3D Breast Cancer Segmentation in DCE-MRI Using Deep Learning With Weak Annotation.

BACKGROUND: Deep learning models require large-scale training to perform confidently, but obtaining annotated datasets in medical imaging is challenging. Weak annotation has emerged as a way to save time and effort. PURPOSE: To develop a deep learning model for 3D breast cancer segmentation in dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) using weak annotation with reliable performance. STUDY TYPE: Retrospective. POPULATION: Seven hundred and thirty-six women with breast cancer from a single institution, divided into the development (N = 544) and test dataset (N = 192). FIELD STRENGTH/SEQUENCE: 3.0-T, 3D fat-saturated gradient-echo axial T1-weighted flash 3D volumetric interpolated brain examination (VIBE) sequences. ASSESSMENT: Two radiologists performed a weak annotation of the ground truth using bounding boxes. Based on this, the ground truth annotation was completed through autonomic and manual correction. The deep learning model using 3D U-Net transformer (UNETR) was trained with this annotated dataset. The segmentation results of the test set were analyzed by quantitative and qualitative methods, and the regions were divided into whole breast and region of interest (ROI) within the bounding box. STATISTICAL TESTS: As a quantitative method, we used the Dice similarity coefficient to evaluate the segmentation result. The volume correlation with the ground truth was evaluated with the Spearman correlation coefficient. Qualitatively, three readers independently evaluated the visual score in four scales. A P-value <0.05 was considered statistically significant. RESULTS: The deep learning model we developed achieved a median Dice similarity score of 0.75 and 0.89 for the whole breast and ROI, respectively. The volume correlation coefficient with respect to the ground truth volume was 0.82 and 0.86 for the whole breast and ROI, respectively. The mean visual score, as evaluated by three readers, was 3.4. DATA CONCLUSION: The proposed deep learning model with weak annotation may show good performance for 3D segmentations of breast cancer using DCE-MRI. LEVEL OF EVIDENCE: 3 TECHNICAL EFFICACY: Stage 2.

SB8, an approved bevacizumab biosimilar based on totality of evidence: scientific justification of extrapolation.

SB8 is a biosimilar of bevacizumab based on its similarity demonstrated by physicochemical, functional, non-clinical and clinical studies. Supported by the concept of extrapolation, SB8 was authorized and is used in a similar manner across all types of tumors as reference bevacizumab. Furthermore, SB8 offers convenience with prolonged stability compared with reference bevacizumab in diluted form. Although a biosimilar must demonstrate biosimilarity to a reference product with the 'totality of evidence' in a stringent regulatory process for marketing authorization, some concerns remain among healthcare practitioners, particularly about extrapolation. This review summarizes the concepts of the totality of evidence and extrapolation in biosimilar development and the role of bevacizumab biosimilars in the management of metastatic colorectal cancer as an extrapolated indication.

Impact of the single site order in LTC: exacerbation of an overburdened system.

BACKGROUND: The long-term care (LTC) sector has been at the epicentre of COVID-19 in Canada. This study aimed to understand the impact that the Single Site Order (SSO) had on staff and leadership in four LTC homes in the Lower Mainland of British Columbia, Canada. METHODS: A mixed method study was conducted by analyzing administrative staffing data. Overtime, turnover, and job vacancy data were extracted and analyzed from four quarters before (April 2019 - March 2020) and four quarters during the pandemic (April 2020 - March 2021) using scatterplots and two-part linear trendlines across total direct care nursing staff and by designation (i.e., registered nurses (RNs), licenced practical nurses (LPNs) and care aids (CAs)). Virtual interviews were conducted with a purposive sample of leadership (10) and staff (18) from each of the four partner care homes (n = 28). Transcripts were analyzed in NVivo 12 using thematic analysis. RESULTS: Quantitative data indicated that the total overtime rate increased from before to during the pandemic, with RNs demonstrating the steepest rate increase. Additionally, while rates of voluntary turnover showed an upward trend before the pandemic for all direct care nursing staff, the rate for LPNs and, most drastically, for RNs was higher during the pandemic, while this rate decreased for CAs. Qualitative analysis identified two main themes and sub-themes: (1) overtime (loss of staff, mental health, and sick leave) and (2) staff turnover (the need to train new staff, and gender/race) as the most notable impacts associated with the SSO. CONCLUSIONS: The results of this study indicate that the outcomes due to COVID-19 and the SSO are not equal across nursing designations, with the RN shortage in the LTC sector highly evident. Quantitative and qualitative data underscore the substantial impact the pandemic and associated policies have on the LTC sector, namely, that staff are over-worked and care homes are understaffed.

