Congruence of multiple patient-related outcomes within a single day.

OBJECTIVE: Clinic-based collection of patient-reported outcome (PRO) quantifying symptom burden provide crucial information for effective care. We have pioneered point-of-care electronic assessment using the Edmonton Symptom Assessment Scale (ESAS) with direct linkage to the electronic medical record (EMR) which has been readily adopted by our oncology patients. As some patients may complete more than one ESAS per day in different clinics, the goal of the current analyses was to compare the within-patient congruence of ESAS assessments completed on the same day. METHODS: A total of 9621 ESAS records from 4021 patients of the Supportive Care Medicine and Radiation Oncology clinics between February and November 2017 were retrieved from the EMR. Patients completed the ESAS-r-CSS, which added sleep disturbance, constipation, and spiritual well-being domains to the standard ESAS-r. RESULTS: A total of 65 patients provided more than one ESAS report within the same day. The data were curated, removing those sporadic missing data and those with obvious technical error. This process left 130 samples for analysis. There was no statistical difference among different ESAS collection intervals for domains of tiredness, nausea, appetite, overall well-being, spiritual well-being, constipation, and difficulty sleeping, but there was a significant difference for pain, drowsiness, shortness of breath, depression, and anxiety. Repeat tests that occurred within 1 h of one another demonstrated higher congruence than those completed over longer periods. CONCLUSION: Patients reported significant worsening of several symptoms over the course of the day, with greatest concordance observed within smaller time periods.

Improved Outcomes of Enhanced Recovery After Surgery (ERAS) Protocol for Radical Cystectomy with Addition of a Multidisciplinary Care Process in a US Comprehensive Cancer Care Center.

INTRODUCTION: Although enhanced recovery after surgery (ERAS) components include both anesthesia and surgical care processes, it is unclear whether a multidisciplinary approach to implementing ERAS care processes improves clinical outcomes. The addition of multidisciplinary care with anesthesiology-related components to an existing ERAS protocol for radical cystectomy at a US comprehensive cancer center provided an opportunity to compare short- and long-term outcomes. METHODS: We retrospectively compared the outcomes of 116 consecutive patients who underwent cystectomy after implementation of a multidisciplinary ERAS protocol with those of a historical control group of 143 consecutive patients who had been treated with a surgical ERAS protocol. Length of stay, return of bowel function, rate of blood transfusion, nausea, pain, and readmission rates were examined. RESULTS: Implementation of a multidisciplinary ERAS protocol was associated with better postsurgical symptom control, as indicated by lower rates of patient-reported nausea (P < .05). Multivariate Poisson regression analysis showed a decrease in estimated intraoperative transfusions (P ≤ .001) after adjusting for the effects of potential confounding variables. There were no statistically significant differences noted in length of stay, return of bowel function, 30- and 90-day complications, or readmissions. CONCLUSION: This is the first study to investigate the effects of adding anesthesia ERAS components to an existing surgical ERAS protocol for radical cystectomy. We found that with the addition of anesthesia-related interventions, there was a decrease in transfusions and nausea.

The Impact of Music Therapy on Anxiety in Cancer Patients Undergoing Simulation for Radiation Therapy.

PURPOSE: Radiation therapy (RT) is associated with high stress levels. The role of music therapy (MT) for patients receiving RT is not well described. This study evaluates the impact of MT on anxiety and distress during simulation in patients with newly diagnosed head and neck or breast cancer. METHODS AND MATERIALS: This institutional review board-approved randomized trial of MT versus no MT at the time of simulation included the pre-State-Trait Anxiety Inventory (STAI-S Anxiety) questionnaire and Symptom Distress Thermometer (SDT). Patients randomized to MT received a consultation with a music therapist, during which music of the patients' choice to be played during simulation was selected. The no-MT patients did not receive the MT consultation, nor did they hear prerecorded music during simulation. Subsequent to the simulation, all patients repeated the STAI-S Anxiety questionnaire and the SDT. RESULTS: Of the 78 patients enrolled (39 in MT group and 39 in no-MT group), 38 had breast cancer and 40 had head and neck cancer. The male-female ratio was 27:51. The overall mean pre- and post-simulation STAI-S scores were 38.7 (range, 20-60) and 35.2 (range, 20-72), respectively. The overall mean pre- and post-simulation SDT scores were 3.2 (range, 0-10) and 2.5 (range, 0-10), respectively. The MT group had mean pre- and post-simulation STAI-S scores of 39.1 and 31.0, respectively (P<.0001), and the mean SDT scores before and after simulation were 3.2 and 1.7, respectively (P<.0001). The no-MT group's mean pre- and post-simulation STAI-S scores were 38.3 and 39.5, respectively (P=.46), and the mean SDT scores were 3 and 3.2, respectively (P=.51). CONCLUSIONS: MT significantly lowered patient anxiety and distress during the simulation procedure on the basis of the STAI-S questionnaire and SDT. Incorporating culturally centered individualized MT may be an effective intervention to reduce stressors. Continued research defining the role of MT intervention in improving the patient experience by reducing anxiety is warranted.

Pediatric phase I trial of oral sorafenib and topotecan in refractory or recurrent pediatric solid malignancies.

