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Western blots indicating PYGB, PYGM, and PYGL are tissue-specific protein. PYGB is highly expressed in heart and brain. PYGM is highly expressed in skeletal muscle. PYGL is highly expressed in liver. Vinculin and tubulin were used as appropriate positive controls.

Western blots display PYGB, PYGM, and PYGL expression. A. EVs from mice treated with saline or DOX. B. PYGB in EVs and heart tissues from wild-type or MnSOD Tg mice treated with saline or DOX. C. PYGB in EVs and heart tissues from mice treated with MnP or DRZ prior to saline or DOX treatment.

Sucrose gradient isolation process for proteomics analysis. A. Diagram showing the process of EV isolation by sucrose gradient method. B. Western blots of EV markers, CD63 and CD81 of sucrose gradient fraction 1 to 5 (from the top to the bottom). C. EV verification of isolation process by electron microscopy (X49,000).

Western blots confirming the existence of PYGB, PYGM, and PYGL in SAL_EVs and DOX_EVs after treatment with proteinase K. Cell lysate was used as a positive control for PYGB, PYGM and PYGL detection. IgG and albumin were measured as a reference for proteinase K efficiency to digest extravesicular proteins.

Western blots of EV markers (CD63 and Alix) and endoplasmic reticulum marker (Calnexin) in SAL_EVs and DOX_EVs. The cell lysate was used as a positive control.

Proteins identified in both SAL_EVs and DOX_EVs

Purpose: Cardiac injury is a major cause of death in cancer survivors, and biomarkers for it are detectable only after tissue injury has occurred. Extracellular vesicles (EV) remove toxic biomolecules from tissues and can be detected in the blood. Here, we evaluate the potential of using circulating EVs as early diagnostic markers for long-term cardiac injury.Experimental Design: Using a mouse model of doxorubicin (DOX)-induced cardiac injury, we quantified serum EVs, analyzed proteomes, measured oxidized protein levels in serum EVs released after DOX treatment, and investigated the alteration of EV content.Results: Treatment with DOX caused a significant increase in circulating EVs (DOX_EV) compared with saline-treated controls. DOX_EVs exhibited a higher level of 4-hydroxynonenal adducted proteins, a lipid peroxidation product linked to DOX-induced cardiotoxicity. Proteomic profiling of DOX_EVs revealed the distinctive presence of brain/heart, muscle, and liver isoforms of glycogen phosphorylase (GP), and their origins were verified to be heart, skeletal muscle, and liver, respectively. The presence of brain/heart GP (PYGB) in DOX_EVs correlated with a reduction of PYGB in heart, but not brain tissues. Manganese superoxide dismutase (MnSOD) overexpression, as well as pretreatment with cardioprotective agents and MnSOD mimetics, resulted in a reduction of EV-associated PYGB in mice treated with DOX. Kinetic studies indicated that EVs containing PYGB were released prior to the rise of cardiac troponin in the blood after DOX treatment, suggesting that PYGB is an early indicator of cardiac injury.Conclusions: EVs containing PYGB are an early and sensitive biomarker of cardiac injury. Clin Cancer Res; 24(7); 1644–53. ©2017 AACR.See related commentary by Zhu and Gius, p. 1516

Experiencing a stroke can lead to difficulties with emotion regulation and mood disorders like depression. It is well documented that poststroke depression (PSD) affects a third of all stroke survivors. Higher levels of depression and depressive symptoms are associated with less efficient use of rehabilitation services, poor functional outcomes, negative impacts on social participation, and increased mortality. Mood in the acute phases of stroke recovery may be a key factor influencing the depression trajectory with early depression predicting poor longitudinal outcomes. The purpose of the study was to examine the effect of one active music therapy (AMT) treatment on mood following a first-time ischemic stroke during acute hospitalization. Forty-four adults received AMT defined as music-making interventions that elicit and encourage active participation. The Faces Scale was used to assess mood immediately prior to and following the treatment. A significant change in mood was found following one treatment. Comment analysis indicated that participants viewed music therapy as a positive experience. Findings here support the use of brief AMT to provide early psychological support to stroke survivors. Continued investigation into the role of music therapy in early stroke recovery is recommended.

Context: Postoperative quadriceps strength weakness after knee surgery is a persistent issue patients and health care providers encounter. Objective: To investigate the effect of neuromuscular electrical stimulation (NMES) parameters on quadriceps strength after knee surgery. Data Sources: CINAHL, MEDLINE, SPORTDiscus, and PubMed were systematically searched in December 2018. Study Selection: Studies were excluded if they did not assess quadriceps strength or if they failed to report the NMES parameters or quadriceps strength values. Additionally, studies that applied NMES to numerous muscle groups or simultaneously with other modalities/treatments were excluded. Study quality was assessed with the Physiotherapy Evidence Database (PEDro) scale for randomized controlled trials. Study Design: Systematic review. Level of Evidence: Level 1. Data Extraction: Treatment parameters for each NMES treatment was extracted for comparison. Quadriceps strength means and standard deviations were extracted and utilized to calculate Hedge g effect sizes with 95% CIs. Results: Eight RCTs were included with an average Physiotherapy Evidence Database scale score of 5 ± 2. Hedge g effect sizes ranged from small (−0.37; 95% CI, −1.00 to 0.25) to large (1.13; 95% CI, 0.49 to 1.77). Based on the Strength of Recommendation Taxonomy Quality of Evidence table, the majority of the studies included were low quality RCTs categorized as level 2: limited quality patient-oriented evidence. Conclusion: Because of inconsistent evidence among studies, grade B evidence exists to support the use of NMES to aid in the recovery of quadriceps strength after knee surgery. Based on the parameters utilized by studies demonstrating optimal treatment effects, it is recommended to implement NMES treatment during the first 2 postoperative weeks at a frequency of ≥50 Hz, at maximum tolerable intensity, with a biphasic current, with large electrodes and a duty cycle ratio of 1:2 to 1:3 (2- to 3-second ramp).

