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The TITAN study is a randomized, double-blind, placebo-controlled, multinational trial that evaluated apalutamide with androgen deprivation therapy in patients with metastatic castration-sensitive prostate cancer. At the first interim analysis in the Japanese subpopulation (median follow-up 25.7 months), there was an improvement in overall survival and radiological progression-free survival with apalutamide versus placebo. Here, we report the final analysis results for the Japanese subpopulation.Patients were randomized 1:1 to receive apalutamide 240 mg or placebo. After the first interim analysis, protocol treatment was unblinded, and crossover was allowed. Efficacy and safety were evaluated in the preplanned, event-driven final analysis.Fifty-one patients were Japanese (apalutamide n = 28; placebo n = 23). After a median follow-up of 46.0 months, the median overall survival was not reached neither in the apalutamide nor the placebo group; the hazard ratio was 0.45, favoring apalutamide, which was consistent with the overall population. Hazard ratios for time to cytotoxic chemotherapy (0.39), time to pain progression (0.87), and time to chronic opioid use (0.82) also favored apalutamide and were comparable with those of the overall population. Time to prostate-specific antigen progression and progression-free survival 2, respectively, was favored in the apalutamide group (0.21 and 0.44). Apalutamide was associated with higher incidences of rash and fracture in the Japanese subpopulation compared with the overall population.The efficacy of apalutamide with androgen deprivation therapy in Japanese patients was consistent with efficacy demonstrated in the overall population. No new safety concerns emerged with long-term follow-up.

Background: The behavioral model of health service use identified health needs, service preferences (predispositions), and service availability (enabling factors) as important predictors, but research has not conceptualized consistently each type of influence nor identified their separate effects on use of substance abuse and mental health services or their value in predicting service outcomes. Objectives: To test hypotheses predicting use of substance abuse and mental health services and residential stability and evaluate peer specialists’ impact. Research Design: Randomized trial of peer support added to standard case management in VA-supported housing program (Housing and Urban Development-VA Supportive Housing program). Subjects: One hundred sixty-six dually diagnosed Veterans in Housing and Urban Development-VA Supportive Housing program in 2 cities. Measures: Average VA service episodes for substance abuse and mental illness; residential instability; preferences for alcohol, drug, and psychological services; extent of alcohol, drug, and psychological problems; availability of a peer specialist. Results: Self-assessed health needs, mediated by service preferences, and assignment to a peer specialist predicted use of VA behavioral health services and residential stability, as did chronic medical problems, sex, and race. Conclusions: The behavioral model identifies major predictors of health service use and residential stability, but must recognize the mediating role of service preferences, the differing effects of alcohol and drug use, the unique influences of social background, and the importance of clinical judgment in needs assessment. Service availability and residential stability can be increased by proactive efforts involving peer specialists even in a health care system that provides services without a financial barrier.

Cancer health care disparities are complex, involve patient, clinician and health care system factors, and are defined as adverse differences in cancer outcomes. This analysis describes NCI's Healthcare Delivery Research Program's (HDRP) portfolio of disparities-focused research and identifies future research opportunities. Grants through HDRP (fiscal years 2012 to 2016) focused on detecting, understanding, and/or intervening on disparities in or among health disparity populations were reviewed by co-authors. Forty-eight funded grants were identified, coded, and characterized. Descriptive analyses are reported. Most studies focused on racial/ethnic minorities and socioeconomically disadvantaged groups. Colorectal, breast, and cervical cancers were most frequently examined. Almost 40% of studies addressed the intervening phase of the disparities research continuum. Few studies focused on clinician-level factors or involved the community in the research design. A sustained disparities research emphasis is essential to addressing the determinants of and cancer burden among health disparity populations across the cancer care continuum.

Peer specialists (PSs) are increasingly deployed in a variety of settings to provide patient-centered care. In the Veterans Health Administration (VHA), efforts are underway to integrate PSs into primary care settings. Little is known about the barriers and enablers to implementing PS services in primary care.To characterize barriers and enablers to implementing PSs in primary care.Qualitative study using semi-structured interviews.PSs and their supervisors from 25 VHA primary care settings.PSs and supervisors were interviewed about their experiences integrating PSs in primary care. Rapid analysis was conducted to identify barriers and enablers to PS integration, as well as to examine the role of external facilitation in implementation experiences.Fifty-two interviews were completed (25 PSs from 19 sites and 27 supervisors from 24 sites). Barriers and enablers to PS integration in VHA primary care settings included PS role clarity and constraints, provider buy-in, supervision, leadership support, and primary care culture. The barriers and enablers were consistent across both external facilitation and control sites.Results describe how the characteristics of the innovation, the recipients, and the context impact successful implementation of PSs in primary care settings. The identification of barriers and enablers holds promise for improving future efforts to embed PSs in primary care.This project is registered at ClinicalTrials.gov with number NCT02732600 (URL: https://clinicaltrials.gov/ct2/show/NCT02732600 ).

Apalutamide plus androgen-deprivation therapy (ADT) has been approved for treatment of patients with metastatic castration-sensitive prostate cancer (mCSPC) based on data from phase 3 TITAN study. This analysis was conducted to describe pharmacokinetics of apalutamide and N-desmethyl-apalutamide and explore relationships between apalutamide exposure and selected clinical efficacy and safety observations.1052 patients were randomized to apalutamide + ADT (n = 525) or placebo + ADT (n = 527). A previously developed population pharmacokinetic model was applied. Cox regression analysis investigated the relationships between apalutamide exposure and overall survival (OS; n = 1004) and radiographic progression-free survival (rPFS; n = 1003). Logistic regression analysis assessed the relationships between apalutamide exposure and selected clinically relevant adverse events (n = 1051).Apalutamide + ADT treatment was efficacious in extending rPFS and OS versus placebo + ADT. Within a relatively narrow apalutamide exposure range (coefficient of variation: 22%), no statistical association was detected between rPFS, OS and apalutamide exposure quartiles. Incidence of skin rash and pruritus increased significantly with increasing apalutamide exposure.Differences in apalutamide exposure were not associated with clinically relevant differences in rPFS or OS in patients with mCSPC. Patients with increased apalutamide exposure are more likely to develop skin rash and pruritus. Dose reductions may improve these adverse events, based on an individual risk-benefit approach.

