Postdischarge Noninvasive Telemonitoring and Nurse Telephone Coaching Improve Outcomes in Heart Failure Patients With High Burden of Comorbidity.

BACKGROUND: Noninvasive telemonitoring and nurse telephone coaching (NTM-NTC) is a promising postdischarge strategy in heart failure (HF). Comorbid conditions and disease burden influence health outcomes in HF, but how comorbidity burden modulates the effectiveness of NTM-NTC is unknown. This study aims to identify patients with HF who may benefit from postdischarge NTM-NTC based on their burden of comorbidity. METHODS AND RESULTS: In the Better Effectiveness After Transition - Heart Failure trial, patients hospitalized for acute decompensated HF were randomized to postdischarge NTM-NTC or usual care. In this secondary analysis of 1313 patients with complete data, comorbidity burden was assessed by scoring complication and coexisting diagnoses from index admissions. Clinical outcomes included 30-day and 180-day readmissions, mortality, days alive, and combined days alive and out of the hospital. Patients had a mean of 5.7 comorbidities and were stratified into low (0-2), moderate (3-8), and high comorbidity (≥9) subgroups. Increased comorbidity burden was associated with worse outcomes. NTM-NTC was not associated with readmission rates in any comorbidity subgroup. Among high comorbidity patients, NTM-NTC was associated with significantly lower mortality at 30 days (hazard ratio 0.25, 95% confidence interval 0.07-0.90) and 180 days (hazard ratio 0.51, 95% confidence interval 0.27-0.98), as well as more days alive (160.1 vs 140.3, P = .029) and days alive out of the hospital (152.0 vs 133.2, P = .044) compared with usual care. CONCLUSIONS: Postdischarge NTM-NTC improved survival among patients with HF with a high comorbidity burden. Comorbidity burden may be useful for identifying patients likely to benefit from this management strategy.

Patient-reported Outcomes After External Beam Radiotherapy With Low Dose Rate Brachytherapy Boost vs Radical Prostatectomy for Localized Prostate Cancer: Five-year Results From a Prospective Comparative Effectiveness Study.

PURPOSE: Data comparing radical prostatectomy and external beam radiation therapy with low dose rate brachytherapy boost are lacking. To better guide shared decision making regarding treatment, we compared patient reported outcomes through 5 years following radical prostatectomy or external beam radiation therapy with low dose rate brachytherapy boost for localized prostate cancer. MATERIALS AND METHODS: From 2011-2012, men aged <80 years with localized prostate adenocarcinoma were enrolled and followed longitudinally. Patient reported outcomes included the Expanded Prostate Index Composite. Regression models adjusted for baseline scores and covariates were constructed. RESULTS: The study population included 112 men treated with external beam radiation therapy with low dose rate brachytherapy boost and 1,553 treated with radical prostatectomy. Compared to radical prostatectomy, external beam radiation therapy with low dose rate brachytherapy boost was associated with clinically meaningful worse urinary irritative/obstructive (adjusted mean score difference [95% confidence interval]: 5.0 [-8.7, -1.3]; P = .008 at 5 years) and better urinary incontinence function (13.3 [7.7, 18.9]; P < .001 at 5 years) through 5 years. Urinary function bother was similar between groups (P > .4 at all timepoints). Treatment with external beam radiation therapy with low dose rate brachytherapy boost was associated with worse bowel function (-4.0 [-6.9, -1.1]; P = .006 at 5 years) through 5 years compared to radical prostatectomy. Treatment with external beam radiation therapy with low dose rate brachytherapy boost was associated with better sexual function at 1 year (12.0 [6.5, 17.5]; P < .001 at 1 year) compared to radical prostatectomy, but there was insufficient evidence to reject the supposition that no difference was seen at 3 or 5 years. CONCLUSIONS: Compared to radical prostatectomy, external beam radiation therapy with low dose rate brachytherapy boost was associated with clinically meaningful worse urinary irritative/obstructive and bowel functions but better urinary incontinence function through 5 years after treatment. These patient-reported functional outcomes may clarify treatment expectations and help inform treatment choices for localized prostate cancer.

Association between Treatment for Localized Prostate Cancer and Mental Health Outcomes.

