Justice implications of health and food security policies for Indigenous peoples facing COVID-19: a qualitative study and policy analysis in Peru.

The spread of COVID-19 in Peru resulted in the declaration of a national health emergency, in which Indigenous peoples were identified as being particularly vulnerable due to their pre-existing poor health indicators and disadvantaged social conditions. The aim of this paper is to examine how the Peruvian government responded to the health and food needs of the Shawi and Ashaninka Indigenous peoples of Peru during the first 18 months of the pandemic (March 2020-August 2021). This study uses both official policy documents and real-world experiences to evaluate policy responses in terms of their immediate impact and their longer-term sustainability and contribution to the improvement of health, well-being and justice for Indigenous communities. Four health and food security responses were evaluated: the Amazon Health Plan and Indigenous Command; food aid; cash aid; and COVID-19 vaccination. We employed the Multidimensional Injustice Framework to analyse the justice implications of the design and implementation of responses. Data collection included 71 interviews with government officials (n = 7), Indigenous leaders (n = 31) and community members (n = 33). The results show how national and regional governments released policies to address the health and food needs of Indigenous peoples directly or indirectly, as part of a broader focus on vulnerable people. However, justice implications were not sufficiently addressed in the design or implementation of the responses. On the distributive dimension, Indigenous communities were prioritized to receive health goods and services, nevertheless, the distribution had shortcomings that impeded their collection and Indigenous food systems and livelihoods were largely overlooked. On the procedural dimension, Indigenous representatives were included to provide culturally sensitive feedback on health interventions, but without funding, and furthermore, the community members had only passive participation. This paper points out the importance of considering and addressing justice implications for more effective and fairer health and food policy responses to current and future health crises.

Policy responses to COVID-19 in Sri Lanka and the consideration of Indigenous Peoples.

COVID-19 has had uneven impacts on health and well-being, with Indigenous communities in the Global South facing some of the highest risks. Focusing on the experience of Sri Lanka, this study identifies key policy responses to COVID-19, documents how they evolved over two years of the pandemic, and examines if and how government responses have addressed issues pertaining to Indigenous Peoples. Drawing upon an analysis of policy documents (n = 110) and interviews with policymakers (n = 20), we characterize seven key policy responses implemented by the Sri Lankan government: i) testing for and identifying COVID-19; ii) quarantine procedures; iii) provisional clinical treatments; iv) handling other diseases during COVID-19; v) movement; vi) guidelines to be adhered to by the general public; and vii) health and vaccination. The nature of these responses changed as the pandemic progressed. There is no evidence that policy development or implementation incorporated the voices and needs of Indigenous Peoples.

Evaluation of geranylgeranyl diphosphate synthase inhibition as a novel strategy for the treatment of osteosarcoma and Ewing sarcoma.

Rab GTPases are critical regulators of protein trafficking in the cell. To ensure proper cellular localization and function, Rab proteins must undergo a posttranslational modification, termed geranylgeranylation. In the isoprenoid biosynthesis pathway, the enzyme geranylgeranyl diphosphate synthase (GGDPS) generates the 20-carbon isoprenoid donor (geranylgeranyl pyrophosphate [GGPP]), which is utilized in the prenylation of Rab proteins. We have pursued the development of GGDPS inhibitors (GGSI) as a novel means to target Rab activity in cancer cells. Osteosarcoma (OS) and Ewing sarcoma (ES) are aggressive childhood bone cancers with stagnant survival statistics and limited treatment options. Here we show that GGSI treatment induces markers of the unfolded protein response (UPR) and triggers apoptotic cell death in a variety of OS and ES cell lines. Confirmation that these effects were secondary to cellular depletion of GGPP and disruption of Rab geranylgeranylation was confirmed via experiments using exogenous GGPP or specific geranylgeranyl transferase inhibitors. Furthermore, GGSI treatment disrupts cellular migration and invasion in vitro. Metabolomic profiles of OS and ES cell lines identify distinct changes in purine metabolism in GGSI-treated cells. Lastly, we demonstrate that GGSI treatment slows tumor growth in a mouse model of ES. Collectively, these studies support further development of GGSIs as a novel treatment for OS and ES.

Variation in Positivity Rates of Computed Tomography Pulmonary Angiograms for the Evaluation of Acute Pulmonary Embolism Among Emergency Department Physicians.

