# Incidence and risk factors of prolonged grief in relatives of patients with terminal cancer in French palliative care units: The Fami-Life multicenter cohort study

Maité Garrouste-Orgeas, Véronique Marché, Nicolas Pujol, Dominique Michel, Adrien Evin, Virginie Fossez-Diaz, Ségolène Perruchio, Anne Vanbésien, Catherine Verlaine, Laure Copel, et al.

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Maité Garrouste-Orgeas, Véronique Marché, Nicolas Pujol, Dominique Michel, Adrien Evin, et al. Incidence and risk factors of prolonged grief in relatives of patients with terminal cancer in French palliative care units: The Fami-Life multicenter cohort study. Palliative and Supportive Care, 2023, pp.1-10. 10.1017/S1478951523000111. hal-04658460

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Original Article

**Cite this article:** Garrouste-Orgeas M et al. (2024) Incidence and risk factors of prolonged grief in relatives of patients with terminal cancer in French palliative care units: The Fami-Life multicenter cohort study. *Palliative and Supportive Care* **22**(5), 961–970. https://doi.org/10.1017/S1478951523000111

Received: 24 July 2022
Revised: 26 November 2022
Accepted: 13 January 2023

**Keywords:**
Grief; Palliative medicine; Family; Stress disorders; Anxiety; Depression

**Author for correspondence:**
Maïté Garrouste-Orgeas, Service de médecine interne, Hôpital Franco Britannique, 4 rue Kléber, Levallois-Perret 92 300, France.
Email: maite.garrouste@cognac-jay.fr

Incidence and risk factors of prolonged grief
in relatives of patients with terminal cancer
in French palliative care units: The Fami-Life
multicenter cohort study

Maité Garrouste-Orgeas, m.D.<sup>1,2,3 ID</sup>, Véronique Marché, m.D.<sup>4</sup>, Nicolas Pujol, Ph.D.<sup>5</sup>, Dominique Michel, m.D.<sup>2</sup>, Adrien Evin, m.D.<sup>6</sup>, Virginie Fossez-Diaz, m.D.<sup>7</sup>, Ségolène Perruchio, m.D.<sup>8</sup>, Anne Vanbésien, m.D.<sup>9</sup>, Catherine Verlaine, m.D.<sup>10</sup>, Laure Copel, m.D.<sup>11</sup>, Willeme Kaczmarek, m.D.<sup>12</sup>, Laurence Birkui de Francqueville, m.D.<sup>13</sup>, Véronique Michonneau-Gandon, m.D.<sup>14</sup>, Emmanuel de Larivière, m.D.<sup>15</sup>, Cécile Poupardin, m.D.<sup>16</sup>, Licia Touzet, m.D.<sup>17</sup>, Virginie Guastella, m.D.<sup>18</sup>, Carmen Mathias, m.D.<sup>19</sup>, Alaa Mhalla, m.D., Ph.D.<sup>20</sup>, Guillaume Bouquet, m.D.<sup>21 ID</sup>, Bruno Richard, m.D., Ph.D.<sup>22</sup>, Dominique Gracia, m.D.<sup>23</sup>, Florent Bienfait, m.D.<sup>24</sup>, Virginie Verliac, m.D.<sup>25</sup>, Gaelle Ranchou, m.D.<sup>26</sup>, Sylvie Kirsch, m.Sc.<sup>27</sup>, Cécile Flahault, Ph.D.<sup>28</sup>, Ambre Loiodice, m.Sc.<sup>29</sup>, Sébastien Bailly, PhARM.D., Ph.D.<sup>30</sup>, Stéphane Ruckly, m.Sc.<sup>29</sup> and Jean-François Timsit, m.D., Ph.D.<sup>1,31</sup>