African American women below screening age disproportionately face greater mortality from breast cancer relative to peers of other races and African American women of screening age. The current study examines breast cancer knowledge and health information seeking of African American women below screening age.We collected survey data from 99 African American women below screening age on their breast cancer knowledge and health information seeking behaviors. As secondary analysis, we harmonized data from a previous study to compare breast cancer knowledge between African American women below and of (N = 209) screening age.The average woman below screening age correctly answered 2.84 (SD=1.08) of six breast cancer knowledge items, 2.67 (SD=1.01) of five mammogram items, 1.44 (SD=0.86) of three treatment items, and had lower knowledge (p .001) in each area relative to screening age women. Women below screening age sought information primarily from medical providers and the internet.A strategy for eliminating early-onset breast cancer disparities impacting African American women is addressing the limited breast cancer knowledge in this age group. Practice Implications In addition to age-appropriate information for this group, guidance for medical providers would be beneficial, as providers are this group's most common source of health information.

Although peer specialists play an increasing role in mental health service delivery, little is known about the best program structures for maximizing effective service delivery. This study reports on qualitative data from a larger study on peer specialists working with veterans in a Veterans Affairs homelessness program who were dually diagnosed with substance abuse and mental health concerns. Peer specialists were trained to deliver a recovery support program that is carried out weekly over 9 months and includes 20 structured sessions using a workbook and 20 unstructured, individually planned sessions. A sample of 20 veterans who were in the program were interviewed, along with 8 case managers and 3 peer specialists involved with the program. Interview transcripts were coded for 3 elements of program structure: time, content, and delivery. Results show that the program structure allowed flexibility for individual needs and that the workbook sessions were useful. Veterans ascribed value to the peer specialist delivering the content, compared to working alone on the material. Deliberate use of unstructured time with the peer specialist was seen as reducing isolation, increasing community integration, and encouraging recovery activities. The weekly, dependable nature of the program was seen as highly positive, whereas the 9-month duration was seen as too short. All groups interviewed expressed satisfaction with the program, although the case managers reported some reservations related to supervision and boundaries. Results suggest that, compared to completely structured or unstructured approaches that are common for peer specialist services, a middle level of structure for peer specialist programs could be a useful alternative. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Objective: AI has demonstrated great promise in learning sophisticated features and relations in data that would otherwise remain hidden to the human eye. Here, we developed a proprietary AI-based multimodal approach to integrate clinical, digitized hematoxylin-eosin (H&E), and radiology bone scan (rBS) data for outcome prediction in ADT-treated nmCRPC patients. Identifying prostate cancer patients who may not benefit from ADT could improve the medical management of this disease beyond current definitive therapy. Methods: Patients in the ADT+placebo arm from SPARTAN clinical trial on nmCRPC with available clinical, H&E, and rBS were used (n=154). These patients were randomly divided into 70% (n=107) discovery and 30% (n=47) hold-out test datasets. Using the discovery set, we developed and trained a multimodal approach that combines survival convolutional neural networks (SCNNs1) and Cox proportional-hazards model (CPH) to learn ADT outcomes for overall survival (OS) and time to PSA progression (TTP) from the integration of imaging data and 11 traditional clinical features (e.g., tumor stage, Gleason score, PSA). The ability of the trained framework in predicting outcomes and risk stratification was evaluated on the hold-out set. Bootstrap analysis with Wilcoxon signed rank test was used to determine the significance of the multimodal framework’s performance improvement compared to clinical CPH. Results: The multimodal framework was predictive of ADT outcomes for OS and TTP in nmCRPC patients. In SPARTAN’s hold-out set, the multimodal framework significantly improved the predictive power of clinical CPH by 14%—16% across both outcomes (Wilcoxon signed rank P Conclusion: AI-based framework that learns from the integration of different data types improves outcome prediction in ADT-treated nmCRPC. The multimodal approach demonstrates promise in treatment decision support for the early use of androgen receptor-directed therapy and patient selection for clinical trials with novel treatment combinations. Reference: 1. Mobadersany, Pooya, et al. "Predicting cancer outcomes from histology and genomics using convolutional networks." Proceedings of the National Academy of Sciences 115.13 (2018): E2970-E2979. Conflict of interest statement P.M., J.L., D.G., C.A., S.M., S.B., M.K.Y., K.T., N.H., J.Z., J.G., N.K., and S.S.F.Y., are employees of Janssen Pharmaceutical, LLC. Citation Format: Pooya Mobadersany, Justin Lucas, Darshana Govind, Clemente Aguilar-Bonavides, Sharon McCarthy, Sabine Brookman-May, Margaret K. Yu, Ken Tian, Natalie Hutnick, Jose Zamalloa, Joel Greshock, Najat Khan, Stephen S.F. Yip. Artificial intelligence (AI)-based multimodal framework predicts androgen-deprivation therapy (ADT) outcomes in non-metastatic castration resistant prostate cancer (nmCRPC) from SPARTAN [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5053.

5066 Background: TITAN, a phase 3 PBO-controlled study in patients (pts) with mCSPC, showed APA + ADT improved radiographic progression-free survival and OS vs PBO + ADT. In this exploratory analysis, we report the relationships between biomarkers and OS in TITAN. Methods: Circulating tumor (ct)DNA and genomic aberrations in 17 PC-related genes, including androgen receptor (AR), were assessed at baseline (BL; 114 pts) and end of study treatment (EOST; 129 pts) using next-generation sequencing. ctDNA was assessed qualitatively; genomic aberrations were assessed within ctDNA-positive samples as inactivation (heterozygous/homozygous deletion or single nucleotide variant [SNV]) or activation (amplification or SNV). Associations of detected ctDNA/aberrations at BL or EOST with OS, and biomarkers at EOST with OS on subsequent therapies, were evaluated using univariate or multivariate analyses and Cox proportional hazards model; results were stratified by treatment arm. Results: Among pts from both treatment groups, 36% had detectable ctDNA, of which 27% had any genomic AR aberration and 24% had AR gene amplification at BL; prevalence of these biomarkers increased significantly from BL to EOST (Table). The most prevalent non-AR aberrations at BL ( TP53, homologous recombination repair [HRR] pathway, PTEN, RB1, and PIK3CA genes) increased at EOST but not significantly (Table). Among assessed aberrations, presence of ctDNA or any AR genomic aberrations at BL (HR, 1.9 or 6.7; all p < 0.05) and any AR genomic aberrations or PI3K pathway activation at EOST (1.7, p < 0.05 or 2.2, p < 0.001) was significantly associated with poor OS in multivariate analyses from both treatment groups. In univariate analyses of pts who received subsequent therapy (chemotherapy: 106; hormonal therapy: 161), worse OS was associated only with PIK3CA activation, PI3K pathway activation, or TP53 inactivation at EOST (3.7, p < 0.05; 2.4, p < 0.05; 3.0, p < 0.01, respectively) in chemo-treated pts. A small sample size in some biomarker subgroups limits interpretation. Conclusions: These hypothesis-generating data from TITAN show that presence of ctDNA or select AR and non-AR biomarkers at BL or EOST were associated with poor OS. The predictive value of these biomarkers for survival in mCSPC needs further confirmation. Clinical trial information: NCT02489318. [Table: see text]

