Recent trends in the characteristics of patients prescribed sitagliptin and other oral antihyperglycaemic agents in a large U.S. claims database.

AIM: This study was designed to determine if differences in baseline characteristics of patients with type 2 diabetes mellitus (T2DM) being treated with sitagliptin vs. other oral antihyperglycaemic agents (OAHA) during the initial 2 years following sitagliptin's introduction in the U.S. continued during the second 2 years of sitagliptin availability. METHODS: Patients with T2DM and at least one new prescription for sitagliptin or another OAHA from Oct 2006 to April 2010 were identified in an insurance claims database. Multivariate logistic regression adjusting for age, gender, treatment type (monotherapy, dual or triple therapy), new or existing T2DM diagnosis, and comorbidities and diabetes complications in the prior 12 months was used to estimate odds ratios for sitagliptin vs. other OAHAs. RESULTS: During 2006-2007 or 2008-2010, new sitagliptin users were older and more likely to be male, have prior diagnosis of T2DM, or initiating combination therapy compared with new users of other OAHAs. Prevalence of comorbidities and complications was consistently higher for new sitagliptin users across most of the conditions assessed during both time periods. CONCLUSIONS: New sitagliptin users consistently tended to be older and have greater comorbidity/complication burden compared with new users of other OAHAs. These differences in baseline characteristics persisted up to 4 years postapproval. This observation has significant implications for observational studies using electronic medical record or insurance claims databases. Appropriate adjustment is needed to try to control for potential confounding and channelling bias resulting from this non-random prescribing pattern, and the limitations of such analyses acknowledged.

Impact of diabetes duration and chronic pancreatitis on the association between type 2 diabetes and pancreatic cancer risk.

AIM: To examine the impact of diabetes duration, chronic pancreatitis and other factors on pancreatic cancer risk. METHODS: This retrospective cohort study using the UK General Practice Research Database compared pancreatic cancer incidence and risk in patients with type 2 diabetes mellitus (T2DM) versus patients without diabetes. Multivariate Cox regression adjusting for age, sex, history of chronic pancreatitis, gallbladder disease, obesity, smoking and alcohol use and Charlson comorbidity index was used to estimate hazard ratio (HR) [95% confidence interval, CI]. Analyses were repeated using various time windows for diabetes duration. RESULTS: A total of 1903 incident pancreatic cancers were identified, 436 in patients with T2DM (78.76 per 100 000 person-years [95% CI: 71.54, 86.51]) and 1467 in patients without diabetes (11.46 per 100 000 person-years [10.88, 12.06]). Pancreatic cancer risk was significant for T2DM (adjusted HR 1.80 [1.52, 2.14]), increasing age, history of chronic pancreatitis and tobacco use. For patients with chronic pancreatitis and T2DM, the adjusted HR was 12.12 [6.02, 24.40]. Incidence was highest in patients with ≥5 year duration of T2DM. In patient populations with duration of T2DM ranging from ≥1 to ≥5 years, adjusted HRs remained significant but point estimates attenuated slightly with longer duration of T2DM. CONCLUSIONS: Patients with T2DM had an 80% increased risk of pancreatic cancer versus patients without diabetes. Patients with T2DM and chronic pancreatitis were 12 times more likely to develop pancreatic cancer.

Risk of acute renal failure in patients with Type 2 diabetes mellitus.

AIMS: Progressive decline in renal function has been well described in patients with Type 2 diabetes mellitus, but few studies have assessed the risk of acute renal failure in a large population of patients with Type 2 diabetes. This study quantified the risk of acute renal failure associated with Type 2 diabetes in the General Practice Research Database from the UK. METHODS: Patients with Type 2 diabetes (n = 119,966) and patients without diabetes (n = 1,794,516) were identified in the General Practice Research Database. Patients with end-stage renal disease were excluded. Crude incidence and multivariate-adjusted hazard ratios of acute renal failure were estimated for patients with diabetes relative to those without diabetes. Cox regression models were adjusted for a variety of comorbidities. Increase of acute renal failure risk resulting from additive effects of specific co-morbidities with Type 2 diabetes was also assessed. RESULTS: Between 2003 and 2007, acute renal failure incidence was 198 per 100,000 person-years in patients with Type 2 diabetes compared with 27 per 100,000 patients-years among patients without diabetes (crude hazard ratio 8.0, 95% CI 7.4-8.7). Risk of acute renal failure for patients with Type 2 diabetes remained significant, but was attenuated in multivariate analyses adjusting for various comorbidities (adjusted hazard ratio 2.5, 95% CI 2.2-2.7). Age and specific comorbidities (chronic kidney disease, hypertension and congestive heart failure) were also associated with increased risk of acute renal failure in Type 2 diabetes. CONCLUSIONS: Patients with Type 2 diabetes have increased risk for acute renal failure compared with patients without diabetes, even after adjustment for known risk factors, particularly in the elderly and those with other comorbidities such as chronic kidney disease, congestive heart failure and hypertension.

