Examining the Potential of Vitamin C Supplementation in Tissue-Engineered Equine Superficial Digital Flexor Tendon Constructs.

Because equine tendinopathies are slow to heal and often recur, therapeutic strategies are being considered that aid tendon repair. Given the success of utilizing vitamin C to promote tenogenesis in other species, we hypothesized that vitamin C supplementation would produce dose-dependent improvements in the tenogenic properties of tendon proper (TP) and peritenon (PERI) cells of the equine superficial digital flexor tendon (SDFT). Equine TP- and PERI-progenitor-cell-seeded fibrin three-dimensional constructs were supplemented with four concentrations of vitamin C. The gene expression profiles of the constructs were assessed with 3'-Tag-Seq and real-time quantitative polymerase chain reaction (RT-qPCR); collagen content and fibril ultrastructure were also analyzed. Moreover, cells were challenged with dexamethasone to determine the levels of cytoprotection afforded by vitamin C. Expression profiling demonstrated that vitamin C had an anti-inflammatory effect on TP and PERI cell constructs. Moreover, vitamin C supplementation mitigated the degenerative pathways seen in tendinopathy and increased collagen content in tendon constructs. When challenged with dexamethasone in two-dimensional culture, vitamin C had a cytoprotective effect for TP cells but not necessarily for PERI cells. Future studies will explore the effects of vitamin C on these cells during inflammation and within the tendon niche in vivo.

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.

A Double-Blind, Randomized, Placebo-Controlled Trial of Panax Ginseng for Cancer-Related Fatigue in Patients With Advanced Cancer.

Background: Despite the high frequency, severity, and effects of cancer-related fatigue (CRF) on the quality of life (QoL) of patients with cancer, limited treatment options are available. The primary objective of this study was to compare the effects of oral Panax ginseng extract (PG) and placebo on CRF. Secondary objectives were to determine the effects of PG on QoL, mood, and function. Methods: In this randomized, double-blind, placebo-controlled study, patients with CRF ≥4/10 on the Edmonton Symptom Assessment System (ESAS) were eligible. Based on a pilot study, we randomized patients to receive either 400 mg of standardized PG twice daily or a matching placebo for 28 days. The primary end point was change in the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) subscale from baseline to day 29. Results: Of 127 patients, 112 (88.2%) were evaluable. The mean (SD) FACIT-F subscale scores at baseline, day 15, and day 29 were 22.4 (10.1), 29.9 (10.6), and 30.1 (11.6) for PG (P<.001), and 24.0 (9.4), 30.0 (10.1), and 30.4 (11.5) for placebo (P<.001). Mean (SD) improvement in the FACIT-F subscale at day 29 was not significantly different in the PG than in the placebo group (7.5 [12.7] vs 6.5 [9.9]; P=.67). QoL, anxiety, depression, symptoms, and functional scores were not significantly different between the PG and placebo groups. Improvement in the FACIT-F subscale correlated with baseline scores (P=.0005), Hospital Anxiety and Depression Scale results (P=.032), and sex (P=.023). There were fewer any-grade toxicities in the PG versus placebo group (28/63 vs 33/64; P=.024). Conclusions: Both PG and placebo result in significant improvement in CRF. PG was not significantly superior to placebo after 4 weeks of treatment. There is no justification to recommend the use of PG for CRF. Further studies are needed. Trial Registration: ClinicalTrials.gov identifier: NCT01375114.

The Evolving Approach to Management of Cancer Cachexia.

Weight loss is distressing to cancer patients and caregivers. Anorexia/cachexia syndrome is characterized by lipolysis and the loss of lean body mass, and is not reversible by increasing caloric intake. The pathophysiology of cancer cachexia is complex and includes symptoms that impact caloric intake, as well as chronic inflammation, hypermetabolism, and hormonal alterations. Cancer patients require routine screening for cachexia and, ideally, interventions should be initiated in the early stages of weight loss. No guidelines exist for the treatment of cancer cachexia. Appetite stimulants, such as megestrol acetate and glucocorticoids, have been shown to increase appetite and weight; however, single pharmaceutical interventions alone for cachexia do not result in meaningful functional outcomes. In the future, clinicians should consider multimodality treatment that is personalized for each patient. These interventions would include nutritional counseling, assessing and treating symptoms that have an impact on caloric intake, and a rational combination of pharmacologic approaches directed at underlying pathophysiology. Use of an appetite stimulant could be considered for patients who exhibit decreased appetite. Treatment with an anti-inflammatory agent should be considered for patients with elevated C-reactive protein, and hormonal alterations resulting from anti-cachexia therapy should be thoughtfully addressed.