¹IAME, INSERM, Université de Paris, Paris, France; ²Palliative Care Unit, Reuilly Diaconesses Fondation, Rueil Malmaison, France; ³Medical Unit, French British Hospital, Levallois-Perret, France; ⁴Palliative Care Unit, Cognac-Jay Hospital, Paris, France; ⁵Research Department Palliative Care Unit, Jeanne Garnier Institution, Paris, France; ⁶Palliative Care Unit, University Teaching Hospital, Nantes, France; ⁷Palliative Care Unit, Bretonneau Hospital, Paris, France; ⁸Palliative Care unit, Rives de Seine Hospital, Puteaux, France; ⁹Palliative Care Unit, General Hospital, Douai, France; ¹⁰Palliative Care Unit, General Hospital, Troyes, France; ¹¹Palliative Care Unit, Diaconesses Croix Saint Simon Hospital, Paris, France; ¹²Palliative Care Unit, La Dracénie Hospital, Draguignan, France; ¹³Palliative Care Unit, Compiègne Noyon Hospital, Compiègne, France; ¹⁴Palliative Care unit, Castres-Mazamet General Hospital, Castres, France; ¹⁵Palliative Care Unit, Marie Galène Institution, Bordeaux Caudéran, France; ¹⁶Palliative Care Unit, General Hospital, Montfermeil, France; ¹⁷Palliative Care Unit, University Teaching Hospital, Lille, France; ¹⁸Palliative Care Unit, University Teaching Hospital, Clermont Ferrand, France; ¹⁹Palliative Care Unit, Mulhouse Sud Alsace Hospital Network, Mulhouse, France; ²⁰Palliative Care Unit, Albert Chenevier Hospital, Créteil, France; ²¹Palliative Care Unit, Tourcoing General Hospital, Tourcoing, France; ²²Palliative Care Unit, University Teaching Hospital, Montpellier, France; ²³Palliative Care Unit, General Hospital, Salon-de-Provence, France; ²⁴Palliative Care Unit, University Teaching Hospital, Angers, France; ²⁵Palliative Care Unit, Saintonge General Hospital, Saintes, France; ²⁶Palliative Care Unit, General Hospital, Périgueux, France; ²⁷Palliative Care Unit, Bligny Hospital, Briis-Sous-Forges, France; ²⁸Laboratory of Psychopathology and Health Process, Paris University Paris, Boulogne-Billancourt, France; ²⁹Biostatistical Department, ICURESEARCH, Paris, France; ³⁰INSERM HP2, Grenoble Alpes University, Grenoble, France and ³¹Medical and infectious diseases ICU (MI2), APHP Bichat Hospital, Paris, France

Abstract

**Objectives.** Psychological consequences of grief among relatives are insufficiently known. We reported incidence of prolonged grief among relatives of deceased patients with cancer.

**Methods.** Prospective cohort study of 611 relatives of 531 patients with cancer hospitalized for more than 72 hours and who died in 26 palliative care units was conducted. The primary outcome was prolonged grief in relatives 6 months after patient death, measured with the Inventory Complicated Grief (ICG > 25, range 0–76, a higher score indicates more severe symptoms) score. Secondary outcomes in relatives 6 months after patient death were anxiety and depression symptoms based on Hospital Anxiety and Depression Scale (HADS) score (range 0 [best]–42 [worst]), higher scores indicate more severe symptoms, minimally important difference 2.5. Post-traumatic stress disorder symptoms were defined by an Impact Event Scale-Revised score >22 (range 0–88, a higher score indicates more severe symptoms).

**Results.** Among 611 included relatives, 608 (99.5%) completed the trial. At 6 months, significant ICG scores were reported by 32.7% relatives (199/608, 95% CI, 29.0–36.4). The median (interquartile range ICG score) was 20.0 (11.5–29.0). The incidence of HADS symptoms was

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87.5% (95% CI, 84.8–90.2%) at Days 3–5 and 68.7% (95% CI, 65.0–72.4) 6 months after patient's death, with a median (interquartile range) difference of –4 (–10 to 0) between these 2 time points. Improvement in HADS anxiety and depression scores were reported by 62.5% (362/579) relatives.

**Significance of results.** These findings support the importance of screening relatives having risk factors of developing prolonged grief in the palliative unit and 6 months after patient's death.

## Introduction

The grieving process has 4 different aspects: anticipatory grief, acute grief, normal grief reactions and complicated grief. The death of a close loved one remains one of the most intense, distressing, and traumatic events a person may experience (Shear et al. 2005). Confronted with imminent loss, families experience an emotional burden that includes feelings of helplessness, compassion fatigue, anxiety, and depression, with a strong tendency to stay close to their loved one and provide overprotection. These manifestations are part of the anticipatory grief phenomenon with the anticipation of the future trauma due to loss representation in advance (Coelho and Barbosa 2017). Bereavement can be considered as a continuum from pre-loss to post-loss reactions (Grassi 2007). Bereavement is an existential condition; in some cases, prolonged grief (PG) may occur, the consequences of which may jeopardize quality of life, job conditions, or social relationships, for months, or even years after the loss (Jacobs and Ostfeld 1997). Most of the bereaved individuals are able to get adjusted rather quickly, emotional consequences resolve in few months, and pre-loss functioning is restored after a variable period of 6 to 12 months (Prigerson et al. 2009). However, some people may experience prolonged or complicated grief, with emotional, behavioral, and cognitive symptoms (yearning, searching, detachment, numbness, bitterness, emptiness, and loss of sense and control) (Simon 2013). These symptoms may result in a mental illness that is distinct from depression, anxiety, or post-traumatic stress disorders symptoms (Shear et al. 2013) and impaired quality of life. PG has been associated with negative outcomes, such as heart disease or changes in eating (Prigerson et al. 1997) and suicidal ideation (Prigerson et al. 1999).