Induction of Mutant Sik3Sleepy Allele in Neurons in Late Infancy Increases Sleep Need.

Sleep is regulated in a homeostatic manner. Sleep deprivation increases sleep need, which is compensated mainly by increased EEG δ power during non-rapid eye movement sleep (NREMS) and, to a lesser extent, by increased sleep amount. Although genetic factors determine the constitutive level of sleep need and sleep amount in mice and humans, the molecular entity behind sleep need remains unknown. Recently, we found that a gain-of-function Sleepy (Slp) mutation in the salt-inducible kinase 3 (Sik3) gene, which produces the mutant SIK3(SLP) protein, leads to an increase in NREMS EEG δ power and sleep amount. Since Sik3Slp mice express SIK3(SLP) in various types of cells in the brain as well as multiple peripheral tissues from the embryonic stage, the cell type and developmental stage responsible for the sleep phenotype in Sik3Slp mice remain to be elucidated. Here, we generated two mouse lines, synapsin1CreERT2 and Sik3ex13flox mice, which enable inducible Cre-mediated, conditional expression of SIK3(SLP) in neurons on tamoxifen administration. Administration of tamoxifen to synapsin1CreERT2 mice during late infancy resulted in higher recombination efficiency than administration during adolescence. SIK3(SLP) expression after late infancy increased NREMS and NREMS δ power in male synapsin1CreERT2; Sik3ex13flox/+ mice. The expression of SIK3(SLP) after adolescence led to a higher NREMS δ power without a significant change in NREMS amounts. Thus, neuron-specific expression of SIK3(SLP) after late infancy is sufficient to increase sleep.SIGNIFICANCE STATEMENT The propensity to accumulate sleep need during wakefulness and to dissipate it during sleep underlies the homeostatic regulation of sleep. However, little is known about the developmental stage and cell types involved in determining the homeostatic regulation of sleep. Here, we show that Sik3Slp allele induction in mature neurons in late infancy is sufficient to increase non-rapid eye movement sleep amount and non-rapid eye movement sleep δ power. SIK3 signaling in neurons constitutes an intracellular mechanism to increase sleep.

Effects of Hexagonal Boron Nitride Insulating Layers on the Driving Performance of Ionic Electroactive Polymer Actuators for Light-Weight Artificial Muscles.

To improve the energy efficiency and driving performance of ionic electroactive polymer actuators, we propose inserting insulating layers of 170 nm hexagonal boron nitride (h-BN) particles between the ionic polymer membrane and electrodes. In experiments, actuators exhibited better capacitance (4.020 × 10-1 F), displacement (6.01 mm), and curvature (35.59 m-1) with such layers than without them. The excellent insulating properties and uniform morphology of the layers reduced the interfacial resistance, and the ion conductivity (0.071 S m-1) within the ionic polymer improved significantly. Durability was enhanced because the h-BN layer is chemically and thermally stable and efficiently blocks heat diffusion and ion hydrate evaporation during operation. The results demonstrate a close relationship between the capacitance and driving performance of actuators. A gripper prepared from the proposed ionic electroactive polymer actuator can stably hold an object even under strong external vibration and fast or slow movement.

Edmonton Symptom Assessment Scale Time Duration of Self-Completion Versus Assisted Completion in Patients with Advanced Cancer: A Randomized Comparison.

INTRODUCTION: To compare the time duration of self-completion (SC) of the Edmonton Symptom Assessment Scale (ESAS) by patients with advanced cancer (ACPs) versus assisted completion (AC) with a health care professional. MATERIALS AND METHODS: In this randomized comparison of ACPs seen in initial consultation at the outpatient Supportive Care Center at MD Anderson, ACPs who have never completed the ESAS at MD Anderson were allocated (1:1) to either SC of the ESAS form versus AC by a nurse. Time of completion was measured by the nurse using a stopwatch. Patients completed the Rapid Estimate of Adult Literacy in Medicine (REALM) test prior to administration of the ESAS. In the SC group, the nurse reviewed the responses to verify that the reported ESAS scores were correct. RESULTS: A total of 126 ACPs were enrolled (69 patients to AC and 57 to SC). Seventy-one patients were female, median age was 60 years, and median REALM score was 65. Median (interquartile range) time (in seconds) of SC was significantly less than AC (73 [42.9-89.1] vs. 109 [79.5-136.7], p < .0001). With nurse review time included, median time of SC increased to 117 seconds, which was not significantly different from AC (p = .28). Lower literacy (REALM) score and shortness of breath were significantly associated with increased completion time (p = .007). CONCLUSION: Regular use of ESAS will have minimal impact on clinical time, as it can be completed in about 1 minute and provides a concise yet comprehensive and multidimensional perspective of symptoms that affect quality of life of patients with cancer. IMPLICATIONS FOR PRACTICE: Because the Edmonton Symptom Assessment Scale can be completed in less than 2 minutes, hopefully the routine use of this simple yet comprehensive and multidimensional symptom assessment tool will be used at all medical visits in all patients with cancer so that the timely management of symptoms affecting patients' lives and treatment courses can occur, further enhancing personalized cancer care.

