Age-related changes in the auditory brainstem response.

PURPOSE: This cross-sectional study had two goals: (1) Identify and quantify the effects of aging on the auditory brainstem response (ABR); (2) Describe how click rate and hearing impairment modify effects of aging. RESEARCH DESIGN AND ANALYSIS: ABR measures were obtained from 131 predominately male Veteran participants aged 26 to 71 yr. Metrics analyzed include amplitude and latency for waves I, III, and V, and the I-V interpeak latency interval (IPI) at three repetition rates (11, 51, and 71 clicks/sec) using both polarities. In order to avoid confounding from missing data due to hearing impairment, participants had hearing thresholds <40 dB HL at 2 kHz and 70 dB HL at 4 kHz in at least one ear. Additionally, the median 2, 3, and 4 kHz pure tone threshold average (PTA2,3,4) for the sample, ∼17 dB HL, was used to delineate subgroups of better and worse hearing ears, and only the better hearing sample was modeled statistically. We modeled ABR responses using age, repetition rate, and PTA2,3,4 as covariates. Random effects were used to model correlation between the two ears of a subject and across repetition rates. Inferences regarding effects of aging on ABR measures at each rate were derived from the fitted model. Results were compared to data from subjects with poorer hearing. RESULTS: Aging substantially diminished amplitudes of all of the principal ABR peaks, largely independent of any threshold differences within the group. For waves I and III, age-related amplitude decrements were greatest at a low (11/sec) click rate. At the 11/sec rate, the model-based mean wave III amplitude was significantly smaller in older compared with younger subjects even after adjusting for wave I amplitude. Aging also increased ABR peak latencies, with significant shifts limited to early waves. The I-V IPI did not change with age. For both younger and older subjects, increasing click presentation rate significantly decreased amplitudes of early peaks and prolonged latencies of later peaks, resulting in increased IPIs. Advanced age did not enhance effects of rate. Instead, the rate effect on wave I and III amplitudes was attenuated for the older subjects due to reduced peak amplitudes at lower click rates. Compared with model predictions from the sample of better hearing subjects, mean ABR amplitudes were diminished in the group with poorer hearing, and wave V latencies were prolonged. CONCLUSIONS: In a sample of veterans, aging substantially reduced amplitudes of all principal ABR peaks, with significant latency shifts limited to waves I and III. Aging did not influence the I-V IPI even at high click rates, suggesting that the observed absolute latency changes associated with aging can be attributed to changes in auditory nerve input. In contrast, ABR amplitude changes with age are not adequately explained by changes in wave I. Results suggest that aging reduces the numbers and/or synchrony of contributing auditory nerve units. Results also support the concept that aging reduces the numbers, though perhaps not the synchrony, of central ABR generators.

Audiometric thresholds and prevalence of tinnitus among male veterans in the United States: data from the National Health and Nutrition Examination Survey, 1999-2006.

Hearing loss and tinnitus are the two most prevalent service-connected disabilities among U.S. veterans. The number of veterans receiving compensation and services from the Department of Veterans Affairs (VA) for these conditions continues to increase annually. However, the majority of veterans in the United States do not use VA medical centers or clinics for healthcare and do not receive VA compensation payments. Therefore, the prevalence of hearing loss and tinnitus among U.S. veterans is unknown. This study used National Health and Nutrition Examination Survey data to estimate the prevalence of these auditory conditions among male veterans. Between 1999 and 2006, pure tone audiometric data collected from 845 male veterans were compared with pure tone thresholds collected from 2,086 male nonveterans. We used questionnaire data collected between 1999 and 2004 to calculate and compare the prevalence of tinnitus for 2,174 veterans and 4,995 nonveterans. In general, pure tone thresholds did not differ significantly between veterans and nonveterans for most frequencies tested (500-8,000 Hz). The overall prevalence of tinnitus was greater for veterans than that for nonveterans (p < 0.001), with statistically significant differences in the 50 to 59 and 60 to 69 age groups.

Adjuvant therapy and survival after resection of pancreatic adenocarcinoma: a population-based analysis.

