Patient-reported outcome measures in dysphagia: a systematic review of instrument development and validation.

OBJECTIVE: Patient-reported outcome (PRO) measures are commonly used to capture patient experience with dysphagia and to evaluate treatment effectiveness. Inappropriate application can lead to distorted results in clinical studies. A systematic review of the literature on dysphagia-related PRO measures was performed to (1) identify all currently available measures and (2) to evaluate each for the presence of important measurement properties that would affect their applicability. DESIGN: MEDLINE via the PubMed interface, the Cumulative Index of Nursing and Allied Health Literature, and the Health and Psychosocial Instrument database were searched using relevant vocabulary terms and key terms related to PRO measures and dysphagia. Three independent investigators performed abstract and full text reviews. Each study meeting criteria was evaluated using an 18-item checklist developed a priori that assessed multiple domains: (1) conceptual model, (2) content validity, (3) reliability, (4) construct validity, (6) scoring and interpretation, and (7) burden and presentation. RESULTS: Of 4950 abstracts reviewed, a total of 34 dysphagia-related PRO measures (publication year 1987-2014) met criteria for extraction and analysis. Several PRO measures were of high quality (MADS for achalasia, SWAL-QOL and SSQ for oropharyngeal dysphagia, PROMIS-GI for general dysphagia, EORTC-QLQ-OG25 for esophageal cancer, ROMP-swallowing for Parkinson's Disease, DSQ-EoE for eosinophilic esophagitis, and SOAL for total laryngectomy-related dysphagia). In all, 17 met at least one criterion per domain. Thematic deficiencies in current measures were evident including: (1) direct patient involvement in content development, (2) empirically justified dimensionality, (3) demonstrable responsiveness to change, (4) plan for interpreting missing responses, and (5) literacy level assessment. CONCLUSION: This is the first comprehensive systematic review assessing developmental properties of all available dysphagia-related PRO measures. We identified several instruments with robust measurement properties in multiple diseases including achalasia, oropharyngeal dysphagia, post-surgical dysphagia, esophageal cancer, and dysphagia related to neurological diseases. Findings herein can assist clinicians and researchers in making more informed decisions in selecting the most fundamentally sound PRO measure for a given clinical, research, or quality initiative.

More Judicious Use of Expectant Management for Localized Prostate Cancer during the Last 2 Decades.

PURPOSE: Urologists have been criticized for overtreating men with low risk prostate cancer and for passively observing older men with higher risk disease. Proponents of active surveillance for low risk disease and critics of watchful waiting for higher risk disease have advocated for more judicious use of observation. Thus, we compared 2 population based cohorts to determine how expectant management has evolved during the last 2 decades. MATERIALS AND METHODS: A total of 5,871 men with localized prostate cancer were enrolled in the PCOS (Prostate Cancer Outcomes Study) or the CEASAR (Comparative Effectiveness Analysis of Surgery and Radiation) study. We compared the use of definitive treatment vs expectant management (watchful waiting or active surveillance) across cohorts, focusing on the influence of disease risk, age and comorbidities. RESULTS: Use of watchful waiting or active surveillance was similar in PCOS and CEASAR (14% in each). Compared to the PCOS, more men in the CEASAR study with low risk disease selected watchful waiting or active surveillance (25% vs 15%, respectively), whereas fewer men with intermediate (7% vs 14%) and high risk (3% vs 10%) disease chose watchful waiting or active surveillance (p <0.001 for each). The association of disease risk with watchful waiting or active surveillance was significantly larger in CEASAR than in PCOS (OR 7.3, 95% CI 3.4 to 15.7). Older age was associated with watchful waiting or active surveillance in both cohorts but there was no association between comorbidity and watchful waiting or active surveillance in the CEASAR study. CONCLUSIONS: Use of watchful waiting or active surveillance was more aligned with disease risk in CEASAR compared to PCOS, suggesting there has been a pivot from watchful waiting to active surveillance. While older men were more likely to be observed, comorbidity had little, if any, influence.

Bone complications among prostate cancer survivors: long-term follow-up from the prostate cancer outcomes study.

