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BackgroundNoninvasive 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 resultsIn 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.ConclusionsPostdischarge 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.

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.

PurposeThe 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 methodsWe 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.ResultsA 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.ConclusionsAmong 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.

BackgroundThe role of pelvic irradiation in men receiving external beam radiotherapy (EBRT) for prostate cancer is unclear, in part due to a lack of data on patient-reported outcomes. We sought to compare functional outcomes for men receiving prostate and pelvic versus prostate-only radiotherapy, longitudinally over 5 years.Materials and methodsWe performed a population-based, prospective cohort study of men with clinically-localized prostate cancer undergoing EBRT. We examined the effect of prostate and pelvic (n = 102) versus prostate-only (n = 485) radiotherapy on patient-reported disease-specific (using the Expanded Prostate Cancer Index Composite[EPIC]-26) and general health-related (using the SF-36) function, over 5 years. Regression models were adjusted for outcome-specific baseline function, clinicopathologic characteristics, and androgen deprivation therapy (ADT).Results587 men (median [quartiles] age 69 [64-73] years) met inclusion criteria and completed ≥1 post-treatment survey. More men treated with prostate and pelvic radiotherapy had high-risk disease (58% vs. 18%, P < 0.01) and received ADT (75% vs. 41%, P < 0.01). These men reported worse sexual (6 months-5 years), hormonal (at 6 months), and physical (6 months-5 years) function. Accounting for baseline function, patient and tumor characteristics, and use of ADT, pelvic irradiation was not associated with statistically or clinically significant differences in bowel function, urinary incontinence, irritative voiding symptoms or sexual function through 5-years (all P > 0.05). Marginally clinically important differences were noted in hormonal function at 3-years (adjusted mean difference 4.7, 95% confidence interval [1.2-8.3]; minimally clinically important difference (MCID) 4 to 6) and 5-years (4.2, [0.4-8.0]) following treatment. After adjustment, there was a transient statistically significant, but not clinically important, difference in emotional well-being at 6 months (3.0, [0.19-5.8]; MCI

PurposeWe aimed to compare patient-reported mental health outcomes for men undergoing treatment for localized prostate cancer longitudinally over 5 years.Materials and methodsWe 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.ResultsA 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).ConclusionsThis 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.

BackgroundFinancial toxicity is emerging as an important patient-centered outcome and is understudied in prostate cancer patients. We sought to understand the association between financial burden and treatment regret in men with localized prostate cancer to better evaluate the role of financial discussions in patient counseling.MethodsUtilizing the Comparative Effectiveness Analysis of Surgery and Radiation dataset, we identified all men accrued between 2011 and 2012 who underwent surgery, radiation, or active surveillance for localized prostate cancer. Financial burden and treatment regret were assessed at 3- and 5-year follow-up. The association between financial burden and regret was assessed using multivariable longitudinal logistic regression controlling for demographic and disease characteristics, treatment, functional outcomes, and patient expectations.ResultsOf the 2924 eligible patients, regret and financial burden assessments for 3- and/or 5-year follow-up were available for 81% (n = 2359). After adjustment for relevant covariates, financial burden from "finances in general" was associated with treatment regret at 3 years (odds ratio [OR] = 2.47, 95% confidence interval [CI] = 1.33 to 4.57; P = .004); however, this association was no longer statistically significant at 5-year follow-up (OR = 1.19, 95% CI = 0.56 to 2.54; P = .7).ConclusionsIn this population-based sample of men with localized prostate cancer, we observed associations between financial burden and treatment regret. Our findings suggest indirect treatment costs, especially during the first 3 years after diagnosis, may impact patients more profoundly than direct costs and are important for inclusion in shared decision making.

Objective: Visual acuity (VA), the most common and simple measurement of visual function, is used worldwide in clinical practice and clinical research to quantify vision. However, rather than the full-letter width spacing standard on traditional visual acuity charts that might induce crowding, increased test-retest variability and bias, the visual acuity test on ColorDx is a single letter scoring, logMAR scaled and fast performed visual acuity measurement. The study aim is to study the reliability and validity of the visual acuity test on ColorDx on both healthy subjects and those with eye diseases. Methods: This is a prospective comparative clinical study. A total of 54 participants subjects were enrolled with their right eyes. All subjects underwent test and retest visual acuity measurements at 4 meters using ColorDx and Early Treatment Diabetic Retinopathy Study (ETDRS) charts. All results were scored with logMAR units. Paired sample t-test, Pearson’s correlation and independent sample t-test were performed.Results: The mean difference between the two visits of ColorDx was 0.03 ± 0.05 and that for ETDRS chart was 0.01 ± 0.03. None of the differences between the two visits were statistically significant (P>0.05). In Pearson correlation, r was 0.794 with a p-value less than 0.001. The mean differences between healthy and unhealthy groups were 0.23 for both tests. P-values were 0.03 and 0.01 of ETDRS chart and ColorDx, respectively.Conclusion: The visual acuity test on ColorDx is a simple, reliable and standardized procedure for visual acuity measurement. The pilot data in our study provides preliminary evidence that it can be used as a valid alternative to ETDRS chart worldwide without the Latin alphabet barrier. The simple operation could be suitable for fast-paced clinical settings. More disease groups and larger sample size need to be evaluated in future studies.

