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The rice resistance gene Xa21 confers resistance against the bacterial pathogen Xanthomonas oryzae pv. oryzae (Xoo). The molecular genetic mechanism controlling the integration of the Xa21-mediated disease resistance response with the developmental program in rice is under study in this model system. Reproducible means of infecting plants at certain developmental stages were designed based on the timing of full expansion of the leaf. Xa21-resistance progressively increases from the susceptible juvenile leaf 2 stage through later stages, with 100% resistance at the adult leaf 9/10 stage. We found that Xa21 expression is independent of plant developmental stage, infection with Xoo, or wounding. Expression of the Xa21 gene transcript is not correlated with expression of Xa21 disease resistance indicating that the developmental regulation of Xa21-resistance is either controlled post-transcriptionally or by other factors.

Introduction: Cancer-related anorexia is traditionally considered part of a complex but ill-defined anorexia-cachexia syndrome in which anorexia is intimately associated with other gastrointestinal (GI) symptoms and weight loss. We surveyed cancer patients with anorexia to learn more about the relationship between anorexia and these symptoms.Materials and Methods: A 22-item GI questionnaire assessed the severity of anorexia and the prevalence of concurrent GI symptoms, including taste changes, food aversions, altered sense of smell, and diurnal food intake changes. The relationship between anorexia severity and anticancer therapy and prior menstrual or pregnancy-related appetite changes was also assessed.Results: Ninety-five of 101 patients with anorexia surveyed had complete data. Seventy-eight percent of them had moderate or severe anorexia. Abnormal diurnal appetite variation, taste changes, and food aversions were present in over 50% of all those with anorexia. Judged by the numerical rating scale, the worse the anorexia, the more prevalent were early satiety, constipation, vomiting, and food aversions. Those with more severe anorexia had greater weight loss, and worse performance status. Anorexia severity did not correlate with that during prior menses/pregnancy or antitumor therapy.Conclusions: Evaluation of multiple other GI symptoms is important in understanding the total experience of cancer anorexia. Early satiety, taste changes, food aversions, and altered sense of smell are important accompanying GI symptoms. Most validated anorexia tools do not assess these commonly associated GI symptoms. Future research should develop a comprehensive anorexia symptom questionnaire. [ABSTRACT FROM AUTHOR]

We present a retrospective study of the frequency, pattern, and management of infections in advanced cancer. Three hundred ninety-three patients were admitted to an acute care palliative medicine unit in an 8-month period for evaluation and palliation of cancer-related symptoms and complications. One hundred fifteen had at least one positive bacteriological culture, and 100 of these patients were evaluable. One hundred fifty-two infections and 192 isolates were identified. Sixty-eight patients had polymicrobial infections. Sixty-six patients had urinary tract infections. Forty-one were found to have multisystemic infections. Eighty-one had invasive devices; 32 had more than one invasive device. Fifty-three were taking corticosteroids at the time of infection. Only 3 were neutropenic. Urinary tract infections were significantly more common in those taking corticosteroids. The median duration of antibiotic treatment was 11 days and the median hospital stay, 14 days. Twenty-eight patients died in the hospital; 10 of those who died had lung cancer, which was a statistically significant observation. In conclusion, infections are an underrecognized but common complication in nonneutropenic hospitalized patients with advanced solid tumors. Urinary tract infections appear to be associated with the use of corticosteroids. Lung cancer patients are at greater risk for fatal infections. Infections increase morbidity in debilitated patients with solid tumors, are a frequent cause of hospital admission, and are associated with significant mortality. [ABSTRACT FROM AUTHOR]

Since the establishment of the WHO three-step ladder for management of cancer pain, several controversies have arisen, which are partly due to new drug development, reformulations of older analgesics, and technological advancements. As a result, clinicians need clarification of several questions. Is morphine the opioid of choice for moderate to severe pain in cancer? Should combinations of opioids be used? When should spinal opioids be used to treat pain in cancer? What are the appropriate opioid doses for breakthrough pain? Should selective cyclo-oxygenase (COX) 2 inhibitors be used? What is the best tactic to treat neuropathic pain, and what first-line adjuvant analgesic should be used? And do bisphosphonates relieve bone pain in cancers other than breast cancer and myeloma? This review addresses these questions. [ABSTRACT FROM AUTHOR]

Nausea and vomiting are difficult symptoms to manage in patients with advanced cancer. Several classes of antiemetics are available, including phenothiazines, butyrophenones, substituted benzamides and selective serotonin antagonists, as well as corticosteroids. Most patients will respond to either single agents or combinations that frequently include corticosteroids. A minority of patients will have nausea that fails to respond. The atypical antipsychotic, olanzapine, relieves nausea in some patients failing to respond to the usual antiemetics. Two case reports are presented and the rationale for olanzapine's benefit is discussed. [ABSTRACT FROM AUTHOR]

