Evaluation of audiometric threshold shift criteria for ototoxicity monitoring.

BACKGROUND: There is disagreement about ototoxicity monitoring methods. Controversy exists about what audiometric threshold shift criteria should be used, which frequencies should be tested, and with what step size. An evaluation of the test performance achieved using various criteria and methods for ototoxicity monitoring may help resolve these issues. PURPOSE: (1) Evaluate test performance achieved using various significant threshold shift (STS) definitions for ototoxicity monitoring in a predominately veteran population; and (2) determine whether testing in (1/6)- or (1/3)-octave steps improves test performance compared to (1/2)-octave steps. RESEARCH DESIGN: A prospective, observational study design was used in which STSs were evaluated at frequencies within an octave of each subject's high-frequency hearing limit at two time points, an early monitoring test and the final monitoring test. STUDY SAMPLE: Data were analyzed from 78 ears of 41 patients receiving cisplatin and from 53 ears of 28 hospitalized patients receiving nonototoxic antibiotics. Cisplatin-treated subjects received a cumulative dosage > or =350 mg by the final monitoring test. Testing schedule, age, and pre-exposure hearing characteristics were similar between the subject groups. DATA COLLECTION AND ANALYSIS: Threshold shifts relative to baseline were examined to determine whether they met criteria based on magnitudes of positive STS (shifts of > or =5, 10, 15, or 20 dB) and numbers of frequencies affected (shifts at > or =1, 2, or 3 adjacent frequencies) for data collected using approximately (1/6)-, (1/3)-, or (1/2)-octave steps. Thresholds were confirmed during monitoring sessions in which shifts were identified. Test performance was evaluated with receiver operating characteristic (ROC) curves developed using a surrogate "gold standard"; true positive (TP) rates were derived from the cisplatin-exposed group and false positive (FP) rates from the nonexposed, control group. Best STS definitions were identified that achieved the greatest areas under ROC curves or resulted in the highest TP rates for a fixed FP rate near 5%, chosen to minimize the number of patients incorrectly diagnosed with ototoxic hearing loss. RESULTS: At the early monitoring test, average threshold shifts differed only slightly across groups. Test-frequency step size did not affect performance, and changes at one or more frequencies yielded the best test performance. At the final monitoring test, average threshold shifts were +10.5 dB for the cisplatin group, compared with -0.2 dB for the control group. Compared with the (1/2)-octave step size used clinically, use of smaller frequency steps improved test performance for threshold shifts at > or =2 or > or =3 adjacent frequencies. Best overall test performance was achieved using a criterion cutoff of > or =10 dB threshold shift at > or =2 adjacent frequencies tested in (1/6)-octave steps. Best test performance for the (1/2)-octave step size was achieved for shifts > or =15 dB at one or more frequencies. CONCLUSIONS: An ototoxicity monitoring protocol that uses an individualized, one-octave range of frequencies tested in (1/6)-octave steps is quick to administer and has an acceptable FP rate. Similar test performance can be achieved using (1/3)-octave test frequencies, which further reduces monitoring test time.

Determinants of outcomes of sinus surgery: a multi-institutional prospective cohort study.

OBJECTIVES: 1) To measure the proportion of patients with chronic rhinosinusitis (CRS) who experience clinically significant improvement after endoscopic sinus surgery (ESS) in a prospective, multi-institutional fashion. 2) To identify preoperative characteristics that predict clinically significant improvement in quality of life (QOL) after ESS. STUDY DESIGN: Prospective, multi-institutional cohort study. SETTING: Academic tertiary care centers. SUBJECTS AND METHODS: A total of 302 patients with CRS from three centers were enrolled between July 2004 and December 2008 and followed for an average of 17.4 months postoperatively. Preoperative patient characteristics, CT scan, endoscopy score, and pre- and postoperative quality of life (QOL) data were collected. Univariate and multivariate analyses were performed. RESULTS: Patients improved an average of 15.8 percent (18.9 points) on the Rhinosinusitis Disability Index and 21.2 percent (21.2 points) on the Chronic Sinusitis Survey (both P < 0.001). Patients significantly improved on all eight Medical Outcomes Study Short Form-36 (SF-36) subscales (all P < 0.001). Among patients with poor baseline QOL, 71.7 percent of patients experienced clinically significant improvement on the RSDI and 76.1 percent on the CSS. Patients undergoing primary surgery were 2.1 times more likely to improve on the RSDI (95% confidence interval [CI], 1.2, 3.4; P = 0.006) and 1.8 times more likely to improve on the CSS (95% CI, 1.1, 3.1; P = 0.020) compared with patients undergoing revision surgery. CONCLUSION: In this prospective, multi-institutional study, most patients experienced clinically significant improvement across multiple QOL outcomes after ESS. Specific patient characteristics provided prognostic value with regard to outcomes.