6079 Background: Overexpression of AR is identified as a potential molecular target of SGC treatment. Combined androgen blockade (CAB) with bicalutamide has been evaluated previously, but the clinical usefulness of CAB with a next generation AR inhibitor has been unclear in SGC. We prospectively assessed the efficacy and safety of APA+GOS for pts with AR-expressing SGC. Methods: Eligible pts had fLA/RM SGC, and AR expression with at least 1% of cell nuclei immunohistochemistry staining positive. Pts were treated with APA 240 mg orally once daily and GOS 3.6 mg subcutaneously once 28 days. Primary endpoint was overall response rate (ORR) by central review according to RECIST v1.1, and a response (complete response [CR] or partial response [PR]) was confirmed by repeat assessments at least 4 weeks after the initial evaluation showing a response. Primary analysis was performed based on first 24 response evaluable (RE) pts who had been observed at least 24 weeks (Primary RE pts). The ORR was tested using exact test based on the binominal distribution, the null hypothesis for ORR of 14% was rejected when at least 8 of the 24 Primary RE pts were responders, and the efficacy was to be declared. Key secondary endpoints included clinical benefit rate (CBR), disease control rate (DCR), duration of response (DOR), and time to response (TTR) in the Primary RE pts, and overall survival (OS), progression free survival (PFS), and safety in the treated pts. Results: Twenty-six of the 31 pts treated with APA+GOS were regarded as RE by central review. For the 24 Primary RE pts, ORR was 25.0% (6/24), while 37.5% (9/24) including unconfirmed PR. Clinical benefit rate and DCR in the Primary RE pts were 50.0% and 70.8%, respectively. At the data cut-off (Apr 28, 2021), 5 of 6 pts with confirmed response were still on protocol treatment. Median PFS and OS in the treated pts were 7.43 months (mos) and not reached, respectively, with the median follow-up period of 8.57 mos. Grade 3 or higher treatment-related adverse events were reported in 4/31 (12.9%) pts, and the events were rash maculo-papular (n=2), anemia (n=1), and leukopenia (n=1). Conclusions: This is the first prospective trial evaluating CAB with APA for AR-expressing SGC. Although this study did not meet the predefined criteria of efficacy, clinically meaningful activity with well-tolerated safety profile of APA+GOS was shown. Clinical trial information: NCT04325828. [Table: see text]

5084 Background: Current management of HRLPC includes long-term ADT with primary RT. Despite definitive primary treatment, these pts have a high risk of metastasis and death. The phase 3 ATLAS study (NCT02531516) is investigating whether treatment intensification with the addition of APA to neoadjuvant and adjuvant treatment with gonadotropin-releasing hormone agonist (GnRHa) and external beam radiation therapy (EBRT) will improve metastasis-free survival (MFS) in high-risk pts. Here we describe (1) the distribution of baseline characteristics in this high-risk pt population and (2) the application of different RT regimens reflecting recent international guidelines and clinical practice changes for pts with HRLPC. Methods: Eligible HRLPC pts (Gleason score [GS] ≥ 8 or 7 and prostate-specific antigen [PSA] ≥ 20 ng/mL and stage ≥ cT2c), with ECOG PS 0/1 and Charlson Comorbidity Index (CCI) ≤ 3 are stratified by GS, pelvic nodal status, use of brachytherapy boost, and region; pts are randomized 1:1 to APA or PBO plus GnRHa for 30 (28-d) treatment cycles. Study treatment is applied neoadjuvant/concurrent to RT with APA 240 mg/d vs bicalutamide 50 mg/d for 4 cycles; another 26 cycles are completed adjuvantly after RT with APA 240 mg/d vs PBO. Primary end point is MFS (time from randomization to first distant metastasis on CT/MRI/bone scan by independent central review blinded to treatment or death from any cause). Imaging is conducted at baseline and q6m from biochemical failure until MFS. The protocol has been amended to include PET imaging (PSMA, fluciclovine, or choline). Results: Pts (N = 1503) were randomized at 266 sites in 24 countries in North America, Latin America, Europe, and Asia. The study is fully enrolled, but ongoing. Baseline characteristics for the total population: median age, 67 yrs; ECOG PS 0/1; 89%/11%; tumor classification at study entry: high-risk, 66%/very high–risk, 34%; median PSA, 6.3 ng/mL; cT2, 44%/cT3, 50%; cN1, 13%. In 90% of ATLAS pts, RT used was standard EBRT to prostate/pelvis over 6-8 weeks (cumulative 78-81 Gy); in 10%, recent hypofractionation schedules (per CHHiP or NRG/RTOG 0415) were applied (20x3 Gy/d or 28x2.5 Gy/d). 5.6% of pts had EBRT combined with brachytherapy (per ASCENDE-RT). Conclusions: Baseline characteristics of the ATLAS study population are reflective of pts with high- and very high–risk features and pelvic nodal involvement undergoing primary RT in clinical practice. The RT schedules applied reflect recent evidence and guideline changes for the use of hypofractionation in this pt population. ATLAS is an example of how RT can be included in phase 3 trials of HRLPC, in combination with next-generation androgen receptor inhibitors (eg, APA). Clinical trial information: NCT02531516.