Background: Over the past two decades, pain and suffering caused by the U.S. opioid crisis have resulted in significant morbidity, policy reforms and healthcare resource strain, and affected healthcare providers' efforts to manage their patients' pain. In 2017, Cleveland Clinic's Department of Palliative and Supportive Care established their Opioid Management Review Committee (OMRC), which focuses on patient safety, opioid stewardship, education on specialist pain management and addiction medicine skills, and offers emotional and informational support to colleagues managing complex pain cases., Objectives: This quality assessment and improvement activity describes the organization and effects of the OMRC on healthcare workers in the department., Methods: On February 1, 2023, an online survey was distributed to attendees of the OMRC. Participants were asked to provide their demographic information and free text responses to questions about the purpose of the OMRC, their judgment about the extent to which the OMRC has changed their approach to pain management, the OMRC's impact on their approach to opioid management, its impact on the clinicians' confidence in managing nonmedical opioid use or comorbid substance use, and suggestions to improve future meetings., Results: Fifty-nine out of 79 clinicians completed the survey (75% response rate). Participants' aggregate responses indicated that the committee fostered interdisciplinary collaboration, provided emotional and professional support, increased awareness of responsible opioid prescribing, and enhanced confidence in managing complex cases involving non-medical opioid use or comorbid substance use., Conclusion: The OMRC represents a comprehensive interdisciplinary approach to safely manage opioid therapy during the contemporary opioid overdose crisis., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Context: Methylnaltrexone is a peripherally-acting mu-opioid receptor antagonist studied in both cancer and non-cancer patients with opioid-induced constipation (OIC), but mostly in the outpatient setting. For adult hospitalized cancer patients with OIC, its effectiveness is unknown. Objectives: Describe the efficacy of methylnaltrexone for OIC in the inpatient setting, defined as bowel movement (BM) within 24 hours of methylnaltrexone administration. Methods: We performed a single-center, retrospective chart review of all hospitalized, adult patients with a cancer diagnosis who received methylnaltrexone from the palliative care team between January 1st, 2012 and July 1st, 2019. Results: We identified 194 patients. The mean age was 59, 50.5% were male and 88% were white. 192 patients (98%) received the 8 mg dose subcutaneously. The median oral morphine equivalent (OME) was 135 mg (IQR 70-354 mg). 45% (95% confidence interval, 38-53%) had a BM within 24 hours. Higher OME was correlated with successful BM, with a response in 93% (86/92) of patients receiving ≥150 OME and 2% (2/102) of patients receiving <150 OME ( P < .0001). Prior laxative use did not predict response at 24 hours whether these were osmotic laxatives (40.7% vs 47.1%, P = .52), stimulant laxatives (45.7% vs 45.2%, P > .99), or stool softeners (44.7% vs 46.1%, P = .89). Conclusion: Methylnaltrexone has a high response rate when used as treatment for OIC in hospitalized adult cancer patients, especially for patients taking ≥150 OME.

Background: The association of pain and suffering seems intuitive, but evidence substantiating this association is lacking. In studies of cancer patients, fatigue, rather than pain, is the most prevalent and debilitating symptom. This study aimed to compare the correlation of pain and fatigue to suffering, and identify other potential sources of suffering in cancer patients treated in a palliative care unit., Methods: One hundred fifty cancer patients were surveyed. Fifteen variables were measured on a 0- to 10-point scale: suffering, pain, level of acceptable pain, effect of pain on quality of life, fatigue, level of acceptable fatigue, effect of fatigue on quality of life, and specific types of suffering. Univariable associations with suffering were made with Pearson correlation (continuous variables) or t test (binary predictors). Multivariable associations with suffering were assessed with linear regression analysis and bootstrapping., Results: In multivariable analysis, highest pain (parameter estimate 0.38) had a greater impact on suffering than highest fatigue (parameter estimate 0.21). When other variables were assessed, 38% of the variability in suffering was accounted for by pain "now", fatigue in the past 24 hours, and age., Conclusion: The most important predictors of greater suffering in hospitalized cancer patients are pain, younger age, and fatigue. Despite their significant effect on suffering, other underlying contributors to suffering have yet to be identified. Designing interventions to reduce fatigue, in addition to pain management, may help in alleviating overall suffering.