PURPOSE: We aimed to compare patient-reported mental health outcomes for men undergoing treatment for localized prostate cancer longitudinally over 5 years. MATERIALS AND METHODS: We conducted a prospective population-based analysis using the Comparative Effectiveness Analysis of Surgery and Radiation (CEASAR) study. Patient-reported depressive symptoms (Centers for Epidemiologic Studies Depression [CES-D]) and domains of the Medical Outcomes Study 36-item Short Form survey evaluating emotional well-being and energy/fatigue were assessed through 5 years after treatment with surgery, radiotherapy (with or without androgen deprivation therapy) and active surveillance. Regression models were adjusted for outcome-specific baseline function, demographic and clinicopathological characteristics, and treatment approach. RESULTS: A total of 2,742 men (median [quartiles] age 64 [59-70]) met inclusion criteria. Baseline depressive symptoms, as measured by the CES-D, were low (median 4, quartiles 1-8) without differences between groups. We found no effect of treatment modality on depressive symptoms (p=0.78), though older age, poorer health, being unmarried and baseline CES-D score were associated with declines in mental health. There was no clinically meaningful association between treatment modality and scores for either emotional well-being (p=0.81) or energy/fatigue (p=0.054). CONCLUSIONS: This prospective, population-based cohort study of men with localized prostate cancer showed no clinically important differences in mental health outcomes including depressive symptoms, emotional well-being, and energy/fatigue according to the treatment received (surgery, radiotherapy, or surveillance). However, we identified a number of characteristics associated with worse mental health outcomes including: older age, poorer health, being unmarried, and baseline CES-D score which may allow for early identification of patients most at risk of these outcomes following treatment.

Five-year outcomes from a prospective comparative effectiveness study evaluating external-beam radiotherapy with or without low-dose-rate brachytherapy boost for localized prostate cancer.

BACKGROUND: To inform patients who are in the process of selecting prostate cancer treatment, the authors compared disease-specific function after external-beam radiotherapy (EBRT) alone versus EBRT plus a low-dose-rate (LDR) brachytherapy boost (EBRT-LDR). METHODS: For this prospective study, men who had localized prostate cancer in 2011 and 2012 were enrolled. Assessments at baseline, 0.5, 1, 3, and 5 years included the patient-reported Expanded Prostate Index Composite, the 36-item Medical Outcomes Study Short-Form Health Survey, and treatment-related regret. Regression models were adjusted for baseline function and for patient and treatment characteristics. The minimum clinically important difference in scores on the Expanded Prostate Index Composite 26-item instrument was from 5 to 7 for urinary irritation and from 4 to 6 for bowel function. RESULTS: Six-hundred ninety-five men met inclusion criteria and received either EBRT (n = 583) or EBRT-LDR (n = 112). Patients in the EBRT-LDR group were younger (median age, 66 years [interquartile range [IQR], 60-71 years] vs 69 years [IQR, 64-74 years]; P < .001), were less likely to receive pelvic radiotherapy (10% vs 18%; P = .040), and had higher baseline 36-item Medical Outcomes Study Short-Form Health Survey physical function scores (median score, 95 [IQR, 86-100] vs 90 [IQR, 70-100]; P < .001). Over a 3-year period, compared with EBRT, EBRT-LDR was associated with worse urinary irritative scores (adjusted mean difference at 3 years, -5.4; 95% CI, -9.3, -1.6) and bowel function scores (-4.1; 95% CI, -7.6, -0.5). The differences were no longer clinically meaningful at 5 years (difference in urinary irritative scores: -4.5; 95% CI, -8.4, -0.5; difference in bowel function scores: -2.1; 95% CI, -5.7, -1.4). However, men who received EBRT-LDR were more likely to report moderate or big problems with urinary function bother (adjusted odds ratio, 3.5; 95% CI, 1.5-8.2) and frequent urination (adjusted odds ratio, 2.6; 95% CI, 1.2-5.6) through 5 years. There were no differences in survival or treatment-related regret between treatment groups. CONCLUSIONS: Compared with EBRT alone, EBRT-LDR was associated with clinically meaningful worse urinary irritative and bowel function over 3 years after treatment and more urinary bother at 5 years. LAY SUMMARY: In men with prostate cancer who received external-beam radiation therapy (EBRT) with or without a brachytherapy boost (EBRT-LDR), EBRT-LDR was associated with clinically worse urinary irritation and bowel function through 3 years but resolved after 5 years. Men who received EBRT-LDR continued to report moderate-to-big problems with urinary function bother and frequent urination through 5 years. There was no difference in treatment-related regret or survival between patients who received EBRT and those who received EBRT-LDR. These intermediate-term estimates of function may facilitate counseling for men who are selecting treatment.

Patient-Reported Financial Toxicity Associated with Contemporary Treatment for Localized Prostate Cancer.