Peer specialists are individuals with mental illness and substance use disorders trained to use their experiences to help others with similar disorders. Evidence for the effectiveness of peer specialist services has been mixed in previous randomized trials using intent-to-treat analyses, possibly because of variation in the intensity of treatment delivered. This study, which was part of a larger randomized trial, assessed whether level of peer specialist engagement was associated with reliable positive change on measures of psychiatric symptoms and hope.The Reliable Change Index was used to compute whether veterans (N=140) achieved reliable positive change on standardized baseline-to-posttest assessments of psychiatric symptoms and hope. Logistic regression analyses were conducted to predict positive change in symptoms and hope by level of peer specialist engagement, with controls for relevant demographic factors, several baseline mental health and substance abuse measures, and service use during the study.Logistic regression models showed that veterans with higher peer specialist engagement were more likely than those in a control group to show reliable positive change in psychiatric symptoms but not in hope. Compared with the control group, those with lower peer specialist engagement did not show positive change on either measure. White veterans were less likely than those from minority groups to exhibit positive change in psychiatric symptoms.Results suggest that peer specialists can benefit those with mental illnesses and substance use disorders who engage in more frequent interactions. Studies are needed to further assess the circumstances under which peer specialists can be effective.

The success of fecal occult blood-based colorectal cancer screening programs is dependent on repeating screening at short intervals (i.e., every one to two years). We conducted a literature review to assess measures that have been used to assess longitudinal adherence to fecal-based screening. Among 46 citations identified and included in this review, six broad classifications of longitudinal adherence were identified: (1) stratified single-round attendance, (2) all possible adherence permutations, (3) consistent/inconsistent/never attendance, (4) number of times attended, (5) program adherence, and (6) proportion of time covered. Advantages and disadvantages of these measures are described, and recommendations on which measures to use based on data availability and scientific question are also given. Stratified single round attendance is particularly useful for describing the yield of screening, while programmatic adherence measures are best suited to evaluating screening efficacy. We recommend that screening programs collect detailed longitudinal, individual level data, not only for the screening tests themselves but additionally for diagnostic follow-up and surveillance exams, to allow for maximum flexibility in reporting adherence patterns using the measure of choice.

Background Over 1100 veterans work in the Veterans Health Administration (VHA) as peer specialists (PSs)—those with formal training who support other veterans with similar diagnoses. A White House Executive Action mandated the pilot reassignment of VHA PSs from their usual placement in mental health to 25 primary care Patient Aligned Care Teams (PACTs) in order to broaden the provision of wellness services that can address many chronic illnesses. An evaluation of this initiative was undertaken to assess the impact of outside assistance on the deployment of PSs in PACTs, as implementation support is often needed to prevent challenges commonly experienced when first deploying PSs in new settings. Methods This study was a cluster-randomized hybrid II effectiveness-implementation trial to test the impact of minimal implementation support vs. facilitated implementation on the deployment of VHA PSs in PACT over 2 years. Twenty-five Veterans Affairs Medical Centers (VAMCs) were recruited to reassign mental health PSs to provide wellness-oriented care in PACT. Sites in three successive cohorts (n = 7, 10, 8) over 6-month blocks were matched and randomized to each study condition. In facilitated implementation, an outside expert worked with site stakeholders through a site visit and regular calls, and provided performance data to guide the planning and address challenges. Minimal implementation sites received a webinar and access to the VHA Office of Mental Health Services work group. The two conditions were compared on PS workload data and veteran measures of activation, satisfaction, and functioning. Qualitative interviews collected information on perceived usefulness of the PS services. Results In the first year, sites that received facilitation had higher numbers of unique veterans served and a higher number of PS visits, although the groups did not differ after the second year. Also, sites receiving external facilitation started delivering PS services more quickly than minimal support sites. All sites in the external facilitation condition continued in the pilot into the second year, whereas two of the sites in the minimal assistance condition dropped out after the first year. There were no differences between groups on veterans’ outcomes—activation, satisfaction, and functioning. Most veterans were very positive about the help they received as evidenced in the qualitative interviews. Discussion These findings demonstrate that external facilitation can be effective in supporting the implementation of PSs in primary care settings. The lack of significant differences across conditions after the second year highlights the positive outcomes associated with active facilitation, while also raising the important question of whether longer-term success may require some level of ongoing facilitation and implementation support. Trial registration This project is registered at ClinicalTrials.gov with number NCT02732600 (URL: https://clinicaltrials.gov/ct2/show/NCT02732600).

Background In 2018, the Department of Veterans Affairs (VA) issued Notice 2018-08 requiring facilities to complete “case reviews” for Veterans identified in the Stratification Tool for Opioid Risk Mitigation (STORM) dashboard as high risk for adverse outcomes among patients prescribed opioids. Half of the facilities were randomly assigned to a Notice version including additional oversight. We evaluated implementation strategies used, whether strategies differed by randomization arm, and which strategies were associated with case review completion rates. Methods Facility points of contact completed a survey assessing their facility’s use of 68 implementation strategies based on the Expert Recommendations for Implementing Change taxonomy. We collected respondent demographic information, facility-level characteristics, and case review completion rates (percentage of high-risk patients who received a case review). We used Kruskal-Wallis tests and negative binomial regression to assess strategy use and factors associated with case reviews. Results Contacts at 89 of 140 facilities completed the survey (64%) and reported using a median of 23 (IQR 16–31) strategies. The median case review completion rate was 71% (IQR 48–95%). Neither the number or types of strategies nor completion rates differed by randomization arm. The most common strategies were using the STORM dashboard (97%), working with local opinion leaders (80%), and recruiting local partners (80%). Characteristics associated with case review completion rates included respondents being ≤ 35 years old (incidence rate ratio, IRR 1.35, 95% CI 1.09–1.67) and having < 5 years in their primary role (IRR 1.23; 95% CI 1.01–1.51), and facilities having more prior academic detailing around pain and opioid safety (IRR 1.40, 95% CI 1.12–1.75). Controlling for these characteristics, implementation strategies associated with higher completion rates included (1) monitoring and adjusting practices (adjusted IRR (AIRR) 1.40, 95% CI 1.11–1.77), (2) identifying adaptations while maintaining core components (AIRR 1.28, 95% CI 1.03–1.60), (3) conducting initial training (AIRR 1.16, 95% CI 1.02–1.50), and (4) regularly sharing lessons learned (AIRR 1.32, 95% CI 1.09–1.59). Conclusions In this national evaluation of strategies used to implement case reviews of patients at high risk of opioid-related adverse events, point of contact age and tenure in the current role, prior pain-related academic detailing at the facility, and four specific implementation strategies were associated with case review completion rates, while randomization to additional centralized oversight was not. Trial registration This project is registered at the ISRCTN Registry with number ISRCTN16012111. The trial was first registered on May 3, 2017.

