Estradiol mediates greater germinal center responses to influenza vaccination in female than male mice.

Adult females of reproductive age develop greater antibody responses to inactivated influenza vaccines (IIV) than males. How sex, age, and sex steroid concentrations impact B cells and durability of IIV-induced immunity and protection over 4 months post-vaccination (mpv) was analyzed. Vaccinated adult females had greater germinal center B cell and plasmablast frequencies in lymphoid tissues, higher neutralizing antibody responses 1-4 mpv, and better protection against live H1N1 challenge than adult males. Aged mice, regardless of sex, had reduced B cell frequencies, less durable antibody responses, and inferior protection after challenge than adult mice, which correlated with diminished estradiol among aged females. To confirm that greater IIV-induced immunity was caused by sex hormones, four core genotype (FCG) mice were used, in which the testes-determining gene, Sry, was deleted from chromosome Y (ChrY) and transferred to Chr3 to separate gonadal sex (i.e., ovaries or testes) from sex chromosome complement (i.e., XX or XY complement). Vaccinated, gonadal female FCG mice (XXF and XYF) had greater numbers of B cells, higher antiviral antibody titers, and reduced pulmonary virus titers following live H1N1 challenge than gonadal FCG males (XYM and XXM). To establish that lower estradiol concentrations cause diminished immunity, adult and aged females received either a placebo or estradiol replacement therapy prior to IIV. Estradiol replacement significantly increased IIV-induced antibody responses and reduced morbidity after the H1N1 challenge among aged females. These data highlight that estradiol is a targetable mechanism mediating greater humoral immunity following vaccination among adult females.IMPORTANCEFemales of reproductive ages develop greater antibody responses to influenza vaccines than males. We hypothesized that female-biased immunity and protection against influenza were mediated by estradiol signaling in B cells. Using diverse mouse models ranging from advanced-age mice to transgenic mice that separate sex steroids from sex chromosome complement, those mice with greater concentrations of estradiol consistently had greater numbers of antibody-producing B cells in lymphoid tissue, higher antiviral antibody titers, and greater protection against live influenza virus challenge. Treatment of aged female mice with estradiol enhanced vaccine-induced immunity and protection against disease, suggesting that estradiol signaling in B cells is critical for improved vaccine outcomes in females.

Integrating Tobacco Use Assessment and Treatment in the Oncology Setting: Quality Improvement Results from the Georgetown Lombardi Smoking Treatment and Recovery Program.

As part of the NCI's Cancer Center Cessation (C3i) initiative, we initiated, expanded, and maintained an evidence-based tobacco treatment program at the Georgetown Lombardi Comprehensive Cancer Center. We present a quality improvement (QI) assessment of the implementation process and patient-level outcomes. At two hematology/oncology outpatient clinical sites, five oncology-based teams (clinical administrators, clinical staff, pharmacy, information technology, and tobacco treatment staff) developed implementation strategies for opt-out patient assessment and enrollment, centralized tobacco treatment, audit, feedback, and staff training. Among eligible patients (tobacco use in ≤30 days), we assessed demographic, clinical, and tobacco-related characteristics to examine predictors of enrollment (baseline completed), treatment engagement (≥one sessions completed), and self-reported 7-day abstinence (6 months post-enrollment). Across both sites, medical assistants screened 19,344 (82.4%) patients for tobacco use, which identified 1345 (7.0%) current tobacco users, in addition to 213 clinician referrals. Of the 687/1256 (54.7%) eligible patients reached, 301 (43.8%) enrolled, and 199 (29.0%) engaged in treatment, of whom 74.5% were African American and 68% were female. At the larger site, significant multivariate predictors of enrollment included African American race (vs. white/other) and clinician referral (vs. MA assessment). Treatment engagement was predicted by greater nicotine dependence, and abstinence (27.4%) was predicted by greater treatment engagement. In summary, the systematic utilization of multiple oncology-based teams and implementation strategies resulted in the development and maintenance of a high-quality, population-based approach to tobacco treatment. Importantly, these strategies addressed inequities in tobacco treatment, as the program reached and engaged a majority-African-American patient population. Finally, the opt-out patient assessment strategy has been implemented in multiple oncology settings at MedStar Health through the Commission on Cancer's Just Ask program.

A novel rodent model of chronic spinal implant-associated infection.

