Unpacking overuse of androgen deprivation therapy for prostate cancer to inform de-implementation strategies.

BACKGROUND: Many men with prostate cancer will be exposed to androgen deprivation therapy (ADT). While evidence-based ADT use is common, ADT is also used in cases with no or limited evidence resulting in more harm than benefit, i.e., overuse. Since there are risks of ADT (e.g., diabetes, osteoporosis), it is important to understand the behaviors facilitating overuse to inform de-implementation strategies. For these reasons, we conducted a theory-informed survey study, including a discrete choice experiment (DCE), to better understand ADT overuse and provider preferences for mitigating overuse. METHODS: Our survey used the Action, Actor, Context, Target, Time (AACTT) framework, the Theoretical Domains Framework (TDF), the Capability, Opportunity, Motivation-Behavior (COM-B) Model, and a DCE to elicit provider de-implementation strategy preferences. We surveyed the Society of Government Service Urologists listserv in December 2020. We stratified respondents based on the likelihood of stopping overuse as ADT monotherapy for localized prostate cancer ("yes"/"probably yes," "probably no"/"no"), and characterized corresponding Likert scale responses to seven COM-B statements. We used multivariable regression to identify associations between stopping ADT overuse and COM-B responses. RESULTS: Our survey was completed by 84 respondents (13% response rate), with 27% indicating "probably no"/"no" to stopping ADT overuse. We found differences across respondents who said they would and would not stop ADT overuse in demographics and COM-B statements. Our model identified 2 COM-B domains (Opportunity-Social, Motivation-Reflective) significantly associated with a lower likelihood of stopping ADT overuse. Our DCE demonstrated in-person communication, multidisciplinary review, and medical record documentation may be effective in reducing ADT overuse. CONCLUSIONS: Our study used a behavioral theory-informed survey, including a DCE, to identify behaviors and context underpinning ADT overuse. Specifying behaviors supporting and gathering provider preferences in addressing ADT overuse requires a stepwise, stakeholder-engaged approach to support evidence-based cancer care. From this work, we are pursuing targeted improvement strategies. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03579680.

Neighborhood Deprivation, Race and Ethnicity, and Prostate Cancer Outcomes Across California Health Care Systems.

Importance: Non-Hispanic Black (hereafter, Black) individuals experience worse prostate cancer outcomes due to socioeconomic and racial inequities of access to care. Few studies have empirically evaluated these disparities across different health care systems. Objective: To describe the racial and ethnic and neighborhood socioeconomic status (nSES) disparities among residents of the same communities who receive prostate cancer care in the US Department of Veterans Affairs (VA) health care system vs other settings. Design, Setting, and Participants: This cohort study obtained data from the VA Central Cancer Registry for veterans with prostate cancer who received care within the VA Greater Los Angeles Healthcare System (VA cohort) and from the California Cancer Registry (CCR) for nonveterans who received care outside the VA setting (CCR cohort). The cohorts consisted of all males with incident prostate cancer who were living within the same US Census tracts. These individuals received care between 2000 and 2018 and were followed up until death from any cause or censoring on December 31, 2018. Data analyses were conducted between September 2022 and December 2023. Exposures: Health care setting, self-identified race and ethnicity (SIRE), and nSES. Main Outcomes and Measures: The primary outcome was all-cause mortality (ACM). Cox proportional hazards regression models were used to estimate hazard ratios for associations of SIRE and nSES with prostate cancer outcomes in the VA and CCR cohorts. Results: Included in the analysis were 49 461 males with prostate cancer. Of these, 1881 males were in the VA cohort (mean [SD] age, 65.3 [7.7] years; 833 Black individuals [44.3%], 694 non-Hispanic White [hereafter, White] individuals [36.9%], and 354 individuals [18.8%] of other or unknown race). A total of 47 580 individuals were in the CCR cohort (mean [SD] age, 67.0 [9.6] years; 8183 Black individuals [17.2%], 26 206 White individuals [55.1%], and 13 191 individuals [27.8%] of other or unknown race). In the VA cohort, there were no racial disparities observed for metastasis, ACM, or prostate cancer-specific mortality (PCSM). However, in the CCR cohort, the racial disparities were observed for metastasis (adjusted odds ratio [AOR], 1.36; 95% CI, 1.22-1.52), ACM (adjusted hazard ratio [AHR], 1.13; 95% CI, 1.04-1.24), and PCSM (AHR, 1.15; 95% CI, 1.05-1.25). Heterogeneity was observed for the racial disparity in ACM in the VA vs CCR cohorts (AHR, 0.90 [95% CI, 0.76-1.06] vs 1.13 [95% CI, 1.04-1.24]; P = .01). No evidence of nSES disparities was observed for any prostate cancer outcomes in the VA cohort. However, in the CCR cohort, heterogeneity was observed for nSES disparities with ACM (AHR, 0.82; 95% CI, 0.80-0.84; P = .002) and PCSM (AHR, 0.86; 95% CI, 0.82-0.89; P = .007). Conclusions and Relevance: Results of this study suggest that racial and nSES disparities were wider among patients seeking care outside of the VA health care system. Health systems-related interventions that address access barriers may mitigate racial and socioeconomic disparities in prostate cancer.