An evidence-based approach to navigation, shared decision making, and tobacco cessation education, tailored to lung cancer screening, is needed nationwide at imaging centers to achieve maximal mortality reductions from lung cancer screening.

Background Limited descriptions of preoperative education programs for total knee replacement (TKR) surgery are provided in the literature, and the most effective program design is currently unknown. Purpose The purpose of this qualitative study is to describe orthopaedic nurses' perceptions of preoperative education prior to TKR surgery. Methods Ten participants completed phone interviews and transcripts were analyzed qualitatively for themes among participants. Results Participants believed that preoperative education was a significant component impacting patient outcomes following surgery. Interprofessional preoperative education was valued, but pragmatic factors were identified as barriers to the inclusion of other disciplines within these programs. Education programs were constantly evolving on the basis of evidence-based practice and changes to orthopaedic protocols. Pragmatic factors influenced all aspects of program design, such as the timing and length of education sessions. Conclusions Results from this study provide descriptions of factors that influence program design and can be used to restructure education programs for improved patient outcomes.

BACKGROUND Preoperative education aids in reducing the incidence of poor outcomes after total knee replacement (TKR) and increasing patient readiness for discharge home but is not well described in the literature. PURPOSE The purpose of the study is to describe the current design of preoperative education for TKR across the United States. METHODS A large, national sample of orthopaedic nurses completed an online survey to describe preoperative education at their facilities. RESULTS Most participants provided preoperative education as part of interprofessional teams in either a group format or combined group and individual education. Verbal instruction was the most common educational delivery method, followed by written instruction. Education typically lasted between 1 and 1.5 hours, was delivered in a single session, and included a variety of topics. CONCLUSION Results of this study describe preoperative educational practices and can support future research to improve patient outcomes following TKR surgery.

Background The purpose of this paper is to describe the Automated Heart-Health Assessment (AH-HA) study protocol, which demonstrates an agile approach to cancer care delivery research. This study aims to assess the effect of a clinical decision support tool for cancer survivors on cardiovascular health (CVH) discussions, referrals, completed visits with primary care providers and cardiologists, and control of modifiable CVH factors and behaviors. The COVID-19 pandemic has caused widespread disruption to clinical trial accrual and operations. Studies conducted with potentially vulnerable populations, including cancer survivors, must shift towards virtual consent, data collection, and study visits to reduce risk for participants and study staff. Studies examining cancer care delivery innovations may also need to accommodate the increased use of virtual visits. Methods/design This group-randomized, mixed methods study will recruit 600 cancer survivors from 12 National Cancer Institute Community Oncology Research Program (NCORP) practices. Survivors at intervention sites will use the AH-HA tool with their oncology provider; survivors at usual care sites will complete routine survivorship visits. Outcomes will be measured immediately after the study visit, with follow-up at 6 and 12 months. The study was amended during the COVID-19 pandemic to allow for virtual consent, data collection, and intervention options, with the goal of minimizing participant-staff in-person contact and accommodating virtual survivorship visits. Conclusions Changes to the study protocol and procedures allow important cancer care delivery research to continue safely during the COVID-19 pandemic and give sites and survivors flexibility to conduct study activities in-person or remotely., Highlights • We present a protocol to examine the effectiveness of an electronic health record (EHR)-embedded CVH assessment tool for cancer survivors. • The protocol was adapted to include virtual data collection and study visits to continue in the COVID-19 era. • Flexibility to conduct study activities in-person or remotely supports accrual during the COVID-19 pandemic and beyond.

BACKGROUND: Lower extremity injuries in soccer players are extremely common. Implementation of group injury prevention programs has gained popularity due to time and cost-effectiveness. Unfortunately, players with greater number of risk factors are most likely to sustain an injury, yet less likely to benefit from a group injury prevention program. The purpose of this study was to determine if targeting these high risk players with one-on-one treatment would result in a reduction in the number of risk factors they possess. The authors hypothesized that fifty percent or more of subjects receiving one-on-one intervention would have a reduction of ≥1 risk factor(s). STUDY DESIGN: Quasi-experimental pretest-posttest design. METHODS: Division I men's and women's soccer players were screened for modifiable risk factors using a battery of tests which assessed mobility, fundamental movement pattern performance, motor control, and pain. Players with ≥ 3 risk factors (“high risk”) received one-on-one treatment from a physical therapist via an algorithm twice per week for four weeks. Players with

Total knee replacement (TKR) surgery has been found to achieve positive outcomes for many patients such as reduced pain and increased function. However, some patients experience suboptimal outcomes including falls, readmission to hospital, and reduced functional performance. Preparation for discharge after TKR surgery is often defined related to pain control, walking, knee function, and ability to climb stairs. These measures may not fully encompass aspects of recovery that impact patients' readiness for discharge after surgery. The purpose of this article is to review discharge readiness following TKR surgery and discuss factors that are known to impact preparedness for discharge.