BACKGROUND CONTEXT: Bacterial infection of spinal instrumentation is a significant challenge in spinal fusion surgery. Although the intraoperative local application of powdered vancomycin is common practice for mitigating infection, the antimicrobial effects of this route of administration are short-lived. Therefore, novel antibiotic-loaded bone grafts as well as a reliable animal model to permit the testing of such therapies are needed to improve the efficacy of infection reduction practices in spinal fusion surgery. PURPOSE: This study aims to establish a clinically relevant rat model of spinal implant-associated infection to permit the evaluation of antimicrobial bone graft materials used in spinal fusion. STUDY DESIGN: Rodent study of chronic spinal implant-associated infection. METHODS: Instrumentation anchored in and spanning the vertebral bodies of L4 and L5 was inoculated with bioluminescent methicillin-resistant Staphylococcus aureus bacteria (MRSA). Infection was monitored using an in vivo imaging system (IVIS) for 8 weeks. Spines were harvested and evaluated histologically, and colony-forming units (CFUs) were quantified in harvested implants and spinal tissue. RESULTS: Postsurgical analysis of bacterial infection in vivo demonstrated stratification between MRSA and phosphate-buffered saline (PBS) control groups during the first 4 weeks of the 8-week infection period, indicating the successful establishment of acute infection. Over the 8-week chronic infection period, groups inoculated with 1 × 105 MRSA CFU and 1 × 106 MRSA CFU demonstrated significantly higher bioluminescence than groups inoculated with PBS control (p = 0.009 and p = 0.041 respectively). Histological examination at 8 weeks postimplantation revealed the presence of abscesses localized to implant placement in all MRSA inoculation groups, with the most pervasive abscess formation in samples inoculated with 1 × 105 MRSA CFU and 1 × 106 MRSA CFU. Quantification of CFU plated from harvested spinal tissue at 8 weeks post-implantation revealed the 1 × 105 MRSA CFU inoculation group as the only group with a significantly greater average CFU count compared to PBS control (p = 0.017). Further, CFU quantification from harvested spinal tissue was greater than CFU quantification from harvested implants across all inoculation groups. CONCLUSION: Our model demonstrated that the inoculation dosage of 1 × 105 MRSA CFU exhibited the most robust chronic infection within instrumented vertebral bodies. This dosage had the greatest difference in bioluminescence signal from control (p < 0.01), the lowest mortality (0% compared to 50% for samples inoculated with 1 × 106 MRSA CFU), and a significantly higher amount of CFUs from harvested spine samples than CFUs from control harvested spine samples. Further, histological analysis confirmed the reliability of this novel rodent model of implanted-associated infection to establish infection and biofilm formation of MRSA for all inoculation groups. CLINICAL SIGNIFICANCE: This model is intended to simulate the infection of instrumentation used in spinal fusion surgeries concerning implant locality and material. This model may evaluate potential antimicrobial and osteogenic biomaterials and investigate the relationship between implant-associated infection and failed fusion.

A Randomized Trial of Telephone-Based Smoking Cessation Treatment in the Lung Cancer Screening Setting.

BACKGROUND: Lung cancer mortality is reduced via low-dose computed tomography screening and treatment of early-stage disease. Evidence-based smoking cessation treatment in the lung screening setting can further reduce mortality. We report the results of a cessation trial from the National Cancer Institute's Smoking Cessation at Lung Examination collaboration. METHODS: Eligible patients (n = 818) aged 50-80 years were randomly assigned (May 2017-January 2021) to the intensive vs minimal arms (8 vs 3 phone sessions plus 8 vs 2 weeks of nicotine patches, respectively). Bio-verified (primary) and self-reported 7-day abstinence rates were assessed at 3, 6, and 12 months post random assignment. Logistic regression analyses evaluated the effects of study arm. All statistical tests were 2-sided. RESULTS: Participants reported 48.0 (SD = 17.2) pack-years, and 51.6% were not ready to quit in less than 30 days. Self-reported 3-month quit rates were statistically significantly higher in the intensive vs minimal arm (14.3% vs 7.9%; odds ratio [OR] = 2.00, 95% confidence interval [CI] = 1.26 to 3.18). Bio-verified abstinence was lower but with similar relative differences between arms (9.1% vs 3.9%; OR = 2.70, 95% CI = 1.44 to 5.08). Compared with the minimal arm, the intensive arm was more effective among those with greater nicotine dependence (OR = 3.47, 95% CI = 1.55 to 7.76), normal screening results (OR = 2.58, 95% CI = 1.32 to 5.03), high engagement in counseling (OR = 3.03, 95% CI = 1.50 to 6.14), and patch use (OR = 2.81, 95% CI = 1.39 to 5.68). Abstinence rates did not differ statistically significantly between arms at 6 months (OR = 1.2, 95% CI = 0.68 to 2.11) or 12 months (OR = 1.4, 95% CI = 0.82 to 2.42). CONCLUSIONS: Delivering intensive telephone counseling and nicotine replacement with lung screening is an effective strategy to increase short-term smoking cessation. Methods to maintain short-term effects are needed. Even with modest quit rates, integrating cessation treatment into lung screening programs may have a large impact on tobacco-related mortality.