Comparison of the Results of Five SARS-CoV-2 Antibody Assays before and after the First and Second ChAdOx1 nCoV-19 Vaccinations among Health Care Workers: a Prospective Multicenter Study.

Reliable results for serological positivity to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibody after the second dose of AstraZeneca (AZ) vaccination are important to estimate the real efficacy of vaccination. We evaluated positivity rates and changes in semiquantitative antibody titers before and after the first and second ChAdOx1 nCoV-19 vaccinations using five SARS-CoV-2 antibody assays, including two surrogate virus neutralization tests. A total of 674 serum samples were obtained from 228 participants during three blood sampling periods. A questionnaire on symptoms, severity, and adverse reaction duration was completed by participants after the second vaccination. The overall positive rates for all assays were 0.0 to 0.9% before vaccination, 66.2 to 92.5% after the first vaccination, and 98.2 to 100.0% after the second vaccination. Median antibody titers in five assays after the second dose of vaccination were increased compared to those after the first dose (106.4-fold increase for Roche total antibody, 3.6-fold for Abbott IgG, 3.6-fold for Siemens, 1.2-fold for SD Biosensor V1 neutralizing antibody, and 2.2-fold for GenScript neutralizing antibody). Adverse reactions were reduced after the second dose in 89.9% of participants compared to after the first dose. Overall, the second vaccination led to almost 100% positivity rates based on these SARS-CoV-2 antibody assays. The results should be interpreted with caution, considering the characteristics of the applied assays. Our findings could inform decisions regarding vaccination and the use of immunoassays, thus contributing to SARS-CoV-2 pandemic control.

Comparing Results of Five SARS-CoV-2 Antibody Assays Before and After the First Dose of ChAdOx1 nCoV-19 Vaccine among Health Care Workers.

Reliable results regarding serologic positivity for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibody before and after AstraZeneca (AZ) vaccination are essential for estimating the efficacy of vaccination. We assessed positivity rates and associated factors using five SARS-CoV-2 antibody assays. A total of 228 paired serum samples (456 samples) were obtained from 228 participants. After baseline sampling, the second sampling was conducted between 11 and 28 days after the first dose of the AZ vaccine. Sera were tested using five SARS-CoV-2 antibody assays, including two surrogate virus neutralization tests. A questionnaire on the symptoms, severity, and duration of adverse reactions was completed by all participants. The overall positivity rates for SARS-CoV-2 antibody were 84.6% for the Roche assay, 92.5% for the Abbott assay, 75.4% for the Siemens assay, 90.7% for the SD Biosensor assay, and 66.2% for the GenScript assay after the first dose of the AZ vaccine. The positivity rates and antibody titers of sera obtained between 21 and 28 days were significantly higher than those obtained between 11 and 20 days in all five assays. More-severe adverse reactions and longer durations of adverse reactions were related to higher SARS-CoV-2 antibody levels. The agreements and correlations among the assays applied were substantial (к, 0.73 to 0.95) and strong (ρ, 0.83 to 0.91). A single dose of the AZ vaccine led to high positivity rates based on the five assays. Days after vaccination and adverse reactions could help estimate serologic conversion rates. The results should be interpreted cautiously considering the assays and cutoffs applied. Our findings could inform decisions regarding vaccination and laboratory settings and could thus contribute to the control of the spread of SARS-CoV-2 infection.

Evaluation of Combined Cancer Markers With Lactate Dehydrogenase and Application of Machine Learning Algorithms for Differentiating Benign Disease From Malignant Ovarian Cancer.

