Evaluation of Bebtelovimab for Treatment of Covid-19 During the SARS-CoV-2 Omicron Variant Era.

Background: Monoclonal antibody (mAb) treatment is associated with decreased risk of hospitalization and death in high-risk outpatients with mild to moderate coronavirus disease 2019 (COVID-19) caused by early severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants. Bebtelovimab exhibits in vitro activity against the Omicron variant and its sublineages; however, clinical data are lacking. Methods: A retrospective cohort study was conducted comparing bebtelovimab-treated patients with propensity score-adjusted and matched nontreated control groups. Participants included high-risk outpatients eligible for bebtelovimab treatment under Emergency Use Authorization with a positive SARS-CoV-2 test from March 30 to May 28, 2022. Treated patients received single-dose intravenous treatment with bebtelovimab. The primary outcome was hospitalization or death over 28 days. Results: Before matching/statistical adjustment, mAb-treated patients were, on average, 10 years older than nontreated patients (61.6 vs 51.3 years) and had higher prevalence of obstructive sleep apnea, hypertension, chronic kidney disease, cancer, organ or cell transplant, and immunocompromised status (standardized mean differences ≥0.20). The adjusted odds ratio (OR) of hospitalization or death comparing 1006 treated with 2023 nontreated patients was 0.50 (95% CI, 0.31-0.80). Among 930 treated and 930 propensity score-matched nontreated patients, the incidence of hospitalization or death was 3.1% vs 5.5%, respectively (conditional OR, 0.53; 95% CI, 0.32-0.86). The lower odds ratio of hospitalization or death associated with bebtelovimab treatment was most evident in older patients, those with immunocompromised status, and fully vaccinated patients. Conclusions: Monoclonal antibody treatment with bebtelovimab among COVID-19 outpatients is associated with lower odds of hospitalization or death, particularly among immunocompromised and older patients.

Translational Genomic Research: The Association between Genetic Profiles and Cognitive Functioning or Cardiac Function Among Breast Cancer Survivors Completing Chemotherapy.

Introduction: Emerging evidence suggests that Chemotherapy (CT) treated breast cancer survivors (BCS) who have "risk variants" in genes may be more susceptible to cognitive impairment (CI) and/or poor cardiac phenotypes. The objective of this preliminary study was to examine whether there is a relationship between genetic variants and objective/subjective cognitive or cardiac phenotypes. Methods and Analysis: BCS were recruited from Moffitt Cancer Center, Morsani College of Medicine, AdventHealth Tampa and Sarasota Memorial Hospital. Genomic DNA were collected at baseline for genotyping analysis. A total of 16 single nucleotide polymorphisms (SNPs) from 14 genes involved in cognitive or cardiac function were evaluated. Three genetic models (additive, dominant, and recessive) were used to test correlation coefficients between genetic variants and objective/subjective measures of cognitive functioning and cardiac outcomes (heart rate, diastolic blood pressure, systolic blood pressure, respiration rate, and oxygen saturation). Results: BCS (207 participants) with a mean age of 56 enrolled in this study. The majority were non-Hispanic white (73.7%), married (63.1%), and received both CT and radiation treatment (77.3%). Three SNPs in genes related to cognitive functioning (rs429358 in APOE, rs1800497 in ANKK1, rs10119 in TOMM40) emerged with the most consistent significant relationship with cognitive outcomes. Among five candidate SNPs related to cardiac functioning, rs8055236 in CDH13 and rs1801133 in MTHER emerged with potential significant relationships with cardiac phenotype. Conclusions: These preliminary results provide initial targets to further examine whether BCS with specific genetic profiles may preferentially benefit from interventions designed to improve cognitive and cardiac functioning following CT.

Association of Subcutaneous or Intravenous Administration of Casirivimab and Imdevimab Monoclonal Antibodies With Clinical Outcomes in Adults With COVID-19.

