Improving clinician agreement and comfort through the development of a pediatric behavioral health huddle tool.

BACKGROUND: Hospitalized pediatric patients with behavioral health (BH) diagnoses awaiting transfer can exhibit behaviors that may lead to workplace violence such as aggression. Workplace violence can lead to discomfort in caring for these patients. Huddles can be used as a tool to identify potential for violence, to help address workplace violence, and improve clinician situational awareness. METHODS: Utilizing QI methodology, a BH specific huddle tool was created and implemented on an Acute Care floor that identified key components such as triggers and behavioral stability. Mixed methods were used to study the intervention including focus groups, surveys and measurement of agreement (surrogate for situational awareness). The aims of this quality improvement (QI) project were to 1) improve situational awareness by increasing agreement between team members 2) improve the overall comfort of the clinical team caring for BH patients by 10%. RESULTS: Agreement between clinicians on patient stability increased by 20%. Comfort in caring for BH patients increased by 4%. Providers reported the tool increased their understanding (89%) and communication (81%) regarding plan of care. APPLICATION TO PRACTICE: Standardized huddle tool can be utilized to increase situational awareness among team members caring for patients with behavioral health diagnoses and may help to address workplace violence.

Injury prevention for women and girls playing Australian Football: programme cocreation, dissemination and early adopter coach feedback.

Background: Adherence to injury prevention programmes may improve with greater end-user involvement and application of implementation frameworks during development. We describe the cocreation, initial dissemination and feedback from programme early adopters (coaches), to develop the first evidence-informed injury prevention programme for women playing community Australian Football (Prep-to-Play). Methods: We used a pragmatic seven-step process for developing sports injury prevention programmes to (1) gain organisational support, (2) compile research evidence, (3) consult experts, (4) engage end-users, (5) test programme acceptability, (6) evaluate against theory and (7) gain early adopter feedback. All Australian Football-registered coaches of women's/girls' teams were sent a postseason survey to determine initial awareness, adoption and implementation (steps 5 and 6). Purposively selected coaches were invited to interviews/focus groups (step 7) to identify competency, organisational and leadership implementation drivers with a deductive thematic analysis applied. Results: Prep-to-Play was cocreated using previous efficacious programmes and expert input (steps 1-4), and disseminated via the national sporting organisation in preseason 2019 to all registered coaches (step 5). 343 coaches (90 women) completed the postseason survey and 22 coaches (5 women) participated in an interview (n=9) or focus group (n=13) (steps 6 and 7). 268 coaches (78%) were aware of Prep-to-Play. Of those aware, 218 (81%) had used (at least one element) Prep-to-Play, and 143 (53%) used it at least twice per week. Competency drivers included local expert-delivered face-to-face workshops complimented by online content and ongoing support. Organisational drivers included coach education integrated into existing league/club. Leadership drivers included compulsory injury prevention education integrated into coach reaccreditation processes or incentivisation via recognition (eg, professional development points). Conclusions: Cocreation and organisational support resulted in high programme awareness and adoption. However, high fidelity implementation and maintenance may need to be facilitated by competency, organisational and leadership drivers. Responsibility should be shared among all stakeholders.

Team debriefing in the COVID-19 pandemic: a qualitative study of a hospital-wide clinical event debriefing program and a novel qualitative model to analyze debriefing content.

BACKGROUND: Healthcare workers faced unique challenges during the early months of the COVID-19 pandemic which necessitated rapid adaptation. Clinical event debriefings (CEDs) are one tool that teams can use to reflect after events and identify opportunities for improving their performance and their processes. There are few reports of how teams have used CEDs in the COVID-19 pandemic. Our aim is to explore the issues discussed during COVID-19 CEDs and propose a framework model for qualitatively analyzing CEDs. METHODS: This was a descriptive, qualitative study of a hospital-wide CED program at a quaternary children's hospital between March and July 2020. CEDs were in-person, team-led, voluntary, scripted sessions using the Debriefing in Suspected COVID-19 to Encourage Reflection and Team Learning (DISCOVER-TooL). Debriefing content was qualitatively analyzed using constant comparative coding with an integrated deductive and inductive approach. A novel conceptual framework was proposed for understanding how debriefing content can be employed at various levels in a health system for learning and improvement. RESULTS: Thirty-one debriefings were performed and analyzed. Debriefings had a median of 7 debriefing participants, lasted a median of 10 min, and were associated with multiple systems-based process improvements. Fourteen themes and 25 subthemes were identified and categorized into a novel Input-Mediator-Output-Input Debriefing (IMOID) model. The most common themes included communication, coordination, situational awareness, team member roles, and clinical standards. CONCLUSIONS: Teams identified diverse issues in their debriefing discussions related to areas of high performance and opportunities for improvement in their care of COVID-19 patients. This model may help healthcare systems to understand how CED tools can be used to accelerate organizational learning to promote safety and improve outcomes in changing clinical environments.

