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The association between androgen deprivation therapy (ADT) and dementia in men with prostate cancer remains inconclusive. We assessed the association between cumulative ADT exposure and the onset of dementia in a nationwide longitudinal registry of men with prostate cancer.A retrospective analysis of men aged ≥50 years from the CaPSURE (Cancer of the Prostate Strategic Urologic Research Endeavor) registry was performed. The primary outcome was onset of dementia after primary treatment. ADT exposure was expressed as a time-varying independent variable of total ADT exposure. The probability of receiving ADT was estimated using a propensity score. Cox proportional hazards regression was performed to determine the association between ADT exposure and dementia with competing risk of death, adjusted for propensity score and clinical covariates among men receiving various treatments.Of 13,570 men 317 (2.3%) were diagnosed with dementia after a median of 7.0 years (IQR 3.0-12.0) of followup. Cumulative ADT use was significantly associated with dementia (HR 2.02; 95% CI 1.40-2.91; p0.01) after adjustment. In a subset of 8,506 men, where propensity score matched by whether or not they received ADT, there was also an association between ADT use and dementia (HR 1.59; 95% CI 1.03-2.44; p=0.04). There was no association between primary treatment type and onset of dementia in the 8,489 men in the cohort who did not receive ADT.Cumulative ADT exposure was associated with dementia. This increased risk should be accompanied by a careful discussion of the needs and benefits of ADT in those being considered for treatment.

Background Individual behaviours are associated with prostate cancer (PC) progression. Behavioural scores, comprised of multiple risk factors, allow assessment of the combined impact of multiple behaviours. Methods We examined the association between six a priori scores and risk of PC progression and mortality among 2156 men with PC in the Cancer of the Prostate Strategic Urologic Research Endeavor (CaPSURE) cohort: two scores developed based on the PC survivorship literature (‘2021 Score [+ Diet]’); a score developed based on pre-diagnostic PC literature (‘2015 Score’); and three scores based on US recommendations for cancer prevention (‘WCRF/AICR Score’) and survival (‘ACS Score [+ Alcohol]’). Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated for progression and PC mortality via parametric survival models (interval censoring) and Cox models, respectively. Results Over a median (IQR) of 6.4 (1.3, 13.7) years, we observed 192 progression and 73 PC mortality events. Higher (i.e., healthier) 2021 Score + Diet and WCRF/AICR Scores were inversely associated with risk of PC progression (2021 + Diet: HRcontinuous = 0.76, 95% CI: 0.63–0.90. WCRF/AICR: HRcontinuous = 0.83, 95% CI: 0.67–1.02) and mortality (2021 + Diet: HRcontinuous = 0.65, 95% CI: 0.45–0.93. WCRF/AICR: HRcontinuous = 0.71; 95% CI: 0.57–0.89). The ACS Score + Alcohol was only associated with progression (HRcontinuous = 0.89, 95% CI: 0.81–0.98) while the 2021 Score was only associated with PC mortality (HRcontinuous = 0.62, 95% CI: 0.45–0.85). The 2015 was not associated with PC progression or mortality. Conclusion Findings strengthen the evidence that behavioural modifications following a prostate cancer diagnosis may improve clinical outcomes.

IntroductionA single-arm pre-post pilot study in an academic setting found that pre-consultation decision support was associated with improved patient knowledge among men with early-stage prostate cancer. We now report on exploratory analyses from a controlled study featuring patients from both academic and community settings.MethodsWe enrolled 58 men to usual care and 61 men to the intervention. We evaluated whether the intervention was associated with patients answering key knowledge items correctly just before their urology visit.ResultsJust prior to the urology visit, 39/56 or 70% in the intervention group replied correctly to key knowledge items, compared to 31/55 or 56% in the usual care group (p=0.15). At baseline, the intervention group started with 42/60 or 70% correct and the usual care group started with 28/56 or 50% (p=0.03). This imbalance at baseline created a ceiling effect: more men in the usual care group had room to improve on their knowledge scores. Indeed, seven men moved from incorrect to correct in the usual care group, versus 5 in the intervention group; and five men in the intervention group moved from correct to incorrect versus 3 in the usual care group (p=0.44).DiscussionIn addition to small sample size, reasons for the null findings may include clustering of highly educated participants at the academic site combined with over-representation of academic site participants in the intervention group. We confirmed, from the pilot study, the feasibility of using pre-health student interns as health coaches. Future research should explore whether increasing adoption of telehealth will improve the feasibility of delivering pre-visit decision support in community settings.

As with many chronic illnesses, recurrent prostate cancer generally requires sustained treatment to prolong survival. However, initiating treatment immediately after recurrence may negatively impact quality of life without any survival gains. Therefore, we consider sustained strategies for initiating treatment based on specific characteristics of prostate-specific antigen (PSA), which can indicate disease progression. We define the protocol for a target trial comparing treatment strategies based on PSA doubling time, in which androgen deprivation therapy is initiated only after doubling time decreases below a certain threshold. Such a treatment strategy means the timing of treatment initiation (if ever) is not known at baseline, and the target trial protocol must explicitly specify the frequency of PSA monitoring until the threshold is met, as well as the duration of treatment. We describe these and other components of a target trial that need to be specified in order for such a trial to be emulated in observational data. We then use the parametric g-formula and inverse-probability weighted dynamic marginal structural models to emulate our target trial in a cohort of prostate cancer patients from clinics across the United States.

Background: Inflammatory and insulin pathways have been linked to prostate cancer; postdiagnostic behaviors activating these pathways may lead to poor outcomes. The empirical dietary inflammatory pattern (EDIP), empirical dietary index for hyperinsulinemia (EDIH), and empirical dietary index for insulin resistance (EDIR), and associated lifestyle indices (ELIH, ELIR) predict biomarkers of inflammation (EDIP: IL6, TNFaR2, CRP) and insulin secretion (EDIH/ELIH: c-peptide; EDIR/ELIR: TAG:HDL) from whole foods and behaviors. Methods: Associations of these indices with time to prostate cancer progression (primary, n = 2,056) and prostate cancer–specific mortality (PCSM; secondary, n = 2,447) were estimated among men diagnosed with nonmetastatic prostate cancer in the Cancer of the Prostate Strategic Urologic Research Endeavor cohort diet and lifestyle sub-study. Because the true (versus clinically documented) date of progression is unobserved, we used parametric (Weibull) survival models to accommodate interval-censoringand estimated adjusted HR and 95% confidence intervals (CI) for prostate cancer progression per 1-SD increase in index. Cox proportional hazards models were used to estimate PCSM associations. Results: During a median [interquartile range (IQR)] 6.4 years (IQR, 1.3–12.7), 192 progression and 73 PCSM events were observed. Inflammatory (EDIP: HR, 1.27; CI, 1.17–1.37), hyperinsulinemic (EDIH: HR, 1.24; CI, 1.05–1.46. ELIH: HR, 1.34; CI, 1.17–1.54), and insulin-resistant (EDIR: HR, 1.22; CI, 1.00–1.48. ELIR: HR, 1.36; CI, 1.12–1.64) indices were positively associated with risk of prostate cancer progression. There was no evidence of associations between the indices and PCSM. Conclusions: Both inflammatory and insulinemic dietary and lifestyle patterns are associated with risk of prostate cancer progression. Impact: For men with prostate cancer, consuming dietary patterns that limit chronic systemic inflammation and insulin hypersecretion may improve survivorship, especially when coupled with active lifestyle and healthy body weight. See related commentary by Kucuk, p. 1673

INTRODUCTION AND OBJECTIVE:Little is known about the long-term, indirect burden of prostate cancer (PCa) treatment on paid work and unpaid responsibilities such as days of work missed. Using the Ca...

