight the common features of materials optimization problems that can be efficiently modeled via mixed-integer linear optimization models. To take advantage of these commonalities, we have created MatOpt, a Python package that formalizes the process of representing the design space and formulating optimization models for the on-demand design of nanostructured materials. This tool serves to bridge the gap between practitioners with expertise in materials science and those with expertise in formulating and solving mathematical optimization models, effectively lowering the barriers for applying rigorous numerical optimization capabilities during nanostructured materials development.

Impact of Decipher Biopsy testing on clinical outcomes in localized prostate cancer in a prospective statewide collaborative.

BACKGROUND: Decipher Biopsy is a commercially available gene expression classifier used in risk stratification of newly diagnosed prostate cancer (PCa). Currently, there are no prospective data evaluating its clinical utility. We seek to assess the clinical utility of Decipher Biopsy in localized PCa patients. METHODS: A multi-institutional study of 855 men who underwent Decipher Biopsy testing between February 2015 and October 2019. All patients were tracked through the prospective Michigan Urological Surgery Improvement Collaborative and linked to the Decipher Genomics Resource Information Database (GRID®; NCT02609269). Patient matching was performed by an independent third-party (ArborMetrix Inc.) using two or more unique identifiers. Cumulative incidence curves for time to treatment (TTT) and time to failure (TTF) were constructed using Kaplan-Meier estimates. Multivariable Cox proportional hazard models were used to evaluate the independent association of high-risk Decipher scores with the conversion from AS to radical therapy and treatment failure (biochemical failure or receipt of salvage therapy). RESULTS AND LIMITATIONS: Eight hundred fifty-five patients underwent Decipher Biopsy testing during the study period. Of the 855 men, 264 proceeded to AS (31%), and 454 (53%) received radical therapy. In men electing AS, after adjusting for NCCN risk group, age, PSA, prostate volume, body mass index, and percent positive cores, a high-risk Decipher score was independently associated with shorter TTT (HR 2.51, 95% CI 1.52-4.13 p < 0.001). Similarly, in patients that underwent radical therapy, a high-risk Decipher score was independently associated with TTF (HR 2.98, 95% CI 1.22-7.29, p = 0.01) on multivariable analysis. Follow-up time was a limitation. CONCLUSION: In a prospective statewide registry, high-risk Decipher Biopsy score was strongly and independently associated with conversion from AS to definitive treatment and treatment failure. These real-world data support the clinical utility of Decipher Biopsy. An ongoing phase 3 randomized trial (NCT04396808) will provide level 1 evidence of the clinical impact of Decipher biopsy testing.

Evaluation of Inpatient Opioid Prescribing Resulting in Outpatient Opioid Prescriptions for Previously Opioid-Naive Internal Medicine Patients.

BACKGROUND: Little data exist regarding inpatient opioid prescriptions as a potential contribution to the current opioid crisis. While pain management is essential to inpatient care, the ease of which opioids may be prescribed for all levels of pain may contribute to unnecessary inpatient exposure and new outpatient prescriptions. The aim of this study was to observe patterns of opioid prescribing potentially leading to new opioid prescriptions at hospital discharge for previously opioid-naive patients. METHODS: This study was a single-center observational study of opioid-naïve internal medicine patients who were prescribed inpatient opioids. Patient charts were reviewed to assess the patterns of inpatient opioid and non-opioid analgesic use, new opioid prescriptions upon discharge and medical record documentation justifying the need for outpatient therapy. RESULTS: Among the 101 patients included in this study, 71 were prescribed IV opioids and 45 were prescribed both IV and oral opioids. Non-opioid analgesics were available for 78 patients. Twenty patients were discharged with a new prescription. The mean duration of outpatient prescriptions was 3.85 +/- 1.85 days with mean morphine milligram equivalents (MME) of 44.25 +/- 22.16. Among patients receiving these outpatient prescriptions, 11 had reference to the therapy in the discharge summary. CONCLUSIONS: This observational study describes an opportunity to improve inpatient opioid prescribing practices which may reduce new prescriptions for continued outpatient therapy. Further work should focus on optimizing use of non-opioid analgesia, minimizing use of IV opioids and requiring prescribers to justify the indication for new opioid prescriptions upon hospital discharge.

Failure of High Flow Nasal Cannula and Subsequent Intubation Is Associated With Increased Mortality as Compared to Failure of Non-Invasive Ventilation and Mechanical Ventilation Alone: A Real-World Retrospective Analysis.