BACKGROUND: To assess the relationship between androgen deprivation therapy (ADT) exposure and self-reported bone complications among men in a population-based cohort of prostate cancer survivors followed for 15 years after diagnosis. METHODS: The Prostate Cancer Outcomes Study enrolled 3533 patients diagnosed with prostate cancer between 1994 and 1995. This analysis included participants with non-metastatic disease at the time of diagnosis who completed 15-year follow-up surveys to report development of fracture, and use of bone-related medications. The relationship between ADT duration and bone complications was assessed using multivariable logistic regression models. RESULTS: Among 961 surviving men, 157 (16.3%) received prolonged ADT (>1 year), 120 (12.5%) received short-term ADT (⩽ 1 year) and 684 (71.2%) did not receive ADT. Men receiving prolonged ADT had higher odds of fracture (OR 2.5; 95% confidence interval (CI): 1.1-5.7), bone mineral density testing (OR 5.9; 95% CI: 3.0-12) and bone medication use (OR 4.3; 95% CI: 2.3-8.0) than untreated men. Men receiving short-term ADT reported rates of fracture similar to untreated men. Half of men treated with prolonged ADT reported bone medication use. CONCLUSIONS: In this population-based cohort study with long-term follow-up, prolonged ADT use was associated with substantial risks of fracture, whereas short-term use was not. This information should be considered when weighing the advantages and disadvantages of ADT in men with prostate cancer.

Eosinophilic esophagitis: dilate or medicate? A cost analysis model of the choice of initial therapy.

Eosinophilic esophagitis (EoE) is an increasingly recognized clinical entity. The optimal initial treatment strategy in adults with EoE remains controversial. The aim of this study was to employ a decision analysis model to determine the less costly option between the two most commonly employed treatment strategies in EoE. We constructed a model for an index case of a patient with biopsy-proven EoE who continues to be symptomatic despite proton-pump inhibitor therapy. The following treatment strategies were included: (i) swallowed fluticasone inhaler (followed by esophagogastroduodenoscopy [EGD] with dilation if ineffective); and (ii) EGD with dilation (followed by swallowed fluticasone inhaler if ineffective). The time horizon was 1 year. The model focused on cost analysis of initial treatment strategies. The perspective of the healthcare payer was used. Sensitivity analyses were performed to assess the robustness of the model. For every patient whose symptoms improved or resolved with the strategy of fluticasone first followed by EGD, if necessary, it cost an average of $1078. Similarly, it cost an average of $1171 per patient if EGD with dilation was employed first. Sensitivity analyses indicated that initial treatment with fluticasone was the less costly strategy to improve dysphagia symptoms as long as the effectiveness of fluticasone remains at or above 0.62. Swallowed fluticasone inhaler (followed by EGD with dilation if necessary) is the more economical initial strategy when compared with EGD with dilation first.

Early prostate cancer: prevention, treatment modalities, and quality of life issues.

Our understanding of the screening, prevention and treatment of early prostate cancer is improving. This is a result of new data from clinical trials and the incorporation of efficacy measures based on risk assessment and quality of life (QoL). This review aims to examine completed and ongoing clinical trials that address issues in early prostate cancer, including screening, prevention, treatment, and QoL. Prostate-specific antigen (PSA) testing has a crucial and evolving role in detecting primary prostate cancer, evaluating prevention interventions and assessing the effectiveness of treatment. Questions remain about the optimal PSA parameters appropriate for primary screening and for diagnosing relapse. Emerging and established data provide evidence that early intervention with hormone therapy, either as immediate or adjuvant therapy, delays progression in prostate cancer patients with intermediate or poor prognosis. The impact of therapeutic modality on QoL has become better characterized, as QoL instruments have been developed, validated and applied.

Health related quality of life differences between black and white men with prostate cancer: data from the cancer of the prostate strategic urologic research endeavor.

