Monitoring policy in the context of preventive treatment of cardiovascular disease.

Preventing chronic diseases is an essential aspect of medical care. To prevent chronic diseases, physicians focus on monitoring their risk factors and prescribing the necessary medication. The optimal monitoring policy depends on the patient's risk factors and demographics. Monitoring too frequently may be unnecessary and costly; on the other hand, monitoring the patient infrequently means the patient may forgo needed treatment and experience adverse events related to the disease. We propose a finite horizon and finite-state Markov decision process to define monitoring policies. To build our Markov decision process, we estimate stochastic models based on longitudinal observational data from electronic health records for a large cohort of patients seen in the national U.S. Veterans Affairs health system. We use our model to study policies for whether or when to assess the need for cholesterol-lowering medications. We further use our model to investigate the role of gender and race on optimal monitoring policies.

Development and Validation of Models to Predict Pathological Outcomes of Radical Prostatectomy in Regional and National Cohorts.

PURPOSE: Prediction models are recommended by national guidelines to support clinical decision making in prostate cancer. Existing models to predict pathological outcomes of radical prostatectomy (RP)-the Memorial Sloan Kettering (MSK) models, Partin tables, and the Briganti nomogram-have been developed using data from tertiary care centers and may not generalize well to other settings. MATERIALS AND METHODS: Data from a regional cohort (Michigan Urological Surgery Improvement Collaborative [MUSIC]) were used to develop models to predict extraprostatic extension (EPE), seminal vesicle invasion (SVI), lymph node invasion (LNI), and nonorgan-confined disease (NOCD) in patients undergoing RP. The MUSIC models were compared against the MSK models, Partin tables, and Briganti nomogram (for LNI) using data from a national cohort (Surveillance, Epidemiology, and End Results [SEER] registry). RESULTS: We identified 7,491 eligible patients in the SEER registry. The MUSIC model had good discrimination (SEER AUC EPE: 0.77; SVI: 0.80; LNI: 0.83; NOCD: 0.77) and was well calibrated. While the MSK models had similar discrimination to the MUSIC models (SEER AUC EPE: 0.76; SVI: 0.80; LNI: 0.84; NOCD: 0.76), they overestimated the risk of EPE, LNI, and NOCD. The Partin tables had inferior discrimination (SEER AUC EPE: 0.67; SVI: 0.76; LNI: 0.69; NOCD: 0.72) as compared to other models. The Briganti LNI nomogram had an AUC of 0.81 in SEER but overestimated the risk. CONCLUSIONS: New models developed using the MUSIC registry outperformed existing models and should be considered as potential replacements for the prediction of pathological outcomes in prostate cancer.

Correction: Benefit and harm of intensive blood pressure treatment: Derivation and validation of risk models using data from the SPRINT and ACCORD trials.

[This corrects the article DOI: 10.1371/journal.pmed.1002410.].

Prospective monitoring of imaging guideline adherence by physicians in a surgical collaborative: comparison of statistical process control methods for detecting outlying performance.

BACKGROUND: Systematic, automated methods for monitoring physician performance are necessary if outlying behavior is to be detected promptly and acted on. In the Michigan Urological Surgery Improvement Collaborative (MUSIC), we evaluated several statistical process control (SPC) methods to determine the sensitivity and ease of interpretation for assessing adherence to imaging guidelines for patients with newly diagnosed prostate cancer. METHODS: Following dissemination of imaging guidelines within the Michigan Urological Surgery Improvement Collaborative (MUSIC) for men with newly diagnosed prostate cancer, MUSIC set a target of imaging < 10% of patients for which bone scan is not indicated. We compared four SPC methods using Monte Carlo simulation: p-chart, weighted binomial CUSUM, Bernoulli cumulative sum (CUSUM), and exponentially weighted moving average (EWMA). We simulated non-indicated bone scan rates ranging from 5.9% (within target) to 11.4% (above target) for a representative MUSIC practice. Sensitivity was determined using the average run length (ARL), the time taken to signal a change. We then plotted actual non-indicated bone scan rates for a representative MUSIC practice using each SPC method to qualitatively assess graphical interpretation. RESULTS: EWMA had the lowest ARL and was able to detect changes significantly earlier than the other SPC methodologies (p < 0.001). The p-chart had the highest ARL and thus detected changes slowest (p < 0.001). EWMA and p-charts were easier to interpret graphically than CUSUM methods due to their ability to display historical imaging rates. CONCLUSIONS: SPC methods can be used to provide informative and timely feedback regarding adherence to healthcare performance target rates in quality improvement collaboratives. We found the EWMA method most suited for detecting changes in imaging utilization.