Prevention of Latent Safety Threats: A Quality Improvement Project to Mobilize a Portable CT.

INTRODUCTION: Transporting critically ill patients to diagnostic imaging for needed studies can be challenging and even prohibitive. A portable computerized tomography (CT) scanner allows the patient to remain in the intensive care unit, but presents new positioning and team challenges. Before activation of a portable CT scanner in our pediatric intensive care unit and through the use of iterative simulation-based Plan-Do-Study-Act (PDSA) cycles in the clinical environment, a multidisciplinary team of bedside caregivers determined optimal patient positioning, equipment needs, and specific staffing and choreography to develop detailed portable CT guidelines. METHOD: Our team engaged stakeholders from radiology, critical care, respiratory therapy, environmental services, facilities operations, and the CT vendor to develop scenarios. Simulations included infant and pediatric patients who required critical invasive monitoring and treatment devices, such as ventilators, and high-risk intracardiac and intravascular lines. Scenario objectives centered on the safe positioning, transfer, and scanning of the patient. Trained simulation specialists from the hospital's simulation center facilitated simulation sessions. RESULTS: Simulation-based PDSA testing identified 31 latent safety threats, including the need for a custom bed adapter due to pediatric patients' variable size. We paused portable CT activation pending the custom adapter's availability and remediation of other latent safety threats. Additional simulation-based PDSA cycles further refined the process once the custom adapter was available. CONCLUSIONS: Simulation identified unanticipated latent safety threats before the implementation of a portable CT scanner.

EXIT (ex utero Intrapartum Treatment) to Airway Procedure for Twin Fetuses With Oropharyngeal Teratomas: Lessons Learned.

Ex utero intrapartum treatment (EXIT) to airway has been described as a safe method to secure challenging fetal airways while on placental support. Herein, we present a unique case of a monochorionic-diamniotic twin pregnancy where both fetuses presented with oropharyngeal tumors requiring airway securement on placental bypass. A multidisciplinary tabletop simulation was convened to allow for personnel coordination between multiple services, OR equipment allocation, and preparation for a range of possible clinical scenarios. A tabletop simulation was chosen for planning since this is a simulation methodology commonly used for preparation in acute, high intensity multidisciplinary situations such as disaster preparation, and allows for exploration of multiple potential scenarios when outcomes are uncertain. The twins were urgently delivered for decreased fetal movement and decelerations in Twin B at 28 weeks 6 days. Twin A was delivered via EXIT to airway while Twin B had debulking of the tumor on placental support, with subsequent airway securement through a tracheostomy. In conclusion, for complex fetal procedures, detailed pre-operative planning with tabletop simulation may be a useful tool in achieving successful patient outcomes.

Preferences for breast cancer survivorship care by rural/urban residence and age at diagnosis.

PURPOSE: Preferences for survivorship care among recently treated breast cancer survivors may vary by rural-urban residence and age, but potential differences have not been examined. METHODS: We conducted a cross-sectional survey of survivorship preferences among women treated for non-metastatic breast cancer 6-24 months prior to recruitment. RESULTS: We surveyed 203 women (66% response) with American Joint Committee on Cancer Stage I or II breast cancer. Rural residents comprised 36.5% of respondents (82.7% White, non-Hispanic; 52.5% < college education) and 29.6% were ≥ 65 years. More than 95% indicated that checking for recurrence, receiving additional treatment, evaluation of side effects, and identification of late effects were "very important" reasons for follow-up care. The most common topics identified as "very important" for survivorship care discussions were recommendations for healthy behaviors (65.3%), best sources for breast cancer information (65.3%), and effects on family (53.3%) and job (53.8%). Women 65 years and older preferred to discuss follow-up care at the time of diagnosis (p = 0.002), with younger women preferring during (32%) or after treatment (39.1%). Rural survivors were significantly more likely to identify follow-up care reasons not related to the initial breast cancer as "very important" than urban survivors, including screening for other cancers, and examinations or tests for non-cancer diseases (both p = 0.01). CONCLUSIONS: Survivorship care in accordance with national recommendations will likely be accepted by breast cancer survivors. Tailoring breast cancer survivorship care by timing, integration of primary care services, and specific psychosocial topics may best meet the needs of different ages and demographics.