BACKGROUND: The differential diagnosis of ovarian cancer is important, and there has been ongoing research to identify biomarkers with higher performance. This study aimed to evaluate the diagnostic utility of combinations of cancer markers classified by machine learning algorithms in patients with early stage ovarian cancer, which has rarely been reported. METHODS: In total, 730 serum samples were assayed for lactate dehydrogenase (LD), neutrophil-to-lymphocyte ratio (NLR), human epididymis protein 4 (HE4), cancer antigen 125 (CA125), and risk of ovarian malignancy algorithm (ROMA). Among them, 53 were diagnosed with early stage ovarian cancer, and the remaining 677 were diagnosed with benign disease. RESULTS: The areas under the receiver operating characteristic curves (ROC-AUCs) of the ROMA, HE4, CA125, LD, and NLR for discriminating ovarian cancer from non-cancerous disease were .707, .680, .643, .657, and .624, respectively. ROC-AUC of the combination of ROMA and LD (.709) was similar to that of single ROMA in the total population. In the postmenopausal group, ROC-AUCs of HE4 and CA125 combined with LD presented the highest value (.718). When machine learning algorithms were applied to ROMA combined with LD, the ROC-AUC of random forest was higher than that of other applied algorithms in the total population (.757), showing acceptable performance. CONCLUSION: Our data suggest that the combinations of ovarian cancer-specific markers with LD classified by random forest may be a useful tool for predicting ovarian cancer, particularly in clinical settings, due to easy accessibility and cost-effectiveness. Application of an optimal combination of cancer markers and algorithms would facilitate appropriate management of ovarian cancer patients.

Immature granulocyte percentage for prediction of sepsis in severe burn patients: a machine leaning-based approach.

BACKGROUND: Of the existing sepsis markers, immature granulocytes (IG) most frequently reflect the presence of an infection. The importance of IG as an early predictor of sepsis and bacteremia is evaluated differently for each study. This study aimed to evaluate the effectiveness of the Sysmex XN series' IG% as an independent prognostic indicator of sepsis using machine learning. METHODS: A total of 2465 IG% results from 117 severe burn patients in the intensive care unit of one institution were retrospectively analyzed. We evaluated the IG% for sepsis using the receiver operating characteristic, logistic regression, and partial dependence plot analyses. Clinical characteristics and other laboratory markers associated with sepsis, including WBC, procalcitonin, and C-reactive protein, were compared with the IG% values. RESULTS: Twenty-six of the 117 patients were diagnosed with sepsis. The median IG% value was 2.6% (95% CI: 1.4-3.1). The area under the receiver operating characteristic curve was 0.77 (95% CI: 0.78-0.84) and the optimal cut-off value was 3%, with a sensitivity of 76.9% and specificity of 68.1%. The partial dependence plot of IG% on predicting sepsis showed that an IG% < 4% had low predictability, but increased thereafter. The interaction plot of IG% and C-reactive protein showed an increase in sepsis probability at an IG% of 6% and C-reactive protein of 160 mg/L. CONCLUSIONS: IG% is moderately useful for predicting sepsis. However, since it can be determined from routine laboratory test results and requires no additional intervention or cost, it could be particularly useful as an auxiliary marker.

Challenging the Status Quo of Physician Attire in the Palliative Care Setting.

BACKGROUND, AIM, AND HYPOTHESIS: This randomized controlled trial aimed to compare the impact of a physician's attire on the perceptions of patients with cancer of compassion, professionalism, and physician preference. Our hypothesis was that patients would perceive the physician with formal attire as more compassionate than the physician wearing casual attire. MATERIALS AND METHODS: One hundred five adult follow-up patients with advanced cancer were randomized to watch two standardized, 3-minute video vignettes with the same script, depicting a routine physician-patient clinic encounter. Videos included a physician in formal attire with tie and buttoned-up white coat and casual attire without a tie or white coat. Actors, patients, and investigators were all blinded to the purpose and videos watched, respectively. After each video, patients completed validated questionnaires rating their perception of physician compassion, professionalism, and their overall preference for the physician. RESULTS: There were no significant differences between formal and casual attire for compassion (median [interquartile range], 25 [10-31] vs. 20 [8-27]; p = .31) and professionalism (17 [13-21] vs. 18 [14-22]; p = .42). Thirty percent of patients preferred formal attire, 31% preferred casual attire, and 38% had no preference. Subgroup analysis did not show statistically significant differences among different cohorts of age, sex, marital status, and education level. CONCLUSION: Doctors' attire did not affect the perceptions of patients with cancer of physician's level of compassion and professionalism, nor did it influence the patients' preference for their doctor or their trust and confidence in the doctor's ability to provide care. There is a need for more studies in this area of communications skills. Clinical trial identification number. NCT03168763 IMPLICATIONS FOR PRACTICE: The significance of physician attire as a means of nonverbal communication has not been well characterized. It is an important element to consider, as patient preferences vary geographically, are influenced by cultural beliefs, and may vary based on particular care settings. Previous studies consisted of nonblinded surveys and found increasing confidence in physicians wearing a professional white coat. Unfortunately, there are no randomized controlled trials, to the authors' knowledge, to confirm the survey findings. In this randomized, blinded clinical trial the researchers found that physician's attire did not affect patients' perception of the physician's level of compassion and professionalism. Attire also did not influence the patients' preferences for their doctor or their trust and confidence in the doctor's ability to provide care.

