Functional Outcomes After Localized Prostate Cancer Treatment.

Importance: Adverse outcomes associated with treatments for localized prostate cancer remain unclear. Objective: To compare rates of adverse functional outcomes between specific treatments for localized prostate cancer. Design, Setting, and Participants: An observational cohort study using data from 5 US Surveillance, Epidemiology, and End Results Program registries. Participants were treated for localized prostate cancer between 2011 and 2012. At baseline, 1877 had favorable-prognosis prostate cancer (defined as cT1-cT2bN0M0, prostate-specific antigen level <20 ng/mL, and grade group 1-2) and 568 had unfavorable-prognosis prostate cancer (defined as cT2cN0M0, prostate-specific antigen level of 20-50 ng/mL, or grade group 3-5). Follow-up data were collected by questionnaire through February 1, 2022. Exposures: Radical prostatectomy (n = 1043), external beam radiotherapy (n = 359), brachytherapy (n = 96), or active surveillance (n = 379) for favorable-prognosis disease and radical prostatectomy (n = 362) or external beam radiotherapy with androgen deprivation therapy (n = 206) for unfavorable-prognosis disease. Main Outcomes and Measures: Outcomes were patient-reported sexual, urinary, bowel, and hormone function measured using the 26-item Expanded Prostate Cancer Index Composite (range, 0-100; 100 = best). Associations of specific therapies with each outcome were estimated and compared at 10 years after treatment, adjusting for corresponding baseline scores, and patient and tumor characteristics. Minimum clinically important differences were 10 to 12 for sexual function, 6 to 9 for urinary incontinence, 5 to 7 for urinary irritation, and 4 to 6 for bowel and hormone function. Results: A total of 2445 patients with localized prostate cancer (median age, 64 years; 14% Black, 8% Hispanic) were included and followed up for a median of 9.5 years. Among 1877 patients with favorable prognosis, radical prostatectomy was associated with worse urinary incontinence (adjusted mean difference, -12.1 [95% CI, -16.2 to -8.0]), but not worse sexual function (adjusted mean difference, -7.2 [95% CI, -12.3 to -2.0]), compared with active surveillance. Among 568 patients with unfavorable prognosis, radical prostatectomy was associated with worse urinary incontinence (adjusted mean difference, -26.6 [95% CI, -35.0 to -18.2]), but not worse sexual function (adjusted mean difference, -1.4 [95% CI, -11.1 to 8.3), compared with external beam radiotherapy with androgen deprivation therapy. Among patients with unfavorable prognosis, external beam radiotherapy with androgen deprivation therapy was associated with worse bowel (adjusted mean difference, -4.9 [95% CI, -9.2 to -0.7]) and hormone (adjusted mean difference, -4.9 [95% CI, -9.5 to -0.3]) function compared with radical prostatectomy. Conclusions and Relevance: Among patients treated for localized prostate cancer, radical prostatectomy was associated with worse urinary incontinence but not worse sexual function at 10-year follow-up compared with radiotherapy or surveillance among people with more favorable prognosis and compared with radiotherapy for those with unfavorable prognosis. Among men with unfavorable-prognosis disease, external beam radiotherapy with androgen deprivation therapy was associated with worse bowel and hormone function at 10-year follow-up compared with radical prostatectomy.

Navigational Bronchoscopy versus Computed Tomography-guided Transthoracic Needle Biopsy for the Diagnosis of Indeterminate Lung Nodules: protocol and rationale for the VERITAS multicenter randomized trial.

