Changes in prostate cancer detection rate of MRI-TRUS fusion vs systematic biopsy over time: evidence of a learning curve.

BACKGROUND: To determine the effect of urologist and radiologist learning curves and changes in MRI-TRUS fusion platform during 9 years of NCI's experience with multiparametric magnetic resonance imaging (mpMRI)/TRUS fusion biopsy. METHODS: A prospectively maintained database of patients undergoing mpMRI followed by fusion biopsy (Fbx) and systematic biopsy (Sbx) from 2007 to 2016 was reviewed. The patients were stratified based on the timing of first biopsy. Cohort 1 (7/2007-12/2010) accounted for learning curve. Cohort 2 (1/2011-5/2013) and cohort 3 (5/2013-4/2016) included patients biopsied prior to and after debut of a new software platform, respectively. Clinically significant (CS) disease was defined as Gleason 7 (3+4) or higher. McNemar's test compared cancer detection rates (CDRs) of Sbx and Fbx between time periods. RESULTS: 1528 patients were included in the study with 230, 537 and 761 patients included in three respective cohorts. Median age (interquartile range) was 61.0 (±9.0), 62.0 (±7.3), and 64.0 (±11.0) years in three cohorts, respectively (P<0.001). Fbx and Sbx had comparable CS CDR in cohort 1 (24.8 vs 22.2%, P=0.377). Fbx detected significantly more CS disease compared to Sbx in the following two periods (cohort 2: 31.5 vs 25.0%, P=0.001; cohort 3: 36.4 vs 30.3%, P<0.001) and detected significantly less low risk disease in the same period (cohort 2: 14.5 vs 19.6%, P<0.001; cohort 3: 12.6 vs 16.7%, P<0.001). Even after multivariate adjustment with age, PSA, race, clinical stage and MRI suspicion score, Fbx CS cancer detection increased in successive cohorts (cohort 2: OR 2.23, P=0.043; cohort 3: OR 2.92, P=0.007). CONCLUSIONS: In the past 9 years, there has been significant improvement in the accuracy of Fbx. Our results show that after an early learning period, Fbx detected higher rates of CS cancer and lower rates of clinically insignificant cancer than Sbx. Software advances allowed for even greater detection of CS disease.

Quality-adjusted time without symptoms or toxicity analysis of interferon maintenance in multiple myeloma.

PURPOSE: In a randomized trial conducted by the National Cancer Institute of Canada Clinical Trials Group (NCIC CTG), interferon alpha-2b (IFN) maintenance therapy (2 mU/m2 subcutaneously three times per week) after successful induction with melphalan and prednisone was found to prolong time to progression in patients with multiple myeloma. A favorable effect on survival was also present, but this difference was of borderline significance. However, IFN toxicity was a concern. To evaluate the trade-off between the clinical benefits of IFN and the associated toxicity, we applied the method of quality-adjusted time without symptoms or toxicity (Q-TWiST). MATERIALS AND METHODS: Three clinical health states were defined in this analysis: time with toxicity (TOX), time without disease relapse or toxicity (TWiST), and time following disease relapse (REL). Toxicity information for IFN had been collected using patient-completed diaries so the actual duration of each adverse event could be determined. The health states TOX and REL were weighted using utility scores to account for a possible decrement in quality of life, a weighted sum of the health state durations is used as a measure of quality-adjusted time. RESULTS: The health state durations were calculated at 72 months median follow-up. Patients in the IFN group gained an average of 9.8 months without disease relapse (P = .001) and 5.8 months of overall survival (P = .074) versus the control group. However, the IFN group suffered an average of 4.1 months of moderate or worse toxicity (P < .001). CONCLUSION: The clinical benefits of IFN outweigh the negative effects associated with treatment toxicity for a wide range of plausible utilities.

Quality-of-life-adjusted survival analysis of interferon alfa-2b treatment for advanced follicular lymphoma: an aid to clinical decision making.

PURPOSE: To evaluate the trade-off of toxicity versus improved clinical outcome with interferon alfa-2b (IFN) administered concomitantly with a doxorubicin-containing regimen for the treatment of advanced follicular lymphoma. PATIENTS AND METHODS: A quality-of-life-adjusted survival analysis (Quality-Adjusted Time Without Symptoms or Toxicity [Q-TWiST]) was applied to the Groupe d'Etude des Lymphomes Folliculaires (GELF) trial 86, which compared a regimen of cyclophosphamide, doxorubicin, teniposide, and prednisone (CHVP) versus CHVP plus IFN in 242 patients with confirmed follicular lymphoma. CHVP was administered monthly for 6 months then every other month for 12 months. The IFN dosage was 5 x 10(6) U three times weekly for 18 months. RESULTS: After a median follow-up duration of 72 months, the IFN group gained a mean of 12.3 months of progression-free survival (PFS) and 7.4 months of overall survival (OS), but also experienced additional time with grade 3 or worse toxicity compared with the CHVP group. Sensitivity analysis demonstrated that CHVP plus IFN provided a greater amount of quality-adjusted survival regardless of the relative quality-of-life valuations placed on time with toxicity due to CVHP alone, time with toxicity due to CHVP plus IFN, and time following disease progression. This gain was significant (P < .05) in all cases except for patients who consider time with toxicity to have a low relative value and time following disease progression to have a high relative value. CONCLUSION: In patients with advanced follicular lymphoma, the clinical benefits of concomitant IFN can significantly offset the associated grade 3 or worse toxic effects. The magnitude of this clinical benefit depends on an individual patient's relative quality-of-life valuations for time with toxicity and time following disease progression.