Examination of referral criteria for outpatient palliative care among patients with advanced cancer.

BACKGROUND: An international panel achieved consensus on 9 need-based and 2 time-based major referral criteria to identify patients appropriate for outpatient palliative care referral. To better understand the operational characteristics of these criteria, we examined the proportion and timing of patients who met these referral criteria at our Supportive Care Clinic. METHODS: We retrieved data on consecutive patients with advanced cancer who were referred to our Supportive Care Clinic between January 1, 2016, and February 18, 2016. We examined the proportion of patients who met each major criteria and its timing. RESULTS: Among 200 patients (mean age 60, 53% female), the median overall survival from outpatient palliative care referral was 14 (95% confidence interval 9.2, 17.5) months. A majority (n = 170, 85%) of patients met at least 1 major criteria; specifically, 28%, 30%, 20%, and 8% met 1, 2, 3, and ≥ 4 criteria, respectively. The most commonly met need-based criteria were severe physical symptoms (n = 140, 70%), emotional symptoms (n = 36, 18%), decision-making needs (n = 26, 13%), and brain/leptomeningeal metastases (n = 25, 13%). For time-based criteria, 54 (27%) were referred within 3 months of diagnosis of advanced cancer and 63 (32%) after progression from ≥ 2 lines of palliative systemic therapy. The median duration from patient first meeting any criterion to palliative care referral was 2.4 (interquartile range 0.1, 8.6) months. CONCLUSIONS: Patients were referred early to our palliative care clinic and a vast majority (85%) of them met at least one major criteria. Standardized referral based on these criteria may facilitate even earlier referral.

Meaning in life in patients with advanced cancer: a multinational study.

BACKGROUND: Few studies have examined meaning in life, a novel existential outcome, in patients with advanced cancer across countries. OBJECTIVES: We examined differences in meaning in life across 5 countries and identified factors associated with meaning in life. METHODS: This is a pre-planned secondary analysis of a prospective longitudinal multicenter observational study of patients with advanced cancer. Meaning in life was assessed using a validated scale which examined four domains of meaning: values, purpose, goals, and reflection. The total score ranged from 8 to 32, with a higher score indicating greater meaning in life. RESULTS: Among 728 patients, the median meaning in life score was 25/32 (interquartile range 23, 28). There was no significant difference in the total meaning in life score among 5 countries (P = 0.11), though there were differences in domain sub-scores. In the univariate analysis, patients with higher intensity of physical symptoms by ESAS score (pain, fatigue, drowsiness, dyspnea, insomnia), depression, anxiety, spiritual pain, and financial distress had significantly lower meaning in life. However, patients with higher levels of education, who were married, and who had higher optimism had significantly higher meaning in life. In the multivariate analysis, higher total meaning in life scores were significantly associated with greater optimism (multivariate estimate = 0.33, p < 0.001), lower depression (- 0.26, < 0.001), spiritual pain (- 0.19, < 0.001), and financial distress (- 0.16, < 0.001). CONCLUSION: Country of origin was not a determinant of meaning in life. However, meaning in life was significantly associated with optimism, depression, spiritual pain, and financial distress, underscoring the multidimensional nature of this construct and potential opportunities for improvement in addressing meaning in life of patients with advanced cancer.

Predicting survival in patients with advanced cancer in the last weeks of life: How accurate are prognostic models compared to clinicians' estimates?

