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Background: Elevated serum prostate-specific antigen (PSA) levels are predictive of a future diagnosis of prostate cancer. To test the hypothesis that older men with low PSA levels may require less intensive PSA testing because of a reduced prostate cancer detection rate, we evaluated the association between age, baseline PSA level, and prostate cancer detection. Methods: We conducted a prospective cohort study among participants in a study of aging who had serial PSA measurements taken from age 60 or 65 years until they either were diagnosed with prostate cancer (cancer case subjects) or reached the age of 75 years (subjects without prostate cancer). The time of cancer detection among cancer case subjects was defined as the measurement date on which a PSA level above 4.0 ng/mL was detected (i.e., PSA conversion). Cancer case subjects and subjects without prostate cancer were analyzed according to baseline PSA level and age. Results: All cancer case subjects in the 60-year-old cohort had baseline PSA levels above 0.5 ng/mL, and 14 of 15 cancer cases that would have been detected by a PSA conversion among the 65-year-old cohort were associated with baseline PSA levels of 1.1 ng/mL or more. If PSA testing were discontinued in men aged 65 years with PSA levels of 0.5 ng/mL or less, 100% (95% confidence interval [CI] = 78%-100%) of the cancers would still be detected by age 75 years; if PSA testing were discontinued in men aged 65 years who had PSA levels of 1.0 ng/mL or less, 94% (95% CI = 70%-100%) of the cancers would still be detected by age 75 years. Conclusions: These data suggest that a decrease in the intensity of screening among older men with low PSA values may not lead to an increase in undetected prostate cancer. [J Natl Cancer Inst 1999;91:1733-7]

The extent to which socially-assigned and culturally mediated social identity affects health depends on contingencies of social identity that vary across and within populations in day-to-day life. These contingencies are structurally rooted and health damaging inasmuch as they activate physiological stress responses. They also have adverse effects on cognition and emotion, undermining self-confidence and diminishing academic performance. This impact reduces opportunities for social mobility, while ensuring those who "beat the odds" pay a physical price for their positive efforts. Recent applications of social identity theory toward closing racial, ethnic, and gender academic achievement gaps through changing features of educational settings, rather than individual students, have proved fruitful. We sought to integrate this evidence with growing social epidemiological evidence that structurally-rooted biopsychosocial processes have population health effects. We explicate an emergent framework, Jedi Public Health (JPH). JPH focuses on changing features of settings in everyday life, rather than individuals, to promote population health equity, a high priority, yet, elusive national public health objective. We call for an expansion and, in some ways, a re-orienting of efforts to eliminate population health inequity. Policies and interventions to remove and replace discrediting cues in everyday settings hold promise for disrupting the repeated physiological stress process activation that fuels population health inequities with potentially wide application.

In the U.S., Black adults consistently have higher allostatic load – an indicator of physiological dysregulation – than White adults. Education is considered a likely mechanism given racial differences in attainment, but evidence is mixed. This may be due, in part, to data limitations that have made it difficult for scholars to account for the structurally rooted systemic racism that shaped the U.S. education system and led to large racial inequities in school term length and school attendance among older adults who grew up in the Jim Crow South. Our study addresses this limitation by linking historical data on Black and White segregated school systems in the U.S. South from 1919 to 1954 to the Health and Retirement Study (HRS) to determine if a new measure of educational attainment that accounts for structural racism that led to differences in the number of school days attended by Black and White students across years and states better explains Black-White inequities in allostatic load among older adults who attended school during Jim Crow. We restrict our sample to HRS respondents racialized as White or Black, who resided in the South when they were school-aged, completed primary/secondary school between 1919 and 1954, and provided a measure of allostatic load (n = 1932). We find that our new measure of schooling – duration in school – reduced the Black-White inequity in allostatic load more so than self-reported years of schooling whether we measured allostatic load continuously (34% vs 16%) or categorically (45% vs 20%). Our findings highlight the importance of identifying and using historically informed measures of schooling that account for structurally rooted systemic racism when trying to understand how education shapes the health of individuals racialized as Black in the United States.

