Improving lifestyle behaviors during chemotherapy for breast cancer: The Lifestyle, Exercise, and Nutrition Early After Diagnosis (LEANer) Trial.

BACKGROUND: Little is known about improving physical activity (PA) and diet during and after chemotherapy for breast cancer. This secondary analysis examines changes in PA and diet quality during a yearlong intervention for patients with breast cancer undergoing chemotherapy and evaluates factors associated with these changes. METHODS: Newly diagnosed patients with breast cancer (N = 173) undergoing chemotherapy were randomized to a year-long nutrition and exercise intervention (n = 87) or usual care (UC, n = 86). Mixed models compared 1-year changes in PA and diet quality via the Healthy Eating Index (HEI)-2015 by study arm. Among the intervention group, baseline factors associated with change in PA and diet were assessed with multivariable linear and logistic regression. RESULTS: At 1 year, compared with UC, the intervention arm increased PA more (mean difference = 136.1 minutes/week; 95% CI, 90.2-182.0), participated in more strength training (56% vs. 15%; p < .001), and had suggestive improvements in HEI-2015 (mean difference = 2.5; 95% CI, -0.3 to 5.3; p = .08). In the intervention arm, lower fatigue was associated with improved PA (p = .04) and higher education was associated with improved HEI-2015 (p = .001) at 1 year. Higher HEI-2015 (p = .04) and married/living with someone (p = .05) were associated with higher odds of participating in strength training at 1 year. CONCLUSIONS: This year-long lifestyle intervention for patients with breast cancer undergoing chemotherapy resulted in increases in PA and suggestive improvements in diet quality. Behavior change was associated with baseline fatigue, diet quality, education, and married/living with someone. Addressing these factors in interventions may improve uptake of lifestyle behaviors in trials during and after chemotherapy.

The Impact of Extended Treatment With Artemether-lumefantrine on Antimalarial Exposure and Reinfection Risks in Ugandan Children With Uncomplicated Malaria: A Randomized Controlled Trial.

BACKGROUND: Artemether-lumefantrine (AL) is the most widely used artemisinin-based combination therapy in Sub-Saharan Africa and is threatened by the emergence of artemisinin resistance. Dosing is suboptimal in young children. We hypothesized that extending AL duration will improve exposure and reduce reinfection risks. METHODS: We conducted a prospective, randomized, open-label pharmacokinetic/pharmacodynamic study of extended duration AL in children with malaria in high-transmission rural Uganda. Children received 3-day (standard 6-dose) or 5-day (10-dose) AL with sampling for artemether, dihydroartemisinin, and lumefantrine over 42-day clinical follow-up. Primary outcomes were (1) comparative pharmacokinetic parameters between regimens and (2) recurrent parasitemia analyzed as intention-to-treat. RESULTS: A total of 177 children aged 16 months to 16 years were randomized, contributing 227 total episodes. Terminal median lumefantrine concentrations were significantly increased in the 5-day versus 3-day regimen on days 7, 14, and 21 (P < .001). A predefined day 7 lumefantrine threshold of 280 ng/mL was strongly predictive of recurrence risk at 28 and 42 days (P < .001). Kaplan-Meier estimated 28-day (51% vs 40%) and 42-day risk (75% vs 68%) did not significantly differ between 3- and 5-day regimens. No significant toxicity was seen with the extended regimen. CONCLUSIONS: Extending the duration of AL was safe and significantly enhanced overall drug exposure in young children but did not lead to significant reductions in recurrent parasitemia risk in our high-transmission setting. However, day 7 levels were strongly predictive of recurrent parasitemia risk, and those in the lowest weight-band were at higher risk of underdosing with the standard 3-day regimen. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov number NCT03453840.

Percutaneous Ablation, Osteoplasty, Reinforcement, and Internal Fixation for Pain and Ambulatory Function in Periacetabular Osteolytic Malignancies.