PURPOSE: Understanding the potential consequences of racial differences in prostate cancer outcomes, from survival rates to quality of life considerations, is important for the clinician and patient. We examined demographic, clinical and health related quality of life data comparing black with white patients just after treatment of prostate cancer and 1 year later. MATERIALS AND METHODS: We analyzed data on 1,178 patients who were newly diagnosed with prostate cancer in the Cancer of the Prostate Strategic Urologic Research Endeavor, a national observational database of men recruited from 35 community and academic urology practices throughout the United States. Patient demographics, clinical characteristics and validated health related quality of life questionnaires were reviewed. A total of 958 white and 161 black patients with prostate cancer who completed at least 2 surveys were compared. RESULTS: The black patients were younger, and had lower income and education levels than white patients. Controlling for age, education and income differences, black patients generally had worse clinical characteristics at presentation and lower baseline health related quality of life data scores in most generic and disease specific categories at treatment. The most notable exception was sexual function, which was the only score that was higher in black patients at treatment. With time, health related quality of life improved in both groups but black patients had slower rates of improvement for general health, bodily pain, physical function, role function, disease worry and bowel function. They continued to have higher sexual function. CONCLUSIONS: Significant differences exist in clinical presentation, sociodemographic characteristics, and health related quality of life between black and white men with prostate cancer. These health related quality of life differences remain after treatment. Physicians should not assume that outcomes in black men would be similar to other patients.

The association between socioeconomic status, health insurance coverage, and quality of life in men with prostate cancer.

The objective of this study was to examine the effect of socioeconomic status and insurance status on health-related quality of life (HRQOL) outcomes in men with prostate cancer. The design was a retrospective cohort study using multiple sites, including both academic and private practice settings. A cohort of 860 men with newly diagnosed, biopsy-proven prostate cancer of any stage was identified within CaPSURE, a longitudinal disease registry of prostate cancer patients. HRQOL was assessed with validated instruments, including the RAND 36-item Health Survey (SF-36) and the UCLA Prostate Cancer Index. Covariates included insurance status, education level, annual income, age, stage, comorbidity, Gleason grade, baseline PSA, marital status, ethnicity and primary treatment. HRQOL measurements were taken at 3-6-month intervals. Analysis of covariance was used to determine the effect of SES and insurance status on the HRQOL domains at baseline and over time. Patients with lower annual income had significantly lower baseline HRQOL scores in the all of the domains of the SF-36 and four of eight disease-specific HRQOL domains. No relationship was seen between annual income and HRQOL outcomes over time. Conversely, health insurance status was associated with HRQOL over time, but not at baseline. Health insurance status appears to have a unique effect on general HRQOL outcomes in men after treatment for prostate cancer. This study confirms the commonly held belief that patients of lower SES tend to have worse quality of life at baseline and following treatment for their disease. These findings have important ramifications for clinicians, researchers and policy makers.

Relationship of first-year costs of treating localized prostate cancer to initial choice of therapy and stage at diagnosis: results from the CAPSURE database.

OBJECTIVES: To determine the relationship among the initial choice of therapy, stage at presentation, and first-year treatment costs in men with newly diagnosed localized prostate cancer. METHODS: First-year resource use and clinical data were collected for 235 subjects with newly diagnosed localized prostate cancer. The costs were estimated from the standard Medicare payment schedules. The relationship among the initial therapy, stage at presentation, and overall cost was examined for the entire cohort and in the subgroup of patients who underwent radical prostatectomy. In addition, the inpatient, outpatient, and medication cost components were evaluated separately to determine what influenced the changes in cost by stage. RESULTS: The mean first-year cost of treating localized prostate cancer in CaPSURE was $6375. When broken down by stage, the mean first-year cost for patients with Stage T1c was $5731, with T2a/b was $6426, and with Stage T2c was $6810 (P = 0.059). The initial treatment choice was significantly associated with the total first-year costs (P <0.001). The mean cost specifically for radical prostatectomy patients with Stage T1c disease was $6881, with T2a/b was $7216, and with T2c was $8027 (P = 0.004). The increases in the first-year cost with higher stage appeared to primarily be associated with increased inpatient resource use and the greater use of adjuvant hormonal therapy. CONCLUSIONS: The first-year costs of treating localized prostate cancer in CaPSURE are associated with the choice of primary and adjuvant therapy. This supports the notion that cost savings may be possible with earlier detection of disease or by minimizing the use of hormonal adjuvant therapy.

The effect of erectile dysfunction on quality of life following treatment for localized prostate cancer.