In light of the need to expand the reach and access of clinically proven digital Diabetes Prevention Programs (d-DPPs) and the need for rigorous evidence of effectiveness, the purpose of this study was to determine the effectiveness of a digital Diabetes Prevention Program for improving weight, HbA1c, and cardiovascular risk factors among people with prediabetes compared to enhanced standard care plus waitlist control.This was a single-blind RCT among participants at risk of developing type 2 diabetes and included 12 months of follow-up.A total of 599 volunteer patients with prediabetes were recruited primarily through electronic medical records and primary care practices.Participants were randomized to either a d-DPP (n=299) or a single-session small-group diabetes-prevention education class (n=300) focused on action planning for weight loss. The d-DPPs consisted of 52 weekly sessions, lifestyle coaching, virtual peer support, and behavior tracking tools.The primary outcome was a change in HbA1c from baseline to 12 months using intent-to-treat analyses. On the basis of multiple comparisons of endpoints, 95% CIs are presented and 2-sided p0.025 was required for statistical significance. Secondary outcomes included body weight and cardiovascular disease risk factors.Among 599 randomized participants (mean age=55.4 years, 61.4% women), 483 (80%) completed the study. The d-DPPs produced significantly greater reductions in HbA1c (0.08%, 95% CI= -0.12, -0.03) and percentage change in body weight (-5.5% vs -2.1%, p0.001) at 12 months. A greater proportion of the d-DPPs group achieved a clinically significant weight loss ≥5% (43% vs 21%, p0.001), and more participants shifted from prediabetes to normal HbA1c range (58% vs 48%, p=0.04). Engagement in d-DPPs was significantly related to improved HbA1c and weight loss.This d-DPPs demonstrated clinical effectiveness and has significant potential for widespread dissemination and impact, particularly considering the growing demand for telemedicine in preventive healthcare services.This study is registered at www.gov (ClinicalTrials.gov Identifier: NCT03312764).

Population health management (PHM) strategies to address diabetes prevention have the potential to engage large numbers of at-risk individuals in a short duration. We examined a PHM approach to recruit participants to a diabetes prevention clinical trial in a metropolitan health system. We examined reach and representativeness and assessed differences from active and passive respondents to recruitment outreach, and participants enrolled through two clinical screening protocols. The PHM approach included an electronic health record (EHR) query, physician review of identified patients, letter invitation, and telephone follow-up. Data describe the reach and representativeness of potential participants at multiple stages during the recruitment process. Subgroup analyses examined proportional reach, participant differences based on passive versus active recruitment response, and clinical screening method used to determine diabetes risk status. The PHM approach identified 10,177 potential participants to receive a physician letter invitation, 60% were contacted by telephone, 2,796 (46%) completed telephone screening, 1,961 were eligible from telephone screen, and 599 were enrolled in 15 months. Accrual was unaffected by shifting clinical screening protocols despite the increase in participant burden. Relative to census data, study participants were more likely to be obese, female, older, and Caucasian. Relative to the patient population, enrolled participants were less likely to be Black and were older. Active respondents were more likely to have a higher income than passive responders. PHM strategies have the potential to reach a large number of participants in a relatively short period, though concerted efforts are needed to increase participant diversity.

Background Cardiovascular health is of increasing concern to breast cancer survivors and their health care providers, as many survivors are more likely to die from cardiovascular disease than cancer. Implementing clinical decision support tools to address cardiovascular risk factor awareness in the oncology setting may enhance survivors’ attainment or maintenance of cardiovascular health. Objective We sought to evaluate survivors’ awareness of cardiovascular risk factors and examine the usability of a novel electronic health record enabled cardiovascular health tool from the perspective of both breast cancer survivors and oncology providers. Methods Breast cancer survivors (n=49) recruited from a survivorship clinic interacted with the cardiovascular health tool and completed pre and posttool assessments about cardiovascular health knowledge and perceptions of the tool. Oncologists, physician assistants, and nurse practitioners (n=20) who provide care to survivors also viewed the cardiovascular health tool and completed assessments of perceived usability and acceptability. Results Enrolled breast cancer survivors (84% White race, 4% Hispanic ethnicity) had been diagnosed 10.8 years ago (SD 6.0) with American Joint Committee on Cancer stage 0, I, or II (45/49, 92%). Prior to viewing the tool, 65% of survivors (32/49) reported not knowing their level for one or more cardiovascular health factors (range 0-4). On average, only 45% (range 0%-86%) of survivors’ known cardiovascular health factors were at an ideal level. More than 50% of survivors had ideal smoking status (45/48, 94%) or blood glucose level (29/45, 64%); meanwhile, less than 50% had ideal blood pressure (12/49, 24%), body mass index (12/49, 24%), cholesterol level (17/35, 49%), diet (7/49, 14%), and physical activity (10/49. 20%). More than 90% of survivors thought the tool was easy to understand (46/47, 98%), improved their understanding (43/47, 91%), and was helpful (45/47, 96%); overall, 94% (44/47 survivors) liked the tool. A majority of survivors (44/47, 94%) thought oncologists should discuss cardiovascular health during survivorship care. Most (12/20, 60%) oncology providers (female: 12/20, 60%; physicians: 14/20, 70%) had been practicing for more than 5 years. Most providers agreed the tool provided useful information (18/20, 90%), would help their effectiveness (18/20, 90%), was easy to use (20/20, 100%), and presented information in a useful format (19/20, 95%); and 85% of providers (17/20) reported they would use the tool most or all of the time when providing survivorship care. Conclusions These usability data demonstrate acceptability of a cardiovascular health clinical decision support tool in oncology practices. Oncology providers and breast cancer survivors would likely value the integration of such apps in survivorship care. By increasing awareness and communication regarding cardiovascular health, electronic health record–enabled tools may improve survivorship care delivery for breast cancer and ultimately patient outcomes.

