Margaret Gradison

Prognostic significance of functional capacity and exercise behavior in patients with metastatic non-small cell lung cancer

BACKGROUND To investigate the prognostic importance of functional capacity and exercise behavior in patients with metastatic non-small cell lung cancer (NSCLC). PATIENTS AND METHODS Using a prospective design, 118 consecutive participants with histologically confirmed metastatic (inoperable) NSCLC and Eastern Cooperative Oncology group (ECOG) 0-3 completed a six-minute walk test to assess functional capacity and questionnaire that assessed self-reported exercise behavior. Cox proportional models were used to estimate the risk of all-cause mortality according to six-minute walk distance (6MWD) (<358.5m, 358.5-450 m, ≥450 m) and exercise behavior (MET-hrswk(-1)) categories with adjustment for important covariates. RESULTS Median follow-up was 26.6 months; 77 deaths were reported during this period. Functional capacity was an independent predictor of survival (P(trend)=0.003) and added incremental prognostic value beyond that provided by PS plus other traditional markers of prognosis (P(trend)=0.025). Compared with patients achieving a 6MWD <358.5m, the adjusted hazard ratio (HR) for all-cause mortality was 0.61 (95% CI, 0.34-1.07) for a 6MWD of 358.5-450 m, and 0.48 (95% CI, 0.24-0.93) for a 6MWD >450 m. In unadjusted analysis, there was a borderline significant effect of exercise behavior on survival (p=0.052). Median survival was 12.89 months (95% CI, 9.11-21.05 months) for those reporting <9MET-hrswk(-1) compared with 25.63 months (95% CI, 11.28 to ∞ months) for those reporting ≥9MET-hrswk(-1). CONCLUSIONS Functional capacity is a strong independent predictor of survival in advanced NSCLC that adds to the prediction of survival beyond traditional risk factors. This parameter may improve risk stratification and prognostication in NSCLC.

Quality Measures for Palliative Care in Patients With Cancer: A Systematic Review

PURPOSE Quality assessment is a critical component of determining the value of medical services, including palliative care. Characterization of the current portfolio of measures that assess the quality of palliative care delivered in oncology is necessary to identify gaps and inform future measure development. METHODS We performed a systematic review of MEDLINE/PubMed and the gray literature for quality measures relevant to palliative care. Measures were categorized into National Quality Forum domains and reviewed for methodology of development and content. Measures were additionally analyzed to draw summative conclusions on scope and span. RESULTS Two hundred eighty-four quality measures within 13 measure sets were identified. The most common domains for measure content were Physical Aspects of Care (35%) and Structure and Processes of Care (22%). Of symptom-related measures, pain (36%) and dyspnea (26%) were the most commonly addressed. Spiritual (4%) and Cultural (1%) Aspects of Care were least represented domains. Generally, measures addressed processes of care, did not delineate benchmarks for success, and often did not specify intended interventions to address unmet needs. This was most evident regarding issues of psychosocial and spiritual assessment and management. CONCLUSION Within a large cohort of quality measures for palliative, care is often a focus on physical manifestations of disease and adverse effects of therapy; relatively little attention is given to the other aspects of suffering commonly observed among patients with advanced cancer, including psychological, social, and spiritual distress.

Stroke-Related Knowledge Among Patients With Access to Medical Care in the Stroke Belt

North Carolina lies in the countrys Stroke Belt, which is a region where cerebrovascular disease is a major public health problem. We performed an open survey of patients residing in a Stroke Belt community who had access to medical care to determine their level of knowledge about stroke risk factors, symptoms, and emergency procedures. Between June and December 1997, a random sample of patients, over age 55, at 13 primary care medical practices in central North Carolina were asked to complete an open questionnaire. Responses were obtained from 202 patients (78% Caucasian, 18% African American, 4% other or unstated). Overall, 80% of those who responded believed that stroke could be, prevented, and 95% felt that stroke could be treated. Although only 12% could not correctly name any stroke risk factors, 53% could not list any of the symptoms of a transient ischemic attack (TIA), and 25% could not provide any stroke, symptoms. Multiple regression analyses showed that knowledge of stroke risk factors was independently related to both age and race (multiple r=.29, P<.0004; P<.01, for age and P<.01 for race) and that knowledge of stroke symptoms was independently related to age with a trend towards an effect of race (multiple r=.18, P<.04; P=.05 for age and P=.08 for race). This study shows that even for patients with access to medical care residing in a portion of the country with a particularly high incidence of cerebrovascular disease, knowledge of stroke risk factors, TIA symptoms, and stroke symptoms remains relatively poor. Those at higher epidemiological risk for cerebrovascular disease were relatively less knowledgeable. Based on these data, the need for local public education, particularly within Stroke Belt communities, requires further emphasis.