The incidence of hypoglycaemia in Muslim patients with type 2 diabetes treated with sitagliptin or a sulphonylurea during Ramadan: a randomised trial.

AIMS: To compare the incidence of symptomatic hypoglycaemia in fasting Muslim patients with type 2 diabetes treated with sitagliptin or a sulphonylurea during Ramadan. METHODS: Patients with type 2 diabetes (age ≥ 18 years) who were treated with a stable dose of a sulphonylurea with or without metformin for at least 3 months prior to screening, who had an HbA(1c) < 10% and who expressed their intention to daytime fast during Ramadan were eligible for this open-label study. Patients were randomised in a 1 : 1 ratio to either switch to sitagliptin 100 mg qd or to remain on their prestudy sulphonylurea. Patients completed daily diary cards to document information on hypoglycaemic symptoms and complications. The primary end-point was the overall incidence of symptomatic hypoglycaemia recorded during Ramadan. RESULTS: Of the 1066 patients randomised, 1021 (n = 507 for sitagliptin and n = 514 for sulphonylurea) returned at least one completed diary card and were included in the analysis. The proportion of patients who recorded one or more symptomatic hypoglycaemic events during Ramadan was lower in the sitagliptin group (6.7%) compared with the sulphonylurea group (13.2%). The risk of symptomatic hypoglycaemia was significantly decreased with sitagliptin relative to sulphonylurea treatment (Mantel-Haenszel relative risk ratio [95% CI] = 0.51 [0.34, 0.75]; p < 0.001). There were no reported events that required medical assistance (i.e. visits to physician or emergency room or hospitalisations) or were considered severe (i.e. events that caused loss of consciousness, seizure, coma or physical injury) during Ramadan. CONCLUSIONS: In Muslim patients with type 2 diabetes who observed the fast during Ramadan, switching to a sitagliptin-based regimen decreased the risk of hypoglycaemia compared with remaining on a sulphonylurea-based regimen. The incidence of hypoglycaemia was lower with gliclazide relative to the other sulphonylurea agents and similar to that observed with sitagliptin.

The Finnish Diabetes Risk Score is associated with insulin resistance but not reduced ß-cell function, by classical and model-based estimates.

AIMS: The Finnish Diabetes Risk Score (FINDRISC) is widely used for risk stratification in Type 2 diabetes prevention programmes. Estimates of ß-cell function vary widely in people without diabetes and reduced insulin secretion has been described in people at risk for diabetes. The aim of this analysis was to evaluate FINDRISC as a tool to characterize reduced ß-cell function in individuals without known diabetes. METHODS: In this population-based cohort from the Hoorn municipal registry, subjects received an oral glucose tolerance test and a meal tolerance test on separate days, in random order, within 2 weeks. One hundred and eighty-six subjects, age 41-66 years, with no known Type 2 diabetes were included. Of those, 163 (87.6%) had normal glucose metabolism and 23 (12.4%) had abnormal glucose metabolism (19 with impaired glucose metabolism; four with newly diagnosed Type 2 diabetes based on study results). Insulin sensitivity and ß-cell function (classical: insulinogenic index; ratio of areas under insulin/glucose curves; model-based: glucose sensitivity; rate sensitivity; potentiation) estimates were calculated from oral glucose tolerance test and meal tolerance test data. RESULTS: FINDRISC was associated with insulin sensitivity (r = -0.41, P < 0.0001), insulin/glucose areas under the curve (meal tolerance test: r = 0.29, P < 0.0001; oral glucose tolerance test: r = 0.21, P = 0.01) and potentiation factor (meal tolerance test: r = 0.21, P = 0.01). After adjusting for insulin sensitivity, these associations with ß-cell function were no longer significant. CONCLUSIONS: After adjustment for insulin sensitivity, FINDRISC was not associated with reduced ß-cell function in subjects without known Type 2 diabetes. While insulin secretion and insulin sensitivity are both components in Type 2 diabetes development, insulin sensitivity appears to be the dominant component behind the association between FINDRISC and diabetes risk.