Importance: Monoclonal antibody (mAb) treatment decreases hospitalization and death in high-risk outpatients with mild to moderate COVID-19; however, only intravenous administration has been evaluated in randomized clinical trials of treatment. Subcutaneous administration may expand outpatient treatment capacity and qualified staff available to administer treatment, but the association with patient outcomes is understudied. Objectives: To evaluate whether subcutaneous casirivimab and imdevimab treatment is associated with reduced 28-day hospitalization and death compared with nontreatment among mAb-eligible patients and whether subcutaneous casirivimab and imdevimab treatment is clinically and statistically similar to intravenous casirivimab and imdevimab treatment. Design, Setting, and Participants: This prospective cohort study evaluated high-risk outpatients in a learning health system in the US with mild to moderate COVID-19 symptoms from July 14 to October 26, 2021, who were eligible for mAb treatment under emergency use authorization. A nontreated control group of eligible patients was also studied. Exposures: Subcutaneous injection or intravenous administration of the combined single dose of 600 mg of casirivimab and 600 mg of imdevimab. Main Outcomes and Measures: The primary outcome was the 28-day adjusted risk ratio or adjusted risk difference for hospitalization or death. Secondary outcomes included 28-day adjusted risk ratios and differences in hospitalization, death, a composite end point of emergency department admission and hospitalization, and rates of adverse events. Among 1959 matched adults with mild to moderate COVID-19, 969 patients (mean [SD] age, 53.8 [16.7] years; 547 women [56.4%]) who received casirivimab and imdevimab subcutaneously had a 28-day rate of hospitalization or death of 3.4% (22 of 653 patients) compared with 7.0% (92 of 1306 patients) in nontreated controls (risk ratio, 0.48; 95% CI, 0.30-0.80; P = .002). Among 2185 patients treated with subcutaneous (n = 969) or intravenous (n = 1216; mean [SD] age, 54.3 [16.6] years; 672 women [54.4%]) casirivimab and imdevimab, the 28-day rate of hospitalization or death was 2.8% vs 1.7%, which resulted in an adjusted risk difference of 1.5% (95% CI, -0.6% to 3.5%; P = .16). Among all infusion patients, there was no difference in intensive care unit admission (adjusted risk difference, 0.7%; 95% CI, -3.5% to 5.0%) or need for mechanical ventilation (adjusted risk difference, 0.2%; 95% CI, -5.8% to 5.5%). Conclusions and Relevance: In this cohort study of high-risk outpatients with mild to moderate COVID-19 symptoms, subcutaneously administered casirivimab and imdevimab was associated with reduced hospitalization and death when compared with no treatment. These results provide preliminary evidence of potential expanded use of subcutaneous mAb treatment, particularly in areas that are facing treatment capacity and/or staffing shortages.

Breast cancer mortality as a function of age.

BACKGROUND: Incidence of breast cancer (BC) in US women continues to increase with age as the strongest risk factor. We aimed to compare clinical, pathological and sociological variables associated to BC diagnosis, as well as the relative mortality rates of BC patients compared to the general US population. METHODS: We performed a retrospective, single-institution study evaluating 52,509 patients diagnosed with unilateral BC at the University of Pittsburgh Medical Center (UPMC) between 1990-2020. Primary outcome was death from any cause with cancer recurrence as a secondary outcome, evaluated for 4 age groups: 20-44, 45-55, 56-69, and 70-90. A dataset of expected mortality for women in the general population over a 10-year period was constructed using the Surveillance, Epidemiology, and End Results (SEER) Program. Observed vs. expected mortality and standardized mortality ratios (SMR) for each age group were calculated. RESULTS: Youngest patients with BC demonstrated the highest SMR at 10-year follow-up from time of diagnosis compared to the general US population (SMR 9.68, 95% CI: 8.99to 10.42), and remained highest compared to other age groups when analysis was limited to Stage 0/1 disease (10-year SMR 3.11, 95% CI: 2.54 to 3.76). SMRs decreased with increasing age at diagnosis with an SMR <1.0 in patients diagnosed with stage 0/1 at ages 70-90 at 5-year follow-up. CONCLUSIONS: Younger BC patients have the highest SMR which declines gradually with age. In the elderly, lower stage 0/1 SMR's are found compared to the general population, suggesting the possibility of an associated protective effect.

Mindfulness-based stress reduction for breast cancer survivors (MBSR(BC)): evaluating mediators of psychological and physical outcomes in a large randomized controlled trial.

