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Background: : Delirium has been the most frequent neuropsychiatric complication in patients with advanced cancer. This exploratory study aimed to determine the proportion of patients who were able to recall their experience of delirium and the level of distress experienced by patients, family caregivers, and healthcare professionals., Methods: : Patients with advanced cancer who had completely recovered from an acute delirium episode, had Memorial Delirium Assessment Scale score <13, and had a family caregiver present during the delirium were studied. Patients were given the Delirium Experience Questionnaire. Patients' and family caregivers' demographics, and the frequency and distress associated with different delirium symptoms were also collected. Bedside nurses and palliative care specialists reported the frequency of recalled delirium symptoms and their distress score., Results: : A total of 99 patient/family caregiver dyads participated in the study. The main identified causes for delirium were opioids, infection, brain metastases, hypercalcemia, and dehydration. There were 73 patients (74%) who remembered the episode of being delirious, with 59 of 73 patients (81%) reporting the experience as distressing (median distress level of 3). The median overall delirium distress score was higher in family caregivers (median, 3; 25%-75% quartile, 2-4) than in patients (median, 2; 25%-75% quartile, 0-3) (P = .0004). Bedside nurses and palliative care specialists expressed low median overall delirium distress scores (median, 0; 25%-75% quartile 0-1)., Conclusions: : The majority of patients with advanced cancer recalled their experience of delirium, causing moderate to severe distress in both patients and family caregivers. Appropriate interventions to reduce this distress are needed. Cancer 2009. (c) 2009 American Cancer Society.

Medical training teaches physicians to sit when breaking bad news, though there have been no controlled studies to support this advice. We aimed to establish cancer patients' preference for physician posture when physicians break bad news using a randomized controlled crossover trial in a department of palliative care at a large US cancer center. Referred patients were blind to the hypothesis and watched video sequences of a sitting or standing physician breaking bad news to a cancer patient and 168 of 173 participants (88 female) completed the study. Sitting physicians were preferred and viewed as significantly more compassionate than standing physicians (P < 0.0001) but other physician attributes and behaviours were generally rated as of equal or more importance than posture. In summary, cancer patients, especially females, prefer physicians to sit when breaking bad news and rate physicians who adopt this posture as more compassionate. However, sitting posture alone is unlikely to compensate for poor communication skills and lack of other respectful gestures during a consultation.

Purpose: To evaluate the effectiveness of patient-controlled methylphenidate as compared with placebo in cancer patients with fatigue, as measured by the Functional Assessment for Chronic Illness Therapy-Fatigue (FACIT-F)., Patients and Methods: Patients with a fatigue score of at least 4 on a scale of 0 to 10 (0 = no fatigue, 10 = worst possible fatigue) and hemoglobin level of at least 10 g/dL were included. Patients were randomly assigned to receive 5 mg methylphenidate or placebo every 2 hours as needed (maximum of four capsules a day), for 7 days. Patients completed a daily diary including study drug record and fatigue intensity. A research nurse telephoned patients daily to assess toxicity and fatigue level. All patients were offered open-label methylphenidate for 4 weeks. FACIT-F and the Edmonton Symptom Assessment System (ESAS) were assessed at baseline, and days 8, 15, and 36. The FACIT-F fatigue subscore on day 8 was considered the primary end point., Results: Of 112 patients randomly assigned, 52 patients in the methylphenidate and 53 in the placebo group were assessable for analysis. Fatigue intensity improved significantly on day 8 in both the methylphenidate and placebo groups. However, there was no significant difference in fatigue improvement by FACIT-F (P = .31) or ESAS (P = .14) between groups. In open-label phase, fatigue intensity maintained low as compared with baseline. No significant toxicities were observed., Conclusion: Both methylphenidate and placebo resulted in significant symptom improvement. Methylphenidate was not significantly superior to placebo after 1 week of treatment. Longer study duration is justified. The role of daily telephone calls from a research nurse should be explored as a palliative care intervention.