National Institute on Aging /Alzheimer's Association criteria for Mild Cognitive Impairment applied to chemotherapy treated breast cancer survivors.

BACKGROUND: In this analysis we use the National Institute on Aging/Alzheimer's Association (NIA/AA) criteria to identify Mild Cognitive Impairment (MCI) in a sample of breast cancer survivors treated with chemotherapy. METHODS: Sixty women ages 39-79 on a prospective clinical trial of donepezil were assessed at baseline using a battery of standardized/validated neurocognitive measures. Cognitive status was adjudicated to identify MCI by a panel of dementia experts. RESULTS: Fifty percent were not cognitively impaired, 43% met the NIA/AA criteria for MCI, 2% had dementia, and 5% could not be classified. DISCUSSION: In this sample, nearly half of breast cancer survivors met the NIA/AA criteria for MCI. We propose these criteria be used to define cancer-related Mild Cognitive Impairment (cMCI), providing a framework for conducting additional studies to further characterize cMCI and identify clinical, imaging, and genetic factors associated with the progression of cMCI to more advanced stages of cognitive impairment.

Analysis of Risk of Recurrence by Subtype in ≤ 1-cm Breast Tumors.

INTRODUCTION: Triple negative breast cancer (TNBC) is an aggressive subtype of breast cancer with higher recurrence rates than other breast cancer subtypes. Increasing numbers of women are being diagnosed with early-stage breast cancer because of improvements in screening mammography. TNBC is known to be highly sensitive to chemotherapy; however, the benefit of adjuvant chemotherapy among women with ≤ 1-cm, lymph node-negative TNBC is unknown. MATERIALS AND METHODS: We evaluated the recurrence rates and recurrence-free survival of 437 women diagnosed with stage T1a-T1bN0 breast cancer from 1997 to 2009 at 2 institutions, with a median follow-up time of 6.2 years. Furthermore, we examined the treatment regimens of these women and evaluated the association of adjuvant chemotherapy with recurrence-free survival. RESULTS: Chemotherapy was administered more often to younger women and to women with high-grade, human epidermal growth factor receptor 2-positive or TNBC. Recurrence-free survival did not differ significantly between TNBC and estrogen receptor-positive breast cancer (hazard ratio [HR], 0.33; 95% confidence interval [CI], 0.10-1.04; P = .058). After appropriate adjustments, no significant differences were detected in recurrence-free survival between the women who had received chemotherapy and those who had not among the women with TNBC (P = .132) or within any of the breast cancer subtypes (HR, 0.6; 95% CI, 0.2-1.9; P = .392). CONCLUSION: Prospective trials of this subcentimeter node-negative breast cancer population are warranted to guide adjuvant chemotherapy decisions.

Comorbidity, age, and mortality among adults treated intensively for acute myeloid leukemia (AML).

INTRODUCTION: Our goal was to characterize comorbidities among adults receiving intensive therapy for AML, and investigate their association with outcomes. METHODS: We retrospectively analyzed 277 consecutive patients with newly diagnosed AML treated intensively at the Comprehensive Cancer Center of Wake Forest University from 2002 to 2009. Pretreatment comorbidities were identified by ICD-9 codes and chart review. Comorbidity burden (modified Charlson Comorbidity Index [CCI]) and specific conditions were analyzed individually. Outcomes were overall survival (OS), remission, and 30-day mortality. Covariates included age, gender, cytogenetic characteristics, hemoglobin, white cell count, lactate dehydrogenase, body mass index, and insurance type. Cox proportional hazards models were used to evaluate OS; logistic regression was used for remission and 30-day mortality. RESULTS: In this series, 144 patients were ≥ 60 years old (median age 70 years, median survival 8.7 months) and 133 were <60 years (median age 47 years, median survival 23.1 months). Older patients had a higher comorbidity burden (CCI≥1 58% versus 26%, P<0.001). Prevalent comorbid conditions differed by age (diabetes 19.2% versus 7.5%; cardiovascular disease 12.5% versus 4.5%, for older versus younger patients, respectively). The CCI was not independently associated with OS or 30-day mortality in either age group. Among older patients, diabetes was associated with higher 30-day mortality (33.3% vs. 12.0% in diabetic vs. non-diabetic patients, p=0.006). Controlling for age, cytogenetic characteristics and other comorbidities, the presence of diabetes increased the odds of 30-day mortality by 4.9 (CI 1.6-15.2) times. DISCUSSION: Diabetes is adversely associated with 30-day survival in older AML patients receiving intensive therapy.