Software is Policy: Electronic Health Record Governance and the Implications of Clinical Standardization.

BACKGROUND: Electronic health record (EHR) implementations, whether replacing paper or electronic systems, are major social and organizational transformations. Yet studies of EHR-to-EHR transitions have largely neglected to elucidate accompanying social and organizational changes. One such underexplored change is the standardization of clinical practice in the context of EHR transitions. The Department of Veterans Affairs (VA) has begun a decade-long process of replacing the approximately 130 separate versions of its homegrown EHR with a single commercial EHR system. This provides an opportunity to explore the standardization of clinical practice amidst an EHR transition. OBJECTIVE: To identify, in the context of a large-scale EHR transition, (1) the scope and content of clinical standardization and (2) the anticipated implications of such standardization. DESIGN: Qualitative study. PARTICIPANTS: Twenty-nine members of VA councils established for the EHR transition. APPROACH: We conducted semi-structured interviews, which were professionally transcribed, and analyzed first using rapid analysis methods, followed by coding and content analysis. KEY RESULTS: Clinical standardization across facilities was a central goal of the EHR transition, encompassing computerized recommendations, order sets, professional roles/permissions, and clinical documentation. The anticipated implications of this standardization include (i) potential efficiency gains, with less duplicated effort across facilities; (ii) expanded bureaucracy; and (iii) increased uniformity, reducing both wanted and unwanted variation in care. CONCLUSIONS: EHR systems shape a wide range of clinical processes, particularly in a large organization like VA with a long history of EHR use. This makes standardization of EHR content a powerful mechanism for standardizing clinical practice itself, which can bring dramatic collateral consequences. Organizations undergoing EHR transitions need to recognize the important role that clinical standardization plays by treating EHR transitions as major organizational transformations in the governance of clinical practice.

Medical Gaslighting and Lyme Disease: The Patient Experience.

Even though there are approximately half a million new cases of Lyme disease in the US annually, according to the CDC, it is often undiagnosed or misdiagnosed, which can result in a chronic, multisystemic condition. Lyme disease is a recognized public health threat and is a designated "notifiable disease". As such, Lyme disease is mandated to be reported by the CDC. Despite this, both acute and chronic Lyme disease (CLD) have been relegated to the category of "contested illnesses", which can lead to medical gaslighting. By analyzing results from an online survey of respondents with Lyme disease (n = 986), we elucidate the lived experiences of people who have been pushed to the margins of the medical system by having their symptoms attributed to mental illness, anxiety, stress, and aging. Further, respondents have had their blood tests and erythema migrans (EM) rashes discounted and were told that CLD simply does not exist. As a result, a series of fruitless consultations often result in the delay of a correct diagnosis, which has deleterious consequences. This is the first study that addresses an extensive range of gaslighting techniques experienced by this patient population.