All forms of prostate cancer therapy carry significant risk of erectile dysfunction, but patients value sexual function so highly that they are often willing to choose a therapy that offers a shorter life expectancy but better potency following treatment. Advances in research methodology now allow reliable collection of meaningful data regarding patients' health-related quality of life, including both objective evaluation of patients' functional status and their perceptions of their own health and its impact on their existence. In the past decade, several validated and reliable questionnaires have been developed that are specifically designed to measure HRQOL in men with prostate cancer. Studies using these instruments have found that function and perceived bother may not be correlated; patients may express satisfaction with their therapy despite loss of sexual function. Erectile aids, including sildenafil, can be helpful for patients following treatment for localized prostate cancer.

Comparison of complications after radical and partial nephrectomy: results from the National Veterans Administration Surgical Quality Improvement Program.

OBJECTIVE: To determine whether radical nephrectomy causes less morbidity, less mortality and is associated with a shorter hospital stay than is partial nephrectomy. PATIENTS AND METHODS: A total of 1885 nephrectomies (1373 radical and 512 partial) conducted between 1991 and 1998 in the Department of Veterans Affairs (VA) National Surgical Quality Improvement Program were evaluated. Using multivariate analyses, outcomes were risk-adjusted based on 45 preoperative variables to compare mortality and morbidity rates. RESULTS: The unadjusted 30-day mortality was 2.0% for radical and 1.6% for partial nephrectomy (P = 0.58). Risk-adjusting the two groups did not result in a statistically significant difference in mortality. The 30-day overall morbidity rate was 15% for radical and 16.2% for partial nephrectomy (P = 0.52); risk-adjusted morbidity rates were not statistically different. There were no statistically significant differences in the rates of postoperative progressive renal failure, acute renal failure, urinary tract infection, prolonged ileus, transfusion requirement, deep wound infection, or extended length of stay. CONCLUSIONS: Partial nephrectomy carried out in the VA program has low morbidity and mortality rates, comparable with the complication rates after radical nephrectomy.

Validation of a staging system for evaluating prognosis in prostate cancer.

BACKGROUND: The purposes of our research were to validate a previously published clinical-anatomic staging system for evaluating prognosis in prostate cancer and to explore the predictive ability of additional factors. METHODS: All patients diagnosed with prostate cancer by physicians affiliated with Yale-New Haven Hospital during 1991 were eligible for the study. Patient and tumor characteristics at baseline were extracted from medical records with up to five-year follow-up for mortality. The original system was validated using Cox proportional hazards analysis and conjunctive consolidation. Prostate specific antigen (PSA) and Gleason score were also explored as factors to be included in an updated staging system. RESULTS: Five-year survival was 76% among 121 patients included in the study. The original staging system, when applied to the current cohort, was validated: Five-year survival ranged from 100% (low-risk) to 27% (high-risk). PSA and Gleason score were associated with survival but did not change results substantially in this population. CONCLUSION: By predicting distinct mortality outcomes in men with prostate cancer, prognostic staging systems can be used to help patients and physicians make informed treatment decisions.

Quality of life following prostate cancer treatments.

Quality of life is of major concern to patients when choosing a treatment for prostate cancer. Health-related quality of life (HRQOL) is a patient-centered variable from the field of health services research that can be assessed in a valid and reliable manner. Using standardized questionnaires specifically designed to measure HRQOL in men with prostate cancer, we can now study the effect of various treatments on patients' quality of life. Treatments for metastatic prostate cancer can have significant effects in all areas of patients' quality of life. Patients with localized disease undergoing radical prostatectomy (RP) tend to have more sexual and urinary dysfunction than do men undergoing external beam radiation therapy (EBRT), although both groups have worse quality of life in these areas than age-matched controls. Men undergoing EBRT have worse bowel function than age-matched controls or men undergoing RP. Recent studies of men undergoing interstitial brachytherapy indicate that these patients have less urinary leakage than those who undergo RP, but experience considerably more irritative voiding symptoms, which can profoundly affect quality of life. Patients need to be informed of the possible impact of therapy on quality of life when choosing treatment.

Does site specific labeling of sextant biopsy cores predict the site of extracapsular extension in radical prostatectomy surgical specimen.