Background: Lung nodule incidence is increasing. Many nodules require biopsy to discriminate between benign and malignant etiologies. The gold-standard for minimally invasive biopsy, computed tomography-guided transthoracic needle biopsy (CT-TTNB), has never been directly compared to navigational bronchoscopy, a modality which has recently seen rapid technological innovation and is associated with improving diagnostic yield and lower complication rate. Current estimates of the diagnostic utility of both modalities are based largely on non-comparative data with significant risk for selection, referral, and publication biases. Methods: The VERITAS trial (na V igation E ndoscopy to R each Indeterminate lung nodules versus T ransthoracic needle A spiration, a randomized controlled S tudy) is a multicenter, 1:1 randomized, parallel-group trial designed to ascertain whether electromagnetic navigational bronchoscopy with integrated digital tomosynthesis is noninferior to CT-TTNB for the diagnosis of peripheral lung nodules 10-30 mm in diameter with pre-test probability of malignancy of at least 10%. The primary endpoint is diagnostic accuracy through 12 months follow-up. Secondary endpoints include diagnostic yield, complication rate, procedure duration, need for additional invasive diagnostic procedures, and radiation exposure. Discussion: The results of this rigorously designed trial will provide high-quality data regarding the management of lung nodules, a common clinical entity which often represents the earliest and most treatable stage of lung cancer. Several design challenges are described. Notably, all nodules are centrally reviewed by an independent interventional pulmonology and radiology adjudication panel relying on pre-specified exclusions to ensure enrolled nodules are amenable to sampling by both modalities while simultaneously protecting against selection bias favoring either modality. Conservative diagnostic yield and accuracy definitions with pre-specified criteria for what non-malignant findings may be considered diagnostic were chosen to avoid inflation of estimates of diagnostic utility. Trial registration: ClinicalTrials.gov NCT04250194.

Commercially Available Mobile Apps With Family Behavioral Goal Setting and Tracking for Parents: Review and Quality Evaluation.

BACKGROUND: Goal setting and tracking are well established behavior change techniques. Little is known about the extent to which commercially available mobile apps are designed to guide parents in using these strategies, their evidence base, and their quality. OBJECTIVE: This study aims to review commercially available apps that target parents in relation to setting and tracking behavioral goals for their children. The objectives were to classify the apps' general characteristics, features, evidence base, and target behaviors and assess app quality overall and separately for apps that target health-related behaviors (HRBs) and apps without a health-related behavior (WHRB). METHODS: Apps were identified using keyword searches in the Apple App Store and Google Play in the United States. Apps were included if their primary purpose was to assist with setting goals, tracking goals, tracking behaviors, or giving feedback pertaining to goals for children by parents. App characteristics and common features were documented and summarized. Two reviewers assessed app quality using the Mobile App Rating Scale (MARS). Descriptive statistics summarized the MARS total score, 4 quality subscales, and 6 app-specific items that reflect the perceived impact of the app on goal setting and tracking, overall and with subgroup analysis for HRB and WHRB apps. RESULTS: Of the 21 apps identified, 16 (76%) met the review criteria. Overall, 9 apps defined and targeted the following HRBs: nutrition and mealtime (6/16, 38%), physical activity and screen time (5/16, 31%), sleep (7/16, 44%), and personal hygiene (6/16, 38%). Three apps targeted specific age groups (2 apps were for children aged 6-13 years and 1 app was for children aged ≥4 years). None of the apps provided tailored assessments or guidance for goal setting. None of the apps indicated that they were intended for the involvement of a health professional or had been tested for efficacy. The MARS total score indicated moderate app quality overall (mean 3.42, SD 0.49) and ranged from 2.5 to 4.2 out of 5 points. The Habitz app ranked highest on the MARS total score among HRB apps (score=4.2), whereas Thumsters ranked highest (score=3.9) among the WHRB apps. Subgroup analysis revealed a pattern of higher quality ratings in the HRB group than the WHRB group, including the mean MARS total score (mean 3.67, SD 0.34 vs mean 3.09, SD 0.46; P=.02); the engagement and information subscales; and the app-specific items about perceived impact on knowledge, attitudes, and behavior change. CONCLUSIONS: Several high-quality commercially available apps target parents to facilitate goal setting and tracking for child behavior change related to both health and nonhealth behaviors. However, the apps lack evidence of efficacy. Future research should address this gap, particularly targeting parents of young children, and consider individually tailored guided goal setting and involvement of health professionals.

Hypothesis testing procedure for binary and multi-class F1 -scores in the paired design.