MBSR(BC) is known to have a positive impact on psychological and physical symptoms among breast cancer survivors (BCS). The cognitive mechanisms of "how" MBSR(BC) works was addressed in a recent study that found that there was strong consistent evidence that reduced emotional reactivity is a mediator and moderate consistent evidence that mindfulness, rumination, and worry were mediators. The purpose of this study, as part of a larger R01 trial, was to test whether positive effects achieved from the MBSR(BC) program were mediated through changes in increased mindfulness, decreased fear of breast cancer recurrence, and perceived stress. Female BCS > 21 years diagnosed with Stage 0-III breast cancer were randomly assigned to a 6-week MBSR(BC) or a Usual Care (UC)regimen. Potential mediators of 6- and 12-week outcomes were identified by analysis of covariance (ANCOVA), followed by formal mediational analyses of main effects of MBSR(BC) on 6- and 12-week outcomes, including percentage of total effects explained. Among 322 BCS (167 MBSR(BC) and 155 UC), fear of recurrence and perceived stress, but not mindfulness, mediated reductions in anxiety and fatigue at weeks 6 and 12, partially supporting our hypothesis of cognitive mechanisms of MBSR(BC). TRIAL REGISTRATION: Registration Number: NCT01177124 http://www.ClinicalTrials.gov.

Cardiovascular Toxicity and Mortality Associated With Adoptive Cell Therapy and Tumor-infiltrating Lymphocytes for Advanced Stage Melanoma.

Adoptive cellular therapy (ACT) with tumor-infiltrating lymphocytes (TILs) has emerged as an effective treatment option for unresectable stage III/IV metastatic melanoma. Acute toxicities, particularly cardiovascular (CV), can have a significant effect on the completion of therapy. We abstracted information on 43 patients who received ACT-TIL treatment for melanoma at the Moffitt Cancer Center between 2010 and 2016. The Student t tests and χ2 tests were used to compare patient characteristics by presence versus absence of specific CV complications. In this cohort, 32.6% developed hypotension requiring treatment with intravenous fluids and pressors, 14% atrial fibrillation, and 2.3% troponin elevations suggestive of myocardial damage. No patients developed clinical heart failure, and among the patients that underwent echocardiography, there was no significant difference in mean left ventricular ejection fraction before or after therapy (62.9% vs. 63.5%, respectively, P=0.79). There was also no statistically significant difference in survival between those with and without CV complications (overall survival=61.9%, mean: 26.0 mo and progression-free survival=45.2%, mean: 18.1 mo). CV toxicities are common in ACT-TIL protocols; however, survival does not appear to be significantly affected. Further research is needed to define mechanisms and potential prevention strategies to help clinicians manage these complications and mitigate risk.

Usefulness of the American Heart Association's Ideal Cardiovascular Health Measure to Predict Long-term Major Adverse Cardiovascular Events (From the Heart SCORE Study).

To further reduce the burden of cardiovascular disease (CVD) and expand prevention efforts, the American Heart Association (AHA) introduced in 2010 the concept of Ideal Cardiovascular Health (ICH), which includes 7 metrics (smoking status, body mass index, physical activity, diet, total cholesterol, blood pressure, and fasting plasma glucose). Limited data exist on the relation between ICH and long-term CVD risk. The Heart Strategies Concentrating on Risk Evaluation (Heart SCORE) study cohort was used to examine the relation between ICH and incident major adverse cardiovascular events (MACE: first occurrence of death, myocardial infarction, stroke, acute ischemic syndrome, or coronary revascularization). The 7 factors of the ICH were scored at study entry on a 0 to 2 scale, resulting in possible range of 0 to 14, with higher scores representing "better" health. Cox regression analyses were used to estimate hazard ratios (HR) of MACE, along with 95% confidence intervals. Over a median follow-up of 12 years, the study population (n = 1,863, 67% women, 42% Black race, mean age 59 years [range 45 to 75]) had 218 MACE. In unadjusted analysis, the ICH score (per 1 unit) was associated with an estimated 12% lower risk of MACE (HR [95% Confidence Interval]: 0.88 [0.82, 0.93]). Adjusting for demographics, education, and quality of life, ICH score was associated with a 10% lower risk of MACE (HR 0.90 [0.84, 0.96]). In a community-based sample of adults, the AHA ICH construct, which includes 7 modifiable CVD risk factors, appears to be a valid measure for predicting long-term risk of MACE.

Challenges in Obtaining and Assessing Salivary Cortisol and α-Amylase in an Over 60 Population Undergoing Psychotherapeutic Treatment for Complicated Grief: Lessons Learned.