Psychological predictors of delayed active treatment following active surveillance for low-risk prostate cancer: The Patient REported outcomes for Prostate cARE prospective cohort study.

Objectives: In a prospective, comparative effectiveness study, we assessed clinical and psychological factors associated with switching from active surveillance (AS) to active treatment (AT) among low-risk prostate cancer (PCa) patients. Methods: Using ultra-rapid case identification, we conducted pretreatment telephone interviews (N = 1139) with low-risk patients (PSA ≤ 10, Gleason≤6) and follow-up interviews 6-10 months post-diagnosis (N = 1057). Among men remaining on AS for at least 12 months (N = 601), we compared those who continued on AS (N = 515) versus men who underwent delayed AT (N = 86) between 13 and 24 months, using Cox proportional hazards models. Results: Delayed AT was predicted by time dependent PSA levels (≥10 vs. <10; HR = 5.6, 95% CI 2.4-13.1) and Gleason scores (≥7 vs. ≤6; adjusted HR = 20.2, 95% CI 12.2-33.4). Further, delayed AT was more likely among men whose urologist initially recommended AT (HR = 2.13, 95% CI 1.07-4.22), for whom tumour removal was very important (HR = 2.18, 95% CI 1.35-3.52), and who reported greater worry about not detecting disease progression early (HR = 1.67, 1.05-2.65). In exploratory analyses, 31% (27/86) switched to AT without evidence of progression, while 4.7% (24/515) remained on AS with evidence of progression. Conclusions: After adjusting for clinical evidence of disease progression over the first year post-diagnosis, we found that urologists' initial treatment recommendation and patients' early treatment preferences and concerns about AS each independently predicted undergoing delayed AT during the second year post-diagnosis. These findings, along with almost one-half undergoing delayed AT without evidence of progression, suggest the need for greater decision support to remain on AS when it is clinically indicated.

Topologically correct synthetic reconstruction of pathogen social behavior found during Yersinia growth in deep tissue sites.

Within deep tissue sites, extracellular bacterial pathogens often replicate in clusters that are surrounded by immune cells. Disease is modulated by interbacterial interactions as well as bacterial-host cell interactions resulting in microbial growth, phagocytic attack and secretion of host antimicrobial factors. To overcome the limited ability to manipulate these infection sites, we established a system for Yersinia pseudotuberculosis (Yptb) growth in microfluidics-driven microdroplets that regenerates microbial social behavior in tissues. Chemical generation of nitric oxide (NO) in the absence of immune cells was sufficient to reconstruct microbial social behavior, as witnessed by expression of the NO-inactivating protein Hmp on the extreme periphery of microcolonies, mimicking spatial regulation in tissues. Similarly, activated macrophages that expressed inducible NO synthase (iNOS) drove peripheral expression of Hmp, allowing regeneration of social behavior observed in tissues. These results argue that topologically correct microbial tissue growth and associated social behavior can be reconstructed in culture.

Selecting Active Surveillance: Decision Making Factors for Men with a Low-Risk Prostate Cancer.