PURPOSE: Contemporary treatment modalities for localized prostate cancer provide comparable overall and cancer-specific survival. However, the degree of financial burden imposed by treatment, the factors contributing to that burden, and how different treatments compare with regard to financial toxicity remain poorly understood. MATERIALS AND METHODS: The Comparative Effectiveness Analysis of Surgery and Radiation (CEASAR) study enrolled men with localized prostate cancer from 2011 to 2012. Questionnaires were collected at 6, 12, 36, and 60 months after enrollment. Differences in patient-reported financial burden were compared between active surveillance, radical prostatectomy, and external beam radiotherapy using multivariable logistic regression. RESULTS: Among 2,121 patients meeting inclusion criteria, 15% reported large or very large burden of treatment costs within 6 months, declining to 3% by year 5. When controlling for age, education, income and other covariates, external beam radiotherapy was associated with greater financial burden than active surveillance and radical prostatectomy at 1 year (OR 2.2, 95% CI 1.2-4.1 and OR 1.5, 95% CI 1.0-2.3, respectively) and 3 years (OR 3.1 95% CI 1.1-8.8 and OR 2.1, 95% CI 1.2-3.7, respectively). Radical prostatectomy and active surveillance had similar rates of financial burden at all time points. Age, race, education, and D'Amico risk group were associated with financial burden. CONCLUSIONS: External beam radiotherapy was associated with the highest financial burden, even when controlling for age, education and income. Prospective studies that directly measure out-of-pocket and indirect costs and account more thoroughly for baseline socioeconomic differences are warranted in order to identify those most at risk.

Assessing the Quality of Surgical Care for Clinically Localized Prostate Cancer: Results from the CEASAR Study.

PURPOSE: Prior studies suggest that nationally endorsed quality measures for prostate cancer care are not linked closely with outcomes. Using a prospective, population based cohort we measured clinically relevant variation in structure, process and outcome measures in men undergoing radical prostatectomy. MATERIALS AND METHODS: The Comparative Effectiveness Analysis of Surgery and Radiation (CEASAR) Study enrolled men with clinically localized prostate cancer diagnosed from 2011 to 2012 with 1,069 meeting the final inclusion criteria. Quality of life was assessed using the Expanded Prostate Index Composite (EPIC-26) and clinical data by chart review. Six quality measures were assessed, including pelvic lymphadenectomy with risk of lymph node involvement 2% or greater, appropriate nerve sparing, negative surgical margins, urinary and sexual function, treatment by high volume surgeon, and 30-day and 1-year complications. Receipt of high quality care was compared across categories of race, age, surgeon volume and surgical approach via multivariable analysis. RESULTS: There were no significant differences in quality across race, age or surgeon volume strata, except for worse urinary incontinence in Black men. However, robotic surgery patients experienced fewer complications (3% vs 9.3% short-term and 11% vs 16% long-term), were more likely to be treated by a high volume surgeon (47% vs 25%) and demonstrated better sexual function. CONCLUSIONS: In this cohort we did not identify meaningful variation in quality of care across racial groups, age groups and surgeon volume strata, suggesting that men are receiving comparable quality of care across these strata. However, we did find variation between open and robotic surgery with fewer complications, improved sexual function and increased use of high volume surgeons in the robotic group, possibly reflecting differences in quality between approaches, differences in practice patterns and/or biases in patient selection.

Patient-Reported Outcomes Through 5 Years for Active Surveillance, Surgery, Brachytherapy, or External Beam Radiation With or Without Androgen Deprivation Therapy for Localized Prostate Cancer.