Characteristics of patients prescribed sitagliptin and other oral antihyperglycaemic agents in a large US claims database.

BACKGROUND AND AIMS: Non-randomised comparative studies of pharmacological agents can be biased because of differences in baseline demographics, medical history and health status of patients prescribed different therapies. Characteristics of patients with type 2 diabetes mellitus (T2DM) taking sitagliptin were compared with patients taking other oral antihyperglycaemic agents (OAHA) in a large US insurance claims database. MATERIALS AND METHODS: Using the United Health Care database, we identified T2DM patients with at least one OAHA prescription, and at least 1 year prior enrollment. Patients were classified into subcohorts including sitagliptin or other OAHA, add-on to monotherapy, and triple or more therapy. Comorbidities 12 months before the first OAHA prescription in study window were based on ICD-9 diagnostic codes and NDC codes for prescriptions. RESULTS: Prevalence of comorbidities was consistently higher for patients with sitagliptin prescriptions across most comorbidities (p < 0.05 for 20 of 30 assessed comorbidities). Overall, baseline differences were apparent (p < 0.0001) for retinopathy (5.7% vs. 3.4%), renal failure (5.1% vs. 2.6%), proteinuria (2.8% vs. 2.0%), hypertension (76.9% vs. 68.2%), congestive heart failure (3.4% vs. 2.6%), myocardial infarction (18.0% vs. 14.4%) and chronic neurological conditions (8.1% vs. 6.6%). Differences were most pronounced for initial monotherapy subcohorts. A higher proportion of sitagliptin users had prescriptions for cardiovascular medication (84.2% vs. 74.9%). CONCLUSION: Sitagliptin users had higher proportions of comorbidities and greater use of prescription medications and physician visits. Researchers should be aware that sitagliptin is prescribed to patients with seemingly worse health status. Ability to analyse observational, non-randomised studies may be limited by substantial differences in patient characteristics between different treatments.

Patients with type 2 diabetes mellitus have higher risk for acute pancreatitis compared with those without diabetes.

AIM: The aetiology of acute pancreatitis (AP) is complex, and many risk factors for AP are shared by patients with type 2 diabetes mellitus (T2DM). However, few have assessed risk factors for AP specifically in T2DM patients. METHODS: Patients in the General Practice Research Database (2 984 755, 5.0% with T2DM) were used to estimate incidence of AP for T2DM relative to non-diabetes, adjusting for prior pancreatitis, gallbladder disease, obesity, smoking and alcohol use. Multivariate Cox regression analysis adjusting for risk factors and Charlson comorbidity index (CCI) was used to estimate hazard ratios (HR) with 95% confidence intervals (CI). RESULTS: Between 2003 and 2007, 301 of 148 903 patients with T2DM and 2434 of almost 3 million patients without diabetes developed AP. Patients with T2DM had higher risk for AP compared with patients without diabetes (crude HR: 2.89, 95% CI: 2.56-3.27). Patients with T2DM had significantly higher rates of prior alcohol and tobacco exposure (44.2 and 61.9% vs. 34.1 and 35.9%, p < 0.001) and of comorbid conditions (14.7% with CCI > or =1 vs. 4.3%, p < 0.001). Histories of obesity, pancreatitis, gallbladder disease, smoking or alcohol use were significant predictors of AP. After adjusting for these factors, age, gender and comorbidities, the risk of developing AP remained elevated in patients with T2DM (adjusted HR: 1.49, 95% CI: 1.31-1.70). CONCLUSION: After adjusting for risk factors, patients with T2DM had an elevated risk of AP compared with patients without diabetes. Physicians should be aware of the increased risk in patients with T2DM, particularly in those with prior pancreatitis.

The value, qualification, and regulatory use of surrogate end points in drug development.