Grade Groups Provide Improved Predictions of Pathological and Early Oncologic Outcomes Compared with Gleason Score Risk Groups.

PURPOSE: The GG (Grade Group) system was introduced in 2013. Data from academic centers suggest that GG better distinguishes between prostate cancer risk groups than the Gleason score (GS) risk groups. We compared the performance of the 2 systems to predict pathological/recurrence outcomes using data from the MUSIC (Michigan Urological Surgery Improvement Collaborative). MATERIALS AND METHODS: Patients who underwent biopsy and radical prostatectomy in the MUSIC from March 2012 to June 2017 were classified according to GG and GS. Outcomes included the presence or absence of extraprostatic extension, seminal vesical invasion, positive lymph nodes, positive surgical margins and time to cancer recurrence (defined as postoperative prostate specific antigen 0.2 ng/ml or greater). Logistic and Cox regression models were used to compare the difference in outcomes. RESULTS: A total of 8,052 patients were identified. When controlling for patient characteristics, significantly higher risks of extraprostatic extension, seminal vesical invasion and positive lymph nodes were observed for biopsy GG 3 vs 2 and for GG 5 vs 4 (p <0.001). Biopsy GGs 3, 4 and 5 also showed shorter time to biochemical recurrence than GGs 2, 3 and 4, respectively (p <0.001). GGs 3, 4 and 5 at radical prostatectomy were each associated with a greater probability of recurrence compared to the next lower GG (p <0.001). GG (vs GS) had better predictive power for extraprostatic extension, seminal vesical invasion, positive lymph nodes and biochemical recurrence. CONCLUSIONS: GG at biopsy and radical prostatectomy allows for better discrimination of recurrence-free survival between individual risk groups than GS risk groups with GGs 2, 3, 4 and 5 each incrementally associated with increased risk.

Probabilistic sensitivity analysis on Markov models with uncertain transition probabilities: an application in evaluating treatment decisions for type 2 diabetes.

Markov models are commonly used for decision-making studies in many application domains; however, there are no widely adopted methods for performing sensitivity analysis on such models with uncertain transition probability matrices (TPMs). This article describes two simulation-based approaches for conducting probabilistic sensitivity analysis on a given discrete-time, finite-horizon, finite-state Markov model using TPMs that are sampled over a specified uncertainty set according to a relevant probability distribution. The first approach assumes no prior knowledge of the probability distribution, and each row of a TPM is independently sampled from the uniform distribution on the row's uncertainty set. The second approach involves random sampling from the (truncated) multivariate normal distribution of the TPM's maximum likelihood estimators for its rows subject to the condition that each row has nonnegative elements and sums to one. The two sampling methods are easily implemented and have reasonable computation times. A case study illustrates the application of these methods to a medical decision-making problem involving the evaluation of treatment guidelines for glycemic control of patients with type 2 diabetes, where natural variation in a patient's glycated hemoglobin (HbA1c) is modeled as a Markov chain, and the associated TPMs are subject to uncertainty.

Optimizing active surveillance strategies to balance the competing goals of early detection of grade progression and minimizing harm from biopsies.