Objectives This study tested the impacts of peer specialists on housing stability, substance abuse, and mental health status for previously homeless Veterans with cooccurring mental health issues and substance abuse. Methods Veterans living in the US Housing and Urban Development-Veterans Administration Supported Housing (HUD-VASH) program were randomized to peer specialist services that worked independently from HUD-VASH case managers (ie, not part of a case manager/peer specialist dyad) and to treatment as usual that included case management services. Peer specialist services were community-based, using a structured curriculum for recovery with up to 40 weekly sessions. Standardized self-report measures were collected at 3 timepoints. The intent-to-treat analysis tested treatment effects using a generalized additive mixed-effects model that allows for different nonlinear relationships between outcomes and time for treatment and control groups. A secondary analysis was conducted for Veterans who received services from peer specialists that were adherent to the intervention protocol. Results Treated Veterans did not spend more days in housing compared with control Veterans during any part of the study at the 95% level of confidence. Veterans assigned to protocol adherent peer specialists showed greater housing stability between about 400 and 800 days postbaseline. Neither analysis detected significant effects for the behavioral health measures. Conclusions Some impact of peer specialist services was found for housing stability but not for behavioral health problems. Future studies may need more sensitive measures for early steps in recovery and may need longer time frames to effectively impact this highly challenged population.

Context The use of ethnic identifiers in health systems is recommended in several European countries as a means to identify and address heath inequities. There are barriers to implementation that have not been researched. Objective This study examines whether and how ethnicity data can be collected in Irish general practices in a meaningful and acceptable way. Methods Qualitative case study data generation was informed by Normalization Process Theory (NPT) constructs about ‘sense’ making and ‘engagement’. It consisted of individual interviews and focus group discussions based on visual participatory techniques. There were 70 informants, including 62 general practitioner (GP) users of diverse ethnic backgrounds recruited through community organisations and eight GPs identified through an inter-agency steering group. Data were analysed according to principles of thematic analysis using NPT. Results The link between ethnicity and health was often considered relevant because GP users grasped connections with genetic (skin colour, lactose intolerance), geographic (prevalence of disease, early years exposure), behavioural (culture/food) and social determinant (housing) factors. The link was less clear with religion. There was some scepticism and questions about how the collection of data would benefit GP consultations and concerns regarding confidentiality and the actual uses of these data (e.g. risk of discrimination, social control). For GPs, the main theme discussed was relevance: what added value would it bring to their consultations and was it was their role to collect these data? Their biggest concern was about data protection issues in light of the European Union (EU) General Data Protection Regulation (GDPR). The difficulty in explaining a complex concept such as ‘ethnicity’ in the limited time available in consultations was also worrying. Conclusions Implementation of an ethnicity identifier in Irish general practices will require a strong rationale that makes sense to GP users, and specific measures to ensure that its benefits outweigh any potential harm. This is in line with both our participants’ views and the EU GDPR.

Understanding consumer service preferences is important for recovery-oriented care.To test the influence of perceived service needs on importance attached to treatment for alcohol, drug, mental health, and physical health problems and identify the influence of service needs and preferences on service use.Formerly homeless dually diagnosed Veterans in supported housing were surveyed in three waves for 1 year, with measures of treatment interests, health problems, social support, clinician-assessed risk of housing loss, and sociodemographics. Multiple regression analysis was used to identify independent influences on preferences in each wave. Different health services at the VA were distinguished in administrative records and baseline predictors for services used throughout the project were identified with multiple regression analysis.Self-assessed problem severity was associated with the importance of treatment for alcohol, drug, mental health, and physical health problems. Social support also had some association with treatment interest for alcohol abuse, as did baseline clinician risk rating at the project's end. Preferences, but not perceived problem severity, predicted the use of the corresponding health services.The health beliefs model of service interests was supported, but more integrated service delivery models may be needed to strengthen the association of health needs with service use.

Peer specialists are individuals with behavioral disorders who complete training to use their experiences to help others with similar disorders. Recent analyses have suggested that greater engagement with peer specialist services is associated with fewer psychiatric symptoms. This study assessed predictors of engagement with peer specialist services.Using the Andersen model of health service utilization with a sample of veterans (N=71) receiving housing support, investigators constructed a negative binomial regression model to evaluate the association between peer specialist service engagement and the model's three factors assessed at baseline of a larger trial: predisposing (personal demographic and social variables); enabling (support variables), and need (perceived and evaluated health problems). Demographic characteristics and behavioral health service use six months before baseline were also predictors.Greater hope (predisposing), psychiatric symptoms (need), and service utilization significantly predicted greater peer specialist engagement.These results suggest subpopulations with whom peer specialists would be most likely to engage successfully, perhaps improving their efficiency.

7047 Background: While new interventions have improved cancer screening, treatment, and survivorship, the costs and other economic impacts of interventions may affect their uptake and availability. It is unknown what proportion of recently-funded National Cancer Institute (NCI) grants include economic outcomes. Methods: We used the NIH Query/View/Report (QVR) System to determine the number of competitive grants funded by NCI 2015-2020 that included economic outcomes. Grants were identified using the NIH Research, Condition, and Disease Categorization (RCDC) category “Cost Effectiveness Research”; 19 RCDC terms/concepts related to economic analyses; and 18 economic phrases searched for in grant titles, abstracts, and specific aims. The specific aims and abstracts of all grants meeting any of these search criteria were reviewed by an NCI scientist to ensure the presence of economic study outcomes. Results: Among over 13,700 competitive grants awarded by NCI 2015-2020, the search identified 149 grants; following abstract/specific aims review, 102 of these grants (0.74% of all grants) included an economic outcome. Most (69 of 102, 67.6%) included cost-effectiveness analysis; 24 included other cost analyses, 7 assessed financial hardship or similar outcomes, and 2 focused on developing economic methods. Among RCDC terms, more than half (53) listed modeling (9 listing Cancer Intervention and Surveillance Modeling Network), 24 randomized controlled trials, 15 QALYs, 11 implementation science, 3 willingness to pay. The most common cancer sites listed were breast (28), lung (23), cervical (19), and colorectal (17) cancer. Almost half (48) mentioned screening and 24 cancer prevention. Risk factors listed included 28 for smoking, 18 HPV, 8 HIV, 8 physical activity, 6 obesity, 4 nutrition. Ten listed treatment efficacy, 6 chemotherapy, 4 radiation therapy, 3 hormone therapy, and 1 chemoradiation. “Treatment as usual” was listed by 16, symptom management 4, and telehealth 4. Survivors were listed for 15, caregivers 3, health disparity 18, rural 15, young adult 4. The majority of grant mechanisms were R01 (76, 74.5%); 3 were R21/R03, 4 other R mechanisms, 7 K awards, 6 U grants, 6 P, F, or L grants. Conclusions: While this search may not have identified all funded NCI grants over the past 5 years involving economic analyses, we found that less than 1% included economic outcomes. Recommendations to assist NCI in supporting health economics research focused on cancer across the entire care spectrum should be considered.

