Cognitive functioning following brain irradiation as part of cancer treatment: Characterizing better cognitive performance.

OBJECTIVE: Although brain radiation therapy (RT) impacts cognitive function, little is known about the subset of survivors with minimal cognitive deficits. This study compares the characteristics of patients receiving brain irradiation as part of cancer treatment with minimal cognitive deficits to those with poorer cognitive functioning. METHODS: Adults at least 6 months postbrain RT (N = 198) completed cognitive measures of attention, memory, and executive functions. Cognitive functioning was categorized into better- and poorer-performing groups, with better-performing survivors scoring no worse than 1.5 standard deviations below the published normative mean on all cognitive measures. Logistic regression was used to identify variables associated with better-performing group membership. RESULTS: Approximately 25% of the sample met the criteria for the better-performing group. In unadjusted analyses, RT type (whole brain irradiation and partial brain irradiation), sedating medications, and fatigue were independently associated with cognition. Sociodemographic and other clinical characteristics were not significant. In adjusted analyses, only fatigue remained significantly associated with group membership (OR = 1.05, 95% CI = 1.01-1.09, P = .009). CONCLUSIONS: There is a subgroup of survivors with minimal long-term cognitive deficits despite undergoing a full course of brain RT as part of cancer treatment. Lower fatigue had the strongest association with better cognitive performance. Interventions targeting cancer-related fatigue may help buffer the neurotoxic effects of brain RT.

Long-term Weight Loss Maintenance in the Continuation of a Randomized Diabetes Prevention Translational Study: The Healthy Living Partnerships to Prevent Diabetes (HELP PD) Continuation Trial.

OBJECTIVE: HELP PD was a clinical trial of 301 adults with prediabetes. Participants were randomized to enhanced usual care (EUC) or to a lifestyle weight loss (LWL) intervention led by community health workers that consisted of a 6-month intensive phase (phase 1) and 18 months of maintenance (phase 2). At 24 months, participants were asked to enroll in phase 3 to assess whether continued group maintenance (GM) sessions would maintain improvements realized in phases 1 and 2 compared with self-directed maintenance (SM) or EUC. RESEARCH DESIGN AND METHODS: In phase 3, LWL participants were randomly assigned to GM or SM. EUC participants remained in the EUC arm and, along with participants in SM, received monthly newsletters. All participants received semiannual dietitian sessions. Anthropometrics and biomarkers were assessed every 6 months. Mixed-effects models were used to assess changes in outcomes over time. RESULTS: Eighty-two of the 151 intervention participants (54%) agreed to participate in phase 3; 41 were randomized to GM and 41 to SM. Of the 150 EUC participants, 107 (71%) continued. Ninety percent of clinic visits were completed. Over 48 months of additional follow-up, outcomes remained relatively stable in the EUC participants; the GM group was able to maintain body weight, BMI, and waist circumference; and these measures all increased significantly (P < 0.001) in the SM group. CONCLUSIONS: Participants in the GM arm maintained weight loss achieved in phases 1 and 2, while those in the SM arm regained weight. Because group session attendance by the participants in the GM arm was low, it is unclear what intervention components led to successful weight maintenance.

Safely Identifying Emergency Department Patients With Acute Chest Pain for Early Discharge.