The acceptance and use of either surrogate end points (SEPs) or efficient clinical end points are associated with greater and more rapid availability of new medicines as compared with disease situations for which clinical end points are inefficient or no surrogates exist. This review of the history of the development, qualification, and acceptance of key SEPs shows that both successes and failures had three key characteristics: (i) apparent biologic plausibility, (ii) prognostic value for the outcome of the disease, and (iii) an association between changes in the SEP and changes in outcome with therapeutic intervention--the three factors recommended for SEPs in the International Conference on Harmonisation's "Statistical Principles for Clinical Trials." We recommend that only prognostic value be an absolute prerequisite for surrogacy, because therapeutic interventions may not exist a priori, and biological plausibility can be subjective. Ideally, all three of these factors would be traded off against one another in a consistent and transparent risk-management process.

A prototypical process for creating evidentiary standards for biomarkers and diagnostics.

A framework for developing evidentiary standards for qualification of biomarkers is a key need identified in the Food and Drug Administration's Critical Path Initiative. This article describes a systematic framework that was developed by Pharmaceutical Research and Manufacturers of America (PhRMA) committees and tested at a workshop in collaboration with the Food and Drug Administration and academia. With some necessary refinements, this could be applied to create an appropriately individualized evidentiary standard for any biomarker purpose.

Initial monotherapy with either metformin or sulphonylureas often fails to achieve or maintain current glycaemic goals in patients with Type 2 diabetes in UK primary care.

AIMS: To describe initial achievement of glycaemic targets and subsequent hyperglycaemia in patients with Type 2 diabetes managed with oral agent monotherapy in UK primary care from 1998 to 2004. METHODS: Electronic medical records of patients initiating metformin (n = 3362) or a sulphonylurea agent (n = 3070) in 290 UK primary care practices were retrieved from the General Practice Research Database (GPRD). Patients included had an HbA(1c) recorded 0-90 days before and 90-365 days after initiating monotherapy. The probability of achieving glycaemic thresholds in the first year, and for those achieving such targets, the probability of inadequate glycaemic control (HbA(1c) > 6.5%, > 7.0%, > 7.5%) over time is described. RESULTS: Low baseline HbA(1c) and drug initiation within 3 months of diabetes diagnosis were the strongest predictors of initial achievement of glycaemic targets. The proportion of patients with diabetes duration > or = 4 months who achieved HbA(1c) < 7% in the first year ranged from 24% to 88% for highest to lowest baseline HbA(1c) category in sulphonylurea initiators and from 19% to 86% in metformin initiators, with slightly higher proportions for newly diagnosed patients. Kaplan-Meier analyses suggested that 55% and 70% of patients who initially achieved glycaemic targets had HbA(1c) measurements above these targets at 2 and 3 years. CONCLUSIONS: Many patients fail to achieve glycaemic goals with initial monotherapy and, of those who achieve current goals, few consistently maintain these targets over 3 years. Research is needed to evaluate whether more aggressive treatment or alternative treatments can improve the long-term maintenance of glycaemic control in patients with Type 2 diabetes.

Development of a multiregional United States Spanish version of the international prostate symptom score and the benign prostatic hyperplasia impact index.

PURPOSE: The International Prostate Symptom Score (I-PSS) and Benign Prostatic Hyperplasia Impact Index (BII) have gained widespread use in clinical practice and clinical trials. Although Spanish translations of the I-PSS are available, to our knowledge none was developed for the Spanish speaking population in the United States using a methodology to ensure appropriateness for the diverse United States Spanish speaking population. An existing translation intended for another Spanish speaking country, such as Mexico, or a translation developed without input from each language group may not be understood by those who immigrated from other Latin American regions. Hence, the development of a Spanish translation for the United States should involve input from translators from each region of Latin America. MATERIALS AND METHODS: We reviewed and modified an existing United States Spanish translation of I-PSS using a multiregional reconciliation panel comprised of representatives from each of the major Spanish language groups in the United States. For BII full translation methodology was used to develop a translation for the United States, including 2 forward translations using translators from more than 1 region, a multiregional reconciliation panel meeting, a back translation evaluation, cognitive debriefing interviews with representatives from each language group, developer review, a final evaluation for consistency and proofreading. RESULTS: The revised I-PSS better reflects common Spanish wording in the United States, while the BII translation was confirmed to be comprehended by Spanish speakers in the United States originating from multiple regions of Latin America. CONCLUSIONS: United States Spanish translations of patient reported outcome measures should consider the diversity of the growing Spanish speaking population in the United States to ensure comprehension across the broad population originating from the multiple regions of Latin America.

Distribution of the Brief Male Sexual Inventory in community men.