Background. Men with a low-risk prostate cancer (PCa) should consider observation, particularly active surveillance (AS), a monitoring strategy that avoids active treatment (AT) in the absence of disease progression. Objective. To determine clinical and decision-making factors predicting treatment selection. Design. Prospective cohort study. Setting. Kaiser Permanente Northern California (KPNC). Patients. Men newly diagnosed with low-risk PCa between 2012 and 2014 who remained enrolled in KPNC for 12 months following diagnosis. Measurements. We used surveys and medical record abstractions to measure sociodemographic and clinical characteristics and psychological and decision-making factors. Men were classified as being on observation if they did not undergo AT within 12 months of diagnosis. We performed multivariable logistic regression analyses. Results. The average age of the 1171 subjects was 61.5 years (s = 7.2 years), and 81% were white. Overall, 639 (57%) were managed with observation; in adjusted analyses, significant predictors of observation included awareness of low-risk status (odds ratio 1.75; 95% confidence interval 1.04-2.94), knowing that observation was an option (3.62; 1.62-8.09), having concerns about treatment-related quality of life (1.21, 1.09-1.34), reporting a urologist recommendation for observation (8.20; 4.68-14.4), and having a lower clinical stage (T1c v. T2a, 2.11; 1.16-3.84). Conversely, valuing cancer control (1.54; 1.37-1.72) and greater decisional certainty (1.66; 1.18-2.35) were predictive of AT. Limitations. Results may be less generalizable to other types of health care systems and to more diverse populations. Conclusions. Many participants selected observation, and this was associated with tumor characteristics. However, nonclinical decisional factors also independently predicted treatment selection. Efforts to provide early decision support, particularly targeting knowledge deficits, and reassurance to men with low-risk cancers may facilitate better decision making and increase uptake of observation, particularly AS.

Iron-Sulfur Cluster Repair Contributes to Yersinia pseudotuberculosis Survival within Deep Tissues.

To successfully colonize host tissues, bacteria must respond to and detoxify many different host-derived antimicrobial compounds, such as nitric oxide (NO). NO has direct antimicrobial activity through attack on iron-sulfur (Fe-S) cluster-containing proteins. NO detoxification plays an important role in promoting bacterial survival, but it remains unclear if repair of Fe-S clusters is also important for bacterial survival within host tissues. Here we show that the Fe-S cluster repair protein YtfE contributes to the survival of Yersinia pseudotuberculosis within the spleen following nitrosative stress. Y. pseudotuberculosis forms clustered centers of replicating bacteria within deep tissues, where peripheral bacteria express the NO-detoxifying gene hmp. ytfE expression also occurred specifically within peripheral cells at the edges of microcolonies. In the absence of ytfE, the area of microcolonies was significantly smaller than that of the wild type (WT), consistent with ytfE contributing to the survival of peripheral cells. The loss of ytfE did not alter the ability of cells to detoxify NO, which occurred within peripheral cells in both WT and ΔytfE microcolonies. In the absence of NO-detoxifying activity by hmp, NO diffused across ΔytfE microcolonies, and there was a significant decrease in the area of microcolonies lacking ytfE, indicating that ytfE also contributes to bacterial survival in the absence of NO detoxification. These results indicate a role for Fe-S cluster repair in the survival of Y. pseudotuberculosis within the spleen and suggest that extracellular bacteria may rely on this pathway for survival within host tissues.

Study protocol for a telephone-based smoking cessation randomized controlled trial in the lung cancer screening setting: The lung screening, tobacco, and health trial.

Lung cancer mortality can be reduced by 20% via low dose CT lung cancer screening (LCS) and treatment of early-stage disease. Providing tobacco use treatment to high risk cigarette smokers in the LCS setting may result in health benefits beyond the impact of LCS. As one of the nine trials in the National Cancer Institute's Smoking Cessation at Lung Examination (SCALE) collaboration, the goal of the Lung Screening, Tobacco, and Health (LSTH) trial is to develop a scalable and cost-effective cessation intervention for subsequent implementation by LCS programs. Guided by the RE-AIM Framework, the LSTH trial is a two-arm RCT (N = 1330) enrolling English- and Spanish-speaking smokers registered for LCS at one of seven collaborating sites. Participants are randomly assigned to Usual Care (UC; three proactive telephone counseling sessions/two weeks of nicotine patches) vs. Intensive Telephone Counseling (ITC; eight proactive sessions/eight weeks of nicotine patches, plus discussion of the LCS results to increase motivation to quit). Telephone counseling is provided by tobacco treatment specialists. To increase continuity of care, referring physicians are notified of participant enrollment and smoking status following the intervention. Outcomes include: 1) self-reported 7-day, 30-day, and sustained abstinence, and biochemically-verified at 3-, 6-, and 12-months post-randomization, 2) reach and engagement of the interventions, and 3) cost-effectiveness of the interventions. The Cancer Intervention and Surveillance Modeling Network (CISNET) will model long-term impacts of six SCALE trials on the cost per life year saved, quality-adjusted life years saved, lung cancer mortality reduction, and population mortality. CLINICAL TRIALS REGISTRATION: The trial is registered at clinical trials.gov: NCT03200236.

