Association Between Common Urologic Medications and Onset of Alzheimer's Disease and Related Dementias in Men With Prostate Cancer Managed by Different Primary Treatment Modalities.

OBJECTIVE: To understand the relationship between common urologic medications phosphodiesterase-5 inhibitors (PDE5i) and anticholinergics (AC) and risk of dementia onset in men who underwent different primary treatments for prostate cancer. MATERIALS AND METHODS: Patients (>50years) with prostate cancer (1998-2022) without Alzheimer's disease or related dementias were selected from Cancer of the Prostatic Strategic Urologic Research Endeavor Registry. Minimum medication use was 3months. Fine-Gray regression was performed to determine the association between medication exposure and dementia onset ≥12months after primary treatment in men matched on age, race, comorbid conditions, smoking, and type of clinical site, with competing risk of death. RESULTS: Among 5937 men (53% PDE5i; 14% AC), PDE5i users were younger (63 vs 70, P < .01) with less CAD, CVA, DM (all P < .01); AC users were older (68 vs 66, P < .01) with higher incidence of comorbidities (P < .01). Median months of use was 24.3 (IQR 12.1, 48.7) for PDE5i and 12.2 (IQR 6.1, 24.3) for AC users. Cumulative incidence of Alzheimer's disease or related dementias was 6.5% at 15years. PDE5i (P = .07) and AC (P = .06) were not associated with dementia regardless of primary treatment modality. CONCLUSION: In this retrospective cohort study, PDE5i and AC use do not appear independently associated with risk of dementia. Notably, our cohort was generally healthy and younger which may limit our ability to detect significance. We recommend prospective investigation into association between PDE5i and dementia and advise continued judicious stewardship of AC in older patient populations.

Impact of Stress Urinary Incontinence After Radical Prostatectomy on Time to Intervention, Quality of Life and Work Status.

OBJECTIVE: To characterize the incidence of stress urinary incontinence (SUI) after radical prostatectomy (RP), its treatment, and impact on quality of life (QoL) and work status 1year after RP. MATERIALS AND METHODS: Prostate cancer patients treated by RP (1998-2016) were selected from CaPSURE. SUI was defined as any pads per day (ppd) 1 year after RP. SUI procedures were tracked by CPT codes (sling and artificial sphincter). Patients reported work status (full-time, part-time, unpaid), UCLA PCa Index urinary function (UF) and bother (UB) and SF36 Index physical function (PF). Associations of incontinence with UF, UB, and PF and work status changes were assessed (ANOVA). Lifetable estimates and Cox proportional hazards regression evaluated risk of undergoing SUI procedures. RESULTS: 664/2989 (22%) men treated with RP reported SUI at 1 year. More men with SUI had ≥GG2, intermediate to high-risk disease and non-nerve-sparing surgery (all P < .01). Cumulative incidence of SUI procedures was 1.4% at 10years after RP. Age (HR 2.68 per 10years, 95% CI 1.41-5.08) and number of ppd at 1 year (HR 3.20, 95% CI 2.27-4.50) were associated with undergoing SUI procedures. UF declined at 1year after RP, while UB and PF remained stable. UF, UB, and PF were inversely associated with number of ppd (all P < .01). Change in work status was not associated with incontinence or QoL scores. CONCLUSION: Incontinence affected QoL without impacting work status, suggesting that men with SUI after RP may continue working and go under-treated despite impact on QoL.

Untreated Gleason Grade Progression on Serial Biopsies during Prostate Cancer Active Surveillance: Clinical Course and Pathological Outcomes.

