Repurposing screen identifies novel candidates for broad-spectrum coronavirus antivirals and druggable host targets.

Libraries composed of licensed drugs represent a vast repertoire of molecules modulating physiological processes in humans, providing unique opportunities for the discovery of host-targeting antivirals. We screened the Repurposing, Focused Rescue, and Accelerated Medchem (ReFRAME) repurposing library with approximately 12,000 molecules for broad-spectrum coronavirus antivirals and discovered 134 compounds inhibiting an alphacoronavirus and mapping to 58 molecular target categories. Dominant targets included the 5-hydroxytryptamine receptor, the dopamine receptor, and cyclin-dependent kinases. Gene knock-out of the drugs' host targets including cathepsin B and L (CTSB/L; VBY-825), the aryl hydrocarbon receptor (AHR; Phortress), the farnesyl-diphosphate farnesyltransferase 1 (FDFT1; P-3622), and the kelch-like ECH-associated protein 1 (KEAP1; Omaveloxolone), significantly modulated HCoV-229E infection, providing evidence that these compounds inhibited the virus through acting on their respective host targets. Counter-screening of all 134 primary compound candidates with SARS-CoV-2 and validation in primary cells identified Phortress, an AHR activating ligand, P-3622-targeting FDFT1, and Omaveloxolone, which activates the NFE2-like bZIP transcription factor 2 (NFE2L2) by liberating it from its endogenous inhibitor KEAP1, as antiviral candidates for both an Alpha- and a Betacoronavirus. This study provides an overview of HCoV-229E repurposing candidates and reveals novel potentially druggable viral host dependency factors hijacked by diverse coronaviruses.

Living with prostate cancer: a mixed-method evaluation of group therapy intervention to alleviate psychological distress in a Canadian setting.

PURPOSE: To assess the effects of group therapy focused on the experience of living with prostate cancer (PC) on depression and mental well-being among men with the disease and to explore participant experiences of a guided opportunity to 'speak the unspeakable' as it pertains to living with PC. METHODS: We used a mixed-method convergent design. Participants completed four validated self-report questionnaires at baseline, immediately after the final session, and at three, six, and 12 months follow-up. A repeated measures mixed-effect model examined the effects of the program on depression, mental well-being, and masculinity. Seven focus groups (n = 37) and 39 semi-structured individual interviews explored participant reactions at follow-up. RESULTS: Thirty-nine (93%) participants completed the questionnaires at all follow-ups. Responses indicated improved mental well-being up to three months (p < 0.01) and a decrease in depressive symptoms to 12 months (p < 0.05). Qualitative analysis revealed how the cohesive group environment alleviated psychological stress, enabled participants to identify significant issues and concerns in their lives, and improved communication and relationship skills that were of value in the group as well as with family and friends. The facilitation was essential to guiding participants to 'speak the unspeakable.' CONCLUSION: Men with PC who speak of their experience in a group setting with a guided process incorporating features of a life review appear to gain insight into the impact of PC in their lives, experience diminished features of depression and isolation, and enhance their communication skills within the groups as well as with family members and friends.

More comprehensively measuring quality of life in life-threatening illness: the McGill Quality of Life Questionnaire - Expanded.

BACKGROUND: Domains other than those commonly measured (physical, psychological, social, and sometimes existential/spiritual) are important to the quality of life of people with life-threatening illness. The McGill Quality of Life Questionnaire (MQOL) - Revised measures the four common domains. The aim of this study was to create a psychometrically sound instrument, MQOL - Expanded, to comprehensively measure quality of life by adding to MQOL-Revised the domains of cognition, healthcare, environment, (feeling like a) burden, and possibly, finance. METHODS: Confirmatory factor analyses were conducted on three datasets to ascertain whether seven new items belonged with existing MQOL-Revised domains, whether good model fit was obtained with their addition as five separate domains to MQOL-Revised, and whether a second-order factor representing overall quality of life was present. People with life-threatening illnesses (mainly cancer) or aged > 80 were recruited from 15 healthcare sites in seven Canadian provinces. Settings included: palliative home care and inpatient units; acute care units; oncology outpatient clinics. RESULTS: Good model fit was obtained when adding each of the five domains separately to MQOL-Revised and for the nine correlated domains. Fit was acceptable for a second-order factor model. The financial domain was removed because of low importance. The resulting MQOL-Expanded is a 21-item instrument with eight domains (fit of eight correlated domains: Comparative Fit Index = .96; Root Mean Square Error of Approximation = .033). CONCLUSIONS: MQOL-Expanded builds on MQOL-Revised to more comprehensively measure the quality of life of people with life-threatening illness. Our analyses provide validity evidence for the MQOL-Expanded domain and summary scores; the need for further validation research is discussed. Use of MQOL-Expanded will enable a more holistic understanding of the quality of life of people with a life-threatening illness and the impact of treatments and interventions upon it. It will allow for a better understanding of less commonly assessed but important life domains (cognition, healthcare, environment, feeling like a burden) and their relationship to the more commonly assessed domains (physical, psychological, social, existential/spiritual).