INTRODUCTION AND OBJECTIVE:Radiotherapy (RT) for prostate cancer are associated with distinct treatment-related morbidity, primarily in domains of urinary and bowel health-related quality of life (...

INTRODUCTION AND OBJECTIVE:Radiotherapy (RT) for prostate cancer is associated with a distinct constellation of treatment-related complications and morbidities. However, few studies have reported t...

Background The onset of the COVID-19 pandemic led to the postponement of low-acuity surgical procedures in an effort to conserve resources and ensure patient safety. This study aimed to characterize patient-reported concerns about undergoing surgical procedures during the pandemic. Methods We administered a cross-sectional survey to patients who had their general and plastic surgical procedures postponed at the onset of the pandemic, asking about barriers to accessing surgical care. Questions addressed dependent care, transportation, employment and insurance status, as well as perceptions of and concerns about COVID-19. Mixed methods and inductive thematic analyses were conducted. Results One hundred thirty-five patients were interviewed. We identified the following patient concerns: contracting COVID-19 in the hospital (46%), being alone during hospitalization (40%), facing financial stressors (29%), organizing transportation (28%), experiencing changes to health insurance coverage (25%), and arranging care for dependents (18%). Nonwhite participants were 5 and 2.5 times more likely to have concerns about childcare and transportation, respectively. Perceptions of decreased hospital safety and the consequences of possible COVID-19 infection led to delay in rescheduling. Education about safety measures and communication about scheduling partially mitigated concerns about COVID-19. However, uncertainty about timeline for rescheduling and resolution of the pandemic contributed to ongoing concerns. Conclusions Providing effective surgical care during this unprecedented time requires both awareness of societal shifts impacting surgical patients and system-level change to address new barriers to care. Eliciting patients’ perspectives, adapting processes to address potential barriers, and effectively educating patients about institutional measures to minimize in-hospital transmission of COVID-19 should be integrated into surgical care.

PurposePost-diagnostic coffee and tea consumption and prostate cancer progression is understudied.MethodsWe examined 1,557 men from the Cancer of the Prostate Strategic Urologic Research Endeavor who completed a food frequency questionnaire a median of 28months post-diagnosis. We estimated associations between post-diagnostic coffee (total, caffeinated, decaffeinated) and tea (total, non-herbal, herbal) and risk of prostate cancer progression (recurrence, secondary treatment, bone metastases, or prostate cancer death) using Cox proportional hazards regression. We also examined whether smoking (current, former, never) modified these associations.ResultsWe observed 167 progression events (median follow-up 9years). Higher coffee intake was associated with higher risk of progression among current smokers (n = 95). The hazard ratio (HR) [95% confidence interval (CI)] for 5 vs 0 cups/day of coffee was 0.5 (CI 0.2, 1.7) among never smokers, but 4.5 (CI 1.1, 19.4) among current smokers (p-interaction: 0.001). There was no association between total coffee intake and prostate cancer progression among never and former smokers. However, we observed an inverse association between decaffeinated coffee (cups/days) and risk of prostate cancer progression in these men (HR > 0 to

BACKGROUND Diet and exercise may be associated with quality of life and survival in men with prostate cancer. OBJECTIVE This study aimed to determine the feasibility and acceptability of a remotely delivered web-based behavioral intervention among men with prostate cancer. METHODS We conducted a multi-site 4-arm pilot randomized controlled trial of a 3-month intervention (TrueNTH Community of Wellness). Eligibility included self-reported prostate cancer diagnosis, having a personal device that connected to the internet, age ≥18 years, and ability to read English and receive text messages and emails. Men receiving chemotherapy or radiation, or those who reported contraindications to exercise, could participate with physician clearance. Participants were randomized (1:1:1:1) to additive intervention levels: website; website and personalized diet and exercise prescription; website, personalized prescription, Fitbit, and text messages; and website, personalized prescription, Fitbit, text messages, and 2 30-minute phone calls—one with an exercise trainer and one with a registered dietician. Primary outcomes were feasibility (accrual and attrition) and acceptability (survey data and website use). We described self-reported diet and exercise behavior at the time of enrollment, 3 months, and 6 months as secondary outcomes. RESULTS In total, 202 men consented and were randomized between August 2017 and September 2018 (level 1: 49, level 2: 51, level 3: 50, level 4: 52). A total of 160 men completed the onboarding process and were exposed to their randomly assigned intervention (38, 38, 42, and 42 in levels 1, 2, 3, and 4, respectively). The follow-up rate was 82.7% (167/202) at 3 months and 77.2% (156/202) at 6 months. Participants had a median age of 70 years and were primarily White and college educated. Website visit frequency over the 3-month intervention period increased across levels (median: 2, 9, 11, and 16 visits for levels 1, 2, 3, and 4, respectively). Most were satisfied or very satisfied with the intervention (20/39, 51%; 27/42, 64%; 23/44, 52%; and 27/42, 64% for levels 1, 2, 3, and 4, respectively). The percentage of men who reported being very satisfied was highest among level 4 participants (10/42, 24% vs 4/39, 10%; 5/42, 12%; and 5/44, 11% for levels 1, 2, and 3, respectively). Dissatisfaction was highest in level 1 (5/39, 13% vs 1/42, 2%; 3/44, 7%; and 2/42, 5% for levels 2, 3, and 4, respectively). We observed small improvements in diet and physical activity at 3 months among men in level 4 versus those in level 1. CONCLUSIONS A web-based, remotely delivered, tailored behavioral intervention for men with prostate cancer is feasible. Future studies are warranted to increase the effect of the intervention on patient behavior while maintaining sustainability and scalability as well as to design and implement interventions for more diverse populations. CLINICALTRIAL ClinicalTrials.gov NCT03406013; http://clinicaltrials.gov/ct2/show/NCT03406013