BACKGROUND: It is unclear if validated prognostic scores such as the Palliative Performance Scale, Palliative Prognostic Index, and Palliative Prognostic Score are more accurate than clinician prediction of survival in patients admitted to an acute palliative care unit with only days of survival. AIM: We compared the prognostic accuracy of Palliative Performance Scale, Palliative Prognostic Index, Palliative Prognostic Score, and clinician prediction of survival in this setting. DESIGN: This is a pre-planned secondary analysis of a prospective study. SETTING/PARTICIPANTS: We assessed Palliative Performance Scale, Palliative Prognostic Index, Palliative Prognostic Score, and clinician prediction of survival at baseline. We computed their prognostic accuracy using the Concordance index and area under the receiver operating characteristics curve for 7-, 14-, and 30-day survival. RESULTS: A total of 204 patients were included with a median overall survival of 10 days (95% confidence interval: 8-11 days). The Concordance index for Palliative Performance Scale, Palliative Prognostic Index, Palliative Prognostic Score, and clinician prediction of survival were 0.74, 0.71, 0.70, and 0.75, respectively. The areas under the curve for these approaches were 0.82-0.87 for 30-day survival, 0.75-0.80 for 14-day survival, and 0.74-0.81 for 7-day survival. The four prognostic approaches had similar accuracies, with the exception of 7-day survival in which clinician prediction of survival was significantly more accurate than Palliative Prognostic Score (difference: 7%) and Palliative Prognostic Index (difference: 8%). CONCLUSION: In patients with advanced cancer with days of survival, clinician prediction of survival and Palliative Performance Scale alone were as accurate as Palliative Prognostic Score and Palliative Prognostic Index. These four approaches may be useful for prognostication in acute palliative care units. Our findings highlight how patient population may impact the accuracy of prognostic scores.

Currently Applied Molecular Assays for Identifying ESR1 Mutations in Patients with Advanced Breast Cancer.

Approximately 70% of breast cancers, the leading cause of cancer-related mortality worldwide, are positive for the estrogen receptor (ER). Treatment of patients with luminal subtypes is mainly based on endocrine therapy. However, ER positivity is reduced and ESR1 mutations play an important role in resistance to endocrine therapy, leading to advanced breast cancer. Various methodologies for the detection of ESR1 mutations have been developed, and the most commonly used method is next-generation sequencing (NGS)-based assays (50.0%) followed by droplet digital PCR (ddPCR) (45.5%). Regarding the sample type, tissue (50.0%) was more frequently used than plasma (27.3%). However, plasma (46.2%) became the most used method in 2016-2019, in contrast to 2012-2015 (22.2%). In 2016-2019, ddPCR (61.5%), rather than NGS (30.8%), became a more popular method than it was in 2012-2015. The easy accessibility, non-invasiveness, and demonstrated usefulness with high sensitivity of ddPCR using plasma have changed the trends. When using these assays, there should be a comprehensive understanding of the principles, advantages, vulnerability, and precautions for interpretation. In the future, advanced NGS platforms and modified ddPCR will benefit patients by facilitating treatment decisions efficiently based on information regarding ESR1 mutations.

Association between tobacco use, pain expression, and coping strategies among patients with advanced cancer.

BACKGROUND: The objective of the current study was to evaluate the association between tobacco use, symptom expression, and coping strategies in patients with advanced cancer. METHODS: The authors prospectively enrolled patients with advanced cancer and collected data regarding patient demographics, cancer diagnosis, morphine equivalent daily dose, cigarette smoking status using the Behavioral Risk Factor Surveillance System, symptom expression as measured by the Edmonton Symptom Assessment System, the Cut down/Annoyed/Guilty/Eye opener alcoholism questionnaire, the Screener and Opioid Assessment for Patients with Pain-short form survey, and the Brief COPE Questionnaire. RESULTS: Among 399 patients, 195 (49%) were never-smokers, 158 (40%) were former smokers, and 46 (11%) were current smokers. The most common malignancies were gastrointestinal (21%) and breast (19%). Current smokers demonstrated significantly higher pain scores at the time of consultation compared with former or never-smokers (mean 6.4 vs 5.9 vs 5.1, respectively; P = .015), demonstrated increased morphine equivalent daily dose (median 90 mg/day vs 60 mg/day vs 50 mg/day, respectively; P = .002), were more likely to screen as positive on the Cut down/Annoyed/Guilty/Eye opener questionnaire (33% vs 24% vs 8.7%, respectively; P < .0001) and were more likely to screen as positive (≥4) on the Screener and Opioid Assessment for Patients with Pain-short form survey (74% vs 13% vs 9.3%, respectively; P < .0001). Compared with former and never-smokers, current smokers were significantly more likely to cope maladaptively with substance use (P = .02), denial (P = .007), and self-blame (P < .0001). CONCLUSIONS: Among patients with advanced cancer, current and former smokers appear to be significantly more likely to have higher pain expression and thus require higher opioid doses, and to have more risk factors for using opioids in a nonprescribed manner. The results of the current study highlight the need to provide closer monitoring and increased psychosocial support for patients with cancer who smoke while receiving chronic opioid therapy.