BACKGROUND: Active surveillance (AS) for prostate cancer includes follow-up with serial prostate biopsies. The optimal biopsy frequency during follow-up has not been determined. The goal of this investigation was to use longitudinal AS biopsy data to assess whether the frequency of biopsy could be reduced without substantially prolonging the time to the detection of disease with a Gleason score ≥ 7. METHODS: With data from 1375 men with low-risk prostate cancer enrolled in AS at Johns Hopkins, a hidden Markov model was developed to estimate the probability of undersampling at diagnosis, the annual probability of grade progression, and the 10-year cumulative probability of reclassification or progression to Gleason score ≥ 7. It simulated 1024 potential AS biopsy strategies for the 10 years after diagnosis. For each of these strategies, the model predicted the mean delay in the detection of disease with a Gleason score ≥ 7. RESULTS: The model estimated the 10-year cumulative probability of reclassification from a Gleason score of 6 to a Gleason score ≥ 7 to be 40.0%. The probability of undersampling at diagnosis was 9.8%, and the annual progression probability for men with a Gleason score of 6 was 4.0%. On the basis of these estimates, a simulation of an annual biopsy strategy estimated the mean time to the detection of disease with a Gleason score ≥ 7 to be 14.1 months; however, several strategies eliminated biopsies with only small delays (<12 months) in detecting grade progression. CONCLUSIONS: Although annual biopsy for low-risk men on AS is associated with the shortest time to the detection of disease with a Gleason score ≥ 7, several alternative strategies may allow less frequent biopsying without sizable delays in detecting grade progression. Cancer 2018;124:698-705. © 2017 American Cancer Society.

The Challenge of Measuring Surgeon Spending for Payment Policies.

OBJECTIVE: Our objective was to understand the reliability of profiling surgeons on average health care spending. SUMMARY OF BACKGROUND DATA: Under its Merit-based Incentive Payment System (MIPS), Medicare will measure surgeon spending and tie performance to payments. Although the intent of this cost-profiling is to reward low-cost surgeons, it is unknown whether surgeons can be accurately distinguished from their peers. METHODS: We used Michigan Medicare and commercial payer claims data to construct episodes of surgical care and to calculate average annual spending for individual surgeons. We then estimated the "reliability" (ie, the ability to distinguish surgeons from their peers) of these cost-profiles and the case-volume that surgeons would need in order to achieve high reliability [intraclass correlation coefficient (ICC) >0.8]. Finally, we calculated the reliability of 2 alternative methods of profiling surgeons (ie, using multiple years of data and grouping surgeons by hospitals). RESULTS: We found that annual cost-profiles of individual surgeons had poor reliability; the ICC ranged from <0.001 for CABG to 0.061 for cholecystectomy. We found that few surgeons in the state of Michigan have sufficient case-volume to be reliably compared; 1% had the minimum yearly case. Finally, we found that the reliability of the cost-profiles can be improved by measuring spending at the hospital-level and/or by incorporating additional years of data. CONCLUSION: These findings suggest that the Medicare program should measure surgeon spending at a group level or incorporate multiple years of data to reduce misclassification of surgeon performance in the MIPS program.

Cost-effectiveness of magnetic resonance imaging and targeted fusion biopsy for early detection of prostate cancer.

OBJECTIVE: To determine how best to use magnetic resonance imaging (MRI) and targeted MRI/ultrasonography fusion biopsy for early detection of prostate cancer (PCa) in men with elevated prostate-specific antigen (PSA) concentrations and whether it can be cost-effective. METHODS: A Markov model of PCa onset and progression was developed to estimate the health and economic consequences of PCa screening with MRI. Patients underwent PSA screening from ages 55 to 69 years. Patients with elevated PSA concentrations (>4 ng/mL) underwent MRI, followed by targeted fusion or combined (standard + targeted fusion) biopsy on positive MRI, and standard or no biopsy on negative MRI. Prostate Imaging Reporting and Data System (PI-RADS) score on MRI was used to determine biopsy decisions. Deaths averted, quality-adjusted life-years (QALYs), cost and incremental cost-effectiveness ratio (ICER) were estimated for each strategy. RESULTS: With a negative MRI, standard biopsy was more expensive and had lower QALYs than performing no biopsy. The optimum screening strategy (ICER $23 483/QALY) recommended combined biopsy for patients with PI-RADS score ≥3 and no biopsy for patients with PI-RADS score <3, and reduced the number of screening biopsies by 15%. Threshold analysis suggests MRI continues to be cost-effective when the sensitivity and specificity of MRI and combined biopsy are simultaneously reduced by 19 percentage points. CONCLUSIONS: Our analysis suggests MRI followed by targeted MRI/ultrasonography fusion biopsy can be a cost-effective approach to the early detection of PCa.