BACKGROUND: The HEART Pathway (history, ECG, age, risk factors, and initial troponin) is an accelerated diagnostic protocol designed to identify low-risk emergency department patients with chest pain for early discharge without stress testing or angiography. The objective of this study was to determine whether implementation of the HEART Pathway is safe (30-day death and myocardial infarction rate <1% in low-risk patients) and effective (reduces 30-day hospitalizations) in emergency department patients with possible acute coronary syndrome. METHODS: A prospective pre-post study was conducted at 3 US sites among 8474 adult emergency department patients with possible acute coronary syndrome. Patients included were ≥21 years old, investigated for possible acute coronary syndrome, and had no evidence of ST-segment-elevation myocardial infarction on ECG. Accrual occurred for 12 months before and after HEART Pathway implementation from November 2013 to January 2016. The HEART Pathway accelerated diagnostic protocol was integrated into the electronic health record at each site as an interactive clinical decision support tool. After accelerated diagnostic protocol integration, ED providers prospectively used the HEART Pathway to identify patients with possible acute coronary syndrome as low risk (appropriate for early discharge without stress testing or angiography) or non-low risk (appropriate for further in-hospital evaluation). The primary safety and effectiveness outcomes, death, and myocardial infarction (MI) and hospitalization rates at 30 days were determined from health records, insurance claims, and death index data. RESULTS: Preimplementation and postimplementation cohorts included 3713 and 4761 patients, respectively. The HEART Pathway identified 30.7% as low risk; 0.4% of these patients experienced death or MI within 30 days. Hospitalization at 30 days was reduced by 6% in the postimplementation versus preimplementation cohort (55.6% versus 61.6%; adjusted odds ratio, 0.79; 95% CI, 0.71-0.87). During the index visit, more MIs were detected in the postimplementation cohort (6.6% versus 5.7%; adjusted odds ratio, 1.36; 95% CI, 1.12-1.65). Rates of death or MI during follow-up were similar (1.1% versus 1.3%; adjusted odds ratio, 0.88; 95% CI, 0.58-1.33). CONCLUSIONS: HEART Pathway implementation was associated with decreased hospitalizations, increased identification of index visit MIs, and a very low death and MI rate among low-risk patients. These findings support use of the HEART Pathway to identify low-risk patients who can be safely discharged without stress testing or angiography. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov . Unique identifier: NCT02056964.

Analysis of a Step-Up Approach Versus Primary Open Surgical Necrosectomy in the Management of Necrotizing Pancreatitis: Experience in a Cohort of Patients at a US Academic Medical Center.

OBJECTIVES: An increasing number of providers have begun to use a minimally invasive step-up approach as opposed to traditional surgical necrosectomy in the management of acute necrotizing pancreatitis. Studies have shown mixed results, thus we hypothesized that the step-up approach is safer and associated with decreased mortality and length of stay (LOS). METHODS: This is a retrospective cohort study of patients admitted from January 2010 to March 2015 who underwent interventions for walled-off pancreatic necrosis (WOPN). Primary outcomes included LOS after intervention and mortality, in-hospital and 90-day, with secondary outcomes of procedural complications. RESULTS: Sixty-nine patients developed WOPN requiring intervention during the study period. In-hospital mortality was 5.6% (n = 2) in the step-up cohort compared with 18.2% (n = 6) in the surgical cohort (relative risk, 3.27; 95% confidence interval, 0.71-15.09). Ninety-day mortality was 9.1% (n = 3) in the step-up cohort and 21.9% (n = 7) in the surgical cohort (relative risk, 2.41; 95% confidence interval, 0.68-8.50). Postintervention LOS was 8 days in the step-up cohort and 17 days in the surgical cohort (P = 0.62). CONCLUSIONS: A step-up approach, as compared with primary surgical necrosectomy in the management of WOPN, results in clinically significant decreases in mortality and LOS.

Quality of life of irradiated brain tumor survivors treated with donepezil or placebo: Results of the WFU CCOP research base protocol 91105.

BACKGROUND: The health-related quality of life (HRQL) and fatigue of brain cancer survivors treated with donepezil or placebo for cognitive symptoms after radiation therapy were examined. METHODS: One hundred ninety-eight patients who completed >30 Gy fractionated whole or partial brain irradiation at least 6 months prior to enrollment were randomized to either placebo or donepezil (5 mg for 6 weeks followed by 10 mg for 18 weeks) in a phase 3 trial. A neurocognitive battery, the Functional Assessment of Cancer Therapy-Brain (FACT-Br) and the Functional Assessment of Chronic Illness Therapy (FACIT)-fatigue, was administered at baseline, 12 weeks, and 24 weeks. RESULTS: At 12 weeks, donepezil resulted in improvements in only emotional functioning (P = .04), with no significant effects at week 24. Associations by level of baseline cognitive symptoms (above or below the median score of the baseline FACT-Br "additional concerns/brain" subscale), indicated that participants with more baseline symptoms who received donepezil versus placebo, showed improvements in social (P = .02) and emotional well-being (P = .038), other concerns/brain (P = .003) and the FACT-Br total score (P = .004) at 12 weeks, but not 24 weeks. However, participants with fewer baseline symptoms randomized to donepezil versus placebo reported lower functional well-being at both 12 (P = .015) and 24 weeks (P = .009), and greater fatigue (P = .02) at 24 weeks. CONCLUSIONS: The positive impact of donepezil on HRQL was greater in survivors reporting more baseline cognitive symptoms. Donepezil had significantly worse effects on fatigue and functional well-being among participants with fewer baseline symptoms. Future interventions with donepezil should target participants with more baseline cognitive complaints to achieve greater therapeutic impact and lessen potential side effects of treatment.