Importance: Understanding adverse effects of contemporary treatment approaches for men with favorable-risk and unfavorable-risk localized prostate cancer could inform treatment selection. Objective: To compare functional outcomes associated with prostate cancer treatments over 5 years after treatment. Design, Setting, and Participants: Prospective, population-based cohort study of 1386 men with favorable-risk (clinical stage cT1 to cT2bN0M0, prostate-specific antigen [PSA] ≤20 ng/mL, and Grade Group 1-2) prostate cancer and 619 men with unfavorable-risk (clinical stage cT2cN0M0, PSA of 20-50 ng/mL, or Grade Group 3-5) prostate cancer diagnosed in 2011 through 2012, accrued from 5 Surveillance, Epidemiology and End Results Program sites and a US prostate cancer registry, with surveys through September 2017. Exposures: Treatment with active surveillance (n = 363), nerve-sparing prostatectomy (n = 675), external beam radiation therapy (EBRT; n = 261), or low-dose-rate brachytherapy (n = 87) for men with favorable-risk disease and treatment with prostatectomy (n = 402) or EBRT with androgen deprivation therapy (n = 217) for men with unfavorable-risk disease. Main Outcomes and Measures: Patient-reported function, based on the 26-item Expanded Prostate Index Composite (range, 0-100), 5 years after treatment. Regression models were adjusted for baseline function and patient and tumor characteristics. Minimum clinically important difference was 10 to 12 for sexual function, 6 to 9 for urinary incontinence, 5 to 7 for urinary irritative symptoms, and 4 to 6 for bowel and hormonal function. Results: A total of 2005 men met inclusion criteria and completed the baseline and at least 1 postbaseline survey (median [interquartile range] age, 64 [59-70] years; 1529 of 1993 participants [77%] were non-Hispanic white). For men with favorable-risk prostate cancer, nerve-sparing prostatectomy was associated with worse urinary incontinence at 5 years (adjusted mean difference, -10.9 [95% CI, -14.2 to -7.6]) and sexual function at 3 years (adjusted mean difference, -15.2 [95% CI, -18.8 to -11.5]) compared with active surveillance. Low-dose-rate brachytherapy was associated with worse urinary irritative (adjusted mean difference, -7.0 [95% CI, -10.1 to -3.9]), sexual (adjusted mean difference, -10.1 [95% CI, -14.6 to -5.7]), and bowel (adjusted mean difference, -5.0 [95% CI, -7.6 to -2.4]) function at 1 year compared with active surveillance. EBRT was associated with urinary, sexual, and bowel function changes not clinically different from active surveillance at any time point through 5 years. For men with unfavorable-risk disease, EBRT with ADT was associated with lower hormonal function at 6 months (adjusted mean difference, -5.3 [95% CI, -8.2 to -2.4]) and bowel function at 1 year (adjusted mean difference, -4.1 [95% CI, -6.3 to -1.9]), but better sexual function at 5 years (adjusted mean difference, 12.5 [95% CI, 6.2-18.7]) and incontinence at each time point through 5 years (adjusted mean difference, 23.2 [95% CI, 17.7-28.7]), than prostatectomy. Conclusions and Relevance: In this cohort of men with localized prostate cancer, most functional differences associated with contemporary management options attenuated by 5 years. However, men undergoing prostatectomy reported clinically meaningful worse incontinence through 5 years compared with all other options, and men undergoing prostatectomy for unfavorable-risk disease reported worse sexual function at 5 years compared with men who underwent EBRT with ADT.

Interpretation of Domain Scores on the EPIC-How Does the Domain Score Translate into Functional Outcomes?

PURPOSE: The EPIC-26 (Expanded Prostate Cancer Index Composite-Short Form) is a validated questionnaire for measuring health related quality of life. However, the relationship between domain scores and functional outcomes remains unclear, leading to potential confusion about expectations after treatment. For instance, does a sexual function domain score of 80 mean that a patient can achieve erection sufficient for intercourse? Consequently we sought to determine the relationship between the domain score and the response to obtaining the best possible outcome for each question. MATERIALS AND METHODS: Using data from the CEASAR (Comparative Effectiveness Analysis of Surgery and Radiation) study, a multicenter, prospective study of men diagnosed with localized prostate cancer, we analyzed 11,464 EPIC-26 questionnaires from a total of 2,563 men at baseline through 60 months of followup who were treated with robotic prostatectomy, radiotherapy or active surveillance. We dichotomized every item into its best possible outcome and assessed the percent of men at each domain score who achieved the best result. RESULTS: For every EPIC-26 item the frequency of the best possible outcome was reported by domain score category. For example, a score of 80 to 100 on sexual function corresponded to 97% of men reporting erections sufficient for intercourse while at a score of 40 to 60 only 28% reported adequate erections. Also, at a score of 80 to 100 on the urinary incontinence domain 93% of men reported rarely or never leaking vs 6% at a score of 61 to 80. CONCLUSIONS: Our findings indicate a novel way to interpret EPIC-26 domain scores, demonstrating large variations in the percent of respondents reporting the best possible outcomes over narrow domain score differences. This information may be valuable when counseling men on treatment options.

The Effect of Nerve Sparing Status on Sexual and Urinary Function: 3-Year Results from the CEASAR Study.

PURPOSE: Nerve sparing contributes to the recovery of sexual and urinary function after radical prostatectomy but it may be ineffective in some patients or carry the risk of a positive surgical margin. We evaluated sexual and urinary function outcomes according to the degree of nerve sparing in patients with prostate cancer treated with radical prostatectomy. MATERIALS AND METHODS: The CEASAR (Comparative Effectiveness Analysis of Surgery and Radiation) study is a prospective, population based, observational study of men diagnosed with localized prostate cancer in 2011 to 2012. Patient reported sexual and urinary functions were measured using the 26-item Expanded Prostate Index Composite at baseline within 6 months after diagnosis, and 6, 12 and 36 months after enrollment. Study inclusion criteria included radical prostatectomy as primary treatment, documentation of nerve sparing status and absent androgen deprivation therapy. Nerve sparing status was defined as none, unilateral or bilateral according to the operative report. RESULTS: The final analytical cohort included 991 men. The 11 men treated with unilateral nerve sparing and the 75 treated with a nonnerve sparing procedure were grouped together. In the multivariable model there was a significant difference in the sexual function score 3 years after radical prostatectomy in the bilateral nerve sparing group compared with the unilateral and nonnerve sparing group (6.1 points, 95% CI 2.0-10.3, p = 0.004). This was more pronounced in men with high baseline sexual function (8.23 points, 95% CI 1.6-14.8, p = 0.014) but not in those with low baseline function (4.0 points, 95% CI -0.6-8.7, p = 0.090). Similar effects were demonstrated on urinary incontinence scores. CONCLUSIONS: Bilateral nerve sparing resulted in better sexual and urinary function outcomes than unilateral or nonnerve sparing but the difference was not significant in men with low baseline sexual function.