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.

Chronic statin administration may attenuate early anthracycline-associated declines in left ventricular ejection function.

BACKGROUND: Recent studies have shown an association between statin therapy and a reduced risk of heart failure among breast cancer survivors. Our goal was to evaluate whether statin therapy for prevention of cardiovascular (CV) disease would ameliorate declines in the left ventricular ejection fraction (LVEF) that is often observed during anthracycline-based chemotherapy (Anth-bC). METHODS: There were 51 participants (33 women and 18 men, aged 48 ± 2 years). We obtained cardiovascular magnetic resonance imaging (CMRI) measurements of LVEF before and 6 months after initiation of Anth-bC for patients with breast cancer, leukemia, or lymphoma. Fourteen individuals received statin therapy, and 37 patients received no statins. MR image analysts were blinded to participant identifiers. RESULTS: Individuals receiving statins were older and often had diabetes mellitus (DM), hypertension (HTN), and hyperlipidemia (HLD). For those receiving statins, LVEF was 56.6% ± 1.4% at baseline and 54.1% ± 1.3% 6 months after initiating anthracycline treatment (P = 0.15). For those not receiving statins, LVEF was 57.5% ± 1.4% at baseline and decreased to 52.4% ± 1.2% over a similar 6-month interval (P = 0.0003). In a multivariable model accounting for age, sex, DM, HTN, HLD, and cumulative amount of anthracycline received, LVEF remained unchanged in participants receiving a statin (+1.1% ± 2.6%) vs a -6.5% ± 1.5% decline among those not receiving a statin (P = 0.03). CONCLUSIONS: These data highlight the finding that individuals receiving statin therapy for prevention of cardiovascular disease may experience less deterioration in LVEF with early receipt of Anth-bC than individuals not receiving statins. Further studies with large numbers of participants are warranted to determine if statins protect against LVEF decline in patients receiving Anth-bC.

Feasibility of implementing a community-based randomized trial of yoga for women undergoing chemotherapy for breast cancer.

BACKGROUND: Treatment-related symptoms and decreased health-related quality of life (HRQoL) frequently occur during chemotherapy for breast cancer. Although research findings suggest that yoga can reduce symptoms and Improve HRQoL after treatment, potential benefits of yoga during chemotherapy have received minimal attention. OBJECTIVE: To estimate accrual, adherence, study retention, and preliminary efficacy of a yoga intervention compared with an active control group for breast cancer patients during chemotherapy. METHODS: Women with stage I-III breast cancer were recruited from 3 community cancer clinics and randomized to 10 weeks of gentle yoga or wellness education. Depressive symptoms, fatigue, sleep, and HRQoL were assessed at baseline, mid-intervention (Week 5), and after intervention (Week 10). RESULTS: 40 women aged 29-83 years (median, 48 years; 88% white) were randomized to yoga (n = 22) or wellness education (n = 18). The groups did not differ significantly on baseline characteristics, adherence, or study retention. Participant feedback was positive and comparable between groups. Meaningful within-group differences were identified For sleep adequacy and quantity in yoga participants and for somnolence in wellness-education participants. LIMITATIONS: Small sample size and lack of a usual-care control group. CONCLUSIONS: This study established Feasibility of a community-based randomized trial of yoga and an active comparison group for women undergoing chemotherapy for breast cancer. Preliminary efficacy estimates suggest that yoga improves sleep adequacy Symptom severity and interference remained stable during chemotherapy for the yoga group and snowed a trend toward increasing in the control group. The study highlighted obstacles to multisite yoga research during cancer treatment. FUNDING/SPONSORSHIP: National Cancer Institute (3U10 CA081851, PI; Shaw; R25 CA122061, PI: Avis); Translational Science Institute, Wake Forest School of Medicine.