Self-reported adherence and biomarker levels of CoQ10 and alpha-tocopherol.

PURPOSE: Women with breast cancer were randomized to receive coenzyme Q10 (CoQ10) plus Vitamin E or placebo in a clinical trial. The objective of this evaluation is to examine the association between participant self-reported adherence to the study supplements and changes in plasma biomarker levels. PATIENTS AND METHODS: Correlation coefficients quantified the association between changes in alpha-tocopherol and CoQ10 levels and the association between self-reported adherence and changes in biomarkers. Participants were categorized by self-reported adherence; Kruskal- Wallis tests compared changes in alpha-tocopherol and CoQ10 levels between self-reported adherence groups. RESULTS: Women (N=155) provided baseline and post-treatment biomarkers; 147 completed at least one diary. While changes in alpha-tocopherol and CoQ10 levels were moderately correlated, correlations ranged from 0.40 to 0.48, association between self-reported adherence and plasma alpha-tocopherol or CoQ10 levels was weak; correlations ranged from 0.10 to 0.29 at weeks 8, 16, and 24. Some participants with high self-reported adherence actually had decreases in their biomarker levels. CONCLUSION: These findings support that self-reported adherence is likely to be overestimated. Biological and other measures of adherence that can better identify true adherence to study pills provided in clinical trials are greatly needed as they may assist in improving the interpretation of findings of future clinical trials.

A Randomized Double-Blind Placebo-Controlled Trial of Fruit and Vegetable Concentrates on Intermediate Biomarkers in Head and Neck Cancer.

BACKGROUND: Head and neck cancer (HNC) patients are at an increased risk for developing second primary tumors (SPTs). Diets rich in fruits and vegetables (FVs) may lower HNC risk. FV concentrates may offer a potential alternative to increasing FV intake. METHODS: We conducted a randomized, double-blind, placebo-controlled trial to evaluate whether Juice PLUS+ (JP; a commercial product with multiple FV concentrates) has an effect on p27 and Ki-67, biomarkers associated with the risk of SPTs. During 2004-2008, we randomized 134 HNC patients to 12 weeks of JP (n = 72) or placebo (n = 62). Oral cavity mucosal biopsies and whole blood were obtained at baseline and after 12 weeks. All participants were given the opportunity to receive JP for 5 years following the end of the intervention period, and they were followed yearly for the development of SPTs. RESULTS: After 12 weeks, patients on JP had significantly higher serum α-carotene ( P = .009), ß-carotene ( P < .0001), and lutein ( P = .003) but did not differ significantly in p27 ( P = .23) or Ki-67 ( P = .95). JP use following the initial 12-week trial was not significantly associated with SPT prevention. CONCLUSIONS: Despite increased serum micronutrient levels, our results do not suggest a clinical benefit of JP in HNC patients. Future studies should focus on longer intervention periods and/or modified supplement formulations with demonstrated chemopreventive properties.

The 24-month metabolic benefits of the healthy living partnerships to prevent diabetes: A community-based translational study.

