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To determine whether the place of death for patients with cancer is associated with patients' quality of life (QoL) at the end of life (EOL) and psychiatric disorders in bereaved caregivers.
Prospective, longitudinal, multisite study of patients with advanced cancer and their caregivers (n = 342 dyads). Patients were followed from enrollment to death, a median of 4.5 months later. Patients' QoL at the EOL was assessed by caregiver report within 2 weeks of death. Bereaved caregivers' mental health was assessed at baseline and 6 months after loss with the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, and the Prolonged Grief Disorder interview.
In adjusted analyses, patients with cancer who died in an intensive care unit (ICU) or hospital experienced more physical and emotional distress and worse QoL at the EOL (all P ≤ .03), compared with patients who died at home with hospice. ICU deaths were associated with a heightened risk for posttraumatic stress disorder, compared with home hospice deaths (21.1% [four of 19] v 4.4% [six of 137]; adjusted odds ratio [AOR], 5.00; 95% CI, 1.26 to 19.91; P = .02), after adjustment for caregivers' preexisting psychiatric illnesses. Similarly, hospital deaths were associated with a heightened risk for prolonged grief disorder (21.6% [eight of 37] v 5.2% [four of 77], AOR, 8.83; 95% CI, 1.51 to 51.77; P = .02), compared with home hospice deaths.
Patients with cancer who die in a hospital or ICU have worse QoL compared with those who die at home, and their bereaved caregivers are at increased risk for developing psychiatric illness. Interventions aimed at decreasing terminal hospitalizations or increasing hospice utilization may enhance patients' QoL at the EOL and minimize bereavement-related distress.
Patients with advanced cancer are receiving increasingly aggressive care at the end of life (EOL).1–5 Although most patients with cancer prefer to die at home,6 36% die in a hospital and 8% die in an intensive care unit (ICU).7,8 Nearly 25% of Medicare expenditures are spent on intensive care in the final month of life,9–11 despite limited evidence of improved patient outcomes.12 A few studies have found that hospice care is associated with better patient quality of life (QoL) at the EOL13,14 and lower rates of major depressive disorder among bereaved caregivers.15 Research is needed, however, to examine prospectively whether patients' place of death is associated with QoL at the EOL and caregivers' bereavement adjustment.
In 1995, SUPPORT (the Study to Understand Prognoses and Preferences for Risks and Outcomes of Treatment) found that 50% of hospitalized patients experienced moderate to severe pain at the EOL.16 Another study found that 55% to 75% of patients with cancer in an ICU reported moderate to severe pain, discomfort, or anxiety, despite the routine integration of palliative care services.17 Other research suggests that family members of critically ill patients experience greater psychological distress relative to the general population, including anxiety, depression, posttraumatic stress, and prolonged grief.18–20
To date, only one study has used the Structured Clinical Interview for the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (SCID), a sensitive and specific tool for diagnosing psychiatric illness, to examine bereaved family members' mental health.21 This study did not measure posttraumatic stress disorder (PTSD), however, and could not account for caregivers' preexisting psychiatric illnesses as a result of its cross-sectional design.
The first aim of this prospective, longitudinal, cohort study was to examine associations between the place of death of patients with cancer and their QoL at the EOL. We hypothesized that ICU deaths would be associated with worse QoL compared with hospital or home deaths. Our second aim was to examine associations between patients' place of death and their bereaved caregivers' risk of developing psychiatric illnesses. We hypothesized that caregivers of patients who die in an ICU would witness more trauma (ie, events “involving death, injury, or a threat to the personal integrity of another person” evoking feelings of “intense fear, helplessness or horror,” Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, criterion A1 and A2 for PTSD) than caregivers of patients who died elsewhere as a result of the often frightening nature of aggressive, life-prolonging care, which would heighten the risk for onset of PTSD after an ICU death.22
Coping with Cancer was a prospective, longitudinal, multisite psychiatric epidemiologic study of terminally ill patients with cancer and their informal caregivers designed to determine the rates, causes, and consequences of psychiatric illness in terminally ill patients with cancer and their bereaved caregivers.13
Patients were recruited from September 2002 to August 2008 from seven outpatient sites: Yale Cancer Center, the West Haven Veterans' Affairs Connecticut Comprehensive Cancer Clinic, Parkland Hospital, Simmons Comprehensive Cancer Center, Memorial Sloan-Kettering Cancer Center, Dana-Farber/Partners Cancer Center, and New Hampshire Oncology-Hematology. The institutional review boards of participating sites approved all study procedures.