Validating the total illness burden index for prostate cancer (TIBI-CaP) in men with castration-resistant prostate cancer: data from TRUMPET.

AIM: To validate the total illness burden index for prostate cancer (TIBI-CaP) in castration-resistant prostate cancer (CRPC) patients. PATIENTS & METHODS: Baseline comorbidity scores collected using the TIBI-CaP were compared with the baseline patient-reported health-related quality of life using the SF-12v2 and FACT-P questionnaires in 302 patients enrolled in the Treatment Registry for Outcomes in CRPC Patients (TRUMPET). RESULTS: Baseline TIBI-CaP scores were negatively correlated with all baseline SF-12v2 domain/composite (p < 0.001) and FACT-P subscale/total (p < 0.020) scores. There was a significant decreasing linear trend in SF12v2 and FACT-P scores over the categories based on TIBI-CaP quartiles of comorbidity burden (from 'least' to 'severe'). CONCLUSION: The TIBI-CaP is a valid measure of comorbidity burden in patients with CRPC in the real world.

Association Between Radiation Therapy, Surgery, or Observation for Localized Prostate Cancer and Patient-Reported Outcomes After 3 Years.

Importance: Understanding the adverse effects of contemporary approaches to localized prostate cancer treatment could inform shared decision making. Objective: To compare functional outcomes and adverse effects associated with radical prostatectomy, external beam radiation therapy (EBRT), and active surveillance. Design, Setting, and Participants: Prospective, population-based, cohort study involving 2550 men (≤80 years) diagnosed in 2011-2012 with clinical stage cT1-2, localized prostate cancer, with prostate-specific antigen levels less than 50 ng/mL, and enrolled within 6 months of diagnosis. Exposures: Treatment with radical prostatectomy, EBRT, or active surveillance was ascertained within 1 year of diagnosis. Main Outcomes and Measures: Patient-reported function on the 26-item Expanded Prostate Cancer Index Composite (EPIC) 36 months after enrollment. Higher domain scores (range, 0-100) indicate better function. Minimum clinically important difference was defined as 10 to 12 points for sexual function, 6 for urinary incontinence, 5 for urinary irritative symptoms, 5 for bowel function, and 4 for hormonal function. Results: The cohort included 2550 men (mean age, 63.8 years; 74% white, 55% had intermediate- or high-risk disease), of whom 1523 (59.7%) underwent radical prostatectomy, 598 (23.5%) EBRT, and 429 (16.8%) active surveillance. Men in the EBRT group were older (mean age, 68.1 years vs 61.5 years, P < .001) and had worse baseline sexual function (mean score, 52.3 vs 65.2, P < .001) than men in the radical prostatectomy group. At 3 years, the adjusted mean sexual domain score for radical prostatectomy decreased more than for EBRT (mean difference, -11.9 points; 95% CI, -15.1 to -8.7). The decline in sexual domain scores between EBRT and active surveillance was not clinically significant (-4.3 points; 95% CI, -9.2 to 0.7). Radical prostatectomy was associated with worse urinary incontinence than EBRT (-18.0 points; 95% CI, -20.5 to -15.4) and active surveillance (-12.7 points; 95% CI, -16.0 to -9.3) but was associated with better urinary irritative symptoms than active surveillance (5.2 points; 95% CI, 3.2 to 7.2). No clinically significant differences for bowel or hormone function were noted beyond 12 months. No differences in health-related quality of life or disease-specific survival (3 deaths) were noted (99.7%-100%). Conclusions and Relevance: In this cohort of men with localized prostate cancer, radical prostatectomy was associated with a greater decrease in sexual function and urinary incontinence than either EBRT or active surveillance after 3 years and was associated with fewer urinary irritative symptoms than active surveillance; however, no meaningful differences existed in either bowel or hormonal function beyond 12 months or in in other domains of health-related quality-of-life measures. These findings may facilitate counseling regarding the comparative harms of contemporary treatments for prostate cancer.

The Comparative Harms of Open and Robotic Prostatectomy in Population Based Samples.