Suicidal ideation among family practice residents at the University of British Columbia.

OBJECTIVE: To determine the prevalence of suicidal ideation and burnout among family practice residents at the University of British Columbia (UBC), and to compare the identified rates with those found in other studies. DESIGN: Web-based survey. SETTING: University of British Columbia in Vancouver. PARTICIPANTS: A total of 235 family practice residents from UBC. MAIN OUTCOME MEASURES: The Web-based survey included an evaluation of suicide risk with questions adapted from the Meehan Inventory, and an evaluation of burnout with the Maslach Burnout Inventory. A univariate descriptive analysis and a bivariate analysis were used to define the prevalence of suicidal ideation and burnout, as well as relationships with demographic variables. RESULTS: In the fall of 2010, among the 109 survey respondents (46.4% response rate), the rate of suicidal ideation during family practice residency was 33.3%, the rate of suicidal ideation with a plan during residency was 18.1%, and the rate of suicide attempt during residency was 2.9%. The prevalence of burnout during residency was identified in 73.5% of respondents and was represented by a perceived lack of personal accomplishment. The identified prevalence of suicidal ideation was considerably higher than in other studies, and the identified prevalence of burnout was comparable to similar studies. CONCLUSION: This study identified a high rate of suicidal ideation and burnout among Canadian family medicine residents at UBC. Further research is needed to improve suicide prevention, as well as identification and support of residents in distress.

Building positive relationships in healthcare: evaluation of the Teams of Interprofessional Staff interprofessional education program.

The Teams of Interprofessional Staff (TIPS) project consisted of five healthcare teams from across Ontario, participating in three, two-day face-to-face interprofessional educational (IPE) sessions over an 8-month period. The purpose of TIPS was to explore whether interprofessional team development for practicing healthcare professionals, makes a difference in team functioning, team member satisfaction, ability to work effectively both individually and as a team, and improved patient well-being. A comprehensive formative and summative evaluation revealed that all teams perceived they benefitted from and engaged in successful team development. Success meant different things to each team reflecting the continuum of team development from building a safe, trusted group to becoming leaders of team development for other interprofessional teams. Effective teamwork is crucial to nurses who often take on the role of coordinator of care on a day-to-day basis, or are in managerial roles in interprofessional clinics or clinical program teams.

Burnout, compassion fatigue and work-related stressors among organ donation and transplantation coordinators: A qualitative study.

AIM: Organ and Tissue Donation Coordinators (OTDCs) are healthcare professionals who manage deceased organ donation cases. This study investigated the experiences and perceptions of OTDCs, pertaining to compassion fatigue, burnout, and resilience as it relates to their daily work. METHODOLOGY: A qualitative descriptive study was undertaken using semi-structured interviews conducted with a convenience sample of OTDCs. SETTING: A Canadian Organ Donation Organization. FINDINGS: Seven out of the ten OTDCs contacted participated in this study. Coordinators all agreed that they work in a high-pressure and demanding environment and the constant exposure to work-related stress and grief has resulted in the majority of them experiencing signs and symptoms of burnout and compassion fatigue occurring throughout their career. Participants described that the emotional toll of work-related stressors and difficult cases led them to use a variety of defence strategies to protect and support their well-being. They also recognised that more strategies to help mitigate work-related stressors and to prevent burnout and compassion fatigue are needed and that management and institutions should lead the development of such interventions. CONCLUSION: Our results describe how coordinators' mental health is affected by their daily work. Further research is needed to comprehensively examine these work-related stressors and to generate additional data to support the development of interventions to mitigate burnout and compassion fatigue among OTDCs.

Health literacy and the quality of pharmacist-patient communication among those prescribed anticoagulation therapy.