Learning from the "tail end" of de-implementation: the case of chemical castration for localized prostate cancer.

BACKGROUND: Men with prostate cancer are often treated with the suppression of testosterone through long-acting injectable drugs termed chemical castration or androgen deprivation therapy (ADT). In most cases, ADT is not an appropriate treatment for localized prostate cancer, indicating low-value care. Guided by the Theoretical Domains Framework (TDF) and the Behavior Change Wheel's Capability, Opportunity, Motivation Model (COM-B), we conducted a qualitative study to identify behavioral determinants of low-value ADT use to manage localized prostate cancer, and theory-based opportunities for de-implementation strategy development. METHODS: We used national cancer registry and administrative data from 2016 to 2017 to examine the variation in low-value ADT use across Veterans Health Administration facilities. Using purposive sampling, we selected high- and low-performing sites to conduct 20 urology provider interviews regarding low-value ADT. We coded transcripts into TDF domains and mapped content to the COM-B model to generate a conceptual framework for addressing low-value ADT practices. RESULTS: Our interview findings reflected provider perspectives on prescribing ADT as low-value localized prostate cancer treatment, including barriers and facilitators to de-implementing low-value ADT. We characterized providers as belonging in 1 of 3 categories with respect to low-value ADT use: 1) never prescribe 2); willing, under some circumstances, to prescribe: and 3) prescribe as an acceptable treatment option. Provider capability to prescribe low-value ADT depended on their knowledge of localized prostate cancer treatment options (knowledge) coupled with interpersonal skills to engage patients in educational discussion (skills). Provider opportunity to prescribe low-value ADT centered on the environmental resources to inform ADT decisions (e.g., multi-disciplinary review), perceived guideline availability, and social roles and influences regarding ADT practices, such as prior training. Provider motivation involved goals of ADT use, including patient preferences, beliefs in capabilities/professional confidence, and beliefs about the consequences of prescribing or not prescribing ADT. CONCLUSIONS: Use of the TDF domains and the COM-B model enabled us to conceptualize provider behavior with respect to low-value ADT use and clarify possible areas for intervention to effect de-implementation of low-value ADT prescribing in localized prostate cancer. TRIAL REGISTRATION: ClinicalTrials.gov , NCT03579680.

Ascertainment of Veterans With Metastatic Prostate Cancer in Electronic Health Records: Demonstrating the Case for Natural Language Processing.

PURPOSE: Prostate cancer (PCa) is among the leading causes of cancer deaths. While localized PCa has a 5-year survival rate approaching 100%, this rate drops to 31% for metastatic prostate cancer (mPCa). Thus, timely identification of mPCa is a crucial step toward measuring and improving access to innovations that reduce PCa mortality. Yet, methods to identify patients diagnosed with mPCa remain elusive. Cancer registries provide detailed data at diagnosis but are not updated throughout treatment. This study reports on the development and validation of a natural language processing (NLP) algorithm deployed on oncology, urology, and radiology clinical notes to identify patients with a diagnosis or history of mPCa in the Department of Veterans Affairs. PATIENTS AND METHODS: Using a broad set of diagnosis and histology codes, the Veterans Affairs Corporate Data Warehouse was queried to identify all Veterans with PCa. An NLP algorithm was developed to identify patients with any history or progression of mPCa. The NLP algorithm was prototyped and developed iteratively using patient notes, grouped into development, training, and validation subsets. RESULTS: A total of 1,144,610 Veterans were diagnosed with PCa between January 2000 and October 2020, among which 76,082 (6.6%) were identified by NLP as having mPCa at some point during their care. The NLP system performed with a specificity of 0.979 and sensitivity of 0.919. CONCLUSION: Clinical documentation of mPCa is highly reliable. NLP can be leveraged to improve PCa data. When compared to other methods, NLP identified a significantly greater number of patients. NLP can be used to augment cancer registry data, facilitate research inquiries, and identify patients who may benefit from innovations in mPCa treatment.