Objective: Visual acuity (VA), the most common and simple measurement of visual function, is used worldwide in clinical practice and clinical research to quantify vision. However, rather than the full-letter width spacing standard on traditional visual acuity charts that might induce crowding, increased test-retest variability and bias, the visual acuity test on ColorDx is a single letter scoring, logMAR scaled and fast performed visual acuity measurement. The study aim is to study the reliability and validity of the visual acuity test on ColorDx on both healthy subjects and those with eye diseases. Methods: This is a prospective comparative clinical study. A total of 54 participants subjects were enrolled with their right eyes. All subjects underwent test and retest visual acuity measurements at 4 meters using ColorDx and Early Treatment Diabetic Retinopathy Study (ETDRS) charts. All results were scored with logMAR units. Paired sample t-test, Pearson’s correlation and independent sample t-test were performed.Results: The mean difference between the two visits of ColorDx was 0.03 ± 0.05 and that for ETDRS chart was 0.01 ± 0.03. None of the differences between the two visits were statistically significant (P>0.05). In Pearson correlation, r was 0.794 with a p-value less than 0.001. The mean differences between healthy and unhealthy groups were 0.23 for both tests. P-values were 0.03 and 0.01 of ETDRS chart and ColorDx, respectively.Conclusion: The visual acuity test on ColorDx is a simple, reliable and standardized procedure for visual acuity measurement. The pilot data in our study provides preliminary evidence that it can be used as a valid alternative to ETDRS chart worldwide without the Latin alphabet barrier. The simple operation could be suitable for fast-paced clinical settings. More disease groups and larger sample size need to be evaluated in future studies.

Introduction and objectiveThe timing of radiotherapy (RT) after prostatectomy is controversial, and its effect on sexual, urinary, and bowel function is unknown. This study seeks to compare patient-reported functional outcomes after radical prostatectomy (RP) and postprostatectomy radiation as well as elucidate the timing of radiation to allow optimal recovery of function.MethodsThe Comparative Effectiveness Analysis of Surgery and Radiation (CEASAR) study is a prospective, population-based, observational study of men with localized prostate cancer. Patient-reported sexual, urinary, and bowel functional outcomes were measured using the 26-item Expanded Prostate Index Composite at baseline and at 6, 12, 36, and 60 months after enrollment. Functional outcomes were compared among men undergoing RP alone, post-RP adjuvant radiation (RP + aRT), and post-RP salvage radiation (RP + sRT) using multivariable models controlling for baseline clinical, demographic, and functional characteristics.ResultsAmong 1,482 CEASAR participants initially treated with RP for clinically localized prostate cancer, 11.5% (N = 170) received adjuvant (aRT, N = 57) or salvage (sRT, N = 113) radiation. Men who received post-RP RT had worse scores in all domains (sexual function [-9.0, 95% confidence interval {-14.5, -3.6}, P < 0.001], incontinence [-8.8, {-14.0, -3.6}, P < 0.001], irritative voiding [-5.9, {-9.0, -2.8}, P < 0.001], bowel irritative [-3.5, {-5.8, -1.2}, P = 0.002], and hormonal function [-4.5, {-7.2, -1.7}, P = 0.001]) compared to RP alone at 5 years of follow-up. Compared to men treated with RP alone in an adjusted linear model, sRT was associated with significantly worse scores in all functional domains. aRT was associated with significantly worse incontinence, urinary irritation, and hormonal function domain scores compared to RP alone at 5 years of follow-up. On multivariable modeling, RT administered approximately 24 months after RP was associated with the smallest d

BackgroundShared decision making to guide treatment of localized prostate cancer requires delivery of the anticipated quality of life (QOL) outcomes of contemporary treatment options (including radical prostatectomy [RP], intensity-modulated radiation therapy [RT], and active surveillance [AS]). Predicting these QOL outcomes based on personalized features is necessary.ObjectiveTo create an easy-to-use tool to predict personalized sexual, urinary, bowel, and hormonal function outcomes after RP, RT, and AS.Design, setting, and participantsA prospective, population-based cohort study was conducted utilizing US cancer registries of 2563 men diagnosed with localized prostate cancer in 2011-2012.InterventionPatient-reported urinary, sexual, and bowel function up to 5 yr after treatment.Outcome measurements and statistical analysisPatient-reported urinary, sexual, bowel, and hormonal function through 5 yr after treatment were collected using the 26-item Expanded Prostate Index Composite (EPIC-26) questionnaire. Comprehensive models to predict domain scores were fit, which included age, race, D'Amico classification, body mass index, EPIC-26 baseline function, treatment, and standardized scores measuring comorbidity, general QOL, and psychosocial health. We reduced these models by removing the instrument scores and replacing D'Amico classification with prostate-specific antigen (PSA) and Gleason score. For the final model, we performed bootstrap internal validation to assess model calibration from which an easy-to-use web-based tool was developed.Results and limitationsThe prediction models achieved bias-corrected R-squared values of 0.386, 0.232, 0.183, 0.214, and 0.309 for sexual function, urinary incontinence, urinary irritative, bowel, and hormonal domains, respectively. Differences in R-squared values between the comprehensive and parsimonious models were small in magnitude. Calibration was excellent. The web-based tool is available at https://statez.shinyapps.io/PCDSPr

PurposeThe 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 methodsUsing 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.ResultsFor 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.ConclusionsOur 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.

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.