BACKGROUND: Adequate counseling from a pharmacist concerning anticoagulation therapy is crucial to the wellbeing of patients. No studies have fully examined the relationship between health literacy, patient-pharmacist communication, and anticoagulation control. OBJECTIVE(S): To evaluate the relationship between health literacy and the perceived quality of patient-pharmacist communication among those receiving anticoagulation therapy. METHODS: This investigation utilized structured telephone interviews to evaluate the relationship between health literacy and perceived quality patient-pharmacist communication among patients receiving anticoagulation therapy. Two hundred-twenty participants prescribed anticoagulation therapy continuously for at least 6-months served as the sample for this study. A previously validated one-item screening tool was utilized to estimate health literacy. The primary outcome was patients' perceptions regarding the general communication process with pharmacists, according to the Interpersonal Process of Care questionnaire. RESULTS: Patients possessing inadequate health literacy reported significantly less favorable ratings for the perceived quality of pharmacist communication on the domains of general clarity (p = 0.02), responsiveness to patient concerns (p=<0.01), empowerment (p = 0.01), and consideration of patients' desire and ability to comply with recommendations (p = 0.01). Inadequate health literacy was found to be independently associated with poorer quality interpersonal processes of care across the domains of responsiveness to patient concerns and empowerment, (ß = -0.207, P = <0.01 and ß = -0.137, P = 0.04, respectively). Patients with inadequate health literacy did not differ significantly from those with adequate health literacy in terms of time within therapeutic INR range or percent of INRs in therapeutic range over the previous 12 months. CONCLUSIONS: Patients receiving anticoagulation therapy and possessing inadequate health literacy appear more likely to percieve poorer communication with pharmacists. This seems especially true as it relates to the percieved time and attention pharmacist devote to the communication encounter, as well as the sense pharmacists provide patients concerning their ability to influence health outcomes.

Evaluation of medication reconciliation in an ambulatory setting before and after pharmacist intervention.

OBJECTIVES: To determine the accuracy of medication reconciliation in an internal medicine clinic and to evaluate pharmacist interventions targeted at improving the accuracy of medication reconciliation. DESIGN: Prospective case series. SETTING: Memphis, TN, from October 2007 to March 2008. PATIENTS: 180 adults attending an internal medicine appointment. INTERVENTION: On patient arrival, a nurse completed the medication reconciliation form. In Phase 1 of the study, a pharmacist randomly selected and reviewed a patient's medication reconciliation form, interviewed the patient, and verified information if indicated. A total of 90 forms were reviewed and compared to determine baseline medication reconciliation accuracy. Education interventions were held with the medical and nursing staff, targeting areas for improvement. In Phase 2 of the study, 90 additional medication reconciliation forms were reviewed in the same manner. Phase 1 and Phase 2 results were compared to evaluate differences in accuracy after the pharmacist's education interventions. MAIN OUTCOME MEASURES: Accuracy of medication reconciliation forms and number of potentially significant errors at baseline and after pharmacist interventions. RESULTS: In Phase 1, 14.4% of medication reconciliation forms were correct. The remaining forms contained 190 potentially significant errors. After the education interventions, 18.9% of medication reconciliation forms were correct and the others contained 139 potentially significant errors. CONCLUSION: Medication reconciliation accuracy is poor. Although education interventions showed a trend toward improvement, continued education training for staff and patients is needed in addition to other interventions to optimize this process and prevent medication errors.

Prevalence and correlates of pain in the Canadian National Palliative Care Survey.

BACKGROUND: Pain is a common problem for people with cancer who are nearing the ends of their lives. OBJECTIVE: In the present multicentre Canadian study of palliative cancer care, the prevalence of pain, its perceived severity and its correlates across a range of physical, social, psychological, and existential symptoms and concerns were examined. METHODS: Semistructured interviews were conducted with 381 patients. In addition to inquiring about pain, the interview also assessed 21 other symptoms and concerns, and collected information about demographic characteristics, functional status and medication use. RESULTS: Pain of any intensity was reported by 268 (70.3%) participants, although for 139 (36.5%), the severity was rated as minimal or mild. For 129 (33.9%) individuals, pain was reported as moderate to extreme, and considered by the respondents to be an important ongoing problem. Patients who reported moderate to extreme pain were younger than other participants, but had lower functional status and a shorter median survival duration. They were more likely than other participants to be treated with opioid medications (P<0.001) and, less reliably, with benzodiazepines (P=0.079). Compared with participants with no, minimal or mild pain, those with moderate to extreme pain had a higher prevalence of distressing problems on 11 of 21 other symptoms and concerns. The strongest correlations were with general malaise (rho = 0.44), suffering (rho = 0.40), nausea (rho = 0.34), weakness (rho = 0.31), drowsiness (rho = 0.29) and anxiety (rho = 0.29). CONCLUSIONS: Pain continues to be a difficult problem for many patients who are receiving palliative cancer care, particularly younger individuals who are nearing death.