The opioid rotation ratio of strong opioids to transdermal fentanyl in cancer patients.

BACKGROUND: Transdermal fentanyl (TDF) is 1 of the most common opioids prescribed to patients with cancer. However, the accurate opioid rotation ratio (ORR) from other opioids to TDF is unknown, and various currently used methods result in wide variation of the ORR. The objective of this study was to determine the ORR of the oral morphine equivalent daily dose (MEDD) to the TDF dose when correcting for the MEDD of breakthrough opioids (the net MEDD) in cancer outpatients. METHODS: The records of 6790 consecutive patients were reviewed at the authors' supportive care center from 2010 to 2013 to identify those who underwent rotation from other opioids to TDF. Data regarding Edmonton Symptom Assessment Scale scores and MEDDs were collected for patients who returned for a follow-up visit within 5 weeks. Linear regression analysis was used to estimate the ORR between the TDF dose and the net MEDD (the MEDD before opioid rotation [OR] minus the MEDD of the breakthrough opioid used along with TDF after OR). RESULTS: In total, 129 patients underwent OR from other opioids to TDF. The mean patient age was 56 years, 59% were men, and 88% had advanced cancer. Uncontrolled pain (80%) was the most frequent reason for OR. In 101 patients who underwent OR and had no worsening of pain at follow-up, the median ORR from net MEDD to TDF (in mg per day) was 0.01 (range, -0.02 to 0.04), and the correlation coefficient of the TDF dose to the net MEDD was 0.77 (P < .0001). The ORR was not significantly impacted by body mass index or serum albumin. The ORR of 0.01 suggests that an MEDD of 100 mg is equivalent to 1 mg TDF daily or approximately 40 micrograms per hour of TDF (1000 micrograms/24 hours). CONCLUSIONS: The median ORR from MEDD to TDF in mg per day was 0.01. These results warrant further studies.

Frequency, Predictors, and Medical Record Documentation of Chemical Coping Among Advanced Cancer Patients.

BACKGROUND: In this prospective study, we determined the frequency of opioid-related chemical coping among advanced cancer patients, as diagnosed by palliative medicine specialists. We also determined predictors for chemical coping and the concordance between the physician's diagnosis and documentation in the medical records. PATIENTS AND METHODS: Palliative medicine specialists evaluated and diagnosed consecutive patients seen for chemical coping. The proportion of patients identified as chemically coping was compared with the proportion documented in the medical records. Demographic data; cancer diagnosis; history of smoking; substance abuse; psychiatric disease; morphine equivalent daily dosage; Cut-down, Annoyed, Guilty, and Eye-opener (CAGE) questionnaire scores; and Edmonton Symptom Assessment System scores were also collected. RESULTS: A total of 432 patients were evaluated. Overall, 76 patients (18%; 95% confidence interval [CI]: 14%-21%) were diagnosed as chemically coping. Documentation of chemical coping in the medical records was reported for only 15 patients (4%; 95% CI: 2%-6%). CAGE positivity (odds ratio [OR]: 2.89), younger age (OR: 0.97 per year), better performance status (OR: 0.68 per point), pain (OR: 1.20 per point), and well-being (OR: 1.28 per point) were found to be significant predictors of chemical coping by protocol definition. After recursive partitioning, 21 of 50 patients (42%) who were CAGE positive and had an Eastern Cooperative Oncology Group performance status ≤2 were diagnosed as chemically coping. CONCLUSION: Approximately 18% of palliative care patients seen were diagnosed as chemically coping by palliative medicine specialists. The frequency of documentation in the medical records was significantly lower. Better and safer ways for physicians to assess and report chemical coping are needed. IMPLICATIONS FOR PRACTICE: Cancer pain is a multidimensional symptom for which opioids are the mainstay of treatment. However, opioids can have a double effect resulting in drug-seeking behaviors. Chemical coping occurs when a patient uses opioids in a nonprescribed way to cope with various stressful events. This can lead to misuse of opioids and complications including neurotoxicities, respiratory depression, and death. Proper diagnosis and documentation is needed to ensure proper management of pain and to avoid unnecessary harm. The findings of this study suggest that ∼18% of advanced cancer patients seen by a palliative care service were diagnosed as chemical coping, but only 4% were documented in the medical records.