Quality of life among men with low-risk prostate cancer during the first year following diagnosis: the PREPARE prospective cohort study.

As many as 40% of men diagnosed with prostate cancer have low-risk disease, which results in the need to decide whether to undergo active treatment (AT) or active surveillance (AS). The treatment decision can have a significant effect on general and prostate-specific quality of life (QOL). The purpose of this study was to assess the QOL among men with low-risk prostate cancer during the first year following diagnosis. In a prospective cohort study, we conducted pretreatment telephone interviews (N = 1,139; 69.3% response rate) with low-risk PCa patients (PSA ≤ 10, Gleason ≤ 6) and a follow-up assessment 6-10 months postdiagnosis (N = 1057; 93%). We assessed general depression, anxiety, and physical functioning, prostate-specific anxiety, and prostate-specific QOL at both interviews. Clinical variables were obtained from the medical record. Men were 61.7 (SD = 7.2) years old, 82% white, 39% had undergone AT (surgery or radiation), and 61.0% had begun AS. Linear regression analyses revealed that at follow-up, the AS group reported significantly better sexual, bowel, urinary, and general physical function (compared to AT), and no difference in depression. However, the AS group did report greater general anxiety and prostate-specific anxiety at follow-up, compared to AT. Among men with low-risk PCa, adjusting for pretreatment functioning, the AS group reported better prostate-related QOL, but were worse off on general and prostate-specific anxiety compared to men on AT. These results suggest that, within the first year postdiagnosis, men who did not undergo AT may require additional support in order to remain comfortable with this decision and to continue with AS when it is clinically indicated.

Decision-making processes among men with low-risk prostate cancer: A survey study.

OBJECTIVE: To characterize decision-making processes and outcomes among men expressing early-treatment preferences for low-risk prostate cancer. METHODS: We conducted telephone surveys of men newly diagnosed with low-risk prostate cancer in 2012 to 2014. We analyzed subjects who had discussed prostate cancer treatment with a clinician and expressed a treatment preference. We asked about decision-making processes, including physician discussions, prostate-cancer knowledge, decision-making styles, treatment preference, and decisional conflict. We compared the responses across treatment groups with χ2 or ANOVA. RESULTS: Participants (n = 761) had a median age of 62; 82% were white, 45% had a college education, and 35% had no comorbidities. Surveys were conducted at a median of 25 days (range 9-100) post diagnosis. Overall, 55% preferred active surveillance (AS), 26% preferred surgery, and 19% preferred radiotherapy. Participants reported routinely considering surgery, radiotherapy, and AS. Most were aware of their low-risk status (97%) and the option for AS (96%). However, men preferring active treatment (AT) were often unaware of treatment complications, including sexual dysfunction (23%) and urinary complications (41%). Most men (63%) wanted to make their own decision after considering the doctor's opinion, and about 90% reported being sufficiently involved in the treatment discussion. Men preferring AS had slightly more uncertainty about their decisions than those preferring AT. CONCLUSIONS: Subjects were actively engaged in decision making and considered a range of treatments. However, we found knowledge gaps about treatment complications among those preferring AT and slightly more decisional uncertainty among those preferring AS, suggesting the need for early decision support.

The challenge of measuring intra-individual change in fatigue during cancer treatment.

PURPOSE: To evaluate how well three different patient-reported outcomes (PROs) measure individual change. METHODS: Two hundred and fourteen patients (from two sites) initiating first or new chemotherapy for any stage of breast or gastrointestinal cancer participated. The 13-item FACIT Fatigue scale, a 7-item PROMIS® Fatigue Short Form (PROMIS 7a), and the PROMIS® Fatigue computer adaptive test (CAT) were administered monthly online for 6 months. Reliability of measured change was defined, under a population mixed effects model, as the ratio of estimated systematic variance in rate of change to the estimated total variance of measured individual differences in rate of change. Precision of individual measured change, the standard error of measurement of change, was given by the square root of the rate-of-change sampling variance. Linear and quadratic models were examined up to 3 and up to 6 months. RESULTS: A linear model for measured change showed the following by 6 and 3 months, respectively: PROMIS CAT (0.363 and 0.342); PROMIS SF (0.408 and 0.533); FACIT (0.459 and 0.473). Quadratic models offered no noteworthy improvement over linear models. Both reliability and precision results demonstrate the need to improve the measurement of intra-individual change. CONCLUSIONS: These results illustrate the challenge of reliably measuring individual change in fatigue with a level of confidence required for intervention. Optimizing clinically useful measurement of intra-individual differences over time continues to pose a challenge for PROs.