Impact of the COVID-19 Pandemic on Urological Care Delivery in the United States.

PURPOSE: We examined changes in urological care delivery due to COVID-19 in the U.S. based on patient, practice, and local/regional demographic and pandemic response features. MATERIALS AND METHODS: We analyzed real-world data from the American Urological Association Quality (AQUA) Registry collected from electronic health record systems. Data represented 157 outpatient urological practices and 3,165 providers across 48 U.S. states and territories, including 3,297,721 unique patients, 12,488,831 total outpatient visits and 2,194,456 procedures. The primary outcome measure was the number of outpatient visits and procedures performed (inpatient or outpatient) per practice per week, measured from January 2019 to February 2021. RESULTS: We found large (>50%) declines in outpatient visits from March 2020 to April 2020 across patient demographic groups and states, regardless of timing of state stay-at-home orders. Nonurgent outpatient visits decreased more across various nonurgent procedures (49%-59%) than for procedures performed for potentially urgent diagnoses (38%-52%); surgical procedures for nonurgent conditions also decreased more (43%-79%) than those for potentially urgent conditions (43%-53%). African American patients had similar decreases in outpatient visits compared with Asians and Caucasians, but also slower recoveries back to baseline. Medicare-insured patients had the steepest declines (55%), while those on Medicaid and government insurance had the lowest percentage of recovery to baseline (73% and 69%, respectively). CONCLUSIONS: This study provides real-world evidence on the decline in urological care across demographic groups and practice settings, and demonstrates a differential impact on the utilization of urological health services by demographics and procedure type.

Does thermal history influence thermal tolerance of the freshwater fish Galaxias zebratus in a global biodiversity hotspot?

Compared to other climate regions of the world, Mediterranean regions are likely to experience more severe effects of climate change as rainfall decreases and temperatures increase. Global climate change models predict a reduction in rainfall and rise in the temperature of rivers in South Africa's Cape Fold Ecoregion (CFE) - a Mediterranean region in the south-west corner of the country. In the climate change context and with the prediction that stream temperatures will increase, determining thermal thresholds of freshwater fish in relation to their thermal history is a key element in understanding the potential impacts climate change and a rise in stream temperatures will have on already threatened freshwater fish. The ability of aquatic species to withstand warming in the CFE will be determined by its upper tolerance limit (critical thermal maximum, CTmax). A fish's CTmax can be influenced by several factors, including the thermal characteristics of its environment (thermal history). In this study, we set out to examine whether the thermal tolerance of an endemic CFE fish species, the Cape Galaxias, Galaxias zebratus Castelnau, 1861, is influenced by its thermal history. We hypothesised that CTmax of G. zebratus individuals from warmer sites will have higher CTmax values than individuals from cooler sites. Hourly in situ water temperature data were collected and the CTmax values were determined for fish (n = 15 per site) from ten sites on six rivers on the Cape Peninsula of the CFE, and regression analyses revealed that G. zebratus upper thermal tolerance limits are indeed significantly influenced by its thermal history (as characterised by the seven day moving average of daily mean, Mean_7). CTmax was positively related to the thermal history of the rivers, indicating that G. zebratus, and potentially other stenothermic CFE freshwater fish species, is likely to be particularly vulnerable to climate warming. These findings broaden our understanding of thermal history patterns on fish thermal tolerances in Mediterranean rivers, and support G. zebratus conservation by determining its biological temperature thresholds and thermal requirements. Thermal data should be used to monitor and manage stream temperatures to ensure Mediterranean stenotherms can persist in their natural environment.

A 5-Year Single-Institution Experience Integrating Telehealth Into Urologic Care Delivery.