Background Osteolytic neoplasms to periacetabular bone frequently cause pain and fractures. Immediate recovery is integral to lifesaving ambulatory oncologic care and maintaining quality of life. Yet, open acetabular reconstructive surgeries are associated with numerous complications that delay cancer treatments. Purpose To determine the effectiveness for short- and long-term pain and ambulatory function following percutaneous ablation, osteoplasty, reinforcement, and internal fixation (AORIF) for periacetabular osteolytic neoplasm. Materials and Methods This retrospective observational study evaluated clinical data from 50 patients (mean age, 65 years ± 14 [SD]; 25 men, 25 women) with osteolytic periacetabular metastases or myeloma. The primary outcome of combined pain and ambulatory function index score (range, 1 [bedbound] through 10 [normal ambulation]) was assessed before and after AORIF at 2 weeks and then every 3 months up to 40 months (overall median follow-up, 11 months [IQR, 4-14 months]). Secondary outcomes included Eastern Cooperative Oncology Group (ECOG) score, infection, transfusion, 30-day readmission, mortality, and conversion hip arthroplasty. Serial radiographs and CT images were obtained to assess the hip joint integrity. The paired t test or Wilcoxon signed-rank test and Kaplan-Meier analysis were used to analyze data. Results Mean combined pain and ambulatory function index scores improved from 4.5 ± 2.4 to 7.8 ± 2.1 (P < .001) and median ECOG scores from 3 (IQR, 2-4) to 1 (IQR, 1-2) (P < .001) at the first 2 weeks after AORIF. Of 22 nonambulatory patients, 19 became ambulatory on their first post-AORIF visit. Pain and functional improvement were retained beyond 1 year, up to 40 months after AORIF in surviving patients. No hardware failures, surgical site infections, readmissions, or delays in care were identified following AORIF. Of 12 patients with protrusio acetabuli, one patient required a conversion hemiarthroplasty at 24 months. Conclusion The ablation, osteoplasty, reinforcement, and internal fixation, or AORIF, technique was effective for short- and long-term improvement of pain and ambulatory function in patients with periacetabular osteolytic neoplasm. © RSNA, 2023.

Blood Pressure Trajectory Groups and Outcome After Endovascular Thrombectomy: A Multicenter Study.

BACKGROUND: Elevated blood pressure after endovascular thrombectomy (EVT) has been associated with an increased risk of hemorrhagic transformation and poor functional outcomes. However, the optimal hemodynamic management after EVT remains unknown, and the blood pressure course in the acute phase of ischemic stroke has not been well characterized. This study aimed to identify patient subgroups with distinct blood pressure trajectories after EVT and study their association with radiographic and functional outcomes. METHODS: This multicenter retrospective cohort study included consecutive patients with anterior circulation large-vessel occlusion ischemic stroke who underwent EVT. Repeated time-stamped blood pressure data were recorded for the first 72 hours after thrombectomy. Latent variable mixture modeling was used to separate subjects into five groups with distinct postprocedural systolic blood pressure (SBP) trajectories. The primary outcome was functional status, measured on the modified Rankin Scale 90 days after stroke. Secondary outcomes included hemorrhagic transformation, symptomatic intracranial hemorrhage, and death. RESULTS: Two thousand two hundred sixty-eight patients (mean age [±SD] 69±15, mean National Institutes of Health Stroke Scale 15±7) were included in the analysis. Five distinct SBP trajectories were observed: low (18%), moderate (37%), moderate-to-high (20%), high-to-moderate (18%), and high (6%). SBP trajectory group was independently associated with functional outcome at 90 days (P<0.0001) after adjusting for potential confounders. Patients with high and high-to-moderate SBP trajectories had significantly greater odds of an unfavorable outcome (adjusted odds ratio, 3.5 [95% CI, 1.8-6.7], P=0.0003 and adjusted odds ratio, 2.2 [95% CI, 1.5-3.2], P<0.0001, respectively). Subjects in the high-to-moderate group had an increased risk of symptomatic intracranial hemorrhage (adjusted odds ratio, 1.82 [95% CI, 1-3.2]; P=0.04). No significant association was found between trajectory group and hemorrhagic transformation. CONCLUSIONS: Patients with acute ischemic stroke demonstrate distinct SBP trajectories during the first 72 hours after EVT that have differing associations with functional outcome. These findings may help identify potential candidates for future blood pressure modulation trials.

Association of iron infusion reactions with ABO blood type.