AIMS: Large-scale clinical trials and translational studies have demonstrated that weight loss achieved through diet and physical activity reduced the development of diabetes in overweight individuals with prediabetes. These interventions also reduced the occurrence of metabolic syndrome and risk factors linked to other chronic conditions including obesity-driven cancers and cardiovascular disease. The Healthy Living Partnerships to Prevent Diabetes (HELP PD) was a clinical trial in which participants were randomized to receive a community-based lifestyle intervention translated from the Diabetes Prevention Program (DPP) or an enhanced usual care condition. The objective of this study is to compare the 12 and 24 month prevalence of metabolic syndrome in the two treatment arms of HELP PD. MATERIALS AND METHODS: The intervention involved a group-based, behavioral weight-loss program led by community health workers monitored by personnel from a local diabetes education program. The enhanced usual care condition included dietary counseling and written materials. RESULTS: HELP PD included 301 overweight or obese participants (BMI 25-39.9kg/m2) with elevated fasting glucose levels (95-125mg/dl). At 12 and 24 months of follow-up there were significant improvements in individual components of the metabolic syndrome: fasting blood glucose, waist circumference, HDL, triglycerides and blood pressure and the occurrence of the metabolic syndrome in the intervention group compared to the usual care group. CONCLUSIONS: This study demonstrates that a community diabetes prevention program in participants with prediabetes results in metabolic benefits and a reduction in the occurrence of the metabolic syndrome in the intervention group compared to the enhanced usual care group.

The healthy living partnerships to prevent diabetes and the diabetes prevention program: a comparison of year 1 and 2 intervention results.

A number of research studies have attempted to translate the behavioral lifestyle intervention delivered in the Diabetes Prevention Program (DPP). To compare the active interventions of two trials, Diabetes Prevention Program DPP and Healthy Living Partnerships to Prevent Diabetes (HELP PD), after 1 and 2 years of intervention. DPP included 3234 adults with prediabetes randomized to intensive lifestyle intervention, metformin, troglitazone, or placebo. The lifestyle intervention, professionally delivered to individuals in a clinical setting, focused on diet and increased physical activity. HELP PD, a community-based translation of DPP, included 301 adults randomized to receive intensive lifestyle intervention or enhanced usual care. Mean weight-losses at 1 year (6.9 kg in DPP, 6.4 kg in HELP PD) and 2 years (5.5 kg in DPP, 4.4 kg in HELP PD) were similar across studies. Reductions in glucose were also similar across studies at both time points (5.2 mg/dL in DPP and 4.1 mg/dL in HELP PD at 1 year; 1.8 mg/dL and 1.6 mg/dL at 2 years). HELP PD participants achieved larger reductions in triglycerides at 1 and 2 years (38.4 mg/dL and 34.9 mg/dL, respectively) than DPP participants (24.8 mg/dL and 22.4 mg/dL). High-density lipoprotein decreased in HELP PD participants at year 1 (-0.6 mg/dL) and increased in DPP (1.2 mg/dL) but there were no significant differences in year 2. HELP PD, a community model for diabetes prevention, was similar to DPP in reducing body weight and lowering blood glucose, both important risk factors that should be controlled to reduce risk for developing type 2 diabetes.

Standardized Rehabilitation and Hospital Length of Stay Among Patients With Acute Respiratory Failure: A Randomized Clinical Trial.