Benefit and harm of intensive blood pressure treatment: Derivation and validation of risk models using data from the SPRINT and ACCORD trials.

BACKGROUND: Intensive blood pressure (BP) treatment can avert cardiovascular disease (CVD) events but can cause some serious adverse events. We sought to develop and validate risk models for predicting absolute risk difference (increased risk or decreased risk) for CVD events and serious adverse events from intensive BP therapy. A secondary aim was to test if the statistical method of elastic net regularization would improve the estimation of risk models for predicting absolute risk difference, as compared to a traditional backwards variable selection approach. METHODS AND FINDINGS: Cox models were derived from SPRINT trial data and validated on ACCORD-BP trial data to estimate risk of CVD events and serious adverse events; the models included terms for intensive BP treatment and heterogeneous response to intensive treatment. The Cox models were then used to estimate the absolute reduction in probability of CVD events (benefit) and absolute increase in probability of serious adverse events (harm) for each individual from intensive treatment. We compared the method of elastic net regularization, which uses repeated internal cross-validation to select variables and estimate coefficients in the presence of collinearity, to a traditional backwards variable selection approach. Data from 9,069 SPRINT participants with complete data on covariates were utilized for model development, and data from 4,498 ACCORD-BP participants with complete data were utilized for model validation. Participants were exposed to intensive (goal systolic pressure < 120 mm Hg) versus standard (<140 mm Hg) treatment. Two composite primary outcome measures were evaluated: (i) CVD events/deaths (myocardial infarction, acute coronary syndrome, stroke, congestive heart failure, or CVD death), and (ii) serious adverse events (hypotension, syncope, electrolyte abnormalities, bradycardia, or acute kidney injury/failure). The model for CVD chosen through elastic net regularization included interaction terms suggesting that older age, black race, higher diastolic BP, and higher lipids were associated with greater CVD risk reduction benefits from intensive treatment, while current smoking was associated with fewer benefits. The model for serious adverse events chosen through elastic net regularization suggested that male sex, current smoking, statin use, elevated creatinine, and higher lipids were associated with greater risk of serious adverse events from intensive treatment. SPRINT participants in the highest predicted benefit subgroup had a number needed to treat (NNT) of 24 to prevent 1 CVD event/death over 5 years (absolute risk reduction [ARR] = 0.042, 95% CI: 0.018, 0.066; P = 0.001), those in the middle predicted benefit subgroup had a NNT of 76 (ARR = 0.013, 95% CI: -0.0001, 0.026; P = 0.053), and those in the lowest subgroup had no significant risk reduction (ARR = 0.006, 95% CI: -0.007, 0.018; P = 0.71). Those in the highest predicted harm subgroup had a number needed to harm (NNH) of 27 to induce 1 serious adverse event (absolute risk increase [ARI] = 0.038, 95% CI: 0.014, 0.061; P = 0.002), those in the middle predicted harm subgroup had a NNH of 41 (ARI = 0.025, 95% CI: 0.012, 0.038; P < 0.001), and those in the lowest subgroup had no significant risk increase (ARI = -0.007, 95% CI: -0.043, 0.030; P = 0.72). In ACCORD-BP, participants in the highest subgroup of predicted benefit had significant absolute CVD risk reduction, but the overall ACCORD-BP participant sample was skewed towards participants with less predicted benefit and more predicted risk than in SPRINT. The models chosen through traditional backwards selection had similar ability to identify absolute risk difference for CVD as the elastic net models, but poorer ability to correctly identify absolute risk difference for serious adverse events. A key limitation of the analysis is the limited sample size of the ACCORD-BP trial, which expanded confidence intervals for ARI among persons with type 2 diabetes. Additionally, it is not possible to mechanistically explain the physiological relationships explaining the heterogeneous treatment effects captured by the models, since the study was an observational secondary data analysis. CONCLUSIONS: We found that predictive models could help identify subgroups of participants in both SPRINT and ACCORD-BP who had lower versus higher ARRs in CVD events/deaths with intensive BP treatment, and participants who had lower versus higher ARIs in serious adverse events.

A Statewide Intervention Improves Appropriate Imaging in Localized Prostate Cancer.