Background: Cancer-related financial hardship is associated with poor care outcomes and reduced quality of life for patients and families. Scalable intervention development to address financial hardship requires knowledge of current screening practices and services within community cancer care. Methods: The NCI Community Oncology Research Program (NCORP) 2017 Landscape Assessment survey assessed financial screening and financial navigation practices within U.S. community oncology practices. Logistic models evaluated associations between financial hardship screening and availability of a cancer-specific financial navigator and practice group characteristics (e.g., safety-net designation, critical access hospital, proportion of racial and ethnic minority patients served). Results: Of 221 participating NCORP practice groups, 72% reported a financial screening process and 50% had a cancer-specific financial navigator. Practice groups with more than 10% of new patients with cancer enrolled in Medicaid (adjOR = 2.81, P = 0.02) and with less than 30% racial/ethnic minority cancer patient composition (adjOR = 3.91, P < 0.01) were more likely to screen for financial concerns. Practice groups with less than 30% racial/ethnic minority cancer patient composition (adjOR = 2.37, P < 0.01) were more likely to have a dedicated financial navigator or counselor for patients with cancer. Conclusions: Most NCORP practice groups screen for financial concerns and half have a cancer-specific financial navigator. Practices serving more racial or ethnic minority patients are less likely to screen and have a designated financial navigator. Impact: The effectiveness of financial screening and navigation for mitigating financial hardship could be tested within NCORP, along with specific interventions to address cancer care inequities. See related commentary by Yabroff et al., p. 593

Background: Chemotherapy-induced cognitive impairment (CICI), ‘chemo-brain,’ involves concentration and executive functioning difficulty and slowed processing speed and memory. Although cognitive changes in CICI can be subtle and difficult to quantify, CICI affects up to 75% of cancer survivors and impacts quality of life. Objectives: The objective of our study was to add to the definition of CICI by quantifying changes in specific cognitive domains before and after administration of platinum/taxane-based chemotherapy in gynecologic cancer patients using a tailored battery of neurocognitive tests. Methods: Following institutional review board approval, chemotherapy-naive gynecologic cancer patients scheduled to receive six cycles of intravenous platinum/taxane-based chemotherapy were identified. Baseline demographic, social, and clinical characteristics were obtained. Eleven neurocognitive assessments measured cognitive domains of interest (Table 1), including a brief cognitive screen, evaluation of fine motor skills, verbal fluency, working memory, information processing speed, visuospatial learning and memory, attention, mental flexibility, and abstract problem-solving skills. The European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire Core-30 and Psychiatric Diagnostic Screening Questionnaire assessed emotional functioning. The Functional Assessment of Cancer Therapy - Cognitive Function assessed self-perceived cognitive functioning. Testing was performed prior to the first and three to four weeks after the last cycle of chemotherapy. Descriptive statistics identified trends in individual indices of cognitive dysfunction and quality of life. Results: Fourteen patients enrolled and nine were eligible for complete analyses. The mean age was 60.6 years. The mean full scale intelligence quotient prior to therapy was 103.5. Most patients were White (8/9, 89%), had obtained at least a Bachelor's degree (5/9, 55.6%), and were diagnosed with high grade (6/9, 66.7%) stage III or IV disease (5/9, 55.6%). The majority of patients declined on cognitive screening performance (5/9, 55.6%) as well as worse scores on indices of attention (7/9, 77.8%), mental flexibility (5/8, 62.5%) verbal learning (5/9, 55.6%), and fine motor skills (5/9, 55.6%) after completion of chemotherapy. Most patients improved on indices of verbal memory (7/9, 77.8%), visuospatial learning (6/8, 75%), and verbal fluency (5/9, 55.6%). Despite changes in indices of cognitive function, most patients’ perceived quality of life improved (5/9, 55.6%) after chemotherapy. Download : Download high-res image (219KB) Download : Download full-size image Conclusions: Although gynecologic cancer patients complain of CICI, there is discrepancy regarding its incidence and affected cognitive domains. This pilot study highlights attention and mental flexibility as indices of cognitive dysfunction that may be at risk following receipt of chemotherapy in gynecologic cancer patients. Future research may focus on targeted assessment strategies.

Background American Society of Clinical Oncology guidelines recommend that patients ≥65 years of age starting chemotherapy undergo a geriatric assessment (GA) to inform and guide management; however, little is known about resources available in community oncology practices to implement these guidelines and to facilitate geriatric oncology research. Materials and Methods Oncology practices within the National Cancer Institute Community Oncology Research Program (NCORP) were electronically surveyed in 2017 regarding the availability of specialty providers, supportive services, and practice characteristics, as part of a larger survey of cancer care delivery research capacity. Results Of the 943 NCORP practices, 504 (54%) responded to the survey, representing 210 practice groups. The median new cancer cases per year ≥65 years of age was 457 (interquartile range 227–939). Of respondents, only 2.0% of practices had a fellowship-trained geriatric oncologist on staff. Geriatricians were available for consultation or comanagement at 37% of sites, and of those, only 13% had availability within the oncology clinic (5% of overall). Practice size of ≥1,000 new adult cancer cases (ages ≥18) per year was associated with higher odds (1.81, confidence interval 1.02–3.23) of geriatrician availability. Other multidisciplinary care professionals that could support GA were variably available onsite: social worker (84%), nurse navigator (81%), pharmacist (77%), dietician (71%), rehabilitative medicine (57%), psychologist (42%), and psychiatrist (37%). Conclusion Only a third of community oncology practices have access to a geriatrician within their group and only 5% of community sites have access within the oncology clinic. Use of primarily self-administered GA tools that direct referrals to available services may be an effective implementation strategy for guideline-based care. Implications for Practice Only a minority of community oncology practices in the U.S. have access to geriatric specialty care. Developing models of care that use patient-reported measures and/or other geriatric screening tools to assess and guide interventions in older adults, rather than geriatric consultations, are likely the most practical methods to improve the care of this vulnerable population.