Computed tomography pulmonary angiography (CTPA) is an imaging study for which there is substantial evidence for its overuse in the evaluation of acute pulmonary embolism (PE). Prior literature has reported low positive PE rates, but the variability in positive rates among the ordering physicians has not been as well studied. The purpose of this study was to evaluate variation in ordering and positive rates among physicians in an emergency department (ED) within an integrated health care system.This study was based in a single ED that is part of a geographically isolated integrated health care system. We reviewed the patient records for all patients who underwent a CTPA for the evaluation for acute PE in the ED between January 1, 2018, and December 31, 2019. For each CTPA examination, we recorded the ordering ED physician, serum d-dimer value (mcg/mL), if any, and the results of the CTPA.Review of CTPAs over the 2-year period revealed 1380 CTPAs ordered by 23 ED physicians with a range of 25-141 studies per physician (mean of 60 + 31 CTPAs). The overall positive rate for PE was 6.9%. Individual ED physician positivity rates showed wide variability ranging from 0% to 18.4% (mean positive rate 7.6 + 4.4%). The results of this study confirm the need for greater adherence to existing guidelines using clinical decision rules and d-dimer testing when appropriate among all ED physicians but especially those who order a greater number of studies and have low rates for positive PE.

Prehospital Testing and Surveillance for SARS-CoV-2: A Special Report from the Sacramento (California USA) Mobile Integrated Health Unit.

INTRODUCTION: Coronavirus disease 2019 (COVID-19), caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), has killed nearly 800,000 Americans since early 2020. The disease has disproportionately affected older Americans, men, persons of color, and those living in congregate living facilities. Sacramento County (California USA) has used a novel Mobile Integrated Health Unit (MIH) to test hundreds of patients who dwell in congregate living facilities, including skilled nursing facilities (SNF), residential care facilities (ie, assisted living facilities [ALF] and board and care facilities [BCF]), and inpatient psychiatric facilities (PSY), for SARS-CoV-2. METHODS: The MIH was authorized and rapidly created at the beginning of the COVID-19 pandemic as a joint venture between the Sacramento County Department of Public Health (SCDPH) and several fire-based Emergency Medical Services (EMS) agencies within the county to perform SARS-CoV-2 testing and surveillance in a prehospital setting at a number of congregate living facilities. All adult patients (≥18 years) who were tested for SARS-CoV-2 infection by the MIH from March 31, 2020 through April 30, 2020 and lived in congregate living facilities were included in this retrospective descriptive cohort. Demographic and laboratory data were collected to describe the cohort of patients tested by the MIH. RESULTS: During the study period, the MIH tested a total of 323 patients from 15 facilities in Sacramento County. The median age of patients tested was 66 years and the majority were female (72%). Overall, 72 patients (22%) tested positive for SARS-CoV-2 in congregate living settings, a higher rate of positivity than was measured across the county during the same time period. CONCLUSION: The MIH was a novel method of epidemic surveillance that succeeded in delivering effective and efficient testing to patients who reside in congregate living facilities and was able to accurately identify pockets of infection within otherwise low prevalence areas. Cooperative prehospital models are an effective model to deliver out-of-hospital testing and disease surveillance that may serve as a blueprint for community-based care delivery for a number of disease states and future epidemics or pandemics.

Sustainment of Integrated Care in Addiction Treatment Settings: Primary Outcomes From a Cluster-Randomized Controlled Trial.

OBJECTIVE: Integrated treatment services are the gold standard for addressing co-occurring mental and substance use disorders, yet they are not readily available. The Network for the Improvement of Addiction Treatment (NIATx) was hypothesized to be an effective strategy to implement and sustain integrated mental health and substance use care in addiction treatment programs. This study examined sustainment of integrated services for up to 2 years after the active implementation phase. METHODS: The effectiveness of NIATx strategies to implement and sustain integrated services was evaluated by using a cluster-randomized, waitlist control group design. Forty-nine addiction treatment organizations were randomly assigned to either NIATx1 (active implementation strategy) or NIATx2 (waitlist control). The Dual Diagnosis Capability in Addiction Treatment Index was used to evaluate organizations' capability to provide integrated care. The NIATx Stages of Implementation Completion scale was used to assess participation in and adherence to the NIATx implementation process. Linear mixed-effects modeling was used to evaluate changes from baseline to end of the sustainment period. RESULTS: Both cohorts sustained their capability to provide integrated treatment services. Both groups achieved successful implementation and sustained integrated services to a similar degree, regardless of sustainment year. Sustainment did not vary as a function of NIATx adherence. CONCLUSIONS: The delivery of integrated treatment services was sustained for 2 years after receipt of active implementation support. Future research should consider how contextual factors may predict, mediate, and moderate sustainment outcomes.