A prospective study of weight gain after premenopausal hysterectomy.

PURPOSE Many women who have had hysterectomies have the perception that they gained weight after surgery that cannot be attributed to changes in diet or physical activity. The purpose of this analysis was to assess weight gain in premenopausal women in the first year after hysterectomy compared with a control group of women with intact uteri and ovaries. METHODS As part of a prospective cohort study designed to assess the risk for ovarian failure after premenopausal hysterectomy, weight was measured at baseline and 1-year follow-up in 236 women undergoing hysterectomy and 392 control women. Changes in measured weight and reported weight were assessed. Unconditional logistic regression analyses were used to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for weight gains of >10 pounds. RESULTS Women with hysterectomies weighed more and had a higher mean body mass index (BMI) than control women at baseline. Mean weight gain was 1.36 kg ( approximately 3 pounds) for women with hysterectomies vs. 0.61 kg ( approximately 1.3 pounds) for control women (p = 0.07). Weight gain of >10 pounds occurred in 23% of women with hysterectomies compared with 15% of control women (multivariable OR = 1.61, 95% CI 1.04 = 2.48). CONCLUSIONS Women undergoing hysterectomies appear to be at higher risk for weight gain in the first year after surgery. Heavier women and women who have had weight fluctuations throughout adulthood may be at greater risk for postsurgical weight gain, suggesting that lifestyle interventions to maintain or lose weight may be particularly helpful for these women in the months following hysterectomy.

Medical Directors' Roles in the Strategic Planning for Physician Assistant Education.

With the unprecedented expansion of physician assistant (PA) programs, we face challenges to guaranteeing high-quality education at each of our programs—whether they are new, expanding, or continuing. Physician Assistant Education Association (PAEA) strategic planning has focused on 2major goals for this decade. These include (1) increasing the number of PAs working in primary care with an emphasis on medically underserved areas andpopulations; and (2) the creation of innovative clinical training experiences to accommodate the increase in the number of PA students. Individual programs have unique perspectives on these goals with our own distinctive characteristics and barriers. As medical directors, we are in a key position to support our program directors and PAEA in achieving thesegoals. In fact, our relationshipwithour program directors has the potential to ensure success in this process.

Abstract B01: PEG3 DNA methylation and cervical intraepithelial neoplasia in African American and European American women