Eligibility criteria included diagnosis of advanced cancer (distant metastases and disease refractory to first-line chemotherapy), age at least 20 years, presence of an informal caregiver, and clinic staff/interviewer assessment that the patient had adequate stamina to complete the interview. Patient–caregiver dyads in which either the patient or caregiver refused to participate, met criteria for dementia or delirium (by neuro-behavioral cognitive status examination), or did not speak English or Spanish were excluded.
Of 993 eligible patients, 718 (72.3%) enrolled. Sociodemographic characteristics of participants and nonparticipants did not differ, except that participants were more likely to be Hispanic (12.1% v 5.8%; P = .005). For this analysis assessing place of death, we restricted our sample to patients who died by August 2008 (n = 414). We excluded patients who died in miscellaneous other settings (ie, nursing homes, inpatient hospices, in transit, other, or unknown; total n = 72) because numbers were too small for analyses, or who had missing data on more than seven variables (n = 9). As expected, deceased patients had worse performance status and were more often younger, nonwhite, unmarried, less well educated, and uninsured than the full cohort (all P ≤ .05). At follow-up 6 months after loss, 93 bereaved caregivers could not be reached; these subjects did not differ significantly from assessed bereaved caregivers on baseline mental health measures or sociodemographic characteristics, except they were more likely to be nonwhite (35.8% v 21.4%; P = .004). All participants provided written informed consent.
Patients and caregivers were interviewed at baseline in English or Spanish and received a $25 payment. A chart review was performed at enrollment and after death. Within 2 weeks of death, a postmortem questionnaire was administered to the caregiver most closely involved in the patient's care during the last week of life. The caregiver assessed at baseline was interviewed again 6 months after loss. This time point was chosen so caregivers would likely be beyond a state of acute grief,23 but close enough to the death to avoid recall bias.
During the postmortem interview, caregivers were asked about patients' QoL at the EOL: “In your opinion, how would you rate the overall quality of the patients' last week of life?”13; caregivers responded to a Likert scale from 0 (“worst possible”) to 10 (“best possible”). Caregivers also rated the level of physical and psychological distress separately. Patients' QoL has been previously correlated with the validated Quality of Dying and Death scale24 and bereaved caregivers' QoL, self-reported health, and physical functioning 6 months after loss.13
The SCID, a sensitive and specific tool for diagnosing psychiatric illness, was used at baseline and 6 months after loss to assess whether caregivers met established criteria for psychiatric disorders.22,25 The validated Prolonged Grief Disorder (PGD) scale assessed caregivers' preloss grief and identified caregivers with intense, disabling grief 6 months after loss.26
The patients' place of death (ICU, hospital, home with hospice, or home without hospice) was determined through chart review and caregiver interviews. Patients who died at home with hospice services were analyzed separately from patients who died at home without hospice because hospice is associated with better patient QoL at EOL and less depression in bereaved caregivers.13–15
Patient and caregiver factors found in the literature to be associated with site of death, EOL medical care, and caregivers' bereavement adjustment13–21,26–44 were examined as potential confounders. These include the following:
Patients and caregivers reported their sex, age, race/ethnicity, marital status, household size, insurance status, and education.