Treatment Preferences for Active Surveillance versus Active Treatment among Men with Low-Risk Prostate Cancer.

BACKGROUND: Due to the concerns about the overtreatment of low-risk prostate cancer, active surveillance (AS) is now a recommended alternative to the active treatments (AT) of surgery and radiotherapy. However, AS is not widely utilized, partially due to psychological and decision-making factors associated with treatment preferences. METHODS: In a longitudinal cohort study, we conducted pretreatment telephone interviews (N = 1,140, 69.3% participation) with newly diagnosed, low-risk prostate cancer patients (PSA ≤ 10, Gleason ≤ 6) from Kaiser Permanente Northern California. We assessed psychological and decision-making variables, and treatment preference [AS, AT, and No Preference (NP)]. RESULTS: Men were 61.5 (SD, 7.3) years old, 24 days (median) after diagnosis, and 81.1% white. Treatment preferences were: 39.3% AS, 30.9% AT, and 29.7% NP. Multinomial logistic regression revealed that men preferring AS (vs. AT) were older (OR, 1.64; CI, 1.07-2.51), more educated (OR, 2.05; CI, 1.12-3.74), had greater prostate cancer knowledge (OR, 1.77; CI, 1.43-2.18) and greater awareness of having low-risk cancer (OR, 3.97; CI, 1.96-8.06), but also were less certain about their treatment preference (OR, 0.57; CI, 0.41-0.8), had greater prostate cancer anxiety (OR, 1.22; CI, 1.003-1.48), and preferred a shared treatment decision (OR, 2.34; CI, 1.37-3.99). Similarly, men preferring NP (vs. AT) were less certain about treatment preference, preferred a shared decision, and had greater knowledge. CONCLUSIONS: Although a substantial proportion of men preferred AS, this was associated with anxiety and uncertainty, suggesting that this may be a difficult choice. IMPACT: Increasing the appropriate use of AS for low-risk prostate cancer will require additional reassurance and information, and reaching men almost immediately after diagnosis while the decision-making is ongoing. Cancer Epidemiol Biomarkers Prev; 25(8); 1240-50. ©2016 AACR.

Robust bioengineered 3D functional human intestinal epithelium.

Intestinal functions are central to human physiology, health and disease. Options to study these functions with direct relevance to the human condition remain severely limited when using conventional cell cultures, microfluidic systems, organoids, animal surrogates or human studies. To replicate in vitro the tissue architecture and microenvironments of native intestine, we developed a 3D porous protein scaffolding system, containing a geometrically-engineered hollow lumen, with adaptability to both large and small intestines. These intestinal tissues demonstrated representative human responses by permitting continuous accumulation of mucous secretions on the epithelial surface, establishing low oxygen tension in the lumen, and interacting with gut-colonizing bacteria. The newly developed 3D intestine model enabled months-long sustained access to these intestinal functions in vitro, readily integrable with a multitude of different organ mimics and will therefore ensure a reliable ex vivo tissue system for studies in a broad context of human intestinal diseases and treatments.

A comparison of web-based versus print-based decision AIDS for prostate cancer screening: participants' evaluation and utilization.

BACKGROUND: Patient decision aids facilitate informed decision making for medical tests and procedures that have uncertain benefits. OBJECTIVE: To describe participants' evaluation and utilization of print-based and web-based prostate cancer screening decision aids that were found to improve decisional outcomes in a prior randomized controlled trial. DESIGN: Men completed brief telephone interviews at baseline, one month, and 13 months post-randomization. PARTICIPANTS: Participants were primary care patients, 45-70 years old, who received the print-based (N = 628) or web-based decision aid (N = 625) and completed the follow-up assessments. MAIN MEASURES: We assessed men's baseline preference for web-based or print-based materials, time spent using the decision aids, comprehension of the overall message, and ratings of the content. KEY RESULTS: Decision aid use was self-reported by 64.3 % (web) and 81.8 % (print) of participants. Significant predictors of decision aid use were race (white vs. non-white, OR = 2.43, 95 % CI: 1.77, 3.35), higher education (OR = 1.68, 95 % CI: 1.06, 2.70) and trial arm (print vs. web, OR = 2.78, 95 % CI: 2.03, 3.83). Multivariable analyses indicated that web-arm participants were more likely to use the website when they preferred web-based materials (OR: 1.91, CI: 1.17, 3.12), whereas use of the print materials was not significantly impacted by a preference for print-based materials (OR: 0.69, CI: 0.38, 1.25). Comprehension of the decision aid message (i.e., screening is an individual decision) did not significantly differ between arms in adjusted analyses (print: 61.9 % and web: 68.2 %, p = 0.42). CONCLUSIONS: Decision aid use was independently influenced by race, education, and the decision aid medium, findings consistent with the 'digital divide.' These results suggest that when it is not possible to provide this age cohort with their preferred decision aid medium, print materials will be more highly used than web-based materials. Although there are many advantages to web-based decision aids, providing an option for print-based decision aids should be considered.