OBJECTIVES: We sought to determine risk factors for iv iron infusion-related reactions (IRR), and identify strategies for iron repletion after IRR. METHODS: We conducted a retrospective chart review of patients treated in the classical hematology clinic at Yale Cancer Center (n = 330 consecutive patients) from 2016 to 2021, who received iv ferumoxytol (60.3%), iron sucrose (14.8%), or iron dextran (10.9%). RESULTS: The iv iron IRR was noted in 58 (17.6%) patients, 62.1% of whom had previously tolerated iv iron. The severity of IRR was mild in 22, moderate in 23, and severe in 11 patients. Most (72.4%) patients who experienced IRR tolerated a subsequent iv iron infusion. On multivariable analysis, a history of non-medication allergies was associated with greater odds of IRR (odds ratio [OR] 2.12, 95% confidence interval (CI): 1.16-3.87, p = .01). No patients with type AB blood, and few with type A blood (n = 6), had IRR; compared to type A or AB together, patients with type B (OR 5.00, 95% CI: 1.56-16.06, p = .007) or type O (OR 3.71, 95% CI: 1.44-9.55, p = .007) blood had greater odds of IRR. CONCLUSIONS: This study highlights a possible association of blood type with iv iron IRR; prospective studies with larger patient numbers are warranted to explore this association.

Resection of Cavity Shave Margins in Stage 0-III Breast Cancer Patients Undergoing Breast Conserving Surgery: A Prospective Multicenter Randomized Controlled Trial.

OBJECTIVE: Single-center studies have demonstrated that resection of cavity shave margins (CSM) halves the rate of positive margins and re-excision in breast cancer patients undergoing partial mastectomy (PM). We sought to determine if these findings were externally generalizable across practice settings. METHODS: In this multicenter randomized controlled trial occurring in 9 centers across the United States, stage 0-III breast cancer patients undergoing PM were randomly assigned to either have resection of CSM ("shave" group) or not ("no shave" group). Randomization occurred intraoperatively, after the surgeon had completed their standard PM. Primary outcome measures were positive margin and re-excision rates. RESULTS: Between July 28, 2016 and April 13, 2018, 400 patients were enrolled in this trial. Four patients (2 in each arm) did not meet inclusion criteria after randomization, leaving 396 patients for analysis: 196 in the "shave" group and 200 to the "no shave" group. Median patient age was 65 years (range; 29-94). Groups were well matched at baseline for demographic and clinicopathologic factors. Prior to randomization, positive margin rates were similar in the "shave" and "no shave" groups (76/196 (38.8%) vs. 72/200 (36.0%), respectively, P = 0.604). After randomization, those in the "shave" group were significantly less likely than those in the "no shave" group to have positive margins (19/196 (9.7%) vs. 72/200 (36.0%), P < 0.001), and to require re-excision or mastectomy for margin clearance (17/196 (8.7%) vs. 47/200 (23.5%), P < 0.001). CONCLUSION: Resection of CSM significantly reduces positive margin and re-excision rates in patients undergoing PM.

Association of relative dose intensity with BMI and pathologic complete response in patients treated with neoadjuvant chemotherapy for breast cancer.

PURPOSE: Previous work found that lower BMI is associated with a pathologic complete response (pCR) following neoadjuvant chemotherapy for breast cancer. Relative dose intensity (RDI) of chemotherapy is an important marker of treatment tolerability. We hypothesized that patients with low BMI would have higher RDI than patients with high BMI, explaining the mechanism for the association between BMI and pCR. METHODS: We conducted a retrospective study of women treated with neoadjuvant chemotherapy for stage I-III breast cancer at Yale New Haven Hospital-Smilow Cancer Hospital. We reviewed medical records to determine tumor characteristics, chemotherapy doses, and reasons for dose reductions or delays. The treatment RDI was calculated using published methods. Chi-squared analyses were conducted to determine the associations between RDI and BMI and between RDI and pCR. RESULTS: Our cohort (n = 237) had an average age of 53 years (SD 13) and mean BMI of 29.5 kg/m2 (SD 7.0). Fifty-eight patients (24%) received <85% RDI, and 61% of patients experienced at least one dose reduction or delay. BMI was not associated with RDI (p = 0.71), and RDI was not associated with pCR (p = 0.31); however, fewer dose delays was associated with pCR (p = 0.02). The most common reasons for dose reduction or delays were neuropathy, myelosuppression, and personal reasons. CONCLUSIONS: Nearly one quarter of our cohort had RDI <85%. Although RDI overall was not associated with pCR, having fewer dose delays was associated with pCR. Our results highlight a need for improved patient adherence to and tolerability of neoadjuvant chemotherapy to minimize treatment delays.

Examining the effect of obesity-associated gene variants on breast cancer survivors in a randomized weight loss intervention.