Biomarkers may serve as objective measures in complicated grief (CG) potentially capturing responses to stress reduction treatment. This paper reports challenges in obtaining and assessing salivary cortisol and α-amylase (sAA) for a recent randomized clinical trial. Within-session changes in salivary cortisol and sAA for 54 older adults with CG who received Accelerated Resolution Therapy were compared with perceived stress measured by Subjective Units of Distress Scale. Bivariate correlations and multiple regressions examined changes in biomarkers. Protocols, study logs, and audit reports identified challenges. Challenges included obtaining unstimulated passive drool salivary samples and their analyses. Our sample of older females on multiple medications may have resulted in a perfect storm of moderating and intervening variables which affected the stress response. This paper contributes to the discussion on designing clinical trials for older adults which must account for physiologic changes, multimorbidity, and polypharmacy common in this population and makes recommendations moving forward.

Temporal trends in patient characteristics, injury mechanisms and outcomes in pediatric trauma admissions between 2010 and 2017.

INTRODUCTION: Injuries are a leading cause of preventable morbidity and mortality in children. Mechanisms of injuries and presentations are diverse in pediatric injuries and require special attention. Dedicated pediatric trauma care centers are ideal for management of children with injuries simultaneously serving as sources of research data. The objective of the current study was to identify changes in injury mechanisms, modifiable risk factors, and outcomes independently associated with admissions at a large pediatric trauma center in Tampa, Florida. METHODS: We conducted retrospective analysis of 8-years (2010-2017) of pediatric trauma admissions to a large trauma center. Demographic factors and injury characteristics were examined for temporal trends over two year increments. Temporal changes in admissions with major trauma, admission to ICU, and length of stay were examined using logistic regression analysis, and factors associated with independent temporal trends were identified using ordinal logistic regression modeling. RESULTS: During the study period, there were 4,934 trauma admissions with a predominance of falls (45.1%) and traffic injuries (20.5%). Trends were observed with less frequent head injuries (2010-2011: 35.7% vs 2016-2017: 28.3%, p < .01) and abdominal injuries (2010-2011:10.3% vs 2016-2017: 8.2%, p = .03), and more frequent chest injuries (2010-2011: 9.0% vs 2016-2017: 11.4%, p < .01). Over the study period, evaluated in 2-year increments, higher use of private insurance (Adjusted Odds Ratio (AOR)=1.44, 95% Confidence Interval (CI) 95% CI: 1.29-1.61) and helicopter transport (AOR=1.91, 95% CI: 1.58 -2.30) was observed. Admissions for drownings (AOR=1.50, 95% CI: 1.10 -2.02) and animal bites (AOR=1.99, 95% CI: 1.46 -2.71) increased during the study period. Improvement in patient outcomes (adjusted for injury severity) were observed with shorter, ≤1 day length of stay (LOS) (AOR=1.19, 95% CI: 1.06 -1.33), reduction in complications (AOR=0.47, 95% CI: 0.33 -0.66), and more admissions without an intensive care unit (ICU) stay (AOR=1.6 95% CI = 1.36 -1.88). CONCLUSIONS: Significant reductions in LOS, ICU stay, and complications were temporally observed despite an increase in admissions with higher use of helicopter transport. These results can most likely be attributed to dedicated pediatric trauma experts and resources available at an integrated pediatric trauma center.

Patterns of Anticoagulation Use in Patients With Cancer With Atrial Fibrillation and/or Atrial Flutter.

BACKGROUND: Atrial fibrillation (AF) is a common cardiovascular complication affecting patients with cancer, but management strategies are not well established. OBJECTIVES: The purpose of this retrospective cohort study was to evaluate cross-sectional patterns of anticoagulation (AC) use in patients with cancer with AF or atrial flutter (AFL) on the basis of their risk for stroke and bleeding. METHODS: Patients with cancer and electrocardiograms showing AF or AFL performed at Moffitt Cancer Center in either the inpatient or outpatient setting were included in this retrospective analysis. We described percentages of AC prescription by stroke and bleeding risk, as determined by individual CHA2DS2-VASc and HAS-BLED scores, respectively. Multivariable logistic regression evaluated clinical variables independently associated with anticoagulant prescription. RESULTS: The prevalence of electrocardiography-documented AF or AFL was 4.8% (n = 472). The mean CHA2DS2-VASc score was 2.8 ± 1.4. Among patients with CHA2DS2-VASc scores ≥2 and HAS-BLED scores <3, 44.3% did not receive AC, and of these, only 18.3% had platelet values <50,000/µl. In multivariable analysis, older age, hypertension, prior stroke, and history of venous thromboembolism were each directly associated with AC use, while current chemotherapy use, prior bleeding, renal disease, and thrombocytopenia were each inversely associated with AC use. CONCLUSIONS: Nearly one-half of patients with cancer, the majority with normal platelet counts, had an elevated risk for stroke but did not receive AC. In addition to known predictors, current chemotherapy use was independently associated with a lower odds of AC use. This study highlights the need to improve the application of AF treatment algorithms to cancer populations.

