Proceedings of the 13th annual conference of INEBRIA

CITATION: Watson, R., et al. 2016. Proceedings of the 13th annual conference of INEBRIA. Addiction Science & Clinical Practice, 11:13, doi:10.1186/s13722-016-0062-9.The original publication is available at https://ascpjournal.biomedcentral.comENGLISH SUMMARY : Meeting abstracts.https://ascpjournal.biomedcentral.com/articles/10.1186/s13722-016-0062-9Publisher's versio

Hidden Mortality Attributable to Rocky Mountain Spotted Fever: Immunohistochemical Detection of Fatal, Serologically Unconfirmed Disease

Rocky Mountain spotted fever (RMSF) is the most severe tickborne infection in the United States and is a nationally notifiable disease. Since 1981, the annual case-fatality ratio for RMSF has been determined from laboratory-confirmed cases reported to the Centers for Disease Control and Prevention (CDC). Herein, a description is given of patients with fatal, serologically unconfirmed RMSF for whom a diagnosis of RMSF was established by immunohistochemical (IHC) staining of tissues obtained at autopsy. During 1996-1997, acute-phase serum and tissue samples from patients with fatal disease compatible with RMSF were tested at the CDC. As determined by indirect immunofluorescence assay, no patient serum demonstrated IgG or IgM antibodies reactive with Rickettsia rickettsii at a diagnostic titer (i.e., ≥64); however, IHC staining confirmed diagnosis of RMSF in all patients. Polymerase chain reaction validated the IHC findings for 2 patients for whom appropriate samples were available for testing. These findings suggest that dependence on serologic assays and limited use of IHC staining for confirmation of fatal RMSF results in underestimates of mortality and of case-fatality ratios for this disease

Theoretical design of a space bioprocessing system to produce recombinant proteins

Abstract Space-based biomanufacturing has the potential to improve the sustainability of deep space exploration. To advance biomanufacturing, bioprocessing systems need to be developed for space applications. Here, commercial technologies were assessed to design space bioprocessing systems to supply a liquid amine carbon dioxide scrubber with active carbonic anhydrase produced recombinantly. Design workflows encompassed biomass dewatering of 1 L Escherichia coli cultures through to recombinant protein purification. Non-crew time equivalent system mass (ESM) analyses had limited utility for selecting specific technologies. Instead, bioprocessing system designs focused on minimizing complexity and enabling system versatility. Three designs that differed in biomass dewatering and protein purification approaches had nearly equivalent ESM of 357–522 kg eq. Values from the system complexity metric (SCM), technology readiness level (TRL), integration readiness level (IRL), and degree of crew assistance metric identified a simpler, less costly, and easier to operate design for automated biomass dewatering, cell lysis, and protein affinity purification

Development and Internal Validation of a Web-based Tool to Predict Sexual, Urinary, and Bowel Function Longitudinally After Radiation Therapy, Surgery, or Observation.

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/PCDSPred/.ConclusionsFunctional outcomes after treatment for localized prostate cancer can be predicted at the time of diagnosis based on age, race, PSA, biopsy grade, baseline function, and a general question regarding overall health. Providers and patients can use this prediction tool to inform shared decision making.Patient summaryIn this report, we studied patient-reported sexual, urinary, hormonal, and bowel function through 5 yr after treatment with radical prostatectomy, radiation therapy, or active surveillance for localized prostate cancer. We developed a web-based predictive tool that can be used to predict one's outcomes after treatment based on age, race, prostate-specific antigen, biopsy grade, pretreatment baseline function, and a general question regarding overall health. We hope both patients and providers can use this tool to better understand expected outcomes after treatment, further enhancing shared decision making between providers and patients

The Association Between Financial Toxicity and Treatment Regret in Men With Localized Prostate Cancer

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

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

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

Association between pelvic nodal radiotherapy and patient-reported functional outcomes through 5 years among men undergoing external-beam radiotherapy for prostate cancer: An assessment of the comparative effectiveness analysis of surgery and radiation (CEASAR) cohort.

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]; MCID 6) that resolved by 1 year and no differences in physical functioning or energy and fatigue.ConclusionThis prospective, population-based cohort study of men with localized prostate cancer treated with EBRT, showed no clinically important differences in disease-specific or general health-related quality of life with the addition of pelvic irradiation to prostate radiotherapy, supporting the use of pelvic radiotherapy when it may be of clinical benefit, such as men with increased risk of nodal involvement

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

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

Radiotherapy after radical prostatectomy: Effect of timing of postprostatectomy radiation on functional outcomes

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 decline in sexual domain score, with an adjusted mean decrease of 8.85 points (95% confidence interval [-19.8, 2.1]) from post-RP, pre-RT baseline.ConclusionsIn men with localized prostate cancer, post-RP RT was associated with significantly worse sexual, urinary, and bowel function domain scores at 5 years compared to RP alone. Radiation delayed for approximately 24 months after RP may be optimal for preserving erectile function compared to radiation administered closer to the time of RP