Objective: Telehealth is increasingly used in urology, but few studies have evaluated how it can be integrated with urology face-to-face (FTF) encounters and primary care (PC). We describe the 5-year experience of a Veterans Affairs urology service that has incorporated telehealth into their patient care program. Methods: We performed a retrospective review of encounters from 2013 to 2018 in telehealth urology clinics. To examine the way telehealth and FTF visits were utilized together, the key components of care were defined for the evaluation of three common referrals: elevated prostate-specific antigen (PSA), microscopic hematuria, and obstructive lower urinary tract symptoms (LUTS). A random convenience sample of 20 patients from each condition was abstracted to describe the setting of care for each component over a 2-year period. Results: We reviewed 811 unique patients who had a total of 2,008 telehealth visits. The mean utilization of telehealth (2.48) and FTF (2.42) encounters per patient were similar. The most common reasons for referral to telehealth clinics were sexual dysfunction (26.8%), LUTS (20.6%), hematuria (15.0%), prostate cancer (13.3%), and an elevated PSA (12.1%). Thirty-six percent of patients were managed by telehealth alone; 64% were by a combination of telehealth and FTF encounters. Telehealth was often used in conjunction with PC and FTF visits to perform components such as the physical exam and procedures. Conclusions: Telehealth was utilized for a wide array of diseases and often used in conjunction with PC and urologic FTF visits to deliver complete care for the three disease states we evaluated.

The clinical utility of the cervical vestibular-evoked myogenic potential (cVEMP) in university-level athletes with concussion.

INTRODUCTION: Concussion is defined as a mild traumatic brain injury that can occur in all sport activities. Cervical vestibular-evoked myogenic potentials (cVEMPs) are accepted to demonstrate the vestibulocollic reflex. MAIN: To evaluate subclinical cervical abnormalities in the vestibulospinal pathway in subjects with concussion history with and without related symptoms via evoked vestibular potential. METHODS: Monaurally air conduction cVEMP (500 Hz tone bursts) at intensity of 100 dBnHL and 200 sweeps. All responses were replicated. RESULTS: One hundred fifty-four participants were initially tested; however, three (03) participants did not produce usable data (no response) and were eliminated for the dataset cutoff values analysis, being considered just as abnormal response. One hundred fifty-one responses consisted of 45 non-athlete individuals without any history of a concussion or concussion symptoms (normative group), 45 athletes without any history of a concussion or concussion symptoms (control group), 33 athletes with a history of at least one concussion but no concussion symptoms related (history group), and 28 athletes with a history of at least one concussion and concussion symptoms (symptoms group). The history and symptoms groups had statistically higher latency scores than the control and the normative groups. The Index Ratio data and Threshold data did not produce a significant effect for four groups. But, a pattern of abnormal cVEMP was found when comparing those without a history of concussion (0% abnormal response) versus the history group (24%) and symptoms group (32.3%). CONCLUSION: The study provides data which supports the positive impact of cVEMP when evaluating athletes and identifying concussion processes.

Life expectancy estimates for patients diagnosed with prostate cancer in the Veterans Health Administration.

PURPOSE: Accurate life expectancy estimates are required to inform prostate cancer treatment decisions. However, few models are specific to the population served or easily implemented in a clinical setting. We sought to create life expectancy estimates specific to Veterans diagnosed with prostate cancer. MATERIALS AND METHODS: Using national Veterans Health Administration electronic health records, we identified Veterans diagnosed with prostate cancer between 2000 and 2015. We abstracted demographics, comorbidities, oncologic staging, and treatment information. We fit Cox Proportional Hazards models to determine the impact of age, comorbidity, cancer risk, and race on survival. We stratified life expectancy estimates by age, comorbidity and cancer stage. RESULTS: Our analytic cohort included 145,678 patients. Survival modeling demonstrated the importance of age and comorbidity across all cancer risk categories. Life expectancy estimates generated from age and comorbidity data were predictive of overall survival (C-index 0.676, 95% CI 0.674-0.679) and visualized using Kaplan-Meier plots and heatmaps stratified by age and comorbidity. Separate life expectancy estimates were generated for patients with localized or advanced disease. These life expectancy estimates calibrate well across prostate cancer risk categories. CONCLUSIONS: Life expectancy estimates are essential to providing patient-centered prostate cancer care. We developed accessible life expectancy estimation tools for Veterans diagnosed with prostate cancer that can be used in routine clinical practice to inform medical-decision making.