BACKGROUND Exercise and a healthy diet can improve the quality of life and prognosis of prostate cancer survivors, but there have been limited studies on the feasibility of web-based lifestyle interventions in this population. OBJECTIVE This study aims to develop a data-driven grounded theory of web-based engagement by prostate cancer survivors based on their experience in the Community of Wellness, a 12-week randomized clinical trial designed to support healthy diet and exercise habits. METHODS TrueNTH’s Community of Wellness was a four-arm pilot study of men with prostate cancer (N=202) who received progressive levels of behavioral support (level 1: website; level 2: website with individualized diet and exercise recommendations; level 3: website with individualized diet and exercise recommendations, Fitbit, and text messages; and level 4: website with individualized diet and exercise recommendations, Fitbit and text messages, and separate phone calls with an exercise trainer and a registered dietitian). The primary aim of the study is to determine the feasibility and estimate the effects on behaviors (results reported in a separate paper). Following the 12-week intervention, we invited participants to participate in 4 focus groups, one for each intervention level. In this report, we used grounded theory analyses including open, axial, and selective coding to generate codes and themes from the focus group transcripts. Categories were refined across levels using embodied categorization and constant comparative methods. RESULTS In total, 20 men with prostate cancer participated in the focus groups: 5, 4, 5, and 6 men in levels 1, 2, 3, and 4, respectively. Participants converged on 5 common factors influencing engagement with the intervention: environment (home environment, competing priorities, and other lifestyle programs), motivation (accountability and discordance experienced within the health care system), preparedness (technology literacy, health literacy, trust, and readiness to change), program design (communication, materials, and customization), and program support (education, ally, and community). Each of these factors influenced the survivors’ long-term impressions and habits. We proposed a grounded theory associating these constructs to describe the components contributing to the intuitiveness of a web-based lifestyle intervention. CONCLUSIONS These analyses suggest that web-based lifestyle interventions are more intuitive when we optimize participants’ technology and health literacy; tailor interface design, content, and feedback; and leverage key motivators (ie, health care providers, family members, web-based coach) and environmental factors (ie, familiarity with other lifestyle programs). Together, these grounded theory–based efforts may improve engagement with web-based interventions designed to support prostate cancer survivorship.

Background Exercise and a healthy diet can improve the quality of life and prognosis of prostate cancer survivors, but there have been limited studies on the feasibility of web-based lifestyle interventions in this population. Objective This study aims to develop a data-driven grounded theory of web-based engagement by prostate cancer survivors based on their experience in the Community of Wellness, a 12-week randomized clinical trial designed to support healthy diet and exercise habits. Methods TrueNTH’s Community of Wellness was a four-arm pilot study of men with prostate cancer (N=202) who received progressive levels of behavioral support (level 1: website; level 2: website with individualized diet and exercise recommendations; level 3: website with individualized diet and exercise recommendations, Fitbit, and text messages; and level 4: website with individualized diet and exercise recommendations, Fitbit and text messages, and separate phone calls with an exercise trainer and a registered dietitian). The primary aim of the study is to determine the feasibility and estimate the effects on behaviors (results reported in a separate paper). Following the 12-week intervention, we invited participants to participate in 4 focus groups, one for each intervention level. In this report, we used grounded theory analyses including open, axial, and selective coding to generate codes and themes from the focus group transcripts. Categories were refined across levels using embodied categorization and constant comparative methods. Results In total, 20 men with prostate cancer participated in the focus groups: 5, 4, 5, and 6 men in levels 1, 2, 3, and 4, respectively. Participants converged on 5 common factors influencing engagement with the intervention: environment (home environment, competing priorities, and other lifestyle programs), motivation (accountability and discordance experienced within the health care system), preparedness (technology literacy, health literacy, trust, and readiness to change), program design (communication, materials, and customization), and program support (education, ally, and community). Each of these factors influenced the survivors’ long-term impressions and habits. We proposed a grounded theory associating these constructs to describe the components contributing to the intuitiveness of a web-based lifestyle intervention. Conclusions These analyses suggest that web-based lifestyle interventions are more intuitive when we optimize participants’ technology and health literacy; tailor interface design, content, and feedback; and leverage key motivators (ie, health care providers, family members, web-based coach) and environmental factors (ie, familiarity with other lifestyle programs). Together, these grounded theory–based efforts may improve engagement with web-based interventions designed to support prostate cancer survivorship.

INTRODUCTION AND OBJECTIVE:Recent studies have suggested an association between androgen deprivation therapy (ADT) and an increased risk of Alzheimer’s disease and/or dementia (ADD) in men with pro...

BACKGROUND/OBJECTIVES: Older adults undergoing surgery face potential outcomes that can adversely impact their quality of life. For this reason, advance care planning (ACP) is a recommended component of preoperative care. An emerging opportunity to incorporate ACP is through preoperative optimization programs. This report details an innovative model of care, the Surgery Wellness Program (SWP), which utilizes a multidisciplinary team to develop and implement preoperative care plans for older adults and describes its impact on ACP engagement. DESIGN: Retrospective analysis of a clinical demonstration project. SETTING: A preoperative optimization program for older adults undergoing surgery at a 796-bed academic tertiary hospital. PARTICIPANTS: Older adults (N=131) who participated in the SWP from February 2015 to August 2017. INTERVENTION: All SWP patients met with a geriatrician who engaged them in a semi-structure ACP discussion. Trained medical and nurse practitioner students were used as health coaches who contact patients regularly to address and document ACP. MEASUREMENTS: Patient self-report of ACP engagement before and after participation in the SWP was determined with SWP geriatrician and health coach progress notes. Medical records were assessed for the presence of scanned documentation. Feasibility data on the number of health coach calls was collected. RESULTS: After completion of the program, the proportion of patients with a designated surrogate increased from 67% to 78% (p

Background: The association of obesity at diagnosis with prostate cancer progression is uncertain. This study aimed to examine the relationship between body mass index (BMI; 18.5– Methods: We examined men enrolled in CaPSURE who underwent radical prostatectomy between 1995 and 2017. Multiple imputation methods were used to handle missing data and reported along with complete case findings. Results: Participants (n = 5,200) were followed for a median of 4.5 years; 685 experienced recurrence. Obesity was associated with higher prognostic risk at time of diagnosis (ORobese = 1.5; ORvery obese = 1.7) and upward reclassification of disease between biopsy and surgery, driven by change in tumor stage (ORobese = 1.3; ORvery obese = 1.6). We observed an association between BMI and recurrence with adjustment for disease severity using diagnostic factors (HRvery obese = 1.7); this association disappeared when adjusting for disease severity factors obtained at surgery. Conclusions: Our findings suggest that residual confounding may partially explain the conflicting evidence regarding obesity's influence on prostate cancer progression. Assessing T-stage via digital rectal exam may be complicated in larger men, potentially affecting clinical treatment decisions. A strong association with all-cause mortality demonstrates healthier BMI at diagnosis may still improve overall survival. Impact: Patients with greater BMI are prone to more advanced disease at diagnosis and may be more likely to have their tumor stage underestimated at diagnosis.

Objectives Development and pilot evaluation of a personalized decision support intervention to help men with early‐stage prostate cancer choose among active surveillance, surgery, and radiation. Methods We developed a decision aid featuring long‐term survival and side effects data, based on focus group input and stakeholder endorsement. We trained premedical students to administer the intervention to newly diagnosed men with low‐risk prostate cancer seen at the University of California, San Francisco. Before the intervention, and after the consultation with a urologist, we administered the Decision Quality Instrument for Prostate Cancer (DQI‐PC). We hypothesized increases in two knowledge items from the DQI‐PC: How many men diagnosed with early‐stage prostate cancer will eventually die of prostate cancer? How much would waiting 3 months to make a treatment decision affect chances of survival? Correct answers were: “Most will die of something else” and “A little or not at all.” Results The development phase involved 6 patients, 1 family member, 2 physicians, and 5 other health care providers. In our pilot test, 57 men consented, and 44 received the decision support intervention and completed knowledge surveys at both timepoints. Regarding the two knowledge items of interest, before the intervention, 35/56 (63%) answered both correctly, compared to 36/44 (82%) after the medical consultation (P = .04 by chi‐square test). Conclusions The intervention was associated with increased patient knowledge. Data from this pilot have guided the development of a larger scale randomized clinical trial to improve decision quality in men with prostate cancer being treated in community settings., Men with low‐risk prostate cancer are at risk for making decisions based on misconceptions about treatment options and outcomes. A decision support intervention, delivered by premedical students acting as health coaches, increased patient knowledge of key facts about prognosis.