Universal Screening of Gastrointestinal Malignancies for Mismatch Repair Deficiency at Stanford.

BACKGROUND: In light of recent Food and Drug Administration (FDA) approval of immune checkpoint inhibitors for mismatch repair deficient (dMMR) malignancies, identifying patients with dMMR malignancies has become increasingly important. Although screening for dMMR in colorectal cancer (CRC) is recommended, it is less common for extracolonic gastrointestinal (GI) malignancies. At Stanford Comprehensive Cancer Institute (SCCI), all GI malignancies have been screened for dMMR via immunohistochemistry since January 2016. METHODS: In this study, we conducted a retrospective review of all patients with GI malignancies screened for dMMR between January 2016 and December 2017. Tumor sequencing was performed on cases negative for germline pathogenic variants where tumor material was available. RESULTS: A total of 1425 consecutive GI malignancies were screened for dMMR at SCCI during the study period, and 1374 were included for analysis. dMMR was detected in 7.2% of all GI malignancies. We detected the highest prevalence of dMMR in gastric (15 of 150, 10.0%) followed by colorectal (63 of 694, 9.1%), pancreatic (13 of 244, 5.3%), and gastroesophageal malignancy (6 of 132, 4.5%) patients. Lynch syndrome was the most common etiology for dMMR in colorectal cancer (41.5%), double somatic (confirmed or possible) pathogenic variants the most common etiology in pancreatic cancer (44.4%), and somatic MLH1 hypermethylation the most common etiology in gastric (73.3%) and gastroesophageal cancer (83.3%). CONCLUSIONS: Given the relatively high incidence of dMMR in GI malignancies, we recommend screening all GI malignancies. Our results suggest that although a rare occurrence, double somatic pathogenic variants may be a biologically significant pathway causing dMMR in pancreatic cancer.

Germline Testing for Patients With BRCA1/2 Mutations on Somatic Tumor Testing.

BACKGROUND: The National Comprehensive Cancer Network (NCCN) recommends germline testing for pathogenic BRCA1/2 mutations identified by somatic tumor sequencing. The aim of this study was to explore whether patients at Stanford with somatic BRCA1/2 mutations were recommended germline testing in accordance with NCCN guidelines. METHODS: We retrospectively collected all Stanford patients with BRCA1/2 mutations found by tumor sequencing. Medical records were reviewed for each patient to identify those recommended germline testing. A multivariable logistic regression model was fit associating baseline characteristics with whether or not a recommendation was made. RESULTS: Of 164 participants, 51 (31.1%) had no recommendation for germline testing. Of the 97 available germline-testing results, 54 (55.7%) were positive for pathogenic BRCA1/2 mutations. After adjusting for possible confounders, patients with genitourinary cancer (odds ratio [OR] = 0.03, 95% confidence interval [CI] = 0.00 to 0.03; P = .003), lung cancer (OR = 0.04, 95% CI = 0.01 to 0.21; P < .001), sarcoma (OR = 0.02, 95% CI = 0.00 to 0.14; P < .001), skin cancer (OR = 0.01, 95% CI = 0.98 to 1.03; P = .002), or "other" diagnoses (OR = 0.01, 95% CI = 0.00 to 0.16; P < .001) were statistically significantly less likely to be recommended germline testing compared with patients with breast or gynecological cancers. CONCLUSIONS: Our study highlights the importance of provider education outside of the oncologic specialties typically associated with BRCA-related cancers and continued exploration of referrals to genetics for germline testing on the basis of somatic findings.

Two Novel TMPRSS6 Variants in a Compound Heterozygous Child With Iron Refractory Iron Deficiency Anemia.