PURPOSE: Our study examined whether common variants of obesity-associated genes FTO, MC4R, BDNF, and CREB1 moderated the effects of a lifestyle intervention on weight change among breast cancer survivors. METHODS: 151 breast cancer survivors with a body mass index ≥ 25 kg/m2 were randomly assigned to a 6-month weight loss intervention or usual care group. Genotyping of FTO rs9939609, MC4R rs6567160, BDNF rs11030104, CREB1 rs17203016 was performed. Linear mixed models were used including the main effects of genotype (assuming a dominant genetic model), treatment arm on weight and percent body fat changes, and genotype by treatment interaction variable. All statistical tests were evaluated against a Bonferroni-corrected alpha of 0.0125. RESULTS: Women in the intervention group achieved significantly greater weight loss than the usual care group (5.9% vs 0.4%, p < 0.001), regardless of genotype. Changes in weight and percent body fat did not differ significantly between carriers of the FTO rs9939609, MC4R rs6567160, BDNF rs11030104, and CREB1 rs17203016 risk alleles compared to non-carriers (p-interaction > 0.0125 for each single-nucleotide polymorphisms). CONCLUSIONS: Women who are genetically predisposed to obesity and recently diagnosed with breast cancer may achieve significant and clinically meaningful weight loss through healthy eating and exercise. CLINICAL TRIAL REGISTRATION: NCT02863887 (Date of Registration: August 11, 2016); NCT02110641 (Date of Registration: April 10, 2014).

Demographic Characteristics Driving Disparities in Receipt of Long-term Services and Supports in the Community Setting.

BACKGROUND: Research suggests that growth in Black and Hispanic (minority) older adults' nursing home (NH) use may be the result of disparities in access to community-based and alternative long-term services and supports (LTSS). OBJECTIVE: We aimed to determine whether minority groups receiving care in NHs versus the community had fewer differences in their functional needs compared with the differences in nonminority older adults, suggesting a disparity. METHODS: We identified respondents aged 65 years or above with a diagnosis of Alzheimer disease or dementia in the 2016 Health and Retirement Study who reported requiring LTSS help. We performed unadjusted analyses to assess the difference in functional need between community and NH care. Functional need was operationalized using a functional limitations score and 6 individual activities of daily living. We compared the LTSS setting for minority older adults to White older adults using difference-in-differences. RESULTS: There were 186 minority older adults (community=75%, NH=25%) and 357 White older adults (community=50%, NH=50%). Between settings, minority older adults did not differ in education or marital status, but were younger and had greater income in the NH versus the community. The functional limitations score was higher in NHs than in the community for both groups. Functional needs for all 6 activities of daily living for the minority group were greater in NHs compared with the community. CONCLUSION: Functional need for minority older adults differed by setting while demographics varied in unexpected ways. Factors such as familial and financial support are important to consider when implementing programs to keep older adults out of NHs.

"Randomized trial of physical activity on quality of life and lung cancer biomarkers in patients with advanced stage lung cancer: a pilot study".

BACKGROUND: Lung cancer survivors need more options to improve quality of life (QoL). It is unclear to what extent patients with advanced stage disease are willing to participate in home-based physical activity (PA) and if these interventions improve QoL. The goal of our study was to determine interest in participating in our 3-month home-based walking regimen in patients with advanced stage lung cancer. We used a randomized design to evaluate for potential benefit in PA and patient-reported outcomes. METHODS: We performed an open-label, 1:1 randomized trial in 40 patients with stage III/IV non-small cell lung cancer (NSCLC) evaluating enrollment rate, PA, QoL, dyspnea, depression, and biomarkers. Compared to usual care (UC), the intervention group (IG) received an accelerometer, in-person teaching session, and gain-framed text messages for 12 weeks. RESULTS: We enrolled 56% (40/71) of eligible patients. Participants were on average 65 years and enrolled 1.9 years from diagnosis. Most patients were women (75%), and receiving treatment (85%) for stage IV (73%) adenocarcinoma (83%). A minority of patients were employed part-time or full time (38%). Both groups reported low baseline PA (IG mean 37 (Standard deviation (SD) 46) vs UC 59 (SD 56) minutes/week; p = 0.25). The IG increased PA more than UC (mean change IG + 123 (SD 212) vs UC + 35 (SD 103) minutes/week; p = 0.051)). Step count in the IG was not statistically different between baseline (4707 step/day), week 6 (5605; p = 0.16), and week 12 (4606 steps/day; p = 0.87). The intervention improved EORTC role functioning domain (17 points; p = 0.022) with borderline improvement in dyspnea (- 13 points; p = 0.051) compared to UC. In patients with two blood samples (25%), we observed a significant increase in soluble PD-1 (219.8 (SD 54.5) pg/mL; p < 0.001). CONCLUSIONS: Our pilot trial using a 3-month, home-based, mobile health intervention enrolled over half of eligible patients with stage III and IV NSCLC. The intervention increased PA, and may improve several aspects of QoL. We also identified potential biomarker changes relevant to lung cancer biology. Future research should use a larger sample to examine the effect of exercise on cancer biomarkers, which may mediate the association between PA and QoL. CLINICAL TRIAL REGISTRATION: Clinicaltrials.gov ( NCT03352245 ).