BACKGROUND: Despite the increasing use of high flow nasal cannula oxygenation systems (HFNC) in clinical practice, little is known about its role in all cause respiratory failure as compared to traditional non-invasive ventilation (BiPAP). Furthermore, the effect of HFNC on mortality is unknown. METHODS: We conducted a retrospective analysis of 49,853 patients with respiratory failure treated with non-invasive respiratory support (HFNC or BiPAP) and/or invasive mechanical ventilation (IMV) between 2017 and 2018. RESULTS: Patients initially treated with HFNC who underwent subsequent intubation and IMV had a higher mortality rate as compared to patients who were initially treated with BiPAP and underwent subsequent intubation and IMV (34.8% vs 26.3%, p < 0.0001, OR 1.49, 95% CI 1.26,1.76). Patients first treated with HFNC who underwent subsequent intubation and IMV had a significantly increased mortality compared to patients who underwent immediate intubation and IMV (34.8% vs. 21.5%, p ≤ 0.0001, OR 1.94, 95% CI 1.67, 2.27). Stratified based on ICD-10 diagnosis, patients with a diagnosis of COPD exacerbation or heart failure treated with HFNC and subsequent intubation and IMV had higher mortality as compared to those treated with immediate IMV alone. This trend did not hold true for patients with a diagnosis of pneumonia. CONCLUSION: In a real-world retrospective analysis, use of HFNC was associated with increased mortality as compared to BiPAP and IMV alone. Further study is needed to confirm these associations.

Ranking Important Factors for Using Postoperative Chemotherapy in Nonmuscle Invasive Bladder Cancer: Conjoint Analysis Results From the Michigan Urological Surgery Improvement Collaborative (MUSIC).

PURPOSE: National and international guidelines recommend the use of 1 dose of intravesical chemotherapy immediately following surgery for nonmuscle invasive bladder cancer, which is performed infrequently on a population level. We sought to understand the importance of potential environmental and clinical dimensions involved in the decision to offer this therapy. MATERIALS AND METHODS: Urologists from the Michigan Urological Surgery Improvement Collaborative (MUSIC) rated 8 distinct clinical vignettes involving patients with nonmuscle invasive bladder cancer. A ratings-based conjoint analysis method was used to evaluate the clinical vignette responses. Each vignette included 4 clinical dimensions and 2 environmental dimensions, with each dimension consisting of 2 possible attributes. The relative importance of each attribute was derived from the regression model and ranked in order. RESULTS: A total of 58 urologists answered the clinical vignettes which represents >75% of MUSIC sites. The median age of urologists was 53, most were male, and median years in practice was 20 years post residency. An environmental attribute, having a recovery room protocol for instilling and disposing of the chemotherapy, ranked as the most influential attribute for giving postoperative chemotherapy (utility=8.6). The clinical attribute yielding the strongest preference for giving chemotherapy was tumor grade (utility=4.9). These preferences varied by different subgroups of urologists, particularly regarding the type of practice a urologist was in. CONCLUSIONS: This study demonstrates that urologists have clear preferences for when they offer postoperative immediate chemotherapy. Factors beyond just clinical variables play a role in this decision making process such as the structure of the recovery room.

Prostate cancer clinical trial completion: The role of geography.

BACKGROUND/AIMS: One in five cancer clinical trials fails with another third failing to meet enrollment goals. Prior efforts to improve enrollment focus on patient facing interventions, but geographic factors such as regional cancer incidence may doom trials before they even begin. For these reasons, we examined associations of regional prostate cancer incidence with trial termination, and identified scientifically-underserved areas where future trials might thrive. METHODS: We merged US phase 2-3 prostate cancer clinical trial data from ClinicalTrials.gov with prostate cancer incidence data from statecancerprofiles.cancer.gov. We matched trial information from 293 closed and 560 active trials with incidence data for 2947 counties. Using multivariable logistic regression, we identified associations with trial termination. We identified 'scientifically-underserved' counties with the highest cancer incidence quintile (>61 annual cases) but lowest active trials quintile (0 or 1 trial). RESULTS: Of 293 closed trials, one in three was terminated (n = 96, 32.8%). On multivariable analysis, only lower regional prostate cancer incidence was associated with higher likelihood of premature trial termination (OR 0.98, 95% CI [0.96-0.99] for every 100 cases, p = 0.03). We identified 188 counties with >61 annual prostate cancer cases but 0 or 1 active trials, indicating potential scientifically-underserved areas. CONCLUSIONS: In this novel study, we found prostate cancer trials in areas with low prostate cancer incidence were more likely to fail. We also identified scientifically-underserved areas where trials might thrive. Our findings provide a more nuanced understanding of clinical trial feasibility and upstream opportunities for improvement.

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

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.

Do Corticosteroid Injections for the Treatment of Pain Influence the Efficacy of mRNA COVID-19 Vaccines?