PURPOSE: We implemented a statewide intervention to improve imaging utilization for the staging of patients with newly diagnosed prostate cancer. MATERIALS AND METHODS: MUSIC (Michigan Urological Surgery Improvement Collaborative) is a quality improvement collaborative comprising 42 diverse practices representing approximately 85% of the urologists in Michigan. MUSIC has developed imaging appropriateness criteria (prostate specific antigen greater than 20 ng/ml, Gleason score 7 or higher and clinical stage T3 or higher) which minimize unnecessary imaging with bone scan and computerized tomography. After baseline rates of radiographic staging were established in 2012 and 2013, we used multidimensional interventions to deploy these criteria in 2014. Imaging utilization was then remeasured in 2015 to evaluate for changes in practice patterns. RESULTS: A total of 10,554 newly diagnosed patients with prostate cancer were entered into the MUSIC registry from January 1, 2012 through December 31, 2013 and January 1, 2015 through December 31, 2015. Of these patients 7,442 (79%) and 7,312 (78%) met our criteria to avoid bone scan and computerized tomography imaging, respectively. The use of bone scan imaging when not indicated decreased from 11.0% at baseline to 6.5% after interventions (p <0.0001). The use of computerized tomography when not indicated decreased from 14.7% at baseline to 7.7% after interventions (p <0.0001). Variability among practices decreased substantially after the interventions as well. The use of recommended imaging remained stable during these periods. CONCLUSIONS: An intervention aimed at appropriate use of imaging was associated with decreased use of bone scans and computerized tomography among men at low risk for metastases.

Anticipatory Positive Urine Tests for Bladder Cancer.

PURPOSE: The aim of this study was to establish the criteria defining an anticipatory positive test for bladder cancer. METHODS: We reviewed all patients at our institution who underwent urine cytology or UroVysion fluorescence in situ hybridization (FISH) and cystoscopy from 2003 to 2012. Test performance and cancer anticipation was assessed using generalized linear mixed models, mixed-effects proportional hazards models, and cumulative incidence curves using tests performed within 30 days of each other as well as within a lag time of 1 year. RESULTS: Overall, 6729 urine tests (4729 cytology and 2040 UroVysion FISH) were paired with gold-standard cystoscopies. Sensitivity and specificity were 63 and 41% for cytology, and 37 and 84% for UroVysion FISH, respectively. A 1-year lag time allowed for cancer anticipation and neither test improved. Among patients with positive cytology and initially negative cystoscopy, the hazard ratio of developing a bladder tumor at 1 year was 1.83; 76% of these patients developed a tumor within 1 year. Similarly, among patients with a positive FISH and initially negative cystoscopy, the hazard ratio of developing a bladder tumor at 1 year was 1.56; 40% of these patients developed a tumor within 1 year. CONCLUSIONS: Urine-based tests for bladder cancer are frequently falsely positive. With further follow-up time, some of these false positive tests are vindicated as true (anticipatory) positive tests, although many will remain false positives. We developed statistical criteria to determine if a test anticipates future cancers or not.

Assessment of long-term outcomes associated with urinary prostate cancer antigen 3 and TMPRSS2:ERG gene fusion at repeat biopsy.

BACKGROUND: In men with clinically localized prostate cancer who have undergone at least 1 previous negative biopsy and have elevated serum prostate-specific antigen (PSA) levels, long-term health outcomes associated with the assessment of urinary prostate cancer antigen 3 (PCA3) and the transmembrane protease, serine 2 (TMPRSS2):v-ets erythroblastosis virus E26 oncogene homolog (avian) (ERG) gene fusion (T2:ERG) have not been investigated previously in relation to the decision to recommend a repeat biopsy. METHODS: The authors performed a decision analysis using a decision tree for men with elevated PSA levels. The probability of cancer was estimated using the Prostate Cancer Prevention Trial Risk Calculator (version 2.0). The use of PSA alone was compared with the use of PCA3 and T2:ERG scores, with each evaluated independently, in combination with PSA to trigger a repeat biopsy. When PCA3 and T2:ERG score evaluations were used, predefined thresholds were established to determine whether the patient should undergo a repeat biopsy. Biopsy outcomes were defined as either positive (with a Gleason score of <7, 7, or >7) or negative. Probabilities and estimates of 10-year overall survival and 15-year cancer-specific survival were derived from previous studies and a literature review. Outcomes were defined as age-dependent and Gleason score-dependent 10-year overall and 15-year cancer-specific survival rates and the percentage of biopsies avoided. RESULTS: Incorporating the PCA3 score (biopsy threshold, 25; generated based on the urine PCA3 level normalized to the amount of PSA messenger RNA) or the T2:ERG score (biopsy threshold, 10; based on the urine T2:ERG level normalized to the amount of PSA messenger RNA) into the decision to recommend repeat biopsy would have avoided 55.4% or 64.7% of repeat biopsies for the base-case patient, respectively, and changes in the 10-year survival rate were only 0.93% or 1.41%, respectively. Multi-way sensitivity analyses suggested that these results were robust with respect to the model parameters. CONCLUSIONS: The use of PCA3 or T2:ERG testing for repeat biopsy decisions can substantially reduce the number of biopsies without significantly affecting 10-year survival.