In modern medicine, medical tests are used for various purposes including diagnosis, disease screening, prognosis, and risk prediction. To quantify the performance of the binary medical test, we often use sensitivity, specificity, and negative and positive predictive values as measures. Additionally, the F 1 $$ {F}_1 $$ -score, which is defined as the harmonic mean of precision (positive predictive value) and recall (sensitivity), has come to be used in the medical field due to its favorable characteristics. The F 1 $$ {F}_1 $$ -score has been extended for multi-class classification, and two types of F 1 $$ {F}_1 $$ -scores have been proposed for multi-class classification: a micro-averaged F 1 $$ {F}_1 $$ -score and a macro-averaged F 1 $$ {F}_1 $$ -score. The micro-averaged F 1 $$ {F}_1 $$ -score pools per-sample classifications across classes and then calculates the overall F 1 $$ {F}_1 $$ -score, whereas the macro-averaged F 1 $$ {F}_1 $$ -score computes an arithmetic mean of the F 1 $$ {F}_1 $$ -scores for each class. Additionally, Sokolova and Lapalme 1 $$ {}^1 $$ gave an alternative definition of the macro-averaged F 1 $$ {F}_1 $$ -score as the harmonic mean of the arithmetic means of the precision and recall over classes. Although some statistical methods of inference for binary and multi-class F 1 $$ {F}_1 $$ -scores have been proposed, the methodology development of hypothesis testing procedure for them has not been fully progressing yet. Therefore, we aim to develop hypothesis testing procedure for comparing two F 1 $$ {F}_1 $$ -scores in paired study design based on the large sample multivariate central limit theorem.

Eosinophils Exert Antitumorigenic Effects in the Development of Esophageal Squamous Cell Carcinoma.

BACKGROUND AND AIMS: Eosinophils are present in several solid tumors and have context-dependent function. Our aim is to define the contribution of eosinophils in esophageal squamous cell carcinoma (ESCC), as their role in ESCC is unknown. METHODS: Eosinophils were enumerated in tissues from 2 ESCC cohorts. Mice were treated with 4-NQO for 8 weeks to induce precancer or 16 weeks to induce carcinoma. The eosinophil number was modified by a monoclonal antibody to interleukin-5 (IL5mAb), recombinant IL-5 (rIL-5), or genetically with eosinophil-deficient (ΔdblGATA) mice or mice deficient in eosinophil chemoattractant eotaxin-1 (Ccl11-/-). Esophageal tissue and eosinophil-specific RNA sequencing was performed to understand eosinophil function. Three-dimensional coculturing of eosinophils with precancer or cancer cells was done to ascertain direct effects of eosinophils. RESULTS: Activated eosinophils are present in higher numbers in early-stage vs late-stage ESCC. Mice treated with 4-NQO exhibit more esophageal eosinophils in precancer vs cancer. Correspondingly, epithelial cell Ccl11 expression is higher in mice with precancer. Eosinophil depletion using 3 mouse models (Ccl11-/- mice, ΔdblGATA mice, IL5mAb treatment) all display exacerbated 4-NQO tumorigenesis. Conversely, treatment with rIL-5 increases esophageal eosinophilia and protects against precancer and carcinoma. Tissue and eosinophil RNA sequencing revealed eosinophils drive oxidative stress in precancer. In vitro coculturing of eosinophils with precancer or cancer cells resulted in increased apoptosis in the presence of a degranulating agent, which is reversed with NAC, a reactive oxygen species scavenger. ΔdblGATA mice exhibited increased CD4 T cell infiltration, IL-17, and enrichment of IL-17 protumorigenic pathways. CONCLUSION: Eosinophils likely protect against ESCC through reactive oxygen species release during degranulation and suppression of IL-17.

Exposure to ambient air pollutants and acute respiratory distress syndrome risk in sepsis.