Practices and perceptions regarding intravenous opioid infusion and cancer pain management.

BACKGROUND: In view of the recent opioid crisis, ways to promote safe and effective opioid-related practices are needed. Faster intravenous (iv) opioid infusion rates can result in increased adverse effects and risk for nonmedical opioid use. Data on best practices regarding safe iv opioid administration for cancer pain are limited. This study examined iv opioid bolus infusion practices and perceptions about opioids in cancer pain among 4 groups of inpatient oncology nurses. METHODS: An anonymous cross-sectional survey was conducted among oncology nurses working in medical, surgical, intensive care unit (ICU), and emergency department (ED) settings. An iv opioid bolus infusion speed less than 120 seconds was considered too fast. RESULTS: The participant response rate was 59% (731 of 1234). Approximately 58%, 54%, and 58% of all nurses administered morphine, hydromorphone, and fentanyl, respectively, in less than 120 seconds. The median morphine infusion speeds were 55, 60, 60, and 85 seconds for ICU, surgical, ED, and medical unit nurses, respectively (P = .0002). The odds ratios for infusing too fast were 2.04 and 2.52 for ED (P = .039) and ICU nurses (P = .003), respectively, in comparison with medical unit nurses, and they were 0.27 and 0.18 with frequent (P = .003) and very frequent use of a timing device (P = .0001), respectively, in comparison with no use. CONCLUSIONS: More than half the nurses working in the inpatient setting reported administering iv opioids too fast. ICU nurses administered opioids the fastest. Nurses who frequently used a timing device were less likely to infuse too fast. Further research is needed to standardize and improve the safe intermittent administration of iv opioids to patients with cancer.

Concurrent use of opioids with benzodiazepines or nonbenzodiazepine sedatives among patients with cancer referred to an outpatient palliative care clinic.

BACKGROUND: The concurrent use of opioids with benzodiazepines (BZD) or nonbenzodiazepine sedatives (S) recently was found to be associated with an increased risk of overdose death compared with the use of opioids alone. In the current study, the authors examined the frequency and trend of concurrent opioid/BZD-S use and its associated risk factors among patients with cancer. METHODS: Data regarding the frequency and trend of concurrent opioid/BZD-S use were extracted for 1500 randomly selected patients referred to the outpatient palliative care clinic at The University of Texas MD Anderson Cancer Center between the calendar years of 2011 and 2016. To explore associated risk factors, the authors compared the demographic and clinical predictors of 418 patients each in the concurrent opioid/BZD-S group and opioids-only group. RESULTS: In 2011, at the time of referral to the palliative care clinic, 96 of 221 patients with cancer (43%) were prescribed concurrent opioids/BZD-S. This rate progressively declined to 67 of 217 patients (31%) by 2016 (P = .0008). Patients in the concurrent opioid/BZD-S group had a higher percentage of females (233 individuals; 55% [P = .007]) and whites (323 individuals; 77% [P = .002]), and patients reported higher scores regarding depression (P = .0001), anxiety (P ≤ .0001), drowsiness (P = .048), and worst feeling of well-being (P = .001). The morphine equivalent daily dose was significantly higher in concurrent opioid/BZD-S group (median of 67.5 mg/day [interquartile range (IQR), 30-135 mg/day] vs 60 mg/day [IQR, 30-105 mg/day]; P = .034). Multivariate analysis demonstrated that anxiety (P ≤ .0001), white race (P = .0092), and poor Eastern Cooperative Oncology Group performance status (P = .0017) were significantly associated with concurrent use. CONCLUSIONS: The concurrent use of opioids with BZD-S has declined but continues to be frequent among patients with cancer. Anxiety, white race, and poor Eastern Cooperative Oncology Group performance status were associated with its use. More research is needed to explore which medications can replace these agents.