BACKGROUND Cardiovascular health is of increasing concern to breast cancer survivors and their health care providers, as many survivors are more likely to die from cardiovascular disease than cancer. Implementing clinical decision support tools to address cardiovascular risk factor awareness in the oncology setting may enhance survivors’ attainment or maintenance of cardiovascular health. OBJECTIVE We sought to evaluate survivors’ awareness of cardiovascular risk factors and examine the usability of a novel electronic health record enabled cardiovascular health tool from the perspective of both breast cancer survivors and oncology providers. METHODS Breast cancer survivors (n=49) recruited from a survivorship clinic interacted with the cardiovascular health tool and completed pre and posttool assessments about cardiovascular health knowledge and perceptions of the tool. Oncologists, physician assistants, and nurse practitioners (n=20) who provide care to survivors also viewed the cardiovascular health tool and completed assessments of perceived usability and acceptability. RESULTS Enrolled breast cancer survivors (84% White race, 4% Hispanic ethnicity) had been diagnosed 10.8 years ago (SD 6.0) with American Joint Committee on Cancer stage 0, I, or II (45/49, 92%). Prior to viewing the tool, 65% of survivors (32/49) reported not knowing their level for one or more cardiovascular health factors (range 0-4). On average, only 45% (range 0%-86%) of survivors’ known cardiovascular health factors were at an ideal level. More than 50% of survivors had ideal smoking status (45/48, 94%) or blood glucose level (29/45, 64%); meanwhile, less than 50% had ideal blood pressure (12/49, 24%), body mass index (12/49, 24%), cholesterol level (17/35, 49%), diet (7/49, 14%), and physical activity (10/49. 20%). More than 90% of survivors thought the tool was easy to understand (46/47, 98%), improved their understanding (43/47, 91%), and was helpful (45/47, 96%); overall, 94% (44/47 survivors) liked the tool. A majority of survivors (44/47, 94%) thought oncologists should discuss cardiovascular health during survivorship care. Most (12/20, 60%) oncology providers (female: 12/20, 60%; physicians: 14/20, 70%) had been practicing for more than 5 years. Most providers agreed the tool provided useful information (18/20, 90%), would help their effectiveness (18/20, 90%), was easy to use (20/20, 100%), and presented information in a useful format (19/20, 95%); and 85% of providers (17/20) reported they would use the tool most or all of the time when providing survivorship care. CONCLUSIONS These usability data demonstrate acceptability of a cardiovascular health clinical decision support tool in oncology practices. Oncology providers and breast cancer survivors would likely value the integration of such apps in survivorship care. By increasing awareness and communication regarding cardiovascular health, electronic health record–enabled tools may improve survivorship care delivery for breast cancer and ultimately patient outcomes.

Background Supportive care interventions have demonstrated benefits for both informal and/or family cancer caregivers and their patients, but uptake generally is poor. To the authors' knowledge, little is known regarding the availability of supportive care services in community oncology practices, as well as engagement practices to connect caregivers with these services. Methods Questions from the National Cancer Institute Community Oncology Research Program (NCORP)'s 2017 Landscape Survey examined caregiver engagement practices (ie, caregiver identification, needs assessment, and supportive care service availability). Logistic regression was used to assess the relationship between the caregiver engagement outcomes and practice group characteristics. Results A total of 204 practice groups responded to each of the primary outcome questions. Only 40.2% of practice groups endorsed having a process with which to systematically identify and document caregivers, although approximately 76% were routinely using assessment tools to identify caregiver needs and approximately 63.7% had supportive care services available to caregivers. Caregiver identification was more common in sites affiliated with a critical access hospital (odds ratio [OR], 2.44; P = .013), and assessments were less common in safety-net practices (OR, 0.41; P = .013). Supportive care services were more commonly available in the Western region of the United States, in practices with inpatient services (OR, 2.96; P = .012), and in practices affiliated with a critical access hospital (OR, 3.31; P = .010). Conclusions Although many practice groups provide supportive care services, fewer than one-half systematically identify and document informal cancer caregivers. Expanding fundamental engagement practices such as caregiver identification, assessment, and service provision will be critical to support recent calls to improve caregivers' well-being and skills to perform caregiving tasks.

Preoperative education aids in reducing the incidence of poor outcomes after total knee replacement (TKR) and increasing patient readiness for discharge home but is not well described in the literature.The purpose of the study is to describe the current design of preoperative education for TKR across the United States.A large, national sample of orthopaedic nurses completed an online survey to describe preoperative education at their facilities.Most participants provided preoperative education as part of interprofessional teams in either a group format or combined group and individual education. Verbal instruction was the most common educational delivery method, followed by written instruction. Education typically lasted between 1 and 1.5 hours, was delivered in a single session, and included a variety of topics.Results of this study describe preoperative educational practices and can support future research to improve patient outcomes following TKR surgery.

The primary purpose was to determine if there is a difference between the median frequency slopes of 5 posterior shoulder muscles during the initial portion of the Posterior Shoulder Endurance Test (PSET) at the 90° and 135° shoulder abduction positions. Fifty-five healthy volunteers (31 females) participated. The median frequency of the posterior deltoid (PD), upper trapezius (UT), middle trapezius (MT), lower trapezius (LT), and infraspinatus (INF) was measured during the PSET at 90° and 135° of shoulder abduction. External torque of 13 ± 1 Nm was used for females and 21 ± 1 Nm for males. A fixed effect multi-variable regression model was used to investigate the median frequency slopes. Males and females were analyzed separately. Median frequency slopes demonstrated fatigue in all 5 of the muscles. The PD fatigued greater than the UT in males (p = 0.0215) and greater than the LT in females (p = 0.008). The time to task failure (TTF) was greater at 90° than 135° for females and males (p = 0.016; p = 0.0193) respectively. The PSET causes fatigue in all of the muscles that were tested, with the PD fatiguing at a greater rate compared to one muscle for each sex. This investigation supports using TTF as a clinical measure of shoulder girdle endurance at 90° shoulder abduction.

