Citations

Background: New technology and healthcare delivery approaches may help improve blood pressure (BP) control. Randomized controlled trials (RCTs) can demonstrate effectiveness of these emerging approaches, both overall and especially within underserved populations, but RCTs are expensive. Our objective is to establish a national platform to support BP control surveillance and efficient RCTs. Methods: The PCORnet BP Control Laboratory, designed and launched in partnership with the American Heart Association (AHA) and the American Medical Association (AMA), leverages electronic health record (EHR) systems throughout the US, the National Patient-Centered Outcomes Research Network (PCORnet), and the NIH-funded Eureka Research Platform, which enables direct-to-participant research including collection of patient-reported outcomes and mHealth data from wearable devices and smartphones. We will use these resources to 1) Conduct national surveillance through quarterly EHR data queries to calculate and track institution- and clinic-level BP control metrics across 23 PCORnet institutions, overall and within key subgroups, and support participation in the AHA/AMA’s Target:BP recognition program (BP Track); 2) Compare effectiveness of a Full Support versus Self-Guided version of the AMA’s Measure Accurately, Act Rapidly, and Partner with Patients (MAP) program at improving BP control in a cluster randomized trial of 24 safety net clinics (BP MAP); and 3) Compare effectiveness of Smartphone-linked versus standard home BP monitoring at reducing systolic BP in an individual-level, direct-to-participant RCT of 2000 patients with uncontrolled BP (BP Home). Results: Preliminary BP Track queries demonstrate an overall BP control rate of 56%, lower control in Black patients (51%), substantial heterogeneity in clinic-level metrics (e.g., 33% vs. 64% BP control), and low rates of medication intensification (9% prescribed a new medication class when BP was high). BP Track will launch PCORnet-wide queries in June; BP MAP in May; and BP Home in August 2019. Conclusions: Feasibility testing is underway to determine if the PCORnet BP Control Laboratory will be useful for investigators interested in conducting efficient RCTs of BP control interventions.

AbstractBackgroundThe incidence of human papillomavirus (HPV)‐related oropharyngeal squamous cell carcinoma (OPSCC) is rising, even in elderly patients. The outcomes of transoral surgery (TOS) in this population are not entirely known.MethodsA retrospective review was performed at two institutions from October 2003 to September 2016 on patients 70 years or older with HPV‐related OPSCC treated with TOS.ResultsA total of 75 patients were included with a mean age of 74 years (70‐87 years). At a median follow‐up of 35.7 months, 3‐year overall survival was 81.5% and disease‐specific survival was 94.3%. Advanced cT stage (odds ratio, 2.74; 95% confidence interval, 1.13‐6.64) negatively impacted OS. Conjunctive consolidation was performed to create a staging system with patients older than 80 years, severe comorbidity, and cT3‐4 having worse survival.ConclusionsElderly patients with HPV‐related OPSCC treated with TOS have excellent survival and therefore should not be excluded from such therapy based on age alone.

BackgroundMagnetic resonance elastography (MRE) can determine the presence and stage of liver fibrosis. Data on normative MRE values, while reported in adults, are limited in children.PurposeTo determine the distribution of MRE‐measured liver stiffness in children without liver disease.Study TypeProspective, observational.PopulationEighty‐one healthy children (mean 12.6 ± 2.6 years, range 8–17 years).Field Strength/Sequence3.0T Signa HDxt, General Electric MR Scanner; 2D GRE MRE sequence.AssessmentHistory, examination, laboratory evaluation, and (MR) exams (proton density fat fraction, PDFF, and MRE) were performed. MR elastograms were analyzed manually at two reading centers and compared with each other for agreement and with published values in healthy adults and thresholds for fibrosis in adult and pediatric patients.Statistical TestsDescriptive statistics, Bland–Altman analysis, t‐test to compare hepatic stiffness values with reference standards.ResultsStiffness values obtained at both reading centers were similar, without significant bias (P = 0.362) and with excellent correlation (intraclass correlation coefficient [ICC] = 0.782). Mean hepatic stiffness value for the study population was 2.45 ± 0.35 kPa (95th percentile 3.19 kPa), which was significantly higher than reported values for healthy adult subjects (2.10 ± 0.23 kPa, P < 0.001). In all, 74–85% of subjects had stiffness measurements suggestive of no fibrosis.Data ConclusionMean liver stiffness measured with MRE in this cohort was significantly higher than that reported in healthy adults. Despite rigorous screening, some healthy children had stiffness measurements suggestive of liver fibrosis using current published thresholds. Although MRE has the potential to provide noninvasive assessment in patients with suspected hepatic disease, further refinement of this technology will help advance its use as a diagnostic tool for evidence of fibrosis in pediatric populations.Level of Evidence: 1Technical Efficacy: 5J. Magn. Reson. Imaging 2020;51:919–927.