BACKGROUND:Whether prostate cancer severity modifies patient-reported functional outcomes after radical prostatectomy (RP) or external beam radiotherapy (EBRT) for localized cancer is unknown. OBJECTIVE:The purpose of this study was to determine whether differences in predicted function over time between RP and EBRT varied by risk group. DESIGN, SETTING, AND PARTICIPANTS:The Comparative Effectiveness Analysis of Surgery and Radiation (CEASAR) study is a prospective, population-based, observational study that enrolled men with localized prostate cancer in 2011-2012. Among 2117 CEASAR participants who underwent RP or EBRT, 817 had low-risk, 902 intermediate-risk, and 398 high-risk disease. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS:Patient-reported, disease-specific function was measured using the 26-item Expanded Prostate Index Composite (at baseline and 6, 12, and 36 mo). Predicted function was estimated using regression models and compared by disease risk. RESULTS AND LIMITATIONS:Low-risk EBRT patients reported 3-yr sexual function scores 12 points higher than those of low-risk RP patients (RP, 39 points [95% confidence interval {CI}, 37-42] vs EBRT, 52 points [95% CI, 47-56]; p<0.001). The difference in 3-yr scores for high-risk patients was not clinically significant (RP, 32 points [95% CI, 28-35] vs EBRT, 38 points [95% CI, 33-42]; p=0.03). However, when using a commonly used binary definition of sexual function (erections firm enough for intercourse), no major differences were noted between RP and EBRT at 3 yr across low-, intermediate-, and high-risk disease strata. No clinically significant interactive effects between treatment and cancer severity were observed for incontinence, bowel, irritative voiding, and hormone domains. The primary limitation is the lack of firmly established thresholds for clinically significant differences in Expanded Prostate Index Composite domain scores. CONCLUSIONS:For men with low-risk prostate cancer, EBRT was associated w

PurposeTo compare patient-reported disease-specific functional outcomes after external beam radiation therapy (EBRT) and EBRT combined with low-dose-rate brachytherapy prostate boost (EB-LDR) among men with localized prostate cancer.Methods and materialsThe prospective, population-based Comparative Effectiveness Analysis of Surgery and Radiation study enrolled men with localized prostate cancer in 2011 to 2012. The 26-item Expanded Prostate Cancer Index Composite measured patient-reported disease-specific function at baseline and at 6, 12, and 36 months. Higher domain scores indicate better function. Minimal clinically important difference was defined as 6 for urinary incontinence, 5 for urinary irritative function, 4 for bowel function, 12 for sexual function, and 4 for hormonal function. Multivariable linear and logistic regression models were fit to estimate the effect of treatment on patient-reported outcomes.ResultsFive-hundred seventy-eight men received EBRT and 109 received EB-LDR. Median patient age was 69 years, and 70% had intermediate- or high-risk disease. Men in the EB-LDR group were younger (P < .001) and less likely to receive androgen deprivation therapy (P < .001). Baseline urinary, bowel, sexual, and hormonal function was similar between treatment groups (P > .05). On multivariable analyses, men receiving EB-LDR reported worse urinary irritative function at 6 months (adjusted mean difference [AMD] -14.4, P < .001), 12 months (AMD -12.9, P < .001), and 36 months (AMD -4.7, P = .034) than men receiving EBRT. At 12 months, men receiving EB-LDR reported worse bowel function (AMD -5.8, P = .002), but these differences were not seen at 36 months. There were no significant differences in sexual or hormone function between treatment groups.ConclusionsMen treated with EB-LDR report worse bowel function at 1 year and worse urinary irri

PurposeQuality measures represent the standards of appropriate treatment agreed upon by experts in the field and often supported by data. The extent to which providers in the community adhere to quality measures in radiation therapy (RT) is unknown.Methods and materialsThe Comparative Effectiveness Analysis of Surgery and Radiation study enrolled men with clinically localized prostate cancer in 2011 and 2012. Patients completed surveys and medical records were reviewed. Patients were risk-stratified according to D'Amico classification criteria. Patterns of care and compliance with 8 quality measures as endorsed by national consortia as of 2011 were assessed.ResultsOverall, 926 men underwent definitive RT (69% external beam radiation therapy [EBRT]), 17% brachytherapy (BT), and 14% combined EBRT and BT with considerable variation in radiation techniques across risk groups. Most men who received EBRT had dose-escalated EBRT (>75 Gy; 93%) delivered with conventional fractionation (<2 Gy; 95%), intensity modulated RT (76%), and image guided RT (85%). Most men treated with BT received I125 (77%). Overall, 73% of the men received EBRT that was compliant with the quality measures (dose-escalation, image-guidance, appropriate use of androgen deprivation therapy, and appropriate treatment target) but only 60% of men received BT that was compliant with quality measures (postimplant dosimetry and appropriate dose). African-American men (64%) and other minorities (62%) were less likely than white men (77%) to receive EBRT that was compliant with quality measures.ConclusionsMost men who received RT for localized prostate cancer were treated with an appropriately high dose and received image guidance and intensity modulated RT. However, compliance with some nationally recognized quality measures was relatively low and varied by race. There are significant opportunities to improve the delivery of RT and especially for men of a minority race.