The BCR–ABL T315I mutation represents a major mechanism of resistance to tyrosine kinase inhibitors (TKIs). The objectives of this retrospective observational study were to estimate overall and progression-free survival for chronic myeloid leukemia in chronic-phase (CP), accelerated-phase (AP), or blastic-phase (BP) and Philadelphia chromosome—positive (Ph)+ acute lymphoblastic leukemia (ALL) patients with T315I mutation. Medical records of 222 patients from 9 countries were reviewed; data were analyzed using log-rank tests and Cox proportional hazard models. Median age at T315I mutation detection was 54 years; 57% cases were men. Median time between TKI treatment initiation and T315I mutation detection was 29.2, 15.4, 5.8, and 9.1 months, respectively, for CP, AP, BP, and Ph+ ALL patients. After T315I mutation detection, second-generation TKIs were used in 56% of cases, hydroxyurea in 39%, imatinib in 35%, cytarabine in 26%, MK-0457 in 11%, stem cell transplantation in 17%, and interferon-α in 6% of cases. Median overall survival from T315I mutation detection was 22.4, 28.4, 4.0, and 4.9 months, and median progression-free survival was 11.5, 22.2, 1.8, and 2.5 months, respectively, for CP, AP, BP, and Ph+ ALL patients. These results confirm that survival of patients harboring a T315I mutation is dependent on disease phase at the time of mutation detection.

The BCR–ABL T315I mutation represents a major mechanism of resistance to tyrosine kinase inhibitors (TKIs). The objectives of this retrospective observational study were to estimate overall and progression-free survival for chronic myeloid leukemia in chronic-phase (CP), accelerated-phase (AP), or blastic-phase (BP) and Philadelphia chromosome—positive (Ph)+acute lymphoblastic leukemia (ALL) patients with T315I mutation. Medical records of 222 patients from 9 countries were reviewed; data were analyzed using log-rank tests and Cox proportional hazard models. Median age at T315I mutation detection was 54 years; 57% cases were men. Median time between TKI treatment initiation and T315I mutation detection was 29.2, 15.4, 5.8, and 9.1 months, respectively, for CP, AP, BP, and Ph+ALL patients. After T315I mutation detection, second-generation TKIs were used in 56% of cases, hydroxyurea in 39%, imatinib in 35%, cytarabine in 26%, MK-0457 in 11%, stem cell transplantation in 17%, and interferon-α in 6% of cases. Median overall survival from T315I mutation detection was 22.4, 28.4, 4.0, and 4.9 months, and median progression-free survival was 11.5, 22.2, 1.8, and 2.5 months, respectively, for CP, AP, BP, and Ph+ALL patients. These results confirm that survival of patients harboring a T315I mutation is dependent on disease phase at the time of mutation detection.

In spite of significant increases in biodefense spending in the 7 years since the 2001 anthrax attacks, the United States may not yet be fully prepared to respond effectively to many potential biothreats. The principal reasons appear to be that: (1) the problem is extremely complex, and the metrics for success are often unclear; (2) although the US Congress has allocated substantial resources for this effort, these funds are insufficient for the task as initially conceived, i.e., “one drug for each bug;” and (3) there is insufficient coordination among the many agencies working to achieve the goal of protecting the nation from biothreats. In the last few years, much of the biodefense community has come to recognize that an approach that focuses on developing and stockpiling a medical countermeasure (MCM) for each possible biothreat agent is unachievable for reasons of cost, time, and the sheer diversity of emerging threats. Promising alternative models are emerging, including broad spectrum and technology platform approaches, but the requisite cross‐agency planning and coordination, although improving, is still problematic. We have developed a set of software tools and methods for using them that could support the desired coordination and that could also provide for more rapid, comprehensive, and shared identification of key enabling technologies for accomplishing the development of effective medical countermeasures in time to counter or prevent a biothreat. The tools and methods could also make possible a collaborative public‐private partnership for the development of MCM, which many believe is critical to success. Drug Dev Res 70:327–334, 2009 © 2009 Wiley‐Liss, Inc.