The objectives of the study were to characterize male sexual functioning as related to age in community-dwelling older men. In 1989, a random sample of men aged 40-79 y (n=2115) without prior prostate surgery, prostate cancer, or other conditions known to affect voiding function (except benign prostatic hyperplasia) was invited (55% agreed) to participate in the Olmsted County Study of Urinary Symptoms and Health Status Among Men. In 1996, a previously validated male sexual function questionnaire was administered to the cohort. The questionnaire has 11 questions measuring sexual drive (two questions); erectile function (three) and ejaculatory function (two), as well as assessing problems with sex drive, erections, or ejaculation (three); and overall satisfaction with sex life (one). Each question is scored on a scale of 0-4, with higher scores indicating better functioning. Cross-sectional age-specific means (+/-s.d.) for drive, erections, ejaculation, problems, and overall satisfaction declined from 5.2 (+/-1.5), 9.8 (+/-2.5), 7.4 (+/-1.4), 10.7 (+/-2.2), and 2.6 (+/-1.0), respectively, for men in their 40s to 2.4 (+/-1.6), 3.3 (+/-3.4), 3.6 (+/-3.2), 7.7 (+/-3.8), and 2.1 (+/-1.2) for men 70 y and older (all P<0.001). The cross-sectional decline in function with age was not constant, with age-related patterns differing by domain. The percentage of men reporting erections firm enough to have intercourse in the past 30 days declined from 97% (454/468) among those in their 40s to 51% (180/354) among those in their 80s (P&<0.001). In age-adjusted analyses, men reporting regular sexual partners had statistically significantly higher levels of sex drive, erectile function, ejaculatory function, and overall satisfaction than those who did not report regular sexual partners. Sexual drive, erectile functioning, ejaculatory functioning, and overall sexual satisfaction in men show somewhat differing cross-sectional patterns of decline with advancing age. Active sexual functioning is maintained well into the 80s in a substantial minority of community-dwelling men.

Responsiveness of the Acne-Specific Quality of Life Questionnaire (Acne-QoL) to treatment for acne vulgaris in placebo-controlled clinical trials.

The Acne-Specific Quality of Life Questionnaire (Acne-QoL) was developed to measure the impact of facial acne across four dimensions of patient quality of life. The main objective of the current study was to evaluate the responsiveness of this instrument. Secondarily, this study provided an opportunity to extend the developer's psychometric validation. The Acne-QoL was utilized in two randomized, double-blind, placebo-controlled studies of the efficacy of Estrostep (norethindrone acetate/ethinyl estradiol) in the treatment of facial acne; a total of 296 Estrostep and 295 placebo patients were evaluated. The Acne-QoL was completed at the beginning, middle (cycle 3), and end (cycle 6) of the 6-month treatment period. The responsiveness of the Acne-QoL was demonstrated through its ability to detect both small (baseline to mid-study) and moderate (baseline to study end) treatment advantages for Estrostep patients. Confirmatory factor analysis supported the subscale structure, and internal consistency estimates were excellent. Convergent and discriminant validity were supported by correlations between Acne-QoL scores and clinical measures that were both in the direction and relative magnitude hypothesized. Finally, item response theory analyses confirmed that each item is highly related to its subscale's latent construct and that each subscale is sensitive across a broad range of the underlying continuum. The results of this evaluation confirm that the Acne-QoL is responsive, internally consistent, and valid.

The impact of osteoporosis on quality-of-life: the OFELY cohort.

Although the long-term outcomes of osteoporosis (Op) such as fracture, kyphosis, and pain are well known, the physical, psychological, and social consequences, beyond fracture and pain, are less clear. The Osteoporosis-targeted Quality-of-life (OPTQoL) questionnaire aimed at assessing the physical difficulty, fears, and adaptations to one's daily life was developed as a cross-sectional instrument to characterize the burden of Op within a community. The purpose of this study was to assess the impact of Op and related factors on community women participating in the OFELY study in France. Femoral neck bone mineral density (BMD) and OPTQoL questionnaire data were collected from women randomly selected from a large insurance company. Data were obtained for 756 women (mean age 59 years, range 36-92), most of whom were white. Women were classified into five groups based on the extent of physical manifestations and family history of Op. Women who had prior fractures, height loss, and/or kyphosis or both reported greater physical difficulty, more adaptations to their lives, and greater fears than women reporting no such changes. Scores on the Physical Difficulty domain, however, did not differ significantly based on BMD alone (BMD T score

Natural history of benign prostatic hyperplasia.