Randomized trial of exercise on depressive symptomatology and brain derived neurotrophic factor (BDNF) in ovarian cancer survivors: The Women's Activity and Lifestyle Study in Connecticut (WALC).

OBJECTIVES: Depression is one of the most prevalent mental disorders, and rates are higher among cancer survivors than the general population, and higher in ovarian cancer patients compared to cohorts of other cancer survivors. Physical activity has been associated with lower depressive symptoms in cancer survivors, yet no trial has examined this association in women with ovarian cancer. We examined the effect of exercise on depression symptomatology and serum brain derived neurotrophin factor (BDNF) which has been associated with depression, in women with ovarian cancer. METHODS: We conducted a 6-month home-based randomized trial of exercise vs. attention-control (AC) in 144 ovarian cancer survivors. Depressive symptomatology was measured via the Center for Epidemiologic Studies Depression Scale (CES-D). Serum total and free BDNF was measured at baseline and 6-months. Student's t-statistic and mixed-model repeated measures analysis was used to evaluate six-month change between arms in CES-D scores and BDNF. RESULTS: Women were 57.3 ±â€¯8.6 (mean ±â€¯SD) years old, 1.7 ±â€¯1.0 years post-diagnosis with a baseline CES-D score of 11.79 ±â€¯10.21. The majority (55%) were diagnosed with stage III/IV ovarian cancer. CES-D scores decreased in the exercise arm by 2.7 points (95% CI: -4.4, -0.9) or a 21% decrease compared to a 0.3 point decrease (-2.2, 1.5) (3% decrease) in the AC arm (P = 0.05). There was no difference in change in total or free BDNF between the exercise and AC arms. CONCLUSIONS: Ovarian cancer survivors are able to exercise at recommended levels, and exercise was associated with a significant reduction in depressive symptomatology.

Depression predicts cognitive and functional decline one month after coronary artery bypass graft surgery (Neuropsychiatric Outcomes After Heart Surgery study).

BACKGROUND: Prior research on cognitive and functional outcomes after coronary artery bypass graft (CABG) surgery has largely explored these two domains in isolation. In this study, we assess baseline depression and cognition as risk factors for decline in the Clinical Dementia Rating Sum-of-Boxes (CDR-SB) 1 month post-CABG surgery, which a combined measure of cognition and function. DESIGN: The Neuropsychiatric Outcomes After Heart Surgery study is a prospective observational cohort study. SETTING: A tertiary care, academic center. PARTICIPANTS: Of a total study sample of 148 patients undergoing CABG surgery, 124 (83.8%) completed 1-month follow-up assessment. Mean age was 66.3, 32 (25.8%) female and 112 (90.3%) White. MEASUREMENTS: Cognition, function, and depression were assessed on semi-structured clinical interviews. Cognitive and functional status were defined using CDR-SB; mild or major depression was defined by the Hamilton Depression Rating Scale. Additionally, neuropsychological battery was performed at baseline. RESULTS: CDR-SB decline occurred in 18 (14.5%) subjects. Older age, depression, baseline CDR-SB, and postoperative delirium were associated with 1-month decline on univariate analysis. Older age (OR 1.1 [1.0-1.2]) and depression (OR 6.2 [1.1-35.0]) remained significant on multivariate regression. In separate models, baseline performance on visual Wechsler memory scale (delayed), Hopkins verbal learning test (immediate and delayed), controlled oral word fluency test, and Trails B predicted CDR-SB decline. CONCLUSION: Roughly one in seven patients experienced CDR-SB decline 1 month after CABG surgery. Also, preoperative depression deserves recognition for being a predictor of CDR-SB decline one month post-CABG.

Skin Cancer Incidence in Organ Transplant Recipients Referred for Benign Skin Conditions.