PURPOSE: We describe the outcomes of patients with low risk localized prostate cancer who were upgraded on a surveillance biopsy while on active surveillance and evaluated whether delayed treatment was associated with adverse outcome. MATERIALS AND METHODS: We included men in the study with lower risk disease managed initially with active surveillance and upgraded to Gleason score 3+4 or greater. Patient demographics and disease characteristics were compared. Kaplan-Meier curve was used to estimate the treatment-free probability stratified by initial upgrade (3+4 vs 4+3 or greater), Cox regression analysis was used to examine factors associated with treatment and multivariate logistic regression analysis was used to evaluate the factors associated with adverse outcome at surgery. RESULTS: The final cohort comprised 219 men, with 150 (68%) upgraded to 3+4 and 69 (32%) to 4+3 or greater. Median time to upgrade was 23 months (IQR 11-49). A total of 163 men (74%) sought treatment, the majority (69%) with radical prostatectomy. The treatment-free survival rate at 5 years was 22% for 3+4 and 10% for 4+3 or greater upgrade. Upgrade to 4+3 or greater, higher prostate specific antigen density at diagnosis and shorter time to initial upgrade were associated with treatment. At surgical pathology 34% of cancers were downgraded while 6% were upgraded. Cancer volume at initial upgrade was associated with adverse pathological outcome at surgery (OR 3.33, 95% CI 1.19-9.29, p=0.02). CONCLUSIONS: After Gleason score upgrade most patients elected treatment with radical prostatectomy. Among men who deferred definitive intervention, few experienced additional upgrading. At radical prostatectomy only 6% of cases were upgraded further and only tumor volume at initial upgrade was significantly associated with adverse pathological outcome.

A risk-adjusted definition of biochemical recurrence after radical prostatectomy.

BACKGROUND: To determine whether a variable definition of biochemical recurrence (BCR) based on clincopathologic features facilitates early identification of patients likely to suffer from disease progression. The definition of BCR after radical prostatectomy (RP) bears important implications for patient counseling and management; however, there remains a significant debate regarding the appropriate definition. METHODS: The study cohort consisted of 3619 men who underwent RP for localized prostate cancer from 1989 to 2007, with data abstracted from the Cancer of the Prostate Strategic Urologic Research Endeavor (CaPSURE) registry. Patients were stratified into three risk groups according to Cancer of the Prostate Risk Assessment post-Surgical (CAPRA-S) score. Three single threshold PSA cut-points for BCR were evaluated (PSA > or =0.05, > or =0.2 and > or =0.4 ng ml(-1)) as well as a variable cut-point defined by risk group. After reaching the cut-points, patients were followed for further PSA progression. RESULTS: The proportion of patients with BCR differed by cut-point and risk group, ranging from 7 to 37% (low risk), 22 to 58% (intermediate risk) and 60 to 86% (high risk). The positive-predictive value (PPV) for predicting further PSA progression was 49% for the PSA > or =0.05 ng ml(-1), 62% for the PSA > or =0.2 ng ml(-1), 65% for the PSA > or =0.4 ng ml(-1) and 68% for the risk-adjusted definition. Five-year progression-free survival was 39% for the risk-adjusted definition compared with 45-52% for the other definitions of BCR. CONCLUSIONS: These data suggest that a variable definition of BCR determined by clinicopathologic risk may improve the identification of early recurrence after RP without increasing the overdiagnosis of BCR. By using a risk-adjusted BCR definition, clinicians can better predict future PSA progression and more appropriately counsel patients regarding salvage therapies.

Active surveillance: does serial prostate biopsy increase histological inflammation?

BACKGROUND: Active surveillance (AS) is an appropriate management strategy for men with low-risk prostate cancer. Most protocols recommend repeated prostate biopsy every 12-24 months. The purpose of this paper is to describe histological inflammation patterns in men on AS who underwent serial prostate biopsy for disease monitoring. METHODS: We reviewed records of men on AS from January 1999 through February 2011 who had a diagnostic plus ≥1 repeat transrectal ultrasound-guided biopsies performed at our institution. The type and degree of inflammatory infiltrate were grossly reviewed and scored for each patient's biopsy by a single pathologist. Relationship of inflammation severity and number of serial biopsies was assessed using a repeated measures mixed model. Unpaired t-test and χ(2)-square analysis assessed variance in degree of inflammation and location of inflammation relative to cancer grade progression defined as Gleason sum increase. RESULTS: Fifty-six men met study inclusion criteria. Mean age was 62.1 (6.5) years, 71% were stage cT1c, 79% had a PSA level <10 ng ml(-1), and 98% had diagnostic Gleason sum ≤6. A small, statistically significant increase in maximum chronic inflammation (CI) scores with greater number of repeat biopsies was observed. CI scores were not associated with number of biopsies based on upgrade status. The main limitation to our study is our small sample size. Potential unmeasured confounders, such as unreported antibiotic use or symptomatic prostatitis, may have also affected our findings. CONCLUSIONS: In this pilot study of 56 men on AS for localized prostate cancer, degree of chronic histological inflammation increased with greater number of prostate biopsies, but was not associated with subsequent risk of grade progression.