PURPOSE: Exposures to ambient air pollutants may prime the lung enhancing risk of acute respiratory distress syndrome (ARDS) in sepsis. Our objective was to determine the association of short-, medium-, and long-term pollutant exposures and ARDS risk in critically ill sepsis patients. METHODS: We analyzed a prospective cohort of 1858 critically ill patients with sepsis, and estimated short- (3 days), medium- (6 weeks), and long- (5 years) term exposures to ozone, nitrogen dioxide (NO2), sulfur dioxide (SO2), carbon monoxide (CO), particulate matter < 2.5 µm (PM2.5), and PM < 10 µm (PM10) using weighted averages of daily levels from monitors within 50 km of subjects' residences. Subjects were followed for 6 days for ARDS by the Berlin Criteria. The association between each pollutant and ARDS was determined using multivariable logistic regression adjusting for preselected confounders. In 764 subjects, we measured plasma concentrations of inflammatory proteins at presentation and tested for an association between pollutant exposure and protein concentration via linear regression. RESULTS: ARDS developed in 754 (41%) subjects. Short- and long-term exposures to SO2, NO2, and PM2.5 were associated with ARDS risk (SO2: odds ratio (OR) for the comparison of the 75-25th long-term exposure percentile 1.43 (95% confidence interval (CI) 1.16, 1.77); p < 0.01; NO2: 1.36 (1.06, 1.74); p = 0.04, PM2.5: 1.21 (1.04, 1.41); p = 0.03). Long-term exposures to these three pollutants were also associated with plasma interleukin-1 receptor antagonist and soluble tumor necrosis factor receptor-1 concentrations. CONCLUSION: Short and long-term exposures to ambient SO2, PM2.5, and NO2 are associated with increased ARDS risk in sepsis, representing potentially modifiable environmental risk factors for sepsis-associated ARDS.

Effect of propranolol and clonidine after severe traumatic brain injury: a pilot randomized clinical trial.

OBJECTIVE: To evaluate the safety, feasibility, and efficacy of combined adrenergic blockade with propranolol and clonidine in patients with severe traumatic brain injury (TBI). BACKGROUND: Administration of adrenergic blockade after severe TBI is common. To date, no prospective trial has rigorously evaluated this common therapy for benefit. METHODS: This phase II, single-center, double-blinded, pilot randomized placebo-controlled trial included patients aged 16-64 years with severe TBI (intracranial hemorrhage and Glasgow Coma Scale score ≤ 8) within 24 h of ICU admission. Patients received propranolol and clonidine or double placebo for 7 days. The primary outcome was ventilator-free days (VFDs) at 28 days. Secondary outcomes included catecholamine levels, hospital length of stay, mortality, and long-term functional status. A planned futility assessment was performed mid-study. RESULTS: Dose compliance was 99%, blinding was intact, and no open-label agents were used. No treatment patient experienced dysrhythmia, myocardial infarction, or cardiac arrest. The study was stopped for futility after enrolling 47 patients (26 placebo, 21 treatment), per a priori stopping rules. There was no significant difference in VFDs between treatment and control groups [0.3 days, 95% CI (- 5.4, 5.8), p = 1.0]. Other than improvement of features related to sympathetic hyperactivity (mean difference in Clinical Features Scale (CFS) 1.7 points, CI (0.4, 2.9), p = 0.012), there were no between-group differences in the secondary outcomes. CONCLUSION: Despite the safety and feasibility of adrenergic blockade with propranolol and clonidine after severe TBI, the intervention did not alter the VFD outcome. Given the widespread use of these agents in TBI care, a multi-center investigation is warranted to determine whether adrenergic blockade is of therapeutic benefit in patients with severe TBI. Trial Registration Number NCT01322048.

Eosinophils exert direct and indirect anti-tumorigenic effects in the development of esophageal squamous cell carcinoma.