Purpose: Evidence has demonstrated the positive effects of music therapy on symptom management for palliative medicine patients. Previous studies have addressed patient needs, with limited discussion involving the relationship between interventions utilized to improve symptoms. The purpose of this study was to understand the impact of music therapy sessions; identify common music therapy goals and interventions and assess their effect; and investigate the effects of gender, age, and type of cancer on symptoms in patients who experienced music therapy., Methods: This was a retrospective study of data collected during music therapy sessions. Patients scored their symptoms (pain, anxiety, depression, shortness of breath, and mood) before and after sessions. Data collected from over 1500 patients included symptom evaluation, goals, interventions, music used, patient/family reactions, and narratives., Results: Among 293 patients who met all study inclusion criteria, significant improvement in pain, anxiety, depression, shortness of breath, mood, facial expression, and vocalization scores was noted. In addition, 96% of patients had positive responses to participating in music therapy. Vocal and emotional were the 2 most effective interventions in improving symptoms. All 5 patient-reported symptoms improved when the therapist focused on these symptoms as goals. Age, gender, and diagnosis had no impact on symptom improvement., Conclusions: This study demonstrated the importance of music therapy for addressing symptoms and behaviors of palliative medicine patients. Statistically and clinically significant effects were noted. The most effective interventions were identified. More research needs to be conducted to better understand the benefits of music therapy for palliative medicine patients.

Background: Oral thrush is a common fungal infection of the mouth experienced by palliative medicine and hospice patients who have advanced cancer. Individuals often experience distressing symptoms that affect their oral intake with most regimens adding to pill burden. This is an open-label prospective observational study to assess the efficacy of a single-dose fluconazole 150 mg for oral thrush., Methods: Palliative medicine and hospice patients with a clinical diagnosis of oral thrush, a life expectancy of more than 1 week, and were able to swallow were enrolled. Signs and symptoms were evaluated on day 1 prior to administration of 150 mg of fluconazole and between days 3 to 5 after treatment., Results: Of 57 patients, 55 (96.5%) had more than 50% improvement in signs and symptoms. Both the number and severity of symptoms changed significantly posttreatment ( P < .001). Side effects were few., Conclusion: Single-dose fluconazole 150 mg is an effective treatment of oral thrush for individuals with advanced cancer.

The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Antiemesis address all aspects of management for chemotherapy-induced nausea and vomiting. These NCCN Guidelines Insights focus on recent updates to the NCCN Guidelines for Antiemesis, specifically those regarding carboplatin, granisetron, and olanzapine., (Copyright © 2017 by the National Comprehensive Cancer Network.)

Purpose: Evidence shows that music therapy aids in symptom management and improves quality of life for palliative medicine and hospice patients. The majority of previous studies have addressed patient needs, while only a few addressed the needs of family members. The primary purpose of this study was to understand family members' perceptions of music therapy experienced by a relative in palliative medicine or hospice. Patient self-reported scales and music therapist assessment of change were also investigated., Methods: Patients scored their symptoms (pain, anxiety, depression, shortness of breath, and mood) before and after music therapy sessions. One family member present during the session assessed perceived effect on the patient's pain, anxiety, depression, shortness of breath, stress level, restlessness, comfort level, mood, and quality of life. The effect on family member's stress level, quality of life, and mood and helpfulness of the music therapy session for the patient and self were studied. Recommendations about future patient participation in music therapy and qualitative comments were also solicited., Results: Fifty family member/patient dyads participated in the study. Family member perceptions were positive, with 82% of responders indicating improvement for self and patient in stress, mood, and quality of life; 80% rating the session as extremely helpful; and 100% of 49 recommending further music therapy sessions for the patient. Patients reported statistically significant improvement in pain, depression, distress, and mood scores., Conclusions: Family members of patients in palliative medicine and hospice settings reported an immediate positive impact of music therapy on the patient and on themselves. More research needs to be conducted to better understand the benefits of music therapy for family members.

Background: Hope is important to patients with cancer. Identifying factors that influence hope is important. Anxiety, depression, fatigue, and pain are reported to impair hope. The objective of this study was to determine whether age, gender, marital status, duration of cancer, symptoms, or symptom burden measured by the sum of severity scores on the Edmonton Symptom Assessment Scale (ESAS) correlated with hope measured by the Herth Hope Index (HHI)., Methods: Patients with advanced cancer in a palliative care unit participated. Demographics including age, gender, marital status, cancer site, and duration of cancer were collected. Individuals completed the ESAS and HHI. Spearman correlation and linear regression were used to assess associations adjusting for gender (male vs female), age (< 65 vs ≥ 65 years), marital status (married or living with a partner vs other), and duration of cancer (≤ 12 vs > 12 months)., Results: One hundred and ninety-seven were participated in the study, of which 55% were female with a mean age of 61 years (standard deviation 11). Hope was not associated with gender, age, marital status, or duration of cancer. In univariable analysis, hope inversely correlated with ESAS score (-0.28), lack of appetite (-0.22), shortness of breath (-0.17), depression (-0.39), anxiety (-0.32), and lack of well-being (-0.33); only depression was clinically relevant. In multivariable analysis, total symptom burden weakly correlated with hope; only depression remained clinically significant., Discussion: This study found correlation between symptom burden and hope was not clinically relevant but was so for depression., Conclusion: Among 9 ESAS symptoms, only depression had a clinically relevant correlation with hope.