BACKGROUND: Solid organ transplant recipients (SOTRs) are at ∼100-fold increased risk for developing skin cancers compared with the general population, with increased morbidity and mortality. These patients are closely followed by dermatology; however, it is unclear how referral reasons from nondermatologic providers affect care in these patients. OBJECTIVE: This study examines the reason SOTRs are referred to dermatologic care by nondermatologic providers as a potential predictor of nonmelanoma skin cancer (NMSC) outcomes. MATERIALS AND METHODS: A retrospective case-control study was conducted with the records of 353 adult SOTRs referred to a specialized transplant dermatology clinic within an academic tertiary care center between 2007 and mid-2012. RESULTS: Eighty-one patients were diagnosed with 491 total premalignant and malignant skin lesions. A considerable proportion of patients diagnosed with NMSC were referred for benign skin conditions such as rash or acne. CONCLUSION: These results indicate that some SOTRs referred to dermatology for benign skin disorders are incidentally diagnosed with cutaneous malignancies; this is concerning given that referrals for benign skin conditions may delay appropriate care for cutaneous malignancies and preventative care. Better risk stratification, improved interdisciplinary collaboration, and prompt referrals for dermatologic care are needed in the care of SOTRs.

First help-seeking attempt before and after psychosis onset: measures of delay and aversive pathways to care.

PURPOSE: Delay in receiving effective treatment for psychosis adversely impacts outcomes. We investigated the timing of the first help-seeking attempt in individuals with recent onset non-affective psychosis by comparing those who sought help during the prodrome to those who sought help after psychosis onset across sociodemographic and clinical characteristics, overall functioning, and occurrence of aversive events during their pathways to care. METHODS: Patients were admitted from February 1st, 2014 to January 31st, 2019 to the Program for Specialized Treatment Early in Psychosis (STEP) in New Haven, CT. Psychosis-onset date was ascertained using the Structured Interview for Psychosis-risk Syndromes. Key dates before and after psychosis onset, along with initiators and aversive events, were collected via semi-structured interview. RESULTS: Within 168 individuals, 82% had their first help-seeking episode after psychosis onset and did not differ in terms of sociodemographic characteristics from prodrome help seekers. When the first help-seeking episode started before (i.e., during prodrome) vs after psychosis onset it was mostly initiated by patients vs family members (Cramer's V = 0.23, p = 0.031) and led to a faster prescription of an antipsychotic once full-blown psychosis emerged (time to antipsychotic since psychosis onset = 21 vs 56 days, p = 0.03). No difference in aversive events before STEP enrollment was detected across groups. CONCLUSION: Help seeking during the prodrome is associated with faster initiation of antipsychotic treatment and is more likely to be self-initiated, compared to help seeking after psychosis onset. Early detection efforts that target prodromal samples may improve the length and experience of pathways to care.

Pilot study of combined aerobic and resistance exercise on fatigue for patients with head and neck cancer: Inflammatory and epigenetic changes.

This pilot study examined whether a combined aerobic resistance exercise program reduced fatigue and the potential inflammatory and epigenetic mechanisms in patients with head and neck cancer (HNC) receiving intensity-modulated radiotherapy. The exercise group (N = 12) received a 3-month supervised aerobic resistance exercise intervention that was initiated before a 6-week radiotherapy regimen; the control group (N = 14) received standard care. Fatigue was measured using Multidimensional Fatigue Inventory-20; physical function measures included a 6-minute walk distance (6MWD), chair stands, bicep curls, and hand grip strength. Inflammatory markers and DNA methylation data were acquired using standardized protocol. Patients were mostly white (93%) and male (81%) with a mean age of 57 years. At the end of the intervention, the exercise group had a marginal decrease in fatigue compared with the control (-5.0 vs. 4.9; P = 0.10). The exercise group had a significantly greater improvement in 6MWD (29.8 vs. -55.5 m; P = 0.04), and a marginally smaller decline in hand grip (-0.3 vs. -5.8 lbs; P = 0.05) at the end of the intervention than the control. No significant difference in inflammatory markers was observed between groups. Lower plasma interleukin (IL) 6, IL1 receptor antagonist, tumor necrosis factor α (TNFα), soluble TNF receptor II and C-reactive protein were significantly associated with increased 6MWD, chair stand, and bicep curl at the end of the intervention (p < 0.05). Among the 1152 differentially methylated sites (DMS) after intervention (p < 0.001), 163 DMS were located in gene promoter regions. Enrichment analysis suggested that the top 10 upstream regulators were associated with tumor (HNF4A, RPP38, HOXA9, SAHM1, CDK7, NDN, RPS15) and inflammation (IRF7, CRKL, ONECUT1). The top 5 diseases or functions annotations of the 62 hypermethylated DMS indicated anti-tumor and anti-inflammatory effects that might be linked to exercise. These findings suggest that exercise may improve physical performance and reduce fatigue, which could be further linked to decreased inflammation, during active radiotherapy for HNC patients. Larger studies are warranted.