Glioblastoma in children is an aggressive disease with no defined standard therapy. We evaluated hospital‐based demographic and survival patterns obtained through the National Cancer Database to better characterize children with glioblastoma. Our study identified 1173 patients from 0 to 19 years of age between 1998 and 2011. Comparisons were made among demographics, clinical characteristics, treatment, and survival variables. Fifty‐four percent of patients were over 10 years of age. Approximately 80% of patients underwent either partial or complete resection. Adjuvant therapy was used variably, and its use increased with patient age. Forty‐eight percent of patients received the combination of surgery, radiation, and chemotherapy, and 4% did not receive any treatment. As expected, patients ≤5 years of age had better 5‐year survival than those ages 6–10 (P = 0.01) or 11–19 years (P = 0.0077). Other factors associated with poor survival included black race and central tumor location. Better outcomes were associated with treatment that included surgery, radiotherapy, and chemotherapy compared to any other treatment combinations. Radiotherapy had no impact on survival in the 0 to 10‐year‐old age group, but was associated with improved survival for patients 11–19 years. We report an extensive demographic and survival analysis of pediatric glioblastoma. The observed differences likely reflect variances in tumor biology and likelihood of treatment receipt. Improved survival was associated with the use of surgery, radiotherapy, and chemotherapy. Radiation therapy was not associated with survival in patients younger than 10 years of age.

Background Recent publication of Suppression of Ovarian Function (SOFT) and Tamoxifen and Exemestane (TEXT) trials provides additional options for premenopausal women with hormone receptor (HR)-positive breast cancer in improving estrogen blockade - tamoxifen (T) plus ovarian function suppression (OFS) and aromatase inhibitors (AI) plus OFS. Analysis of these trials conclude that, for a premenopausal woman with HR-positive breast cancer with high risk features for recurrence have an absolute benefit for five-year breast cancer free interval (BCFI) would be 5% with the use of T + OFS and 10 - 15% with AI + OFS compared to the usof T-alone. However, therapeutic option decision-making is dependent on the oncologists' perception of the benefit and risk for adjuvant anti-estrogen therapy. We aimed to evaluate an oncologist's perception of the absolute benefit for anti-estrogen therapy options in HR–positive breast cancer and identify predictors for variations in perceptions of benefit. Methods We designed a survey using a clinical vignette of a young, premenopausal woman with stage IIIA HR-positive breast cancer with high risk of recurrence. After obtaining Institutional Review Board (IRB) approval from the University of Kentucky, we sent online and paper survey forms to a convenience sample of 510 oncologists in the United States. Using a scale between 0 and 100, the oncologists were asked to estimate the five-year BCFI (first occurrence of invasive locoregional, distant or contralateral breast cancer) for a woman with similar characteristics if treated with the following: 1) lumpectomy (L) + Radiation (RT); 2) L + RT + chemotherapy (C); 3) L + RT + C + T x five years; 4) L + RT + C + T + OFS; and 5) L + RT + C + AI + OFS. Baseline demographics such as gender, practice setting (academic vs community), years in practice and proportion of breast cancer patients in practice were also collected. Results The highest estimated mean five-year BCFI for the study patient was 76.5% with the addition of AI + OFS to L + RT + C. The estimated absolute benefit for anti-estrogen therapy options: T + OFS vs T-alone was 3.4% (95% CI: 2.7 – 4.0) and for AI + OFS vs T-alone was 5.9% (95% CI: 5.1 – 6.7). Oncologists' Perception of Absolute Benefit Therapy in Premenopausal Women with Breast CancerAnti-Estrogen Therapy5-year BCFI (mean)Standard DeviationL+ RT43.6+/- 18.6L + RT + C59.5+/- 15.5L + RT + C + T x 5 year70.6+/- 13.4L + RT + C + T + OFS74.1+/- 12.9L + RT + C + AI + OFS76.5+/- 12.7 There was no difference in perception of benefit with these anti-estrogen therapy options by gender, practice setting, years in practice or proportion of breast cancer patients seen in practice. Discussion Regardless of their gender, practice setting, clinical experience or volume of breast cancer patients, oncologists significantly underestimate the absolute benefit for various estrogen blockade therapies when compared to the estimated benefit of data from randomized, controlled SOFT and TEXT clinical trial data. We highlight an area for improvement in quality of care that offers an immediate impact on positive outcomes for large numbers of premenopausal women with breast cancer. Citation Format: Patel RA, Maxwell S, Yan D, Dressler E, Mathew A. Oncologists' perception of anti-estrogen therapy benefit [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P1-15-05.