This report describes the GRID-Hamilton Depression Rating Scale (GRID-HAMD), an improved version of the Hamilton Depression Rating Scale that was developed through a broad-based international consensus process. The GRID-HAMD separates the frequency of the symptom from its intensity for most items, refines several problematic anchors, and integrates both a structured interview guide and consensus-derived conventions for all items. Usability was established in a small three-site sample of convenience, evaluating 29 outpatients, with most evaluators finding the scale easy to use. Test–retest (4-week) and interrater reliability were established in 34 adult outpatients with major depressive disorder, as part of an ongoing clinical trial. In a separate study, interrater reliability was found to be superior to the Guy version of the HAMD, and as good as the Structured Interview Guide for the Hamilton Depression Rating Scale (SIGH-D), across 30 interview pairs. Finally, using the SIGH-D as the criterion standard, the GRID-HAMD demonstrated high concurrent validity. Overall, these data suggest that the GRID-HAMD is an improvement over the original Guy version as well as the SIGH-D in its incorporation of innovative features and preservation of high reliability and validity.

We determine the effects of treatment with rofecoxib and placebo in patients with chronic prostatitis.

To compare the 2.0 dorzolamide/0.5 timolol fixed combination (COSOPT; Merck & Co., Whitehouse Station, NJ) to 0.5 timolol plus 2.0 pilocarpine given concomitantly, and to determine patient preference, tolerability, and impact on daily life in patients with elevated intraocular pressure (IOP).

An evaluation of longitudinal changes in PSA in men with and without prostate disease revealed that with age, the development of prostate disease is the most important factor influencing changes in PSA. Furthermore, the PSA changes with age are significantly different in men with and without prostate disease. The PSA velocity is greater in men with prostate cancer than in men with BPH and greater in men with prostate cancer and BPH than in men without any prostate disease. Thus, evaluation of PSA changes may help distinguish between men with prostate cancer and those without the disease. This idea will need to be confirmed prospectively. Finally, estimation of PSA doubling time from changes in PSA suggests that changes reflect prostatic growth. Therefore, PSA velocity could be of benefit in identifying men with prostate cancer that is destined to progress.

Studies of age‐associated changes in forced expiratory volume at one second (FEV1) have varied in the degree of screening for health and smoking, and have not examined age differences in variability in FEV1. Longitudinal rates of change and variability in FEV1among healthy lifetime‐non‐smoking White men and women in the Baltimore Longitudinal Study of Aging (BLSA) are reported. Longitudinal FEV1data collected at 2‐year intervals for up to 28 yr in 91 men (417 observations) and 14 yr in 82 women (248 observations) were modelled using mixed‐effects regression models. Longitudinal percentile distributions of FEV1were calculated which reflect age differences in between‐subjects variability. The results show that longitudinal rate of decline in FEV1is more rapid in men than women (340 ml/decade in men compared to 240–330 ml/decade in women), but similar on a percentage basis (10%) and the difference is not statistically significant; FEV1decline begins in early adulthood and progresses at a relatively constant rate over the adult lifespan; longitudinal decline in FEV1in BLSA participants is not statistically different from cross‐sectional estimates from the BLSA and Crapo et al. (1981); and between‐subjects variability is greater in men than women and increases with age. The results document a relatively steady progressive longitudinal decline in FEV1in healthy non‐smoking White adults, as well as age and gender differences in variability in FEV1. The percentile distribution curves reported here are apparently the first reference values for FEV1to be derived using longitudinal methods that reflect age‐specific differences in variability. Am. J. Hum. Biol. 10:471–481, 1998. Published 1998 Wiley‐Liss, Inc.This article is a US Government work and, as such, is in the public domain in the United States of America.

Clinical stage, Gleason score and serum prostate specific antigen (PSA) levels are used separately to predict pathological stage in patients with localized prostate cancer. Because the degree of tumor differentiation has a profound influence on the expression of serum PSA, serum PSA levels alone do not reflect tumor burden accurately. To overcome this obstacle we tested these 3 variables alone and in combinations as predictors of final pathological stage in 703 men with clinically localized prostate cancer at our institution. All patients were assigned a clinical stage by 1 urologist. The Gleason score was determined from preoperative needle biopsy and serum PSA levels were measured on an ambulatory basis. Final pathological stage was determined to be either organ confined, established capsular penetration, seminal vesicle involvement or lymph node involvement. Logistic regression analysis with the likelihood ratio chi-square test determined that serum PSA, Gleason score and clinical stage all predicted final pathological stage well. The results were improved with combinations of the 3 variables (serum PSA, Gleason score and clinical stage) and the combination provided the best separation. From these analyses probability plots and nomograms have been constructed to assist urologists in the preoperative prediction of final pathological stage for patients with clinically localized prostate cancer.