PSA screening: determinants of primary-care physician practice patterns.

BACKGROUND: The effect of practice guidelines and the European Randomised Screening for Prostate Cancer (ERSPC) and Prostate, Lung, Colorectal and Ovarian (PLCO) trials on PSA screening practices of primary-care physicians (PCPs) is unknown. METHODS: We conducted a national cross-sectional on-line survey of a random sample of 3010 PCPs from July to August 2010. Participants were queried about their knowledge of prostate cancer, PSA screening guidelines, the ERSPC and PLCO trials, and about their PSA screening practices. Factors associated with PSA screening were identified using multivariable linear regression. RESULTS: A total of 152 (5%) participants opened and 89 completed the on-line survey, yielding a response rate of 58% for those that viewed the invitation. Eighty percent of respondents correctly identified prostate cancer risk factors. In all, 51% and 64% reported that they discuss and order PSA screening for men aged 50-75 years, respectively. Fifty-four percent were most influenced by the US Preventative Services Task Force (USPSTF) guidelines. Also, 21% and 28% of respondents stated that their PSA screening practices were influenced by the ERSPC and PLCO trials, respectively. Medical specialty was the only variable associated with propensity to screen, with family medicine physicians more likely to use PSA screening than internists (ß=0.21, P=0.02). CONCLUSIONS: Half of the physicians surveyed did not routinely discuss PSA screening with eligible patients. The impact of the ERSPC and PLCO trials on PSA screening practices was low among US PCPs. USPSTF recommendations for PSA screening continue to be the strongest influence on PCPs' propensity to use PSA screening.

Effects of elevated CO2 on intra-specific competition in Sinapis alba: an examination of the role of growth responses to red:far-red ratio.

Response of plants to elevated CO2 differs markedly between individually- and competitively-grown plants, both in terms of mean size and variation about the mean. Using Sinapis alba, we explored whether these contrasting effects are a consequence of the effect of competition on the red:far red (R:FR) light ratio. Plants were grown at both ambient and elevated (700 microl.l(-1)) CO2 in competitive stands, and as individuals at either a low (0.7) or high (1.25) R:FR ratio at a constant photosynthetic photon fluence rate. Elevated CO2 increased stand biomass by enhancing the growth of canopy dominants, but not the subordinates. As a consequence, elevated CO2 increased the coefficient of variation in size within the stands. Elevated CO2 did not enhance the growth of individually-grown plants at the low R:FR ratio, but did at the high R:FR ratio. Both the poor response of subordinate plants to elevated CO2 and the increased size inequalities of individuals within the stand can be explained in terms of the effect of the R:FR ratio on CO2 responsiveness. The effect of the R:FR ratio on CO2 response may be related to its effect on allocation patterns and nutrient uptake.

Quality of life in young men after radical prostatectomy.