Background: Glioblastoma is a highly aggressive brain cancer that leads to death within 15 months of diagnosis. Despite active research in the field, effective treatment options are currently limited to surgery, radiotherapy, and chemotherapy. Recently, there has been a push towards characterizing glioblastoma tumors genetically, epigenetically, transcriptionally, and proteomically in order to develop new, more targeted and individualized therapeutic approaches to glioblastoma.Aims: The aim of this thesis is to develop a study proposal for the characterization of one of the genes believed to be over-expressed in glioblastoma, EMP2. The study proposed will evaluate EMP2 role’s in glioblastoma pathogenesis and evaluate the therapeutic potential of antibodies developed against EMP2 expressed on the glioblastoma surface membrane.Methods: In-vitro and in-vivo background studies performed in our labs as well as those found in the literature are presented and discussed as the foundation and groundwork for the proposed study. The study proposal is then outlined in detail.Results: The purpose of the proposed study is to demonstrate the efficacy of targeting EMP2 on glioblastoma tumor cells using an antibody against EMP2. A detailed description of the proposed study design is given followed by the dissemination and implementation potential of the results of this study. We hypothesize that the functional consequence of EMP2 up-regulation in glioblastoma cells is to orchestrate the membrane expression of proteins required for cell migration, invasion, and neoangiogenesis. Additionally, we predict that the expression of EMP2 can be therapeutically exploited as a novel treatment target using antibodies against EMP2.Discussion: Our results from the background studies and the expected results from the study proposal suggest that EMP2 may be a promising molecular therapeutic target in glioblastoma. Additional work will be needed to determine whether anti-EMP2 antibodies can be combi

Background: Glioblastoma is a highly aggressive brain cancer that leads to death within 15 months of diagnosis. Despite active research in the field, effective treatment options are currently limited to surgery, radiotherapy, and chemotherapy. Recently, there has been a push towards characterizing glioblastoma tumors genetically, epigenetically, transcriptionally, and proteomically in order to develop new, more targeted and individualized therapeutic approaches to glioblastoma.Aims: The aim of this thesis is to develop a study proposal for the characterization of one of the genes believed to be over-expressed in glioblastoma, EMP2. The study proposed will evaluate EMP2 role’s in glioblastoma pathogenesis and evaluate the therapeutic potential of antibodies developed against EMP2 expressed on the glioblastoma surface membrane.Methods: In-vitro and in-vivo background studies performed in our labs as well as those found in the literature are presented and discussed as the foundation and groundwork for the proposed study. The study proposal is then outlined in detail.Results: The purpose of the proposed study is to demonstrate the efficacy of targeting EMP2 on glioblastoma tumor cells using an antibody against EMP2. A detailed description of the proposed study design is given followed by the dissemination and implementation potential of the results of this study. We hypothesize that the functional consequence of EMP2 up-regulation in glioblastoma cells is to orchestrate the membrane expression of proteins required for cell migration, invasion, and neoangiogenesis. Additionally, we predict that the expression of EMP2 can be therapeutically exploited as a novel treatment target using antibodies against EMP2.Discussion: Our results from the background studies and the expected results from the study proposal suggest that EMP2 may be a promising molecular therapeutic target in glioblastoma. Additional work will be needed to determine whether anti-EMP2 antibodies can be combi

BackgroundRelatively little is known about the relationship between race/ethnicity and patient-reported outcomes after contemporary treatments for localized prostate cancer.ObjectiveTo test the hypothesis that treatment-related changes in urinary, bowel, sexual, and hormonal function vary by race/ethnicity.Design, setting, and participantsThe Comparative Effectiveness Analysis of Surgery and Radiation (CEASAR) study is a prospective, population-based, observational study that enrolled 3708 men diagnosed with localized prostate cancer in 2011-2012.Outcome measurements and statistical analysisPatient-reported disease-specific function was measured using the 26-item Expanded Prostate Index Composite (EPIC) at baseline and 6 and 12 mo after enrollment. Mean treatment differences in function were compared by race using risk-adjusted generalized estimating equations.Results and limitationsWhile all race/ethnic groups reported considerable declines in scores for urinary incontinence after radical prostatectomy (RP) when compared to active surveillance, African-American men reported a greater difference than white men did (adjusted difference-in-differences 8.4 points, 95% confidence interval 2.0-14.8; p=0.01). No difference in bother scores was noted and the overall proportion of explained variation attributable to race/ethnicity was relatively small in comparison to primary treatment and baseline function. No clinically significant racial variation was noted for the sexual, bowel, irritative voiding, or hormone domains. Limitations include the lack of well-established thresholds for clinical significance using the EPIC instrument.ConclusionWhile these data demonstrate that incontinence at 1 yr after RP may be worse for African-American compared to white men, the difference appears to be modest overall. Treatment selection and baseline function explain a much greater proportion of the variation in function after treatment.Patient summaryWe observed that the effect of treat

ImportanceUnderstanding the adverse effects of contemporary approaches to localized prostate cancer treatment could inform shared decision making.ObjectiveTo compare functional outcomes and adverse effects associated with radical prostatectomy, external beam radiation therapy (EBRT), and active surveillance.Design, setting, and participantsProspective, 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.ExposuresTreatment with radical prostatectomy, EBRT, or active surveillance was ascertained within 1 year of diagnosis.Main outcomes and measuresPatient-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.ResultsThe 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 (-1

ObjectiveTo evaluate the influence of psychosocial factors such as prostate cancer (PCa) anxiety, social support, participation in medical decision-making (PDM), and educational level on patient decisions to discontinue PCa active surveillance (AS) in the absence of disease progression.MethodsThe Comparative Effectiveness Analysis of Surgery and Radiation study is a prospective, population-based cohort study of men with localized PCa diagnosed in 2011-2012. PCa anxiety, social support, PDM, educational level, and patient reasons for discontinuing AS were assessed through patient surveys. A Cox proportional hazards model examined the relationship between psychosocial variables and time to discontinuation of AS.ResultsOf 531 patients on AS, 165 (30.9%) underwent treatment after median follow-up of 37 months. Whereas 69% of patients cited only medical reasons for discontinuing AS, 31% cited at least 1 personal reason, and 8% cited personal reasons only. Patients with some college education discontinued AS significantly earlier (hazard ratio: 2.0, 95% confidence interval: 1.2, 3.2) than patients with less education. PCa anxiety, social support, and PDM were not associated with seeking treatment.ConclusionWe found that 31% of men who choose AS for PCa discontinue AS within 3 years. Eight percent of men who sought treatment did so in the absence of disease progression. Education, but not psychosocial factors, seems to influence definitive treatment-seeking. Future research is needed to understand how factors unrelated to disease severity influence treatment decisions among patients on AS to identify opportunities to improve adherence to AS.