Translational genomic research: the role of genetic polymorphisms in MBSR program among breast cancer survivors (MBSR[BC]).

Genetic variations of breast cancer survivors (BCS) may contribute to level of residual symptoms, such as depression, stress, fatigue, and cognitive impairment. The objective of this study was to investigate whether particular single-nucleotide polymorphisms (SNPs) moderated symptom improvement resulting from the Mindfulness-Based Stress Reduction for Breast Cancer (MBSR[BC]) program. An overarching goal of personalized medicine is to identify individuals as risk for disease and tailor interventions based on genetic profiles of patients with diseases including cancer. BCS were recruited from Moffitt Cancer Center and University of South Florida's Breast Health Program and were randomized to either the 6-week MBSR(BC) program (n = 92) or Usual Care (n = 93). Measures of symptoms, demographic, and clinical history data were attained at baseline, 6 weeks, and 12 weeks. A total of 10 SNPs from eight genes known to be related to these symptoms were studied using genomic DNA extracted from blood. Our results were examined for effect sizes, consistency, and statistical significance (p < .05). Three SNPs (rs4680 in COMT, rs6314 in HTR2A, and rs429358 in APOE) emerged as having the strongest (though relatively weak) and most consistent effects in moderating the impact of the MBSR program on symptom outcomes. Although effects were generally weak, with only one effect withstanding multiple comparisons correction for statistical significance, this translational behavioral research may help start the identification of genetic profiles that moderate the impact of MBSR(BC). The ultimate goal of this study is the development of personalized treatment programs tailored to the genetic profile of each patient.

Particulate Matter Air Pollution and Racial Differences in Cardiovascular Disease Risk.

OBJECTIVE: We aimed to assess racial differences in air pollution exposures to ambient fine particulate matter (particles with median aerodynamic diameter <2.5 µm [PM2.5]) and black carbon (BC) and their association with cardiovascular disease (CVD) risk factors, arterial endothelial function, incident CVD events, and all-cause mortality. APPROACH AND RESULTS: Data from the HeartSCORE study (Heart Strategies Concentrating on Risk Evaluation) were used to estimate 1-year average air pollution exposure to PM2.5 and BC using land use regression models. Correlates of PM2.5 and BC were assessed using linear regression models. Associations with clinical outcomes were determined using Cox proportional hazards models, adjusting for traditional CVD risk factors. Data were available on 1717 participants (66% women; 45% blacks; 59±8 years). Blacks had significantly higher exposure to PM2.5 (mean 16.1±0.75 versus 15.7±0.73µg/m3; P=0.001) and BC (1.19±0.11 versus 1.16±0.13abs; P=0.001) compared with whites. Exposure to PM2.5, but not BC, was independently associated with higher blood glucose and worse arterial endothelial function. PM2.5 was associated with a higher risk of incident CVD events and all-cause mortality combined for median follow-up of 8.3 years. Blacks had 1.45 (95% CI, 1.00-2.09) higher risk of combined CVD events and all-cause mortality than whites in models adjusted for relevant covariates. This association was modestly attenuated with adjustment for PM2.5. CONCLUSIONS: PM2.5 exposure was associated with elevated blood glucose, worse endothelial function, and incident CVD events and all-cause mortality. Blacks had a higher rate of incident CVD events and all-cause mortality than whites that was only partly explained by higher exposure to PM2.5.

Feasibility of the mobile mindfulness-based stress reduction for breast cancer (mMBSR(BC)) program for symptom improvement among breast cancer survivors.