Current studies are inconclusive regarding specific patterns of gender differences in age‐associated hearing loss. This paper presents results from the largest and longest longitudinal study reported to date of changes in pure‐tone hearing thresholds in men and women screened for otological disorders and noise‐induced hearing loss. Since 1965, the Baltimore Longitudinal Study of Aging has collected hearing thresholds from 500 to 8000 Hz using a pulsed‐tone tracking procedure. Mixed‐effects regression models were used to estimate longitudinal patterns of change in hearing thresholds in 681 men and 416 women with no evidence of otological disease, unilateral hearing loss, or noise‐induced hearing loss. The results show (1) hearing sensitivity declines more than twice as fast in men as in women at most ages and frequencies, (2) longitudinal declines in hearing sensitivity are detectable at all frequencies among men by age 30, but the age of onset of decline is later in women at most frequencies and varies by frequency in women, (3) women have more sensitive hearing than men at frequencies above 1000 Hz but men have more sensitive hearing than women at lower frequencies, (4) learning effects bias cross‐sectional and short‐term longitudinal studies, and (5) hearing levels and longitudinal patterns of change are highly variable, even in this highly selected group. These longitudinal findings document gender differences in hearing levels and show that age‐associated hearing loss occurs even in a group with relatively low‐noise occupations and with no evidence of noise‐induced hearing loss.

In 1981 extensive questionnaire and interview data were collected on some 100 young Samoan adults. Five years later in 1986 we determined their whereabouts and divided the data in accordance with migration status. The answers of the 35 who had migrated in the intervening period were contrasted to those 65 who remained in Samoa. The migrants differed in several distinct areas. Migrants reported a higher degree of peer-reliance as a personal adaptive strategy. Migrants also reported larger numbers of individuals in social support networks, a higher quality of support and more community involvement. They also report less expressive display of anger. Those who did not migrate reported a slightly better view of life in Samoa and abroad, as well as better relations with their friends and neighbors. These findings support a hypothesis that migrants are pre-selected to fit into migrant communities and do not appear to be misfits who are unhappy with life in Samoa.

This paper presents age‐specific reference ranges for hearing level and change in hearing level for men and women at 500, 1000, 2000, and 4000 Hz. The percentiles are constructed from data obtained from persons in the Baltimore Longitudinal Study of Aging who were rigorously screened for otological disorders and evidence of noise‐induced hearing loss. The resulting percentile curves represent norms for changes in hearing level in the absence of any known otologic disease. These percentile curves provide a reference for detecting when a person deviates from a normal pattern of change, thus helping in diagnosing problems with hearing or in monitoring hearing in occupational settings. The smoothed means and standard deviations of the hearing levels were used to construct the longitudinal percentiles. The percentiles for cross‐sectional change were constructed using the skew normal distribution to allow for the percentiles to be asymmetric on either side of the median level. These percentiles are the first reference curves that (1) provide standards for hearing level changes over periods of up to 15 years, (2) account for age differences in the distribution of hearing levels, and (3) are based on data from persons who have been systematically screened for otological disorders and evidence of noise‐induced hearing loss. © 1996 Acoustical Society of America.