PG reactions at 8 months were reported in 24.4% (Chiu et al. 2010) and at 6 months in 25.4% (Newson et al. 2011), 28.6% (Coelho et al. 2015), 30% (Wiese et al. 2010), and 40% (Guldin et al. 2012) of relatives of a heterogeneous population of patients with cancer. Common factors that complicated grief included pre-loss risk factors (female gender, preexisting trauma such as childhood trauma, prior loss, insecure attachment, preexisting mood and anxiety disorders, and nature of the relationships) (Fujisawa et al. 2010; Kersting et al. 2011; Newson et al. 2011), loss-related factors (relationships of caregivers taking roles and nature of the death itself) (Fujisawa et al. 2010; Neria et al. 2007; Newson et al. 2011), and peri-loss factors (social circumstances, resources available after death, poor understanding of the circumstances of death, interference between natural healing process, and culture practices of death) (Bui et al. 2013; Hargrave et al. 2012; Mutabaruka et al. 2012). Although complicated grief decreases over time, its expression varies greatly between individuals, circumstances of death, and culture. Few studies investigated PG reactions in France (Fasse et al. 2015); specifically, depression was reported in 25% of spouses of palliative cancer patients between 1 and 6 months after death (Fasse et al. 2015).

To bridge this gap, we investigated the incidence and risk factors of PG in a large population of relatives of patients who died in a palliative care unit.

## Methods

### Study design

This was a prospective multicenter cohort study in 26 French palliative care units. Written inform consent was obtained from both patients and their relatives. Written inform consent was obtained from each relative of patient admitted in the palliative care unit within the first 48 hours of admission. For patients able to make decision, inform consent was obtained directly from the patient, and in other cases, from their surrogate or other relative member if the patient had no surrogate. The trial protocol has been published in Garrouste-Orgeas et al. (2019a). The statistical plan is available in Supplement 1.
## Setting

Palliative care units from the French Association of Palliative Care (SFAP) were invited to participate in the study by mail. Participating units were required to have ≥10 beds and a physician or a nurse or a psychologist who would take responsibility for the study organization and inclusions of relatives and patients. Palliative care units recruited patients from January 2019 to February 2020 (e-Table S1 in Supplement 2). Follow-up was completed in August 2020.

## Participants

### Inclusion criteria

Consecutive patients with cancer and their relatives admitted in the palliative care unit were approached by physicians or psychologists or nurses. Eligible patients had to be aged at least 18 years to be hospitalized for more than 72 hours for end-of-life issues and to have at least one relative present during the inclusion period and able to visit the patient during the palliative stay. The study was proposed to all relatives present at admission because grief reactions are unique to each relative. The prognostication of end of life was left to the discretion of the physician who examined the patient at admission. Both patients and relatives had to have sufficient French language skills for follow-up telephone interviews. The inclusion period was within 48 hours after palliative care admission.

### Exclusion criteria

Patients were ineligible if they had no relatives visiting them during the inclusion period, were under legal guardianship, if their status was considered by the investigator as highly likely to lead to death before 72 hours after admission, if they were not hospitalized for end-of-life issues, and if they had no cancer. Relatives who were mute or deaf or included in another trial with a telephone interview after patient death were also excluded.

## Data collection and outcomes

We collected data from centers, patients, and relatives (Supplement 1). Outcomes were measured by 2 psychologists specifically hired for the study (MS and MAL) during telephone interviews conducted 6 months after patient's death. A relative was declared lost to follow-up if he or she could not be contacted by phone after 7 phone calls at different times of the day.

### Primary outcome

The primary outcome was the incidence of PG, measured by the Inventory Complicated Grief (ICG) (Zisook et al. 2010a, 2010b) of relatives 6 months after the patient's death in a palliative care unit. Significant PG symptoms were defined by an ICG > 25 (range 0–76, higher scores indicate more severe symptoms). No minimal clinically significant difference was reported for the ICG.

### Prespecified secondary outcomes

Anxiety and depression syndrome were evaluated based on the Hospital Anxiety and Depression Scale (HADS) score (Zigmond and Snaith 1983) (range 0 [best]–42 [worst]). Significant anxiety and depression symptoms were defined by a score >8 for anxiety and depression subscales. The minimal clinically important difference is 2.5 for each subscale (Chan et al. 2016). The evaluation was performed in relatives at Day 3 to Day 5 after patient admission and 6 months after patient's death.

Post-traumatic stress disorder symptoms were evaluated in relatives at 6 months after patient's death, through the Impact Event

Scale-Revised (IES-R) questionnaire (Rash et al. 2008), with significant symptoms defined as an IES-R score >22 (range 0–88, higher score indicates more severe symptoms) (de Miranda et al. 2011; Garrouste-Orgeas et al. 2019b). There is no minimal clinically significant difference reported for the IES-R score. We reported scores in the 3 domains (intrusion, avoidance, and hyper arousal) that make up the IES-R score.