Targeted kinase inhibitors and camptothecins have shown preclinical and clinical activity in several cancers. This trial evaluated the maximum tolerated dose (MTD) and dose-limiting toxicities of sorafenib and topotecan administered orally in pediatric patients with relapsed solid tumors. Sorafenib was administered twice daily and topotecan once daily on days 1-5 and 8-12 of each 28-day course. The study utilized a standard 3 + 3 dose escalation design. Three dose levels (DL) were evaluated: (1) sorafenib 150 mg/m(2) and topotecan 1 mg/m(2) ; (2) sorafenib 150 mg/m(2) and topotecan 1.4 mg/m(2) ; and (3) sorafenib 200 mg/m(2) and topotecan 1.4 mg/m(2) . Pharmacokinetics were ascertained and treatment response assessed. Thirteen patients were enrolled. DL2 was the determined MTD. Grade 4 thrombocytopenia delaying therapy for >7 days was observed in one of six patients on DL2, and grade 4 neutropenia that delayed therapy in two of three patients on DL3. A patient with preexisting cardiac failure controlled with medication developed a transient drop in the left ventricular ejection fraction that improved when sorafenib was withheld. Sorafenib exposure with or without topotecan was comparable, and the concentration-time profiles for topotecan alone and in combination with sorafenib were similar. One objective response was noted in a patient with fibromatosis. We determined MTD to be sorafenib 150 mg/m(2) twice daily orally on days 1-28 combined with topotecan 1.4 mg/m(2) once daily on days 1-5 and 8-12. While these doses are 1 DL below the MTD of the agents individually, pharmacokinetic studies suggested adequate drug exposure without drug interactions. The combination had limited activity in the population studied.

Multi-gene expression predictors of single drug responses to adjuvant chemotherapy in ovarian carcinoma: predicting platinum resistance.

Despite advances in radical surgery and chemotherapy delivery, ovarian cancer is the most lethal gynecologic malignancy. Standard therapy includes treatment with platinum-based combination chemotherapies yet there is no biomarker model to predict their responses to these agents. We here have developed and independently tested our multi-gene molecular predictors for forecasting patients' responses to individual drugs on a cohort of 55 ovarian cancer patients. To independently validate these molecular predictors, we performed microarray profiling on FFPE tumor samples of 55 ovarian cancer patients (UVA-55) treated with platinum-based adjuvant chemotherapy. Genome-wide chemosensitivity biomarkers were initially discovered from the in vitro drug activities and genomic expression data for carboplatin and paclitaxel, respectively. Multivariate predictors were trained with the cell line data and then evaluated with a historical patient cohort. For the UVA-55 cohort, the carboplatin, taxol, and combination predictors significantly stratified responder patients and non-responder patients (p = 0.019, 0.04, 0.014) with sensitivity = 91%, 96%, 93 and NPV = 57%, 67%, 67% in pathologic clinical response. The combination predictor also demonstrated a significant survival difference between predicted responders and non-responders with a median survival of 55.4 months vs. 32.1 months. Thus, COXEN single- and combination-drug predictors successfully stratified platinum resistance and taxane response in an independent cohort of ovarian cancer patients based on their FFPE tumor samples.

In vitro transcriptomic prediction of hepatotoxicity for early drug discovery.

Liver toxicity (hepatotoxicity) is a critical issue in drug discovery and development. Standard preclinical evaluation of drug hepatotoxicity is generally performed using in vivo animal systems. However, only a small number of preselected compounds can be examined in vivo due to high experimental costs. A more efficient yet accurate screening technique that can identify potentially hepatotoxic compounds in the early stages of drug development would thus be valuable. Here, we develop and apply a novel genomic prediction technique for screening hepatotoxic compounds based on in vitro human liver cell tests. Using a training set of in vivo rodent experiments for drug hepatotoxicity evaluation, we discovered common biomarkers of drug-induced liver toxicity among six heterogeneous compounds. This gene set was further triaged to a subset of 32 genes that can be used as a multi-gene expression signature to predict hepatotoxicity. This multi-gene predictor was independently validated and showed consistently high prediction performance on five test sets of in vitro human liver cell and in vivo animal toxicity experiments. The predictor also demonstrated utility in evaluating different degrees of toxicity in response to drug concentrations, which may be useful not only for discerning a compound's general hepatotoxicity but also for determining its toxic concentration.

Developmental expression of the oligodendrocyte myelin glycoprotein in the mouse telencephalon.

The oligodendrocyte myelin glycoprotein is a glycosylphosphatidylinositol-anchored protein expressed by neurons and oligodendrocytes in the central nervous system. Attempts have been made to identify the functions of the myelin-associated inhibitory proteins (MAIPs) after axonal lesion or in neurodegeneration. However, the developmental roles of some of these proteins and their receptors remain elusive. Recent studies indicate that NgR1 and the recently discovered receptor PirB restrict cortical synaptic plasticity. However, the putative factors that trigger these effects are unknown. Because Nogo-A is mostly associated with the endoplasmic reticulum and myelin associated glycoprotein appears late during development, the putative participation of OMgp should be considered. Here, we examine the pattern of development of OMgp immunoreactive elements during mouse telencephalic development. OMgp immunoreactivity in the developing cortex follows the establishment of the thalamo-cortical barrel field. At the cellular level, we located OMgp neuronal membranes in dendrites and axons as well as in brain synaptosome fractions and axon varicosities. Lastly, the analysis of the barrel field in OMgp-deficient mice revealed that although thalamo-cortical connections were formed, their targeting in layer IV was altered, and numerous axons ectopically invaded layers II-III. Our data support the idea that early expressed MAIPs play an active role during development and point to OMgp participating in thalamo-cortical connections.