A prognostic nomogram for prediction of recurrence in desmoid fibromatosis.

OBJECTIVE: To construct a postoperative nomogram to estimate the risk of local recurrence for patients with desmoid tumors. BACKGROUND: The standard management of desmoid tumors is resection, but many recur locally. Other options include observation or novel chemotherapeutics, but little guidance exists on selecting treatment. METHODS: Patients undergoing resection during 1982-2011 for primary or locally recurrent desmoids were identified from a single-institution prospective database. Cox regression analysis was used to assess risk factors and to create a recurrence nomogram, which was validated using an international, multi-institutional data set. RESULTS: Desmoids were treated surgically in 495 patients (median follow-up of 60 months). Of 439 patients undergoing complete gross resection, 100 (23%) had recurrence. Five-year local recurrence-free survival was 69%. Eight patients died of disease, all after R2 resection. Adjuvant radiation was not associated with improved local recurrence-free survival. In multivariate analysis, factors associated with recurrence were extremity location, young age, and large tumor size, but not margin. Abdominal wall tumors had the best outcome (5-year local recurrence-free survival rate of 91%). Age, site, and size were used to construct a nomogram with concordance index of 0.703 in internal validation and 0.659 in external validation. Integration of additional variables (R1 margin, sex, depth, and primary vs recurrent presentation) did not importantly improve concordance (internal concordance index of 0.707). CONCLUSIONS: A postoperative nomogram including only size, site, and age predicts local recurrence and can aid in counseling patients. Systemic therapies may be appropriate for young patients with large, extremity desmoids, but surgery alone is curative for most abdominal wall lesions.

Impact of obesity on perioperative complications and long-term survival of patients with gastric cancer.

BACKGROUND: The prevalence of obesity is increasing in the United States. Obesity has been associated with worse surgical outcomes, but its impact on long-term outcomes in gastric cancer is unclear. The aim of this study was to evaluate the effects of being overweight on surgical and long-term outcomes for patients with gastric cancer. METHODS: Patients who underwent curative intent resection for gastric carcinoma from 1985 to 2007 were identified from a prospectively collected gastric cancer database. Overweight was defined as a body mass index (BMI) of 25 kg/m(2) or higher. Clinical outcomes of overweight and nonoverweight patients were compared. RESULTS: From the total population of 1,853 patients, 1,125 (60.7%) were overweight. Overweight patients tended to have more proximal tumors and a lower T stage. Accurate complication data were available on a subset of patients from 2000 to 2007. A BMI of ≥25 was associated with increased postoperative complications (47.9 vs. 35.8%, p < 0.001). This was mainly due to an increase in the rate of wound infections (8.9 vs. 4.7%, p = 0.02) and anastomotic leaks (11.8 vs. 5.4%, p = 0.002). Multivariate logistic regression analysis showed that higher BMI, total gastrectomy, and use of neoadjuvant chemotherapy were associated with increased wound infection and anastomotic leak. Overweight patients were less likely to have adequate lymph node staging (73.3 vs. 79.2%, p = 0.047). There was no difference in overall survival or disease-specific survival between the two groups. CONCLUSIONS: Increased BMI is a predictor of increased postoperative complications, including anastomotic leak, but it is not a predictor of survival in gastric cancer.