Background/Aims: Eosinophils are present in several solid tumors and have context-dependent function. Our aim is to define the contribution of eosinophils in esophageal squamous cell carcinoma (ESCC), since their role in ESCC is unknown. Methods: Eosinophils were enumerated in tissues from two ESCC cohorts. Mice were treated with 4-nitroquinolone-1-oxide (4-NQO) for 8 weeks to induce pre-cancer or 16 weeks to induce carcinoma. Eosinophil number was modified by monoclonal antibody to IL-5 (IL5mAb), recombinant IL-5 (rIL-5), or genetically with eosinophil-deficient (ΔdblGATA) mice or mice deficient in eosinophil chemoattractant eotaxin-1 ( Ccl11 -/- ). Esophageal tissue and eosinophil specific RNA-sequencing was performed to understand eosinophil function. 3-D co-culturing of eosinophils with pre-cancer or cancer cells was done to ascertain direct effects of eosinophils. Results: Activated eosinophils are present in higher numbers in early stage versus late stage ESCC. Mice treated with 4-NQO exhibit more esophageal eosinophils in pre-cancer versus cancer. Correspondingly, epithelial cell Ccl11 expression is higher in mice with pre-cancer. Eosinophil depletion using three mouse models ( Ccl11 -/- mice, ΔdblGATA mice, IL5mAb treatment) all display exacerbated 4-NQO tumorigenesis. Conversely, treatment with rIL-5 increases esophageal eosinophilia and protects against pre-cancer and carcinoma. Tissue and eosinophil RNA-sequencing revealed eosinophils drive oxidative stress in pre-cancer. In vitro co-culturing of eosinophils with pre-cancer or cancer cells resulted in increased apoptosis in the presence of a degranulating agent, which is reversed with N-acetylcysteine, a reactive oxygen species (ROS) scavenger. ΔdblGATA mice exhibited increased CD4 T cell infiltration, IL-17, and enrichment of IL-17 pro-tumorigenic pathways. Conclusion: Eosinophils likely protect against ESCC through ROS release during degranulation and suppression of IL-17.

Feasibility of stone recurrence risk stratification using the recurrence of kidney stone (ROKS) nomogram.

This study seeks to evaluate the recurrence of kidney stones (ROKS) nomogram for risk stratification of recurrence in a retrospective study. To do this, we analyzed the performance of the 2018 ROKS nomogram in a case-control study of 200 patients (100 with and 100 without subsequent recurrence). All patients underwent kidney stone surgery between 2013 and 2015 and had at least 5 years of follow-up. We evaluated ROKS performance for prediction of recurrence at 2- and 5-year via area under the receiver operating curve (ROC-AUC). Specifically, we assessed the nomogram's potential for stratifying patients based on low or high risk of recurrence at: a) an optimized cutoff threshold (i.e., optimized for both sensitivity and specificity), and b) a sensitive cutoff threshold (i.e., high sensitivity (0.80) and low specificity). We found fair performance of the nomogram for recurrence prediction at 2 and 5 years (ROC-AUC of 0.67 and 0.63, respectively). At the optimized cutoff threshold, recurrence rates for the low and high-risk groups were 20 and 45% at 2 years, and 50 and 70% at 5 years, respectively. At the sensitive cutoff threshold, the corresponding recurrence rates for the low and high-risk groups were of 16 and 38% at 2 years, and 42 and 66% at 5 years, respectively. Kaplan-Meier analysis revealed a recurrence-free advantage between the groups for both cutoff thresholds (p < 0.01, Fig. 2). Therefore, we believe that the ROKS nomogram could facilitate risk stratification for stone recurrence and adherence to risk-based surveillance protocols.

Esophageal Epithelium and Lamina Propria Are Unevenly Involved in Eosinophilic Esophagitis.