Urinary and sexual function and bother are important outcomes following radical prostatectomy (RP). Since urinary and sexual function are age-related, post-operative bother may vary by age. This study explores the disease-specific quality-of-life outcomes in young men compared with older men undergoing RP. Using CaPSURE data, we identified men who underwent RP and completed the UCLA Prostate Cancer Index (PCI) before and 1-year post-RP. Men were stratified by age (< 55 years, 55-64, > or = 65). Multivariate regression models were created: a linear model for predictors of PCI scores and a logistic model for predictors of severe declines in PCI domains. Younger men scored significantly better than older men in urinary function (P=0.04), urinary bother (P=0.02) and sexual function (P<0.0001) 1-year post-RP. Severe declines in urinary bother (odds ratio (OR)=1.54, 1.01-2.35) and sexual function (OR=3.20, 1.97-5.19) were more common in men > or = 65 years. Men with relationships had less urinary bother (P=0.03) and were less likely to experience severe worsening of urinary bother (OR=0.32, 0.17-0.60) while having a greater risk of severe worsening of sexual bother (OR=2.74, 1.28-5.89). The use of sexual aids was associated with worse sexual bother (P<0.0001) and greater risk of severe worsening of sexual bother (OR=2.29, 1.54-3.30). Baseline PCI scores were independent predictors in all models. One year after RP, younger men (age < 55) have similar, or better, urinary and sexual function and bother. Baseline scores are strongly associated with post-RP scores and severity of declines. Current relationships and use of sexual aids have significant roles in post-RP bother.

Arch-length asymmetry related to an odontoma in a three-year-old.

Odontomas are often discovered after they affect the eruption and position of the permanent teeth. This case report pointed out that as early as thirty months the primary dentition can be altered.

A voluntary serosurvey and behavioral risk assessment for human immunodeficiency virus infection among college students.

The authors conducted a voluntary serosurvey and educational campaign among 3394 undergraduate students attending the University of Maryland at College Park to determine the prevalence of and risk factors for human immunodeficiency virus type 1 (HIV-1) infection. Two students were seropositive (0.06%, 95% confidence interval 0-0.15%). Both were homosexual men with multiple sexual partners. Despite the low prevalence of infection, potential risk factors for transmission of HIV-1 were common, as assessed by a self-administered anonymous questionnaire. These included a previous sexually transmitted disease (12.6%), male homosexual intercourse (4.8% of men), heterosexual anal intercourse (25.3%), heterosexual intercourse with a person at risk (an HIV-1 infected person, a bisexual man, a parenteral drug user, a female prostitute, or a hemophiliac) (5.2%), multiple sexual partners (21% reported 10 or more lifetime partners), and intravenous drug use (1.3%). Assessment of the efficacy of our program by comparing responses on pre- and post-test questionnaires showed gains in knowledge about heterosexual transmission of HIV-1 and an increase in the reported frequency of condom use 1-2 months after participating in the survey. The authors conclude that HIV-1 infections are occurring among college students but in our study group remain confined to persons with known high-risk behavior; however, practices that may support transmission are common, and programs designed to diminish these behaviors among college students are needed.

Assessment of the prevalence and risk factors for human immunodeficiency virus type 1 (HIV-1) infection among college students using three survey methods.

To evaluate the seroprevalence and risk factors for human immunodeficiency virus type 1 (HIV-1) infection among undergraduate college students, the authors simultaneously conducted three types of surveillance on a large university campus (27,902 undergraduates) in the Baltimore-Washington metropolitan area: a voluntary HIV-1 serosurvey with a linked risk assessment questionnaire (n = 3,394), a blinded serosurvey using blood specimens collected for routine purposes in the Student Health Center (n = 1,829), and a random sample risk assessment and case identification mail survey (n = 1,017 respondents of 3,000 solicited). The proportion of students belonging to a known risk group (a homosexual or bisexual man, intravenous drug user, or a sexual partner of a bisexual man, an HIV-1-infected person, a female prostitute, or an intravenous drug user) was 5.9% in the mail survey and 8.8% in the voluntary serosurvey. Whereas no infections were detected in the blinded serosurvey, two infected persons were identified in the mail survey (0.2%) and two in the voluntary serosurvey (0.06%), all among high-risk persons. Although derived from independent samples and subject to different biases, these three survey methods yielded a consistent pattern of HIV-1 epidemiology on this campus, whereby the overall prevalence of infection was low and confined to members of high-risk groups, despite the common occurrence of behaviors that might facilitate sexual transmission of HIV-1 among many other students.