Purpose: Reducing 30-day unplanned hospital readmissions is a national policy priority. We examined the impact of a quality improvement project focused on reducing oncology readmissions among patients with cancer who were admitted to palliative and general medical oncology services at the Cleveland Clinic., Methods: Baseline rates of readmissions were gathered during the period from January 2013 to April 2014. A quality improvement project designed to improve outpatient care transitions was initiated during the period leading to April 1, 2014, including: (1) provider education, (2) postdischarge nursing phone calls within 48 hours, and (3) postdischarge provider follow-up appointments within 5 business days. Nursing callback components included symptom management, education, medication review/compliance, and follow-up appointment reminder., Results: During the baseline period, there were 2,638 admissions and 722 unplanned 30-day readmissions for an overall readmission rate of 27.4%. Callbacks and 5-day follow-up appointment monitoring revealed a mean monthly compliance of 72% and 78%, respectively, improving over time during the study period. Readmission rates declined by 4.5% to 22.9% (P < .01; relative risk reduction, 18%) during the study period. The mean direct cost of one readmission was $10,884, suggesting an annualized cost savings of $1.04 million with the observed reduction in unplanned readmissions., Conclusion: Modest readmission reductions can be achieved through better systematic transitions to outpatient care (including follow-up calls and early provider visits), thereby leading to a reduction in use of inpatient resources. These data suggest that efforts focused on improving outpatient care transition were effective in reducing unplanned oncology readmissions., (Copyright © 2016 by American Society of Clinical Oncology.)

Introduction: Insomnia is underrecognized in patients with cancer. By identifying clinical correlations and predisposing factors of insomnia, interventions may be initiated to treat insomnia., Methods: Consecutive patients referred to palliative medicine services were screened with a single question. Patients answering affirmatively completed the Insomnia Severity Index (ISI). Patients were screened for depression, fatigue, and pain. Spearman correlation was performed for associations., Results: Of 715 consecutive patients, 102 had sleep problems and 64 had clinical insomnia by the ISI criteria. Insomnia correlated with depression (r = .32), pain (r = .29), and tiredness (r = .40) but not with age or precipitating factors., Discussion: Insomnia severity moderately correlates with depression, pain, and tiredness. We found no association of insomnia severity with age or medications., Conclusion: Insomnia, pain, depression, and tiredness are a symptom cluster.

Introduction: To develop a shorter and less burdensome cancer-related fatigue (CRF) questionnaire, the Four-Item Fatigue Scale (FIFS) was tested for validity against the Brief Fatigue Index (BFI)., Methods: On day 1, patients with cancer completed the BFI and FIFS in a random order and the reverse on day 7. Sixty-five patients were needed for an 80% power and a Spearman correlation of .7 or greater. The FIFS was compared with the BFI in fatigue severity and changes in fatigue over time. Bonferroni corrections were made for multiple comparisons with International Classification of Diseases, Tenth Revision (ICD-10) fatigue criteria., Results: Seventy-nine patients were enrolled, 65 patients completed both surveys. Spearman correlation between FIFS and BFI for day 1 was 0.69 (95% confidence interval [CI] 0.50-0.87) and 0.73 (95% CI 0.56-0.90) 1 week later. Fatigue severity did not predict survival with either questionnaire. Brief Fatigue Index severity correlated with ICD-10 items 1, 3, 7, and 10B. Regression analysis showed that on day 7 BFI correlated with ICD-10 items 1, 7, and 10. When the model was adjusted for day 1, only the ICD-10 item 5 correlated well in BFI over 1 week. The ICD-10 items 7 and 10 significantly correlated with day 1 FIFS fatigue changes over 7 days after adjustment for FIFS baseline score., Conclusions: Four-Item Fatigue Scale has concurrent validity for fatigue using the BFI. The FIFS and BFI correlated modestly over time. Certain ICD-10 items correlated with CRF severity depending on the questionnaire.