IMPORTANCE: Physical rehabilitation in the intensive care unit (ICU) may improve the outcomes of patients with acute respiratory failure. OBJECTIVE: To compare standardized rehabilitation therapy (SRT) to usual ICU care in acute respiratory failure. DESIGN, SETTING, AND PARTICIPANTS: Single-center, randomized clinical trial at Wake Forest Baptist Medical Center, North Carolina. Adult patients (mean age, 58 years; women, 55%) admitted to the ICU with acute respiratory failure requiring mechanical ventilation were randomized to SRT (n=150) or usual care (n=150) from October 2009 through May 2014 with 6-month follow-up. INTERVENTIONS: Patients in the SRT group received daily therapy until hospital discharge, consisting of passive range of motion, physical therapy, and progressive resistance exercise. The usual care group received weekday physical therapy when ordered by the clinical team. For the SRT group, the median (interquartile range [IQR]) days of delivery of therapy were 8.0 (5.0-14.0) for passive range of motion, 5.0 (3.0-8.0) for physical therapy, and 3.0 (1.0-5.0) for progressive resistance exercise. The median days of delivery of physical therapy for the usual care group was 1.0 (IQR, 0.0-8.0). MAIN OUTCOMES AND MEASURES: Both groups underwent assessor-blinded testing at ICU and hospital discharge and at 2, 4, and 6 months. The primary outcome was hospital length of stay (LOS). Secondary outcomes were ventilator days, ICU days, Short Physical Performance Battery (SPPB) score, 36-item Short-Form Health Surveys (SF-36) for physical and mental health and physical function scale score, Functional Performance Inventory (FPI) score, Mini-Mental State Examination (MMSE) score, and handgrip and handheld dynamometer strength. RESULTS: Among 300 randomized patients, the median hospital LOS was 10 days (IQR, 6 to 17) for the SRT group and 10 days (IQR, 7 to 16) for the usual care group (median difference, 0 [95% CI, -1.5 to 3], P = .41). There was no difference in duration of ventilation or ICU care. There was no effect at 6 months for handgrip (difference, 2.0 kg [95% CI, -1.3 to 5.4], P = .23) and handheld dynamometer strength (difference, 0.4 lb [95% CI, -2.9 to 3.7], P = .82), SF-36 physical health score (difference, 3.4 [95% CI, -0.02 to 7.0], P = .05), SF-36 mental health score (difference, 2.4 [95% CI, -1.2 to 6.0], P = .19), or MMSE score (difference, 0.6 [95% CI, -0.2 to 1.4], P = .17). There were higher scores at 6 months in the SRT group for the SPPB score (difference, 1.1 [95% CI, 0.04 to 2.1, P = .04), SF-36 physical function scale score (difference, 12.2 [95% CI, 3.8 to 20.7], P = .001), and the FPI score (difference, 0.2 [95% CI, 0.04 to 0.4], P = .02). CONCLUSIONS AND RELEVANCE: Among patients hospitalized with acute respiratory failure, SRT compared with usual care did not decrease hospital LOS. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00976833.

Trajectories of depressive symptoms following breast cancer diagnosis.

BACKGROUND: This longitudinal study sought to identify groups of breast cancer survivors exhibiting distinct trajectories of depressive symptoms up to 24 months following diagnosis, and to describe characteristics associated with these trajectories. METHODS: A total of 653 women completed baseline questionnaires within 8 months of breast cancer diagnosis on patient characteristics, symptoms, and psychosocial variables. Depressive symptoms were assessed at baseline and 6, 12, and 18 months after baseline. Chart reviews provided cancer and treatment-related data. Finite mixture modeling identified trajectories of depressive symptoms measured with the Beck Depression Inventory (BDI). RESULTS: Six distinct trajectories were identified. Just over half of the sample had consistently very low (3.8%) or low (47.3%) BDI scores well below the traditional BDI cutoff point of 10 thought to be indicative of clinically significant depression; 29.2% had consistently borderline scores; 11.3% had initially high scores that declined over time, but remained above the cutoff point; 7.2% showed increased BDI over time; and a small but unique group (1.1%) reported chronically high scores above 25. Women in groups with lower depressive symptom levels were older, had less rigorous chemotherapy, fewer physical symptoms (fatigue and pain), and lower levels of illness intrusiveness. CONCLUSIONS: Approximately 20% of women had levels of depressive symptoms indicative of clinical depression that were maintained 2 years postdiagnosis. Factors related to trajectory membership such as illness intrusiveness, social support, fatigue, pain, and vasomotor symptoms suggest targets for possible intervention. IMPACT: Results demonstrate the heterogeneity of depressive symptoms following breast cancer and the need for continued screening posttreatment.

Effect of ArginMax on sexual functioning and quality of life among female cancer survivors: results of the WFU CCOP Research Base Protocol 97106.

