A prospective study of cognitive function in men with non-seminomatous germ cell tumors.

OBJECTIVE: Longitudinal neuropsychological assessments were performed to determine if adjuvant chemotherapy was associated with cognitive dysfunction in men with non-seminomatous germ cell tumors (NSGCT). METHODS: Patients with NSGCT status post-orchiectomy that either received adjuvant chemotherapy (n = 55) or did not (n = 14) were recruited. Patients were tested before chemotherapy, 1 week post-chemotherapy (or 3 months later in the surveillance group) and 12 months after the baseline evaluation. RESULTS: Compared with the surveillance group, patients treated with chemotherapy had higher rates of cognitive decline at 12 months (overall cognitive decline: 0%, 52%, and 67% in the surveillance, low exposure (LE), and high exposure (HE) group, respectively), greater number of tests that declined (mean of 0.1, 1.4, and 2.0 in the surveillance, LE, and HE group, respectively), and more frequent worsening in motor dexterity (0%, 48%, and 46% in the surveillance, LE, and HE group, respectively). Compared with the surveillance group, patients receiving more cycles of chemotherapy demonstrated worse psychomotor speed and learning and memory. Younger age was associated with greater incidence of overall cognitive decline at 12-month follow-up. CONCLUSIONS: Men with NSGCT that received chemotherapy demonstrated greater rates of cognitive decline in a dose-response manner. Reductions in motor dexterity were most common. Decline in learning and memory also was evident particularly at later follow-up time points and in men receiving more chemotherapy. Men that receive chemotherapy for NSGCT are at risk for cognitive decline and may benefit from monitoring and referral for psychosocial care.

Mapping FACT-melanoma quality-of-life scores to EQ-5D health utility weights.

OBJECTIVES: We sought to develop a mapping function from functional assessment of cancer therapy-melanoma (FACT-M) quality of life scores to the EuroQol-5D (EQ-5D) utility scores. METHODS: FACT-M and EQ-5D scores were collected during a prospective study of melanoma-related quality of life at a tertiary cancer care center in the United States. The study sample was divided into development and validation datasets with equal distributions by cancer stage and treatment status. Censored Least Absolute Deviation (CLAD) and Ordinary Least Squares (OLS) regression analyses were performed using the developmental dataset to derive mapping functions, and model performance was examined through comparisons of residuals and measures of fit in the validation dataset. Exploratory analyses examined the predictive ability of clinical factors and individual subscales. RESULTS: Of 273 patients, 75 were undergoing treatment with 198 in follow-up surveillance. Relatively even distributions were observed by melanoma stage: I/II (n = 102), III (n = 100), and IV (n = 71). OLS regression resulted in a mapping function of EQ-5D = 0.0037*FACT-M+0.2238 with an R(2) 0.499. CLAD regression resulted in a mapping function of EQ-5D = 0.0042*FACT-M+0.1648 with pseudo R(2) 0.328. When applied to the validation dataset, correlations between observed and predicted values resulted in identical coefficients (r = 0.824, P < 0.001). Though the mapping functions were similar, residuals were smaller at the 20th, 40th, and 60th percentiles using the OLS model. The CLAD derived mapping function resulted in smaller residuals only for patients whose EQ-5D = 1. CONCLUSIONS: The OLS mapping function demonstrated better predictive ability and will facilitate the derivation of utilities when direct population preference measures are not available.

Long-term quality of life after radical prostatectomy in wives of men in the postoperative adjuvant androgen deprivation trial.

PURPOSE: We examined quality of life in spouses of men in the Post-Adjuvant Androgen Deprivation trial after radical prostatectomy. METHODS: Men at high risk of prostate cancer recurrence were randomized to receive androgen deprivation therapy or observation. Forty-three couples completed telephone interviews every 6 months for 2 years assessing women's mood disturbance, mental and physical health, and sexual function and bother as well as men's symptoms and sociodemographic and marital variables. We used linear mixed modeling to explore relationships between wives' quality of life and time, treatment group, and men's symptoms. RESULTS: Women's mental health functioning improved over time (p < 0.05). Furthermore, women with husbands in the observation group had worse mood disturbance (p = 0.01) and poorer mental health (p = 0.02) than women with husbands in treatment. Men's symptoms were associated with worse physical health in wives (p = 0.02). Women also reported worse sexual function at 18 and 24 months compared with baseline (p = 0.02), but ratings of sexual bother were unrelated to time, treatment, and symptoms. CONCLUSIONS: These exploratory results are consistent with research demonstrating that spousal cancer-related distress decreases over time. Treatment group differences suggest that an examination of caregiving in the context of uncertainty is warranted. Also, the physical burden of caregiving may intensify when men have more symptoms. To inform interventions, future studies should clarify how treatment and symptoms influence wives' distress by examining expectations and communication.