Changes in the management of benign liver tumours: an analysis of 285 patients.

OBJECTIVES: Benign liver tumours (BLTs) are common and their management remains controversial. This study assesses the safety of a selective management approach. METHODS: Patients with BLT were identified from an institutional database. Patients with simple cysts or an incidental BLT in the setting of metastasis or concomitant malignancy were excluded. RESULTS: A total of 285 patients presenting during the period from January 1992 to December 2009 with haemangioma (53.0%), focal nodular hyperplasia (23.9%), adenoma (10.2%) or indeterminate/other lesions (13.0%) were evaluated. Of these, 117 patients (41.1%) underwent immediate resection and 168 patients (58.9%) were followed with serial imaging (median follow-up: 30 months). During observation, eight patients (4.8%) underwent resection for tumour growth, inability to exclude malignancy or symptoms; no patients demonstrated malignant transformation or tumour-related complications. During the study period, the number of BLTs evaluated and the proportion of patients observed increased from 129 BLTs of which 36.4% were observed in 1992-2002 to 156 BLTs of which 71.2% were observed in 2003-2009 (P < 0.001). Diagnostic uncertainty led to resection in 29.5% of patients during the earlier period, but in only 13.4% during the more recent 7 years (P < 0.05). CONCLUSIONS: Asymptomatic BLTs without concern for malignancy or adenoma can be safely observed with minimal risk for misdiagnosis. Patients selected for observation rarely require resection or develop tumour-related complications.

Costs of medical care after open or minimally invasive prostate cancer surgery: a population-based analysis.

BACKGROUND: Evidence suggests that minimally invasive radical prostatectomy (MRP) and open radical prostatectomy (ORP) have similar short-term clinical and functional outcomes. MRP with robotic assistance is generally more expensive than ORP, but it is not clear whether subsequent costs of care vary by approach. METHODS: In the Surveillance, Epidemiology, and End Results (SEER) cancer registry linked with Medicare claims, men aged 66 years or older who received MRP or ORP in 2003 through 2006 for prostate cancer were identified. Total cost of care was estimated as the sum of Medicare payments from all claims for hospital care, outpatient care, physician services, home health and hospice care, and durable medical equipment in the first year from the date of surgical admission. The impact of surgical approach on costs was estimated, controlling for patient and disease characteristics. RESULTS: Of 5445 surgically treated prostate cancer patients, 4454 (82%) had ORP and 991 (18%) had MRP. Mean total first-year costs were more than $1200 greater for MRP compared with ORP ($16,919 vs $15,692; P = .08). Controlling for patient and disease characteristics, MRP was associated with 2% greater mean total payments, but this difference was not statistically significant. First-year costs were greater for men who were older, black, lived in the Northeast, had lymph node involvement, more advanced tumor stage, or greater comorbidity. CONCLUSIONS: In this population-based cohort of older men, MRP and ORP had similar economic outcomes. From a payer's perspective, any benefits associated with MRP may not translate to net savings compared with ORP in the first year after surgery.

Analysis of incidence and clinical outcomes in patients with thromboembolic events and invasive exocrine pancreatic cancer.

BACKGROUND: Pancreatic adenocarcinoma is among the most common malignancies associated with thromboembolic events (TEs); however, reported incidence figures vary significantly and contain small patient cohorts. Pancreatic cancer-specific thrombosis studies examining the correlation between clinical variables, including thrombosis timing and the impact of thrombosis on survival, have not been reported. METHODS: Survival analyses were performed relating to the development and timing of a TE in 1915 patients administered chemotherapy at Memorial Sloan-Kettering Cancer Center with invasive exocrine pancreatic cancer from January 1, 2000 to December 31, 2009. TE timing, relative to clinical parameters including laboratory data, erythropoietin-stimulating agent use, and body mass index (BMI), were also analyzed. RESULTS: A thrombosis was identified in 690 (36%) patients. After adjusting for patients with pancreatic surgery and thrombosis (n = 127), developing a TE significantly increased the risk of death (hazard ratio [HR], 2.6; 95% confidence interval [CI], 2.3-2.8; P < .01). Patients with an early TE (within 1.5 months from pancreatic cancer diagnosis) had a significantly higher risk of death (HR, 2.1; 95% CI, 1.7-2.5; P < .01) compared with patients with late TE or no TE. Erythropoietin-stimulating agent use and an elevated international normalized ratio were associated with significantly shorter time to thrombosis. Low BMI was associated with significantly longer time to thrombosis. CONCLUSIONS: TEs are common in exocrine pancreatic cancer, with coagulopathy, erythropoietin-stimulating agent use, and underweight BMI influencing thrombosis timing. TEs, particularly early ones, confer a significantly worse prognosis, suggesting a biological significance, underscoring the relevance of ongoing prophylaxis trials, and raising the question of whether early TEs should be considered a stratification factor for clinical trials.