Phase Angle and the Diagnosis of Impending Death in Patients with Advanced Cancer: Preliminary Findings.

BACKGROUND: Phase angle is a prognostic factor in patients with months of survival, but its accuracy has not been examined in patients with weeks/days of survival. We determined the association between phase angle and survival in patients with advanced cancer admitted to an acute palliative care unit (APCU). SUBJECTS, MATERIALS, AND METHODS: We prospectively assessed phase angle in consecutive patients with advanced cancer admitted to our APCU. We conducted univariate and multivariate survival analyses adjusting for established prognostic factors. Post hoc subgroup analyses examined patients with and without edema. RESULTS: Among 204 patients, the median overall survival was 10 days (95% confidence interval [CI] 8-11 days). Seventy-four (36%) did not have edema. The median phase angle was 3.7° for the entire cohort, 3.9° for the nonedematous subgroup and 3.6° for the edematous subgroup. In univariate analysis, a low phase angle was associated with decreased survival for the entire cohort (≤3° vs. >3°, median survival 7 vs. 10 days, p = .045) and the nonedematous subgroup (5 vs. 18 days, p < .001) but not the edematous subgroup (9 vs. 9 days, p = .84). In multivariate analysis, phase angle did not reach significance for the entire cohort but remained significant in the nonedematous subgroup (hazard ratio 2.46, 95% CI 1.14-5.31, p < .001). Specifically, phase angle ≤3° had an accuracy of 86% (95% CI 77%-93%) for 3-day survival in patients without edema. CONCLUSION: Phase angle had limited prognostic utility in unselected APCU patients but was significant in the nonedematous subgroup. Further studies are required to confirm these preliminary findings. IMPLICATIONS FOR PRACTICE: In this prospective study involving 204 patients with advanced cancer, phase angle as measured by bioelectric impedance analysis was a significant predictor of mortality independent of known prognostic factors in patients without edema but not patients with edema. Among patients without edema, a phase angle ≤3° had an accuracy of 86% for 3-day survival, which may inform the diagnosis of impending death and potentially end-of-life decision making.

Response to Oral Immediate-Release Opioids for Breakthrough Pain in Patients with Advanced Cancer with Adequately Controlled Background Pain.

BACKGROUND: There is limited evidence about the response of breakthrough pain (BTP) to the most commonly used oral immediate-release (IR) opioids. Our aim was to determine response rate to oral IR opioids for BTP control in patients with advanced cancer. MATERIALS AND METHODS: In this prospective study, palliative care outpatients, with advanced cancer and adequately managed background pain, were asked to complete a self-administered survey. We assessed patients' baseline demographics, pain characteristics, alcoholism (CAGE questionnaire), tobacco and substance abuse, and Edmonton Symptom Assessment Scores (ESAS). We determined the effectiveness of oral IR BTP opioids by using a 7-point Likert scale ranging from "very ineffective" to "very effective." "Effective" and "very effective" were defined a priori as a good response to IR opioids for BTP. RESULTS: Of 592 evaluable patients, 192 (32%) had background pain of ≤3 (ESAS pain scale 0-10). Among these 192 patients, 152 (79%) reported BTP, 143/152 (94%) took oral IR opioids for BTP, and 127/143 (89%) responded to a median dose of 10% of the total morphine equivalent daily dose. In univariate logistic regression analysis, younger age (odds ratio [OR], 0.94 per year; p = .008), higher ESAS scores for pain (OR, 1.32; p = .012), anxiety (OR, 1.24; p = .017), and dyspnea (OR, 1.31; p = .007) had statistically significant association with poor response to IR opioids for BTP. In multicovariate logistic regression, adjusted for age, a higher ESAS dyspnea score was significantly associated with poor response to oral IR opioids (OR, 1.44; p = .002). CONCLUSION: The vast majority of patients with advanced cancer with adequately controlled background pain reported a good response to oral IR opioids for BTP, supporting their use in clinical practice. IMPLICATIONS FOR PRACTICE: Oral immediate-release opioids are standard treatment for cancer breakthrough pain. However, information regarding treatment response to these commonly used opioids is limited. This study provides information that the vast majority of patients with advanced cancer, with adequately controlled background pain, reported good response to oral immediate release opioids for managing their breakthrough pain episodes. Results of this study support the use of conventional oral immediate release opioids that are relatively inexpensive and readily available for management of breakthrough pain in patients with advanced cancer.