Studies in varied settings have provided estimates of the prevalence of surrogate markers of benign prostatic hyperplasia (BPH). In population-based studies, the prevalence of moderate-to-severe lower urinary tract symptoms and depressed peak urinary flow rates increases across successively older age groups. Prostatic volume follows a similar pattern. Unlike clinic-based studies in which correlations are almost nonexistent, the population-based studies demonstrate a modest correlation among lower urinary tract symptoms, peak urinary flow rates, and prostatic volume. These cross-sectional observations extend to serum prostate-specific antigen levels and postvoid residual urine volumes. Data collected during the longitudinal follow-up study of men participating in the Olmsted County Study of Urinary Symptoms and Health Status Among Men provide a more detailed description of the natural history of changes in these surrogate markers of BPH. They also provide insights into their relation with each other and with long-term outcomes of BPH, such as acute urinary retention and treatment of BPH. These data demonstrate the progressive nature of BPH and are useful for the design and interpretation of clinical trials. Furthermore, they suggest that observational studies of etiology and prognosis should take advantage of the spectrum of disease reflected by the full range of values of these quantitative traits, rather than an arbitrary dichotomized outcome.

Prostate volume and prostate-specific antigen in the absence of prostate cancer: a review of the relationship and prediction of long-term outcomes.

BACKGROUND: The risk for long-term outcomes associated with benign prostatic hyperplasia (BPH) has not been well characterized. Untreated, BPH can lead to complications and negative outcomes, such as deterioration of bladder function, urinary tract infection, acute urinary retention (AUR), and surgery. METHODS: A literature review was conducted to summarize the results of studies investigating the relationship of prostate volume and PSA with prediction of long-term outcomes in the absence of prostate cancer. RESULTS: In the studies reviewed, men with moderate to severe symptoms, depressed uroflow, prostatic enlargement and elevated PSA were at greater risk for developing subsequent AUR or surgery. Men with prostatic enlargement had a 3-fold higher risk for acute urinary retention and were 4 times more likely to have had any treatment for BPH. CONCLUSIONS: The results of these studies may assist physicians in discussing treatment options as well as long-term complications with patients.

Health-related quality of life among patients with facial acne -- assessment of a new acne-specific questionnaire.

The psychosocial effects of facial acne are well accepted but until recently few validated instruments existed which were suitable for use in clinical trials. The aim of this study was to assess measurement characteristics (reproducibility, correlation with acne severity, and sensitivity to detect change after acne therapy) of a new acne-specific quality of life instrument, the Acne-QoL. We found that the Acne-QoL is reliable, valid and able to distinguish differences across severity groups and improvement over 16 weeks of standard therapy. The use of the Acne-QoL should aid physicians in understanding the impact of facial acne on young adults, and may be useful in assessing therapeutic effects in acne clinical trials.

Clinical predictors of spontaneous acute urinary retention in men with LUTS and clinical BPH: a comprehensive analysis of the pooled placebo groups of several large clinical trials.

OBJECTIVES: To comprehensively evaluate clinical predictors of spontaneous acute urinary retention (AUR) across pooled data of placebo-treated patients from clinical trials conducted in men with lower urinary tract symptoms and clinically diagnosed benign prostatic hyperplasia. METHODS: Data from the placebo-treatment groups of several prospective, randomized clinical trials conducted in the United States (n = 3040), Scandinavia, Canada, and worldwide (n = 2295) were combined in the analyses. More than 110 variables were considered individually and in combination as predictors of AUR using logistic regression analysis and classification and regression tree methods with a split-sample approach to cross-validation. RESULTS: The different methods of analysis identified consistent potential predictors of episodes of AUR. When prostate volume was included in the analyses, it was selected as the initial variable discriminating men with and without subsequent AUR. Omitting prostate volume because of its availability in only a subset of men, a logistic model including serum prostate-specific antigen (PSA), urinating more than every 2 hours, symptom problem index, maximum urinary flow rate, and hesitancy of urination had good predictive properties (area under the receiver-operating characteristic curve [AUC] = 0.742 +/- 0.047), as did a model with PSA (AUC = 0.716 +/- 0.045). A classification and regression decision tree with the same variables predicted AUR (AUC = 0.74, sensitivity = 72%, specificity = 67%) as well as did a tree with PSA alone (AUC = 0.70, sensitivity = 75%, specificity = 64%). CONCLUSIONS: Prostate volume and serum PSA are strong predictors of AUR in placebo-treated men with lower urinary tract symptoms and clinically diagnosed benign prostatic hyperplasia who were screened for prostate cancer. From more than 110 variables, logistic models and decision trees with PSA alone were comparable to expanded models that included PSA, urinary frequency and hesitancy, flow rate parameters, and symptom problem index, and to a scoring algorithm.