## Statistical analysis

Results are reported as the median and interquartile range (IQR) or as counts (%). Categorical variables were compared using Chi-square test, and continuous variables were compared using Mann–Whitney test.

To assess the risk factor of PG, we used univariate mixed logistic regression with random effects on patients and centers. Centers with less than 10 patients were grouped together. The log linearity of all continuous variables was checked. The non-log linear variables were discretized into categorical variables. Nonlinear and medically logical variables with a *p* < 0.1 were used in a multivariate mixed model with random family and center effect after backward selection.

Anxiety and depression syndrome between Day 3 and Day 5 after patient admission and 6 months after patient's death and post-traumatic stress disorder symptoms 6 month after patient's death were investigated using the same methodology.

The confidence intervals were calculated according to a binomial distribution approximated by a normal distribution. Missing values for univariate and multivariate analyses were considered by a simple imputation method if less than 20% of data were missing. Variables with more than 20% of data missing were not used in the analyses.

The relationship between outcomes and period of COVID-19-related lockdown was tested in the analysis. Analyses were performed using SAS 9.4 (SAS, Inc., Cary, NC) software, and 2-sided *p* < 0.05 was considered statistically significant.

## Results

### Study population and follow-up

Among the 108 invitations sent out, 17 (15.7%) centers declined participation and 65 (60%) did not answer, leaving 26 (24%) palliatives care centers that participated on the study. Recruitment period is reported in e-Table S1 in Supplement 2. Reasons for non-participation were lack of interest in the study (n = 3), no time for the study (n = 3), and fear of inclusion of relatives close to the patient admission (n = 11). Characteristics of the 26 palliatives care units are reported in Table 1. Overall, 609 patients and 854 relatives were assessed for eligibility, and 531 patients and 611 relatives were included. Follow-up at 6 months with full completion of the ICG was obtained in 608/611 (99.5%) relatives (Figure 1). Baseline characteristics of patients and eligible, excluded and included relatives are reported, respectively, in e-Tables S2 and S3 in Supplement 2.

### Primary outcome

Six months after patient's death, the incidence of relatives with an ICG score greater than 25 was 199/608 (32.7%, 95% CI: 29.0–36.4) (Table 2).

### Prespecified secondary outcomes

Within 3 to 5 days after patient admission, symptoms of anxiety (Hospital Anxiety Score [HAS]) were reported by 381 of 583
<table><caption>**Table 1.** Characteristics of centers</caption><thead><tr><th>Variables</th><th>Data<sup>a</sup></th></tr></thead><tbody><tr><td><strong>Hospital</strong></td><td></td></tr><tr><td>University hospital, n (%)</td><td>7 (23.9)</td></tr><tr><td><strong>Palliative care unit</strong></td><td></td></tr><tr><td>Number of beds per unit, median (IQR)</td><td>12 (10–14)</td></tr><tr><td>Number of attending physicians, median (IQR)</td><td>2 (1–2.5)</td></tr><tr><td>Number of junior physicians, median (IQR)</td><td>0 (0–1)</td></tr><tr><td>Nurse-to-patient ratio, day, median (IQR)</td><td>5 (4–6)</td></tr><tr><td>Nurse-to-patient ratio, night, median (IQR)</td><td>10 (8–12)</td></tr><tr><td>Number of head nurses, median (IQR)</td><td>0.8 (0.5–1)</td></tr><tr><td>Nursing assistant-to-patient ratio, day, median (IQR)</td><td>5 (4–6)</td></tr><tr><td>Nursing assistant-to-patient ratio, night, median (IQR)</td><td>10 (8–12)</td></tr><tr><td>12-hour shifts for nurses (%)</td><td>11 (42.3)</td></tr><tr><td>12-hour shifts for nursing assistants (%)</td><td>11 (42.3)</td></tr><tr><td>Number of psychologists, median (IQR)</td><td>1 (0.5–1)</td></tr><tr><td>Number of physiotherapists, median (IQR)</td><td>0.4 (0.2–0.5)</td></tr><tr><td>Number music therapist, median (IQR)</td><td>0 (0–0)</td></tr><tr><td>Number of art therapist, median (IQR)</td><td>0 (0–0)</td></tr><tr><td>Number socio-aestheticians, median (IQR)</td><td>0.1 (0–0.1)</td></tr><tr><td>Number of osteopaths, median (IQR)</td><td>0 (0–0)</td></tr><tr><td>Number of psychomotor therapists, median (IQR)</td><td>0 (0–0)</td></tr><tr><td>Number of occupational therapists, median (IQR)</td><td>0 (0–0)</td></tr><tr><td>Number of social workers, median (IQR)</td><td>0.3 (0.2–0.5)</td></tr><tr><td>Number of hospital biographer (%)</td><td>2 (7.2)</td></tr><tr><td>Presence of a support group for caregivers, (%)</td><td>26 (100)</td></tr><tr><td>Presence of a support group for families during the patient stay, (%)</td><td>2 (7.7)</td></tr><tr><td>Availability of a religious service, (%)</td><td>26 (100)</td></tr><tr><td>Availability of interpreter services, (%)</td><td>21 (80.8)</td></tr><tr><td>Availability of volunteers, (%)</td><td>26 (100)</td></tr><tr><td>Presence of a room with drink dispensers, (%)</td><td>17 (64.4)</td></tr><tr><td><strong>Visitation policies</strong></td><td></td></tr><tr><td>Number of units offering 24-hr visitation, (%)</td><td>20 (76.9)</td></tr><tr><td>Family on-site sleep</td><td>26 (100)</td></tr><tr><td>With a bed into the patient room</td><td>25 (96.2)</td></tr><tr><td>With an armchair into the patient room</td><td>22 (84.2)</td></tr><tr><td>Dedicated room available</td><td>11 (42.3)</td></tr><tr><td>Children visitation authorized, regardless of their age, (%)</td><td>26 (100)</td></tr><tr><td>Pet visitation authorized, (%)</td><td>20 (76.9)</td></tr><tr><td>Availability of a mortuary chamber, hours, median (IQR)</td><td>8 (7–9)</td></tr></tbody></table>