An examination of the dynamic changes in prostate-specific antigen occurring in a population-based cohort of men over time.

OBJECTIVE: • To determine whether prostate-specific antigen velocity (PSA-V), PSA doubling time (PSA-DT), or PSA percentage change (PSA-PC) add incremental information to PSA alone for community-based men undergoing prostate cancer (PCa) screening. PARTICIPANTS AND METHODS: • A population-based cohort of 11 872 men from Olmsted County, MN undergoing PSA screening for PCa from 1993 to 2005 was analysed for PSA, PSA-DT, PSA-PC and PSA-V and subsequent PCa. • Receiver-operating characteristics curves and logistic regression were used to calculate the area under the curve (AUC) and Aikaike's information criterion. • Reclassification analysis was performed and the net reclassification improvement and integrated discrimination improvement were measured. • The method of Begg and Greenes was used to adjust for verification bias. RESULTS: • The single best predictor of future PCa was PSA (AUC = 0.773) with PSA-V (AUC = 0.729) and PSA-DT/PSA-PC (AUC = 0.689) performing worse. • After age adjustment, combining PSA with PSA-V (AUC = 0.773) or PSA-DT/PSA-PC (AUC = 0.773) resulted in no better predictions than PSA alone. • Reclassification analysis showed that adding PSA-V or PSA-DT/PSA-PC to PSA did not result in a meaningful amount of reclassification. CONCLUSIONS: • PSA is a better predictor of future PCa than PSA-V, PSA-DT, or PSA-PC. • Adding PSA-V, PSA-DT, or PSA-PC to PSA does not result in clinically relevant improvements in the ability to predict future PCa.

Dynamic prediction of work status for workers with occupational injuries: assessing the value of longitudinal observations.

OBJECTIVE: Occupational injuries (OIs) cause an immense burden on the US population. Prediction models help focus resources on those at greatest risk of a delayed return to work (RTW). RTW depends on factors that develop over time; however, existing methods only utilize information collected at the time of injury. We investigate the performance benefits of dynamically estimating RTW, using longitudinal observations of diagnoses and treatments collected beyond the time of initial injury. MATERIALS AND METHODS: We characterize the difference in predictive performance between an approach that uses information collected at the time of initial injury (baseline model) and a proposed approach that uses longitudinal information collected over the course of the patient's recovery period (proposed model). To control the comparison, both models use the same deep learning architecture and differ only in the information used. We utilize a large longitudinal observation dataset of OI claims and compare the performance of the two approaches in terms of daily prediction of future work state (working vs not working). The performance of these two approaches was assessed in terms of the area under the receiver operator characteristic curve (AUROC) and expected calibration error (ECE). RESULTS: After subsampling and applying inclusion criteria, our final dataset covered 294 103 OIs, which were split evenly between train, development, and test datasets (1/3, 1/3, 1/3). In terms of discriminative performance on the test dataset, the proposed model had an AUROC of 0.728 (90% confidence interval: 0.723, 0.734) versus the baseline's 0.591 (0.585, 0.598). The proposed model had an ECE of 0.004 (0.003, 0.005) versus the baseline's 0.016 (0.009, 0.018). CONCLUSION: The longitudinal approach outperforms current practice and shows potential for leveraging observational data to dynamically update predictions of RTW in the setting of OI. This approach may enable physicians and workers' compensation programs to manage large populations of injured workers more effectively.