F-Actin is associated with a worsening qSOFA score and intensive care unit admission in emergency department patients at risk for sepsis.

Objective: We previously demonstrated that plasma levels of F-actin and Thymosin Beta 4 differs among patients with septic shock, non-infectious systemic inflammatory syndrome and healthy controls and may serve as biomarkers for the diagnosis of sepsis. The current study aims to determine if these proteins are associated with or predictive of illness severity in patients at risk for sepsis in the Emergency Department (ED).Methods: Prospective, biomarker study enrolling patients (>18 years) who met the Shock Precautions on Triage Sepsis rule placing them at-risk for sepsis.Results: In this study of 203 ED patients, F-actin plasma levels had a linear trend of increase when the quick Sequential Organ Failure Assessment (qSOFA) score increased. F-actin was also increased in patients who were admitted to the Intensive Care Unit (ICU) from the ED, and in those with positive urine cultures. Thymosin Beta 4 was not associated with or predictive of any significant outcome measures.Conclusion: Increased levels of plasma F-actin measured in the ED were associated with incremental illness severity as measured by the qSOFA score and need for ICU admission. F-actin may have utility in risk stratification of undifferentiated patients in the ED presenting with signs and symptoms of sepsis.

Endocrine-related quality of life in a randomized trial of exercise on aromatase inhibitor-induced arthralgias in breast cancer survivors.

BACKGROUND: The objective of this study was to evaluate the role of a 12-month exercise intervention on endocrine-related quality of life (QOL) and overall QOL among breast cancer survivors with aromatase inhibitor (AI)-induced arthralgia in the Hormones and Physical Exercise (HOPE) Study. METHODS: This was a randomized controlled trial of 121 breast cancer survivors who were currently receiving AIs and experiencing at least mild arthralgia. QOL was assessed using the Functional Assessment of Cancer Therapy (FACT) questionnaires and the 36-Item Short Form Survey (SF-36) at baseline, 6 months, and 12 months. Participants were randomized to either a 1-year gym-based, supervised exercise intervention group (150 minutes of aerobic exercise and 2 strength-training sessions each week) or a usual care group. Effects of the intervention on QOL were assessed using mixed-model, repeated-measures analysis. RESULTS: At 12 months, the exercise group had greater improvement in the overall QOL measures as well as the breast cancer-specific (scores, 2.2 vs 0.7; P = .02), endocrine-specific (scores, 5.6 vs 1.6; P < .001), and fatigue-specific (score, 5.8 vs 0.5; P < .001) subscales compared with the usual care group. The results indicated a stronger effect at 12 months versus 6 months after the intervention. CONCLUSIONS: Combined aerobic and resistance exercise, such as treadmill walking and strength training, improved endocrine-related and overall QOL among breast cancer survivors who were experiencing adverse side effects from AIs. Because adverse side effects associated with AI use are quite common and this is the main reason for treatment discontinuation, this nonpharmacologic intervention could benefit many breast cancer survivors and increase successful adherence to AIs in breast cancer treatment.

Comparison on simultaneous caillary and venous parasite density and genotyping results from children and adults with uncomplicated malaria: a prospective observational study in Uganda.