PurposeRobotic 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 methodsSubjects 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.ResultsThe 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.ConclusionsThis population based study reveals that men undergoing robotic assisted radical prostatectomy likely experience less decline in early

ImportanceIt remains unclear whether telemonitoring approaches provide benefits for patients with heart failure (HF) after hospitalization.ObjectiveTo evaluate the effectiveness of a care transition intervention using remote patient monitoring in reducing 180-day all-cause readmissions among a broad population of older adults hospitalized with HF.Design, setting, and participantsWe randomized 1437 patients hospitalized for HF between October 12, 2011, and September 30, 2013, to the intervention arm (715 patients) or to the usual care arm (722 patients) of the Better Effectiveness After Transition-Heart Failure (BEAT-HF) study and observed them for 180 days. The dates of our study analysis were March 30, 2014, to October 1, 2015. The setting was 6 academic medical centers in California. Participants were hospitalized individuals 50 years or older who received active treatment for decompensated HF.InterventionsThe intervention combined health coaching telephone calls and telemonitoring. Telemonitoring used electronic equipment that collected daily information about blood pressure, heart rate, symptoms, and weight. Centralized registered nurses conducted telemonitoring reviews, protocolized actions, and telephone calls.Main outcomes and measuresThe primary outcome was readmission for any cause within 180 days after discharge. Secondary outcomes were all-cause readmission within 30 days, all-cause mortality at 30 and 180 days, and quality of life at 30 and 180 days.ResultsAmong 1437 participants, the median age was 73 years. Overall, 46.2% (664 of 1437) were female, and 22.0% (316 of 1437) were African American. The intervention and usual care groups did not differ significantly in readmissions for any cause 180 days after discharge, which occurred in 50.8% (363 of 715) and 49.2% (355 of 722) of patients, respectively (adjusted hazard ratio, 1.03; 95% CI, 0.88-1.20; P = .74). In secondary analyses, there were no significant differences in 30-day readmission or 180-day m

PurposeRobotic 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 methodsSubjects 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.ResultsThe 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.ConclusionsThis population based study reveals that men undergoing robotic assisted radical prostatectomy likely experience less decline in early

ImportanceIt remains unclear whether telemonitoring approaches provide benefits for patients with heart failure (HF) after hospitalization.ObjectiveTo evaluate the effectiveness of a care transition intervention using remote patient monitoring in reducing 180-day all-cause readmissions among a broad population of older adults hospitalized with HF.Design, setting, and participantsWe randomized 1437 patients hospitalized for HF between October 12, 2011, and September 30, 2013, to the intervention arm (715 patients) or to the usual care arm (722 patients) of the Better Effectiveness After Transition-Heart Failure (BEAT-HF) study and observed them for 180 days. The dates of our study analysis were March 30, 2014, to October 1, 2015. The setting was 6 academic medical centers in California. Participants were hospitalized individuals 50 years or older who received active treatment for decompensated HF.InterventionsThe intervention combined health coaching telephone calls and telemonitoring. Telemonitoring used electronic equipment that collected daily information about blood pressure, heart rate, symptoms, and weight. Centralized registered nurses conducted telemonitoring reviews, protocolized actions, and telephone calls.Main outcomes and measuresThe primary outcome was readmission for any cause within 180 days after discharge. Secondary outcomes were all-cause readmission within 30 days, all-cause mortality at 30 and 180 days, and quality of life at 30 and 180 days.ResultsAmong 1437 participants, the median age was 73 years. Overall, 46.2% (664 of 1437) were female, and 22.0% (316 of 1437) were African American. The intervention and usual care groups did not differ significantly in readmissions for any cause 180 days after discharge, which occurred in 50.8% (363 of 715) and 49.2% (355 of 722) of patients, respectively (adjusted hazard ratio, 1.03; 95% CI, 0.88-1.20; P = .74). In secondary analyses, there were no significant differences in 30-day readmission or 180-day m

PurposeWe 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 methodsDemographic 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.ResultsA 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.ConclusionsThis 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 t

BackgroundGender differences in dyslipidemia are widely documented, but the contributors to these differences are not well understood. This study examines whether differences in quality of care, intensity of lipid-lowering medication regimen, and medication adherence can explain this disparity.MethodsSecondary analysis of medical records data and questionnaires collected from adult patients with type 2 diabetes (n = 1,369) from seven outpatient clinics affiliated with an academic medical center as part of the Reducing Racial Disparities in Diabetes: Coached Care (R2D2C2) study. Primary outcome was low-density lipoprotein (LDL) cholesterol.FindingsWomen had higher LDL cholesterol levels than men (mean [SD], 101.2 [35.2] vs. 92.3 [33.0] mg/dL; p < .001), but were no less likely to receive recommended processes of diabetes care, to attain targets for glycemic control and blood pressure, or to be on intensive medication regimens. More women than men reported medication nonadherence related to cost (32.7% vs. 24.2%; p = .040) and related to side effects (47.2% vs. 36.8%; p = .024). For all patients, regimen intensity (p < .05) and nonadherence related to side effects (p < .01) were each associated with higher LDL cholesterol levels. The addition of a new lipid-lowering agent was associated with subsequent nonadherence related to side effects for women (p < .001), but not for men (p = .45; test for interaction p = .048).ConclusionsDespite comparable quality of diabetes care and regimen intensity for lipid management, women with diabetes experienced poorer lipid control than men. Medication nonadherence seemed to be a major contributor to dyslipidemia, particularly for women because of side effects associated with intensifying the lipid-lowering regimen.