Longitudinal assessment of concurrent changes in left ventricular ejection fraction and left ventricular myocardial tissue characteristics after administration of cardiotoxic chemotherapies using T1-weighted and T2-weighted cardiovascular magnetic resonance.

BACKGROUND: In a murine anthracycline-related cardiotoxicity model, increases in cardiovascular magnetic resonance myocardial contrast-enhanced T1-weighted signal intensity are associated with myocellular injury and decreases with left ventricular ejection fraction. We sought to determine whether T1- and T2-weighted measures of signal intensity associate with decreases in left ventricular ejection fraction in human subjects receiving potentially cardiotoxic chemotherapy. METHODS AND RESULTS: In 65 individuals with breast cancer (n=51) or a hematologic malignancy (n=14), we measured left ventricular volumes, ejection fraction, and contrast-enhanced T1-weighted and T2-weighted signal intensity before and 3 months after initiating potentially cardiotoxic chemotherapy using blinded, unpaired analysis of cardiovascular magnetic resonance images. Participants were aged 51 ± 12 years, of whom 55% received an anthracycline, 38% received a monoclonal antibody, and 6% received an antimicrotubule agent. Overall, left ventricular ejection fraction decreased from 57 ± 6% to 54 ± 7% (P<0.001) because of an increase in end-systolic volume (P<0.05). T1-weighted signal intensities also increased from 14.1 ± 5.1 to 15.9 ± 6.8 (P<0.05), with baseline values trending higher among individuals who received chemotherapy before study enrollment (P=0.06). Changes in T1-weighted signal intensity did not differ within the 17 LV myocardial segments (P=0.97). Myocardial edema quantified from T2-weighted images did not change significantly after 3 months (P=0.70). CONCLUSIONS: Concordant with previous animal studies, cardiovascular magnetic resonance measures of contrast-enhanced T1-weighted signal intensity occur commensurate with small but significant left ventricular ejection fraction declines 3 months after the receipt of potentially cardiotoxic chemotherapy. These data indicate that changes in T1-weighted signal intensity may serve as an early marker of subclinical injury related to the administration of potentially cardiotoxic chemotherapy in human subjects.

Weight Loss Intervention in Survivors of ER/PR-negative Breast Cancer.

Numerous studies have found that increased body size (weight or body mass index) is a risk factor for breast cancer development, recurrence, and death. The detrimental relationship between body size and breast cancer recurrence may be more pronounced among women with estrogen receptor (ER)/progesterone receptor (PR)-negative breast cancer. Considering the limited availability of treatments, and the association between body size and recurrence, alternative treatments are needed for ER/PR-negative breast cancer survivors, particularly overweight survivors. The objective of this pilot study was to examine the feasibility of a 12-week, multi-component meal-replacement weight loss intervention among overweight or obese ER/PR-negative breast cancer survivors; and to obtain preliminary data on changes in anthropometrics, biomarkers, and health-related quality of life (QOL). The 12-week intervention included a portion-controlled diet (including meal replacements) and a multi-component intervention (including behavioral techniques, diet modification, physical activity, and social support). The goal of the intervention was to help participants lose 5% or more of their initial weight by reducing their caloric intake and increasing their physical activity (to at least 15 minutes each day). Paired t-tests assessed changes in continuous measures. Body weight was measured weekly and mixed-model regression analysis assessed change in weight over time. Nineteen ER/PR-negative breast cancer survivors with a mean age of 59 years participated in the study. All but two of the participants completed the 12-week intervention. Women lost an average of 6.3 ± 4.9 kg (P < 0.001), equivalent to 7.5% of their baseline weight. There were significant reductions in waist circumference (P = 0.001), percent fat mass (P < 0.001), total cholesterol (P = 0.026), and triglycerides (P = 0.002); and improvements in health-related QOL (P = 0.017). Findings suggested that a meal-replacement weight loss approach among ER/PR-negative breast cancer survivors was feasible and was well received.

The successful use of alemtuzumab for treatment of steroid-refractory acute graft-versus-host disease in pediatric patients.