PURPOSE: We determine whether site specific labeling of sextant prostate biopsy cores predicts the site of extracapsular extension in a radical prostatectomy specimen, thereby justifying increased cost of pathological evaluation. MATERIALS AND METHODS: Between January 1994 and December 1997, 407 radical prostatectomies were performed at our institution by a single surgeon (H. L.). Surgical specimens showing extracapsular extension were examined by a single pathologist (J. M.) to identify the site of extension. Several different methods of submitting transrectal ultrasound guided biopsy cores were used since the majority of cases did not undergo biopsy at our institution. In 243 cases sextant biopsies were labeled right versus left. Of these cases 103 specimen cores were individually labeled. The ability of the positive biopsy core location to predict the location of extracapsular extension in the surgical specimen was determined. Univariate and multivariate logistic regression analyses were performed to assess the ability of biopsy core characteristics, including Gleason score, percentage of cancer in the core, core location and number of positive cores in the specimen, to predict the site of extracapsular extension. A similar analysis was performed for the 243 cases with right versus left core labeling. RESULTS: The positive predictive value was 8.9+/-2.2% for a single positive core to identify the location of extracapsular extension correctly in the individually labeled core cases. The absence of cancer in a sextant biopsy had a negative predictive value of 96.9+/-1.4%. The overall sensitivity was 59.4+/-3.8% for a positive biopsy core. In the right versus left core cases the positive predictive value was 12.9+/-3.0% with a sensitivity of 85.1+/-3.2%. In an individual core Gleason score 8 or greater and/or cancer in more than 50% of tissue enhanced the positive predictive value but not to a clinically useful level. Multivariate logistic regression identified Gleason score, number of positive ipsilateral cores and base position of the positive biopsy as the most predictive variables for the site of extracapsular extension. CONCLUSIONS: When submitting biopsy specimens by individually labeled core or right versus left core, the positive predictive value of an individual positive core for the location of extracapsular extension is not sufficient to guide the surgical decision to spare or excise a neurovascular bundle. Therefore, the clinical information provided by individually labeled or right versus left core labeling does not justify the increased associated costs.

Transitions in health-related quality of life during the first nine months after diagnosis with prostate cancer.

Health-Related Quality of Life (HRQOL) is an important outcome measure in the study of prostate cancer. There are few data regarding the effect of sociodemographic variables, such as insurance status, educational level, marital status or income, on HRQOL. We examined whether these or other sociodemographic and clinical variables are predictive of HRQOL outcomes using an observational database of prostate cancer patients accrued from a wide array of clinical practice settings. We studied 131 patients with newly-diagnosed prostate cancer who had been followed for at least nine months. Patients were enrolled in CaPSURE(TM), a large, observational database of patients with prostate cancer. General and disease-specific HRQOL were measured with established, validated instruments at diagnosis and nine months later. Sociodemographic data and co-morbidity counts were recorded at baseline. Multivariate regression analysis was used to determine whether sociodemographic or clinical variables were predictive of baseline HRQOL or HRQOL changes during the study period. Several sociodemographic and clinical variables demonstrated significant associations with HRQOL. We found improvements in general and disease-specific domains of HRQOL during the nine months after diagnosis. For married patients, Emotional Well-Being and Family Functioning scores were better at baseline (+11.8, P<0.02), but Family Functioning declined over the nine month study period (-18.5, P=0.0006). Older patients had slightly better baseline performance in several domains of HRQOL, but experienced greater HRQOL decrements over time than did younger patients. Increasing comorbidity was associated with worse baseline general HRQOL. Early tumor stage was predictive of better scores in general HRQOL domains at baseline. Limited palpable disease stage (T2A/T2B) was predictive of worse Sexual Function and Sexual Bother at nine months (-8.6, P=0.04; -24, P=0.008). After initial decreases, patients appear to experience an improvement in general and disease-specific HRQOL within nine months of initial diagnosis with prostate cancer. Marital status is associated with better HRQOL, while advancing age is associated with more significant HRQOL declines over time. Patients with lower stage disease were noted to have better general HRQOL at baseline, although decreases in the physical domains were noted at nine months. These data shed new light on patients' experience with prostate cancer and suggest that HRQOL outcomes over time may occur in a predictable manner.

Effect of cryptorchidism on testicular histology in a naturally cryptorchid animal model.