Background Over 1100 Veterans work in the Veterans Health Administration (VHA) as peer specialists (PSs). PSs are Veterans with formal training who provide support to other Veterans with similar diagnoses, primarily in mental health settings. A White House Executive Action mandated the pilot reassignment of VHA PSs from mental health to 25 primary care Patient Aligned Care Teams (PACT) in order to broaden the provision of wellness services that can address many chronic illnesses. An evaluation of this initiative was undertaken to assess the impact of outside assistance on the deployment of PS in PACT, as implementation support is often needed to prevent challenges commonly experienced when first deploying PSs in VHA settings. We present the protocol for this cluster-randomized hybrid type II trial to test the impact of standard implementation (receive minimal assistance) vs. facilitated implementation (receive outside assistance) on the deployment of VHA PSs in PACT. Methods A VHA Office of Mental Health Services work group is recruiting 25 Veterans Affairs Medical Centers to reassign a mental health PSs to provide wellness-oriented care in PACT. Sites in three successive cohorts (n = 8, 8, 9) beginning over 6-month blocks will be matched and randomized to either standard or facilitated implementation. In facilitated implementation, an outside expert works with site stakeholders through a site visit, regular calls, and performance data to guide the planning and address challenges. Standard implementation sites will receive a webinar and access the Office of Mental Health Services work group. The two conditions will be compared on PS workload data, fidelity to the PS model of service delivery, team functioning, and Veteran measures of activation, satisfaction, and functioning. Qualitative interviews will collect information on implementation barriers and facilitators. Discussion This evaluation will provide critical data to guide administrators and VHA policy makers on future deployment of PSs, as their role has been expanding beyond mental health. In addition, development of novel implementation strategies (facilitation tailored to PSs) and the use of new tools (peer fidelity) can be models for monitoring and supporting deployment of PSs throughout VHA. Trial registration ClinicalTrials.gov, NCT02732600 (URL: https://clinicaltrials.gov/ct2/show/NCT02732600 )

OBJECTIVE Research on peer specialists (individuals with serious mental illness supporting others with serious mental illness in clinical and other settings) has not yet included the measurement of fidelity. Without measuring fidelity, it is unclear whether the absence of impact in some studies is attributable to ineffective peer specialist services or because the services were not true to the intended role. This article describes the initial development of a peer specialist fidelity measure for 2 content areas: services provided by peer specialists and factors that either support or hamper the performance of those services. METHOD A literature search identified 40 domains; an expert panel narrowed the number of domains and helped generate and then review survey items to operationalize those domains. Twelve peer specialists, individuals with whom they work, and their supervisors participated in a pilot test and cognitive interviews regarding item content. RESULTS Peer specialists tended to rate themselves as having engaged in various peer service activities more than did the supervisors and individuals with whom they work. A subset of items tapping peer specialist services "core" to the role regardless of setting had higher ratings. Participants stated the measure was clear, appropriate, and could be useful in improving performance. CONCLUSIONS AND IMPLICATIONS FOR PRACTICE Although preliminary, findings were consistent with organizational research on performance ratings of supervisors and employees made in the workplace. Several changes in survey content and administration were identified. With continued work, the measure could crystalize the role of peer specialists and aid in research and clinical administration. (PsycINFO Database Record

Background Incorporating evidence-based integrated treatment for dual disorders into typical care settings has been challenging, especially among those serving Veterans who are homeless. This paper presents an evaluation of an effort to incorporate an evidence-based, dual disorder treatment called Maintaining Independence and Sobriety Through Systems Integration, Outreach, and Networking—Veterans Edition (MISSION-Vet) into case management teams serving Veterans who are homeless, using an implementation strategy called Getting To Outcomes (GTO). Methods This Hybrid Type III, cluster-randomized controlled trial assessed the impact of GTO over and above MISSION-Vet Implementation as Usual (IU). Both conditions received standard MISSION-Vet training and manuals. The GTO group received an implementation manual, training, technical assistance, and data feedback. The study occurred in teams at three large VA Medical Centers over 2 years. Within each team, existing sub-teams (case managers and Veterans they serve) were the clusters randomly assigned. The trial assessed MISSION-Vet services delivered and collected via administrative data and implementation barriers and facilitators, via semi-structured interview. Results No case managers in the IU group initiated MISSION-Vet while 68% in the GTO group did. Seven percent of Veterans with case managers in the GTO group received at least one MISSION-Vet session. Most case managers appreciated the MISSION-Vet materials and felt the GTO planning meetings supported using MISSION-Vet. Case manager interviews also showed that MISSION-Vet could be confusing; there was little involvement from leadership after their initial agreement to participate; the data feedback system had a number of difficulties; and case managers did not have the resources to implement all aspects of MISSION-Vet. Conclusions This project shows that GTO-like support can help launch new practices but that multiple implementation facilitators are needed for successful execution of a complex evidence-based program like MISSION-Vet. Trial registration ClinicalTrials.gov NCT01430741

article i nfo This paper explores what system factors influenced the adoption of Family Group Decision Making (FGDM) in Pennsylvania and what the perceived barriers and facilitators of adoption and sustainability are according to the individualsinvolved in FGDM. A mixed methods design isemployed, using geographic autocorrelation modeling and analysisof qualitative data aboutbarriers and facilitators. The findingsrevealthat maltreatment and poverty ratesandthesizeofthepopulationofchildrenarenon-significantpredictorsofacountyusingFGDM,buthavinga FGDM pilot grant is a significant predictor, along with having had a system of care initiative. Population density and number of caseworkers also are significant, if weaker, predictors; population density became insignificant once the two largest counties, Philadelphia and Allegheny were removed from the model. Having a neighboring county that practices FGDM e.g. the neighborhood effect is the most powerful predictor (z=8.98,p

Evidence-based management (EBM) means managerial decisions and organizational practices informed by the best available scientific evidence. In this essay we describe the core features of educational processes promoting EBM. These include mastering behavioral principles where the science is clear and developing procedural knowledge based on practice, feedback, and reflection. We also identify key factors in organizational research, education, and management practice that inhibit EBM’s use and ways these can be overcome.