SR-aGVHD remains a significant cause of morbidity and mortality in allogeneic HCT recipients. Alemtuzumab has been used with success in adult patients but has not been studied in the pediatric setting. To estimate the effectiveness of alemtuzumab for the treatment of SR-aGVHD in pediatric patients, we retrospectively reviewed the charts of 19 patients (median age 4 yr, range 0.5-28 years) with grades II (n = 3), III (n = 10), or IV (n = 6) SR-aGVHD who received alemtuzumab treatment. Patients received a median dose of 0.9 mg/kg alemtuzumab (range 0.3-2 mg/kg) divided over 2-6 days. Eighty-nine percent of patients received additional courses. A complete response, defined as GVHD of grade 0 at four wk following the first alemtuzumab course, was observed in nine patients (47%). A partial response, defined as an improvement in grade after four wk, was observed in five patients (26%). There was no response in five patients (26%). The overall response rate at four wk was 73%. Infectious complications included bacteremia (47%), presumed or documented fungal infections (21%), adenovirus viremia (52%), EBV viremia (36%), and CMV viremia (36%). We conclude that alemtuzumab is effective for SR-aGVHD in pediatric patients with a tolerable spectrum of complications.

Cognitive factors associated with adherence to oral antiestrogen therapy: results from the cognition in the study of tamoxifen and raloxifene (Co-STAR) study.

Little is known about the cognitive factors associated with adherence to antiestrogen therapy. Our objective was to investigate the association between domain-specific cognitive function and adherence among women in a clinical prevention trial of oral antiestrogen therapies. We performed a secondary analysis of Co-STAR, an ancillary study of the STAR breast cancer prevention trial in which postmenopausal women at increased breast cancer risk were randomized to tamoxifen or raloxifene. Co-STAR enrolled nondemented participants ≥65 years old to compare treatment effects on cognition. The cognitive battery assessed global cognitive function (Modified Mini-Mental State Exam), and specific cognitive domains of verbal knowledge, verbal fluency, figural memory, verbal memory, attention and working memory, spatial ability, and fine motor speed. Adherence was defined by a ratio of actual time taking therapy per protocol ≥80% of expected time. Logistic regression was used to evaluate the association between cognitive test scores and adherence to therapy. The mean age of the 1,331 Co-STAR participants was 67.2 ± 4.3 years. Mean 3MS score was 95.1 (4.7) and 14% were nonadherent. In adjusted analyses, the odds of nonadherence were lower for those with better scores on verbal memory [OR (95% confidence interval): 0.75 (0.62-0.92)]. Larger relative deficits in verbal memory compared with verbal fluency were also associated with nonadherence [1.28 (1.08-1.51)]. Among nondemented older women, subtle differences in memory performance were associated with medication adherence. Differential performance across cognitive domains may help identify persons at greater risk for poor adherence.

Efficacy of the hypomethylating agents as frontline, salvage, or consolidation therapy in adults with acute myeloid leukemia (AML).

The hypomethylating agents (HAs), azacitidine and decitabine, have emerged as an alternative to initial and salvage therapy in patients with acute myeloid leukemia (AML). Little is known about how AML responds to hypomethylating agents after standard therapy, and the activity of these agents in a real-world setting is not well studied. We retrospectively examined data for 75 consecutive AML patients at Wake Forest from 2002 to 2011 treated with HAs either as first-line (n = 34), salvage (n = 28), or consolidation (n = 13) therapy. We collected data on age, gender, race, Charlson comorbidity index (CCI), cytogenetics, type of treatment, complete remission (CR), complete remission with incomplete count recovery (CRi), and survival. Statistical analysis was performed using Kaplan-Meier estimates and Cox proportional hazards models. Frontline response rate (CR + CRi) was 26.5 %, and median overall survival (OS) was 3.4 months (95 % CI 1.3-7.4), with 18 % alive at 1 year. In the salvage cohort, the response rate was significantly lower compared to frontline (3.6 versus 26.5 %, p = 0.017). Despite the reduced response, OS from time of HA treatment was longer than frontline at 8.2 months (CI 4.8-10.3). In the consolidation cohort, OS was 13.8 months (CI 8.0-21.6) with one patient in remission more than 30 months from diagnosis. These data suggest that prior cytotoxic therapy decreases marrow response rates to HAs but not survival. Furthermore, use of hypomethylating agents for consolidation resulted in a median overall survival over 1 year in a cohort of older patients. This suggests that hypomethylating agents have activity in all phases of AML treatment.