Anti-Xa levels in bariatric surgery patients receiving prophylactic enoxaparin.

BACKGROUND: Limited data exist regarding efficacy and dosing of low-molecular-weight heparins, including enoxaparin, for morbidly obese patients. Prophylactic doses of 30 to 60 mg every 12 h have been described in bariatric surgery patients with appropriate anti-Xa levels reported between 0.18 and 0.6 units/mL. METHODS: Fifty-two laparoscopic gastric bypass or banding patients were enrolled. Patients were divided into two groups by the dose of enoxaparin that was given: Group 1--enoxaparin 30 mg every 12 hours--and Group 2--enoxaparin 40 mg every 12 h. Anti-Xa levels were obtained 4 h after the first and third doses. Levels between 0.18-0.44 units/mL were considered appropriate. RESULTS: There were 19 patients (74% female, mean body mass index [BMI] 48.4 kg/m2) in Group 1 and 33 patients (82% female, mean BMI 48.5 kg/m2) in Group 2. In Group 1, anti-Xa levels were 0.06 and 0.08 units/mL after the first and third doses, respectively. In Group 2, anti-Xa levels were 0.14 and 0.15 units/mL after first and third doses, respectively (p = NS). There was a statistically significant difference in anti-Xa levels between Group 1 first dose and Group 2 first dose (p < 0.05) and between Group 1 third dose and Group 2 third dose (p < 0.05). Percentage of appropriate anti-Xa levels at first dose differed 0% vs. 30.8% (Group 1 vs. Group 2; p = 0.01) and at third dose 9.1% vs. 41.7% (Group 1 vs. Group 2; p = 0.155). CONCLUSION: When prophylactic dose enoxaparin of 30 mg every 12 h was changed to 40 mg every 12 h in bariatric surgery patients, anti-Xa levels significantly increased with prophylactic dose enoxaparin in bariatric surgery patients. The percentage of appropriate levels also increased; however, more than half of the patients receiving 40 mg every 12 hours failed to reach therapeutic levels. No levels were supratherapeutic. Dosage of 40 mg every 12 h may not be sufficient for bariatric surgery patients.

Vitamin K-independent warfarin resistance after concurrent administration of warfarin and continuous enteral nutrition.

STUDY OBJECTIVE: To assess the influence of withholding continuous enteral nutrition for 1 hour before and after warfarin administration compared with the coadministration of warfarin with continuous enteral nutrition on changes in international normalized ratios (INRs). DESIGN: Retrospective, crossover case series. SETTING: Intensive care units of a university-affiliated medical center. PATIENTS: Six adults who required nutritional support for at least the first 10 consecutive days of warfarin therapy; during that 10-day period, they had a period of at least 3 consecutive days during which the enteral feeding was withheld for 1 hour before and after warfarin administration, and had a period of at least 3 consecutive days when feedings were not withheld during warfarin administration. Patients with advanced liver disease and those who received therapies, during the observation period, that significantly alter warfarin metabolism were omitted from the study. MEASUREMENTS AND MAIN RESULTS: The change in INR during the 3-day observation period when feedings were withheld for 1 hour before and after warfarin administration was significantly different versus the change in INR during coadministration of warfarin with continuous feeding (mean +/- SD 0.74 +/- 0.66 vs -0.13 +/- 0.81, p < or = 0.05). This difference in INR response occurred despite the administration of similar dosages of warfarin (5.6 +/- 2.1 vs 5.7 +/- 2.1 mg/day, p>0.05). Also noted was a clinically irrelevant, but statistically significant, difference in vitamin K intake between treatment periods (77 +/- 36 mug/day when feedings were withheld vs 102 +/- 28 microg/day when feedings were not withheld, p < or = 0.05). CONCLUSION: Continuous enteral nutrition should be withheld for 1 hour before and after warfarin administration to prevent enteral nutrition-associated warfarin resistance.

Comparison of two low-molecular-weight heparin dosing regimens for patients undergoing laparoscopic bariatric surgery.