BACKGROUND: The use of adjuvant chemoradiation for pancreatic adenocarcinoma (PAC) is accepted in North America, but there is a paucity of data to support this practice. The relation between adjuvant therapy and survival was assessed in a population-based cohort of patients with PAC. METHODS: A review was conducted of all cases of resected PAC from 1996 to 2003 using data from the state cancer registry augmented with data from primary medical record review. Use of adjuvant therapy was ascertained from registry data. Survival was assessed using the Kaplan-Meier method, and a Cox proportional hazards model was developed for multivariate analysis. RESULTS: A total of 298 patients from 27 hospitals met criteria for inclusion. There were 228 patients (76.5%) who were resected with curative intent, with a median overall survival of 12 months. The 6-month, 1-year, and 5-year survival rates were 80.2%, 58.4%, and 6.7%, respectively. Of the 228 patients resected, 122 (53.5%) received adjuvant treatment and had a median survival of 13.0 months versus 11.0 months for those with no adjuvant treatment (P = .16). After adjustment for surrogates of performance status, significant predictors of overall survival included no weight loss, T1/T2 pathologic stage, a microscopically complete resection (R0), and receipt of adjuvant therapy. CONCLUSIONS: An R0 resection and adjuvant therapy were found to be independently associated with an increase in overall survival in patients with resected PAC. These data underscore the importance of adjuvant therapy in resected PAC and the need for ongoing clinical trials to refine the efficacy and timing of adjuvant therapy in this disease.

Diabetes-related changes in auditory brainstem responses.

OBJECTIVES/HYPOTHESIS: Determine effects on auditory brainstem response (ABR) of diabetes mellitus (DM) severity. STUDY DESIGN: A cross-sectional study investigating DM severity and ABR in military Veteran subjects with (166) and without (138) DM and with no more than moderate hearing loss. METHODS: Subjects were classified by three age tertiles (<50, 50-56, and 57+). DM severity was classified as insulin-dependent (IDDM), non-insulin-dependent (NIDDM), or no DM. Other DM measures included serum glucose, HbA1c, and several DM-related complications. ABR measures included wave I, III, and V latencies; I-III, III-V, and I-V latency intervals; and wave V amplitude; for each ear at three repetition rates (11, 51, and 71 clicks/second), and both polarities. Outcomes were stratified by age tertile and adjusted for pure tone threshold at 3 kHz. Repeated measures multivariate analysis of covariance modeled the ABR response at each repetition rate for DM severity (main effect) and hearing at 3 kHz (covariate). Modeled contrasts between ABR variables in subjects with and without DM were examined. RESULTS: Significant differences existed between no DM and IDDM groups in the younger tertile only. Adjusting for threshold at 3 kHz had minimal effect. Self-reported noise exposure was not related to ABR differences, but HbA1c and poor circulation were. CONCLUSIONS: IDDM is associated with an increased wave V latency, wave I-V interval, and reduced wave V amplitude among Veterans under 50 years. Results were related to several DM complications.

Diabetes-related changes in hearing.

OBJECTIVES/HYPOTHESIS: Determine the effects on hearing of diabetes mellitus (DM) severity. STUDY DESIGN: We conducted a cross-sectional study among Veterans to investigate the relationship of diabetes severity and hearing in randomly selected subjects with (165) and without (137) DM and who had no more than a moderate hearing loss. METHODS: Subjects were classified by three age tertiles (<50, 50-56, and 57+ years). Diabetes severity was classified as insulin-dependent (IDDM), noninsulin-dependent (NIDDM), or no DM. Other DM measures included concurrent serum glucose, serum HbA(1c), duration of disease, and several measures of DM-related complications. Pure-tone thresholds were measured in both ears of each subject at frequencies from 250 Hz through 14,000 Hz. Outcome measures were adjusted for age and frequency and analyzed for differences between subject groups using analysis of variance. Contrasts of the mean NIDDM and IDDM thresholds at each frequency to the DM group, and controlled for the effects of frequency, age, and interactions were modeled. RESULTS: There was greater hearing loss in younger tertile DM subjects compared to those without DM. Significant hearing differences were at all frequencies for NIDDM subjects, but for IDDM subjects, differences were at 1,000 Hz and below, and 10,000 Hz and above. Over age 50 years, there were significant associations between hearing at low frequencies and IDDM only. Self-report of prior noise exposure did not explain observed differences. CONCLUSIONS: Diabetes is associated with an increased risk of hearing loss, and this difference is manifest particularly in adults <50 years old.

Incremental lifetime cancer risks computed for benzo[a]pyrene and two tobacco-specific N-nitrosamines in mainstream cigarette smoke compared with lung cancer risks derived from epidemiologic data.