PURPOSE: To determine the effect of naturally occurring cryptorchidism on testicular histology in both the cryptorchid and normally descended testis from birth to adulthood using the LE/ORL rat model. MATERIALS AND METHODS: Testicular histology was assessed using established morphometric measures in bilaterally descended (BD), unilaterally descended (UD), bilaterally cryptorchid (BC) and unilaterally cryptorchid (UC) testis at days 15, 22, 30, 45 and 60 of age. Testicular mass was also measured at these times. RESULTS: Changes in testicular histology in the BC and UC testes were not noted on or prior to day 30 of age. Significant changes were noted by day 45 of age and continued into adulthood at day 60 of age. There were no histological abnormalities noted in the UD and BD groups. CONCLUSIONS: Since histological changes seen in this animal model occur after the time of testicular descent (day 28 of age), we hypothesize that these changes are due to an abnormal anatomical position of the testis as opposed to an inherent testicular defect in the LE/ORL rat. This hypothesis is supported by the fact that no histological differences were noted between the scrotal testes of unilaterally cryptorchid animals and bilaterally descended control animals.

Adrenal control of erectile function and nitric oxide synthase in the rat penis.

Penile erection is a nitric oxide (NO)-mediated process that has been shown to be androgen dependent in rats. Castration reduces the activity of the penile enzyme involved in NO synthesis, nitric oxide synthase (NOS). To determine whether adrenal androgens and/or corticosteroids contribute to this control, the following groups of Fischer 344 adult male rats (n = 5-7) were studied: 1) intact, 2) castrated, 3) adrenalectomized alone, 4) castrated/adrenalectomized, 5) castrated/adrenalectomized with aldosterone (1.25 mg/kg, s.c.) and hydrocortisone (12 mg/kg, s.c.), 6) castrated/adrenalectomized with dihydrotestosterone (1.2-cm SILASTIC-brand tubing pellet; Dow Corning, Midland, MI), 7) castrated/adrenalectomized with dehydroepiandrosterone (2-cm tubing), 8) castrated/adrenalectomized with aldosterone (1.25 mg/kg, s.c.), and 9) castrated/adrenalectomized with hydrocortisone (12 mg/kg, s.c.). After 1 week, EFS was applied, and the maximal intracavernosal pressure (MIP) and mean arterial pressure (MAP) were recorded. The MIP/MAP ratio in the adrenalectomized group (0.37) was reduced to values found in the castrated group (0.40). The values in both groups were significantly less than those in intact controls (0.75). The most significant reduction in MIP/MAP was seen in the adrenalectomized/castrated group (0.16). Erectile response in animals submitted to adrenalectomy and castration was restored close to intact values with the administration of hydrocortisone and aldosterone (0.63). Similar results were obtained by the administration of either of the substances alone (0.56 and 0.67, respectively). Penile NOS activity assayed by the L-arginine/citrulline conversion was decreased by 55% in the castrated group compared with that in the intact group, but was not further reduced in the adrenalectomized/castrated or adrenalectomized groups. Penile neuronal NOS protein content, estimated by Western blot, was decreased only in the adrenalectomized/castrated animals (35%), and endothelial NOS content was not affected. These data suggest that the rat adrenal gland contributes to the maintenance of the erectile mechanism and may affect neuronal NOS content in the penis in the rat model. The possibility that hypotension may play a role in the erectile dysfunction observed in adrenalectomized rats cannot be discarded.

Computer-generated graphical presentations: use of multimedia to enhance communication.

Personal computers may be used to create, store, and deliver graphical presentations. With computer-generated combinations of the five media (text, images, sound, video, and animation)--that is, multimedia presentations--the effectiveness of message delivery can be greatly increased. The basic tools are (1) a personal computer; (2) presentation software; and (3) a projector to enlarge the monitor images for audience viewing. Use of this new method has grown rapidly in the business-conference world, but has yet to gain widespread acceptance at medical meetings. We review herein the rationale for multimedia presentations in medicine (vis-à-vis traditional slide shows) as an improved means for increasing audience attention, comprehension, and retention. The evolution of multimedia is traced from earliest times to the present. The steps involved in making a multimedia presentation are summarized, emphasizing advances in technology that bring the new method within practical reach of busy physicians. Specific attention is given to software, digital image processing, storage devices, and delivery methods. Our development of a urology multimedia presentation--delivered May 4, 1996, before the Society for Urology and Engineering and now Internet-accessible at http://www.usrf.org--was the impetus for this work.