BACKGROUND & AIMS: The nature of the involvement of esophageal tissue in eosinophilic esophagitis (EoE) is unclear. We estimated the intrabiopsy site agreements of the EoE Histologic Scoring System (EoEHSS) scores for the grade (degree) and stage (extent) of involvement of the esophageal epithelial and lamina propria and examined if the EoE activity status influenced the intrabiopsy site agreement. METHODS: Demographic, clinical, and EoEHSS scores collected as part of the prospective Outcome Measures for Eosinophilic Gastrointestinal Diseases Across Ages study were analyzed. A weighted Cohen's kappa agreement coefficient (k) was used to calculate the pairwise agreements for proximal:distal, proximal:middle, and middle:distal esophageal biopsy sites, separately for grade and stage scores, for each of the 8 components of EoEHSS. A k > 0.75 was considered uniform involvement. Inactive EoE was defined as fewer than 15 eosinophils per high-powered field. RESULTS: EoEHSS scores from 1263 esophageal biopsy specimens were analyzed. The k for the stage of involvement of the dilated intercellular spaces across all 3 sites in inactive EoE was consistently greater than 0.75 (range, 0.87-0.99). The k for lamina propria fibrosis was greater than 0.75 across some of the biopsy sites but not across all 3. Otherwise, the k for all other features, for both grade and stage, irrespective of the disease activity status, was 0.75 or less (range, 0.00-0.74). CONCLUSIONS: Except for the extent of involvement of dilated intercellular spaces in inactive EoE, the remaining epithelial features and lamina propria are involved unevenly across biopsy sites in EoE, irrespective of the disease activity status. This study enhances our understanding of the effects of EoE on esophageal tissue pathology.

Association between body mass index and localized prostate cancer management and disease-specific quality of life.

Purpose: The purpose of this work is to describe the association between body mass index (BMI) and (1) management option for localized prostate cancer (PCa) and (2) disease-specific quality of life (ds-QoL) after treatment or active surveillance. Subjects/patients and methods: We analysed data from men with localized PCa managed with radical prostatectomy (RP), radiation therapy (RT), or active surveillance (AS) in a prospective, population-based cohort study. We evaluated the association between BMI and management option with multivariable multinomial logistic regression analysis. The association between BMI and ds-QoL was assessed using multivariable longitudinal linear regression. Regression models were adjusted for baseline domain scores, demographics, and clinicopathologic characteristics. Results: A total of 2378 men were included (medians [quartiles]: age 64 [59-69] years; BMI 27 kg/m2; 77% were non-Hispanic white); 29% were obese (BMI ≥ 30). Accounting for demographic and clinicopathologic features, BMI ≥ 28 kg/m2 was inversely associated with the likelihood of receiving RP (compared with RT) and became statistically significant at BMI ≥ 33 kg/m2 (maximum adjusted relative risk ratio = 0.80, 95% CI 0.67 to 0.95, p = 0.013 for BMI ≥ 33 vs. 25). Conversely, BMI was not significantly associated with the likelihood of receiving AS compared with RT. After stratification by management option, obese men who underwent definitive treatment were not found to have clinically worse ds-QoL. Obese men initially on AS appeared to have worse urinary incontinence than nonobese men, but this was not significant on an as-treated sensitivity analysis. Conclusions: Among men with localized PCa, those with BMI ≥ 33 kg/m2 were less likely to receive surgery than radiation. Obesity was not associated with ds-QoL in men undergoing definitive treatment, nor in men who remained on AS.

Urinary supersaturation in a Randomized trial among Individuals with Nephrolithiasis comparing Empiric versus selective therapy (URINE): design and rationale of a clinical trial.

Clinical guidelines disagree on whether the identification of abnormal urine chemistries should occur before starting diet and medication interventions to prevent the recurrence of kidney stone events. We describe the rationale and design of the Urinary supersaturation in a Randomized trial among Individuals with Nephrolithiasis comparing Empiric versus selective therapy (URINE) study, a randomized trial comparing two multi-component interventions to improve urinary supersaturation. Participants are randomized (1:1 ratio) to the empiric or selective arm. The target sample size is 56 participants. Adults ≥ 18 years of age with idiopathic calcium stone disease and two symptomatic stone events within the previous 5 years. Exclusion criteria include systemic conditions predisposing to kidney stones and pharmacologic treatment for stone prevention at baseline. Participants in the empiric arm receive standard diet therapy recommendations, thiazide, and potassium citrate. Participants in the selective arm receive tailored diet and nutrient recommendations and medications based on baseline and 1-month follow-up of 24-h urine testing results. The primary endpoints are urinary supersaturations of calcium oxalate and calcium phosphate at 2 months of follow-up. Secondary endpoints include side effects, diet and medication adherence, and changes in 24-h urine volume, calcium, oxalate, citrate, and pH. Short-term changes in urinary supersaturation may not reflect changes in future risk of stone events. The URINE study will provide foundational data to compare the effectiveness of two prevention strategies for kidney stone disease.