Patients' cancer type, Karnofsky score,30 Charlson Comorbidity Index,31 and medical care was documented at baseline with input from the treating physician. Patient QoL was assessed with the McGill Quality of Life Index.32
Patients were asked to “describe your current health status” with response options of “relatively healthy,” “seriously ill but not terminally ill,” or “seriously and terminally ill.” Patients responding “seriously and terminally ill” were coded as “understands illness is terminal.” This measure is associated with higher rates of do-not-resuscitate orders and hospice use.33
Patients' preferences for life-extending care were examined with a previously validated measure34–36: “If you could choose, would you prefer: (1) treatment that focused on extending life as much as possible, even if it meant more pain and discomfort, or (2) care that focused on relieving pain and discomfort as much as possible, even if that meant not living as long?”
The validated Brief Religious Coping Scale (RCOPE) was used to identify patients who use positive religious coping (eg, “seeking God's love and care”) to cope with their cancer diagnosis because this is associated with more intensive care near death.37
At baseline, patients were asked (yes/no), “Have you and your doctor discussed any particular wishes you have about the care you would want to receive if you were dying?” A close doctor–patient relationship was defined as one where patients trusted and respected their doctor, felt respected and “seen as a whole person,” and were very comfortable asking questions about their care.38 Patients were also asked if they had a do-not-resuscitate order.
Caregivers' baseline QoL was assessed with a single-item summary measure of the Medical Outcomes Study Short-Form Health Survey, including all eight subscales.39 The Index of Activities of Daily Living measured caregivers' functional status.40
The Caregiving Burden Scale and Covinsky Family Impact Survey assessed caregivers' burden and satisfaction.41,42 The Stressful Caregiving Response to Experiences of Dying scale examined caregivers' exposure to traumatic experiences (eg, witnessing severe pain/discomfort).43 The Interpersonal Support Evaluation List assessed caregivers' social support.44
t tests, analysis of variance, χ2, and Fisher's exact test statistics were used, as appropriate, to identify confounders (ie, patient/caregiver characteristics associated with both the predictor [place of death] and outcomes [patients' QoL at the EOL or caregivers' mental health]). A log-rank test was used to determine whether the groups differed significantly in survival.
Analysis of covariance models were used to examine relationships between patients' place of death and (1) QoL at the EOL and (2) physical/emotional distress. For each model, every variable associated (P < .20) with patients' place of death was entered and retained if significant (P < .05) while controlling for other confounders.
Multivariable logistic regression models examined associations between caregivers' psychiatric illnesses at baseline and 6 months after loss. Next, multivariable logistic regression models estimated the effect of patients' place of death on bereaved caregivers' mental health, adjusting for caregivers' baseline psychiatric illnesses and significant confounders, using home death with hospice services as a reference. Firth's penalized maximum likelihood estimation method was used to minimize bias in parameter estimates because the outcomes were rare in some instances. Statistical analyses were performed with SAS version 9.2 (SAS Institute, Cary, NC).
The cohort consisted of 333 patients with advanced cancer who died a median of 4.5 months after enrollment. Patients' baseline sociodemographic, clinical, and psychosocial characteristics are presented in Table 1. In this study, 58.6% of patients died at home with hospice services, 7.5% died at home without hospice services, 25.5% died in a hospital, and 8.4% died in an ICU.
In unadjusted analyses, patients who died in an ICU were often younger with fewer comorbidities, compared with patients who died elsewhere, and more likely to prefer life-extending therapies (all P ≤ .03). They were also less likely to have had an EOL discussion with a physician compared with patients who died elsewhere (P = .0002). There was no difference in patients' survival by location of death.
As shown in Table 2, 55.4% of caregivers were spouses, 23.3% were adult children, and 21.2% were other relatives/friends. At baseline, caregivers of patients who died in an ICU reported fewer traumatic experiences compared with caregivers (P ≤ .02) of patients who died elsewhere.
In adjusted analyses, patients who died in an ICU or hospital had worse QoL and more physical and emotional distress at the EOL compared with patients who died at home with hospice services (Fig 1). Mean QoL scores were lowest among patients who died in an ICU (5.0) or hospital (5.3) and highest among patients who died at home with hospice services (6.6) or without hospice (7.3; overall F = 4.87; df = 3; P = .003), after adjusting for significant confounds.