PURPOSE: Robotic assisted radical prostatectomy has largely replaced open radical prostatectomy for the surgical management of prostate cancer despite conflicting evidence of superiority with respect to disease control or functional sequelae. Using population cohort data, in this study we examined sexual and urinary function in men undergoing open radical prostatectomy vs those undergoing robotic assisted radical prostatectomy. MATERIALS AND METHODS: Subjects surgically treated for prostate cancer were selected from 2 large population based prospective cohort studies, the Prostate Cancer Outcomes Study (enrolled 1994 to 1995) and the Comparative Effectiveness Analysis of Surgery and Radiation (enrolled 2011 to 2012). Subjects completed baseline, 6-month and 12-month standardized patient reported outcome measures. Main outcomes were between-group differences in functional outcome scores at 6 and 12 months using linear regression, and adjusting for baseline function, sociodemographic and clinical characteristics. Sensitivity analyses were used to evaluate outcomes between patients undergoing open radical prostatectomy and robotic assisted radical prostatectomy within and across CEASAR and PCOS. RESULTS: The combined cohort consisted of 2,438 men, 1,505 of whom underwent open radical prostatectomy and 933 of whom underwent robotic assisted radical prostatectomy. Men treated with robotic assisted radical prostatectomy reported better urinary function at 6 months (mean difference 3.77 points, 95% CI 1.09-6.44) but not at 12 months (1.19, -1.32-3.71). Subjects treated with robotic assisted radical prostatectomy also reported superior sexual function at 6 months (8.31, 6.02-10.56) and at 12 months (7.64, 5.25-10.03). Sensitivity analyses largely supported the sexual function findings with inconsistent support for urinary function results. CONCLUSIONS: This population based study reveals that men undergoing robotic assisted radical prostatectomy likely experience less decline in early urinary continence and sexual function than those undergoing open radical prostatectomy. The clinical meaning of these differences is uncertain and longer followup will be required to establish whether these benefits are durable.

Impact of Adherence to Quality Measures for Localized Prostate Cancer on Patient-reported Health-related Quality of Life Outcomes, Patient Satisfaction, and Treatment-related Complications.

BACKGROUND AND OBJECTIVE: Quality measures used in pay-for-performance systems are intended to address specific quality goals, such as safety, efficiency, effectiveness, timeliness, equity, and patient-centeredness. Given the small number of narrowly focused measures in prostate cancer care, we sought to determine whether adherence to any of the available payer-driven quality measures influences patient-centered outcomes, including health-related quality of life (HRQOL), patient satisfaction, and treatment-related complications. METHODS: The Comparative Effectiveness Analysis of Surgery and Radiation study is a population-based, prospective cohort study that enrolled 3708 men with clinically localized prostate cancer during 2011 and 2012, of whom 2601 completed the 1-year survey and underwent complete chart abstraction. Compliance with 6 quality indicators endorsed by national consortia was assessed. Multivariable regression was used to determine the relationship between indicator compliance and Expanded Prostate Cancer Index Composite (EPIC-26) instrument summary scores, satisfaction scale scores (service satisfaction scale for cancer care), and treatment-related complications. RESULTS: Overall rates of compliance with these quality measures ranged between 64% and 88%. Three of the 6 measures were weakly associated with 1-year sexual function and bowel function scores (ß=-4.6, 1.69, and 2.93, respectively; P≤0.05), whereas the remaining measures had no significant relationship with patient-reported HRQOL outcomes. Satisfaction scores and treatment-related complications were not associated with quality measure compliance. CONCLUSIONS: Compliance with available nationally endorsed quality indicators, which were designed to incentivize effective and efficient care, was not associated with clinically important changes in patient-centered outcomes (HRQOL, satisfaction, or complications) within 1-year.

Predicting the Risk of Breakthrough Urinary Tract Infections: Primary Vesicoureteral Reflux.

PURPOSE: We constructed a risk prediction instrument stratifying patients with primary vesicoureteral reflux into groups according to their 2-year probability of breakthrough urinary tract infection. MATERIALS AND METHODS: Demographic and clinical information was retrospectively collected in children diagnosed with primary vesicoureteral reflux and followed for 2 years. Bivariate and binary logistic regression analyses were performed to identify factors associated with breakthrough urinary tract infection. The final regression model was used to compute an estimation of the 2-year probability of breakthrough urinary tract infection for each subject. Accuracy of the binary classifier for breakthrough urinary tract infection was evaluated using receiver operator curve analysis. Three distinct risk groups were identified. The model was then validated in a prospective cohort. RESULTS: A total of 252 bivariate analyses showed that high grade (IV or V) vesicoureteral reflux (OR 9.4, 95% CI 3.8-23.5, p <0.001), presentation after urinary tract infection (OR 5.3, 95% CI 1.1-24.7, p = 0.034) and female gender (OR 2.6, 95% CI 0.097-7.11, p <0.054) were important risk factors for breakthrough urinary tract infection. Subgroup analysis revealed bladder and bowel dysfunction was a significant risk factor more pronounced in low grade (I to III) vesicoureteral reflux (OR 2.8, p = 0.018). The estimation model was applied for prospective validation, which demonstrated predicted vs actual 2-year breakthrough urinary tract infection rates of 19% vs 21%. Stratifying the patients into 3 risk groups based on parameters in the risk model showed 2-year risk for breakthrough urinary tract infection was 8.6%, 26.0% and 62.5% in the low, intermediate and high risk groups, respectively. CONCLUSIONS: This proposed risk stratification and probability model allows prediction of 2-year risk of patient breakthrough urinary tract infection to better inform parents of possible outcomes and treatment strategies.