BackgroundDespite the paramount importance of patient-reported outcomes, little is known about the evolution of patient-reported urinary and sexual function over time.ObjectiveTo evaluate differences in pretreatment urinary and sexual function in two population-based cohorts of men with prostate cancer enrolled nearly 20 yr apart.Design, setting, and participantsPatients were enrolled in the Prostate Cancer Outcomes Study (PCOS) or the Comparative Effectiveness Analysis of Surgery and Radiation (CEASAR) study, two population-based cohorts that enrolled patients with incident prostate cancer from 1994 to 1995 and from 2011 to 2012, respectively. Participants completed surveys at baseline and various time points thereafter.Outcome measurements and statistical analysisWe performed multivariable logistic and linear regression analysis to investigate differences in pretreatment function between studies.Results and limitationsThe study comprised 5469 men of whom 2334 (43%) were enrolled in PCOS and 3135 (57%) were enrolled in CEASAR. Self-reported urinary incontinence was higher in CEASAR compared with PCOS (7.7% vs 4.7%; adjusted odds ratio [OR]: 1.83; 95% confidence interval [CI], 1.39-2.43). Similarly, self-reported erectile dysfunction was more common among CEASAR participants (44.7% vs 24.0%) with an adjusted OR of 3.12 (95% CI, 2.68-3.64). Multivariable linear regression models revealed less favorable self-reported baseline function among CEASAR participants in the urinary incontinence and sexual function domains. The study is limited by its observational design and possibility of unmeasured confounding.ConclusionsReporting of pretreatment urinary incontinence and erectile dysfunction has increased over the past two decades. These findings may reflect sociological changes including heightened media attention and direct-to-consumer marketing, among other potential explanations.Patient summaryPatient reporting of urinary and sexual function has evolved and is likely c

BackgroundDespite the paramount importance of patient-reported outcomes, little is known about the evolution of patient-reported urinary and sexual function over time.ObjectiveTo evaluate differences in pretreatment urinary and sexual function in two population-based cohorts of men with prostate cancer enrolled nearly 20 yr apart.Design, setting, and participantsPatients were enrolled in the Prostate Cancer Outcomes Study (PCOS) or the Comparative Effectiveness Analysis of Surgery and Radiation (CEASAR) study, two population-based cohorts that enrolled patients with incident prostate cancer from 1994 to 1995 and from 2011 to 2012, respectively. Participants completed surveys at baseline and various time points thereafter.Outcome measurements and statistical analysisWe performed multivariable logistic and linear regression analysis to investigate differences in pretreatment function between studies.Results and limitationsThe study comprised 5469 men of whom 2334 (43%) were enrolled in PCOS and 3135 (57%) were enrolled in CEASAR. Self-reported urinary incontinence was higher in CEASAR compared with PCOS (7.7% vs 4.7%; adjusted odds ratio [OR]: 1.83; 95% confidence interval [CI], 1.39-2.43). Similarly, self-reported erectile dysfunction was more common among CEASAR participants (44.7% vs 24.0%) with an adjusted OR of 3.12 (95% CI, 2.68-3.64). Multivariable linear regression models revealed less favorable self-reported baseline function among CEASAR participants in the urinary incontinence and sexual function domains. The study is limited by its observational design and possibility of unmeasured confounding.ConclusionsReporting of pretreatment urinary incontinence and erectile dysfunction has increased over the past two decades. These findings may reflect sociological changes including heightened media attention and direct-to-consumer marketing, among other potential explanations.Patient summaryPatient reporting of urinary and sexual function has evolved and is likely c

BackgroundGender differences in dyslipidemia are widely documented, but the contributors to these differences are not well understood. This study examines whether differences in quality of care, intensity of lipid-lowering medication regimen, and medication adherence can explain this disparity.MethodsSecondary analysis of medical records data and questionnaires collected from adult patients with type 2 diabetes (n = 1,369) from seven outpatient clinics affiliated with an academic medical center as part of the Reducing Racial Disparities in Diabetes: Coached Care (R2D2C2) study. Primary outcome was low-density lipoprotein (LDL) cholesterol.FindingsWomen had higher LDL cholesterol levels than men (mean [SD], 101.2 [35.2] vs. 92.3 [33.0] mg/dL; p < .001), but were no less likely to receive recommended processes of diabetes care, to attain targets for glycemic control and blood pressure, or to be on intensive medication regimens. More women than men reported medication nonadherence related to cost (32.7% vs. 24.2%; p = .040) and related to side effects (47.2% vs. 36.8%; p = .024). For all patients, regimen intensity (p < .05) and nonadherence related to side effects (p < .01) were each associated with higher LDL cholesterol levels. The addition of a new lipid-lowering agent was associated with subsequent nonadherence related to side effects for women (p < .001), but not for men (p = .45; test for interaction p = .048).ConclusionsDespite comparable quality of diabetes care and regimen intensity for lipid management, women with diabetes experienced poorer lipid control than men. Medication nonadherence seemed to be a major contributor to dyslipidemia, particularly for women because of side effects associated with intensifying the lipid-lowering regimen.