Background: Fatigue has been reported to be associated with anemia in patients receiving cancer treatment. Treatment of anemia such as erythropoietin has been reported to decrease fatigue in these patients., Objective: To investigate the correlation between anemia and fatigue intensity in patients with advanced cancer receiving palliative care., Methods: We reviewed medical charts of 177 consecutive outpatients seen by our palliative care specialists. Information of fatigue intensity and hemoglobin level was collected., Results: Among 147 (83%) evaluable patients, the median hemoglobin level was 11.6 g/dL (range, 7.5-16.1). Eighty-two (56%) patients had a hemoglobin level 12 g/dL or less, whereas 125 (85%) had 10 g/dL or more. The median fatigue score in patients with a hemoglobin level 10 g/dL or more and 10 g/dL or less was 6 (range, 4-8) and 7 (range, 5-8), respectively (p = 0.048). The median fatigue score in patients with a hemoglobin level 12 g/dL or more and 12 g/dL or less was 6 (range, 4-7) and 6 (range, 4-8), respectively (p > 0.5). Spearman's rank correlation coefficient showed a significant association only between the hemoglobin level and the albumin level (r = 0.52, p < 0.0001). Hemoglobin level did not show a significant correlation with fatigue although there was a trend (p = 0.09). In a multivariate regression analysis of the intensity of fatigue and other clinical variables, three variables remained significant in the reverse elimination analysis: depression (p = 0.0067), albumin level (p = 0.0079), and sensation of well-being (p = 0.0569). The overall explained variance for this model was 0.22., Conclusion: Our findings suggest that anemia is not one of the major contributors to fatigue in patients with cancer receiving palliative care.

In recent years, patients with advanced cancer are referred more frequently to palliative care programs. However, the referrals usually occur relatively late for the management of severe physical and psychological distress. The purpose of this retrospective study was to investigate the interval between palliative care referral and death in patients with advanced cancer. We reviewed charts of 240 consecutive patients with advanced cancer referred to the palliative care program at M.D. Anderson Cancer Center between September and December 2003. Demographics, as well as dates of cancer diagnosis, advanced disease diagnosis, palliative care referral, and death were determined. The median age was 61 years old, 173 were male, 304 patients had solid tumors, and 26 had hematologic malignancies. The median time intervals between the diagnosis of the primary cancer and death, diagnosis of advanced disease and death, advanced disease and palliative care referral, and palliative care referral and death were 33.0 months (95% confidence interval [CI]: 25.8-41.9), 9.4 months (95% CI: 7.9-11.1), 5.6 months (95% CI: 4.3-7.7), and 1.9 months (95% CI: 1.6-2.2), respectively. The patients' median time interval from advanced cancer diagnosis to death and from palliative care referral to death was shorter in patients with hematologic malignancies than in those with sold tumors (p = 0.018 and p < 0.001, respectively). Median time interval between palliative care referral and death was longer for patients less than 65 year old than those 65 years old or more (p = 0.03). Our results should help palliative care and oncology programs at comprehensive cancer centers plan how to develop joint programs for patient care.

This study compared the effects of nebulized versus subcutaneous morphine on the intensity of dyspnea in cancer patients. Patients with a resting dyspnea intensity > or =3 on a 0-10 scale (0=no dyspnea, 10=worst possible dyspnea) who received regular oral or parenteral opioids were included. On day 1, patients received either subcutaneous (SC) morphine plus nebulized placebo or nebulized morphine plus SC placebo. On day 2, a crossover was made. Dyspnea intensity, side effects, and blinded preference of treatment were assessed. Eleven patients completed the study. Dyspnea decreased from a median of 5 (range, 3-8) to 3 (range, 0-7) after SC morphine (P=0.025) and from 4 (range, 3-9) to 2 (range, 0-9) after nebulized morphine (P=0.007). There was no significant difference in dyspnea intensity between nebulized and subcutaneous morphine at 60 minutes. Unfortunately, due to limited sample size, there was insufficient power to rule out a significant difference between both routes of administration. Nebulized morphine offered dyspnea relief similar to that of SC morphine. Larger randomized controlled trials in patients with both continuous dyspnea and earlier stages of dyspnea are justified.