Perioperative goal-directed therapy and postoperative outcomes in patients undergoing high-risk abdominal surgery: a historical-prospective, comparative effectiveness study.

INTRODUCTION: Perioperative goal-directed therapy (PGDT) may improve postoperative outcome in high-risk surgery patients but its adoption has been slow. In 2012, we initiated a performance improvement (PI) project focusing on the implementation of PGDT during high-risk abdominal surgeries. The objective of the present study was to evaluate the effectiveness of this intervention. METHODS: This is a historical prospective quality improvement study. The goal of this initiative was to standardize the way fluid management and hemodynamic optimization are conducted during high-risk abdominal surgery in the Departments of Anesthesiology and Surgery at the University of California Irvine. For fluid management, the protocol consisted in standardized baseline crystalloid administration of 3 ml/kg/hour and any additional boluses based on PGDT. The impact of the intervention was assessed on the length of stay in the hospital (LOS) and post-operative complications (NSQIP database). RESULTS: In the 1 year pre- and post-implementation periods, 128 and 202 patients were included. The average volume of fluid administered during the case was 9.9 (7.1-13.0) ml/kg/hour in the pre-implementation period and 6.6 (4.7-9.5) ml/kg/hour in the post-implementation period (p < 0.01). LOS decreased from 10 (6-16) days to 7 (5-11) days (p = 0.0001). Based on the multiple linear regression analysis, the estimated coefficient for intervention was 0.203 (SE = 0.054, p = 0.0002) indicating that, with the other conditions being held the same, introducing intervention reduced LOS by 18% (95% confidence interval 9-27%). The incidence of NSQIP complications decreased from 39% to 25% (p = 0.04). CONCLUSION: These results suggest that the implementation of a PI program focusing on the implementation of PGDT can transform fluid administration patterns and improve postoperative outcome in patients undergoing high-risk abdominal surgeries. TRIAL REGISTRATION: Clinicaltrials.gov NCT02057653. Registered 17 December 2013.

Mental health symptoms and patient-reported diabetes symptom burden: implications for medication regimen changes.

AIMS: To examine the relative contribution of glycaemic control (HbA1C) and depressive symptoms on diabetes-related symptom burden (hypoglycaemia and hyperglycaemia) in order to guide medication modification. METHODS: Secondary analysis of medical records data and questionnaires collected from a racially/ethnically diverse sample of adult patients with type 2 diabetes (n = 710) from seven outpatient clinics affiliated with an academic medical centre over a 1-year period as part of the Reducing Racial Disparities in Diabetes: Coached Care (R2D2C2) study. RESULTS: Results from linear regression analysis revealed that patients with high levels of depressive symptoms had more diabetes-related symptom burden (both hypoglycaemia and hyperglycaemia) than patients with low levels of depressive symptoms (ßs = 0.09-0.17, Ps < 0.02). Furthermore, results from two logistic regression analyses suggested that the odds of regimen intensification at 1-year follow-up was marginally associated with patient-reported symptoms of hypoglycaemia [adjusted odds ratio (aOR) = 1.24, 95% CI: 0.98-1.58; P = 0.08] and hyperglycaemia (aOR = 1.21, 95% CI: 1.00-1.46; P = 0.05), after controlling for patients' HbA1C, comorbidity, insulin use and demographics. These associations, however, were diminished for patients with high self-reported hypoglycaemia and high levels of depressive symptoms, but not low depressive symptoms (interaction terms for hypoglycaemia by depressive symptoms, aOR = 0.98, 95% CI: 0.97-0.99; P = 0.03). CONCLUSIONS: Mental health symptoms are associated with higher levels of patient-reported of diabetes-related symptoms, but the association between diabetes-related symptoms and subsequent regimen modifications is diminished in patients with greater depressive symptoms. Clinicians should focus attention on identifying and treating patients' mental health concerns in order to address the role of diabetes-related symptom burden in guiding physician medication prescribing behaviour.