ObjectivesEvaluation of free and total serum prostate specific antigen (PSA) levels before diagnosis of prostate cancer.MethodsFree and total PSA levels were measured on frozen sera samples of 26 men with no history of prostate disease (controls), 29 men with a histologic diagnosis of benign prostatic hyperplasia (BPH) made at simple prostatectomy (BPH cases), and 23 men with a histologic diagnosis of prostatic cancer (cancer cases). Longitudinal regression analysis was used to evaluate PSA levels as a function of years before diagnosis of prostate disease.ResultsOn average, mean total serum PSA was statistically significantly greater for subjects with cancer (5.0 ng/mL ± 0.9) versus BPH (2.8 ng/mL ± 0.3) and control subjects (0.8 ng/mL ± 0.1) by 4 years before diagnosis, whereas free PSA levels were similar among groups at 4 years before diagnosis. The ratio of free to total serum PSA continuously decreased among cancer cases over the decade before cancer diagnosis. At a time when mean total and free PSA levels were similar among groups (8 years before diagnosis), the ratio of free to total PSA was statistically significantly lower for cancer cases (0.13 ± 0.01) compared with BPH (0.17 ± 0.01) and control cases (0.21 ± 0.02). Use of a free to total PSA ratio of ≤0.12 when total PSA was between 4.0 and 10.0 ng/mL resulted in the highest sensitivity (76%) and specificity (94%) for diagnosis among subjects with and without cancer. Lowering the reflex range to 2.5 ng/mL increased false positive tests more than it increased sensitivity.ConclusionsThe ratio of free to total PSA is the earliest serum marker predicting a subsequent diagnosis of prostate cancer. Measurement of the free to total serum PSA ratio would appear to reduce false positive results among men without prostate cancer.

Finasteride therapy for benign prostatic hyperplasia (BPH) results in a marked lowering of serum prostate specific antigen (PSA) levels. However, little is known about the effect of finasteride on unbound or free serum levels of PSA. Such information would be important since percent free PSA may substantially improve the cancer specificity of PSA testing. Thus, we prospectively studied the effect of finasteride therapy on total and free serum PSA levels.

Until recently, the only information on the growth rate of prostate tumors has been derived from cross-sectional histological labeling studies, autopsy data and clinical studies of patients managed expectantly. However, serial measurements of prostate specific antigen (PSA) may now allow studies of the natural history of the earliest stages of prostate cancer. Frozen sera samples from the Baltimore Longitudinal Study of Aging have been used to compare the patterns of change in PSA levels in men with and without prostate cancer up to 25 years before the diagnosis of cancer. Men with no prostatic disease exhibited a slow linear increase in PSA levels, whereas benign prostatic hyperplasia cases showed a gradual acceleration in the rate of change in PSA. In contrast, cancer cases exhibited an early linear phase followed by an exponential phase of increase in PSA levels before diagnosis. On average, the exponential phase of PSA increases began 7 to 9 years before the tumors were detected clinically. Thus, there is a significant window of opportunity for early detection of prostate cancer. The changes in PSA observed in men with and without prostate cancer are consistent with available information on prostatic growth and the long natural history of prostate cancer. A better understanding of the various factors that affect serum PSA levels may allow more effective use of PSA measurements to detect early stage tumors and predict the biological potential of a tumor.

Current age-specific reference standards for adult hearing thresholds are primarily cross-sectional in nature and vary in the degree of screening of the reference sample for noise-induced hearing loss and other hearing problems. We develop methods to construct age-specific percentiles for longitudinal data that have been modelled using the linear mixed-effects model. We apply these methods to construct percentiles of hearing level using data from a carefully screened sample of women from the Baltimore Longitudinal Study of Aging. However, the variation in the residuals and random effects from the linear mixed-effects model does not remain constant with age and frequency of the stimulus tone. In addition, the distribution of the hearing levels is not symmetric about the mean. We develop a number of methods to use the output from the linear mixed-effects model to construct percentiles that do not have constant variance. We use a transformation of the hearing levels to provide for skewness in the final percentile curves. The change in the variation of the residuals and random effects is modelled as a function of beginning age and frequency and we use this variance function to construct the hearing percentiles. We present a number of approaches. First, we use the absolute values of the population residuals to model the total deviation about the mean as a function of beginning age and frequency. Second, we model the standard deviation in the person-specific (cluster) residuals as well as the standard deviation in the estimated random effects. Finally, we use weighted least squares with the regressions on the absolute cluster residuals and absolute estimated random effects where the weights are the reciprocal of the standard deviations of their estimates. © 1997 John Wiley & Sons, Ltd.