(Continued)

<table><caption>**Table 1.** (Continued.)</caption><thead><tr><th>Variables</th><th>Data<sup>a</sup></th></tr></thead><tbody><tr><td><strong>Communication with families</strong></td><td></td></tr><tr><td>Formal meeting at admission, (%)</td><td>26 (100)</td></tr><tr><td>With a nurse</td><td>24 (92.3)</td></tr><tr><td>With a psychologist</td><td>13 (50)</td></tr><tr><td>Formal weekly meeting, (%)</td><td>19 (73.3)</td></tr><tr><td>Formal meeting at the patient's death, (%)</td><td>14 (53.8)</td></tr><tr><td>Delivery of an information leaflet at admission, (%)</td><td>26 (100)</td></tr><tr><td>Delivery of a leaflet for children, (%)</td><td>6 (23.1)</td></tr><tr><td>Delivery of an information leaflet at patient's death, (%)</td><td>20 (76.9)</td></tr><tr><td><strong>Mourning follow-up</strong></td><td></td></tr><tr><td>Sending a condolence letter</td><td>14 (53.8)</td></tr><tr><td>Proposition of a follow-up with a psychologist</td><td>18 (78.3)</td></tr><tr><td>Proposition of a follow-up with volunteers</td><td>1 (4.3)</td></tr><tr><td>Presence a support grieving group</td><td>7 (26.9)</td></tr><tr><td>Another type of follow-up<sup>b</sup></td><td>3 (17.4)</td></tr></tbody></table>

IQR = interquartile range.

<sup>a</sup>No missing data

<sup>b</sup>Another follow-up (remembrance ceremony with other grieving family, meeting with a physician, and phone call with a caregiver).

(65.4%) relatives. Symptoms of depression (HAD) were reported by 215 of 583 (36.9%) relatives. The incidence of HADS symptoms was 87.5% (95% CI, 84.8–90.2). The median (IQR) HADS anxiety score was 10 (7–13), and the median (IQR) HADS depression score was 7 (4–10) (Table 2). Six months after patient's death, symptoms of anxiety were reported by 229 of 607 (37.7%) relatives and symptoms of depression by 110 of 607 (18.1%). The incidence of HADS symptoms was 68.7% (95% CI, 65.0–72.4). The median (IQR) HADS anxiety score was 7 (5–10) and the median (IQR) HADS depression score was 4 (2–7). The median (IQR) difference between day 3–5 and 6 months after patient's death was –4 (–10 to 0). Improvement of HADS anxiety and depression scores was reported by 362 of 579 (62.5%) of relatives (Table 2).

The number of patients with an IES-R score greater than 22 was 323/607 (53.2%) with a median (IQR) score of 24 (13–35) (Table 2).

Univariate and multivariate analyses assessing the risk factors of the increase of an ICG score to greater than 25 in relatives are reported, respectively, in e-Table S4 in Supplement 2 and Table 3. The occurrence of respiratory symptoms on admission (OR 1.68, 95% CI, 1.09–2.6, *p* = 0.01), being the patient's spouse (OR 2.85, 95% CI 1.53–5.3, *p* = 0.001), having a support group for relatives in palliative care unit (OR 5.16, 95% CI, 1.65–16.13, *p* = 0.005), and suffering from anxiety (OR 2.26, 95% CI, 1.4–3.67, *p* = 0.001) and depression (OR 1.64, 95% CI, 1.06–2.53, *p* = 0.02) symptoms shortly after patient admission were significantly associated with an ICG score greater than 25.