We describe a Caucasian family with asymptomatic, nonconsanguineous parents, and a daughter with unexplained microcytic anemia diagnosed on routine hemoglobin screening at her 12-month well child check. After failed response to oral and parental iron supplementation, iron refractory iron deficiency anemia was suspected. The family underwent genetic testing and the proband was found to be a compound heterozygote for 2 previously unreported TMPRSS6 variants.

Implementing integrated services in routine behavioral health care: primary outcomes from a cluster randomized controlled trial.

BACKGROUND: An estimated 8.2 million adults in the United States live with co-occurring mental health and substance use disorders. Although the benefits of integrated treatment services for persons with co-occurring disorders has been well-established, gaps in access to integrated care persist. Implementation research can address this gap. We evaluated if the Network for the Improvement of Addiction Treatment (NIATx) implementation strategy was effective in increasing integrated services capacity among organizations treating persons with co-occurring disorders. METHODS: This study employed a cluster randomized waitlist control group design. Forty-nine addiction treatment organizations from the State of Washington were randomized into one of two study arms: (1) NIATx strategy (active implementation strategy), or (2) waitlist (control). The primary outcome was a standardized organizational measure of integrated service capability: the Dual Diagnosis in Addiction Treatment (DDCAT) Index. Intent-to-treat analyses and per-protocol analyses were conducted to address the following questions: (1) Is NIATx effective in increasing integrated service capacity? and (2) Are there differences in organizations that actually use NIATx per-protocol versus those that do not? RESULTS: From baseline to one-year post active implementation, both the NIATx strategy and waitlist arms demonstrated improvements over time in DDCAT Index total and DDCAT dimension scores. In intent-to-treat analyses, a moderate but statistically significant difference in improvement between study arms was seen only in the Program Milieu dimension (p = 0.020, Cohen's d = 0.54). In per-protocol analyses, moderate-to-large effects in Program Milieu (p = 0.002, Cohen's d = 0.91) and Continuity of Care (p = 0.026, Cohen's d = 0.63) dimensions, and in total DDCAT Index (p = 0.046, Cohen's d = 0.51) were found. CONCLUSIONS: Overall, organizations in both study arms improved DDCAT Index scores over time. Organizations in the NIATx strategy arm with full adherence to the NIATx protocol had significantly greater improvements in the primary outcome measure of integrated service capacity for persons with co-occurring disorders. TRAIL REGISTRATION: ClinicalTrials.gov, NCT03007940 . Retrospectively registered January 2017.

Multicenter Prospective Cohort Study of the Diagnostic Yield and Patient Experience of Multiplex Gene Panel Testing For Hereditary Cancer Risk.

PURPOSE: Multiplex gene panel testing (MGPT) allows for the simultaneous analysis of germline cancer susceptibility genes. This study describes the diagnostic yield and patient experiences of MGPT in diverse populations. PATIENTS AND METHODS: This multicenter, prospective cohort study enrolled participants from three cancer genetics clinics-University of Southern California Norris Comprehensive Cancer Center, Los Angeles County and University of Southern California Medical Center, and Stanford Cancer Institute-who met testing guidelines or had a 2.5% or greater probability of a pathogenic variant (N = 2,000). All patients underwent 25- or 28-gene MGPT and results were compared with differential genetic diagnoses generated by pretest expert clinical assessment. Post-test surveys on distress, uncertainty, and positive experiences were administered at 3 months (69% response rate) and 1 year (57% response rate). RESULTS: Of 2,000 participants, 81% were female, 41% were Hispanic, 26% were Spanish speaking only, and 30% completed high school or less education. A total of 242 participants (12%) carried one or more pathogenic variant (positive), 689 (34%) carried one or more variant of uncertain significance (VUS), and 1,069 (53%) carried no pathogenic variants or VUS (negative). More than one third of pathogenic variants (34%) were not included in the differential diagnosis. After testing, few patients (4%) had prophylactic surgery, most (92%) never regretted testing, and most (80%) wanted to know all results, even those of uncertain significance. Positive patients were twice as likely as negative/VUS patients (83% v 41%; P < .001) to encourage their relatives to be tested. CONCLUSION: In a racially/ethnically and socioeconomically diverse cohort, MGPT increased diagnostic yield. More than one third of identified pathogenic variants were not clinically anticipated. Patient regret and prophylactic surgery use were low, and patients appropriately encouraged relatives to be tested for clinically relevant results.