OBJECTIVE: The purpose of this pilot study was to test the feasibility of delivering the mobile mindfulness-based stress reduction for breast cancer (mMBSR(BC)) program using an iPad and to evaluate its impact on symptom improvement. METHODS: A single group, pre-posttest design was implemented among female stages 0-III breast cancer survivors (BCS) who completed treatment. Data were collected at baseline and week 6 on measures of psychological and physical symptoms and quality of life. The mMBSR(BC) program is a standardized, stress-reducing intervention that combines sitting and walking meditation, body scan, and yoga and is designed to deliver weekly 2-hour sessions for 6 weeks using an iPad. RESULTS: The mean age of the 15 enrolled BCS was 57 years; one participant was non-Hispanic black, and 14 were non-Hispanic white. Of the 13 who completed the study, there were significant improvements from baseline to 6 weeks post-mMBSR(BC) in psychological and physical symptoms of depression, state anxiety, stress, fear of recurrence, sleep quality, fatigue, and quality of life (P's < .05). Effect sizes for improvements of multiple symptoms ranged from medium to large. CONCLUSIONS: These results provide preliminary support that the mMBSR(BC) program may be feasible and acceptable, showing a clinical impact on decreasing psychological and physical symptoms. This mobile-based program offers a delivery of a standardized MBSR(BC) intervention to BCS that is convenient for their own schedule while decreasing symptom burden in the survivorship phase after treatment for breast cancer.

A Randomized Controlled Trial of the Effects of Mindfulness-Based Stress Reduction (MBSR[BC]) on Levels of Inflammatory Biomarkers Among Recovering Breast Cancer Survivors.

PURPOSE: The purpose of this substudy of a large randomized controlled trial was to evaluate the efficacy of the Mindfulness-Based Stress Reduction (Breast Cancer) (MBSR[BC]) program compared to usual care (UC) in normalizing blood levels of pro-inflammatory cytokines among breast cancer survivors (BCS). METHOD: A total of 322 BCS were randomized to either a 6-week MBSR(BC) program or a UC. At baseline and 6 and 12 weeks, 10 ml of venous blood and demographic and clinical data were collected and/or updated. Plasma cytokines (interleukin [IL]-1ß, IL-6, IL-10, tumor necrosis factor [TNF] α, transforming growth factor [TGF] ß1, soluble tumor necrosis factor receptor [sTNFR] 1) were assayed. Linear mixed models were used to assess cytokine levels across three time points (baseline and 6 and 12 weeks) by group (MBSR[BC] vs. UC). RESULTS: Of the six measured cytokines, three were nondetectable at rates greater than 50% (IL-10, IL-1ß, TGF-ß1) and, because of overall low prevalence, were not analyzed further. For the remaining cytokines (TNFα, IL-6, sTNFR1), results showed that TNFα and IL-6 increased during the follow-up period (between 6 and 12 weeks) rather than during the MBSR(BC) training period (between baseline and 6 weeks), while sTNFR1 levels did not change significantly across the 12-week period. CONCLUSIONS: Study results suggest that MBSR(BC) affects cytokine levels in BCS, mainly with increases in TNFα and IL-6. The data further suggest that B-cell modulation may be a part of immune recovery during breast cancer management and that increases in TNFα and IL-6 may be markers for MBSR(BC)-related recovery.

Mindfulness-Based Stress Reduction in Post-treatment Breast Cancer Patients: Immediate and Sustained Effects Across Multiple Symptom Clusters.

CONTEXT: Breast cancer survivors (BCS) face adverse physical and psychological symptoms, often co-occurring. Biologic and psychological factors may link symptoms within clusters, distinguishable by prevalence and/or severity. Few studies have examined the effects of behavioral interventions or treatment of symptom clusters. OBJECTIVES: The aim of this study was to identify symptom clusters among post-treatment BCS and determine symptom cluster improvement following the Mindfulness-Based Stress Reduction for Breast Cancer (MBSR(BC)) program. METHODS: Three hundred twenty-two Stage 0-III post-treatment BCS were randomly assigned to either a six-week MBSR(BC) program or usual care. Psychological (depression, anxiety, stress, and fear of recurrence), physical (fatigue, pain, sleep, and drowsiness), and cognitive symptoms and quality of life were assessed at baseline, six, and 12 weeks, along with demographic and clinical history data at baseline. A three-step analytic process included the error-accounting models of factor analysis and structural equation modeling. RESULTS: Four symptom clusters emerged at baseline: pain, psychological, fatigue, and cognitive. From baseline to six weeks, the model demonstrated evidence of MBSR(BC) effectiveness in both the psychological (anxiety, depression, perceived stress and QOL, emotional well-being) (P = 0.007) and fatigue (fatigue, sleep, and drowsiness) (P < 0.001) clusters. Results between six and 12 weeks showed sustained effects, but further improvement was not observed. CONCLUSION: Our results provide clinical effectiveness evidence that MBSR(BC) works to improve symptom clusters, particularly for psychological and fatigue symptom clusters, with the greatest improvement occurring during the six-week program with sustained effects for several weeks after MBSR(BC) training. TRIAL REGISTRATION: Name and URL of Registry: ClinicalTrials.gov. Registration number: NCT01177124.