Auditory test result characteristics of subjects with and without tinnitus.

Tinnitus is the perception of sound that does not have an acoustic source in the environment. Ascertaining the presence of tinnitus in individuals who claim tinnitus for compensation purposes is very difficult and increasingly becoming a problem. This study examined the potential to observe differences in loudness and pitch matches between individuals who experience tinnitus versus those who do not. This study follows a previous pilot study we completed that included 12 subjects with and 12 subjects without tinnitus. The current study included 36 subjects with and 36 without tinnitus. Results of this study revealed no significant differences between groups with regard to decibel sensation level (SL) loudness matches and within-session loudness-match reliability. Between-group differences revealed that the tinnitus subjects had (1) greater decibel sound pressure level loudness matches, (2) better between-session loudness-match reliability, (3) better pitch-match reliability, and (4) higher frequency pitch matches. These findings support the data from our pilot study with the exception that decibel SL loudness matches were greater for the tinnitus subjects in the pilot study. Tinnitus loudness and pitch matching may have some value in an overall battery of tests for evaluating tinnitus claims.

Predictors of olfactory dysfunction in patients with chronic rhinosinusitis.

OBJECTIVES: To measure the prevalence of and identify clinical characteristics associated with poor olfactory function in a large cohort of patients with chronic rhinosinusitis (CRS). STUDY DESIGN: Multi-institutional, cross sectional analysis. METHODS: An objective measure of olfactory dysfunction, the Smell Identification Test, demographic data, clinical factors, and comorbidity data were collected from a cohort of 367 patients who presented with CRS at three tertiary care centers. Data were analyzed using univariate and multivariate analyses. RESULTS: Sixty-four percent of men and women aged 18 to 64 had olfactory dysfunction whereas 95% of patients older than or equal to 65 years had olfactory dysfunction (P < .001); no significant difference was noted by gender. By multivariate logistic regression analysis, patients with nasal polyposis [Odds ratio (OR) 2.4, 95% confidence interval (CI) 1.3-4.2, P = .003] and patients older than or equal to 65 years (OR 10.0, 95% CI 2.3-43.7, P = .002) were at increased risk of hyposmia. Patients with nasal polyposis (OR 13.2, 95% CI 5.7-30.7, P < .001), asthma (OR 4.2, 95% CI 1.8-9.8, P = .001), older than or equal to 65 years (OR 15.6, 95% CI 2.3-104.9, P = .005), and smokers (OR 7.6, 95% CI 1.8-31.6, P = .005) were at increased risk of anosmia. CONCLUSIONS: Poor olfactory function is common in patients with CRS. Age, nasal polyposis, smoking, and asthma were significantly associated with olfactory dysfunction in patients with CRS. Neither prior endoscopic sinus surgery nor a history of allergic rhinitis was associated with olfactory dysfunction. Septal deviation and inferior turbinate hypertrophy were associated with normal olfactory function.

Long-term survival after colon cancer surgery: a variation associated with choice of anesthesia.

BACKGROUND: A previously published clinical trial of epidural-supplemented versus general anesthesia, Veterans Affairs Cooperative Study No. 345, showed no difference in 30-day mortality and morbidity rates between the two treatments. We hypothesized that long-term postoperative survival would be increased by epidural anesthesia/analgesia supplementation during colon cancer resection. METHODS: We studied long-term survival after resection of colon cancer in a trial of general anesthesia with and without epidural anesthesia and analgesia supplementation for resection of colon cancer in Veterans Affairs Cooperative Study No. 345. Cox and log-normal survival models were used to test the effects of pathological stage, type of anesthesia and other covariates on survival in 177 patients. RESULTS: The presence of distant metastases had the greatest effect on survival. Thus, analyses were performed separately for patients with and without metastases. For those without metastasis, the hazard ratio for the treatment effects changed at 1.46 years. Before 1.46 years, epidural supplementation was associated with improved survival (P = 0.012), while later, the type of anesthesia did not appear to affect survival (P = 0.27). Hypertension was associated with poorer survival (P = 0.029), as was alcoholism in patients who received epidural anesthesia (P = 0.014). Survival of patients with metastases was unaffected by type of anesthesia. There was a significant age by hypertension interaction (P = 0.002). Patients survived longer if they were hypertensive, but had reduced survival if they were older than 66 years and hypertensive. CONCLUSION: Epidural supplementation was associated with enhanced survival among patients without metastases before 1.46 years. Epidural anesthesia had no effect on survival of patients with metastases. Additional studies to confirm or refute these findings are warranted.

Endoscopic and quality-of-life outcomes after revision endoscopic sinus surgery.