Accidental Overdose Deaths in Oklahoma, 2002-2017: Opioid and Methamphetamine Trends.

To evaluate trends related to accidental overdose deaths in Oklahoma, with a focus on opioids and methamphetamine. All accidental drug overdose deaths in the state of Oklahoma from 2002 to 2017 were reviewed. Opioids were grouped into the following categories: all opioids, prescription opioids, synthetic opioids and heroin. Age-adjusted death rates for methamphetamine and each opioid category were calculated and analyzed. Accidental overdoses accounted for 9,936 deaths during the study period. Of these, opioids were seen in 62.9%, with prescription opioids comprising 53.8%, synthetic opioids 10.3% and heroin 2.8%. Synthetic opioids, despite a recent upward nationwide trend, showed a slight overall decrease (-6.8%) from 2009 to 2017. In contrast, methamphetamine showed a 402.2% increase from 2009 to 2017 and an overall increase of 1,526.7%. Methamphetamine was involved in the most overdoses (1,963), followed by oxycodone (1,724). Opioid-related deaths were most common among white individuals (90.3%) and showed a slight male predilection (56.9%). With the intent of assessing the opioid epidemic as it relates to accidental overdoses in Oklahoma, this study suggests that opioid-related overdoses have slowed in recent years amidst a sharp increase in methamphetamine deaths.

Contemporary Management of Incident Prostate Cancer in Large Community Urology Practices in the United States.

OBJECTIVE: To characterize the contemporary management of prostate cancer patients in large community practices. The optimal management of incident prostate cancer has changed in the last decades to include active surveillance for a large number of men. At the same time, many community practices have merged into larger groups. The adoption of evidence-based guidelines is of increasing importance, but poorly understood in this newer practice setting. METHODS: We conducted a retrospective chart review of men ≤75 years old with very low, low, and intermediate risk incident prostate cancer diagnosed between December 1, 2012 and March 31, 2014, in 9 geographically distributed large urology practices. We used descriptive statistics and multivariable regression to assess predictors of primary management choice. RESULTS: 2029 men were in the study cohort. A majority were white (68.7%). Total of 45.7% had intermediate risk, 36.2% low risk, and 17.9% had very low risk disease cancer. Active surveillance (AS) was the initial treatment for 74.7% of men with very low risk disease, 43.5% of men with low risk disease and 10.8% of men with intermediate risk disease. The probability of choosing surgery vs radiation for men with lower and intermediate risk disease was 0.54 (95% confidence interval: 0.42, 0.65) and 0.59 (95% confidence interval: 0.48, 0.69), respectively. CONCLUSION: We found that the initial management of lower risk prostate cancer in large community urology practices largely followed clinical characteristics, widespread adoption of active surveillance, and equal use of surgery and radiation. However, some variation by practice suggested a need for further investigation and continued improvement.

Three-year Active Surveillance Outcomes in a Contemporary Community Urology Cohort in the United States.

OBJECTIVES: To determine the 3-year outcomes of men with prostate cancer managed with active surveillance (AS) in a cohort of geographically diverse community-based urology practices. AS is the management of choice for a majority of men with lower risk prostate cancer.1,2,3 Little is known about the contemporary "real-world" follow-up and adherence rates in the most common setting of urologic care, community (private) practice.4 METHODS: We retrospectively evaluated outcomes for men diagnosed between January 1, 2013 and May 31, 2014 with National Comprehensive Cancer Network (NCCN) very low, low and intermediate risk prostate cancer who selected AS in 9 large community urology practices. We used univariate and multivariate analyses to describe associations between race, age, insurance status, family history, comorbidity, clinical stage, Gleason score, NCCN risk-group, and PSA density with discontinuation of AS. RESULTS: Five hundred and forty-eight men on AS were followed for a median of 3.35 years. 89% (492) continued to follow-up with diagnosing practice. 32% (171) discontinued AS. On multivariate analysis, increasing NCCN risk classification (Hazard ratio [HR] 1.65, P = 0.02 and HR 2.09, P < 0.01 for low and intermediate risk vs very low risk) was significantly associated with discontinuation. Among those who discontinued AS, surgery and radiation were utilized equally (47% and 53%, respectively, P = 0.48). CONCLUSION: In this community-based cohort of men on AS, a minority was lost to follow-up and adherence to AS was similar to other reports. Disease characteristics more than sociodemographic characteristics correlated with adherence to AS, while surgery and radiotherapy were utilized equally among those discontinuing AS, both suggesting guideline concordant practice of medicine.