The association of long-term treatment-related side effects with cancer-specific and general quality of life among prostate cancer survivors.

OBJECTIVE: To examine the association between treatment-related side effects and cancer-specific and general quality of life (QOL) among long-term prostate cancer survivors. MATERIALS AND METHODS: Within the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial, we conducted telephone interviews with prostate cancer survivors (N = 518) who were 5-10 years after diagnosis. We assessed demographic and clinical information, sexual, urinary, and bowel treatment-related side effects (Expanded Prostate Cancer Index Composite), cancer-specific QOL (Functional Assessment of Cancer Therapy--total score), and general QOL (the Medical Outcomes Study Short Form 12's physical and mental subscales). RESULTS: Participants were aged 74.6 years on average, primarily White (88.4%), and married (81.7%). Pearson correlation coefficients between the 3 treatment-related side effect domains (urinary, sexual, and bowel) and QOL ranged between 0.14 and 0.42 (P <.0001). Multivariable linear regression analyses revealed that poorer urinary and sexual functioning and greater bowel side effects were independently associated with poorer cancer-specific QOL (P <.0001). Bowel and urinary functions were also associated with poorer general QOL on the Medical Outcomes Study Short Form 12's physical component summary and mental component summary (P <.05). Bowel side effects demonstrated the strongest association with all QOL outcomes. CONCLUSION: Treatment-related side effects persisted for up to 10 years after diagnosis and continued to be associated with men's QOL. These results suggest that each of the treatment-related side effects was independently associated with cancer-specific QOL. Compared with the other Expanded Prostate Cancer Index Composite domains, bowel side effects had the strongest association with cancer-specific and general QOL. These associations emphasize the tremendous impact that bowel side effects continue to have for men many years after their initial diagnosis.

Fostering informed decisions: a randomized controlled trial assessing the impact of a decision aid among men registered to undergo mass screening for prostate cancer.

OBJECTIVE: Screening asymptomatic men for prostate cancer is controversial and informed decision making is recommended. Within two prostate cancer screening programs, we evaluated the impact of a print-based decision aid (DA) on decision-making outcomes. METHODS: Men (N=543) were 54.9 (SD=8.1) years old and 61% were African-American. The 2(booklet type: DA vs. usual care (UC))× 2(delivery mode: Home vs. Clinic) randomized controlled trial assessed decisional and screening outcomes at baseline, 2-months, and 13-months. RESULTS: Intention-to-treat linear regression analyses using generalized estimating equations revealed that DA participants reported improved knowledge relative to UC (B=.41, p<.05). For decisional conflict, per-protocol analyses revealed a group by time interaction (B=-.69, p<.05), indicating that DA participants were less likely to report decisional conflict at 2-months compared to UC participants (OR=.49, 95% CI: .26-.91, p<.05). CONCLUSION: This is the first randomized trial to evaluate a DA in the context of free mass screening, a challenging setting in which to make an informed decision. The DA was highly utilized by participants, improved knowledge and reduced decisional conflict. PRACTICE IMPLICATIONS: These results are valuable in understanding ways to improve the decisions of men who seek screening and can be easily implemented within many settings.

Monitoring of health-related quality of life and symptoms in prostate cancer survivors: a randomized trial.