Oral paricalcitol (19-nor-1,25-dihydroxyvitamin D2) in women receiving chemotherapy for metastatic breast cancer: a feasibility trial.

The vitamin D hormone, [1,25(OH) 2D, calcitriol], inhibits proliferation and angiogenesis in breast cancer but its therapeutic use is limited by hypercalcemia. Synthetic analogs of 1,25(OH) 2D that are less calcemic, such as paricalcitol (19-nor-1,25-Dihydroxyvitamin D 2), are used to treat hyperparathyroidism associated with chronic kidney disease. We sought to determine the safety and feasibility of taking oral paricalcitol with taxane-based chemotherapy in women with metastatic breast cancer (MBC). Oral paricalcitol was considered safe if it did not result in excessive toxicity, defined as grade 3 or higher serum calcium levels. It was considered feasible if the majority of women could take eight weeks of continuous therapy in the first three months. Serum calcium was monitored weekly and the paricalcitol dose was adjusted based on its calcemic effect. Intact parathyroid hormone (iPTH) was monitored as a marker of paricalcitol activity. Twenty-four women with MBC were enrolled. Twenty women (83%) received eight weeks of continuous therapy. Paricalcitol was well-tolerated with no instances of hypercalcemia grade 2 or greater. Fourteen women (54%) were able to escalate the dose. The dose range of paricalcitol in the first 3 mo was 2-7 ug/day. Serum iPTH levels at baseline were significantly higher in women with serum 25-Hydroxyvitamin D (25-OHD) levels less than 30 ng/ml (96.4 ± 40.9 pg/ml) vs. 46.2 ± 20.3 pg/ml (p = 0 0.001) (iPTH reference 12-72 pg/ml). We conclude that paricalcitol is safe and feasible in women with MBC who are receiving chemotherapy.

Low to moderate dose anthracycline-based chemotherapy is associated with early noninvasive imaging evidence of subclinical cardiovascular disease.

OBJECTIVES: The goal of this study was to determine if low to moderate doses of anthracycline-based chemotherapy (Anth-bC) are associated with subclinical cardiovascular (CV) injury. BACKGROUND: Cancer survivors who receive Anth-bC experience premature CV events. It is unknown whether low to moderate doses of anthracyclines promote early subclinical CV disease manifested by deteriorations in left ventricular ejection fraction (LVEF) or increases in aortic stiffness, or if these doses are associated with changes in quality of life (QOL). METHODS: In 53 men and women with breast cancer, leukemia, or lymphoma, we assessed left ventricular volumes, LVEF, circumferential strain, aortic pulse wave velocity, late gadolinium enhancement, serum B-type natriuretic peptide, troponin I, and the impact of treatment on QOL before and 1, 3, and 6 months after receipt of Anth-bC. RESULTS: Participants averaged 50 ± 2 (range 19 to 80) years in age, 58% were women, 17% were black, and they each received a range of 50 to 375 mg/m(2) of doxorubicin-equivalent chemotherapy. Left ventricular end-systolic volume (48 ± 3 ml to 54 ± 3 ml; p = 0.02), left ventricular strain (-17.7 ± 0.4 to -15.1 ± 0.4; p = 0.0003), pulse wave velocity (6.7 ± 0.5 m/s to 10.1 ± 1 m/s; p = 0.0006), and QOL deterioration (15.4 ± 3.3 to 28.5 ± 3.9; p = 0.008) increased, whereas LVEF (58 ± 1% to 53 ± 1%; p = 0.0002) decreased within 6 months after low to moderate doses of Anth-bC. All findings persisted after accounting for age, gender, race (white/black), doxorubicin-equivalent dose, doxorubicin administration technique, comorbidities associated with CV events, and cancer diagnosis (p = 0.02 to 0.0001 for all). There were no new late gadolinium enhancement findings after 6 months. CONCLUSIONS: In these study patients, low to moderate doses of Anth-bC were associated with the early development of subclinical abnormalities of cardiac and vascular function that in other populations are associated with the future occurrence of CV events.