Jessica Hoag

Cellular Expression of PD-L1 in the Peripheral Blood of Lung Cancer Patients is Associated with Worse Survival

Background: Lung cancer treatment has become increasingly dependent upon invasive biopsies to profile tumors for personalized therapy. Recently, tumor expression of programmed death-ligand 1 (PD-L1) has gained interest as a potential predictor of response to immunotherapy. Circulating biomarkers present an opportunity for tumor profiling without the risks of invasive procedures. We characterized PD-L1 expression within populations of nucleated cells in the peripheral blood of lung cancer patients in hopes of expanding the role of liquid biopsy in this setting. Methods: Peripheral blood samples from a multi-institutional prospective study of patients with clinical diagnosis of lung cancer were subjected to cytomorphometric and immunohistochemical evaluation using single-cell, automated slide-based, digital pathology. PD-L1 expression was determined by immunofluorescence. Results: PD-L1 expression was detected within peripheral circulating cells associated with malignancy (CCAM) in 26 of 112 (23%) non–small cell lung cancer patients. Two distinct populations of nucleated, nonhematolymphoid, PD-L1–expressing cells were identified; cytokeratin positive (CK+, PD-L1+, CD45−) and cytokeratin negative (CK−, PD-L1+, CD45−) cells, both with cytomorphometric features (size, nuclear-to-cytoplasm ratio) consistent with tumor cells. Patients with >1.1 PD-L1(+) cell/mL (n = 14/112) experienced worse overall survival than patients with ≤1.1 PD-L1(+) cell/mL (2-year OS: 31.2% vs. 78.8%, P = 0.00159). In a Cox model adjusting for stage, high PD-L1(+) cell burden remained a significant predictor of mortality (HR = 3.85; 95% confidence interval, 1.64–9.09; P = 0.002). Conclusions: PD-L1 expression is detectable in two distinct cell populations in the peripheral blood of lung cancer patients and is associated with worse survival. Impact: These findings could represent a step forward in the development of minimally invasive liquid biopsies for the profiling of tumors. Cancer Epidemiol Biomarkers Prev; 26(7); 1139–45. ©2017 AACR.

Association of Lowering Default Pill Counts in Electronic Medical Record Systems With Postoperative Opioid Prescribing

Importance Reliance on prescription opioids for postprocedural analgesia has contributed to the opioid epidemic. With the implementation of electronic medical record (EMR) systems, there has been increasing use of computerized order entry systems for medication prescriptions, which is now more common than handwritten prescriptions. The EMR can autopopulate a default number of pills prescribed, and 1 potential method to alter prescriber behavior is to change the default number presented via the EMR system. Objective To investigate the association of lowering the default number of pills presented when prescribing opioids in an EMR system with the amount of opioid prescribed after procedures. Design, Setting, and Participants A prepost intervention study was conducted to compare postprocedural prescribing patterns during the 3 months before the default change (February 18 to May 17, 2017) with the 3 months after the default change (May 18 to August 18, 2017). The setting was a multihospital health care system that uses Epic EMR (Hyperspace 2015 IU2; Epic Systems Corporation). Participants were all patients in the study period undergoing 1 of the 10 most common operations and discharged by postoperative day 1. Intervention The default number of opioid pills autopopulated in the EMR when prescribing discharge analgesia was lowered from 30 to 12. Main Outcomes and Measures Linear regression estimating the change in the median number of opioid pills and the total dose of opioid prescribed was performed. Opioid doses were converted into morphine milligram equivalents (MME) for comparison. The frequency of patients requiring analgesic prescription refills was also evaluated. Results There were 1447 procedures (mean [SD] age, 54.4 [17.3] years; 66.9% female) before the default change and 1463 procedures (mean [SD] age, 54.5 [16.4] years; 67.0% female) after the default change. After the default change, the median number of opioid pills prescribed decreased from 30 (interquartile range, 15-30) to 20 (interquartile range, 12-30) per prescription (P < .001). The percentage of prescriptions written for 30 pills decreased from 39.7% (554 of 1397) before the default change to 12.9% (183 of 1420) after the default change (P < .001), and the percentage of prescriptions written for 12 pills increased from 2.1% (29 of 1397) before the default change to 24.6% (349 of 1420) after the default change (P < .001). Regression analysis demonstrated a decrease of 5.22 (95% CI, −6.12 to −4.32) opioid pills per prescription after the default change, for a total decrease of 34.41 (95% CI, −41.36 to −27.47) MME per prescription. There was no statistical difference in opioid refill rates (3.0% [4 of 135] before the default change vs 1.5% [2 of 135] after the default change, P = .41). Conclusions and Relevance Lowering the default number of opioid pills prescribed in an EMR system is a simple, effective, cheap, and potentially scalable intervention to change prescriber behavior and decrease the amount of opioid medication prescribed after procedures.