BACKGROUND: Problems with sexual functioning are common following therapy for breast and gynecologic cancers, although there are few effective treatments. OBJECTIVE: To assess the impact of ArginMax, a nutritional supplement comprised of extracts of L-arginine, ginseng, gingko, and damiana, as well as multivitamins and minerals, on sexual functioning and quality of life in female cancer survivors. METHODS: This was a 12-week, randomized, placebo-controlled trial of eligible patients who were 6 months or more from active treatment and reporting problems with sexual interest, satisfaction, and functioning after therapy. The participants took 3 capsules of Arginmax or placebo twice daily. Outcome measures were the Female Sexual Function Inventory (FSFI) and the Functional Assessment of Cancer Therapy - General (FACT-G). Assessments were done at baseline, 4, 8, and 12 weeks. RESULTS: 186 patients with a median age of 50 years were accrued between May 10, 2007 and March 24, 2010. 76% of the patients were non-Hispanic white. Most had breast or a gynecologic cancer (78% and 12%, respectively). At 12 weeks, there were no differences between the ArginMax group (n = 96) and placebo (n = 92) group in sexual desire, arousal, lubrication, orgasm,satisfaction or pain. However, FACT-G total scores were significantly better for participants who took ArginMax compared with those who took placebo (least squares [LS] means, 87.5 vs 82.9, respectively; P = .009). The Fact-G subscales that were most affected were Physical (25.37 vs. 23.51, P = .001) and Functional Well-Being (22.46 vs. 20.72, P = .007). Toxicities were similar for both groups. LIMITATIONS: Study results are limited by a lack of data on the participants' psychological and physical symptoms and sexual partner variables. CONCLUSIONS: ArginMax had no significant impact on sexual functioning, but patient quality of life was significantly better at 12 weeks in participants who received ArginMax.

Tumor-induced loss of mural Connexin 43 gap junction activity promotes endothelial proliferation.

BACKGROUND: Proper functional association between mural cells and endothelial cells (EC) causes EC of blood vessels to become quiescent. Mural cells on tumor vessels exhibit decreased attachment to EC, which allows vessels to be unstable and proliferative. The mechanisms by which tumors prevent proper association between mural cells and EC are not well understood. Since gap junctions (GJ) play an important role in cell-cell contact and communication, we investigated whether loss of GJ plays a role in tumor-induced mural cell dissociation. METHODS: Mural cell regulation of endothelial proliferation was assessed by direct co-culture assays of fluorescently labeled cells quantified by flow cytometry or plate reader. Gap junction function was assessed by parachute assay. Connexin 43 (Cx43) protein in mural cells exposed to conditioned media from cancer cells was assessed by Western and confocal microscopy; mRNA levels were assessed by quantitative real-time PCR. Expression vectors or siRNA were utilized to overexpress or knock down Cx43. Tumor growth and angiogenesis was assessed in mouse hosts deficient for Cx43. RESULTS: Using parachute dye transfer assay, we demonstrate that media conditioned by MDA-MB-231 breast cancer cells diminishes GJ communication between mural cells (vascular smooth muscle cells, vSMC) and EC. Both protein and mRNA of the GJ component Connexin 43 (Cx43) are downregulated in mural cells by tumor-conditioned media; media from non-tumorigenic MCF10A cells had no effect. Loss of GJ communication by Cx43 siRNA knockdown, treatment with blocking peptide, or exposure to tumor-conditioned media diminishes the ability of mural cells to inhibit EC proliferation in co-culture assays, while overexpression of Cx43 in vSMC restores GJ and endothelial inhibition. Breast tumor cells implanted into mice heterozygous for Cx43 show no changes in tumor growth, but exhibit significantly increased tumor vascularization determined by CD31 staining, along with decreased mural cell support detected by NG2 staining. CONCLUSIONS: Our data indicate that i) functional Cx43 is required for mural cell-induced endothelial quiescence, and ii) downregulation of Cx43 GJ by tumors frees endothelium to respond to angiogenic cues. These data define a novel and important role for maintained Cx43 function in regulation of vessel quiescence, and suggest its loss may contribute to pathological tumor angiogenesis.

Disparities in barriers to follow-up care between African American and White breast cancer survivors.

