Multicentre clinical evaluation of the safety and performance of a simple transperineal access system for prostate biopsies for suspected prostate cancer: The CAMbridge PROstate Biopsy DevicE (CamPROBE) study.

OBJECTIVES: To report the prospective multicentre clinical evaluation of a first-in-man disposable device, Cambridge Prostate Biopsy Device, to undertake local anaesthetic outpatient transperineal prostate biopsies. MATERIAL AND METHODS: Disposable single-use Cambridge Prostate Biopsy devices were manufactured based on a previous prototype. The lead site developed a user training course and disseminated the method to other sites. The Cambridge Prostate Biopsy Device (CamPROBE) was offered as an alternative to transrectal ultrasound guided biopsy to men due for a biopsy as part of their clinical management. Data on safety (infections and device performance), clinical utility, patient reported experience, biopsy quality and cancer detection were collected. Procedure time and local anaesthetic use was recorded in the lead site. The study was funded by a United Kingdom National Institute for Health Research (NIHR) i4i product development award. RESULTS: A total of 40 patients were recruited (median age 69 y) across six sites; five sites were new to the procedure. Overall, 19/40 were first prostate biopsies and 21/40 repeat procedures. Both image-targeted and systematic biopsy cores taken. There were no infections, device deficiencies or safety issues reported. The procedure was well tolerated with excellent patient-reported perception and low pain scores (median of 3, scale 0-10). Histopathology quality was good and the overall cancer diagnosis rate (first diagnostic procedures) was 68% (13/19) and for significant cancers (⩾ histological Grade Group 2), 47% (9/19). In the lead centre (most experienced), median procedure time was 25 minutes, and median local anaesthetic use 11 ml (n=17). CONCLUSIONS: Data from this device evaluation study demonstrate that the United Kingdom-developed Cambridge Prostate Biopsy Device/method for transperineal biopsies is safe, transferable and maintains high diagnostic yields. The procedure is well tolerated by patients, suited to the local anaesthetic outpatient setting and could directly replace transrectal ultrasound guided biopsy. LEVEL OF EVIDENCE: Level III.

Accuracy of the Modified Somatic Perception Questionnaire and Pain Disability Index in the detection of malingered pain-related disability in chronic pain.

The Modified Somatic Perception Questionnaire (MSPQ) and the Pain Disability Index (PDI) are both popular clinical screening instruments in general orthopedic, rheumatologic, and neurosurgical clinics and are useful for identifying pain patients whose physical symptom presentations and disability may be non-organic. Previous studies found both to accurately detect malingered pain presentations; however, the generalizability of these results is not clear. This study used a criterion groups validation design (retrospective cohort of patients with chronic pain, n = 328) with a simulator group (college students, n = 98) to determine the accuracy of the MSPQ and PDI in detecting Malingered Pain Related Disability. Patients were grouped based on independent psychometric evidence of MPRD. Results showed that MSPQ and PDI scores were not associated with objective medical pathology. However, they accurately differentiated Not-MPRD from MPRD cases. Diagnostic statistics associated with a range of scores are presented for application to individual cases. Data from this study can inform the clinical management of chronic pain patients by screening for psychological overlay and malingering, thus alerting clinicians to the possible presence of psychosocial obstacles to effective treatment and triggering further psychological assessment and/or treatment.

Necrosis predicts benefit from hypoxia-modifying therapy in patients with high risk bladder cancer enrolled in a phase III randomised trial.