Contemporary prevalence of pretreatment urinary, sexual, hormonal, and bowel dysfunction: Defining the population at risk for harms of prostate cancer treatment.

BACKGROUND: The authors investigated the prevalence of pretreatment urinary, sexual, hormonal, and bowel dysfunction in a contemporary, population-based prostate cancer cohort. They also explored the associations between baseline function and age, comorbidity, and timing of baseline survey completion with respect to treatment. METHODS: The Comparative Effectiveness Analysis of Surgery and Radiation (CEASAR) study is a population-based, prospective cohort study that enrolled 3691 men with incident prostate cancer during 2011 and 2012. Pretreatment function was ascertained using the Expanded Prostate Cancer Index-26 (EPIC-26). Data were stratified by age, comorbidity, and timing of baseline survey completion with respect to treatment. Unadjusted and multivariable linear regression analyses were performed to evaluate the relations between exposures and pretreatment function. RESULTS: After applying exclusion criteria, the study cohort comprised 3072 men. A strikingly high proportion of men reported inability to obtain erections satisfactory for intercourse (45%) and some degree of urinary incontinence (17%) at baseline. Sexual function was particularly age-sensitive, with patients aged ≤60 years reporting summary scores in excess of 30 points higher than patients aged ≥75 years (P < .001). Compared with the healthiest men, highly comorbid patients reported less favorable function in each domain, including urinary incontinence (summary score, 89.5 vs 74.1; P < .001) and sexual function (summary score, 70.8 vs 32.9; P < .001). Although statistically significant differences in summary scores were identified between patients who completed the baseline questionnaire before treatment (52%) versus after treatment (48%), the absolute differences were small (range, 1-3 points). CONCLUSIONS: Patients with newly diagnosed prostate cancer exhibit a wide distribution of pretreatment function. The current data may be used to redefine the population "at risk" for treatment-related harms.

A framework for crafting clinical practice guidelines that are relevant to the care and management of people with multimorbidity.

Many patients of all ages have multiple conditions, yet clinicians often lack explicit guidance on how to approach clinical decision-making for such people. Most recommendations from clinical practice guidelines (CPGs) focus on the management of single diseases, and may be harmful or impractical for patients with multimorbidity. A major barrier to the development of guidance for people with multimorbidity stems from the fact that the evidence underlying CPGs derives from studies predominantly focused on the management of a single disease. In this paper, the investigators from the Improving Guidelines for Multimorbid Patients Study Group present consensus-based recommendations for guideline developers to make guidelines more useful for the care of people with multimorbidity. In an iterative process informed by review of key literature and experience, we drafted a list of issues and possible approaches for addressing important coexisting conditions in each step of the guideline development process, with a focus on considering relevant interactions between the conditions, their treatments and their outcomes. The recommended approaches address consideration of coexisting conditions at all major steps in CPG development, from nominating and scoping the topic, commissioning the work group, refining key questions, ranking importance of outcomes, conducting systematic reviews, assessing quality of evidence and applicability, summarizing benefits and harms, to formulating recommendations and grading their strength. The list of issues and recommendations was reviewed and refined iteratively by stakeholders. This framework acknowledges the challenges faced by CPG developers who must make complex judgments in the absence of high-quality or direct evidence. These recommendations require validation through implementation, evaluation and refinement.

When Will Real-World Data Fulfill Its Promise to Provide Timely Insights in Oncology?

Randomized trials provide high-quality, internally consistent data on selected clinical questions, but lack generalizability for the aging population who are most often diagnosed with cancer and have comorbid conditions that may affect the interpretation of treatment benefit. The need for high-quality, relevant, and timely data is greater than ever. Promising solutions lie in the collection and analysis of real-world data (RWD), which can potentially provide timely insights about the patient's course during and after initial treatment and the outcomes of important subgroups such as the elderly, rural populations, children, and patients with greater social health needs. However, to inform practice and policy, real-world evidence must be created from trustworthy and comprehensive sources of RWD; these may include pragmatic clinical trials, registries, prospective observational studies, electronic health records (EHRs), administrative claims, and digital technologies. There are unique challenges in oncology since key parameters (eg, cancer stage, biomarker status, genomic assays, imaging response, side effects, quality of life) are not recorded, siloed in inaccessible documents, or available only as free text or unstructured reports in the EHR. Advances in analytics, such as artificial intelligence, may greatly enhance the ability to obtain more granular information from EHRs and support integrated diagnostics; however, they will need to be validated purpose by purpose. We recommend a commitment to standardizing data across sources and building infrastructures that can produce fit-for-purpose RWD that will provide timely understanding of the effectiveness of individual interventions.