Spinal epidural lipomatosis (SEL) is the abnormal accumulation of normal fat within the spinal canal. It is more frequent in those patients receiving chronic glucocorticoid therapy or in cases of endogenous hypercortisolism states. We report a case of SEL in a patient with metastatic prostate cancer with history of steroid treatment as part of his chemotherapy regimen, presenting with clinical manifestations of partial cord compression. Magnetic resonance imaging images of the lumbar spine revealed the presence of epidural tumor suspicious for metastatic disease. Operative findings were consistent with epidural lipomatosis. Spinal epidural lipomatosis is a rare condition that needs to be included in the differential diagnosis of patients with risk factors, presenting with symptomatic cord compression.

Nausea and vomiting are common and distressing symptoms in advanced cancer. Both are multifactorial and cause significant morbidity, nutritional failure, and reduced quality of life. Assessment includes a detailed history, physical examination and investigations for reversible causes. Assessment and management will be influenced by performance status, prognosis, and goals of care. Several drug classes are effective with some having the added benefit of multiple routes of administration. It is our institution's practice to recommend metoclopramide as the first drug with haloperidol as an alternative antiemetic. Dexamethasone should be used for patients with central nervous system metastases or bowel obstruction. If your patient is near death, empiric metoclopramide, haloperidol or chlorpromazine is used without further investigation. For patients with a better prognosis, we exclude reversible causes and use the same first-line antiemetics, metoclopramide and haloperidol. For those who do not respond to first-line single antiemetics, olanzapine is second line and ondansetron is third. Rarely do we use combination therapy or cannabinoids. Olanzapine as a single agent has a distinct advantage over antiemetic combinations. It improves compliance, reduces drug interactions and has several routes of administration. Antiemetics, anticholinergics, octreotide and dexamethasone are used in combination to treat bowel obstruction. In opiod-na'ive patients, we prefer haloperidol, glycopyrrolate and an opioid as the first-line treatment and add or substitute octreotide and dexamethasone in those who do not respond. Non-pharmacologic interventions (mechanical stents and percutaneous endoscopic gastrostomy tubes) are used when nausea is refractory to medical management or for home-going management to relieve symptoms, reduce drug costs and rehospitalization.

This was a prospective descriptive study of hospice physician home visits (HVs) conducted by Hospice and Palliative Medicine Fellows. Our objectives were 1) to improve our knowledge of hospice care at home by describing physician HVs 2) to identify the indications for physician HVs and the problems addressed during the HV. Data was collected on 58 consecutive patients using a standardized form completed before and after the home visit. More than half of the persons were women. Most were Caucasian. Median age was 75 years; 57% had cancer; 77% were do-not-resuscitate. 76% HV occurred in the home. The median visit duration was 60 minutes; median travel distance and time 25 miles and 42 minutes, respectively. A hospice nurse case manager was present in 95%. The most common issues addressed during HVs were: health education, symptom management, and psychosocial support. Medication review was prominent. Physicians identified previously unreported issues. Symptom control was usually pain, although 27 symptoms were identified. Medications were important; all home visits included drug review and two thirds drug change. Physicians had unique responsibilities and identified important issues in the HV. Physicians provided both education and symptom management. Physician HVs are an important intervention. HVs were important in continuity of care, however, time-consuming, and incurred considerable travel, and professional time and costs.

The need to ascertain appropriate decision-making capacity is greatest when dealing with refusals of lifesaving or life-prolonging treatment. This may be complicated by delirium, concurrent depression, metabolic disturbances or significant symptom burden, family conflicts, and social issues. This is a case of a 48-year-old patient with a long-standing history of a symptomatic pan-invasive pituitary adenoma who refused life-prolonging treatment. Ultimately, a patient must be able to understand the information given to him, evaluate the consequences of the options presented, deliberate on these options based on his values, communicate this choice, and maintain consistency overtime. These refusals of treatment may fluctuate with time and intensity of the illness. Denial of this right of autonomy and self-determination may worsen the individual's physical and existential suffering.