BACKGROUND AND PURPOSE: Addition of carbogen and nicotinamide (hypoxia-modifying agents) to radiotherapy improves the survival of patients with high risk bladder cancer. The study investigated whether histopathological tumour features and putative hypoxia markers predicted benefit from hypoxia modification. MATERIALS AND METHODS: Samples were available from 231 patients with high grade and invasive bladder carcinoma from the BCON phase III trial of radiotherapy (RT) alone or with carbogen and nicotinamide (RT+CON). Histopathological tumour features examined were: necrosis, growth pattern, growing margin, and tumour/stroma ratio. Hypoxia markers carbonic anhydrase-IX and glucose transporter-1 were examined using tissue microarrays. RESULTS: Necrosis was the only independent prognostic indicator (P=0.04). Necrosis also predicted benefit from hypoxia modification. Five-year overall survival was 48% (RT) versus 39% (RT+CON) (P=0.32) in patients without necrosis and 34% (RT) versus 56% (RT+CON) (P=0.004) in patients with necrosis. There was a significant treatment by necrosis strata interaction (P=0.001 adjusted). Necrosis was an independent predictor of benefit from RT+CON versus RT (hazard ratio [HR]: 0.43, 95% CI 0.25-0.73, P=0.002). This trend was not observed when there was no necrosis (HR: 1.64, 95% CI 0.95-2.85, P=0.08). CONCLUSIONS: Necrosis predicts benefit from hypoxia modification in patients with high risk bladder cancer and should be used to select patients; it is simple to identify and easy to incorporate into routine histopathological examination.

Classification accuracy of the Millon Clinical Multiaxial Inventory-III modifier indices in the detection of malingering in traumatic brain injury.

The present study used criterion groups validation to determine the ability of the Millon Clinical Multiaxial Inventory-III (MCMI-III) modifier indices to detect malingering in traumatic brain injury (TBI). Patients with TBI who met criteria for malingered neurocognitive dysfunction (MND) were compared to those who showed no indications of malingering. Data were collected from 108 TBI patients referred for neuropsychological evaluation. Base rate (BR) scores were used for MCMI-III modifier indices: Disclosure, Desirability, and Debasement. Malingering classification was based on the Slick, Sherman, and Iverson (1999) criteria for MND. TBI patients were placed in one of three groups: MND (n = 55), not-MND (n = 26), or Indeterminate (n = 26).The not-MND group had lower modifier index scores than the MND group. At scores associated with a 4% false-positive (FP) error rate, sensitivity was 47% for Disclosure, 51% for Desirability, and 55% for Debasement. Examination of joint classification analysis demonstrated 54% sensitivity at cutoffs associated with 0% FP error rate. Results suggested that scores from all MCMI-III modifier indices are useful for identifying intentional symptom exaggeration in TBI. Debasement was the most sensitive of the three indices. Clinical implications are discussed.

Detection of malingering in mild traumatic brain injury with the Conners' Continuous Performance Test-II.

Classification accuracy for the detection of malingered neurocognitive dysfunction (MND) in mild traumatic brain injury (TBI) is examined for two selected measures from the Conners' Continuous Performance Test-II (CPT-II) using criterion-groups validation. Individual and joint classification accuracies are presented for Omissions and Hit Reaction Time Standard Error across a range of scores comparing mild TBI malingering (n = 27), mild TBI not-malingering (n = 31), and moderate-to-severe (M/S) TBI not-malingering (n = 24) groups. At cutoffs associated with at least 95% specificity in both mild and M/S TBI, sensitivity to MND in mild TBI was 30% for Omissions, 41% for Hit Reaction Time Standard Error, and 44% using both indicators. These results support the use of the CPT-II as a reliable indicator for the detection of malingering in TBI when used as part of a comprehensive diagnostic system.

The Reliable Digit Span test in chronic pain: classification accuracy in detecting malingered pain-related disability.

This study used criterion groups validation (known-groups design) to examine the classification accuracy of the Reliable Digit Span test (RDS) in a large group of chronic pain patients referred for psychological evaluation. The sample consisted of 612 patients classified into one of six groups based on evidence of malingered pain-related disability (MPRD): No-Incentive, Not MPRD; Incentive-Only, Not MPRD; Indeterminate; Possible MPRD; Probable MPRD; Definite MPRD. A total of 30 college student simulators were also included. Lower average RDS scores and higher rates of RDS failure were seen in patients classified as MPRD and in simulators. Consistent with previous literature in a variety of populations, RDS < = 6 provided the most accurate differentiation between MPRD and non-MPRD pain patients. Clinical implications are discussed.

Executive dysfunction in traumatic brain injury: the effects of injury severity and effort on the Wisconsin Card Sorting Test.