This study describes and compares patients' reports of somatic symptoms and physicians' ratings of the same symptoms in patients with chronic non-cancer-related and cancer-related pain. Ninety-seven patients with chronic non-cancer-related pain and 100 patients with chronic cancer-related pain reported somatic symptoms using a newly developed checklist of somatic symptoms. Patients also completed the Brief Symptom Inventory-18, Courtland Emotional Control Inventory, Catastrophizing scale, two items from the Coping Strategies Questionnaire (one about efficacy to control and another about ability to decrease pain), and a numeric rating of average pain. After they completed medical histories and physical examinations on patients, physicians rated the degree to which the patients' reported somatic symptoms on the checklist were medically unexplainable. Over 80% of patients in both groups reported somatic symptoms that their physicians rated as not fully explainable. Strong associations existed between patient-reported somatic symptoms and negative mood states. For the majority of patients, results supported a concept of combined illness- and affect-related pathology rather than one of pure somatoform disorder. Assessing patients' reports of somatic symptoms and negative mood states and incorporating physicians' ratings of level of medically unexplainable somatic symptoms were useful for distinguishing these diagnoses.

Chronic nausea occurs in most patients with advanced cancer. This study was done to assess the antiemetic effects of dexamethasone in patients with chronic nausea refractory to metoclopramide. Secondary outcomes included appetite, fatigue, and pain. Fifty-one patients who had nausea (> or = 3/10 on a 0-10 scale) for > or = 2 weeks despite 48 hours of oral metoclopramide therapy (40-60 mg/day) were enrolled. Patients received 20 mg/day dexamethasone (DM) orally (n = 25) or placebo (n = 26) for severe nausea in addition to metoclopramide (60 mg/day orally). At baseline the mean nausea intensity ratings in the DM and placebo groups were 8.0 and 7.4. At Day 8 they were 2.1 and 2.0, respectively. At Day 3 and Day 8, the mean difference in nausea intensity for the DM and placebo groups was 4.5 and 2.9 (P = 0.16) and 5.9 and 5.7 (P = 0.85), respectively. Improvement in appetite and fatigue were observed on Day 3 and Day 8 in both groups as compared with the baseline. Pain, vomiting, well-being, and quality of life remained unchanged in both groups at both times. We conclude that DM was not superior to placebo in the management of chronic nausea in our patients with advanced cancer.

To characterize a new, one-stop multidisciplinary palliative care (MD) clinic which offers standardized multidisciplinary assessment, specific care recommendations, patient and family education, and on-site counseling, we retrospectively compared the assessments of 138 consecutive patients with advanced cancer referred to the MD clinic and 77 patients referred to a traditional pain and symptom management (PSM) clinic. The two groups were similar in tumor type, demographics, and symptom distress. The MD clinic team (physicians; nurses; pharmacists; physical, speech, and occupational therapists; social workers; chaplains; nutritionists; psychiatric nurse practitioner) delivered 1,066 non-physician recommendations (median 4 per patient, range 0-37). The PSM clinic team made no non-physician recommendations, but referred 14 patients to other medical specialists. In 80 (58%) MD-clinic patients with follow-up 9 days (median) after assessment, significant improvement was observed in pain, nausea, depression, anxiety, sleep, dyspnea, and well-being, but not in fatigue, anorexia, or drowsiness. In 83 patients interviewed after the MD clinic, satisfaction was rated as excellent (5 out of 5) in 86-97% of seven areas. Assessment at an MD clinic results in a high number of patient care recommendations, improved symptoms, and high levels of patient satisfaction.