MYTH: Corticosteroid injection for the treatment of pain and inflammation is known to decrease the efficacy of the messenger ribonucleic acid (mRNA) vaccines for coronavirus disease 2019 (COVID-19). FACT: There is currently no direct evidence to suggest that a corticosteroid injection before or after the administration of an mRNA COVID-19 vaccine decreases the efficacy of the vaccine.However, based on the known timeline of hypothalamic-pituitary-adrenal (HPA) axis suppression following epidural and intraarticular corticosteroid injections, and the timeline of the reported peak efficacy of the Pfizer-BioNTech and Moderna vaccines, physicians should consider timing an elective corticosteroid injection such that it is administered no less than 2 weeks prior to a COVID-19 mRNA vaccine dose and no less than 1 week following a COVID-19 mRNA vaccine dose, whenever possible.

Evaluation of Patient- and Surgeon-Specific Variations in Patient-Reported Urinary Outcomes 3 Months After Radical Prostatectomy From a Statewide Improvement Collaborative.

Importance: Understanding variation in patient-reported outcomes following radical prostatectomy may inform efforts to reduce morbidity after this procedure. Objective: To describe patient-reported urinary outcomes following radical prostatectomy in the diverse practice settings of a statewide quality improvement program and to explore whether surgeon-specific variations in observed outcomes persist after accounting for patient-level factors. Design, Setting, and Participants: This prospective population-based cohort study included 4582 men in the Michigan Urological Surgery Improvement Collaborative who underwent radical prostatectomy as primary management of localized prostate cancer between April 2014 and July 2018 and who agreed to complete validated questionnaires prior to surgery and at 3, 6, and 12 months after surgery. Data were analyzed from 2019 to June 2019. Exposures: Radical prostatectomy. Main Outcomes and Measures: Patient- and surgeon-level analyses of patient-reported urinary function 3 months after radical prostatectomy. Outcomes were measured using validated questionnaires with results standardized using previously published methods. Urinary function survey scores are reported on a scale from 0 to 100 with good function established as a score of 74 or higher. Results: For the 4582 men undergoing radical prostatectomy within the Michigan Urological Surgery Improvement Collaborative who agreed to complete surveys, mean (SD) age was 63.3 (7.1) years. Survey response rates varied: 3791 of 4582 (83%) responded at baseline, 3282 of 4137 (79%) at 3 months, 2975 of 3770 (79%) at 6 months, and 2213 of 2882 (77%) at 12 months. Mean (SD) urinary function scores were 88.5 (14.3) at baseline, 53.6 (27.5) at 3 months, 68.0 (25.1) at 6 months, and 73.7 (23.0) at 12 months. Regression analysis demonstrated that older age, lower baseline urinary function score, body mass index (calculated as weight in kilograms divided by height in meters squared) of 30 or higher, clinical stage T2 or higher, and lack of bilateral nerve-sparing surgery were associated with a lower probability of reporting good urinary function 3 months after surgery. When evaluating patients with good baseline function, the rate at which individual surgeons' patients reported good urinary function 3 months after surgery varied broadly (0% to 54.5%; P < .001). Patients receiving surgery from top-performing surgeons were more likely to report good 3-month function. This finding persisted after accounting for patient risk factors. Conclusions and Relevance: In this study, patient- and surgeon-level urinary outcomes following prostatectomy varied substantially. Documenting surgeon-specific variations after accounting for patient factors may facilitate identification of surgical factors associated with superior outcomes.

Towards validation of combined-accelerated stress testing through failure analysis of polyamide-based photovoltaic backsheets.

Novel methods for advancing reliability testing of photovoltaic (PV) modules and materials have recently been developed. Combined-accelerated stress testing (C-AST) is one such method which has demonstrated reliable reproduction of some field-failures which were not reproducible by standard certification tests. To increase confidence and assist in the development of C-AST, and other new testing protocols, it is important to validate that the failure modes observed and mechanisms induced are representative of those observed in the field, and not the product of unrealistic stress conditions. Here we outline a method using appropriate materials characterization and modelling to validate the failure mechanisms induced in C-AST such that we can increase confidence in the test protocol. The method is demonstrated by applying it to a known cracking failure of a specific polyamide (PA)-based backsheet material. We found that the failure of the PA-based backsheet was a result of a combination of stress factors. Photo-oxidation from ultra-violet (UV) radiation exposure caused a reduction in fracture toughness, which ultimately lead to the cracking failure. We show that the chemical and structural changes observed in the backsheet following C-AST aging were also observed in field-aged samples. These results increase confidence that the conditions applied in C-AST are representative of the field and demonstrates our approach to validating the failure mechanisms induced.

Aerosol risk with noninvasive respiratory support in patients with COVID-19.