Affect, emotion dysregulation, and sleep quality among low-income women

OBJECTIVES To examine the underlying mechanisms through which steady state emotions, specifically affect and emotion regulation, influence sleep quality among young adult low-income women. DESIGN Cross-sectional. SETTING Stress and Health Study (2006-2012) in southeast Texas. PARTICIPANTS A subgroup (n=392) of racially and ethnically diverse young adult women ages 18-31. MEASUREMENTS Participants provided measures of positive and negative affect, difficulties in emotion regulation, and sleep quality. Structural equation models were designed to identify differential mediating roles of emotion dysregulation in the association between both positive and negative affect and sleep quality. RESULTS The relationship between positive affect and improved sleep quality operated completely through domains of emotion regulation (β= -0.054, 95% CI: -0.08 to -0.03), whereas the adverse effects of negative affect exhibited both direct (β= 0.142, 95% CI: 0.06 to 0.23) and indirect (β= 0.124, 95% CI: 0.08 to 0.16) effects on poor sleep. Negative affect was associated with poor sleep quality via two pathways-it directly influenced sleep quality and it indirectly influenced sleep quality among women experiencing difficulties in emotion regulation. CONCLUSIONS Therapies targeting improvement and maintenance of healthy emotion regulation domains, while delineating the positive affect state from the negative affect state, may lessen the burden of poor sleep quality among low-income women.

Impact of childhood abuse on adult sleep quality among low-income women after Hurricane Ike

OBJECTIVE The objective was to investigate the association between childhood abuse and poor sleep quality in the month following adulthood exposure to a natural disaster. DESIGN Cross-sectional. SETTING Six University of Texas Medical Branch family planning clinics located in Southeast Texas. PARTICIPANTS A subgroup of 375 low-income women aged 18 to 31 years who experienced Hurricane Ike while participating in the Stress and Health Longitudinal Study (2006-2012). MEASUREMENTS Risk profiles considering types and frequency of childhood abuse were identified in latent class analysis performed on the Childhood Trauma Questionnaire, which was measured upon entry to the study. Associations between abuse classes with a global indicator and 7 individual components of sleep quality measured after Hurricane Ike were estimated in adjusted logistic regression models. RESULTS Prevalence of poor sleep quality in the month following Hurricane Ike was 39.7%. Of the 5 classes of childhood abuse identified, the most extreme abuse class--frequent combined emotional, physical, and sexual abuse--exhibited the strongest associations with poor sleep quality after the hurricane (odds ratio: 4.30; 95% confidence interval: 1.72-10.72). Occasional emotional abuse alone was also significantly associated with poor sleep quality after the hurricane (odds ratio: 2.70; 95% confidence interval: 1.48-4.91). Several profiles of childhood abuse were also significantly associated with 6 of the 7 component indicators of sleep quality, including sleep duration, disturbances, onset latency, subjective quality, use of sleep medication, and daytime dysfunction. CONCLUSIONS Low-income women with histories of frequent childhood abuse, or emotional abuse specifically, have increased risk of poor sleep quality following exposure to a hurricane in adulthood.