PurposeWe 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 methodsDemographic 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.ResultsA 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.ConclusionsThis 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 t

BackgroundThe 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.MethodsThe 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.ResultsAfter 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).ConclusionsPatients 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 harm

PurposeThis study examines the use of complementary and alternative medicine (CAM) by ethnicity/race among patients with type 2 diabetes.Subjects and methodsFour hundred and ten (410) patients with type 2 diabetes recruited from an academic-medical center completed a survey assessing CAM use, diabetes status, and sociodemographic characteristics.ResultsSeveral significant ethnic/racial differences were observed in CAM use (both in the types of providers seen as well as in the herbs and dietary supplements used). Although White patients reported using CAM in addition to their diabetes medication (mean [SD] 4.9 [0.4] on a scale from 1=never to 5=always) more frequently than Mexican American patients (3.1 [1.6], p<.05), Mexican American patients (1.4 [1.1]) used CAM instead of their diabetes medications more frequently than non-Hispanic White patients (1.0 [0.1], p<.05). More Mexican American (66.7%) and Vietnamese American patients (73.7%) than non-Hispanic Whites (11.8%, p=.002) described CAM practitioners as being closer to their cultural traditions than Western practitioners, whereas Vietnamese [End Page 1941] patients were more likely to describe use of herbs and supplements as closer to their cultural traditions (84.5% versus 15.3% for White and 30.9% for Mexican American patients, p <.001).ConclusionsConsidering the variability and perceptions in CAM use, providers should discuss with their patients how their CAM use may influence diabetes management behaviors.

BackgroundThe 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.MethodsThe 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.ResultsAfter 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).ConclusionsPatients 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 harm

PurposeThis study examines the use of complementary and alternative medicine (CAM) by ethnicity/race among patients with type 2 diabetes.Subjects and methodsFour hundred and ten (410) patients with type 2 diabetes recruited from an academic-medical center completed a survey assessing CAM use, diabetes status, and sociodemographic characteristics.ResultsSeveral significant ethnic/racial differences were observed in CAM use (both in the types of providers seen as well as in the herbs and dietary supplements used). Although White patients reported using CAM in addition to their diabetes medication (mean [SD] 4.9 [0.4] on a scale from 1=never to 5=always) more frequently than Mexican American patients (3.1 [1.6], p<.05), Mexican American patients (1.4 [1.1]) used CAM instead of their diabetes medications more frequently than non-Hispanic White patients (1.0 [0.1], p<.05). More Mexican American (66.7%) and Vietnamese American patients (73.7%) than non-Hispanic Whites (11.8%, p=.002) described CAM practitioners as being closer to their cultural traditions than Western practitioners, whereas Vietnamese [End Page 1941] patients were more likely to describe use of herbs and supplements as closer to their cultural traditions (84.5% versus 15.3% for White and 30.9% for Mexican American patients, p <.001).ConclusionsConsidering the variability and perceptions in CAM use, providers should discuss with their patients how their CAM use may influence diabetes management behaviors.

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.

BackgroundWhile randomized controlled trials represent the highest level of evidence we can generate in comparative effectiveness research, there are clinical scenarios where this type of study design is not feasible. The Comparative Effectiveness Analyses of Surgery and Radiation in localized prostate cancer (CEASAR) study is an observational study designed to compare the effectiveness and harms of different treatments for localized prostate cancer, a clinical scenario in which randomized controlled trials have been difficult to execute and, when completed, have been difficult to generalize to the population at large.MethodsCEASAR employs a population-based, prospective cohort study design, using tumor registries as cohort inception tools. The primary outcome is quality of life after treatment, measured by validated instruments. Risk adjustment is facilitated by capture of traditional and nontraditional confounders before treatment and by propensity score analysis.ResultsWe have accrued a diverse, representative cohort of 3691 men in the USA with clinically localized prostate cancer. Half of the men invited to participate enrolled, and 86% of patients who enrolled have completed the 6-month survey.ConclusionChallenging comparative effectiveness research questions can be addressed using well-designed observational studies. The CEASAR study provides an opportunity to determine what treatments work best, for which patients, and in whose hands.

BackgroundWhile randomized controlled trials represent the highest level of evidence we can generate in comparative effectiveness research, there are clinical scenarios where this type of study design is not feasible. The Comparative Effectiveness Analyses of Surgery and Radiation in localized prostate cancer (CEASAR) study is an observational study designed to compare the effectiveness and harms of different treatments for localized prostate cancer, a clinical scenario in which randomized controlled trials have been difficult to execute and, when completed, have been difficult to generalize to the population at large.MethodsCEASAR employs a population-based, prospective cohort study design, using tumor registries as cohort inception tools. The primary outcome is quality of life after treatment, measured by validated instruments. Risk adjustment is facilitated by capture of traditional and nontraditional confounders before treatment and by propensity score analysis.ResultsWe have accrued a diverse, representative cohort of 3691 men in the USA with clinically localized prostate cancer. Half of the men invited to participate enrolled, and 86% of patients who enrolled have completed the 6-month survey.ConclusionChallenging comparative effectiveness research questions can be addressed using well-designed observational studies. The CEASAR study provides an opportunity to determine what treatments work best, for which patients, and in whose hands.