We explored the prevalence and trends of self-reported complementary and alternative medicine use among patients with prostate cancer using CaPSURE™ (Cancer of the Prostate Strategic Urologic Research Endeavor).A total of 7,989 CaPSURE participants completed questionnaires between 1996 and 2016 on the use of nearly 70 complementary and alternative medicine types. Participants were defined as users if they indicated that they had ever used complementary and alternative medicines. To evaluate trends among 7,696 patients with newly diagnosed prostate cancer we considered complementary and alternative medicine use within 24 months of diagnosis and calculated the percent change in complementary and alternative medicine use between groups defined by the year of diagnosis.Of patients with prostate cancer 56% reported complementary and alternative medicine use on at least 1 questionnaire. Multivitamin and omega-3 fatty acid use was common at 40% and 24% of patients, respectively. Compared to nonusers greater proportions of complementary and alternative medicine users were college educated, had a higher household income and lived in the West and Midwest. Median prostate specific antigen at diagnosis was 5.8 (IQR 4.4-8.4) and 6.2 ng/ml (IQR 4.7-10.1) among users and nonusers, respectively (p0.01). Between those diagnosed in 1996 to 2000 and 2011 to 2016, complementary and alternative medicine use increased 128% from 24% to 54%. When comparing participants diagnosed in 2006 to 2010 with those diagnosed in 2011 to 2016, a 108% increase was seen in supplemental vitamin D use and a -48% decrease was seen in supplemental vitamin E use.Many patients with prostate cancer reported complementary and alternative medicine use. Multivitamins and omega-3 fatty acids were commonly ingested and vitamin D use increased dramatically from 2006 to 2010 compared to 2011 to 2016. These data can guide clinical discussions and decision making such as nutritionist referral and help prioritize future research.

INTRODUCTION AND OBJECTIVES:We provide updated comparative effectiveness based on long-term, 18-year prostate cancer-specific mortality (PCSM) among men who underwent radical prostatectomy (RP), me...

INTRODUCTION AND OBJECTIVES:Complementary and alternative medicine (CAM) use is common among prostate cancer (PCa) patients. The benefits and risks of the majority of CAM are inconclusive, and thus...

INTRODUCTION AND OBJECTIVES:Evidence regarding the use of adjuvant therapy for patients with adverse features at radical prostatectomy (RP) has evolved over the years. The aims of this study were t...

Background Valid health utility values are essential for comparative effectiveness analyses. However, subjective utilities in long-term survivors of prostate cancer (PCa) with various oncological and functional outcomes have not been well described. Objective To quantify utilities in long-term survivors of PCa using the standard gamble method, generally regarded as the approach best grounded in economic theory. Design, setting, and participants We performed a cross-sectional study nested within a prospective cohort—Cancer of the Prostate Strategic Urologic Research Endeavor (CaPSURE). Overall, 1884 (59.7%) of 3155 active participants across all disease states returned the questionnaire. Intervention Various primary treatments for PCa. Outcome measurements and statistical analysis Utility values for PCa health, sexual function, urinary function, bowel function, and overall health were measured, based on patients' conditions at the time of the survey. Bias correction methods were employed. Results and limitations After exclusion of incomplete or disqualified data, 1740 (92.3% of responding) patients were included in the final analysis. The mean age was 73.1 ± 8.2 yr at a median of 9 yr (interquartile range: 6–11) since diagnosis. Mean utilities for PCa health and overall health were 0.934 ± 0.120 and 0.960 ± 0.100, respectively. After bias correction by probability weighting function, utilities were 0.866 ± 0.154 and 0.897 ± 0.142, and by mixed model correction, 0.845 ± 0.186 and 0.884 ± 0.176, respectively. Measured utilities were similarly high for specific functional outcomes, even with bias corrections. Survivorship bias and skewed proportion of disease status due to natural history of PCa were potential limitations. Conclusions Standard gamble-based utilities in long-term survivors of PCa were much higher than those determined previously. The results indicate substantial human resilience: most PCa patients adapt to their health status over time even if they experience incomplete functional recovery and would not take risk in pursuit of better quality of life. Patient summary We elicited health utilities (measures of quality of life) among long-term survivors of prostate cancer using the most robust method. These were much higher than previously reported values that were based on theoretical scenarios or indirect methods. Long-term survivors of prostate cancer may adapt well to their health conditions over time even if they experience disease-specific or functional problems.

Introduction: For clinically localized prostate cancer (PCa) men must choose between various management options [radical prostatectomy (RP), external beam radiation therapy (EBRT), brachytherapy (BT, with or without EBRT), or active surveillance/watchful waiting (AS/WW)] but little is known about the long-term, indirect impact of management on paid work, unpaid responsibilities, and general health up to 10 years after initial management. Methods: We identified men diagnosed with PCa managed with RP, EBRT, BT, or AS/WW in a longitudinal, observational study of 43 primarily community-based US urology practices with available work type including paid work (full-time, part-time) or unpaid work (retired, on leave/unemployed, disabled, unspecified). Work type, weeks of work missed, general health, and number of clinic visits annually were collected via surveys administered prior to treatment and at 1,3,5 and 10 years after treatment. Using multivariate repeated measures generalized estimating equation modeling we examined the association between primary treatment, work type (paid vs unpaid), race, income, and time since treatment with work weeks missed over time and SF-36 General Health after adjustments for clinicodemographics. Results:6,673 men were identified. Mean age of 64.4 years (standard deviation 8.3). Most were insured (54% private, 43% Medicare, 3% Veteran's), white (90%, 7% Black, 1% Latino) with low- (60%) or intermediate-risk (32%) disease by CAPRA. Most had paid work (44%) or were retired (45%) and underwent RP (62%, 14% BT, 14% EBRT, 10% AS/WW). Median 5.3 weeks missed in first year (IQR 1.6-12.2) with up to 2.1 weeks missed at all other time points. AS/WW (RR 0.62, 95% CI 0.51-0.74) conferred lowest risk of missed weeks [BT (RR 0.70, 95% CI 0.61-0.80), EBRT (RR 0.72, 95% CI 0.62-0.83)] compared to RP. Black patients had lower risk of reporting missed weeks (vs white, RR 0.68, 95% CI 0.55-0.83); job status was not associated. SF-36 General Health declined across 10 years after treatment after adjustments, with RP and BT having better scores than AS/WW and EBRT. Conclusions: Nearly one-quarter of men with PCa reported missed work weeks due to PCa management, up to 10 years after treatment, irrespective of job status. Relative to other treatment types, AS/WW had the lowest risk of missed weeks, independent of job status, although long-term general health scores declined more than with RP or BT. In carefully selected men with PCa, management with AS/WW can confer a lower risk of missed work but the long-term impact of PCa management on QoL and work, irrespective of job type, should be considered when counseling about making treatment decisions. Citation Format: Samuel L. Washington, Peter E. Lonergan, Janet E. Cowan, Shoujun Zhao, Scott Greenberg, Jeanette M. Broering, Nynikka R. Palmer, Matthew R. Cooperberg, Peter R. Carroll. Longitudinal analysis of the indirect burden of prostate cancer management on paid and unpaid work: Data from CaPSURE database [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 686.