Prior research explored reasons for tobacco use among pregnant Alaska Native (AN) women but did not address the postpartum period. This study followed up with AN women one to three years postpartum who had participated in a prenatal smoking cessation intervention study (Motivate Alaska Women (MAW) Phase 3) and had consented to be re-contacted for future studies. Of 47 eligible women, 32 (68%) participated. A semi-structured phone interview was conducted a mean of 2.0 years after delivery (range 1.6–2.8). Measures assessed self-reported tobacco use status in the 12 months after delivery, at 12 months postpartum, and at the time of the interview; reasons for maintaining abstinence, continued use, or relapse; and included the Perceived Stress Scale (PSS) and Negative Affect (NA) scale. Content analysis was used to generate themes from open-ended response items. Tobacco use was reported by 23 women (72%) at delivery, 30 (94%) within the 12 months after delivery, 27 (84%) at 12 months postpartum, and 29 (91%) at the time of the interview. Among nine women not using tobacco at delivery, seven (78%) relapsed during the 12 months after delivery. Of the 29 current tobacco users, 28 (97%) smoked cigarettes. Twenty-seven participants (84%) reported stress and 15 (52%) indicated addiction as reasons for continuing, starting, or resuming tobacco use. Types of stressors were related to parenting and traumatic experiences. Among current tobacco users, mean NA score (18.7) was significantly higher (p = 0.01) than the normative mean (14.8), but no differences were detected for PSS score. In this sample of AN women, postpartum tobacco use was highly prevalent, and stress was a primary reason that women endorsed for using tobacco. These preliminary results have several practice and research implications for exploring ways to support non-tobacco use among postpartum AN women.

Abstract Purpose: The majority of patients with high-grade serous ovarian cancer (HGSC) develop progressive disease following primary treatment, with a five-year survival rate of ~30%. However, a subset of patients have an extraordinary response to treatment and ~15% survive more than ten years (long-term survivors). The Multidisciplinary Ovarian Cancer Outcomes Group (MOCOG) aims to uncover factors that influence long-term survival of HGSC patients. Here, we investigated the genomic and immunologic determinants of exceptional survival of this deadly disease. Experimental Design: Patient characteristics and clinical histories were evaluated to identify patients diagnosed with advanced stage (Stage IIIC/IV) and histopathologically confirmed HGSC with greater than 10-year overall survival. Whole-genome sequencing (WGS) was performed on primary tumors (median 78x coverage) and germline samples (median 39x coverage) of 55 long-term survivors. Primary tumor samples were also characterised by RNA sequencing, DNA methylation profiling and immunohistochemistry. Results: A total 38 (69%) of long-term surviving patients had residual disease following surgery, suggestive of highly chemo-sensitive disease. Most patients (41, 75%) were alive at last follow-up and 26 (47%) were progression-free. Somatic mutation burden was higher in primary tumors of long-term survivors relative to controls (316 unselected HGSC patients in The Cancer Genome Atlas). Genome-wide mutational signatures were predominantly Signature 3 (associated with homologous recombination deficiency), Signature 1 (age related) and Signatures 5, 8 and 16 (unknown etiology). Inactivation of the tumor suppressor RB1 by structural rearrangements or homozygous deletion was frequent in long-term survivors, with 33% of tumors showing associated loss of RB1 protein expression by immunohistochemistry compared to 13% of unselected HGSC controls (n=207; P = 0.001). Staining of adjacent tumor tissue revealed that RB1 loss was associated with increased numbers of PD-1+ tumor-infiltrating lymphocytes (P = 0.015) and MHC class I on tumor cells (P = 0.002). In an independent HGSC cohort (n=847), RB1 protein loss was associated with prolonged survival (HR: 0.75, P &lt; 0.001) compared to patients with RB1 positive tumors. Furthermore, co-occurrence of germline mutations in BRCA1 or BRCA2 and RB1 loss was associated with a significantly longer overall survival compared to patients with retained RB1 protein expression and no germline BRCA mutation (HR: 0.44, P &lt; 0.001). Conclusions: This study delineates the full landscape of genomic alterations in HGSC of long-term survivors. Our findings indicate that specific mutations might be associated with enhanced host immune responses and long-term survival. Citation Format: Dale W. Garsed, Ahwan Pandey, Sian Fereday, Kathryn Alsop, Maartje C. Wouters, Flurina Saner, Jessica A. Beach, Katy Milne, Catherine J. Kennedy, Joy Hendley, Nadia Traficante, Celeste L. Pearce, Malcolm C. Pike, Multidisciplinary Ovarian Cancer Outcomes Group, Susan J. Ramus, Martin Köbel, Brad H. Nelson, Ellen L. Goode, Anna deFazio, David D. Bowtell. The genomic landscape of high-grade serous ovarian cancer in long-term survivors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 2722.