Several letters to the editor are presented in response to articles in previous issues including the political changes in Brazil, another on Brazil's neutralist camp, and updates on the foreign policy of the said country.

Research on rural health needs to represent the diverse demographics of these regions by carefully considering the distinct characteristics, inequities, and stressors occurring in rural communities. Drawing from our own findings and other empirical investigations examining diverse rural communities, we propose several considerations to guide future endeavors toward more inclusive rural health research. These include population-health assessment tools that consider minority stress and intervention strategies designed to reflect both the environmental and socio-cultural contexts of rural residents.

The BCR-ABL T315I mutation is one of the major mechanisms of resistance to tyrosine kinase inhibitors (TKIs). Limited data have suggested that patients harboring a T315I mutation have poor outcomes. The objectives of this study were to estimate overall (OS) and progression-free survival (PFS) for CML in chronic (CP), accelerated (AP), or blastic (BP) phase, and Ph+ ALL patients who developed a T315I mutation; and describe the treatment pattern after T315I detection. Methods: This was a retrospective, multicenter observational study. Eligible patients included CML and Ph+ ALL patients who developed T315I mutation between 1999 and 2008. The medical records of 222 patients from 9 countries (France, Italy, Korea, USA, Germany, Singapore, Denmark, UK and Japan) were abstracted, and Kaplan-Meier plots and Cox proportional hazard models were used for survival analysis. Results: Median age at T315I detection was 54 (range, 18–84) years; 57% were male; 75% were Caucasian and 22% were Asian. Before T315I detection, 97% patients received imatinib (25% as a 1st line) and 50% received second generation TKIs. 16% of patients had other mutations detected before T315I detection. The median time between TKI treatment start and T315I detection was 29 months for CP, 15 for AP, 6 for BP, and 9 for Ph+ ALL. After T315I detection, 56% patients received second generation TKIs (30% started after T315I detection), 39% received hydroxyurea (33% started after T315I detection), 35% received imatinib (13% started after T315I detection), 26% received cytarabine, 21% received investigational drugs including 11% MK-0457, 17% underwent stem cell transplantation, and 6% received interferon alpha (5% started after T315I detection). At the time of T315I detection, T315I formed the predominant clone in 87% of patients; 23% had additional mutations detected (11% of these P-loop mutations). OS and PFS from T315I mutation detection are summarized in Table 1. In a preliminary analysis, the following covariates were associated with worse OS in Cox proportional hazard model (adjusted hazard ratio, 95% confidence interval): older age (by median, 2.30, 1.04–5.09) in Ph+ ALL patients, female gender in BP (1.73, 0.96–3.10); worse performance status in Ph+ ALL (1+ vs. 0; 2.18, 1.02–4.68); and detection of T315I by direct sequencing (vs. other methods) in AP (3.03, 0.89–10.29) and Ph+ ALL (2.33, 1.06–5.12). The effect of different treatments on OS will be available at the time of presentation. Conclusion: These results confirm that survival of patients harboring a T315I mutation is dependent on the disease phase at T315I detection. No clear treatment pattern after T315I detection was observed. Age, gender, performance status, and techniques used for T315I detection might be important prognosis factors affecting OS across different phases of CML and Ph+ ALL. Table 1. OS and PFS of CML and Ph+ ALL patients from T315I detection CML CP (N=82) CML AP (N=38) CML BP (N=56) Ph+ ALL (N=46) * Median survival and survival rates were calculated using Kaplan-Meier method. Median follow up time (months) 12.4 15.2 3.0 3.6 Median OS (months) (95% CI) 22.4 (18.2, 48.5) 28.4 (15.9, 49.8) 4.0 (2.0, 5.0) 4.9 (3.4, 7.3) 1-year OS Rate (95% CI) 71% (58–80%) 69% (50–81%) 23% (13–36%) 12% (3–27%) Median PFS (months) (95% CI) 11.5 (9.2, 15.7) 22.2 (9.0, N/A ) 1.8 (1.2, 4.0) 2.5 (1.8, 3.6) 1-year PFS Rate (95% CI) 46% (34–57%) 56% (38–70%) 16% (7–27%) 7% (1–19%)