Background New data is emerging to guide initial treatment of patients with metastatic prostate cancer (CaP). This study utilizes the Cancer of the Prostate Strategic Urologic Research Endeavor registry to evaluate variations in survival based on initial treatment received by men with metastatic disease at diagnosis or after progression. Materials and methods Cancer of the Prostate Strategic Urologic Research Endeavor is a national registry of men diagnosed with CaP and managed at 43 community, academic, and Veteran's centers. We examined socio-demographic factors, disease biology, initial and subsequent therapy received, and survival among patients who presented with de novo or recurrent metastatic disease stratified by receipt of initial local therapy vs. combined local and hormonal therapy. The outcome was prostate cancer specific mortality (PCSM). We performed Fine and Gray competing risks regression analysis to evaluate the association between timing of metastasis and PCSM, adjusted for age, initial treatment, and subsequent therapy. Results Of the 14,753 patients diagnosed with CaP from 1990 to 2016, 669 (5%) had metastatic disease. Among the examined patients, 303 (45%) had metastatic disease at diagnosis and 366 (55%) progressed to metastatic disease. Overall, 461 (69%) were ≥65 years old, 582 (87%) had Medicare, and 227 (34%) had an annual income 20 ng/ml for 342 (51%) patients and biopsy Gleason grade was ≥4 + 3 for 386 (58%) patients. Among patients with metastatic disease at diagnosis, 31 (10%) received initial local therapy and 272 (90%) received initial hormonal therapy. Among patients who progressed to metastatic disease, 239 (65%) received initial local therapy and 127 (35%) received initial systemic hormonal therapy. Among patients with metastatic disease, the multivariate competing risks model, after adjusting for sociodemographics, marital status, diagnosis year, and comorbidities, revealed a significantly lower risk of PCSM among patients with de novo vs. recurrent metastatic disease (Hazard Ratio 0.66 (95% Confidence Interval 0.51, 0.85) P = 0.002). In the stratified analysis, no difference was seen for patients treated with initial hormonal vs. combined local and hormonal therapy. Conclusions In this analysis of a nationwide cohort of men treated for CaP with all types of therapy over 25 years, we observed that among men with metastatic CaP, the risk of PCSM was lower for de novo vs. recurrent metastatic disease. Additionally, no difference was observed based on initial treatment with combined local and hormonal therapy vs. hormonal therapy alone.

Objectives Valued life activities are those activities an individual deems particularly important or meaningful. Surgery in older adults can affect their ability to perform valued activities, but data are lacking. We characterized these activities and assessed performance of them following surgery. Design Retrospective observational study. Setting Preoperative program for older adults undergoing elective surgery at an academic hospital. Participants Older adults (N = 194) in the program from February 2015 to February 2018. Measurements A preoperative written questionnaire asked, "What are the activities that are most important to you to be able to do when you return home from surgery?" Participants could list up to three activities. Content analysis was used to develop domains of valued life activities and categorize responses. Postoperative questionnaires and medical records were used to determine ability to perform activities 6 months after surgery. Results Of 194 participants (mean age = 74.9 ± 9.1 y), 57.7% were female; 33.5% had more than two comorbid conditions. We elicited 510 valued activities, with a mean of 2.6 (± .7) activities per participant. Content analysis revealed five categories: (1) recreational activities (28.9%); (2) mobility (24.9%); (3) activities of daily living (ADLs; 17.5%); (4) instrumental activities of daily living (IADLs; 16.9%); and (5) social activities (12.0%). Ultimately, 154 participants had surgery, of which 27.3% were unable to perform one of their valued activities at 6 months. Performance varied between activity categories; 91.9% of mobility activities, 90.8% of ADLs, 80.3% of IADLs, 77.3% of social activities, and 65.5% of recreational activities were able to be performed after surgery. Conclusion Older adults expressed a wide range of valued life activities. More than one-quarter were unable to engage in at least one valued life activity after surgery, with recreation the most commonly affected. Assessment of valued life activities should be incorporated into the perioperative management of older adults. J Am Geriatr Soc 67:2305-2310, 2019.

OBJECTIVE To determine trends and predictors of adjuvant therapy in patients with adverse features at radical prostatectomy (RP), and to investigate the associations of adjuvant therapy and adverse feature type with survival. METHODS From the Cancer of the Prostate Strategic Urologic Research Endeavor registry (1990-2017), 2209 men with adverse features (pT3N0M0 disease and/or positive surgical margins), and 108 men with positive lymph nodes (pN1) at RP were identified. Temporal trends were evaluated, and predictors of adjuvant therapy were assessed with multivariate logistic regression. Kaplan-Meier analysis and competing risks regression were used to test cumulative incidence and risk of all-cause and prostate cancer-specific mortality. RESULTS Of 2209 men with adverse features and pN0 disease, 89 (4.0%), 82 (3.7%), and 30 (1.4%) received adjuvant external beam radiation therapy (ERBT) alone, androgen deprivation therapy (ADT) alone, or combined EBRT and ADT, respectively. Of 108 men with pN1 disease, 54 (50%) received ADT with or without EBRT. Adjuvant treatment for patients with adverse features decreased from 13.3% (1990-1994) to 6% or less (2005-2017, Ptrend CONCLUSION Adjuvant therapy declined for men with adverse features at RP. Providers do not treat all adverse feature types the same way, despite broad treatment recommendations in guidelines.

BACKGROUND More than 3.1 million men in the United States are prostate cancer survivors. These men may improve their physical function, quality of life, and potentially their prognosis by adopting healthier lifestyle habits. The internet provides a scalable mechanism to deliver advice and support about improving physical activity and dietary habits, but the feasibility and acceptability of a Web-based lifestyle intervention and the dose of support necessary to improve health behaviors are not yet known. OBJECTIVES The Community of Wellness is a Web-based intervention focused on supporting exercise and healthy dietary practices for men with prostate cancer. The objectives of this study were to determine the feasibility, acceptability, and preliminary efficacy of the Community of Wellness Web portal among prostate cancer survivors by conducting a randomized controlled trial (RCT) comparing 4 levels of additive Web-based content and interaction with participants: Level 1 (Teaching; Control), Level 2 (Teaching + Tailoring), Level 3 (Teaching + Tailoring + Technology), and Level 4 (Teaching + Tailoring + Technology + Touch). METHODS This is a single-blinded RCT comparing 3 levels of behavioral support within the Community of Wellness Web portal intervention (Levels 2 to 4) with each other and with the control condition (Level 1). The control condition receives general static Web-based educational information only on physical activity and dietary habits, self-efficacy for behavior change, motivation for physical activity, and changes in anxiety and treatment-related side effects. We will enroll and randomize 200 men with prostate cancer equally to 4 levels of the Community of Wellness Web-based intervention for 3 months (50 men per level). Surveys will be completed by self-report at baseline, 3 months (immediately postintervention), and 6 months (3 months postintervention). Feasibility and acceptability will be assessed by enrollment statistics, Web-based usage metrics, and surveys at the 3-month time point. We will also conduct focus groups after the postintervention follow-up assessment in a sample of enrolled participants to evaluate elements of usability and acceptability that cannot be obtained via surveys. RESULTS Enrollment is ongoing, with 124 enrolled. Study completion (6-month follow-up) is expected by July 2019. CONCLUSIONS The goal of the study is to identify the level of support that is feasible, acceptable, promotes behavior change, and improves health in men with prostate cancer to inform future efforts to scale the program for broader reach. CLINICALTRIAL ClinicalTrials.gov NCT03406013; https://clinicaltrials.gov/ct2/show/NCT03406013 (Archived by WebCite at http://www.webcitation.org/73YpDIoTX). INTERNATIONAL REGISTERED REPOR PRR1-10.2196/11257