BACKGROUND: Blood smear microscopy remains the gold-standard method to diagnose and quantify malaria parasite density. In addition, parasite genotyping of select loci is the most utilized method for distinguishing recrudescent and new infections and to determine the number of strains per sample. In research settings, blood may be obtained from capillary or venous compartments, and results from these matrices have been used interchangeably. Our aim was to compare quantitative results for parasite density and strain complexity from both compartments. METHODS: In a prospective observational study, children and adults presenting with uncomplicated Plasmodium falciparum malaria, simultaneous capillary and venous blood smears and dried blood spots were collected over 42-days following treatment with artemether-lumefantrine. Blood smears were read by two microscopists, any discrepancies resolved by a third reader. Parasite DNA fingerprinting was conducted using six microsatellites. Bland Altman analysis and paired t-test/McNemar's test were used to assess the difference in density readings and measurements. RESULTS: Two hundred twenty-three participants were included in the analysis (177 children (35 HIV-infected/142 HIV-uninfected), 21 HIV-uninfected pregnant women, and 25 HIV-uninfected non-pregnant adults). Parasite density measurements did not statistically differ between capillary and venous blood smears at the time of presentation, nor over the course of 42-day follow-up. Characterization of merozoite surface protein-2 (MSP-2) genetic polymorphism demonstrated a higher level of strain diversity at the time of presentation in venous samples, as compared with capillary specimens (p = 0.02). There was a high degree of variability in genotype-corrected outcomes when pairs of samples from each compartment were compared using MSP-2 alone, although the variability was reduced with the use of multiple markers. CONCLUSIONS: Parasite density measurements do not statistically differ between capillary and venous compartments in all studied demographic groups at the time of presentation with malaria, or over the course of follow-up. More strains were detected by MSP-2 genotyping in venous samples than in capillary samples at the time of malaria diagnosis. The use of multiple polymorphic markers reduces the impact of variability in strain detection on genotype-corrected outcomes. This study confirms that both capillary and venous compartments can be used for sampling with confidence in the clinical research setting. TRIAL REGISTRATION: The trial was registered at ClinicalTrials.gov under registration no. NCT01717885 .

Effects of Real-time EMS Direction on Optimizing EMS Turnaround and Load-balancing Between Neighboring Hospital Campuses.

Background: Implemented in September 2017, the "nurse navigator program" identified the preferred emergency department (ED) destination within a single healthcare system using real-time assessment of hospital and ED capacity and crowding metrics. Objective: The primary objective of the navigator program was to improve load-balancing between two closely situated emergency departments, both of which feed into the same inpatient facilities of a single healthcare system. A registered nurse in the hospital command center made real-time recommendations to emergency medical services (EMS) providers via radio, identifying the preferred destination for each transported patient based on such factors as chief complaint, ED volume, and waiting room census. The destination decision was made via the utilization of various real-time measures of health system capacity in conjunction with existing protocols dictating campus-specific clinical service availability. The objective of this study was to evaluate the efficacy of this real-time ambulance destination direction program as reflected in changes to emergency medical services (EMS) turnaround time and the incidence of intercampus transports. Methods: A before-and-after time series was performed to determine if program implementation resulted in a change in EMS turnaround time or incidence of intercampus transfers. Results: Implementation of the nurse navigator program was associated with a statistically significant decrease in EMS turnaround times for all levels of dispatch and transport at both hospital campuses. Intercampus transfers also showed significant improvement following implementation of the intervention, although this effect lagged behind implementation by several months. Conclusion: A proactive approach to EMS destination control using a nurse navigator with access to real-time hospital and ED capacity metrics appears to be an effective method of decreasing EMS turnaround time.

Lymphedema in ovarian cancer survivors: Assessing diagnostic methods and the effects of physical activity.

BACKGROUND: Lymphedema is a poorly understood side effect of gynecologic cancer treatment. This study was designed to determine the prevalence of lower limb lymphedema (LLL) in a sample of ovarian cancer survivors via 3 different diagnostic methods and to assess the effect of a randomized exercise intervention. METHODS: Physically inactive ovarian cancer survivors (n = 95) were enrolled in a 6-month randomized trial of exercise (primarily brisk walking) versus attention control. LLL was measured at baseline and 6-month visits via a self-report questionnaire, optoelectronic perometry, and an evaluation by a certified lymphedema specialist. RESULTS: LLL prevalence ranged from 21% to 38% according to the diagnostic method, and there was substantial agreement between the self-report questionnaire and the lymphedema specialist evaluation (κ = 0.61). There was no agreement between the evaluation with optoelectronic perometry and the specialist evaluation. With LLL defined by any method, the baseline prevalence was 38% in both groups. At 6 months, both groups experienced a decreased LLL prevalence: 28% in the exercise group and 35% in the control group. There was no difference in the change in lymphedema prevalence between the 2 groups (P = .64). Body mass index was a significant predictor of LLL. CONCLUSIONS: With a potential prevalence of LLL as high as 40%, further evaluation of diagnostic methods is required to better characterize this side effect of ovarian cancer treatment. No adverse effect of exercise on LLL was found. Further research is strongly needed to evaluate predictors of LLL and the effects of exercise on LLL in order to develop effective physical activity recommendations for women with ovarian cancer. Cancer 2018;124:1929-37. © 2018 American Cancer Society.