The effects of supplemental dietary chitosan on broiler performance and myopathic features of white striping.

White striping (WS) is a common myopathy seen in fast-growing broilers. Studies have demonstrated that chitosan is effective as an antioxidant and has antiobesity and fat-absorption reduction properties. We hypothesized that the dietary supplementation of chitosan would have similar effects when fed to fast-growing broilers and would thus lower WS incidence and improve meat quality. One hundred twenty-six broilers were fed corn-soy diets. The grower and finisher diets contained either 0, 0.2, or 0.4% chitosan. After a 6 wk growth period, birds were euthanized, and then WS and gross pathology scores were assessed. Pectoralis major tissues were collected to evaluate cook loss, drip loss, histopathology scores, and the gene expression of CCR7, LECT2, CD36, PPARG, and PTGS2. There were no significant differences between the broiler weights, thus chitosan did not appear to compromise the overall growth of the broilers. Female broilers fed 0.4% chitosan had the lowest WS incidence, while male broiler fed 0.4% chitosan had the least cook loss. However, gene expression analyses did not offer insight into any grossly or histologically visualized differences in the muscles. Thus, while we can postulate that chitosan could have some positive effect in reducing WS incidence and improving meat quality, further studies are required to better scrutinize the mechanisms by which chitosan affects WS and other such myopathies in fast-growing broilers.

Just-in-Time Decision Making: Preliminary Findings of a Goals of Care Rapid Response Team.

CONTEXT: The COVID-19 pandemic placed the issue of resource utilization front and center. Our comprehensive cancer center developed a Goals of Care Rapid Response Team (GOC RRT) to optimize resource utilization balanced with goal-concordant patient care. OBJECTIVES: Primary study objective was to evaluate feasibility of the GOC RRT by describing the frequency of consultations that occurred from those requested. Secondary objectives included adherence to consultation processes in terms of core team member participation and preliminary efficacy in limiting care escalation. METHODS: We conducted a retrospective chart review of patients referred to GOC RRT (3/23/2020-9/30/2020). Analysis was descriptive. Categorical variables were compared with Fisher's exact or Chi-Square tests and continuous variables with Mann-Whitney U tests. RESULTS: A total of 89 patients were referred. Eighty-five percent (76 of 89) underwent a total of 95 consultations. Median (range) patient age was 61 (49, 69) years, 54% (48 of 89) male, 19% (17 of 89) Hispanic, 48% (43/89) White, 73% (65 of 89) married/partnered and 66% (59 of 89) Christian. Hematologic malignancies and solid tumors were evenly balanced (53% [47/89] vs. 47% [42 of 89, P = 0.199]). Most patients (82%, 73 of 89) had metastatic disease or relapsed leukemia. Seven percent (6 of 89) had confirmed COVID-19. Sixty-nine percent (61 of 89) died during the index hospitalization. There was no statistically significant difference in demographic or clinical characteristics among groups (no consultation, 1 consultation, >1 consultation). Core team members were present at 64% (61 of 95) of consultations. Care limitation occurred in 74% (56 of 76) of patients. CONCLUSION: GOC RRT consultations were feasible and associated with care limitation. Adherence to core team participation was fair.

Physical and Psychosocial Symptoms of Young Adult Patients Referred to the Supportive Care Mobile Team.

Young adult (YA) aged cancer patients have unique psychosocial needs with studies indicating more symptoms and emotional distress compared to older patients. Our study aimed to compare clinical characteristics and symptom distress between YAs and older adults. We retrospectively studied 896 randomly selected patients across 3 age groups: 18-39 YAs (n = 297), 40-64 (n = 300), and 65 and older (n = 299). We compared medical, psychosocial history, Morphine Equivalent Daily Dose (MEDD), Edmonton Symptom Assessment Scale (ESAS) scores, and Eastern Cooperative Oncology Group (ECOG) scores at the time of initial inpatient consultation with supportive care. YAs were more frequently female and white, with higher ECOG scores, had more self-reported psychiatric history and worse ESAS sleep scores compared to the other age cohort groups. YAs had higher pain expression than those of 65 years and older. YAs were more likely to have children younger than 18 years old, which was associated with worse pain, sleep, and financial distress. In general, YAs did not report higher symptoms distress, with the exception of insomnia and self-reported psychiatric history. Importantly, YAs with children was associated with higher ratings of pain, sleep difficulties, and financial distress. Overall, results suggest YAs may benefit from specialized services to address their unique psychosocial needs.