BACKGROUND: Venous thromboembolic events (VTE) are a morbidity and mortality concern for patients undergoing laparoscopic bariatric surgery. Although VTE prophylaxis is recommended in bariatric surgery, data with regard to monitoring and appropriate dosing of low-molecular-weight heparin are limited. Enoxaparin prophylactic doses ranging from 30 to 60 mg every 12 h have been used for this population. The authors hypothesized that higher prophylactic enoxaparin doses (60 mg) would yield more appropriate heparin antifactor Xa (anti-Xa) concentrations than the 40-mg dosage for bariatric surgery patients. METHODS: Patients undergoing laparoscopic bariatric surgery by two surgeons during a 5-month period at one institution received enoxaprin 40 or 60 mg every 12 h. Anti-Xa levels were obtained 4 h after the first and third doses. Therapeutic levels were defined as 0.18 to 0.44 U/ml. Paired and unpaired t-tests and chi-square tests were used for statistical analysis as appropriate. RESULTS: The first-dose mean anti-Xa concentration was 0.173 U/ml in the 40-mg group and 0.261 U/ml in the 60-mg group (p < 0.005), compared with the third-dose mean anti-Xa levels of 0.21 and 0.43 U/ml, respectively (p < 0.001). After the third dose of enoxaparin, the percentage of patients with anti-Xa concentrations who remained subtherapeutic showed a statistically significant difference: 44% in the 40-mg group versus 0% in the 60-mg group (p = 0.02). However, no supratherapeutic anti-Xa concentrations were observed in the 40-mg group, whereas 57% of the third-dose levels in the 60-mg group were supratheraputic. The highest anti-Xa level was 0.54 U/ml, but none of the patients with this level experienced bleeding events. CONCLUSIONS: Enoxaparin 60-mg every 12 h was superior to a dosage of 40 mg every 12 h in achieving therapeutic anti-Xa concentrations and avoiding subtherapeutic anti-Xa levels. However, the 60-mg group had a number of supratherapeutic levels. Future studies evaluating the relationship of anti-Xa concentrations and outcomes with larger numbers of morbidly obese patients are needed.

Desire for euthanasia or physician-assisted suicide in palliative cancer care.

OBJECTIVE: To investigate the attitudes of terminally ill individuals toward the legalization of euthanasia or physician-assisted suicide (PAS) and to identify those who would personally desire such a death. DESIGN: In the Canadian National Palliative Care Survey, semistructured interviews were administered to 379 patients who were receiving palliative care for cancer. Patients who expressed a desire for physician-hastened death were followed prospectively. MAIN OUTCOME MEASURES: Attitudes toward the legalization of euthanasia or PAS were determined, as was the personal interest in receiving a hastened death. Demographic and clinical characteristics were also recorded, including a 22-item structured interview of symptoms and concerns. RESULTS: There were 238 participants (62.8%) who believed that euthanasia and/or PAS should be legalized, and 151 (39.8%) who would consider making a future request for a physician-hastened death. However, only 22 (5.8%) reported that, if legally permissible, they would initiate such a request right away, in their current situations. This desire for hastened death was associated with lower religiosity (p=.010), reduced functional status (p=.024), a diagnosis of major depression (p<.001), and greater distress on 12 of 22 individual symptoms and concerns (p<.025). In follow-up interviews with 17 participants, 2 (11.8%) showed instability in their expressed desire. CONCLUSION: Among patients receiving palliative care for cancer, the desire to receive euthanasia or PAS is associated with religious beliefs; functional status; and physical, social, and psychological symptoms and concerns. Although this desire is sometimes transitory, once firmly established, it can be enduring.

Depression and anxiety disorders in palliative cancer care.

Depression and anxiety disorders are thought to be common in palliative cancer care, but there is inconsistent evidence regarding their relevance for other aspects of quality of life. In the Canadian National Palliative Care Survey, semi-structured interviews assessing depression and anxiety disorders were administered to 381 patients who were receiving palliative care for cancer. There were 212 women and 169 men, with a median survival of 63 days. We found that 93 participants (24.4%, 95% confidence interval=20.2-29.0) fulfilled Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition diagnostic criteria for at least one anxiety or depressive disorder (20.7% prevalence of depressive disorders, 13.9% prevalence of anxiety disorders). The most frequent individual diagnosis was major depression (13.1%, 95% confidence interval=9.9-16.9). Comorbidity was common, with 10.2% of participants meeting criteria for more than one disorder. Those diagnosed with a disorder were significantly younger than other participants (P=0.002). They also had lower performance status (P=0.017), smaller social networks (P=0.008), and less participation in organized religious services (P=0.007). In addition, they reported more severe distress on 14 of 18 physical symptoms, social concerns, and existential issues. Of those with a disorder, 39.8% were being treated with antidepressant medication, and 66.7% had been prescribed a benzodiazepine. In conclusion, it appears that depression and anxiety disorders are indeed common among patients receiving palliative care. These disorders contribute to a greatly diminished quality of life among people who are dying of cancer.