Objectives: The incidence of shoulder and elbow overuse injury continues to rise in youth baseball players. Several throwing programs designed to reduce stress on the elbow have been described, but most are not evidence-based. The aim of this study was to compare the kinetics and kinematics between mound and flat-ground pitching at two different distances with the goal of developing evidenced-based injury prevention and recovery guidelines for youth throwers. Methods: Fifteen healthy, high school varsity-level baseball pitchers (mean age 16.7 ± 0.7 yrs; height 182.2 ± 6.2 cm; weight 76.0 ± 9.4 kg;) participated in the study. Players were fitted with a motusBASEBALLTM sensor and sleeve (Motus Global, Rockville Centre, NY), which has been shown to have good reliability and correlation with in-laboratory measures. Each pitcher was asked to pitch 5 fastballs to a catcher under each of the 4 conditions: mound at 60.5 ft (regulation distance), flat ground at 60.5 ft, mound at 50.5 ft, and flat ground at 50.5 ft. For each pitch, the sensor recorded arm speed, arm slot, shoulder rotation, and elbow varus torque. Ball velocity was tracked with a radar gun (Stalker Radar, Richardson, TX). Linear mixed-effects models were used to account for both within and between-subject variability. A multivariable model was used to evaluate the association of mound pitching (vs flat ground), distance (50.5 vs 60.5 ft), and their interaction on each of the following outcomes: arm speed, arm slot, shoulder rotation, elbow varus torque, and ball velocity. Results: There were no statistically significant effects of mound vs flat ground or distance variation on both arm speed or shoulder rotation. Arm slot was significantly higher on pitches from the mound at 60.5 ft [+4.58 (95% CI: 1.26, 7.90), p=0.007]. Elbow varus torque was significantly lower on throws from the mound [-1.88 (95% CI: -3.56, -0.20), p=0.03] and from a longer distance [-2.21 (95% CI: -3.89, -0.53), p=0.01]. Pitches thrown from the mound were significantly faster compared to flat ground at both distances, with throws at 60.5 ft of greater velocity than at 50.5 ft [+1.03 (95% CI: 0.66, 1.40), p<0.001]. Please see the Table for full results. Conclusion: The findings suggest that throwing from the mound may not be higher risk compared to flat ground, contrary to long-standing notions. The lower elbow varus torque and higher arm slot, which has previously been shown to be associated with reduced stress, from throwing from the mound may even indicate a protective effect. Compared to 50.5 ft, there was lower elbow varus torque and faster ball velocity at the longer distance, indicating that elbow stress and ball velocity may not correlate perfectly, and radar guns may not be an appropriate surrogate measure of elbow varus torque. A better understanding of the kinetic and kinematic implications of various throwing programs will allow for designing programs that are based on objective data to achieve the goal of preventing injuries in young baseball players. [Table: see text]

AbstractBackgroundGlioblastoma (GBM) represents an aggressive cancer type with a median survival of only 14 months. With fewer than 5% of patients surviving 5 years, comprehensive profiling of these rare patients could elucidate prognostic biomarkers that may confer better patient outcomes. We utilized multiple molecular approaches to characterize the largest patient cohort of isocitrate dehydrogenase (IDH)–wildtype GBM long-term survivors (LTS) to date.MethodsRetrospective analysis was performed on 49 archived formalin-fixed paraffin embedded tumor specimens from patients diagnosed with GBM at the Mayo Clinic between December 1995 and September 2013. These patient samples were subdivided into 2 groups based on survival (12 LTS, 37 short-term survivors [STS]) and subsequently examined by mutation sequencing, copy number analysis, methylation profiling, and gene expression.ResultsOf the 49 patients analyzed in this study, LTS were younger at diagnosis (P = 0.016), more likely to be female (P = 0.048), and MGMT promoter methylated (UniD, P = 0.01). IDH-wildtype STS and LTS demonstrated classic GBM mutations and copy number changes. Pathway analysis of differentially expressed genes showed LTS enrichment for sphingomyelin metabolism, which has been linked to decreased GBM growth, invasion, and angiogenesis. STS were enriched for DNA repair and cell cycle control networks.ConclusionsWhile our findings largely report remarkable similarity between these LTS and more typical STS, unique attributes were observed in regard to altered gene expression and pathway enrichment. These attributes may be valuable prognostic markers and are worth further examination. Importantly, this study also underscores the limitations of existing biomarkers and classification methods in predicting patient prognosis.

The NCCN Guidelines for Survivorship provide screening, evaluation, and treatment recommendations for consequences of cancer and cancer treatment to aid healthcare professionals who work with survivors of adult-onset cancer. Guidance is also provided to help promote physical activity, weight management, and proper immunizations in survivors and to facilitate care coordination to ensure that all needs are addressed. These NCCN Insights summarize some of the topics discussed by the NCCN Survivorship Panel during the 2019 update of the guidelines, including the survivorship population addressed, ways to improve care coordination, and pain management.