BACKGROUND: Routine symptom and health-related quality of life (HRQOL) assessments can engage patients, give provider feedback, and improve doctor/patient communication. OBJECTIVE: We compared the impact of a technology-assisted symptom monitoring system versus usual care on HRQOL and doctor/patient communication in early-stage prostate cancer (PCa) survivors. METHODS: Men (N = 94) were on average 62-years old, mostly African American (AA; 61.7%), and 10-19 months post-treatment. They were randomized to symptom monitoring plus feedback (SM + F; n = 49) or usual care (UC; n = 45). SM+F participants completed a 12-item telephoneassisted monitoring intervention. All participants completed a baseline and 2 follow-up interviews. RESULTS: Among the SM+F participants, perceptions of the monitoring system were positive: 97.1% endorsed it as easy/very easy to use and 85% felt all patients could benefit from it. At baseline, men reported favorable general and cancer-specific HRQOL and doctor/patient communication, but poorer urinary and sexual function. Although there was no overall impact of the intervention, post hoc exploratory analyses indicated that among AA men, those who received SM+F improved relative to UC on doctor/patient communication (P < .05), general HRQOL (P < .06), and sexual function (P < .05). LIMITATIONS: Variability in survivor follow-up care, limited access to eligible participants, and minimal physician training in the use of reports likely decreased physician investment. CONCLUSION: Overall, PCa survivors were receptive to this monitoring system. Exploratory analyses suggest that this technology-assisted monitoring system may be of particular benefit to African American men. Additional studies with larger samples, more intervention time-points, and increased physician training are needed to strengthen the intervention's impact.

Low incidence of fatigue after hypofractionated stereotactic body radiation therapy for localized prostate cancer.

BACKGROUND: Fatigue is a common side effect of conventional prostate cancer radiation therapy. The increased delivery precision necessitated by the high dose per fraction of stereotactic body radiation therapy (SBRT) offers the potential of reduce target volumes and hence the exposure of normal tissues to high radiation doses. Herein, we examine the level of fatigue associated with SBRT treatment. METHODS: Forty patients with localized prostate cancer treated with hypofractionated SBRT, and a minimum of 12 months follow-up were included in this analysis. Self-reported fatigue and other quality of life measures were assessed at baseline and at 1, 3, 6, 9, and 12 months post-SBRT. RESULTS: Mean levels of fatigue were elevated at 1 month post-SBRT compared to baseline values (P = 0.02). Fatigue at the 3-month follow-up and later were higher but not statistically significantly different compared to baseline. African-American patients reported higher fatigue post-SBRT than Caucasian patients. Fatigue was correlated with hormonal symptoms as measured by the Expanded Prostate Cancer Index Composite (EPIC) quality of life questionnaire, but not with urinary, bowel, or sexual symptoms. Age, co-morbidities, smoking, prostate specific antigen (PSA) levels, testosterone levels, tumor stage, and treatment variables were not associated with fatigue. CONCLUSION: This is the first study to investigate fatigue as a side effect of SBRT. In contrast to standard radiation therapy, results suggest SBRT-related fatigue is short-term rather than a long-term side effect of SBRT. These results also suggest post-SBRT fatigue to be a more frequent complication in African-Americans than Caucasians.

Long-term disease-specific functioning among prostate cancer survivors and noncancer controls in the prostate, lung, colorectal, and ovarian cancer screening trial.

PURPOSE: Within the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO), we assessed the long-term disease-specific functioning among prostate cancer (PCa) survivors versus noncancer controls, the impact of trial arm (screening/usual care) on functioning, and the effect of treatment modality on functioning. PATIENTS AND METHODS: PCa survivors (n = 529), 5 to 10 years postdiagnosis, were frequency-matched to noncancer controls (n = 514) for race, screening center, year of enrollment, and trial arm. Participants completed a telephone interview regarding PCa-specific symptomatology. Weights accounted for patient selection from the five PLCO screening centers. Propensity-score methods were used to balance groups of interest with respect to demographic and medical characteristics. RESULTS: Weighted linear regression analyses revealed poorer sexual and urinary function among PCa survivors compared with noncancer controls (P < .001). Trial arm was not significantly related to any outcome (P > .31). Compared with radical prostatectomy patients (n = 201), radiation-therapy patients (n = 110) reported better sexual (P < .05) and urinary (P < .001) functioning but poorer bowel outcomes (P < .05). Survivors who received treatment combinations including androgen deprivation (n = 207) reported significantly poorer hormone-related symptoms compared with radical prostatectomy patients (P < .05). CONCLUSION This study demonstrated the persistence of clinically significant, long-term PCa treatment-related sexual and urinary adverse effects up to 10 years postdiagnosis. To our knowledge, this was the first comparison of prostate-related dysfunction among screened survivors versus screened noncancer controls and indicated that these long-term problems were attributable to PCa treatment and not to aging or comorbidities. Finally, differences in long-term adverse effects between treatment modalities are particularly relevant for patients and clinicians when making treatment decisions.