Context: Sixty-five percent of people with advanced cancer suffers from loss of appetite. Several inflammatory cytokines appear to cause appetite loss in animal models. Thalidomide is an immunomodulatory drug that has been associated with improved appetite in those with HIV infections and cancer., Objectives: We completed a two-stage Phase II dose titration study of thalidomide, the primary purpose of which was to assess appetite response to thalidomide in cancer-associated anorexia., Methods: Individuals older than 18 years of age with active cancer, loss of appetite by numerical rating scale (NRS), life expectancy of at least four weeks, and Eastern Cooperative Oncology Group performance status of 0-3 were entered into the study. Pretreatment screening included medical history, neurologic examination, and symptoms by NRS and categorical scale (CAT). Patients received 50mg of thalidomide by mouth at bedtime for two weeks. Individuals who did not respond were dose escalated to 100mg at night for two weeks. Assessment of appetite, early satiety, fatigue, insomnia, night sweats, pain, and quality of life (QOL) occurred at two-week intervals. Toxicity also was assessed. The primary outcome was appetite response defined as a two-point reduction in the NRS or a one-point improvement in the CAT., Results: Thirty-five patients entered the study; 33 completed 14 days of therapy and were analyzed for efficacy and toxicity. Sixty-four percent who completed at least two weeks of thalidomide had improved appetite. The CAT scores for appetite, insomnia, and QOL improved significantly. The 95% confidence intervals did not overlap. Five participants dropped out because of toxicity: two before two weeks and three later., Conclusion: Thalidomide reduced multiple symptoms commonly associated with cancer-related anorexia and improved QOL. Our findings confirmed and validated a previously published single-arm trial. A recent randomized trial demonstrated greater benefits when thalidomide is used combined with other agents to treat cancer-associated anorexia and cachexia. Thalidomide helped cancer-associated anorexia in most patients. It also improved insomnia and QOL in advanced cancer., (Copyright © 2012 U.S. Cancer Pain Relief Committee. Published by Elsevier Inc. All rights reserved.)

Compared to other racial/ethnic groups, Korean, Filipino, and Vietnamese American women experience high incidence rates of cervical cancer but low rates of cervical cancer screenings. This study examines the behaviors and attitudes towards screening in young Korean, Filipino, and Vietnamese American women (n = 304) in the San Francisco Bay Area. Results indicated Vietnamese American (OR = 2.51) and Filipino American (OR = 2.31) women had greater odds of ever having a Pap test than Korean American women. Those older (OR = 1.55), born in the USA (OR = 2.64), and those comfortable with the test (OR = 3.41) also had greater odds of ever having a Pap test. Correct knowledge of cervical cancer and the human papillomavirus did not significantly affect the odds of having a Pap test. Interventions to increase Pap testing in these populations should focus on increasing levels of comfort and should target those younger and foreign born.

Morphine (M) is the opioid analgesic of choice for severe cancer pain. The IV to PO M equipotent switch ratio (CR) is controversial. We designed this prospective observational cohort to confirm the efficacy and safety of M IV to PO CR of 1:3. Consecutive cancer patients admitted to an inpatient palliative medicine unit were screened for inclusion. Pain was managed by palliative medicine specialists. They were blinded to the patient data collected, and the calculated CR. The switch was considered successful if the following criteria were met: (1) Pain adequately controlled: pain rated as none or mild (2) Number of RD less than 4 (for non incident pain) per 24 hours (3) No limiting side effects. We used Day 3 ATC M dose for CR calculations. The major outcome measures were the IV : PO CR ratio, morphine doses (mg/day), pain severity, number of PRN doses, and day 1 and day 3side effects. Descriptive statistics were used to report mean, median, standard deviation and range of different variables. Two hundred and fifty six consecutive admissions were screened, and 106 were eligible for the study. Sixty two underwent a successful M route switch and were included in this analysis. A ratio of 1:3 was safely implemented over a wide M dose range. About 80% were successfully switched with a calculated CR of 1:3. 20% required an oral M dose adjustment after route switch either to better pain control or reduce side effects with a resultant higher (e.g. 1:4) or lower (e.g. 1:2) calculated potency ratios respectively. A potency ratio of 1:3 was safe as evaluated by common M side-effects, the dose also easy to calculate. The 1: 3 M IV to PO relative milligram potency ratio appears correct and practical for most patients over a wide M dose range.

Context: Anorexia is a common symptom in cancer and is usually assessed by multiple questions and multidimensional questionnaires. A simplified questionnaire would be less burdensome to patients and abbreviate the process., Objectives: We compared the reliability at one point in time, sensitivity to change over time, and prognostic accuracy of a two-item questionnaire with the Functional Assessment of Anorexia and Cachexia Therapy shortened 12-question version (A/CS-12)., Methods: Individuals with cancer, who were cognitively intact and verbally agreed to participate, completed a two-item questionnaire and A/CS-12 in random order and again seven days later. We compared the direction of response to the summated two-item questionnaire to the validated A/CS-12 score at a single point in time, then intra-patient changes over a seven-day period of time. Scores of both questionnaires were divided into poor, moderate and good appetite and compared to survival using Kaplan-Meyer curves. Bootstrapping was used to construct confidence intervals for estimated probability agreement. Survival analysis also used hazard ratios from a Cox Proportional Hazards model., Results: One hundred seventeen individuals from a single institution participated, who were either admitted to an inpatient palliative unit or seen in an outpatient/palliative medicine unit. Median age was 58.8 (range 10.7-87.1 years). Agreement at one point in time was 0.64 (95% confidence interval [CI] 0.63 - 0.66). Agreement over time was 0.53 (CI 0.41 - 0.64). The A/CS-12 predicted survival based on scores on Days 1 and 7 (P<0.001), (P=0.003) (HR 0.97 day 1, HR 0.95 day 7), whereas the simplified questionnaire failed to predict survival., Conclusions: A simplified questionnaire has moderate correlation with the A/CS-12 at one point in time but loses sensitivity over time, and lacks the ability to predict survival. A change in the questionnaire may improve reliability. Changing question 2 of the simplified questionnaire to a neutral form (better, same or worse appetite) may improve sensitivity and prognostic capability.