Objective: To determine if future studies of coenzyme Q10 and GPI-1485 in Parkinson disease (PD) may be warranted. Methods: We conducted a randomized, double-blind, calibrated futility clinical trial of coenzyme Q10 and GPI-1485 in early untreated PD using placebo data from the DATATOP study to establish the futility threshold. Results: The primary outcome measure (change in total Unified Parkinson's Disease Rating Scale scores over 1 year) did not meet the prespecified criteria for futility for either agent. Secondary analyses using calibration controls and other more recent placebo data question the appropriateness of the predetermined definition of futility, and suggest that a more restrictive threshold may be needed. Conclusions: Coenzyme Q10 and GPI-1485 may warrant further study in Parkinson disease, although the data are inconsistent. Additional factors (cost, availability of other agents, more recent data on placebo outcomes, other ongoing trials) should also be considered in the selection of agents for Phase III studies. NEUROLOGY 2007;68:20-28

Background The Housing and Urban Development-Veterans Affairs Supportive Housing (HUD-VASH) program is one of the largest initiatives to end Veteran homelessness. However, mental health and substance use disorders continue to reduce client stability and impede program success. HUD-VASH programs do not consistently employ evidence-based practices that address co-occurring mental health and substance use disorders. This paper presents a study protocol to evaluate the implementation of an evidence-based, co-occurring disorder treatment called Maintaining Independence and Sobriety Through Systems Integration, Outreach, and Networking—Veterans Edition (MISSION-Vet) in HUD-VASH using an implementation strategy called Getting To Outcomes (GTO). Methods/design In three large VA Medical Centers, this Hybrid Type III trial will randomize case managers and their clients by HUD-VASH sub-teams to receive either MISSION-Vet Implementation as Usual (IU—standard training and access to the MISSION-Vet treatment manuals) or MISSION-Vet implementation augmented by GTO. In addition to testing GTO, effectiveness of the treatment (MISSION-Vet) will be assessed using existing Veteran-level data from the HUD-VASH data monitoring system. This project will compare GTO and IU case managers and their clients on the following variables: (1) fidelity to the MISSION-Vet intervention; (2) proportion of time the Veteran is housed; (3) mental health, substance use, and functional outcomes among Veterans; and (4) factors key to the successful deployment of a new treatment as specified by the Reach, Effectiveness, Adoption, Implementation, and Maintenance (RE-AIM) model. Discussion This project is an important step for developing an implementation strategy to increase adoption of evidence-based practice use in VA homeless programs, and to further examine efficacy of MISSION-Vet in HUD-VASH. This project has important implications for program managers, policy makers, and researchers within the homelessness field. VA Central IRB approval for this study was granted in October 2011. The three sites were trained on MISSION-Vet and GTO in the first half of 2013. The first GTO planning meetings began after training occurred, between January 2013 and November 2013, across the three sites. The data collection—via a fidelity measure embedded into the VA Computerized Patient Record System—began as each site initiated MISSION-Vet, between April 2013 and January 2014. Trial registration ClinicalTrials.gov: NCT01430741

Before a municipal solid waste incinerator (MSWI) can be operated, it is generally required that a health risk assessment be performed and that human health risks predicted fall below permissible levels. There are several components to the risk assessment paradigm, including: (1) determination of stack emissions for potentially toxic chemicals, (2) calculation of atmospheric dispersion and exposure point concentrations, (3) development of scenarios by which humans become exposed to airborne chemicals, (4) identification of dose-response functions for carcinogenic and noncarcinogenic effects, and (5) prediction of the probability of health impacts. Typical MSWI air contaminants of concern are metals (e.g., Ag, As, Be, Cd, Cr, Hg, Ni, Pb, Sb) and organic compounds (e.g., benzene, PCBs, B(a)P, polychlorinated dioxins/furans). MSWI risk assessments include both direct exposure pathways (air inhalation, incidental ingestion of soil), and indirect pathways (food-chain exposures such as human consumption of produce, beef, fish, and milk). To perform a risk assessment for direct and indirect routes of exposure, both atmospheric concentration and deposition rate are required; assumptions need to be made about toxicity as a function of route of exposure. Interpretation of risk-assessment results requires understanding how some of the conservative assumptions made in the risk-assessment process play out relative to real-world health hazards. Some attempts have been made to verify that predicted concentrations of airborne contaminants are reflected by measured levels, but in most cases the predicted air and soil concentrations fall below limits of detection and always within background variability. In summary, health risk assessments are useful for regulatory guidance, but it has not been possible to verify that health risks of MSWI emissions contribute measurably to population health risks.

Ten hemolytic reactions occurred in our outpatient hemodialysis unit over a 12-month period (December 1989 to December 1990). Eight patients were hospitalized and one died. All patients developed severe abdominal or back pain an average of 2.5 hours into a 4-hour hemodialysis session using a bleach/formaldehyde reprocessed hollow-fiber cupraphan dialyzer (average reuse, three times) with blood flow rates of 375 mL/min. All had visible hemolysis in a spun hematocrit, seven had a significant decrease in hematocrit, and six developed pancreatitis. Hemolysis was further confirmed by a decrease in haptoglobin in all patients and an increase in lactic dehydrogenase in all but the last case. Investigation of each episode failed to find an abnormality in dialysate temperature or tonicity; dialysate or water levels of copper, zinc, nitrates, chloramine, or formaldehyde; or blood pump or venous alarm. Hemolytic reactions continued despite changing to 15-gauge needles, removing bleach from the reuse procedure, or stopping reuse. During the eighth episode, a kink was noted in the arterial blood line. Two subsequent hemolytic reactions occurred, and in each kinks were found in the arterial blood line, either in the excess tubing between the blood pump and drip chamber or in the predialyzer. No further hemolytic reactions occurred after changing to a new arterial blood line without redundant tubing and securing all lines. Hemolytic reactions occurring during hemodialysis have many etiologies, including mechanical trauma, which we report may result from kinking of dialyzer lines. With new blood lines on the market, attention to this aspect of dialysis is mandatory.