Androgen deprivation therapy (ADT) has been shown to improve survival for men with intermediate and high-risk prostate cancer undergoing external-beam radiation therapy (EBRT). Using data from a community-based prospective disease registry, we investigated usage of EBRT with or without neoadjuvant ADT. The CaPSURE database contains 14,863 men with prostate cancer, including 1337 men diagnosed between 1990 and 2014 with localized disease who received EBRT as primary treatment. Prostate cancer risk was calculated using the CAPRA score. Patient characteristics were compared using the Mantel–Haenszel chi-square test for trend and analysis of variance. Between 1990 and 2014, 14,010 men were diagnosed with localized disease within the CaPSURE registry. Of those, 1337 underwent EBRT. Patients had a median age of 71 years. The use of ADT in addition to EBRT increased from 24% in 1990 to 60% in 1996 with a decrease seen to 47% in 2011. Men receiving ADT have differing clinical characteristics including higher PSA at diagnosis, higher Gleason grade, and higher CAPRA scores. Median ADT duration was 4 months. The use of ADT in conjunction with primary EBRT has increased in frequency and duration since 1990. Men receiving ADT have higher risk characteristics than those receiving EBRT alone. There is substantial variability in use of ADT in clinical practice.

In this paper we extend our previous two-dimensional tandem wing study to three-dimensions. In our previous study we found that vortex interactions highly depend on the phase lag angle and spacing between the forewing and hindwing. In this paper the effect of phase lag angle between the fore and hind wings on the wing–wing interactions, force production, and efficiency of the hindwing was studied for three different phase lag angles, 0°, 90° and 180°. The spacing used between the forewing and hindwing was one chord. A single frequency sinusoidal pitch–plunge motion was used at a Strouhal number of 0.3 and a Reynolds number of 200. The aspect ratio of the three dimensional wing was two. The simulations were based on the incompressible Navier–Stokes equations, discretized on overlapping grids. The wing motions were prescribed by a series of composed transformation matrices. A moving overlapping grid technique will be used to handle the moving boundary problems. It was found that the three dimensional cases exhibited a spanwise variation in the LEV structure and a weaker LEV formation at midspan compared to the two-dimensional cases with the same kinematics. The spanwise variation resulted in weaker vortex interactions between the fore and hind wing than predicted by the two dimensional study.

PurposeComparing patient reported outcomes such as urinary and erectile function across institutions is critical for prostate cancer research and quality assurance. Such comparisons are complicated due to the use of different questionnaires. We aimed to develop a method to convert scores among 4 commonly used instruments.Materials and methodsPatient reported data on urinary and sexual function were collected on 1,284 men with localized prostate cancer using the EPIC-26 (Expanded Prostate Index Composite), PCI (UCLA Prostate Cancer Index), SHIM (Sexual Health Inventory for Men) and I-PSS (International Prostate Symptom Scale) questionnaires. We investigated several methods to convert scores among questionnaires.ResultsConversion between EPIC and PCI urinary and sexual function subscales was best achieved using only the subset of questions asked on both questionnaires. For the conversion between EPIC or PCI erectile function scores and SHIM scores, we defined thresholds of poor, intermediate and good function as EPIC/PCI 0 to 40 and SHIM 1 to 7, EPIC/PCI 41 to 59 and SHIM 8 to 16, and EPIC/PCI 60 to 100 and SHIM 17 to 25, respectively. Urinary continence scores highly correlated for PCI and EPIC (r = 0.94). No comparison was possible for I-PSS with EPIC and PCI due to differences in the domains addressed by these questionnaires.ConclusionsWe have introduced methods to convert scores among the EPIC, PCI and SHIM questionnaires. While these conversion methods may introduce minor imprecision, to our knowledge they represent the best available tools to combine and compare patient reported outcomes that are assessed using different instruments in men undergoing radical prostatectomy or active surveillance.

Introduction Randomized clinical trials are considered the gold standard for evidence-based practices but strict inclusion and exclusion criteria, costs to perform them and the time required to design and complete them may limit generalizability, followup and timeliness. Observational studies based on well designed, large volume patient registries may be more flexible in that scope. Such registries can be modified with time to incorporate new treatments as they emerge. Methods We describe the design, objectives, funding mechanisms and results to date of the major prostate cancer registries in the United States, highlighting as examples PCOS, CaPSURE™, PROST-QA, CEASAR, MUSIC and AQUA. Results Registries and collaborations have provided valuable knowledge for prostate cancer regarding oncologic and health related quality of life outcomes among treatments, changes in disease prevalence, staging, national practice trends and health service utilization. Conclusions While there are important limitations to observational data, registries will continue to have an important and growing role in advancing prostate cancer care as a complement to data from clinical trials and traditional cohort studies.

© 2019 IOP Publishing Ltd and Sissa Medialab. A cryogenic apparatus is described that enables a new experiment, nEDM@SNS, with a major improvement in sensitivity compared to the existing limit in the search for a neutron Electric Dipole Moment (EDM). This apparatus uses superfluid 4He to produce a high density of Ultra-Cold Neutrons (UCN) which are contained in a suitably coated pair of measurement cells. The experiment, to be operated at the Spallation Neutron Source at Oak Ridge National Laboratory, uses polarized 3He from an Atomic Beam Source injected into the superfluid 4He and transported to the measurement cells where it serves as a co-magnetometer. The superfluid 4He is also used as an insulating medium allowing significantly higher electric fields, compared to previous experiments, to be maintained across the measurement cells. These features provide an ultimate statistical uncertainty for the EDM of 2-3× 10-28 e-cm, with anticipated systematic uncertainties below this level.