Using NIATx strategies to implement integrated services in routine care: a study protocol.

BACKGROUND: Access to integrated services for individuals with co-occurring substance use and mental health disorders is a long-standing public health issue. Receiving integrated treatment services are both more effective and preferred by patients and families versus parallel or fragmented care. National policy statements and expert consensus guidelines underscore the benefits of integrated treatment. Despite decades of awareness, adequate treatment for individuals with co-occurring substance use and mental health disorders occurs infrequently. The underlying disease burden associated with alcohol, illicit and prescription drug problems, as well as mental health disorders, such as depression, posttraumatic stress disorder and schizophrenia, is substantial. METHODS: This cluster randomized controlled trial (RCT) is designed to determine if the multi-component Network for the Improvement of Addiction Treatment (NIATx) strategies are effective in implementing integrated services for persons with co-occurring substance use and mental health disorders. In this study, 50 behavioral health programs in Washington State will be recruited and then randomized into one of two intervention arms: 1) NIATx implementation strategies, including coaching and learning sessions over a 12-month intervention period to implement changes targeting integrated treatment services; or 2) wait-list control. Primary outcome measures include: 1) fidelity - a standardized organizational assessment of integrated services (Dual Diagnosis in Addiction Treatment [DDCAT] Index); and 2) penetration - proportion of patients screened and diagnosed with co-occurring disorders, proportion of eligible patients receiving substance use and mental health services, and psychotropic or substance use disorder medications. Barriers and facilitators, as determinants of implementation outcomes, will be assessed using the Consolidated Framework for Implementation Research (CFIR) Index. Fidelity to and participation in NIATx strategies will be assessed utilizing the NIATx Fidelity Scale and Stages of Implementation Completion (SIC). DISCUSSION: This study addresses an issue of substantial public health significance: the gap in access to an evidence-based practice for integrated treatment for individuals with co-occurring mental health and substance use disorders. The study utilizes rigorous and reproducible quantitative approaches to measuring implementation determinants and strategies, and may address a longstanding gap in the quality of care for persons with co-occurring disorders. TRIAL REGISTRATION: ClinicalTrials.gov NCT03007940 . Registered 02 January 2017 - Retrospectively Registered.

Strategies For Clinical Implementation: Precision Oncology At Three Distinct Institutions.

Despite rapid advances in molecular diagnostics and targeted therapeutics, the adoption of precision medicine into clinical oncology workflows has been slow. Questions about clinical utility, inconsistent reimbursement for molecular diagnostics, and limited access to targeted therapies are some of the major hurdles that have hampered clinical adoption. Despite these challenges, providers have invested in precision medicine programs in an ongoing search for innovative care models to deliver improved patient outcomes and achieve economic gains. We describe the precision oncology medicine programs implemented by an integrated delivery system, a community care center, and an academic medical center, to demonstrate the approaches and challenges associated with clinical implementation efforts designed to advance this treatment paradigm. Payer policies that include coverage for broad genomic testing panels would support the broader application of precision medicine, deepen research benefits, and bring targeted therapies to more patients with advanced cancer.

Delivering Precision Oncology in a Community Cancer Program: Results From a Prospective Observational Study.

INTRODUCTION: Precision oncology (PO) is a growing treatment approach in the era of next-generation sequencing (NGS) and matched therapies. Effective delivery of PO in the community has not been extensively studied. Our program developed a virtual molecular tumor board (MTB) strategy to help guide PO care. MATERIALS AND METHODS: Over 18 months, eligible adult patients with advanced, incurable solid tumor malignancies were enrolled in a molecular profiling (MP) study using the Foundation Medicine NGS panel. Results were reviewed through a weekly, videoconferenced MTB conducted across our largely rural integrated health system. Recommendations from the MTB were used to identify actionable alterations (AAs). Feasibility of PO care delivery was assessed as the primary outcome. Secondary outcomes included the frequency of AAs, genomic matched treatments, genomic matched clinical trial enrollment, and clinical outcomes. RESULTS: A total of 120 participants with a variety of advanced tumor types were enrolled. Of these, 109 (90.8%) had successful MP. Treatment on the basis of an AA was recommended by the MTB in 58% of patients (63 of 109) who had a successful MP result. For those completing MP, treatments included enrollment in a genomic matched clinical trial (n = 16; 14.6%) and genomic matched treatment with a Food and Drug Administration-approved agent (n = 23; 21.1%). Response and survival data were similar regardless of the matched treatment option chosen. CONCLUSION: A video-conferenced MTB-facilitated NGS testing and treatment delivery system was implemented in our integrated community oncology program. Continued use of this model aims to increase understanding of the impact of PO in this setting.