The manner in which humans smoke cigarettes is an important determinant of smoking risks. Of the few investigators that have predicted cancer risks from smoking on a chemical-specific basis, most used mainstream cigarette smoke (MCS) carcinogen emissions obtained via machine smoking protocols that only approximate human smoking conditions. Here we use data of Djordjevic et al. [Djordjevic, M.V., Stellman, S.D., Zang, E., 2000. Doses of nicotine and lung carcinogens delivered to cigarette smokers. J. Natl. Cancer Inst. 92, 106-111] for MCS emissions of three carcinogens measured under human smoking conditions to compute probability distributions of incremental lifetime cancer risk (ILCR) values using Monte Carlo simulations. The three carcinogens considered are benzo[a]pyrene, N'-nitrosonornicotine (NNN), and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK). Computed NNK ILCR values were compared with lifetime risks of lung cancer (ILCR(CMD)(obsSigma-lung)) derived from American Cancer Society Cancer Prevention Studies (CPS) I and II. Within the Monte Carlo simulation results, NNK was responsible for the greatest ILCR values for all cancer endpoints: median ILCR values for NNK were approximately 18-fold and 120-fold higher than medians for NNN and benzo[a]pyrene, respectively. For "regular" cigarettes, the NNK median ILCR for lung cancer was lower than ILCR(CMD)(obsSigma-lung) from CPS-I and II by >90-fold for men and >4-fold for women. Given what is known about chemical carcinogens in MCS, this study shows that there is a higher incidence of lung cancer from exposure to MCS than can be predicted with current risk assessment methods using available toxicity and emission data.

Evolving preoperative evaluation of patients with pancreatic cancer: does laparoscopy have a role in the current era?

BACKGROUND: Recent years have brought important developments in preoperative imaging and use of laparoscopic staging of patients with pancreatic adenocarcinoma (PAC). There are few data about the optimal combination of preoperative studies to accurately identify resectable patients. STUDY DESIGN: We conducted a statewide review of all patients with surgically managed PAC from 1996 to 2003 using data from the Oregon State Cancer Registry, augmented with clinical information from primary medical record review. We documented the use of all staging modalities, including CT, endoscopic ultrasonography, and laparoscopy. Primary outcomes included resection with curative intent. The association between staging modalities, clinical features, and resection was measured using a multivariate logistic regression model. RESULTS: There were 298 patients from 24 hospitals who met the eligibility criteria. Patients were staged using a combination of CT (98%), laparoscopy (29%), and endoscopic ultrasonography (32%). The overall proportion of patients who went to surgical exploration and were resected was 87%. Of patients undergoing diagnostic laparoscopy, metastatic disease that precluded resection was discovered in 24 (27.6%). For patients who underwent diagnostic laparoscopy and were not resected, vascular invasion was the most common determinant of unresectability (56.6%). In multivariate analysis, preoperative weight loss and surgeon decision to use laparoscopy predicted unresectability at laparotomy. CONCLUSIONS: This population-based study demonstrates that surgeons appear to use laparoscopy in a subset of patients at high risk for metastatic disease. The combination of current staging techniques is associated with a high proportion of resectability for patients taken to surgical exploration. With current imaging modalities, selective application of laparoscopy with a dual-phase CT scan as the cornerstone of staging is a sound clinical approach to evaluate pancreatic cancer patients for potential resectability.

Incidence and prevalence of uveitis in Veterans Affairs Medical Centers of the Pacific Northwest.

PURPOSE: To ascertain the frequency of uveitis in Veterans Affairs (VA) patients in the Pacific Northwest and to compare disease rates with those in previously published epidemiologic studies. DESIGN: Cross-sectional, population based-study. METHODS: The medical records of 152,267 patients seen at six VA Medical Centers in Oregon and Washington during fiscal year 2004 were searched for uveitis-related International Classification of Diseases 9th edition codes. Cases were reviewed and classified anatomically, by associated systemic disease, and as incident or prevalent. Only definite cases were used for disease rate calculations. RESULTS: This study found a crude incidence of 25.6 cases/100,000 person-years and a crude prevalence of 69 cases/100,000 persons. The most common anatomic location for uveitis was anterior. Approximately half of cases were idiopathic, with human leukocyte antigen-B27-related diseases being the most common identified cause. There was no statistical evidence of increased or decreased incidence with age, although uveitis seemed to be more prevalent in the younger age groups. CONCLUSIONS: Our data are consistent with those of most published population-based studies on the epidemiologic features of uveitis, but we detected significantly lower incidence and prevalence than those reported in a recently published study from Kaiser Permanente. The significance of and possible explanations for the differences between our data and that published by the Kaiser group are discussed.

Detection and description of small breast masses by residents trained using a standardized clinical breast exam curriculum.