92 Background: Complementary and alternative medicine (CAM) use is common among prostate cancer (PCa) patients. The benefits and risks of the majority of CAM is inconclusive, and thus understanding trends in use is necessary to guide future research. We sought to investigate the prevalence of CAM use and trends in newly diagnosed PCa patients using the Cancer of the Prostate Strategic Urologic Research Endeavor (CaPSURE). Methods: Between 1996-2017, 7,989 CaPSURE subjects completed questionnaires on use of over 50 CAM types. For prevalence, subjects were identified as users if they ever indicated CAM use. We then performed univariate analyses to examine associations between sociodemographic and clinical characteristics with CAM use using chi-squared tests. To observe trends in CAM use among newly diagnosed patients, we limited subject responses to questionnaires completed within 24 months of diagnosis (7,358 subjects). We then grouped subjects by diagnosis year and calculated percent change in use. Results: Overall, 56% of subjects reported any CAM use. Commonly used CAM were multivitamins (40% of participants) and essential fatty acids and omega-3 (24% of participants). Compared to non-CAM users, a greater proportion of CAM users were college-educated, had a higher household income, and lived in the West and Midwest regions of the U.S (all p < 0.01). In exploring trends, we found that overall CAM use increased by +203% (19% to 56%) between those diagnosed in 1996-1999 and 2010-2017. Between those diagnosed in 2005-2009 and 2010-2017, the largest changes in use were seen in acupuncture (+289%), Vitamin D (+204%), selenium (-59%), and vitamin E (-39%). Conclusions: PCa patients reported widespread CAM use in 1996-2017. Multivitamins were the most prevalent CAM, and use of acupuncture and Vitamin D increased dramatically. This information may help to prioritize research needs and reinforces the importance of discussing CAM use with patients, with referral to specialists (e.g., nutritionists) when indicated.

Dragonfly wings have two distinct features: a tandem configuration and wing corrugation. Both features have been extensively studied with the aim to understand the superior flight performance of dragonflies. In this paper we review recent development of tandem and corrugated wing aerodynamics. With regards to the tandem configuration, this review will focus on wing/wing and wing/vortex interactions at different flapping modes and wing spacing. In addition, the aerodynamics of tandem wings under gusty conditions will be reviewed and compared with isolated wings to demonstrate the gust resistance characteristics of flapping wings. Regarding corrugated wings, we review their structural and aerodynamic characteristics.

In a tandem wing configuration, the hindwing often operates in the wake of the forewing and, hence, its performance is affected by the vortices shed by the forewing. Changes in the phase angle between the flapping motions of the fore and the hind wings, as well as the spacing between them, can affect the resulting vortex/wing and vortex/vortex interactions. This study uses 2D numerical simulations to investigate how these changes affect the leading dege vortexes (LEV) generated by the hindwing and the resulting effect on the lift and thrust coefficients as well as the efficiencies. The tandem wing configuration was simulated using an incompressible Navier-Stokes solver at a chord-based Reynolds number of 5 000. A harmonic single frequency sinusoidal oscillation consisting of a combined pitch and plunge motion was used for the flapping wing kinematics at a Strouhal number of 0.3. Four different spacings ranging from 0.1 chords to 1 chord were tested at three different phase angles, 0°, 90° and 180°. It was found that changes in the spacing and phase angle affected the timing of the interaction between the vortex shed from the forewing and the hindwing. Such an interaction affects the LEV formation on the hindwing and results in changes in aerodynamic force production and efficiencies of the hindwing. It is also observed that changing the phase angle has a similar effect as changing the spacing. The results further show that at different spacings the peak force generation occurs at different phase angles, as do the peak efficiencies.

Novel experimental techniques are required to make the next big leap in neutron electric dipole moment experimental sensitivity, both in terms of statistics and systematic error control. The nEDM experiment at the Spallation Neutron Source (nEDM@SNS) will implement the scheme of Golub & Lamoreaux [Phys. Rep., 237, 1 (1994)]. The unique properties of combining polarized ultracold neutrons, polarized $^3$He, and superfluid $^4$He will be exploited to provide a sensitivity to $\sim 10^{-28}\,e{\rm \,\cdot\, cm}$. Our cryogenic apparatus will deploy two small ($3\,{\rm L}$) measurement cells with a high density of ultracold neutrons produced and spin analyzed in situ. The electric field strength, precession time, magnetic shielding, and detected UCN number will all be enhanced compared to previous room temperature Ramsey measurements. Our $^3$He co-magnetometer offers unique control of systematic effects, in particular the Bloch-Siegert induced false EDM. Furthermore, there will be two distinct measurement modes: free precession and dressed spin. This will provide an important self-check of our results. Following five years of "critical component demonstration," our collaboration transitioned to a "large scale integration" phase in 2018. An overview of our measurement techniques, experimental design, and brief updates are described in these proceedings., Submitted to proceedings of PPNS 2018 - International Workshop on Particle physics at Neutron Sources (https://www.webofconferences.org/epj-web-of-conferences-forthcoming-conferences/1148-ppns-2018)

Background: Processed meat and fish have been shown to be associated with the risk of advanced prostate cancer, but few studies have examined diet after prostate cancer diagnosis and risk of its progression. Objective: We examined the association between postdiagnostic consumption of processed and unprocessed red meat, fish, poultry, and eggs and the risk of prostate cancer recurrence or progression. Design: We conducted a prospective study in 1294 men with prostate cancer, without recurrence or progression as of 2004‐2005, who were participating in the Cancer of the Prostate Strategic Urologic Research Endeavor and who were followed for an average of 2 y. Results: We observed 127 events (prostate cancer death or metastases, elevated prostate-specific antigen concentration, or secondary treatment) during 2610 person-years. Intakes of processed and unprocessed red meat, fish, total poultry, and skinless poultry were not associated with prostate cancer recurrence or progression. Greater consumption of eggs and poultry with skin was associated with 2fold increases in risk in a comparison of extreme quantiles: eggs [hazard ratio (HR): 2.02; 95% CI: 1.10, 3.72; P for trend = 0.05] and poultry with skin (HR: 2.26; 95% CI: 1.36, 3.76; P for trend = 0.003). An interaction was observed between prognostic risk at diagnosis and poultry. Men with high prognostic risk and a high poultry intake had a 4-fold increased risk of recurrence or progression compared with men with low/intermediate prognostic risk and a low poultry intake (P for interaction = 0.003). Conclusions: Our results suggest that the postdiagnostic consumption of processed or unprocessed red meat, fish, or skinless poultry is not associated with prostate cancer recurrence or progression, whereas consumption of eggs and poultry with skin may increase the risk. Am J Clin Nutr 2010;91:712‐21.

A quantitative description of the influence of salts and buffer components on the degradation of proteins is important for the shelf life of pharmaceuticals and operating life of biocatalysts but is currently lacking. By modeling observed protein deactivation as the result of competing chaotrope-dependent and ion hydration-independent processes, we develop a model to fit experimental data and describe Hofmeister effects on the deactivation of a variety of proteins in chaotropic or kosmotropic aqueous solution. We demonstrate that four parameters are required to characterize loss of function of a protein in aqueous salt solution: (i) a protein-dependent kosmotropic deactivation constant k p, (ii) a chaotropic preexponential factor k c, (iii) an ion hydration coefficient omega, and (iv) the B-viscosity coefficient of the salt. This model fits our experimental data on horse-liver alcohol dehydrogenase (HL-ADH), alpha-chymotrypsin, and monomeric red fluorescent protein (mRFP). We calculate the kinetic m values ( m (double dagger)) to indicate whether the transition state of deactivation resembles the native state or the unfolded state. We find that the transition state of deactivation in a strongly chaotropic aqueous solution resembles the unfolded state (thermodynamic control) and infer that with decreasing chaotropicity the resemblance with the native state increases until at B approximately 0 kinetic control dominates. The developed model demonstrates the importance of ion hydration effects for the explanation of Hofmeister effects on proteins and leads to an expression for a kinetic equivalent of the Wyman linkage which can be used as an alternate method for calculating m (double dagger) parameters in aqueous solution at any salt composition and temperature with targeted experimental effort.