PURPOSE: Despite recommendations for breast cancer survivorship care, African American women are less likely to receive appropriate follow-up care, which is concerning due to their higher mortality rates. This study describes differences in barriers to follow-up care between African American and White breast cancer survivors. METHODS: We conducted a mailed survey of women treated for non-metastatic breast cancer in 2009-2011, 6-24 months post-treatment (N = 203). Survivors were asked about 14 potential barriers to follow-up care. We used logistic regression to explore associations between barriers and race, adjusting for covariates. RESULTS: Our participants included 31 African American and 160 White survivors. At least one barrier to follow-up care was reported by 62 %. Compared to White survivors, African Americans were more likely to identify barriers related to out-of-pocket costs (28 vs. 51.6 %, p = 0.01), other health care costs (21.3 vs. 45.2 %, p = 0.01), anxiety/worry (29.4 vs. 51.6 %, p = 0.02), and transportation (4.4 vs. 16.1 %, p = 0.03). After adjustment for covariates, African Americans were three times as likely to report at least one barrier to care (odds ratio (OR) = 3.3, 95 % confidence interval (CI) = 1.1-10.1). CONCLUSIONS: Barriers to care are common among breast cancer survivors, especially African American women. Financial barriers to care may prevent minority and underserved survivors from accessing follow-up care. Enhancing insurance coverage or addressing out-of-pocket costs may help address financial barriers to follow-up care among breast cancer survivors. Psychosocial care aimed at reducing fear of recurrence may also be important to improve access among African American breast cancer survivors.

Trajectories of Posttraumatic Growth and Associated Characteristics in Women with Breast Cancer.

BACKGROUND: Cancer survivors may experience posttraumatic growth (PTG), positive psychological changes resulting from highly stressful events; however, the longitudinal course of PTG is poorly understood. PURPOSE: The purpose of the present study was to determine trajectories of PTG in breast cancer survivors and associated characteristics. METHODS: Women (N = 653) participating in a longitudinal observational study completed questionnaires within 8 months of breast cancer diagnosis and 6, 12, and 18 months later. Group-based modeling identified PTG trajectories. Chi-square tests and ANOVA detected group differences in demographic, medical, and psychosocial variables. RESULTS: Six trajectory groups emerged. Three were stable at different levels of PTG, two increased modestly, and one increased substantially over time. Trajectory groups differed by age, race, receipt of chemotherapy, illness intrusiveness, depressive symptoms, active-adaptive coping, and social support. CONCLUSIONS: This first examination of PTG trajectories in US cancer survivors elucidates heterogeneity in longitudinal patterns of PTG. Future research should determine whether other samples exhibit similar trajectories and whether various PTG trajectories predict mental and physical health outcomes.

Effects of weight regain following intentional weight loss on glucoregulatory function in overweight and obese adults with pre-diabetes.

OBJECTIVE: To assess the extent to which initial, intentional weight loss-associated improvements in glucose tolerance and insulin action are diminished with weight regain. METHODS: 138 overweight and obese (BMI: 32.4±3.9kg/m(2)), adults (59.0±9.7 years), with pre-diabetes were followed through a 6-month weight loss intervention and subsequent 18-month weight maintenance period, or usual care control condition. Longitudinal change in weight (baseline, 6, 24 months) was used to classify individuals into weight pattern categories (Loser/Maintainer (LM), n= 50; Loser/Regainer (LR), n=51; and Weight Stable (WS), n=37). Fasting plasma glucose (FPG), insulin, and insulin resistance (HOMA-IR) were measured at baseline, 6, 12, 18 and 24 months and model adjusted changes, by weight pattern category, were assessed. RESULTS: LMs and LRs lost 8.3±4.7kg (8.7±4.5%) and 9.6±4.7kg (10.2±4.7%) during the first 6 months, respectively. LM continued to lose 1.1±3.4kg over the next 18 months (9.9±6.5% reduction from baseline; p<0.05), while LRs regained 6.5±3.7kg (3.3±5.3% reduction from baseline; p<0.05). Weight change was directly associated with change in all DM risk factors (all p<0.01). Notably, despite an absolute reduction in body weight (from baseline to 24 months) achieved in the LR group, 24-month changes in FPG, insulin, and HOMA-IR did not differ between WS and LR groups. Conversely, LM saw sustained improvements in all measured DM risk factors. CONCLUSIONS: Significant weight loss followed by weight loss maintenance is associated with sustained improvements in FPG, insulin, and HOMA-IR; conversely, even partial weight regain is associated with regression of initial improvements in these risk factors towards baseline values.

Trajectories of illness intrusiveness domains following a diagnosis of breast cancer.