Patients' Perspective of Timeliness and Usefulness of an Outpatient Supportive Care Referral at a Comprehensive Cancer Center.

CONTEXT: Current guidelines recommend early referral to palliative care for patients with advanced cancer; however, no studies have examined the optimal timing of referral from the patients' perspective. OBJECTIVES: To examine patients' perceptions of timeliness of referral and its association with survival among patients with advanced cancer referred to an outpatient supportive care (SC) clinic. METHODS: This cross-sectional prospective study in an SC clinic at a comprehensive cancer center included patients aged 18 years or older with locally advanced, recurrent, or metastatic cancer. Patients were asked to complete an anonymous survey regarding the timeliness and perceived usefulness of SC referral within four weeks of their first SC consultation. RESULTS: Of 253 eligible patients, 209 (83%) enrolled in the study and 200 completed the survey. Median survival was 10.3 months. Most patients (72%) perceived that referral occurred "just in time," whereas 21% felt it was "late," and 7% felt "early." A majority (83%) found the referral useful, and 88% would recommend it to other patients with cancer. The perception of being referred early was associated with lower reported levels of pain (P = 0.043), fatigue (P = 0.004), drowsiness (P = 0.005), appetite loss (P = 0.041), poor well-being (P = 0.041), and lower physical (P = 0.001) and overall symptom distress (P = 0.001). No other associations were found between perceived timeliness and usefulness and patients' baseline characteristics. CONCLUSION: Most patients with a median survival of 10 months perceived that SC referral was timely and useful. Patient care needs rather than the timing of advanced cancer diagnosis drove this perception of referral timing. Lower symptom burden was associated with the perception of being referred to early.

Characteristics of Unscheduled and Scheduled Outpatient Palliative Care Clinic Patients at a Comprehensive Cancer Center.

CONTEXT: There is limited literature regarding outpatient palliative care and factors associated with unscheduled clinic visits. OBJECTIVES: To compare characteristics of patients with unscheduled vs. scheduled outpatient palliative care clinic visits. METHODS: Medical records of 183 unscheduled cancer new outpatients and 104 unscheduled follow-up (FU) patients were compared with random samples of 361 and 314 scheduled new patients and FU patients, respectively. We gathered data on demographics, symptoms, daily opioid usage, and performance status. RESULTS: Compared with scheduled new patients, unscheduled new patients had worse Edmonton Symptom Assessment Scale subscores for pain (P < 0.001), fatigue (P = 0.002), nausea (P = 0.016), depression (P = 0.003), anxiety (P = 0.038), drowsiness (P = 0.002), sleep (P < 0.001), and overall feeling of well-being (P = 0.001); had a higher morphine equivalent daily dose of opioids (median of 45 mg for unscheduled vs. 30 mg for scheduled; P < 0.001); and were more likely to be from outside the greater Houston area (P < 0.001). Most unscheduled and scheduled new and FU visits were for uncontrolled physical symptoms. Unscheduled FU patients, compared with scheduled FU patients, had worse Edmonton Symptom Assessment Scale subscores for pain (P < 0.001), fatigue (P < 0.001), depression (P = 0.002), anxiety (P = 0.004), drowsiness (P = 0.010), appetite (P = 0.023), sleep (P = 0.022), overall feeling of well-being (P < 0.001), and higher morphine equivalent daily dose of opioid (median of 58 mg for unscheduled FU visits vs. 40 mg for scheduled FU visits; P = 0.054). CONCLUSION: Unscheduled new FU patients have higher levels of physical and psychosocial distress and higher opioid intake. Outpatient palliative care centers should consider providing opportunities for walk-in visits for timely management and close monitoring of such patients.

Snapshot of an Outpatient Supportive Care Center at a Comprehensive Cancer Center.