OBJECTIVES: We evaluated the effect of standardized clinical breast examination (CBE) training on residents' ability to detect a 3-mm breast mass in a silicone breast model. METHODS: In this nonrandomized controlled trial, 75 first year residents (R1s) at 8 family medicine, internal medicine, and obstetrics and gynecology training programs received the intervention and second year residents (R2s) did not. Trained residency faculty taught R1s vertical strip, three-pressure method (VS3PM) CBE using a standardized curriculum, including a 1- to 2-hour online self-study with video and 2.5-hour practicum using silicone models and a trained patient surrogate. RESULTS: Solitary mass detection: 84% by R1s, 46% by R2s (RR = 1.82, 95%CI = 1.36, 2.43, P < 0.0001). Of those finding a mass, 62% of R1s and 10% of R2s used at least 5 of 8 standardized descriptors (RR = 6.19, 95%CI = 2.06, 18.59, P = 0.001). R1s false positive findings were not statistically different from R2s (P = 0.54). Both the use of VS3PM and total time spent on CBE were independently highly predictive of finding the mass in either group. CONCLUSIONS: Most untrained primary care residents are not proficient in CBE. Standardized VS3PM CBE training improves the ability to detect and describe a small mass in a silicone breast model. Better CBE training for residents may improve the early detection of breast cancer.

The association between advertising and calls to a tobacco quitline.

OBJECTIVE: This study assessed the cost effectiveness of different types of television and radio advertisements and the time of day in which advertisements were placed in generating calls to the Oregon tobacco quitline. DESIGN: Cost effectiveness was measured by cost per call, calculated as the cost of advertising divided by the number of quitline calls generated by that advertising. Advertising was bought in one-week or two-week blocks and included 27 daytime television buys, 22 evening television buys and 31 radio buys. RESULTS: Cost effectiveness varied widely by medium, time of day and advertisement used. Daytime television was seven times more cost effective than evening television and also more cost effective than radio. The most effective advertisements at generating quitline calls were real life testimonials by people who lost family members to tobacco and advertisements that deal practically with how to quit. CONCLUSIONS: Placement of television advertisements during the day versus the evening can increase an advertisement's effectiveness in generating calls to a quitline. Some advertising messages were more effective than others in generating calls to a quitline. Quitline providers can apply findings from previous research when planning media campaigns. In addition, call volume should be monitored in order to assess the cost effectiveness of different strategies to promote use of the quitline.

Calculated cancer risks for conventional and "potentially reduced exposure product" cigarettes.

Toxicant deliveries (by machine smoking) are compiled and associated cancer risks are calculated for 13 carcinogens from 26 brands of conventional cigarettes categorized as "regular" (R), "light" (Lt), or "ultralight" (ULt), and for a reference cigarette. Eight "potentially reduced exposure product" (PREP) cigarettes are also considered. Because agency-to-agency differences exist in the cancer slope factor (CSF) values adopted for some carcinogens, two CSF sets were used in the calculations: set I [U.S. Environmental Protection Agency (EPA)-accepted values plus California EPA-accepted values as needed to fill data gaps] and set II (vice versa). The potential effects of human smoking patterns on cigarette deliveries are considered. Acetaldehyde, 1,3-butadiene, and acrylonitrile are associated with the largest calculated cancer risks for all 26 brands of conventional cigarettes. The calculated risks are proportional to the smoking dose z (pack-years). Using CSF set I and z = 1 pack-year (7,300 cigarettes), the calculated brand-average incremental lifetime cancer risk ILCR(1)(acetaldehyde) values are R, 6 x 10(-5); Lt, 5 x 10(-5); and ULt, 3 x 10(-5) (cf. typical U.S. EPA risk benchmark of 10(-6)). These values are similar, especially given the tendency of smokers to "compensate" when smoking Lt and ULt cigarettes. ILCR(1)(subSigma-lung) is the brand-average per pack-year subtotal risk for the measured human lung carcinogens. Using CSF set I, the ILCR(1)(subSigma-lung) values for R, Lt, and ULt cigarettes account for

Structured clinical breast examination (CBE) training results in objective improvement in CBE skills.

BACKGROUND: A statewide breast cancer care provider needs assessment had identified CBE training as a target educational need. Accordingly, the authors implemented a one-on-one skills-based course for primary care providers (PCPs) across the state. METHOD: The course had two components: a prerequisite self-study manual, followed by a 1 1/2-hour skills-based practicum. As part of the practicum, pre- and post-course testing were performed on standardized silicone breast models. RESULTS: Pre- and post-testing data were available for 205 PCPs who completed the course. In the pre-test period, 59% of PCPs examined could detect 60-100% of the lumps. In the post-test, that rose to 94% of PCPs detecting 60-100% of the lumps. This improvement reached statistical significance. Further, false-positive lump detection declined in the post-test period to 59% of the pre-test rate (236 to 139). CONCLUSION: Formal CBE training for PCPs significantly improves the sensitivity of lump detection and concurrently reduces false-positive detection. The program is currently being extended to a greater number of providers across the state.