OBJECTIVES: First, to examine the impact of endoscopic sinus surgery (ESS) on endoscopic and quality-of-life (QOL) outcomes after revision ESS as compared to primary ESS. Second, to evaluate whether or not other risk factors and/or co-morbidities influence the relationship between revision surgery status and outcomes of ESS. STUDY DESIGN: Prospective observational study with an internal comparison group. METHODS: Preoperative computed tomography scores, pre and postoperative endoscopy scores, and two validated disease-specific QOL instruments, the Rhinosinusitis Disability Index (RSDI) and Chronic Sinusitis Survey (CSS), were collected on a prospective cohort of patients undergoing ESS for chronic rhinosinusitis. Data were analyzed using Pearson's chi and multiple logistic regression models. RESULTS: Mean preoperative Lund-Mackay computed tomography scan scores were similar in primary and revision surgery patients. In patients without polyps, revision ESS patients were 3.88 times more likely to improve on endoscopy scores than primary ESS patients (95% confidence interval 1.70, 8.83; P = .001). In nasal polyp patients, there was no difference by revision status (odds ratio 0.48; 95% confidence interval 0.15, 1.59; P = .23). The odds of improving on the RSDI (odds ratio 0.51, 95% confidence interval 0.25, 1.04, P = .065) and CSS (odds ratio 0.98, 95% confidence interval 0.51, 1.89, P = .950) were not significantly different by revision status. CONCLUSIONS: Both revision and primary ESS patients improved after ESS with regard to endoscopy, RSDI, and CSS scores. In non-polyp patients, revision ESS patients were more likely to improve on endoscopy scores than primary ESS patients; there was no difference in polyp patients by revision status. Revision ESS patients and primary ESS patients were equally as likely to improve on two QOL instruments.

Randomized clinical trial: group counseling based on tinnitus retraining therapy.

The main component of tinnitus retraining therapy (TRT) is structured counseling. We conducted a randomized clinical trial to test the hypothesis that group educational counseling based on TRT principles would effectively treat veterans who have clinically significant tinnitus. Veterans with clinically significant tinnitus were randomized into one of three groups: educational counseling, traditional support, and no treatment. Subjects in the first two groups attended four 1.5 h group sessions each week. All subjects completed outcome questionnaires at baseline and at 1, 6, and 12 mo. A total of 269 subjects participated: 94 in the educational counseling group, 84 in the traditional support group, and 91 in the no-treatment group. Statistical analyses showed that educational counseling provided significantly more benefit than either traditional support or no treatment, as measured by the Tinnitus Severity Index. Results suggest that group educational counseling can significantly benefit many tinnitus patients and could be integral to a "progressive intervention" approach to tinnitus clinical management.

Impact of aspirin intolerance on outcomes of sinus surgery.

OBJECTIVES: To compare objective and quality of life (QOL) outcomes after endoscopic sinus surgery (ESS) in aspirin (ASA)-tolerant patients and ASA-intolerant patients over intermediate and long-term follow-up. STUDY DESIGN: Prospective analysis of a cohort of patients with chronic rhinosinusitis. METHODS: Preoperative computed tomography (CT), pre- and postoperative endoscopy, and two validated disease specific QOL instruments, the Rhinosinusitis Disability Index (RSDI) and Chronic Sinusitis Survey (CSS), were collected. Differences in the proportions of patients who improved were analyzed using Pearson's chi-square and Fisher's exact test. RESULTS: Nineteen ASA-intolerant patients and 104 ASA-tolerant patients were followed for a mean of 17.7 months. Patients with ASA intolerance had significantly worse preoperative CT (P < .0001) and endoscopy scores (P < .0001). After ESS, 57% to 74% of patients improved on endoscopy scores, 63% to 71% improved on the RSDI, and 58% to 73% improved on the CSS; improvement did not significantly differ by ASA status. CONCLUSIONS: Similar proportions of ASA-tolerant and ASA-intolerant patients showed improvement on endoscopy and QOL measures after ESS.

The influence of physician gender on practice satisfaction among obstetrician gynecologists.

OBJECTIVE: A survey was conducted to investigate the hypothesis that female gender would positively affect job satisfaction among obstetrician gynecologists. STUDY DESIGN: A survey was sent to 500 randomized, age matched American College of Obstetrics and Gynecology members, 50% each men and women: 49.8% responded. Data were analyzed with the chi2 contingency test, Cochran's test for linear trends, Student t tests, and multiple regression. RESULTS: Women considered their gender an asset in deciding on a career in obstetrics and gynecology, in obtaining jobs, and in maintaining their practices. Men considered that their gender limited their practice options and were more likely to report that they would not choose a career in obstetrics and gynecology if they could choose again. The only significant difference between men and women in measures of obtaining and maintaining a practice was that men were more likely to practice in small urban or rural settings. Men reported higher incomes. Both genders were equally satisfied with their jobs. CONCLUSION: Although both genders considered female gender to be an asset in obstetrics and gynecology, this survey showed no difference in their ratings of overall career satisfaction.