Univariate and multivariate analyses of post-traumatic stress disorder symptoms are reported, respectively, in e-Table S5 in Supplement 2 and Table 4. Patient's age < 65 years old (OR 2.75, 95% CI, 1.31–5.79, *p* = 0.008) and between 75 and 65 years (OR 1.99, 95% CI, 1.04–3.79, *p* = 0.036), anxiety/psychological suffering of the patient on admission
<figure><img src="image_4.png" /><figcaption>Fig. 1. Flow chart of the study.</figcaption></figure>

(OR 1.63, 95% CI, 1.09–2.42, *p* = 0.01), being a female for the relative (OR 2.75, 95% CI, 1.81–4.17, *p* < 0.0001), being the spouse/partner of the patient (OR 3.48, 95% CI 1.92–6.31 *p* < 0.001), or being the children of the patient (OR 2.05, 95% CI 1.16–3.65, *p* = 0.014) were independent factors of an IES-R > 22.

Univariate and multivariate analyses of anxiety and depression HADS scores between Day 3 and Day 5 after palliative care admission and 6 months after death are reported, respectively, in e-Table S6 in Supplement 2 and Table 5. Presence of patient anxiety/psychological symptoms on admission (OR 1.59, 95% CI 1.04–2.06, *p* = 0.01) was the only factor independently associated with improvement of HADS symptoms in relatives 6 months after patient's death.

No significant associations were found in the univariate analyses between period of lockdown for COVID-19 in France or not and the different outcomes.

## Discussion

This observational multicenter study of the psychological status of relatives 6 months after the death of their loved one in a palliative care unit reported high distress with PG reactions, mainly among spouses and partners. PG reactions were present in one relative out of three, and post-traumatic stress disorder symptoms in one out of two. Patient's respiratory symptoms at admission and high

psychological distress shortly after patient's admission were significantly associated with PG. Palliative care admission was associated with high incidence of HADS symptoms with an improvement in 62% of them between 3 and 5 days after patient's admission and 6 months following death.

This study was performed in palliative care units trained in multidisciplinary care with physical, social, psychological, cultural, and spiritual support of patients, in order to provide relief of pain and physical symptoms. Relatives were included in this multisystemic approach by being offered on-site psychological support, possibility of being close to the patient and being assured that relief was being provided to their loved one. This global approach aimed at providing support and help to relatives for this intense, emotional experience.

Our study found that PG reactions were frequent, present in one-third of relatives. This was consistent with the proportion of 37% of PG reaction (Prigerson et al. 2009). It is important to note than among our relatives, 61.5% were primary caregivers, and this may have overburdened their post-loss experience (Geng et al. 2018; Ghesquiere et al. 2011; Grosse et al. 2018). Pre-loss symptoms or attachment issues are crucial in creating a vulnerable status for developing PG reactions. Being the spouse or partner of the patient was an independent risk factor for PG, in line with other studies (Thomas et al. 2014; van Doorn et al. 1998). Poor adjustment of spouse/partner to grief derived from elements prior to patient's
<table><caption>**Table 2.** Primary and secondary outcomes among relatives at 6-month follow-up after patient's death in a palliative care unit</caption><thead><tr><th>Variables</th><th></th></tr></thead><tbody><tr><td>Primary outcomes</td><td>(N = 608)</td></tr><tr><td>Presence of prolonged grief<sup>a</sup>, % (ICG &gt; 25)</td><td>199 (32.7)</td></tr><tr><td>ICG score, median (IQR)</td><td>20 (12–29)</td></tr><tr><td>Secondary outcomes</td><td></td></tr><tr><td>Anxiety and depression<sup>b</sup></td><td></td></tr><tr><td>At Day 3 to Day 5</td><td>(N = 583)</td></tr><tr><td>HADS score, median (IQR)</td><td>17 (12–23)</td></tr><tr><td>HAS score, median (IQR)</td><td>10 (7–13)</td></tr><tr><td>HAD score, median (IQR)</td><td>7 (4–10)</td></tr><tr><td>Symptoms of anxiety, %</td><td></td></tr><tr><td>Yes</td><td>381 (65.4)</td></tr><tr><td>Symptoms of depression, %</td><td></td></tr><tr><td>Yes</td><td>215 (36.9)</td></tr><tr><td>At 6-month follow-up</td><td>(N = 607)</td></tr><tr><td>HADS score, median (IQR)</td><td>12 (8–17)</td></tr><tr><td>HAS score, median (IQR)</td><td>7 (5–10)</td></tr><tr><td>HAD score, median (IQR)</td><td>4 (2–7)</td></tr><tr><td>Symptoms of anxiety, % (HAS score &gt; 8)</td><td></td></tr><tr><td>Yes</td><td>229 (37.7)</td></tr><tr><td>Symptoms of depression, % (HAD score &gt; 8)</td><td></td></tr><tr><td>Yes</td><td>110 (18.1)</td></tr><tr><td>PTSD<sup>c</sup> at 6-month follow-up</td><td>(N = 607)</td></tr><tr><td>Presence of PTSD symptoms, % (IES-R &gt; 22)</td><td>323 (53.2)</td></tr><tr><td>IES-R score, median (IQR)</td><td>24 (13–35)</td></tr><tr><td>Intrusion score</td><td>13 (8–9)</td></tr><tr><td>Avoidance, score</td><td>6 (2–11)</td></tr><tr><td>Hyperarousal, score</td><td>3 (0–7)</td></tr></tbody></table>