OBJECTIVE: To identify trajectories of illness intrusiveness over the first 2 years after a breast cancer diagnosis and describe associated patient and treatment characteristics. Illness intrusiveness, or how much an illness disrupts life domains, has been shown to be highly related to quality of life. METHODS: Women recruited within 8 months of a breast cancer diagnosis (n = 653) completed questionnaires at baseline and 6, 12, and 18 months postbaseline. Group-based trajectory modeling was used to identify trajectories in three established domains of illness intrusiveness: instrumental, intimacy, and relationships and personal development. Bivariate analyses identified contextual, disease/treatment, psychological, and social characteristics of women in trajectory groups. RESULTS: Forty-one percent of women fell into a trajectory of consistently low illness intrusiveness (Low) across all three domains. Other women varied such that some reported illness intrusiveness that decreased over time on at least one domain (9-34%), and others reported consistently high intrusiveness on at least one domain (11-17%). A fourth trajectory of increased illness intrusiveness emerged in the relationship and personal development domain (9%). Characteristics of women in the Low group were being older; being less likely to have children at home; and having stage I cancer, fewer symptoms, and better psychosocial status. CONCLUSIONS: Women experienced different patterns of illness intrusiveness in the first 2 years after a diagnosis of breast cancer with a high percentage reporting Low intrusiveness. However, women differentially followed the other trajectory patterns by domain, suggesting that the effect of breast cancer on some women's lives may be specific to certain areas.

Predictors of posttraumatic growth in women with breast cancer.

OBJECTIVE: Posttraumatic growth (PTG) is defined as 'positive psychological change experienced as a result of a struggle with highly challenging life circumstances'. The current study examined change in PTG over 2 years following breast cancer diagnosis and variables associated with PTG over time. METHODS: Women recently diagnosed with breast cancer completed surveys within 8 months of diagnosis and 6, 12, and 18 months later. Linear mixed effects models were used to assess the longitudinal effects of demographic, medical, and psychosocial variables on PTG as measured by the Posttraumatic Growth Inventory (PTGI). RESULTS: A total of 653 women were accrued (mean age = 54.9, SD = 12.6). Total PTGI score increased over time mostly within the first few months following diagnosis. In the longitudinal model, greater PTGI scores were associated with education level, longer time since diagnosis, greater baseline level of illness intrusiveness, and increases in social support, spirituality, use of active-adaptive coping strategies, and mental health. Findings for the PTGI domains were similar to those for the total score except for the Spiritual Change domain. CONCLUSION: PTG develops relatively soon after a breast cancer diagnosis and is associated with baseline illness intrusiveness and increases in social support, spirituality, use of active-adaptive coping strategies, and mental health.

Impact of rural residence on forgoing healthcare after cancer because of cost.

BACKGROUND: Routine follow-up care is recommended to promote the well-being of cancer survivors, but financial difficulties may interfere. Rural-urban disparities in forgoing healthcare due to cost have been observed in the general population; however, it is unknown whether this disparity persists among survivors. The purpose of this study was to examine rural-urban disparities in forgoing healthcare after cancer due to cost. METHODS: We analyzed data from 7,804 cancer survivors in the 2006 to 2010 National Health Interview Survey. Logistic regression models, adjusting for sociodemographic and clinical characteristics, were used to assess rural-urban disparities in forgoing medical care, prescription medications, and dental care due to cost, stratified by age (younger: 18-64, older: 65+). RESULTS: Compared with urban survivors, younger rural survivors were more likely to forgo medical care (P < 0.001) and prescription medications (P < 0.001) due to cost; older rural survivors were more likely to forgo medical (P < 0.001) and dental care (P = 0.05). Rural-urban disparities did not persist among younger survivors in adjusted analyses; however, older rural survivors remained more likely to forgo medical [OR = 1.66, 95% confidence interval (CI) = 1.11-2.48] and dental care (OR = 1.54, 95%CI = 1.08-2.20). CONCLUSIONS: Adjustment for health insurance and other sociodemographic characteristics attenuates rural-urban disparities in forgoing healthcare among younger survivors, but not older survivors. Financial factors relating to healthcare use among rural survivors should be a topic of continued investigation. IMPACT: Addressing out-of-pocket costs may be an important step in reducing rural-urban disparities in healthcare, especially for older survivors. It will be important to monitor how healthcare reform efforts impact disparities observed in this vulnerable population.