This study examined the persistent effects of traumatic brain injury (TBI) on Wisconsin Card Sorting Test (WCST) performance. Since poor effort can contaminate results in populations with incentive to perform poorly, performance validity was explicitly assessed and controlled for using multiple well-validated cognitive malingering indicators. Participants were 109 patients with mild TBI and 67 patients with moderate-to-severe TBI seen for neuropsychological evaluation at least one year post injury. Patients with diffuse neurological impairment and healthy controls were included for comparison. Results suggested a dose-response effect of TBI severity on WCST performance in patients providing good effort; the mild TBI group did not differ from controls while increased levels of impairment were observed in the moderate-to-severe TBI group. Effort during testing had a larger impact on WCST performance than mild or moderate-to-severe TBI. Clinical implications of these findings are discussed.

Detecting malingered pain-related disability: classification accuracy of the test of memory malingering.

This study used criterion groups validation to determine the accuracy of the Test of Memory Malingering (TOMM) in detecting malingered pain-related disability (MPRD) across a range of cutoffs in chronic pain patients undergoing psychological evaluation (n = 604). Data from patients with traumatic brain injury (n = 45) and dementia (n = 59) are presented for comparison. TOMM scores decreased and failure rates increased as a function of greater external evidence of intentional under-performance. The TOMM detected from 37.5% to 60.2% of MPRD patients, depending on the cutoff. False positive (FP) error rates ranged from 0% to 5.1%. Accuracy data for Trial 1 are also reported. In chronic pain the original cutoffs produced no FP errors but were associated with high false negative error rates. Higher cutoffs increased sensitivity without adversely affecting specificity. The relevance of these findings to research and clinical practice is discussed.

Prevalence of malingering in patients with chronic pain referred for psychologic evaluation in a medico-legal context.

OBJECTIVE: To provide an empirical estimate of the prevalence of malingered disability in patients with chronic pain who have financial incentive to appear disabled. DESIGN: Retrospective review of cases. SETTING: A private neuropsychologic clinic in a southeastern metropolitan area. PARTICIPANTS: Consecutive patients (N=508) referred for psychologic evaluation related to chronic pain over a 10-year period (1995-2005). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Prevalence of malingering was examined using 2 published clinical diagnostic systems (Malingered Pain-Related Disability and Malingered Neurocognitive Dysfunction) as well as statistical estimates based on well validated indicators of malingering. RESULTS: The prevalence of malingering in patients with chronic pain with financial incentive is between 20% and 50% depending on the diagnostic system used and the statistical model's underlying assumptions. Some factors associated with the medico-legal context such as the jurisdiction of a workers' compensation claim or attorney representation were associated with slightly higher malingering rates. CONCLUSIONS: Malingering is present in a sizable minority of patients with pain seen for potentially compensable injuries. However, not all excess pain-related disability is a result of malingering. It is important not to diagnose malingering reflexively on the basis of limited or unreliable findings. A diagnosis of malingering should be explicitly based on a formal diagnostic system.

Detecting malingered pain-related disability: classification accuracy of the Portland Digit Recognition Test.

This study used criterion groups validation to determine the classification accuracy of the Portland Digit Recognition Test (PDRT) at a range of cutting scores in chronic pain patients undergoing psychological evaluation (n = 318), college student simulators (n = 29), and patients with brain damage (n = 120). PDRT scores decreased and failure rates increased as a function of greater independent evidence of intentional underperformance. There were no differences between patients classified as malingering and college student simulators. The PDRT detected from 33% to nearly 60% of malingering chronic pain patients, depending on the cutoff used. False positive error rates ranged from 3% to 6%. Scores higher than the original cutoffs may be interpreted as indicating negative response bias in patients with pain, increasing the usefulness and facilitating the clinical application of the PDRT in the detection of malingering in pain.

Are the original and second edition of the California Verbal Learning Test equally accurate in detecting malingering?

This two-part study sought to determine the equivalence of the California Verbal Learning Tests (CVLT-1 and CVLT-2) in the detection of malingering in traumatic brain injury (TBI) and chronic pain. Part 1 compared a variety of scores from the two versions in carefully matched patient groups. Part 2 used criterion groups (known-groups) methodology to examine the relative rates of false positive (FP) errors across the two versions. Participants were 442 TBI (CVLT-1 = 310; CVLT-2 = 132) and 378 chronic pain patients (CVLT-1 = 250; CVLT-2 = 128). Overall, the CVLT-2 was more difficult than the CVLT-1, with the chronic pain patients showing larger version effects than the TBI patients. The two versions of the CVLT were equally accurate in detecting malingering in TBI and chronic pain. However, they were not interchangeable. The use of CVLT-1 cutoffs with the CVLT-2 may result in an increased risk of FP error. Appropriate cutoff adjustment in clinical practice is recommended.