Purpose: To compare the effectiveness and side effects of methadone and morphine as first-line treatment with opioids for cancer pain., Patients and Methods: Patients in international palliative care clinics with pain requiring initiation of strong opioids were randomly assigned to receive methadone (7.5 mg orally every 12 hours and 5 mg every 4 hours as needed) or morphine (15 mg sustained release every 12 hours and 5 mg every 4 hours as needed). The study duration was 4 weeks., Results: A total of 103 patients were randomly assigned to treatment (49 in the methadone group and 54 in the morphine group). The groups had similar baseline scores for pain, sedation, nausea, confusion, and constipation. Patients receiving methadone had more opioid-related drop-outs (11 of 49; 22%) than those receiving morphine (three of 54; 6%; P =.019). The opioid escalation index at days 14 and 28 was similar between the two groups. More than three fourths of patients in each group reported a 20% or more reduction in pain intensity by day 8. The proportion of patients with a 20% or more improvement in pain at 4 weeks in the methadone group was 0.49 (95% CI, 0.34 to 0.64) and was similar in the morphine group (0.56; 95% CI, 0.41 to 0.70). The rates of patient-reported global benefit were nearly identical to the pain response rates and did not differ between the treatment groups., Conclusion: Methadone did not produce superior analgesic efficiency or overall tolerability at 4 weeks compared with morphine as a first-line strong opioid for the treatment of cancer pain.

Context: The symptomatic benefits of oxygen in patients with cancer who have nonhypoxic dyspnea are not well defined., Objective: To determine whether or not oxygen is more effective than air in decreasing dyspnea and fatigue and increasing distance walked during a 6-minute walk test., Patients and Methods: Patients with advanced cancer who had no severe hypoxemia (i.e., had an O2 saturation level of > or = 90%) at rest and had a dyspnea intensity of > or = 3 on a scale of 0-10 (0 = no shortness of breath, 10 = worst imaginable shortness of breath) were recruited from an outpatient thoracic clinic at a comprehensive cancer center. This was a double-blind, randomized crossover trial. Supplemental oxygen or air (5 L/min) was administered via nasal cannula during a 6-minute walk test. The outcome measures were dyspnea at 3 and 6 minutes, fatigue at 6 minutes, and distance walked. We also measured oxygen saturation levels at baseline, before second treatment phase, and at the end of study., Results: In 33 evaluable patients (31 with lung cancer), no significant differences between treatment groups were observed in dyspnea, fatigue, or distance walked (dyspnea at 3 minutes: P = 0.61; dyspnea, fatigue, and distance walked at 6 minutes: P = 0.81, 0.37, and 0.23, respectively)., Conclusions: Currently, the routine use of supplemental oxygen for dyspnea during exercise in this patient population cannot be recommended.

Purpose: To assess the effects of patient-controlled methylphenidate for cancer-related fatigue., Patients and Methods: In this prospective open study, 31 patients with advanced cancer and fatigue who scored >/= 4 on a scale of 0 to 10 received methylphenidate 5 mg by mouth every 2 hours as needed for 7 days (maximum, 20 mg/d). Multiple symptoms were assessed daily; the primary end point, fatigue, was measured using the 0 to 10 scale, and the Functional Assessment for Chronic Illness Therapy-Fatigue (FACIT-F) was performed at baseline, day 7, and day 28., Results: The following mean (+/- standard deviation) scores for 30 assessable patients improved significantly between baseline and day 7: fatigue (0 to 10 scale), 7.2 +/- 1.6 v 3.0 +/- 1.9 (P <.001); overall well-being (0 to 10 scale), 4.5 +/- 2.2 v 2.8 +/- 2.1 (P <.001); fatigue (FACIT-F) subscore, 17.5 +/- 11.3 v 34.7 +/- 10.0 (P <.001); functional well-being, 14.4 +/- 5.9 v 18.3 +/- 6.6 (P <.001); and physical well-being, 13.5 +/- 6.4 v 21.4 +/- 5.0 (P <.001). Anxiety, appetite, pain, nausea, depression, and drowsiness all improved significantly (P <.05). All patients took afternoon or evening doses, and 28 patients (93%) took three or more doses daily. All patients chose to continue taking methylphenidate after 7 days of treatment. No serious side effects were reported., Conclusion: These preliminary results suggest that patient-controlled methylphenidate administration rapidly improved fatigue and other symptoms. Randomized controlled trials are justified.