The king's foot of patient-reported outcomes: current practices and new developments for the measurement of change.

PURPOSE: Assessing change remains a challenge in patient-reported outcomes. In June 2009, a group of psychometricians, biostatisticians, and behavioral researchers from other disciplines convened as a Longitudinal Analysis of Patient-Reported Outcomes Working group as part of the Statistical and Applied Mathematical Sciences Institute Summer Psychometric program to discuss the complex issues that arise when conceptualizing and operationalizing "change" in patient-reported outcome (PRO) measures and related constructs. This white paper summarizes these issues and provides recommendations and possible paths for dealing with the complexities of measuring change. METHODS/RESULTS: This article presents and discusses issues associated with: (1) conceptualizing and operationalizing change in PRO measures; (2) modeling change using state-of-the-art statistical methods; (3) impediments to detecting true change; (4) new developments to deal with these challenges; and (5) important gaps that are fertile ground for future research. CONCLUSIONS: There was a consensus that important research still needs to be performed in order develop and refine high-quality PRO measures and statistical methods to analyze and model change in PRO constructs.

Comparison of CAT Item Selection Criteria for Polytomous Items.

Item selection is a core component in computerized adaptive testing (CAT). Several studies have evaluated new and classical selection methods; however, the few that have applied such methods to the use of polytomous items have reported conflicting results. To clarify these discrepancies and further investigate selection method properties, six different selection methods are compared systematically. The results showed no clear benefit from more sophisticated selection criteria and showed one method previously believed to be superior-the maximum expected posterior weighted information (MEPWI)-to be mathematically equivalent to a simpler method, the maximum posterior weighted information (MPWI).

Reducing patient burden to the FACT-Melanoma quality-of-life questionnaire.

Respondent burden has been defined as the cumulative demand placed on study participants related to the use of questionnaires or measurement instruments. The aim of this study was to reduce respondent burden associated with the Functional Assessment of Cancer Therapy-Melanoma (FACT-M), a melanoma-specific quality-of-life questionnaire, through item reduction using multiple psychometric approaches. Data for this study were pooled from three institutional review board-approved protocols. Poorly performing items were identified through distributional and correlation analyses, confirmatory factor analysis, reliability estimation, and Rasch-based approaches in a developmental dataset, and the reduced scale was assessed in a separate testing cohort. Validity, reliability, goodness of fit, and Rasch-based testing were carried out for both the full and the reduced scales. The clinical characteristics of the development (n=198) and testing (n=204) cohorts were similar. Three items identified through classical psychometric approaches and three items identified by Rasch-based analyses were excluded from the FACT-M subscale. Two additional items were identified for potential reduction but were ultimately maintained due to the adverse consequences to the psychometric integrity of the reduced instrument. The reduced FACT-M module contains 18 items. In addition to psychometric assessment, expert consultation was essential when examining areas of content redundancy and was critical when considering specific items for removal. This methodological approach reduced respondent burden by 25% while maintaining the psychometric integrity of the FACT-M.

Testis cancer survivors' health behaviors: comparison with age-matched relative and demographically matched population controls.

PURPOSE: To determine the prevalence rate of health behaviors in testis cancer survivors and to determine whether the rate of health behaviors in survivors was significantly different than those of their age-matched relative controls and a population-based control group matched for age, sex, education, and income. PATIENTS AND METHODS: The health behaviors of 162 testis cancer survivors were compared with their age-matched relative controls (n = 74) and an age-, sex-, education-, and income-matched population-based control group (n ranged from 1,123 to 9,775). Health behaviors were assessed with the telephone-administered Behavioral Risk Factor and Surveillance Survey. RESULTS: Nearly one in five testis cancer survivors reported current smoking and one third reported problem drinking. Only 11% reported having at least five servings of fruits and vegetables per day. Compared with their relative controls, the survivors were more likely to engage in regular exercise. For those participants who drank, survivors were twice as likely to engage in problem drinking and averaged a higher number of drinks compared to their Centers for Disease Control (CDC) controls. Survivors were also half as likely to have at least five servings of fruits and vegetables per day compared with the CDC controls. CONCLUSION: The overall picture regarding testis cancer survivors' health behaviors was mixed compared with the relative and CDC control groups. Our results suggest that reduced alcohol use and increased fruit and vegetable consumption may be important targets for future disease prevention in testis cancer survivors.

Inverse decision theory with applications to screening and diagnosis of cervical intraepithelial neoplasia.