Examination of Broad Symptom Improvement Resulting From Mindfulness-Based Stress Reduction in Breast Cancer Survivors: A Randomized Controlled Trial.

PURPOSE: The purpose of this randomized trial was to evaluate the efficacy of the Mindfulness-Based Stress Reduction for Breast Cancer (MBSR[BC]) program in improving psychological and physical symptoms and quality of life among breast cancer survivors (BCSs) who completed treatment. Outcomes were assessed immediately after 6 weeks of MBSR(BC) training and 6 weeks later to test efficacy over an extended timeframe. PATIENTS AND METHODS: A total of 322 BCSs were randomly assigned to either a 6-week MBSR(BC) program (n = 155) or a usual care group (n = 167). Psychological (depression, anxiety, stress, and fear of recurrence) and physical symptoms (fatigue and pain) and quality of life (as related to health) were assessed at baseline and at 6 and 12 weeks. Linear mixed models were used to assess MBSR(BC) effects over time, and participant characteristics at baseline were also tested as moderators of MBSR(BC) effects. RESULTS: Results demonstrated extended improvement for the MBSR(BC) group compared with usual care in both psychological symptoms of anxiety, fear of recurrence overall, and fear of recurrence problems and physical symptoms of fatigue severity and fatigue interference (P < .01). Overall effect sizes were largest for fear of recurrence problems (d = 0.35) and fatigue severity (d = 0.27). Moderation effects showed BCSs with the highest levels of stress at baseline experienced the greatest benefit from MBSR(BC). CONCLUSION: The MBSR(BC) program significantly improved a broad range of symptoms among BCSs up to 6 weeks after MBSR(BC) training, with generally small to moderate overall effect sizes.

Cardiovascular Disease and 10-Year Mortality in Postmenopausal Women with Clinical Features of Polycystic Ovary Syndrome.

BACKGROUND: Women with polycystic ovary syndrome (PCOS) have greater cardiac risk factor clustering but the link with mortality is incompletely described. OBJECTIVE: To evaluate outcomes in 295 postmenopausal women enrolled in the National Institutes of Health-National Heart, Lung, and Blood Institute (NIH-NHLBI) sponsored Women's Ischemia Syndrome Evaluation (WISE) study according to clinical features of PCOS. MATERIALS AND METHODS: A total of 25/295 (8%) women had clinical features of PCOS defined by a premenopausal history of irregular menses and current biochemical evidence of hyperandrogenemia, defined as the top quartile of androstenedione (≥701 pg/mL), testosterone (≥30.9 ng/dL), or free testosterone (≥4.5 pg/mL). Cox proportional hazard model estimated death (n = 80). RESULTS: Women with clinical features of PCOS had an earlier menopause (p = 0.01), were more often smokers (p < 0.04), and trended toward more angiographic coronary artery disease (CAD) (p = 0.07) than women without these features. Cumulative 10-year mortality was 28% for women with (n = 25) versus 27% without clinical features of PCOS (n = 270) (p = 0.85). PCOS was not a significant predictor (p = NS) in prognostic models including diabetes, waist circumference, hypertension, and angiographic CAD. CONCLUSION: From this longer-term follow up of a relatively small cohort of postmenopausal women with suspected ischemia, the prevalence of PCOS is similar to the general population, and clinical features of PCOS are not associated with CAD or mortality. These findings question whether identification of clinical features of PCOS in postmenopausal women who already have known cardiovascular disease provides any additional opportunity for risk factor intervention.

Usability and Acceptability of a Web-Based Program for Chemotherapy-Induced Peripheral Neuropathy.