Issues in the design of multisite clinical trials of psychotherapy: VA Cooperative Study No. 494 as an example.

This article describes issues in the design of an ongoing multisite randomized clinical trial of psychotherapy for treating posttraumatic stress disorder (PTSD) in female veterans and active duty personnel. Research aimed at testing treatments for PTSD in women who have served in the military is especially important due to the high prevalence of PTSD in this population. VA Cooperative Study 494 was designed to enroll 384 participants across 12 sites. Participants are randomly assigned to receive 10 weekly sessions of individual psychotherapy: Prolonged Exposure, a specific cognitive-behavioral therapy protocol for PTSD, or present-centered therapy, a comparison treatment that addresses current interpersonal problems but avoids a trauma focus. PTSD is the primary outcome. Additional outcomes are comorbid problems such as depression and anxiety; psychosocial function and quality of life; physical health status; satisfaction with treatment; and service utilization. Follow-up assessments are conducted at the end of treatment and then 3 and 6 months after treatment. Both treatments are delivered according to a manual. Videotapes of therapy sessions are viewed by experts who provide feedback to therapists throughout the trial to ensure adherence to the treatment manual. Discussion includes issues encountered in multisite psychotherapy trials along with the rationale for our decisions about how we addressed these issues in CSP #494.

Repeated split sample validation to assess logistic regression and recursive partitioning: an application to the prediction of cognitive impairment.

Screening strategies play an important part in the identification and diagnosis of illness. Testing of such strategies in a clinical trial can have important implications for the treatment of such illnesses. Before the clinical trial, however, it is important to develop a practical screening/classification procedure that accurately predicts the presence of the illness in question. Recent published studies have shown a growing preference for classification tree/recursive partitioning procedures.This paper compares the application of logistic regression and recursive partitioning to a neuropsychological data set of 252 patients recruited from four Veterans Affairs Medical Centers. Logistic regression and recursive partitioning was used to predict cognitive impairment in 12 randomly selected exploratory/validation samples. We assessed the effect of sampling on variable selection and predictive accuracy.Predictive accuracy of the logistic regression and recursive partitioning procedures was comparable across the exploratory data samples but varied across the validation samples. Based on shrinkage, both classification procedures performed equally well for the prediction of cognitive impairment across the twelve samples. While logistic regression provided an estimated probability of outcome for each patient, it required several mathematical calculations to do so. However, logistic regression selected one or two less predictors than recursive partitioning with comparable predictive accuracy. Recursive partitioning, on the other hand, readily identified patient characteristics and variable interactions, was easy to interpret clinically and required no mathematical calculations. There was a high degree of overlap of the predictor variables between the two procedures.In the context of neuropsychological screening, logistic regression and recursive partitioning performed equally well and were quite stable in the selection of predictors for the identification of patients with cognitive impairment, although recursive partitioning may be easier to use in a clinical setting because it is based on a simple decision tree.

Neuropsychological screening for cognitive impairment using computer-assisted tasks.

The aim of this study was to validate a computer-assisted screening battery for classifying patients into two groups, those with and without cognitive impairment. Participants were all patients referred to the neuropsychology clinics at four VA medical centers during a 1-year period. Patients meeting the study inclusionary criteria (N = 252) were administered the Neurobehavioral Evaluation System-3 (NES3) computer-assisted battery. A detailed neuropsychological examination was carried out by an experienced neuropsychologist, who diagnosed the patient as cognitively impaired or not impaired. The neuropsychologist's diagnosis was the gold standard. Recursive partitioning analyses yielded several classification procedures using the NES3 data to predict the gold standard These procedures produced a set of six NES3 tasks that provide good sensitivity and specificity in predicting di- agnosis. Sensitivity and specificity for the least random classification procedure were 0.87 and 0.67, respectively. The results suggest that computer-assisted screening methods are a promising means of triaging patients.

Interrater reliability of neuropsychological diagnoses: a Department of Veterans Affairs cooperative study.

This study examined the interrater reliability of neuropsychological diagnoses produced by clinical neuropsychologists across 4 medical centers. These diagnoses were based on evaluations using a comprehensive battery of commonly used neuropsychological test instruments, interview, history and medical chart review. The diagnoses of individual neuropsychologists were compared to those made by members of an external review panel for each patient evaluated. Patients were first diagnosed as showing cognitive impairment versus no cognitive impairment. If a patient was diagnosed as impaired, a specific neuropsychological diagnosis was assigned. The diagnostic classification for cognitive impairment was moderately reliable [kappa = .48 +/- s.e.(kappa) = .062]. The interrater reliability for specific diagnoses was in the fair to good range [kappa = .44 +/- s.e.(kappa) = .029]. These levels of reliability are comparable to those found for other psychiatric and neurologic specialties and for medical diagnoses made by other health care disciplines.