Health assessment for chronic HCV infection: results of quality of life.

The perception that chronic hepatitis C is an asymptomatic disease contrasts with many studies that show a strong association between chronic hepatitis C, hepatocellular cancer, and fatal liver disease. In order to resolve these issues, it is logical to directly evaluate the quality of life in patients with chronic hepatitis C and to compare this to the normal population as well as cohorts of patients with other chronic diseases. The Sickness Impact Profile was used to evaluate the impact of disease and interferon therapy on health-related quality of life in patients with chronic hepatitis C. Using this tool, patients with chronic hepatitis C had a total Sickness Impact Profile score of 9.0, compared with a score of 3.6 among the general population (P < 0.05). Patients with chronic hepatitis C also had significantly worse scores in almost every category of the Sickness Impact Profile that could be compared. However, statistically significant differences were observed only at the 24-week evaluation for work and at the end-point evaluation for the sleep and rest and recreation and pastimes categories. A more sophisticated instrument, based on the Medical Outcomes Study 36-item short-form health survey, found that patients with chronic hepatitis C scored significantly lower (P < 0.01) than the general population on each of the subscales in this survey. In addition, they scored significantly lower than patients with hypertension in seven of the subscales and two additional generic scales. Patients with chronic hepatitis C were most comparable to those with type II diabetes. A larger, more comprehensive study is underway to further evaluate these relationships.

Hepatitis C infection risk analysis: who should be screened? Comparison of multiple screening strategies based on the National Hepatitis Surveillance Program.

OBJECTIVES: Hepatitis C, an infection of high prevalence worldwide, is insidiously progressive in many. Reduction of person-to-person spread is possible, and treatment is possible for many, particularly if offered before cirrhosis develops. Screening for hepatitis C (HCV) would be appropriate if strategies could be developed to afford adequate sensitivity and specificity at reasonable cost. We evaluated the performance characteristics of several screening strategies to determine the best balance between cost and performance. METHODS: The database of a national hepatitis screening program was used to define risk factors for HCV. Features associated with increased risk for HCV by multivariable analysis were combined in various ways to construct HCV screening models. Screening Model 1 employed a mathematical model constructed to predict the probability of hepatitis C. Using this model, testing for HCV was done if the probability of HCV was determined to be higher than 7%. Models 2 and 3 called for HCV testing if certain risk factors, stratified as socially intrusive, or nonintrusive in nature, were present. Model 4 calls for testing for HCV only when ALT values are elevated. Costs per case discovered were calculated for each model. RESULTS: Nine thousand two-hundred sixty-nine individuals from a database of 13,997 has sufficient information to be included in the modeling studies. Risk factors considered socially intrusive were intravenous (i.v.) drug use and sex with an i.v. drug user. Risk factors considered not socially intrusive were: history of blood transfusion, age 30-49 yrs, and male gender. The sensitivity of Models 1-4 were 65%, 69%, 53%, and 63%, respectively. Specificities were 84%, 74%, 77%, and 92%, respectively. The cost per case detected was lowest when Models 1 or 2 were used ($357 and $439, respectively) and higher for models 3 and 4 ($487 and $1047, respectively). CONCLUSIONS: The yield and cost of screening for HCV compares favorably with accepted current screening practices for other diseases. Models 1, 2, and 3 may be appropriate in certain clinical and epidemiological settings. Selective screening by a risk factor questionnaire (first three models) is more cost-effective than blood testing with ALT (Model 4).

Excess days lost as an index for identifying jobs with ergonomic stress.

A new health impact index, excess cost, is advocated for identifying jobs in need of further study regarding ergonomic problems. The excess cost index is compared with incidence rate, excess count, and severity rate indices in terms of concept and appropriateness to the purpose. The four indices are illustrated with data regarding medical leave from an automobile assembly plant and evaluated in terms of ability to identify jobs most strongly contributing to excessive days lost.

Detection of cumulative trauma disorders of upper extremities in the workplace.

Surveillance for musculoskeletal disorders of the upper extremity in industry is in its infancy. Research efforts to elucidate the causal factors of these disorders often rely on either the analysis of existing medical records, worker compensation records (passive surveillance), or the surveying of workers with questionnaire and physical examination (active surveillance). The use of either type of data for routine surveillance presents several difficulties illustrated with the results presented in this paper. The analysis of existing records is generally less costly but the reliability of the data is difficult to assess. Standardized questionnaire and physical examinations can be as sensitive as the use of unusually thorough existing occupational medical records; however, it is unclear whether the additional cost of an active surveillance system will deter the routine use of such systems.

A questionnaire to assess the generic and disease-specific health outcomes of patients with chronic hepatitis C.

A 69-item questionnaire measuring generic functioning and well-being and disease-specific health outcomes was developed and tested using the pre-treatment data from patients with chronic hepatitis C (CHC) participating in two randomized trials of interferon alpha-2b (n = 157). The questionnaire included all eight scales from the SF-36 and measures of nine other generic and disease-specific health concepts. Psychometric tests confirmed the assumptions underlying the construction and scoring of all generic and disease-specific scales. Cross-sectional tests of 'known groups' validity showed that CHC patients scored worse on the generic scales than patients with other chronic conditions and worse than a healthy general population. The generic and disease-specific scale scores were lower in the presence of physical findings of CHC, as hypothesized, but only the physical functioning and bodily pain scales were linked to cirrhosis or extreme alanine aminotransferase (ALT) ratios. This instrument will be useful in studies of health outcome among patients with CHC, a condition whose health burden appears to have been underestimated in studies to date.