Objectives: The National Cancer Institute (NCI) Community Oncology Research Program (NCORP) was developed as a platform to study cancer care delivery at 23 community sites and 14 minority/underserved sites, encompassing 943 care delivery locations nationwide. We describe the capacity of the NCORP network to conduct cancer care delivery research for gynecologic cancers. We also characterize community practices where patients are treated for gynecologic cancers without an affiliated gynecologic oncologist, as these patients may be at higher risk for outcomes disparities. Methods: The 2017 Landscape Capacity Assessment (LCA) was designed by the NCI Division of Cancer Prevention and administered to 943 NCORP locations. This survey included elements related to clinical setting (e.g., size, location, characteristics of patients), staffing (e.g., number/types of care providers), and cancer care practices (e.g., genetic testing, patient navigation). Primary populations of interest were practices identified as providing gynecologic cancer services, and the subgroup of practices providing gynecologic cancer services without an affiliated gynecologic oncologist. χ2 tests were used to test for differences in categorical variables. Results: A total of 504/943 locations (54%), representing 227 practices completed the LCA; 17 practices solely providing pediatric care were excluded. A total of 46% of responding practices serve >1000 patients per year, 23% report at least 30% of new patients represent minority populations. 41% and 11% of practices report >10% of patients are insured through Medicaid, or are uninsured, respectively. 36% of practices are independently owned while 54% are owned by a larger health system. 22% of practices are embedded in Critical Access hospitals. 29% participate in the Oncology Care Model through the Centers for Medicare and Medicaid Services. 84% record patient data in an EHR. 30% of sites utilize telemedicine for cancer care and 51% of these practices can adapt telemedicine for research purposes. 93% of practices provide survivorship care. 129 groups (56%) reported GYN cancer services; 48% of all practices have an affiliated gynecologic oncologist (median 0; range 1-48). Practices evaluating >1000 patients annually were significantly more likely to offer GYN cancer services. No association was seen between availability of GYN cancer services and insurance mix, proportion of minority patients, use of telemedicine, or availability of community outreach staff. Of practices providing GYN cancer services, practices without an affiliated gynecologic oncologist were less likely to evaluate >1000 new patients annually (35% vs 76%; p Download : Download high-res image (106KB) Download : Download full-size image Conclusions: NCORP offers a unique opportunity to study cancer care delivery in community settings, including in underserved minority populations. This platform should be considered for the study of interventional trials aimed at ensuring that patients receive high-quality gynecologic cancer care, especially in the high-risk population of patients who are treated in practices without an affiliated gynecologic oncologist.

Purpose To assess for the differences in patients undergoing tracheostomy by the otolaryngology consult service versus other specialties. Materials and methods A series of 1035 tracheostomies performed at our institution from January 2013 through November 2015 was retrospectively reviewed. Patient-related factors that contribute to procedural difficulty were reviewed. Results 805 consecutive tracheostomies were included. Otolaryngology performed 176/805 (21.8%) tracheostomies as a consulting service. Morbidly obese patients were three times as likely to be referred to otolaryngology as other services (adjusted OR: 3.23; 95% CI: 2.21–4.72). Mean BMI was 36.38 kg/m2 for Consults vs. 28.69 kg/m2 for Others and morbidly obese patients had a mean BMI of 49.84 kg/m2 vs. 42.68 kg/m2 for Consults and Others respectively (p Conclusions More complex tracheostomies are being referred to and performed by otolaryngology at our institution. Difficult and challenging tracheostomies seem to be the “standard” for otolaryngologists.

Background Perineural invasion (PNI) and lymphovascular invasion (LVI) are known to be poor prognostic indicators in primary surgery. The purpose of this study was to determine their impact on survival in the setting of salvage laryngectomy. Methods We conducted a retrospective review of patients who underwent salvage laryngectomy between 2006 and 2014. Results Seventy-eight patients were included in this study; PNI was diagnosed in 48 patients (61.54%) and LVI in 25 patients (32.05%). Median overall survival was 32 months; PNI was associated with decreased survival; and the unadjusted hazard ratio (HR) was 2.69 (P = .006). Cases of LVI trended toward a decreased survival; with an unadjusted HR of 1.74 (P = .076). On multivariate analysis, PNI, LVI, or both conferred decreased survival compared to having neither (P = .01). Extracapsular spread and nodal metastases significantly impacted survival, and positive margins trended toward significance. Conclusion The presence of PNI, LVI, nodal disease, and extracapsular spread significantly affected survival in this cohort of patients with laryngeal cancer.

PURPOSE Current theoretical models suggest the importance of a bidirectional relationship between sensation and production in the vocal tract to maintain lifelong speech skills. The purpose of this study was to assess age-related changes in orofacial skilled force production and to begin defining the orofacial perception-action relationship in healthy adults. METHOD Low-level orofacial force control measures (reaction time, rise time, peak force, mean hold force (N) and force hold SD) were collected from 60 adults (19-84 years). Non-parametric Kruskal Wallis tests were performed to identify statistical differences between force and group demographics. Non-parametric Spearman's rank correlations were completed to compare force measures against previously published sensory data from the same cohort of participants. RESULT Significant group differences in force control were found for age, sex, speech usage and smoking status. Significant correlational relationships were identified between labial vibrotactile thresholds and several low-level force control measures collected during step and ramp-and-hold conditions. CONCLUSION These findings demonstrate age-related alterations in orofacial force production. Furthermore, correlational analysis suggests as vibrotactile detection thresholds increase, the ability to maintain low-level force control accuracy decreases. Possible clinical applications and treatment consequences of these findings for speech disorders in the ageing population are provided.

Objectives Prospectively validate an intraoperative surgical staging algorithm to stratify patients with early endometrial cancer by risk of lymph node metastasis. Methods Subjects with endometrial cancer clinically confined to the uterus were prospectively enrolled at an academic cancer center between Jan 2012 and Jun 2015. Study participants were stratified intraoperatively into two groups based on risk of nodal involvement using cell type, tumor grade, myometrial invasion, and tumor size in accordance with an established protocol from the Mayo Clinic. Low risk (LR) subjects received extrafascial hysterectomy with bilateral salpingo-oophorectomy; high risk (HR) patients received complete surgical staging including bilateral pelvic and para-aortic lymphadenectomy. Results Of the 200 subjects enrolled, 194 were eligible for analysis. The algorithm identified 132 (68%) HR and 62 (32%) LR cancers. Of the HR subjects, 126 had lymphadenectomy performed with 14 (11%) positive for nodal metastases. Five HR subjects experienced disease recurrence. Of the 62 LR cancers, two patients developed disease recurrence. Ten LR cancers were upgraded to HR on final pathology due to lesion size (6) and grade (4). None of these patients experienced disease recurrence. The algorithm demonstrated 90% sensitivity (18/20) and 36% specificity (62/174) as determined by positive lymph nodes and/or disease recurrence. Conclusions Intraoperative assessment of early endometrial cancer can be used to determine the extent of surgical staging. The studied algorithm has low specificity and modifications are necessary to better match the surgical procedure to the risk of metastatic cancer.