A Retrospective Analysis of Precision Medicine Outcomes in Patients With Advanced Cancer Reveals Improved Progression-Free Survival Without Increased Health Care Costs.

PURPOSE: The advent of genomic diagnostic technologies such as next-generation sequencing has recently enabled the use of genomic information to guide targeted treatment in patients with cancer, an approach known as precision medicine. However, clinical outcomes, including survival and the cost of health care associated with precision cancer medicine, have been challenging to measure and remain largely unreported. PATIENTS AND METHODS: We conducted a matched cohort study of 72 patients with metastatic cancer of diverse subtypes in the setting of a large, integrated health care delivery system. We analyzed the outcomes of 36 patients who received genomic testing and targeted therapy (precision cancer medicine) between July 1, 2013, and January 31, 2015, compared with 36 historical control patients who received standard chemotherapy (n = 29) or best supportive care (n = 7). RESULTS: The average progression-free survival was 22.9 weeks for the precision medicine group and 12.0 weeks for the control group ( P = .002) with a hazard ratio of 0.47 (95% CI, 0.29 to 0.75) when matching on age, sex, histologic diagnosis, and previous lines of treatment. In a subset analysis of patients who received all care within the Intermountain Healthcare system (n = 44), per patient charges per week were $4,665 in the precision treatment group and $5,000 in the control group ( P = .126). CONCLUSION: These findings suggest that precision cancer medicine may improve survival for patients with refractory cancer without increasing health care costs. Although the results of this study warrant further validation, this precision medicine approach may be a viable option for patients with advanced cancer.

Differences in Regional Brain Volumes Two Months and One Year after Mild Traumatic Brain Injury.

Conventional structural imaging is often normal after mild traumatic brain injury (mTBI). There is a need for structural neuroimaging biomarkers that facilitate detection of milder injuries, allow recovery trajectory monitoring, and identify those at risk for poor functional outcome and disability. We present a novel approach to quantifying volumes of candidate brain regions at risk for injury. Compared to controls, patients with mTBI had significantly smaller volumes in several regions including the caudate, putamen, and thalamus when assessed 2 months after injury. These differences persisted but were reduced in magnitude 1 year after injury, suggesting the possibility of normalization over time in the affected regions. More pronounced differences, however, were found in the amygdala and hippocampus, suggesting the possibility of regionally specific responses to injury.

What Influences Participation in QI? A Randomized Trial of Addiction Treatment Organizations.

Healthcare providers have increased the use of quality improvement (QI) techniques, but organizational variables that affect QI uptake and implementation warrant further exploration. This study investigates organizational characteristics associated with clinics that enroll and participate over time in QI. The Network for the Improvement of Addiction Treatment (NIATx) conducted a large cluster-randomized trial of outpatient addiction treatment clinics, called NIATx 200, which randomized clinics to one of four QI implementation strategies: (1) interest circle calls, (2) coaching, (3) learning sessions, and (4) the combination of all three components. Data on organizational culture and structure were collected before, after randomization, and during the 18-month intervention. Using univariate descriptive analyses and regression techniques, the study identified two significant differences between clinics that enrolled in the QI study (n = 201) versus those that did not (n = 447). Larger programs were more likely to enroll and clinics serving more African Americans were less likely to enroll. Once enrolled, higher rates of QI participation were associated with clinics' not having a hospital affiliation, being privately owned, and having staff who perceived management support for QI. The study discusses lessons for the field and future research needs.

Dynamic contrast-enhanced MRI-based biomarkers of therapeutic response in triple-negative breast cancer.