To evaluate cancer-related fatigue (CRF) by objective measurements to determine if CRF is a more centrally or peripherally mediated disorder, cancer patients and matched noncancer controls completed a Brief Fatigue Inventory (BFI) and underwent neuromuscular testing. Cancer patients had fatigue measured by the BFI, were off chemotherapy and radiation (for more than four weeks), had a hemoglobin level higher than 10 g/dL, and were neither receiving antidepressants nor were depressed on a screening question. The controls were screened for depression and matched by age, gender, and body mass index. Neuromuscular testing involved a sustained submaximal elbow flexion contraction (SC) at 30% maximal level (30% maximum elbow flexion force). Endurance time (ET) was measured from the beginning of the SC to the time when participants could not maintain the SC. Evoked twitch force (TF), a measure of muscle fatigue, and compound action potential (M-wave), an assessment of neuromuscular-junction transmission were performed during the SC. Compared with controls, the CRF group had a higher BFI score (P<0.001), a shorter ET (P<0.001), and a greater TF with the SC (CRF>controls, P<0.05). This indicated less muscle fatigue. There was a greater TF (P<0.05) at the end of the SC, indicating greater central fatigue, in the CRF group, which failed to recruit muscle (to continue the SC), as well as the controls. M-Wave amplitude was lower in the CRF group than in the controls (P<0.01), indicating impaired neuromuscular junction conduction with CRF unrelated to central fatigue (M-wave amplitude did not change with SC). These data demonstrate that CRF patients exhibited greater central fatigue, indicated by shorter ET and less voluntary muscle recruitment during an SC relative to controls.

Introduction: We wished to determine bioelectrical impedance (BIA) correlates before hydration or changes during hydration and determine if these changes were prognostically important., Methods and Materials: Fifty eligible patients underwent BIA measurements 3 consecutive days. Laboratory studies (electrolytes, creatinine, and hemoglobin) on day 1; weights and vital signs were recorded. Kaplan-Meier survival estimates were made at 30 and 60 days. Hazard ratios (HRs) based on Cox proportional hazards model were calculated., Results: Weight loss was associated with shorter survival. A higher phase angle (PA) on day 1 predicted longer survival. Increased PA during hydration predicted shorter survival: increased weight during hydration predicted longer survival., Discussion: Higher phase angle before hydration predicts poorer survival and, paradoxically, an increase in phase angle during hydration predicted poorer survival and preexisting intracellular dehydration, cachexia, or poor membrane function., Conclusions: Phase angle and weight during hydration predict survival in cancer.

Background: Adverse drug interactions are major causes of morbidity, hospitalizations, and mortality. The greatest risk of drug interactions occurs through in the cytochrome system. CYP3A4, the most prevalent cytochrome, accounts for 30-50% of drugs metabolized through type I enzymes., Materials and Methods: Palliative patients received medications for symptoms and co-morbidities, many of which are substrate, inhibitors, or promoters of CYP3A4 activity and expression. A literature review on CYP3A4 was performed pertinent to palliative medicine., Discussion: In this state of the art review, we discuss the CYP3A4 genetics, and kinetics and common medications, which are substrates or inhibitor/promoters of CYP3A4., Conclusion: We made some recommendations for drug choices to avoid clinically important drug interaction.

Goal: This study was to objectively assess the effect of music therapy on patients with advanced disease., Patients and Methods: Two hundred patients with chronic and/or advanced illnesses were prospectively evaluated. The effects of music therapy on these patients are reported. Visual analog scales, the Happy/Sad Faces Assessment Tool, and a behavior scale recorded pre- and post-music therapy scores on standardized data collection forms. A computerized database was used to collect and analyze the data., Results: Utilizing the Wilcoxon signed rank test and a paired t test, music therapy improved anxiety, body movement, facial expression, mood, pain, shortness of breath, and verbalizations. Sessions with family members were also evaluated, and music therapy improved families' facial expressions, mood, and verbalizations. All improvements were statistically significant (P<0.001). Most patients and families had a positive subjective and objective response to music therapy. Objective data were obtained for a large number of patients with advanced disease., Conclusions: This is a significant addition to the quantitative literature on music therapy in this unique patient population. Our results suggest that music therapy is invaluable in palliative medicine.