Objective The objective of this study was to determine the clinical impact of time to antibiotic administration in adult inpatients who have hematologic malignancies and develop febrile neutropenia. Methods A retrospective chart review was conducted to screen for all febrile neutropenia events amongst adult hematologic malignancy patients between 1 January 2010 and 1 September 2014. All included patients were admitted to the hospital at the time of fever onset, having been admitted for a diagnosis other than febrile neutropenia. Descriptive statistics and logistic generalized estimated equations were used to analyze the data. Results Two hundred forty-four neutropenic fever events met inclusion criteria. Thirty-five events (14.34%) led to negative clinical outcomes (in-hospital mortality, intensive care unit transfer, or vasopressor requirement), with an in-house mortality rate of 7.4%. The time to antibiotics ranged from 10 min to 1495 min. The median time to antibiotics in the events that led to negative outcomes was 120 min compared to 102 min in the events that did not lead to the negative outcome ( p = 0.93). Conditional order sets were used to order empiric antibiotics in 176 events (72.1%) and significantly reduced time to antibiotics from 287 min to 143 min ( p = 0.0019). Conclusion Prolonged time to antibiotic administration in hematologic malignancy patients who develop neutropenic fever was not shown to be associated with negative clinical outcomes.

The goal of this study was to identify associations between positron emission tomography/computed tomography (PET/CT) maximum standardized uptake value (SUVmax) in patients presenting with head and neck squamous cell carcinoma (SCC) with tumor site, size, histologic differentiation, smoking, and diabetes. Charts of patients with oropharyngeal and laryngeal SCC who underwent 18F-fluorodeoxyglucose PET/CT scans were reviewed between May 2007 and August 2013. Statistical analyses included modeling log-transformed SUVmax values by tumor site, size, histologic differentiation, smoking status, and diabetes using unadjusted linear regressions. Differences were considered statistically significant for P< 0.05. A total of 111 patients (54 with oropharynx and 57 with larynx cancers) were included, 83 men and 28 women with an average age of 57.5 years old. There was a significantly higher pack-year smoking history (P = 0.005) in the larynx cancer group. While tumor T-stage was found to be significantly different (P < 0.0001), there was no difference in tumor size between the two groups: 3.16 cm and 3.58 cm in the oropharynx and larynx, respectively (P = 0.55). In the oropharynx cohort, SUVmax was associated with both tumor size (P = 0.0001) and stage (P < 0.0002). Interestingly, SUVmax differed by tumor differentiation in the larynx (P = 0.04) but not the oropharynx (P = 0.71). Finally, there was no significant difference in SUVmax relative to diabetes and smoking status. PET/CT SUVmax correlated with both tumor size and stage in oropharyngeal cancer patients, and it correlated only with tumor differentiation but not the size or stage in the larynx. There were no significant differences in SUVmax by diabetes or smoking status.

Background Diabetes prevention remains a top public health priority; digital approaches are potential solutions to existing scalability and accessibility challenges. There remains a gap in our understanding of the relationship between effectiveness, costs, and potential for sustained implementation of digital diabetes prevention strategies within typical healthcare settings. Purpose To describe the methods and design of a type 1 hybrid effectiveness-implementation trial of a digital diabetes prevention program (DPP) using the iPARIHS and RE-AIM frameworks. Methods The trial will contrast the effects of two DPP interventions: (1) small group, in-person class, and (2) a digital DPP consisting of small group support, personalized health coaching, digital tracking tools, and weekly behavior change curriculum. Each intervention includes personal action planning with a focus on key elements of the lifestyle intervention from the CDC National DPP. Adults at risk for diabetes (BMI ≥25 and 5.7% ≤ HbA1c ≤ 6.4) will be randomly assigned to either the intervention group (n = 241) or the small group (n = 241). Assessment of primary (HbA1c) and secondary (weight loss, costs, cardiovascular risk factors) outcomes will occur at baseline, 4, and 12 months. Additionally, the trial will explore the potential for future adoption, implementation, and sustainability of the digitally-based intervention within a regional healthcare system based on key informant interviews and assessments of organizational administrators and primary care physicians. Conclusion This trial of a digital DPP will allow the research team to determine the relationships between reach, effectiveness, implementation, and costs.

This article considers the problem of designing Phase I-II clinical trials with delayed toxicity and efficacy outcomes. The proposed design is motivated by a Phase I-II study evaluating all-trans retinoic acid (ATRA) in combination with a fixed dose of daratumumab in the treatment of relapsed or refractory multiple myeloma. The primary objective of the study is to identify a dose that maximizes efficacy and has an acceptable level of toxicity. The toxicity endpoint is observed in one cycle of therapy (i.e., 4 weeks) while the efficacy endpoint is assessed after 8 weeks of treatment. The difference in endpoint observation windows causes logistical challenges in conducting the trial, since it is not practical to wait until both outcomes for each patient have been fully observed before sequentially assigning the dose of a newly eligible patient. In order to avoid delays in treatment for newly enrolled patients and to accelerate trial progress, we generalize the time-to-event continual reassessment method (TITE-CRM) to bivariate outcomes. Simulation studies are conducted to evaluate the proposed method, and we found that the proposed design is able to accurately select doses that maximize efficacy and have acceptable toxicity, while using all available information in allocating patients at the time of dose assignment. We compare the proposed methodology to two existing methods in the area.