Prostate volume, baseline urinary function, and their association with treatment choice and post-treatment urinary function in men treated for localized prostate cancer.

BACKGROUND: Benign prostatic hyperplasia, lower urinary tract symptoms, and prostate cancer often co-occur. Their effect on urinary function is an important consideration regarding prostate cancer treatment choices. While prostate volume (PV) and urinary symptoms are commonly used in treatment choice decision making, their association with post-treatment urinary function is unknown. We evaluated the associations between PV and baseline urinary function with treatment choice and post-treatment urinary function among men with localized prostate cancer. METHODS: We identified 1647 patients from CEASAR, a multicenter population-based, prospective cohort study of men with localized prostate cancer, for analysis. Primary outcomes were treatment choice and health-related quality of life (HRQOL) assessed by the 26-item Expanded Prostate Index Composite (EPIC-26) at pre-specified intervals up to 5 years. Multivariable analysis was performed, controlling for demographic and clinicopathologic features. RESULTS: Median baseline PV was 36 mL (IQR 27-48), and baseline urinary irritative/obstructive domain score was 87 (IQR 75-100). There was no observed clinically meaningful association between PV and treatment choice or post-treatment urinary function. Among patients with poor baseline urinary function, treatment with radiation or surgery was associated with statistically and clinically significant improvement in urinary function at 6 months which was durable through 5 years (improvement from baseline at 5 years: radiation 20.4 points, surgery 24.5 points). CONCLUSIONS: PV was not found to be associated with treatment modality or post-treatment urinary irritative/obstructive function among men treated for localized prostate cancer. Men with poor baseline urinary irritative/obstructive function improve after treatment with surgery or radiation therapy.

Association between adherence to radiation therapy quality metrics and patient reported outcomes in prostate cancer.

BACKGROUND: Prior studies have shown significant variability in the quality of prostate cancer care in the US with questionable associations between quality measures and patient reported outcomes. We evaluated the impact of compliance with nationally recognized radiation therapy (RT) quality measures on patient-reported health-related quality of life (HRQOL) outcomes in the Comparative Effectiveness Analysis of Surgery and Radiation (CEASAR) cohort. METHODS: CEASAR is a population-based, prospective cohort study of men with localized prostate cancer from which we identified 649 who received primary RT and completed HRQOL surveys for inclusion. Eight quality measures were identified based on national guidelines. We analyzed the impact of compliance with these measures on HRQOL assessed by the 26-item Expanded Prostate Index Composite at pre-specified intervals up to 5 years after treatment. Multivariable analysis was performed controlling for demographic and clinicopathologic features. RESULTS: Among eligible participants, 566 (87%) patients received external beam radiation therapy and 83 (13%) received brachytherapy. Median age was 69 years (interquartile range: 64-73), 33% had low-, 43% intermediate-, and 23% high-risk disease. 28% received care non-compliant with at least one measure. In multivariable analyses, while some statistically significant associations were identified, there were no clinically significant associations between compliance with evaluated RT quality measures and patient reported urinary irritative, urinary incontinence, bowel, sexual or hormonal function. CONCLUSIONS: Compliance with RT quality measures was not meaningfully associated with patient-reported outcomes after prostate cancer treatment. Further work is needed to identify patient-centered quality measures of prostate cancer care.

Post-Traumatic Stress Symptoms in Adolescent Hodgkin Lymphoma Survivors: A Report from Children's Oncology Group AHOD0031.