The Care and Outcomes of Older Persons with Lung Cancer in England and the United States, 2008–2012

Introduction: Although prior research has demonstrated lower lung cancer survival in England than in the United States, more detailed comparisons are needed. We conducted a population‐based analysis to compare diagnostic, treatment, and survival patterns. Methods: Data from cancer registries and administrative databases were linked for older patients with a diagnosis of NSCLC in England and the United States (2008–2012). We compared patient and clinical characteristics, as well as the distribution of age‐standardized receipt of treatment by stage. We compared relative survival overall by stage and treatment. Finally, we assessed the degree to which stage distribution and stage‐specific survival contributed to survival differences. Results: Among patients age 66 years or older with a diagnosis of NSCLC in England (n = 86,978) and the United States (n = 84,415), the rate of pathological confirmation was 63% in England compared with 85% in the United States (a 22.2% difference [99% confidence interval: 22.8%–21.7%]). The rate of receipt of active treatment was lower in England than in the United States (46% versus 60%, for a difference of 14.0% [99% confidence interval: 13.3%–14.7%]). In England, we identified 98 excess deaths per 1000 patients with pathologically confirmed NSCLC; these additional deaths could be partially mitigated by adjusting stage at diagnosis (reduction to 54 excess deaths) or stage‐specific survival (reduction to 36 excess deaths). Conclusions: Compared with patients with NSCLC in the United States, patients with NSCLC in England are less likely to present with early‐stage disease and receive treatment and are more likely to die. Future work should explore whether the intensity of resources directed to diagnostic and therapeutic activity may help mitigate disparities in outcomes.

Minimally Invasive Lung Cancer Surgery Performed by Thoracic Surgeons as Effective as Thoracotomy

Purpose The prevalence of minimally invasive lung cancer surgery using video-assisted thoracic surgery (VATS) has increased dramatically over the past decade, yet recent studies have suggested that the lymph node evaluation during VATS lobectomy is inadequate. We hypothesized that the minimally invasive approach to lobectomy for stage I lung cancer resulted in a longitudinal outcome that was not inferior to thoracotomy. Patients and Methods Patients > 65 years of age who had undergone lobectomy for stage I lung cancer between 2002 and 2013 were analyzed within the Society of Thoracic Surgeons General Thoracic Surgery Database, which had been linked to Medicare data, as part of a retrospective-cohort, noninferiority study. Results A total of 10,597 patients with clinical stage I lung cancer who underwent lobectomy were evaluated (4,448 patients underwent thoracotomy, and 6,149 underwent VATS). VATS patients had a more favorable distribution of all health-related variables, including pulmonary function (59% of VATS patients had intact spirometry v 51% of thoracotomy patients; P < .001). Cox proportional hazards models were performed over two eras to account for an evolving practice standard. The mortality risk associated with the VATS approach was not greater than thoracotomy in either the earlier era (2002 to 2008; hazard ratio, 0.97; 95% CI, 0.87 to 1.09; P = .62) or the more recent era (2009 to 2013; hazard ratio, 0.84; 95% CI, 0.75 to 0.93; P < .001). Kaplan-Meier survival estimates of 2,901 propensity-matched VATS-thoracotomy pairs demonstrated that the 4-year survival associated with VATS (68.6%) was modestly superior to thoracotomy (64.8%; P = .003). The analyses detailed above were replicated in a separate cohort of pathologic stage I patients with similar findings. Conclusion The long-term efficacy of lobectomy for stage I lung cancer performed using the VATS approach by board-certified thoracic surgeons does not seem to be inferior to that of thoracotomy.