BackgroundThe Affordable Care Act is designed to decrease the numbers of uninsured patients in U.S. However, even with insurance, patients who have financial hardships may have difficulty obtaining their medications because of cost issues.ObjectiveAmong patients with type 2 diabetes, to examine the association between patients' self-reported financial pressures on cost-related medication non-adherence and glucose control. Additionally, to examine whether having insurance decrease the financial pressures of diabetes care.Design and participantsRacially/ethnically diverse patients (N = 1,361; 249 non-Hispanic whites, 194 Vietnamese, and 533 Mexican American) with type 2 diabetes were recruited from seven outpatient clinics for a cross-sectional, observational study.Key resultsAlthough both Vietnamese and Mexican-American patients reported having low annual incomes, more Mexican Americans reported the presence of financial barriers to getting medical care and perceived financial burden due to their diabetes, compared to whites and Vietnamese (p < 0.001). Over half (53.2%) of Mexican Americans reported cost-related non-adherence compared to 27.2% of white and 27.6% of Vietnamese patients (p < 0.001). Perceived financial burden was found to be associated with poor glucose control (HbA1c ≥8%), after adjusting for sociodemographic and health characteristics (aOR = 1.70, 95%CI 1.09-2.63), but not when adjusting for non-adherence. Similarly, a significant association between presence of financial barriers and HbA1c (aOR = 1.69, 95%CI 1.23-2.32) was attenuated with the inclusion of insurance status in the model. Being uninsured (aOR = 1.90, 95%CI 1.13-3.21) and non-adherent (aOR = 1.49, 95%CI 1.06-2.08) were each independently associated with HbA1c.ConclusionsWhile having health insurance coverage eliminated some of the financial barriers associated with having diabetes, low-income patients still faced significant financial burdens. Thus, providing health insurance to m

BackgroundThe Affordable Care Act is designed to decrease the numbers of uninsured patients in U.S. However, even with insurance, patients who have financial hardships may have difficulty obtaining their medications because of cost issues.ObjectiveAmong patients with type 2 diabetes, to examine the association between patients' self-reported financial pressures on cost-related medication non-adherence and glucose control. Additionally, to examine whether having insurance decrease the financial pressures of diabetes care.Design and participantsRacially/ethnically diverse patients (N = 1,361; 249 non-Hispanic whites, 194 Vietnamese, and 533 Mexican American) with type 2 diabetes were recruited from seven outpatient clinics for a cross-sectional, observational study.Key resultsAlthough both Vietnamese and Mexican-American patients reported having low annual incomes, more Mexican Americans reported the presence of financial barriers to getting medical care and perceived financial burden due to their diabetes, compared to whites and Vietnamese (p < 0.001). Over half (53.2%) of Mexican Americans reported cost-related non-adherence compared to 27.2% of white and 27.6% of Vietnamese patients (p < 0.001). Perceived financial burden was found to be associated with poor glucose control (HbA1c ≥8%), after adjusting for sociodemographic and health characteristics (aOR = 1.70, 95%CI 1.09-2.63), but not when adjusting for non-adherence. Similarly, a significant association between presence of financial barriers and HbA1c (aOR = 1.69, 95%CI 1.23-2.32) was attenuated with the inclusion of insurance status in the model. Being uninsured (aOR = 1.90, 95%CI 1.13-3.21) and non-adherent (aOR = 1.49, 95%CI 1.06-2.08) were each independently associated with HbA1c.ConclusionsWhile having health insurance coverage eliminated some of the financial barriers associated with having diabetes, low-income patients still faced significant financial burdens. Thus, providing health insurance to m

To examine racial/ethnic differences in the prevalence of depressive symptoms and in provider recognition of depression among Latino, Asian, and non-Hispanic white patients with type 2 diabetes.Patients (n = 1,209) with type 2 diabetes were recruited from five university-affiliated primary care clinics for an observational study.Vietnamese American (133, 59.4%) and Mexican American (351, 50.2%) patients were more likely to report symptoms consistent with clinical depression (Center for Epidemiological Studies Depression [CES-D] scale score ≥ 22) than non-Hispanic whites (119, 41.6%; F [2, 1206] = 8.05, P < 0.001). Despite comparable diabetes care, Vietnamese and Mexican patients with high depressive symptoms were less likely to be diagnosed and treated than non-Hispanic whites (all P values < 0.001). Minority patients who reported low levels of trust in their provider were less likely to have been diagnosed or treated for depression (adjusted odds ratio 0.65, 95% CI 0.44-0.98, P < 0.05).Innovative strategies are needed to improve recognition of depressive symptoms in minority patients.

To examine racial/ethnic differences in the prevalence of depressive symptoms and in provider recognition of depression among Latino, Asian, and non-Hispanic white patients with type 2 diabetes.Patients (n = 1,209) with type 2 diabetes were recruited from five university-affiliated primary care clinics for an observational study.Vietnamese American (133, 59.4%) and Mexican American (351, 50.2%) patients were more likely to report symptoms consistent with clinical depression (Center for Epidemiological Studies Depression [CES-D] scale score ≥ 22) than non-Hispanic whites (119, 41.6%; F [2, 1206] = 8.05, P < 0.001). Despite comparable diabetes care, Vietnamese and Mexican patients with high depressive symptoms were less likely to be diagnosed and treated than non-Hispanic whites (all P values < 0.001). Minority patients who reported low levels of trust in their provider were less likely to have been diagnosed or treated for depression (adjusted odds ratio 0.65, 95% CI 0.44-0.98, P < 0.05).Innovative strategies are needed to improve recognition of depressive symptoms in minority patients.

available at publisher's website.