Purpose: The intrusive thoughts of cancer diagnosis, treatments, re-experiencing, and avoidance associated with post-traumatic stress symptoms (PTSS) can negatively affect Hodgkin lymphoma (HL) survivors. This study investigates the associations between experiences and beliefs and PTSS among adolescent survivors of intermediate-risk HL treated on the Children's Oncology Group (COG) AHOD0031 study. Methods: COG AHOD0031 participants completed self-report surveys at end of therapy concerning post-treatment medical conditions, activity limitations, fatigue, future concerns, exercise, and PTSS. Results: One thousand one hundred ten of 1721 participants in AHOD0031 completed the first survey at a median of 6.7 months post-diagnosis (interquartile range: 5.3-11.5 months), and of these, 736 (66.3%) completed a second survey at a median of 12.4 (10.1-17.6) months following the first. The mean PTSS score (ranging from 0 to 20) was 5.5 (standard deviation [SD] = 5.1) on survey 1 and 4.4 (SD = 4.8) on survey 2. Increased fatigue (odds ratio [OR] = 1.14, p < 0.01), concerns for the future (OR = 1.13, p < 0.01), activity limitations (OR = 1.05, p < 0.01), and relapse history (OR = 2.18, p < 0.05) were associated with higher PTSS scores in the initial survey. Increased fatigue (OR = 1.16, p < 0.01), concerns for the future (OR = 1.14, p < 0.01), activity limitations (OR = 1.05, p < 0.05), and higher PTSS scores on the first survey (OR = 1.19, p < 0.01) were associated with higher PTSS scores in the subsequent survey. Longer time since diagnosis (OR = 0.85, p < 0.05; OR = 0.84, p < 0.05) was associated with lower PTSS scores on both surveys. Conclusions: Based on our findings, future research should examine the onset and trajectory of PTSS among HL survivors, focusing on early recognition and intervention to improve quality of life.

Measurement of provider fidelity to immunization guidelines: a mixed-methods study on the feasibility of documenting patient refusals of the human papillomavirus vaccine.

BACKGROUND: Assessment and feedback is a common implementation strategy to improve healthcare provider fidelity to clinical guidelines. For immunization guidelines, fidelity is often measured with doses administered during eligible visits. Adding a patient refusal measure captures provider fidelity more completely (i.e., all instances of a provider recommending a vaccine, resulting in vaccination or refusal) and enables providers to track patient vaccine hesitancy patterns. However, many electronic health record (EHR) systems have no structured field to document multiple instances of refusals for specific vaccines, and existing billing codes for refusal are not vaccine specific. This study assessed the feasibility of a novel method for refusal documentation used in a study focused on human papillomavirus (HPV) vaccine. METHODS: An observational, descriptive-comparative, mixed-methods study design was used to conduct secondary data analysis from an implementation-effectiveness trial. The parent trial compared coach-based versus web-based practice facilitation, including assessment and feedback, to increase HPV vaccination in 21 community-based private pediatric practices. Providers were instructed to document initial HPV vaccine refusals in the EHR's immunization forms and subsequent refusals using dummy procedure codes, for use in assessment and feedback reports. This analysis examined adoption and maintenance of the refusal documentation method during eligible well visits, identified barriers and facilitators to documentation and described demographic patterns in patient refusals. RESULTS: Seven practices adopted the refusal documentation method. Among adopter practices, documented refusals started at 2.4% of eligible well visits at baseline, increased to 14.2% at the start of implementation, peaked at 24.0%, then declined to 18.8%. Barriers to refusal documentation included low prioritization, workflow integration and complication of the billing process. Facilitators included high motivation, documentation instructions and coach support. Among adopter practices, odds of refusing HPV vaccine were 25% higher for patients aged 15-17 years versus 11-12 years, and 18% lower for males versus females. CONCLUSIONS: We demonstrated the value of patient refusal documentation for measuring HPV vaccination guideline fidelity and ways that it can be improved in future research. Creation of vaccine-specific refusal billing codes or EHR adaptations to enable documenting multiple instances of specific vaccine refusals would facilitate consistent refusal documentation. Trial Registration NCT03399396 Registered in ClinicalTrials.gov on 1/16/2018.