Introduction: The severity of anorexia correlates with the presence of early satiety. The sense of fullness limits nutritional intake. The symptom is poorly understood because most assessment questionnaires do not include early satiety., Methods: Patients rarely volunteer early satiety. Central and peripheral mechanisms may be involved in the genesis of early satiety. These would include central sensory specific satiety, food aversions, diurnal changes in intake, gastric motility and accommodation and as gastrointestinal hormones., Conclusions: Prokinetic medications, such as metoclopramide are used to treat early satiety. However, other medications which influence gastric accommodation such as clonidine, sumatriptan, or sildenafil, or diminish enteric afferent output such as kappa opioid receptor agonists, may favorably influence early satiety and should be subject to future research. Translational research is needed to understand the relationship of early satiety to gastric motility and accommodation.

Purpose: We systematically assessed the efficacy and safety of appetite stimulants in the management of cancer-related anorexia. Literature databases were searched for randomized controlled trials of appetite stimulants in the treatment of cancer anorexia., Materials and Methods: Studies were graded according to quality. Fifty-five studies met inclusion criteria., Results: Only two drugs have evidence to support their use for anorexia (progestins and corticosteroids). There is strong evidence against the use of hydrazine sulfate. The outcomes of these trials have been mixed and patient population heterogeneous., Conclusion: The optimal dose, time to start, and duration of treatment for many appetite stimulants for cancer anorexia is still unknown. A more systematic approach to research methodology with universal outcome measure and prospective randomized studies are need. Combination regimens are needed but this cannot at the present time be supported by the data presented.

The use of combinations of potent opioids is a common clinical practice. The addition of one potent opioid to another has been recommended to reduce opioid side effects, improve pain control, and limit dose escalation of the first opioid. The advantages of using combined opioids have been reported to be relative to differences in receptor activation versus endocytosis (RAVE). However, the advantages and detriment to combining opioids are related to naturally occurring opioid receptor dimers. Dimers and oligomers result in a unique opioid pharmacodynamics which influence opioid binding, G protein interactions, desensitization, receptor trafficking, and endocytosis. The pharmacodynamics of dimers may lead to positive or negative cooperativity when two opioids are combined. The use of multiple opioids in practice can lead to increased risk for dosing errors, reduced patient compliance, increased drug interactions and cost. Opioid combinations should not be used until prospective randomized trials clarify the benefits and safety.

Because of the advent of disease-modifying agents for patients with malignancies, cancer is now a chronic illness. However, most cancer patients will experience significant symptoms and complications during the course of their illness or its treatment. In addition to their physical symptoms, patient and families are burdened with psychological, social, and spiritual difficulties. Palliative medicine addresses all these issues and complements attempts to cure the disease; it is an essential part of modern comprehensive cancer care.

Appetite is governed by peripheral hormones and central neurotransmitters that act on the arcuate nucleus of the hypothalamus and nucleus tactus solitarius of the brainstem. Cancer anorexia appears to be the result of an imbalance between neuropeptide-Y and pro-opiomelanocortin signals favoring pro-opiomelanocortin. Many of the appetite stimulants redress this imbalance. Most of our understanding of appetite neurophysiology and tumor-associated anorexia is derived from animals and has not been verified in humans. There have been few clinical trials and very little translational research on anorexia despite its prevalence in cancer.

Pain remains the most common distressing symptom in advanced cancer. Opioids are the most effective drugs for pain currently available. Analgesia depends largely on appropriate administration. Cancer clinicians should be proficient in opioid pharmacotherapy. Although knowledge of general opioid dosing principles is helpful, in practice, complex clinical scenarios often arise, requiring more sophisticated and precise dosing maneuvers for which there is very little evidence-based literature. Familiarity with specific strategies indicated for common clinical problems provides a more focused approach and increases the likelihood of therapeutic success. This article enumerates cancer pain scenarios compiled from our palliative medicine practice and the opioid dosing strategies used by the palliative medicine department within the Cleveland Clinic Foundation.

The use of nutritional supplements in the general population and in cancer patients has become very popular. These supplements are not perceived as medications and are presumed to be safe by cancer patients, who may however be at risk for hypercalcemia. We note that many of our patients who have developed symptomatic hypercalcemia were taking vitamin D, calcium, or shark cartilage supplements. We report eight cases of hypercalcemia in cancer patients seen at the Cleveland Clinic Foundation in whom these nutritional supplements may have contributed to the prevalence or severity of hypercalcemia.