In adjusted analyses, patients who died in ICUs also had lower mean physical comfort scores (3.6) than patients who died in hospitals (4.7), home without hospice (5.9), or home with hospice (6.6; overall F = 8.86; df = 3; P < .0001). Similarly, patients dying in ICUs and hospitals had lower psychological well-being scores (both 6.0) than patients dying at home with (7.0) or without (8.0) hospice (overall F = 3.27; df = 3; P = .02).
As shown in Table 3, caregivers' preexisting psychiatric morbidity was a significant predictor of psychiatric illness during bereavement. For example, caregivers with panic disorder at baseline had higher odds of panic disorder (odds ratio, 15.31; 95% CI, 3.24 to 72.33) during bereavement than caregivers without this disorder at baseline.
ICU and hospital deaths were associated with more psychiatric illness in bereaved caregivers compared with home hospice deaths, even after adjusting for caregivers' baseline mental health (Table 4). Bereaved caregivers of patients who died in ICUs had a heightened risk of developing PTSD compared with caregivers of patients who died at home with hospice (21.1% [four of 19] v 4.4% [six of 137]; adjusted odds ratio, 5.00; 95% CI, 1.26 to 19.91; P = .02, adjusted for preloss PTSD). Caregivers of patients who died in the hospital had higher odds of meeting criteria for PGD (21.6% [eight of 37] v 5.2% [four of 77]; adjusted odds ratio, 8.83; 95% CI, 1.51 to 51.77; P = .02, adjusted for preloss grief) compared with caregivers of patients who died with home hospice.
Our results suggest that patients with advanced cancer who die in a hospital or ICU have worse QOL and their bereaved caregivers are at increased risk for developing psychiatric illness compared with those who died at home with hospice services. Specifically, bereaved caregivers of patients who die in the ICU had higher odds of developing PTSD and caregivers of patients who died in a hospital were at heightened risk of developing PGD compared with caregivers of patients who died at home with hospice, even after adjustment for caregivers' preexisting psychiatric illnesses.
Few studies have prospectively examined whether patients' EOL experiences differ by their place of death. In a retrospective, cross-sectional study of bereaved family members, patients who died at home with hospice services had fewer unmet needs at the EOL.14 Others have questioned the importance of dying at home, suggesting that physicians may romanticize the experience.45
This study provides evidence that patients with cancer who die at home have better QoL at the EOL than patients who die in hospitals. Surprisingly, patients who received hospice services did not have significantly better QoL than patients who died at home without hospice. This may be because patients who died at home without hospice were a particularly well-adjusted group who either did not need additional services, had more family support, and/or received services we did not assess. Future research is needed to determine why home deaths result in better QoL for patients, but we expect that it may be due to differences in the focus of care provided. Hospital—and especially ICU—care often focuses on keeping patients alive at all costs, whereas home deaths may emphasize patients' QoL and symptom management.
To our knowledge, this is the first study to show that caregivers of patients who die in ICUs are at a heightened risk for developing PTSD. Prior studies have measured caregivers' psychiatric symptoms18–20 or examined other diagnosable psychiatric illnesses cross-sectionally.21 In this study we used the well-validated SCID to determine whether caregivers met clinical criteria for psychiatric illness at baseline and 6 months after loss to better isolate the caregiver's risk of developing psychiatric illness as a result of the patients' place of death. Our finding that bereaved caregivers of critically ill patients have higher odds of developing PTSD suggests that caregivers' ICU experiences may prove traumatic for them. Future research is needed to specifically identify which experiences lead to caregiver PTSD and interventions to mitigate these traumatic exposures.