Chemotherapy-induced neuropathy is a painful and debilitating adverse effect of certain chemotherapy drugs. There have not been any patient-centered, easily accessible Web-based interventions to assist with self-management of chemotherapy-induced neuropathy. The aims of this study were to evaluate usability and acceptability and to estimate an effect size of a Web-based intervention for assessing and managing chemotherapy-induced neuropathy. Participants (N = 14) were instructed to complete the Creativity, Optimism, Planning, and Expert Information for Chemotherapy-Induced Peripheral Neuropathy program and provide verbal responses to the program. Participants completed the Chemotherapy Induced Peripheral Neuropathy Assessment Tool and Post-Study System Usability Questionnaire. Iterative changes were made to the COPE-CIPN. Participants were asked to provide feedback on the revised COPE-CIPN, repeat the Chemotherapy Induced Peripheral Neuropathy Assessment Tool, and evaluate acceptability using the Acceptability e-Scale. The COPE-CIPN demonstrated high usability (mean, 1.98 [SD, 1.12]) and acceptability (mean, 4.40 [SD, 0.52]). Comments indicated that the interface was easy to use, and the information was helpful. While neuropathy symptoms continued to increase in this group of patients receiving neurotoxic chemotherapy, there was a decrease in mean level of interference with activities from 53.71 to 39.29 over 3 to 4 months, which indicated a moderate effect (d = 0.39) size. The COPE-CIPN may be a useful intervention to support self-management of chemotherapy-induced neuropathy.

Endothelial Dysfunction and Racial Disparities in Mortality and Adverse Cardiovascular Disease Outcomes.

BACKGROUND: The contribution of arterial endothelial dysfunction (ED) to increased cardiovascular disease (CVD) risk among Blacks is not known. HYPOTHESIS: We investigated whether peripheral arterial ED explains racial disparity in CVD events. METHODS: Data from the Heart Strategies Concentrating on Risk Evaluation (Heart SCORE) study was used. Endothelial dysfunction was assessed by the Framingham reactive hyperemia index (fRHI), measured using pulse amplitude tonometry (PAT). Lower values of fRHI indicate more severe ED. The primary outcome of interest was combined CVD events and all-cause mortality. RESULTS: 1454 individuals (62% female, 40% Black, mean age 59 ± 8 years) had available data on fRHI (mean [SD]: 0.74 [0.46]). Over a mean follow-up period of 8.0 ± 2.4 years (11,186 person-years), 116 events were observed. Black race, male sex, smoking, diabetes, blood pressure, triglycerides, C-reactive protein, and interleukin-6 were inversely correlated with fRHI in univariate models. In an unadjusted Cox regression model, fRHI was associated with 20% lower risk of the primary outcome events (hazard ratio [HR] per 1-SD higher fRHI: 0.80, 95% confidence interval [CI]: 0.66-0.97). However, this association was no longer significant after adjustment for CVD risk factors (HR: 0.90, 95% CI: 0.74-1.11). In an age- and sex-adjusted model, Blacks had 1.68 (95% CI: 1.16-2.43) higher risk of primary outcome compared with Whites. This association was not significantly attenuated by addition of fRHI to the multivariable models. CONCLUSION: Black race is associated with increased risk of CVD events and mortality independent of its associations with ED, as measured by PAT.

Body Image in Younger Breast Cancer Survivors: A Systematic Review.

BACKGROUND: Body image is a complex issue with the potential to impact many aspects of cancer survivorship, particularly for the younger breast cancer survivor. OBJECTIVE: The purpose of this review is to synthesize the current state of the science for body image in younger women with breast cancer. METHODS: Combinations of the terms "body image," "sexuality intervention," "women," "younger women," and "breast cancer" were searched in the PubMed, PsycINFO, CINAHL, Web of Knowledge, and Science Direct databases through January 2014. Inclusion criteria for this review were (1) original research, (2) published in English from the year 2000 forward, (3) measuring body image as an outcome variable, and (4) results included reporting of age-related outcomes. RESULTS: Thirty-six articles met the inclusion criteria. The majority of studies were cross-sectional, with extensive variation in body image assessment tools. Age and treatment type had a significant impact on body image, and poorer body image was related to physical and psychological distress, sex and intimacy, and the partnered relationship among younger women. Only 1 intervention study found a significant improvement in body image after intervention. CONCLUSIONS: Findings suggest body image is a complex posttreatment concern for breast cancer survivors, particularly younger women. The findings of this review are limited by the high level of variation in the methods for assessing body image. IMPLICATIONS FOR PRACTICE: Further research of interventions to address body image concerns following treatment for breast cancer is warranted. Improvement of body image may improve the quality of life of younger breast cancer survivors.