Increased unfractionated heparin requirements with decreasing body mass index in pregnancy.

BACKGROUND: Pregnant women receiving low-molecular-weight heparin for therapeutic anticoagulation are often converted to unfractionated heparin in anticipation of labor. We aim to characterize the impact of maternal body mass index on attainment of target anticoagulation during the conversion process. METHODS: We conducted a five-year retrospective study of a pregnancy cohort converted from low-molecular-weight heparin to unfractionated heparin in the third trimester. Patient demographics, anticoagulation regimens, and clinical outcomes were extracted from the medical record. Nonparametric statistical methods were used for analysis by body mass index (<30, 30-35, and >35). RESULTS: Thirty-one subjects were evenly distributed by body mass index (p = 0.97). Linear regression revealed an inverse correlation between patient body mass index and unfractionated heparin dose needed to achieve therapeutic anticoagulation (p = 0.04). Subjects with body mass index > 35 attained therapeutic activated partial thromboplastin time levels at 18 U (Units)/kg/h, while subjects with body mass index < 30 required 25 U/kg/h (p = 0.02). CONCLUSION: Higher doses of unfractionated heparin are needed to achieve anticoagulation in patients with body mass index < 30 during pregnancy. This paradoxical relationship may be explained by physiologic characteristics that increase unfractionated heparin elimination, including diminished adiposity and increased renal clearance.

The Utility of the Candida Score in Patients With Sepsis.

BACKGROUND: Candida is a leading cause of infection in the intensive care unit. Colonization versus infection remains a challenge. A Candida Score (CS) of 3 or greater has been used to target antifungal therapy in surgical patients at risk of candidemia but has not been well evaluated in medical patients with sepsis. OBJECTIVES: The aim of this study was to assess utility of the CS in detecting candidemia early in patients with sepsis. METHODS: This was a secondary analysis of patients with sepsis (n = 77) who were followed up for development of new infections. Patients with known fungal infection at admission were excluded. Candida colonization was defined as Candida cultured from any baseline culture, except blood, as a part of routine clinical care. RESULTS: Candidemia was detected in 8 of 77 participants (10.4%; 4 [15.4%] with a CS ≥3 and 4 [7.8%] with a CS <3). Demographic variables (age, race, sex) were similar among those who did and did not develop candidemia. Using the recommended CS of 3 or greater, sensitivity was (4/8) 50%, specificity was (47/69) 68.1%, positive predictive value was (4/26) 15.4%, and negative predictive value was (47/51) 92.2%. Baseline colonization was significantly higher among those who developed candidemia (50% vs 11.6%; P = .02), but no significant differences were observed among CS components or total scores. CONCLUSIONS: Despite a relatively poor sensitivity, a reasonable specificity with a strong negative predictive value makes this tool a viable option for screening medically ill patients who may require antifungal agents. The CS should be evaluated in a larger, more inclusive, medical population.

Mental disorders and the desire for death in patients receiving palliative care for cancer.

OBJECTIVES: The desire for death in terminally ill patients is associated with depression and anxiety, but not all patients who report it meet criteria for mental disorders. We examined the characteristics of subgroups of palliative cancer patients who expressed a desire for death that occurred either with or without a concurrent depressive or anxiety disorder. DESIGN: Cross-sectional survey. SETTING: Eight Canadian palliative care programs. PARTICIPANTS: 377 patients with cancer. MAIN OUTCOME MEASURES: Desire for Death Rating Scale; Structured Interview of Symptoms and Concerns. RESULTS: Most participants (69.5%) had no desire for death. Of the remainder, 69 (18.3%) acknowledged occasional transient thoughts, and 46 (12.2%) reported an apparently genuine desire to die. In the latter group, 24 individuals (52.2%) were diagnosed with a mental disorder and 22 (44.8%) were not. Individuals with no serious desire for death and no mental disorder reported the least distress in physical, social, existential, and psychological symptoms and concerns; those with a mental disorder and a significant desire for death reported the most. The subgroup of patients with a serious desire for death but no concurrent mental disorders still reported increased distress due to physical symptoms and social concerns, as well as a higher prevalence of global suffering. CONCLUSIONS: The expression of a desire for death by a terminally ill patient should raise a suspicion about mental health problems, but is not in itself clearly indicative of one. Nevertheless, it may serve as a catalyst to review the individual's physical symptom management and interpersonal concerns, and overall sense of suffering.