Background In several animal studies of young and aged rats with ischemic stroke, treatment with sildenafil improved functional outcomes compared with placebo. We conducted a safety study of sildenafil (25 mg daily for 2 weeks) shortly after ischemic stroke onset. Methods We recruited patients aged 18 to 80 years with ischemic stroke, National Institutes of Health stroke scale (NIHSS) score 2 to 21, between days 2 and 9 after symptom onset. Patients were treated with sildenafil for 2 weeks (25 mg daily). The primary outcome measure was the adverse occurrence of any of the following during the treatment period: stroke worsening, new stroke, myocardial infarction, vision loss, hearing loss, or death from any cause. Secondary outcome measures were NIHSS score, Barthel indices, and modified Rankin score at 90 days. Results Twelve patients were recruited. Mean age was 57 years, 5 were female, and median NIHSS score at entry was 9.5 (range 2-20). The primary outcome measure occurred in one patient (sudden death). Another patient committed suicide 2 months after study entry (and 6 weeks after treatment with sildenafil had been completed). Among the 10 survivors, at 90 days, median NIHSS score was 2 (range 0-12), median Barthel index was 95 (range 15-100), and median modified Rankin score was 1.5 (range 0-5). Conclusions Sildenafil (25 mg daily for 2 weeks) appeared to be safe in this group of patients with mild to moderately severe stroke. Further studies of higher doses will be tested.

Background: TP53 is commonly mutated in ovarian cancer. As potential agents targeting TP53 mutant or wt are under development, the efficiency and accuracy for determination of TP53 mutations in a clinical trial was evaluated. Methods: Eligible patients, including relapsed, platinum-sensitive ovarian, fallopian tube, or primary peritoneal cancer, underwent pre-screening for a clinical trial with MK1775, eligibility for which was determined by the presence of functional TP53 mutations (Brana I et al, ASCO 2013). Single base substitution and single base deletion mutations in exons 2 - 11 and the flanking splice junction in the TP53 gene were analyzed using AmpliChip p53 Assay (Roche Molecular Diagnostics, California) on archival tumor specimens. Results: Seventy-five women were screened for eligibility based on TP53; 43 had TP53 mutations, 27 were TP53 wild-type (wt), and 5 undetermined (Table 1). No clustering of mutations to define hot spots was evident. The most commonly mutated region was exon 5 (11 mutations). Missense mutations were the most common mutation type (69.7%); although, nonsense (14 %), splice (14 %), and frame shift mutations (2.3%) were also observed (Table 1). Most of the missense mutations were in exons 5 to 8 (90%). The mean turnaround time from sample reception to final TP53 status report was 3 days (range 1:14). Conclusions: The TP53 mutational status has been successfully determined in 93.3% of patients with a short turnaround time, supporting the feasibility of TP53 determination in the clinical setting. In our patient population, 57.3% had a TP53 mutation. Potential geographic differences in the incidence TP53 mutations cannot be evaluated due to the limited sample size; this hypothesis should be further evaluated in a larger patient population Citation Information: Mol Cancer Ther 2013;12(11 Suppl):B181. Citation Format: Irene Brana, Kathleen Moore, Stephen Welch, Ronnie Shapira-Frommer, Darlene Gibbon, Hal Hirte, Saul Rivkin, Robert Coleman, Gerry Prendergast, Katherine M. Moxley, Ying-Ming Jou, Michelle Marinucci, Tomoko Freshwater, Sharon McCarthy, Mark Lee Anthony, Shelonitda Rose, Amit M. Oza. TP53 mutation screening in patients with recurrent platinum-sensitive ovarian cancer. [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2013 Oct 19-23; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2013;12(11 Suppl):Abstract nr B181.

Recent reports have documented an association between patent foramen ovale and obstructive sleep apnea. We report on a 51-year-old man with obstructive sleep apnea and recent stroke who was enrolled in a clinic trial evaluating the efficacy of closure of patent foramen ovale following ischemic stroke. He was randomly assigned to device closure. There was subjective dramatic improvement in sleep-apnea symptoms and objective improvement in polysomnographic testing after device implantation. Aside from a drop in apneas and hypopneas from 181 and 8 on the first polysomnogram to 19 and 0 on the second, there was no significant weight loss nor were there other significant changes in sleep parameters or medications. He stopped using continuous positive airway pressure 2 months after implantation and has had no recurrent sleep complaints during 18 months of follow-up. Further studies evaluating the relationship among patent foramen ovale, sleep apnea, and device implantation are warranted. Citations: Silver B; Greenbaum A; McCarthy S. Improvement in Sleep Apnea Associated With Closure of a Patent Foramen Ovale. J Clin Sleep Med 2007;3(3):295–296

The results of more than 1 yr of air monitoring inside and outside of five homes in each of two communities are presented for SO 2 , NO 2 , mass respirable particles, SO 4 , Al, Br, Cl, Mn, Na, and V. Outdoor measurements across the home site in each city are consistent with proximity to outdoor sources. Looking across indoor residential sites in each city, the home appears to alter outdoor concentrations in several ways. Indoor level of SO 2 , SO 4 , Mn, and V are lower than those measured outdoors. These constituents are thought generally to result from outdoor sources. The other constituents studied are at times found in excess within homes. In some cases the source or sources of excess concentration of a particular constituent could be identified; often, however, the source of excess indoor concentration could not be identified.

This study examined the relationship between the Pythagoreans and Plato in order to further illuminate the derivations of Plato's views of physical education. Concepts from Pythagorean and Platonic writings were examined. A search for historical connections between Plato and the Pythagoreans was made. Possible Pythagorean influences on specific Platonic concepts of physical education were suggested. General concepts in The Republic which appear to be influenced by Pythagoreanism were the theories of soul, forms, harmony, justice, and simplicity. Related to these concepts, but more inherent to physical education specifically, the following concepts were thought to be of Pythagorean origin: that the pre-eminent objective of physical education was character training, that the body was inferior to the soul and needed physical education primarily to prepare it for service to the soul, that simplicity of diet and regimen was to be maintained for an adequate physical education program, and that particip...