Interexaminer reliability of transrectal ultrasound for estimating prostate volume.

PURPOSE: We investigated the interexaminer reliability of transrectal ultrasound measurement of total prostate and transition zone volume among 3 examiners with various levels of experience. MATERIALS AND METHODS: A total of 121 patients 39 to 82 years old (average plus or minus standard deviation 60.7 +/- 10.3) from a single urology clinic volunteered to participate. Patients with prostate cancer, previous prostate surgery or recent invasive prostatic examination were excluded from study. Each individual was examined independently by each of 3 examiners with various levels of experience, including an attending urologist, a PGY-2 resident in the second year of general surgery before urology training and a PGY-4 resident in the second year of urology training. Transrectal ultrasound was performed in each case by each examiner in pre-specified random order. RESULTS: Mean total prostate and transition zone volume was 35.9 +/- 27.2 and 15.6 +/- 18.8 ml., respectively. Interexaminer agreement or reliability of the ultrasound measurements was high for total prostate and transition zone volume (intraclass correlation 0.96, 95% confidence interval [CI] 0.95 to 0.97 and 0.93, 95% CI 0.90 to 0.95, respectively). For individual prostatic dimensions reliability estimates were 0.78 to 0.86, while for transition zone dimensions reliability was 0.85 to 0.90. Total prostate volume reliability was higher for prostate volume greater than 40 ml. versus smaller prostates (intraclass correlation 0.95, 95% CI 0.90 to 0.97 versus 0.77, 95% CI 0.67 to 0.84). Mean differences in transrectal ultrasound measurements by different examiners were highest for the resident with least experience. CONCLUSIONS: The reliability of transrectal ultrasound measured total prostate and transition zone volume is high for examiners with different levels of experience at this institution. Reliability in patients without prostate cancer appears to be better for larger volume prostates and for examiners with more experience.

Interexaminer reliability and validity of a three-dimensional model to assess prostate volume by digital rectal examination.

OBJECTIVES: To evaluate the interexaminer reliability and accuracy compared with transrectal ultrasound (TRUS) of a three-dimensional (3D) model and other scales to improve the estimation of prostate volume by digital rectal examination (DRE). METHODS: Volunteers from a urology clinic (n = 121) were examined independently by three examiners with different levels of experience in randomized order. During DRE, the examiners estimated the prostate size in increments of 5 g, using various rating scales and a 3D sizing model, without access to the findings of the other investigators. TRUS was then performed by each examiner. RESULTS: The 121 volunteers were 39 to 82 years old, with a mean +/- SD total TRUS prostate size of 35.9 +/- 27.2 g. The DRE size estimates ranged from 15 to 100 g across all examiners and patients. The interexaminer reliability across examiners for the best DRE prostate size estimates (in grams) was 0.78 (95% confidence interval 0.70 to 0.84), and the correlation coefficients (r(s)) with the TRUS volume ranged from 0.61 to 0.72 for the three examiners. A 3D model showed good reliability (intraclass correlation coefficient 0.86, 95% confidence interval 0.75 to 0.93), and correlated well with the TRUS volume (r(s) = 0.67 to 0.75). Other scales showed fair reliability (0.58 to 0.68) and correlated with the TRUS measurements (0.57 to 0.67). The area under the receiver operating characteristic curve to identify prostate volumes greater than 40 g ranged from 0.78 to 0.90 for DRE estimates (in grams) and 0.69 to 0.89 for the 3D model. CONCLUSIONS: DRE size estimates and TRUS volume were moderately to highly correlated in men without prostate cancer. A 3D sizing model showed comparable reliability and correlation with TRUS. Although the DRE estimates generally tend to underestimate the TRUS-measured prostate volume, these tools may be useful in identifying men with enlarged prostate glands.