External Validation of the Prostate Cancer Specific Comorbidity Index: A Claims Based Tool for the Prediction of Life Expectancy in Men with Prostate Cancer.

PURPOSE: Accurate assessment of life expectancy is critical to treatment decision making in men with prostate cancer. We sought to externally validate the PCCI (Prostate Cancer Comorbidity Index) to predict long-term mortality in men with prostate cancer and make it operational using claims data. MATERIALS AND METHODS: We performed an observational study of 181,009 men with prostate cancer in the Veterans Affairs Health System who were diagnosed from 2000 to 2013. Overall mortality across the PCCI scores was analyzed using Kaplan-Meier and Cox proportional hazards analysis. Discrimination and calibration were measured using the C-index and the mean prediction error, respectively. RESULTS: Among men with a PCCI score of 0, 1-2, 3-4, 5-6, 7-9 and 10 or greater the 10-year overall mortality rate was 15%, 26%, 36%, 41%, 52% and 69%, respectively. Multivariable Cox analysis showed an increasing hazard of mortality with higher PCCI scores, including 1.22 (95% CI 1.18-1.27), 1.69 (95% CI 1.61-1.76), 2.08 (95% CI 2.00-2.17), 2.88 (95% CI 2.76-3.00) and 4.50 (95% CI 4.32-4.69) for a score of 1 to 2, 3 to 4, 5 to 6, 7 to 9 and 10 or greater, respectively. The C-index to predict overall mortality was 0.773. The mean absolute error to predict 10-year overall mortality was 0.032. Of the men with clinically localized disease, Gleason 6 or less with less than 10-year life expectancy and Gleason 7 or less with life expectancy less than 5 years as defined by the PCCI 3,999 of 12,185 (33%) and 1,038 of 3,930 (26%), respectively, underwent definitive local treatment. CONCLUSIONS: The PCCI is a claims based, externally validated tool to predict mortality in men with prostate cancer. Integrating the PCCI into clinical pathways may improve prostate cancer management through more accurate assessment of life expectancy.

Variation in thermal tolerances of native freshwater fishes in South Africa's Cape Fold Ecoregion: examining the east-west gradient in species' sensitivity to climate warming.

The Cape Fold Ecoregion (CFE) is a biodiversity hotspot with high levels of endemism in its freshwater fish fauna. This study examined inter and intra-specific variation in critical thermal maxima (TCmax ) for eight native species of freshwater fish from the CFE. Cape galaxias Galaxias zebratus, Breede River redfin Pseudobarbus burchelli, Berg River redfin Pseudobarbus burgi, Clanwilliam redfin Pseudobarbus calidus and fiery redfin Pseudobarbus phlegethon were the most thermally sensitive (TCmax = 29.8-32.8°C). Clanwilliam rock-catfish Austroglanis gilli, Eastern Cape redfin Pseudobarbus afer and Cape kurper Sandelia capensis were moderately sensitive (TCmax = 33.0-36.8°C). An increase in intra-specific thermal sensitivity of S. capensis was observed from east to west. The results were related to in situ water temperature, which influenced TCmax for all species, suggesting that thermal history is a major driver of variation in thermal tolerance amongst populations. These thermal tolerance data for freshwater fishes in the CFE demonstrate that resilience to climate warming follows a geographical cline and that the more sensitive western species and regions are conservation priorities.