Opioid-induced sedation is a major complication in patients with cancer pain. This study assessed the effectiveness of donepezil in opioid-induced sedation and related symptoms in patients with cancer pain. Twenty-seven patients who were receiving strong opioids for pain and reported sedation were enrolled. Donepezil 5 mg was given every morning for 7 days. Changes between baseline and Day 7 in sedation, pain, fatigue and other symptoms were evaluated using the Edmonton Symptom Assessment Scale. Fatigue was also measured using the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue). Overall usefulness of donepezil was measured by the patient at the end of the study. In 20 evaluable patients, sedation, fatigue, anxiety, well-being, depression, anorexia and problems with sleep were significantly improved. Side effects included nausea, vomiting, diarrhea, muscle and abdominal cramps, and anorexia. Overall, however, the treatment was well tolerated. Donepezil appears to improve sedation and fatigue in patients receiving opioids for cancer pain. Randomized controlled trials of this agent are justified.

Perception of discomfort in dying patients is a risk factor for distress and bereavement among relatives. This study determined the perception of discomfort, the frequency of observed behaviors, and their association among relatives and among nurses who care for unresponsive dying patients. Sixty unresponsive dying patients' relatives and their nurses were asked to evaluate patient discomfort levels, the frequencies of six observed behaviors, and the suspected reasons for the patient discomfort. The mean levels of perceived discomfort were similar, but the association was poor between the relatives and the nurses. Relatives reported significantly more observed behaviors and associated more pain as a reason for patient discomfort than did nurses. The findings suggest that relatives are intensely attuned to their loved ones' conditions and reactions, and nurses' responses are fairly similar. Further research is warranted, however, to distinguish between the distress that the relatives perceive and the actual suffering of patients.

Purpose: To determine whether high doses of fish oil, administered over 2 weeks, improve symptoms in patients with advanced cancer and decreased weight and appetite., Patients and Methods: Sixty patients were randomly assigned to fish oil capsules or placebo. Appetite, tiredness, nausea, well-being, caloric intake, nutritional status, and function were prospectively assessed at days 1 and 14., Results: The baseline weight loss was 16 +/- 11 and 16 +/- 8 kg in the fish oil (n = 30) and placebo (n = 30) group respectively, whereas the baseline appetite (0 mm = best and 10 mm = worst) was 58 +/- 24 mm and 67 +/- 19 mm, respectively (P = not significant). The mean daily dose was 10 +/- 4 (fish oil group) and 9 +/- 3 (placebo group) capsules, which provided 1.8 g of eicosapentaenoic acid and 1.2 g of docosahexaenoic acid in the fish oil group. No significant differences in symptomatic or nutritional parameters were found (P <.05), and there was no correlation between changes in different variables between days 1 and 14 and the fish oil doses. Finally, the majority of the patients were not able to swallow more than 10 fish oil capsules per day, mainly because of burping and aftertaste., Conclusion: Fish oil did not significantly influence appetite, tiredness, nausea, well-being, caloric intake, nutritional status, or function after 2 weeks compared with placebo in patients with advanced cancer and loss of both weight and appetite.

The primary goal of biochemical and molecular epidemiology is to identify individuals at high cancer risk by obtaining evidence of high exposure to carcinogens, leading to pathobiological lesions in target cells, and/or increased oncogenic susceptibility due to either inherited or acquired host factors. This emerging and multidisciplinary area of cancer research combines epidemiological and laboratory approaches. Because DNA is considered to be an important target for modification by mutagens and carcinogens, damage to DNA can be used as an internal, molecular dosimeter of carcinogen exposure. The reactive species of these carcinogens may directly bind to DNA to form adducts and may indirectly cause secondary DNA lesions, e.g., via induction of free radicals and aldehydes. Highly sensitive and specific methods have been developed to measure the minute amounts of DNA lesions and DNA repair products found in biological specimens from humans exposed to carcinogens. For example, DNA adducts have been measured in cells and tissues from people occupationally exposed to carcinogenic polycyclic aromatic hydrocarbons. Antibodies recognizing carcinogen-DNA adducts have also been detected in human sera. Inherited predisposition to cancer has been revealed by recent advances in molecular genetics, including restriction-fragment-length polymorphism. For example, the hypothesis that rare alleles of the Ha-ras proto-oncogene are associated with an increased risk of lung cancer is currently being tested. These approaches afford the potential of biochemical and molecular epidemiology to predict disease risk for individual persons, instead of for populations, and before the onset of clinically evident disease.