ICG = Inventory Complicated Grief; IQR = interquartile range; HADS = Hospital Anxiety Depression Scale, HAS = Hospital Anxiety Score, HAD = Hospital Depression Score; PTSD = post-traumatic stress disorder.

death (Fasse et al. 2014): presence of cognitive and emotional features, caregiving experience (Marwit et al. 2008), symptoms of the patient's disease (Morita et al. 2007), patient's care and treatments and post-loss factors (perception of cancer in the social network) (Fasse et al. 2014). Low level of active coping in a sample of spouse/partner was the only significant factor associated of developing PG reactions (Miller et al. 2020). Higher levels of inflammatory response were found in the bereaved spouse with severe grief reactions (Fagundes et al. 2019).

Factors of PG were usually explored through the individual relative point of view. Our study added the evaluation of patients and center characteristics. We found that respiratory symptoms in patients at admission were independent factors for PG. Respiratory

<table><caption>**Table 3.** Multivariable analysis of the occurrence of prolonged grief in relatives of patients who died in a palliative care unit</caption><thead><tr><th>Variables</th><th>OR (95% CI)</th><th>p-value</th></tr></thead><tbody><tr><td><strong>Center</strong></td><td></td><td></td></tr><tr><td>Formal meeting after patient's death</td><td>1.53 (0.89–2.64)</td><td>0.11</td></tr><tr><td>Presence of a support group for relatives during the stay</td><td>5.16 (1.65–16.13)</td><td>0.005</td></tr><tr><td>Relatives authorized to prepare the body for funerals<sup>a</sup></td><td>0.43 (0.19–0.97)</td><td>0.043</td></tr><tr><td><strong>Patients</strong></td><td></td><td></td></tr><tr><td>Age</td><td>0.97 (0.95–0.99)</td><td>&lt;0.0001</td></tr><tr><td>Respiratory symptoms on admission</td><td>1.68 (1.09–2.6)</td><td>0.0119</td></tr><tr><td>Digestive symptoms on admission</td><td>0.68 (0.41–1.15)</td><td>0.152</td></tr><tr><td><strong>Relatives</strong></td><td></td><td></td></tr><tr><td>Lockdown period<sup>b</sup></td><td>0.66 (0.4–1.1)</td><td>0.11</td></tr><tr><td>Relationship with the patient</td><td></td><td>0.001</td></tr><tr><td>Spouse/partner</td><td>2.85 (1.53–5.3)</td><td>0.001</td></tr><tr><td>Children</td><td>1.64 (0.88–3.04)</td><td>0.12</td></tr><tr><td>Parents</td><td>2.38 (0.555–10.25)</td><td>0.24</td></tr><tr><td>Other</td><td>1</td><td></td></tr><tr><td>Presence of anxiety symptoms at Day 3 to 5 after admission</td><td>2.26 (1.4–3.67)</td><td>0.001</td></tr><tr><td>Presence of depression symptoms at Day 3 to 5 after admission</td><td>1.64 (1.06–2.53)</td><td>0.026</td></tr></tbody></table>

CI = confidence interval; OR = odds ratio.