Characterising potential bone scan overuse amongst men treated with radical prostatectomy.

OBJECTIVES: To characterise bone scan use, and potential overuse, after radical prostatectomy (RP) using data from a large, national integrated delivery system. Overuse of imaging is well documented in the setting of newly diagnosed prostate cancer, but whether overuse persists after RP remains unknown. PATIENTS AND METHODS: We identified 12 269 patients with prostate cancer treated with RP between 2005 and 2008 using the Veterans Administration Central Cancer Registry. We used administrative and laboratory data to examine rates of bone scan use, including preceding prostate-specific antigen (PSA) levels, and receipt of adjuvant or salvage therapy. We then performed multivariable logistic regression to identify factors associated with post-RP bone scan use. RESULTS: At a median follow-up of 6.8 years, one in five men (22%) underwent a post-RP bone scan at a median PSA level of 0.2 ng/mL. Half of bone scans (48%) were obtained in men who did not receive further treatment with androgen-deprivation or radiation therapy. After adjustment, post-RP bone scan was associated with a prior bone scan (adjusted odds ratio [aOR] 1.55, 95% confidence interval [CI] 1.32-1.84), positive surgical margin (aOR 1.68, 95% CI 1.40-2.01), preoperative PSA level (aOR 1.02, 95% CI 1.01-1.03), as well as Hispanic ethnicity, Black race, and increasing D'Amico risk category, but not with age or comorbidity. CONCLUSION: We found a substantial rate of bone scan utilisation after RP. The majority were performed for PSA levels of <1 ng/mL where the likelihood of a positive test is low. More judicious use of imaging appears warranted in the post-RP setting.

De-implementation of low value castration for men with prostate cancer: protocol for a theory-based, mixed methods approach to minimizing low value androgen deprivation therapy (DeADT).

BACKGROUND: Men with prostate cancer are often castrated with long-acting injectable drugs termed androgen deprivation therapy (ADT). Although many benefit, ADT is also used in patients with little or nothing to gain. The best ways to stop this practice are unknown, and range from blunt pharmacy restrictions to informed decision-making. This study will refine and pilot two different de-implementation strategies for reducing ADT use among those unlikely to benefit in preparation for a comparative effectiveness trial. METHODS/DESIGN: This innovative mixed methods research program has three aims. Aim 1: To assess preferences and barriers for de-implementation of chemical castration in prostate cancer. Guided by the theoretical domains framework (TDF), urologists and patients from facilities with the highest and lowest castration rates across the VA will be interviewed to identify key preferences and de-implementation barriers for reducing castration as prostate cancer treatment. This qualitative work will inform Aim 2 while gathering rich information for two proposed pilot intervention strategies. Aim 2: To use a discrete choice experiment (DCE), a novel barrier prioritization approach, for de-implementation strategy tailoring. The investigators will conduct national surveys of urologists to prioritize key barriers identified in Aim 1 for stopping incident castration as localized prostate cancer treatment using a DCE experiment design. These quantitative results will identify the most important barriers to be addressed through tailoring of two pilot de-implementation strategies in preparation for Aim 3 piloting. Aim 3: To pilot two tailored de-implementation strategies to reduce castration as localized prostate cancer treatment. Building on findings from Aims 1 and 2, two de-implementation strategies will be piloted. One strategy will focus on formulary restriction at the organizational level and the other on physician/patient informed decision-making at different facilities. Outcomes will include acceptability, feasibility, and scalability in preparation for an effectiveness trial comparing these two widely varying de-implementation strategies. DISCUSSION: Our innovative approach to de-implementation strategy development is directly aligned with state-of-the-art complex implementation intervention development and implementation science. This work will broadly advance de-implementation science for low value cancer care, and foster participation in our de-implementation evaluation trial by addressing barriers, facilitators, and concerns through pilot tailoring. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03579680 , First Posted July 6, 2018.