Our finding that caregivers of patients who died in the hospital had increased odds of developing PGD was initially surprising because emotional dependency is the best established risk factor for this disorder.46–50 It may be that attached caregivers cannot accept the patient's impending death and attempt to care for them at home until a medical crisis precipitates a terminal hospitalization.
There are several limitations to this study. This observational study could not randomly assign terminally ill patients with cancer to die in different locations for ethical and logistical reasons. Many patient and caregiver characteristics that influence patients' location of death or caregivers' bereavement were assessed, but other confounding influences may not have been measured. For example, we had insufficient information about patients' clinical status near death and could not directly examine how patients' clinical course (eg, gradual v precipitous decline) influenced their place of death. Future research is needed to disentangle how patients' disease trajectory influences their QoL at the EOL, place of death, and caregivers' bereavement adjustment. In addition, some bereaved caregivers could not be reached for interviews 6 months after loss, and preloss grief and PGD were only assessed in a subset of caregivers because the PG-13 scale underwent revision during the study to match evolving diagnostic criteria. In addition, we may have been underpowered to detect some associations because the sample sizes were small and the rates of psychiatric disorders in bereaved caregivers were low. Finally, our measures of patients' QoL were obtained from caregivers and therefore may not accurately capture patients' true levels of distress at the EOL. In the baseline interview, however, patient/caregiver assessments of patients' QoL were significantly correlated (P < .0001), and more than 35% of patients were confused or unconscious at the EOL, suggesting that a patient measure might have been biased because only 65% of the sample could have participated.51
Despite these limitations, our study has many strengths. First, we assessed caregivers most closely involved in the patients' care within 2 weeks of death, whereas other studies have relied on bereaved caregivers' recall of patients' experiences 3 to 15 months after loss, which may result in more accurate recall. Second, we assessed caregivers' mental health with the SCID and PGD scale both at baseline and 6 months after loss, thereby enabling us to better isolate the effects of place of death on changes in mental health.
Our study demonstrates that patients with advanced cancer who die in a hospital or ICU have worse QoL at the EOL and their caregivers have higher odds of developing bereavement-related psychiatric illnesses compared with those who die at home with hospice. These findings are important because patients with advanced cancer are receiving increasingly aggressive care at the EOL.1–5 Interventions aimed at reducing terminal hospitalizations or increasing the utilization of hospice services may improve the QoL of patients with advanced cancer at the EOL and reduce the risk of psychiatric illness in bereaved caregivers.
Supported in part by the following grants to H.G.P.: Grant No. MH63892 from the National Institute of Mental Health and Grant No. CA 106370 from the National Cancer Institute. Support for A.A.W. was also provided by 5R25CA092203 from the National Cancer Institute, the ASCO Cancer Foundation Young Investigator Award, funded by Susan G. Komen for the Cure, the National Palliative Care Research Center, and the Dana-Farber Cancer Institute Center for Psycho-Oncology and Palliative Care Research.
Any opinions, findings, conclusions, or recommendations expressed in this material are those of the author(s) and do not necessarily reflect those of the American Society of Clinical Oncology (ASCO) and The ASCO Cancer Foundation. The funding institutions did not have any role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; or preparation, review, or approval of the manuscript.
Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.
The author(s) indicated no potential conflicts of interest.
Conception and design: Alexi A. Wright, Holly G. Prigerson
Financial support: Holly G. Prigerson
Administrative support: Holly G. Prigerson
Provision of study materials or patients: Holly G. Prigerson
Collection and assembly of data: Holly G. Prigerson
Data analysis and interpretation: Alexi A. Wright, Nancy L. Keating, Tracy A. Balboni, Ursula A. Matulonis, Susan D. Block, Holly G. Prigerson
Manuscript writing: Alexi A. Wright, Nancy L. Keating, Tracy A. Balboni, Ursula A. Matulonis, Susan D. Block, Holly G. Prigerson
Final approval of manuscript: Alexi A. Wright, Nancy L. Keating, Tracy A. Balboni, Ursula A. Matulonis, Susan D. Block, Holly G. Prigerson