Detecting malingering in traumatic brain injury and chronic pain: a comparison of three forced-choice symptom validity tests.

Individual and joint malingering detection accuracy of the Portland Digit Recognition Test (PDRT), Test of Memory Malingering (TOMM), and Word Memory Test (WMT) was examined in traumatic brain injury (TBI; 43 non-malingering, 27 malingering) and chronic pain (CP; 42 non-malingering, 58 malingering) using a known-groups design. At published cutoffs, the PDRT and TOMM were very specific but failed to detect about 50% of malingerers; the WMT was sensitive but prone to false positive errors. ROC analyses demonstrated comparable accuracy across all three tests. Joint classification accuracy was superior to that of the individual tests. Clinical and research implications are discussed.

Using the Wechsler Memory Scale-III to detect malingering in mild traumatic brain injury.

This study examined the classification accuracy of the WMS-III primary indices in the detection of Malingered Neurocognitive Dysfunction (MND) in Traumatic Brain Injury (TBI) using a known-groups design. Sensitivity, specificity, and positive predictive power are presented for a range of index scores comparing mild TBI non-malingering (n = 34) and mild TBI malingering (n = 31) groups. A moderate/severe TBI non-malingering (n = 28) and general clinical group (n = 93) are presented to examine specificity in these samples. In mild TBI, sensitivities for the primary indices ranged from 26% to 68% at 97% specificity. Three systems used to combine all eight index scores were also examined and all achieved at least 58% sensitivity at 97% specificity in mild TBI. Specificity was generally lower in the moderate/severe TBI and clinical comparison groups. This study indicates that the WMS-III primary indices can accurately identify malingered neurocognitive dysfunction in mild TBI when used as part of a comprehensive classification system.

An investigation into the prognostic significance of necrosis and hypoxia in high grade and invasive bladder cancer.

PURPOSE: We investigated hypoxia and necrosis in high grade and invasive bladder cancer, and related this to prognosis. MATERIALS AND METHODS: We performed a retrospective observational study of 98 primary cystectomy specimens scored for necrosis, and the hypoxia associated markers carbonic anhydrase IX, hypoxia-inducible factor 1 alpha and 2 alpha, and Bcl2/adenovirus EIB 19 kDa interacting protein 3. Tumor tissue array was used with cores taken from representative and perinecrotic tumor regions. Necrosis was scored on whole sections as absent, less than 5 mm (comedo) or more than 5 mm (gross). RESULTS: Of the 98 cases analyzed followup data were available on 91. Median followup was 22 months (IQR 8-35). Stage was T0/1 to T4 in 18, 20, 41 and 12 cases, respectively. The prevalence of necrosis in bladder cancer was high and it increased with stage (17%, 30%, 70% and 71% at stages T0/1 to T4, respectively). Necrosis was significantly associated with stage (p = 0.0001) and nodal status (p = 0.016). Hypoxia-inducible factor 1 alpha showed no association with stage, grade or nodal status. Hypoxia-inducible factor 1 alpha and carbonic anhydrase IX showed a significant association with necrosis, whereas hypoxia-inducible factor 2 alpha and Bcl2/adenovirus EIB 19 kDa interacting protein 3 did not. Stage (p <0.0001), necrosis (p <0.0001) and intense hypoxia-inducible factor 1 positivity (p = 0.048) were the only significant prognostic factors on univariate analysis. Stage (HR 3.29, 95% CI 1.80-6.04, p <0.001) and necrosis (HR 1.92, 95% CI 1.05-3.51, p = 0.04) were independent prognostic factors on multivariate analysis, while hypoxia-inducible factor 1 lost significance (HR 1.36, 95% CI 0.98-1.88, p = 0.07). Node status was only reported in 45% of cases. CONCLUSIONS: Necrosis (the presence and amount) in high grade and invasive bladder cancer is an independent prognostic risk factor.