Objectives: This study evaluates aerosol production with high-flow nasal cannula (HFNC) and noninvasive positive pressure ventilation (NIPPV) compared to 6 L/min by low-flow nasal cannula. Methods: Two healthy volunteers were randomized to control (6 L/min by low-flow nasal cannula), NIPPV, or HFNC using block randomization. NIPPV conditions were studied using continuous positive airway pressures of 5, 10, and 15 cm H2O with an FiO2 of 1.0 delivered via full-face mask. HFNC conditions included flow rates of 30 and 40 L/min with an FiO2 of 1.0 with and without coughing. HFNC and low-flow nasal cannula conditions were repeated with and without participants wearing a surgical mask. Six aerosol sizes (0.3, 1.0, 2.5, 5, and 10 µm) and total aerosol mass were measured at 2 and 6 ft from the participant's nasopharynx. Results: There was no significant difference in aerosol production between either HFNC or NIPPV and control. There was also no significant difference with the use of a procedural mask over the HFNC. There was significant variation between the 2 participants, but in neither case was there a difference compared to control. There was an aerosol-time trend, but there does not appear to be a difference between either flow rate, pressure, or control. Furthermore, there was no accumulation of total aerosol particles over the total duration of the experiment in both HFNC and NIPPV conditions. Conclusions: HFNC and NIPPV did not increase aerosol production compared to 6 L/min by low-flow nasal cannula in this experiment involving healthy volunteers.

Overtreatment and Underutilization of Watchful Waiting in Men With Limited Life Expectancy: An Analysis of the Michigan Urological Surgery Improvement Collaborative Registry.

OBJECTIVE: To determine rates of watchful waiting (WW) vs treatment in prostate cancer (PCa) and limited life expectancy (LE) and assess determinants of management. MATERIALS AND METHODS: Patients diagnosed with PCa between 2012 and 2018 with <10 years LE were identified from the Michigan Urologic Surgery Improvement Collaborative registry. Multinomial logistic regression models were used to identify factors associated with management choice among NCCN low-risk PCa patients. Data from high-volume practices were analyzed to understand practice variation. RESULTS: Total 2393 patients were included. Overall, WW was performed in 8.1% compared to 23.3%, 25%, 11.2%, and 3.6% who underwent AS, radiation (XRT), prostatectomy (RP), and brachytherapy (BT), respectively. In men with NCCN low-risk disease (n = 358), WW was performed in 15.1%, compared to AS (69.3%), XRT (4.2%), RP (6.7%), and BT (2.5%). There was wide variation in management among practices in low-risk men; WW (6%-35%), AS (44%-81%), and definitive treatment (0%-30%). Older age was associated with less likelihood of undergoing AS vs WW (odds ratio [OR] 0.88, P < .001) or treatment vs WW (OR 0.83, P < .0001). Presence of ≥cT2 disease (OR 8.55, P = .014) and greater number of positive biopsy cores (OR 1.41, P = .014) was associated with greater likelihood of treatment vs WW and Charlson comorbidity score of 1 vs 0 (OR 0.23, P = .043) was associated with less likelihood of treatment vs WW. CONCLUSION: Wide practice level variation exists in management for patients with low- and favorable-risk PCa and <10-year LE. Utilization of WW is poor, suggesting overtreatment in men who will experience little benefit.

Improving Colorectal Cancer Screening in a Rural Setting: A Randomized Study.

INTRODUCTION: Colorectal cancer screening has been shown to prevent or detect early colorectal cancer and reduce mortality; yet, adherence to screening recommendations remains low, particularly in rural settings. STUDY DESIGN: RCT. SETTING/PARTICIPANTS: Adults (n=7,812) aged 50-75 years and due for colorectal cancer screening in a largely rural health system were randomly assigned to either the intervention (n=3,906) or the control (n=3,906) group in September 2016, with analysis following through 2018. INTERVENTION: A mailed motivational messaging screening reminder letter with an option to call and request a free at-home fecal immunochemical screening test (intervention) or the standard invitation letter detailing that the individual was due for screening (control). Multifaceted motivational messaging emphasized colorectal cancer preventability and the ease and affordability of screening, and communicated a limited supply of test kits. MAIN OUTCOME MEASURES: Colorectal cancer screening participation within 6 months after mailed invitation was ascertained from the electronic medical record. RESULTS: Colorectal cancer screening participation was significantly improved in the intervention (30.1%) vs the usual care control group (22.5%; p<0.001). Individuals randomized to the intervention group had 49% higher odds of being screened over follow-up than those randomized to the control group (OR=1.49, 95% CI=1.34, 1.65). A total of 13.2 screening invitations were needed to accomplish 1 additional screening over the usual care. Of the 233 fecal immunochemical test kits mailed to participants, 154 (66.1%) were returned, and 18 (11.7%) tested positive. CONCLUSIONS: A mailed motivational messaging letter with a low-cost screening alternative increased colorectal cancer screening in this largely rural community with generally poor adherence to screening recommendations. Mailed colorectal cancer screening reminders using motivational messaging may be an effective method for increasing screening and reducing rural colorectal cancer disparities.