Background: Epigenetic mechanisms are hypothesized to be etiologically involved in progression of cervical intraepithelial neoplasia (CIN) to invasive cervical cancer (ICC), although empirical data are lacking. Methods: A total of 304 women were enrolled at the time of colposcopic evaluation following an abnormal liquid-based cytology screen. HPV was genotyped by HPV linear array. To ascertain the presence of CIN, the biopsies underwent pathologic review. DNA methylation was measured at differentially methylated regions (DMRs) regulating genomic imprinting of IGF2/H19 PEG1/MEST, KCNQ1OT1, MEG3, HYMAI, PEG10 and PEG3 imprinted domains, using Sequenom EpiTYPER assays. Logistic regression models were used to estimate odd ratios (ORs) and to evaluate the associations between HPV infection and DMR methylation, respectively. Results: After accounting for age, HPV infection, parity, hormonal contraceptive use, and cigarette smoking, methylation differences at the PEG3 DMR were associated with a modest but significant higher risk of CIN2/3 (OR=1.08, 95%CI 1.02-1.18, p=0.022) in all women. This association remained significant in European American (OR=1.13, 95%CI 1.03-1.27, p=0.011), but not in African American women (OR=1.03, 95%CI 0.90-1.16, p=0.715). HPV infection was associated with altered PEG3 DMR methylation in both groups of women, an association that was also stronger in European Americans (β= -3.42, p=0.041), than in African Americans (β= -2.55, p=0.132). Though altered methylation at IGF2/H19 and PEG10 DMRs was associated with CIN1, no associations were observed with CIN2/3 lesions. No associations were found for PEG1/MEST, KCNQ1OT1, MEG3, and HYMAI DMRs. Conclusions: Aberrant DNA methylation at the regulatory region of the PEG3 imprinted gene may increase susceptibility to CIN2/3; an association that may be stronger in European American women and which persisted after accounting for HPV infection. If confirmed in larger studies, these findings support the hypothesis that DNA methylation at PEG3 may represent a susceptibility locus that can be exploited to identify, from among a large number of abnormal colposcopy cases, those likely to progress to CIN or worse. Citation Format: Adriana C. Vidal, David Skaar, Zhiquing Huang, Fidel Valea, Rex Bentley, Margaret Gradison, Kimberly S. H. Yarnall, Anne Ford, Francine Overcash, Katherine Grant, Susan K. Murphy, Cathrine Hoyo. PEG3 DNA methylation and cervical intraepithelial neoplasia in African American and European American women. [abstract]. In: Proceedings of the Seventh AACR Conference on The Science of Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; Nov 9-12, 2014; San Antonio, TX. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2015;24(10 Suppl):Abstract nr B01.

Abstract PR01: HPV genotype distribution and cervical intraepithelial neoplasia in African American and white women living in the Southeastern United States

Background: Differential distributions of oncogenic HPV genotypes among racial/ethnic groups may explain observed disparities in ICC incidence and mortality rates. We describe HPV genotypes associated with CIN1-3 in a multiethnic cohort of women visiting colposcopy clinic following a cervical abnormality. Methods: We enrolled 516 women attending colposcopic evaluation following an abnormal liquid-based cytology screen. HPV infection was measured using HPV linear array that measures 37 HPV types, and chi-squared tests were used to compare HPV genotypes in African American and Whites overall, and by CIN stage. Results: Of 516 participants, 373 (72%) were HPV-positive; 137 (37%) had no CIN lesion, 174 (47%) had CIN1, 38 (10%) had CIN2, and 24 (6%) had CIN-3. Twenty-seven percent of women were infected with one HPV genotype, and 73% were infected with multiple HPV genotypes. In women with CIN1, 75% of HPV single infections were of high risk (HR) genotypes, and 70% of women had multiple HR-HPV genotype infections. The most frequent HR-HPV genotypes detected among CIN1 cases were 16, 18, 31, 45, 52, 56, 59 and 66 in White women, while HPV subtypes 33, 35, 58 and 68 were the most common in African American women. Restricting analyses to women with CIN2-3 revealed a change in HR-HPV genotype distribution; HR-HPV 16, 18, 33, 35, 39, and 59 were most common in White women with CIN2-3, whereas HR-HPV 31, 45, 51 and 66 were the most prevalent in African American women. Conclusion: Our data suggest that while HPV 16 and 18 are the most common genotypes among women with CIN in Whites; African Americans may harbor different genotypes. The preponderance of non-16/18 HR-HPV genotypes in African Americans with increasing CIN grade has implications for both reflex testing following cytological abnormalities and vaccine development. This abstract is also presented as Poster B11. Citation Format: Adriana C Vidal, Jennifer S Smith, Edwin Iversen, Fidel Valea, Rex Bentley, Margaret Gradison, Kimberly Yarnall, Anne Ford, Francine Overcash, Katherine Grant, Susan Murphy, Cathrine Hoyo. HPV genotype distribution and cervical intraepithelial neoplasia in African American and white women living in the Southeastern United States. [abstract]. In: Proceedings of the Twelfth Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2013 Oct 27-30; National Harbor, MD. Philadelphia (PA): AACR; Can Prev Res 2013;6(11 Suppl): Abstract nr PR01.