OBJECTIVE: Medical decision makers would like to use decision theory to determine optimal treatment strategies for patients, but this requires priors, likelihoods, and losses. It can be very difficult to specify a loss or utility function in a medical setting, especially when considering both patient health outcomes and economic costs. These issues led to the development of Inverse Decision Theory (IDT), which involves determining the set of losses under which a given decision rule is optimal. METHODS: We apply IDT to the current standard of care for the diagnosis and treatment of precancerous lesions to the cervix, using a Bayesian approach to estimate the probabilities associated with diagnostic tests and make inferences about the region of optimality. There are two ways in which Inverse Decision Theory can be useful: (i) if the decision rule of interest is optimal, then we obtain information about the losses for the optimal treatment strategy, and (ii) if the decision rule of interest is not optimal, then we characterize the losses under which it would be optimal, and assess whether or not it contains reasonable values of the losses. RESULTS: This paper introduces important clinical results: in particular, we find that the current standard of care for cervical precancer is probably not optimal, and a new decision rule which requires a confirmatory biopsy for all patients with a positive Pap smear test result is better. CONCLUSION: We have developed a very general and flexible approach for evaluating treatment strategies that could prove useful in a variety of medical applications.

Mode effects in the center for epidemiologic studies depression (CES-D) scale: personal digital assistant vs. paper and pencil administration.

As interest grows in creating computerized versions of established paper-and-pencil (P&P) questionnaires, it becomes increasingly important to explore whether changing the administration modes of questionnaires affects participants' responses. This study investigated whether mode effects exist when administering the Center for Epidemiologic Studies Depression (CES-D) scale by a personal digital assistant (PDA) versus the classic P&P mode. The Differential Functioning of Items and Tests (DFIT) procedure identified mode effects on the overall test and individual items. A mixed-effects regression model summarized the mode effects in terms of CES-D scores, and identified interactions with covariates. When the P&P questionnaire was administered first, scores were higher on average (2.4-2.8 points) than those of the other administrations (PDA second, PDA first, and P&P second), and all 20 questionnaire items exhibited a statistically significant mode effect. Highly educated people and younger people demonstrated a smaller difference in scores between the two modes. The mode-by-order effect influenced the interpretation of CES-D scores, especially when screening for depression using the established cut-off scores. These results underscore the importance of evaluating the cross-mode equivalence of psychosocial instruments before administering them in non-established modes.

A randomized prospective trial evaluating testosterone, haemoglobin kinetics and quality of life, during and after 12 months of androgen deprivation after prostatectomy: results from the Postoperative Adjuvant Androgen Deprivation trial.

OBJECTIVE: To assess testosterone and haemoglobin kinetics in the Postoperative Adjuvant Androgen Deprivation (PAAD) trial, and correlate these with quality of life (QoL) in this prospective randomized study. PATIENTS AND METHODS: Forty-three patients met the criteria for high-risk cancer after RRP (Gleason score > or = 8, pT3c or Gleason score 7 concomitant with pT3a/b and positive surgical margins) and were prospectively randomized to either observation or AD for 12 months. Haemoglobin and testosterone levels were determined and QoL surveyed at regular intervals for 24 months. RESULTS: Serum testosterone levels were castrate in 19 of 21 treated patients at 3 months and all at 6 months after starting AD. Levels failed to return to normal at 6 months after stopping treatment in six of 16 (38%) patients, and at 12 months in three of 17 (18%). AD caused a delay in the recovery of haemoglobin levels to normal after RRP. There was no statistically significant decline in the Short Form-36 QoL score with AD. Scores on the University of California-Los Angeles Sexual Functioning Scale were decreased during AD, but returned to a level not statistically significantly different from controls after stopping treatment. CONCLUSION: A year of adjuvant AD after RRP affected serum haemoglobin, testosterone and sexual function reversibly, with return to control levels within the subsequent year in most patients. No significant effect on overall QoL with AD was detected in the study.

Classification using the cumulative log-odds in the quantitative pathologic diagnosis of adenocarcinoma of the cervix.

INTRODUCTION: This study develops a method that discriminates between normal and cancerous tissue sections (i.e., populations of cells) using a statistical model applied to high-dimensional quantitative measurements made on a sample of cells. MATERIALS AND METHODS: We use a cumulative log-odds model to create a score for a tissue section using the information from the cells within that tissue section. Then, a threshold is determined using receiver operating characteristic (ROC) curve analysis. The method was tested using data from cervical adenocarcinomas, adenocarcinoma in situ, and normal columnar tissue. RESULTS: Using 120 potential features, we analyzed the data for staining-independent features. Twenty-two features were statistically significant. We then calculated the log-odds and created a score, followed by ROC curve analysis. The operating point which maximizes the sum of the specificity and sensitivity achieved a sensitivity of 100% with a specificity of 85%. CONCLUSION: The cumulative log-odds performs well in classifying tissue sections using high-dimensional data measured at the cellular level, like that of quantitative pathology. This methodology potentially has applications in pathology, radiology, and optical technologies.