US Public Perceptions About Cancer Care Provided by Smaller Hospitals Associated With Large Hospitals Recognized for Specializing in Cancer Care

US Public Perceptions About Cancer Care Provided by Smaller Hospitals Associated With Large Hospitals Recognized for Specializing in Cancer Care Over the past 5 years, smaller hospitals have developed formal relationships with larger hospitals at a historic rate, with more than 100 new mergers, acquisitions, and affiliations being filed each year in the United States.1,2 Applying the brand of a larger hospital to smaller, affiliated hospitals has become commonplace.3 This brand sharing has the potential to influence patient decisions about where to pursue care, particularly for complex conditions such as cancer.4 However, the extent to which patients perceive the care at the smaller hospitals to be affected by affiliation is unclear. In an effort to understand patient expectations associated with brand sharing for complex cancer care at smaller hospitals, we surveyed a nationally representative sample in the United States.

Teens as Teachers: Improving Recruitment and Training of Adolescent Standardized Patients in a Simulated Patient Encounter

Background: Studies in medical education have reliably established the importance of utilizing adolescents as standardized patients. Their realistic portrayals offer authentic learning experiences. Additionally, the curricula can offer the adolescent participants a meaningful educational opportunity. Methods: The “Teens as Teachers” program was developed at the University of Connecticut, School of Medicine, to prepare second year medical students to interview, elicit a history and address issues related to risk behaviors in adolescent standardized patients. In addition, the program offers educational and mentoring opportunities for the teenaged participants. Results: The twenty-four adolescents trained as standardized patients have worked with 359 second year medical students. Results reveal that the adolescents felt the training adequately prepared them for their cases, found the overall experience rewarding and 100% of the adolescents would return to participate if possible. 88.6% of medical students rated the cases authentic, 98.8% found then valuable, 94.2% were able to practice the skills learned during lecture and 96.8% received feedback from the adolescent standardized patients. Conclusion: Utilizing adolescent standardized patients to teach interviewing skills to medical students can prepare them to elicit comprehensive histories and can be a beneficial learning experience for the teenaged participants.

Oncologist Volume and Outcomes in Older Adults Diagnosed With Diffuse Large B Cell Lymphoma: Oncologist Volume and DLBCL Outcomes

Although provider‐level volume is frequently associated with outcomes in cancers requiring complex surgeries, whether similar relations exist for cancers treated primarily with systemic therapy is unknown.

Why Travel for Complex Cancer Surgery? Americans React to ‘Brand-Sharing’ Between Specialty Cancer Hospitals and Their Affiliates

IntroductionLeading cancer hospitals have increasingly shared their ‘brand’ with smaller hospitals through affiliations. Because each brand evokes a distinct reputation for the care provided, ‘brand-sharing’ has the potential to impact the public’s ability to differentiate the safety and quality within hospital networks. The general public was surveyed to determine the perceived similarities and differences in the safety and quality of complex cancer surgery performed at top cancer hospitals and their smaller affiliate hospitals.MethodsA national, web-based KnowledgePanel (GfK) survey of American adults was conducted. Respondents were asked about their beliefs regarding the quality and safety of complex cancer surgery at a large, top-ranked cancer hospital and a smaller, local hospital, both in the presence and absence of an affiliation between the hospitals.ResultsA total of 1010 surveys were completed (58.1% response rate). Overall, 85% of respondents felt ‘motivated’ to travel an hour for complex surgery at a larger hospital specializing in cancer, over a smaller local hospital. However, if the smaller hospital was affiliated with a top-ranked cancer hospital, 31% of the motivated respondents changed their preference to the smaller hospital. When asked to compare leading cancer hospitals and their smaller affiliates, 47% of respondents felt that surgical safety, 66% felt guideline compliance, and 53% felt cure rates would be the same at both hospitals.ConclusionsApproximately half of surveyed Americans did not distinguish the quality and safety of surgical care at top-ranked cancer hospitals from their smaller affiliates, potentially decreasing their motivation to travel to top centers for complex surgical care.