OBJECTIVE: To predict the response of breast cancer patients to neoadjuvant chemotherapy (NAC) using features derived from dynamic contrast-enhanced (DCE) MRI. MATERIALS AND METHODS: 60 patients with triple-negative early-stage breast cancer receiving NAC were evaluated. Features assessed included clinical data, patterns of tumor response to treatment determined by DCE-MRI, MRI breast imaging-reporting and data system descriptors, and quantitative lesion kinetic texture derived from the gray-level co-occurrence matrix (GLCM). All features except for patterns of response were derived before chemotherapy; GLCM features were determined before and after chemotherapy. Treatment response was defined by the presence of residual invasive tumor and/or positive lymph nodes after chemotherapy. Statistical modeling was performed using Lasso logistic regression. RESULTS: Pre-chemotherapy imaging features predicted all measures of response except for residual tumor. Feature sets varied in effectiveness at predicting different definitions of treatment response, but in general, pre-chemotherapy imaging features were able to predict pathological complete response with area under the curve (AUC)=0.68, residual lymph node metastases with AUC=0.84 and residual tumor with lymph node metastases with AUC=0.83. Imaging features assessed after chemotherapy yielded significantly improved model performance over those assessed before chemotherapy for predicting residual tumor, but no other outcomes. CONCLUSIONS: DCE-MRI features can be used to predict whether triple-negative breast cancer patients will respond to NAC. Models such as the ones presented could help to identify patients not likely to respond to treatment and to direct them towards alternative therapies.

Sustainability in primary care and Mental Health Integration projects in Veterans Health Administration.

OBJECTIVE: To explore staff perceptions about sustainability, commitment to change, participation in change process, and information received about the change project within the Veterans Administration Primary Care and Mental Health Integration (PC-MHI) initiative and to examine differences from the Veterans Health Administration Mental Health Systems Redesign (MHSR) initiative. DATA SOURCES: Surveys of change team members involved in the Veterans Affairs PC-MHI and MHSR initiatives. STUDY DESIGN: One-way analysis of variance examined the relationship between commitment, participation and information, and sustainability. Differences in PC-MHI sustainability were explored by location and job classification. Staff sustainability perceptions were compared with MHSR results. PRINCIPAL FINDINGS: Sustainability differed by staff discipline. Difference between MHSR and PC-MHI existed by job function and perceptions about the change benefits. Participation in the change process and information received about the change process were positively correlated with sustainability. Staff commitment to change was positively associated with staff perceptions about the benefits of change and staff attitudes toward change. CONCLUSIONS: Sustainability is an important part of organizational change efforts. Change complexity seems to influence perception about sustainability and impacts staff perceptions about the benefits of change. These perceptions seem to be driven by the information received and opportunities to participate in the change process. Further research is needed to understand how information and participation influence sustainability and affect employee commitment to change.

Intensity-modulated radiotherapy for pancreatic adenocarcinoma.

PURPOSE: To report the outcomes and toxicities in patients treated with intensity-modulated radiotherapy (IMRT) for pancreatic adenocarcinoma. METHODS AND MATERIALS: Forty-seven patients with pancreatic adenocarcinoma were treated with IMRT between 2003 and 2008. Of these 47 patients, 29 were treated adjuvantly and 18 definitively. All received concurrent 5-fluorouracil chemotherapy. The treatment plans were optimized such that 95% of the planning target volume received the prescription dose. The median delivered dose for the adjuvant and definitive patients was 50.4 and 54.0 Gy, respectively. RESULTS: The median age at diagnosis was 63.9 years. For adjuvant patients, the 1- and 2-year overall survival rate was 79% and 40%, respectively. The 1- and 2-year recurrence-free survival rate was 58% and 17%, respectively. The local-regional control rate at 1 and 2 years was 92% and 80%, respectively. For definitive patients, the 1-year overall survival, recurrence-free survival, and local-regional control rate was 24%, 16%, and 64%, respectively. Four patients developed Grade 3 or greater acute toxicity (9%) and four developed Grade 3 late toxicity (9%). CONCLUSIONS: Survival for patients with pancreatic cancer remains poor. A small percentage of adjuvant patients have durable disease control, and with improved therapies, this proportion will increase. Systemic therapy offers the greatest opportunity. The present results have demonstrated that IMRT is well tolerated. Compared with those who received three-dimensional conformal radiotherapy in previously reported prospective clinical trials, patients with pancreatic adenocarcinoma treated with IMRT in our series had improved acute toxicity.