BACKGROUND: Integration of palliative care (PC) in oncology have been found to improve symptom distress, quality of life, and survival in patients with advanced cancer. Early integration is most appropriate in the outpatient setting. However, most PC services in the United States do not have an outpatient component. Our study aims to provide a snapshot of the type of patients and families who are referred to this novel setting for the delivery of early PC. CONCLUSION: Traditionally, PC has been delivered predominantly to patients with advanced disease and to aid in transition to end of life. In recent years, outpatient centers have dramatically changed the nature of PC work as in our snapshot, which shows that in addition to patients regarded as more traditional patients, such as those transitioning to end of life, there are now patients who come in very soon after arrival to a cancer center requiring specialized care to address a variety of symptom and educational needs, thus requiring adaptation of structure and processes to allow access for frequent follow-ups, counseling, and flexibility for walk-in visits. Our findings suggest that Supportive Care Clinic needs to practice in a very different way, which requires certain skills and assessment tools that are not conventionally present in traditional oncology clinic settings. More research is needed to identify the type of patients who would benefit most from a PC referral.

The Conversion Ratio From Intravenous Hydromorphone to Oral Opioids in Cancer Patients.

CONTEXT: The lack of knowledge of the accurate conversion ratio (CR) between intravenous (IV) and oral hydromorphone and opioid rotation ratio (ORR) between IV hydromorphone and oral morphine equivalent daily dose (MEDD) may lead to poorly controlled pain or overdosing in cancer inpatients. OBJECTIVES: We aimed to determine the CR and ORR from IV hydromorphone to oral hydromorphone and MEDD (obtained from oral morphine and oxycodone). METHODS: A total of 4745 consecutive inpatient palliative care consults during 2010-14 were reviewed for conversions from IV hydromorphone to oral hydromorphone, morphine or oxycodone. Patient characteristics, symptoms, and opioid doses were determined in patients successfully discharged on oral opioids without readmission within one week. Linear regression analysis was used to estimate the CR or ORR between the 24 hour IV hydromorphone mg dose before conversion and the oral opioid mg dose used before discharge. RESULTS: Among 394 patients on IV hydromorphone, 147 underwent conversion to oral hydromorphone and 247 underwent rotation to oral morphine (163) or oxycodone (84). The median (interquartile range) CR from IV to PO hydromorphone was 2.5 (2.14-2.75) with correlation of 0.95 (P < 0.0001). The median ORR (interquartile range) from IV hydromorphone to MEDD was 11.46 (9.84-13.00) with correlation of 0.93(P < 0.0001). The median ORR was 11.54 in patients receiving <30 mg of IV hydromorphone/day and 9.86 in patients receiving ≥30 mg (P = 0.0004). CONCLUSION: Our study found that 1 mg of IV hydromorphone is equivalent to 2.5 mg of oral hydromorphone and 11.46 mg of MEDD. Hydromorphone at doses ≥30 mg/day may require a lower ORR to other opioids.

ReCAP: Attitudes, Beliefs, and Awareness of Graduate Medical Education Trainees Regarding Palliative Care at a Comprehensive Cancer Center.

PURPOSE: Palliative care (PC) training and integration with oncology care remain suboptimal. Current attitudes and beliefs of the oncology trainees regarding PC are not fully known. This study was undertaken in an attempt to address this issue. PARTICIPANTS AND METHODS: We conducted a survey to determine awareness of PC among graduate medical trainees at a comprehensive cancer center with an established PC program. One hundred seventy oncology trainees who completed$9 months of training in medical, surgical, gynecologic, and radiation oncology fellowships and residency programs during the 2013 academic year completed an online questionnaire. Descriptive, univariable, and multivariable analyses were performed. RESULTS: The response rate was 78% (132 of 170 trainees); 10 trainees without hands-on patient care were excluded. Medical (53 of 60 [88%]), gynecologic (six of six [100%]), and radiation oncology (20 of 20 [100%]) trainees reported more awareness of PC compared with surgical oncology (22 of 36 [61%]) trainees (P = .001). One hundred twelve of 122 (92%) perceived PC as beneficial to patients and families. One hundred eight of 122 (89%) perceived that PC can reduce health care costs, 78 (64%) believed that PC can increase survival, and 90 (74%) would consult PC for a patient with newly diagnosed cancer with symptoms. Eighty-two trainees (67%) believed a mandatory PC rotation is important. Trainees with previous exposure to PC rotations were more aware of the role of PC services than were trainees without PC rotation (96% [46 of 48] v 74% [55 of 74]; P = .005, respectively). CONCLUSION: Surgical trainees and trainees without previous PC rotation had significantly less awareness of PC. Overall, trainees perceived PC as beneficial to patients and capable of reducing costs while increasing survival; they also supported early PC referrals and endorsed a mandatory PC rotation.