Degradation of proteins is important for the operating life of biocatalysts and the shelf life of protein pharmaceuticals. We have previously found that the deactivating effects of salts on proteins can be correlated to an indicator of ion hydration, the B-viscosity coefficient of the anion in solution. Here, we test the influence of cations on protein kinetic stability by observing deactivation of mRFP (monomeric red fluorescent protein) in ammonium, caesium and chloride salt solutions, and we find that mRFP deactivation does not depend on cation hydration. We also measure mRFP deactivation in solutions containing denaturants (guanidinium chloride or urea) or stabilizing co-solutes (glycerol or sucrose) frequently encountered in many protein formulations to test whether hydration of these co-solutes can be used to indicate their relative effects on protein kinetic stability. We find that mRFP deactivation in solutions containing kosmotropic salts or stabilizers reaches a limiting rate and that hydration of denaturants is not an indicator of their denaturing strength.

BACKGROUND. Among the most pressing challenges that face physicians who care for men with prostate cancer is evaluating the patient's potential for benefiting from treatment. Because prostate cancer often follows an indolent course, the presence and severity of comorbidities may influence the decision to treat the patient aggressively. The authors adapted the Total Illness Burden Index (TIBI) for use in decision-making among men with prostate cancer at the time of the visit. METHODS. An observational study was performed of 2894 participants in the Cancer of the Prostate Strategic Urologic Research Endeavor, a national disease registry of men with prostate cancer, to examine how well the adapted TIBI for prostate cancer (TIBI-CaP) predicted mortality over the subsequent 3.5 years and health-related quality of life over the subsequent 6 months. RESULTS. The men who had the highest global TIBI-CaP scores were 13 times more likely to die of causes other than prostate cancer over a 3.5-year period than the men who had the lowest scores (hazard ratio, 13.1, 95% confidence interval, 6.3–27.4) after controlling for age, education, income, and race/ethnicity. Patients who had the highest TIBI-CaP scores had 44% mortality compared with 4.9% mortality for patients who had the lowest scores. Demographic variables explained 16% of the variance in future physical function; TIBI-CaP scores explained an additional 19% of the variance. CONCLUSIONS. The TIBI-CaP, a patient-reported measure of comorbidity, identified patients at high risk for nonprostate cancer mortality. It predicted both mortality and future quality of life. The TIBI-CaP may aid physicians and patients in making appropriate treatment decisions. Cancer 2007. © 2007 American Cancer Society.

High thermostability of proteins is a prerequisite for their implementation in biocatalytic processes and in the evolution of new functions. Various protein engineering methods have been applied to the evolution of increased thermostability, including the use of combinatorial design where a diverse library of proteins is generated and screened for variants with increased stability. Current trends are toward the use of data-driven methods that reduce the library size by using available data to choose areas of the protein to target, without specifying the precise changes. For example, the half-lives of subtilisin and a Bacillus subtilis lipase were increased 1500-fold and 300-fold, respectively, using a crystal structure to guide mutagenesis choices. Sequence homology based methods have also produced libraries where 50% of the variants have improved thermostability. Moreover, advances in the high-throughput measurement of denaturation curves and the application of selection methods to thermostability evolution have enabled the screening of larger libraries. The combination of these methods will lead to the rapid improvement of protein stability for biotechnological purposes.

Objectives To assess specific complementary and alternative medicine (CAM) use in the Cancer of the Prostate Strategic Urologic Research Endeavor (CaPSURE), a large, community-based national registry of men with prostate cancer. Methods We examined more than 50 types of CAM use in a large, national, community-based registry of men with prostate cancer (CaPSURE). Participants completed biannual surveys within 2 years of diagnosis and treatment. We analyzed associations of CAM use with sociodemographic and clinical features, using chi-square tests and multivariate logistic regression. Results One third of 2582 respondents reported using CAM. Common practices included vitamin and mineral supplements (26%), herbs (16%), antioxidants (13%), and CAM for prostate health (12%; eg, saw palmetto, selenium, vitamin E, lycopene). In multivariate analyses, users were more likely to have other comorbid conditions, worse cancer grade at diagnosis, higher incomes, more education, and to live in the West. Conclusions Complementary and alternative medicine use was associated with sociodemographic and clinical characteristics in this large sample of men with prostate cancer. These results should be considered by health care professionals counseling men with prostate cancer regarding diet and secondary prevention.

Dissolved salts are known to affect properties of proteins in solution including solubility and melting temperature, and the effects of dissolved salts can be ranked qualitatively by the Hofmeister series. We seek a quantitative model to predict the effects of salts in the Hofmeister series on the deactivation kinetics of enzymes. Such a model would allow for a better prediction of useful biocatalyst lifetimes or an improved estimation of protein-based pharmaceutical shelf life. Here we consider a number of salt properties that are proposed indicators of Hofmeister effects in the literature as a means for predicting salt effects on the deactivation of horse liver alcohol dehydrogenase (HL-ADH), α-chymotrypsin, and monomeric red fluorescent protein (mRFP). We find that surface tension increments are not accurate predictors of salt effects but find a common trend between observed deactivation constants and B-viscosity coefficients of the Jones−Dole equation, which are indicative of ion hydration. This trend...

We report on novel developments regarding the influence of temperature and salt on protein biocatalysts. The influence of temperature on the activation, unfolding, and deactivation of enzymes can now be described quantitatively with simple, analytical models. We demonstrate that enzyme deactivation phenomena can be determined via T-ramping and observation of instantaneous rates. We calculate the total turnover number analytically on the basis of the deactivation mechanism. We also report on the latest efforts to quantify the influence of salts on protein biocatalyst stability. While effects cannot yet be rationalized completely, we nevertheless found novel correlations between protein unfolding and deactivation and ion hydration.

Summary Background The aim of this study was to assess the probability of low-grade squamous intra-epithelial lesion (LSIL) regression in young women, and to examine the factors associated with this regression. Methods In a longitudinal study of human papilloma virus (HPV) infection, female adolescents aged 13–22 years were examined every 4 months by cytology, colposcopy, and HPV DNA status. Both prevalent and incident LSIL cases were included in the analysis, with regression defined as at least three consecutive normal Pap smears. Findings Median follow-up time from baseline (defined as the time of first LSIL diagnosis) for the 187 women with LSIL was 61 months (IQR 34–80). Median time they had been sexually active at diagnosis was 3·2 years (2·6–6·5). Probability of regression for the entire cohort was 61% (95% CI 53–70) at 12 months and 91% (84–99) at 36 months of follow-up. No associations were found between LSIL regression and HPV status at baseline, sexual behaviour, contraceptive use, substance or cigarette use, incident sexually transmitted infection, or biopsy. Multivariate analysis showed that only HPV status at the current visit was associated with rate of regression, whether infection was caused by one or more viral types (relative hazard=0·3 [95% CI 0·21–0·42], and 0·14 [0·08–0·25], respectively). Interpretation The high rate of regression recorded in this study lends support to observation by cytology in the management of LSIL in female adolescents. Negative HPV status was associated with regression, suggesting that HPV testing could be helpful in monitoring LSIL.