Variables included in the multivariable analysis: Center's related variables: beds > 15 in palliative care unit, 24 hours visitation policies, family on-site sleep with a dedicated room, authorization for relatives to prepare the body for funerals, organization of an interview with relatives at patient's death, existence of a support group for relatives during palliative care stay; variables related to patient's symptoms: age; symptoms of admission: (anxiety/psychological suffering, sepsis, pain, neurologic, and digestif); relatives' related variables: gender, primary caregiver, relation with the patient, lockdown period in France, presence of anxiety symptoms or presence of depression symptoms between Day 3 and Day 5 after patient admission, on the basis of a p-value <0.1.

symptoms can be traumatizing for relatives with fear that the patient may experience a painful death. Ruminating memories of this period can elicit difficulties of coping (Coelho and Barbosa 2017). Pre-loss anxiety or depression symptoms were independent factors of PG, in line with other studies (Ghesquiere et al. 2013; Lobb et al. 2010; Nielsen et al. 2017; Tsai et al. 2016). Interestingly, our population of relatives of cancer patients suffered anxiety and depression symptoms at the same prevalence than relatives of intensive care patients measured at similar time points after admission (Pochard et al. 2005). Admission in palliative care for some relatives might be a violent phenomenon and might be a witness of unpreparedness to the upcoming patient's death. Screening for emotional distress after palliative care admission could identify relatives at risk of PG reactions and offer them effective interventions starting while the patient is still alive, which may improve their dying experience and facilitate preparedness for the patient's forthcoming death. However, in contrast with small qualitative

<footnote><sup>a</sup>Measured using the ICG score (range 0–76, higher scores indicates more severe symptoms).</footnote>

<footnote><sup>b</sup>Measured using the HADS score (overall range, 0–42; range for anxiety and depression subscales, 0–21; a higher score indicates more severe symptoms).</footnote>

<footnote><sup>c</sup>Measured using the IES-R score (overall range, 0–88; intrusion range: 0–32; avoidance range: 0–28; hyperarousal range: 0–24; a higher score indicates more severe symptoms).</footnote>

<footnote><sup>a</sup>The body preparation for funerals is done by the relatives immediately after death with nurses and nursing assistants (washing and dressing the body for funerals and having the possibility to practice religious rite).</footnote>

<footnote><sup>b</sup>Lockdown period due to Covid-19 pandemic (in France, from 17 March 2020 to 7 June 2020).</footnote>
<table><caption>**Table 4.** Multivariable analysis of the occurrence of post-traumatic stress in relatives of patients died in a palliative care unit</caption><thead><tr><th>Variables</th><th>OR (95% CI)</th><th>p-value</th></tr></thead><tbody><tr><td><strong>Center</strong></td><td></td><td></td></tr><tr><td>Family on-site sleep in a dedicated room</td><td>0.67 (0.45-1)</td><td>0.05</td></tr><tr><td>Relatives authorized to prepare the body for funerals<sup>a</sup></td><td>0.71 (0.34-1.47)</td><td>0.35</td></tr><tr><td><strong>Patients</strong></td><td></td><td></td></tr><tr><td>Age, years</td><td></td><td>0.065</td></tr><tr><td>&lt;65</td><td>2.75 (1.31-5.79)</td><td>0.008</td></tr><tr><td>75 &lt; 65</td><td>1.99 (1.04-3.79)</td><td>0.036</td></tr><tr><td>85 &lt; 75</td><td>1.67 (0.9-3.11)</td><td>0.10</td></tr><tr><td>&ge;85</td><td>1</td><td></td></tr><tr><td>Digestive symptoms on admission</td><td>0.66 (0.42-1.04)</td><td>0.08</td></tr><tr><td>Anxiety/psychology suffering on admission</td><td>1.63 (1.09-2.42)</td><td>0.01</td></tr><tr><td>Patient's surrogate</td><td>1.42 (0.94-2.15)</td><td>0.09</td></tr><tr><td><strong>Relatives</strong></td><td></td><td></td></tr><tr><td>Gender</td><td></td><td></td></tr><tr><td>Female</td><td>2.75 (1.81-4.17)</td><td>&lt;.0001</td></tr><tr><td>Relationship with the patient</td><td></td><td>0.007</td></tr><tr><td>Spouse/partner</td><td>3.48 (1.92-6.31)</td><td>&lt;.0001</td></tr><tr><td>Children</td><td>2.05 (1.16-3.65)</td><td>0.014</td></tr><tr><td>Parents</td><td>2.34 (0.59-9.32)</td><td>0.22</td></tr><tr><td>Other</td><td>1</td><td></td></tr><tr><td>Age, years</td><td></td><td>0.123</td></tr><tr><td>&lt;45</td><td>1.6 (0.78-3.31)</td><td>0.20</td></tr><tr><td>55 &lt; 45</td><td>0.82 (0.42-1.58)</td><td>0.548</td></tr><tr><td>65 &lt; 55</td><td>1.35 (0.78-2.33)</td><td>0.288</td></tr><tr><td>&ge;65</td><td>1</td><td></td></tr></tbody></table>

CI = confidence interval; OR = Odds ratio.

<sup>a</sup>The body preparation for funerals is done by the relatives immediately after death with nurses and nursing assistants (washing and dressing the body for funerals and having the possibility to practice religious rite).

Variables in the multivariable analysis on the basis of a *p*-value < 0.1 included the following: Center variables: beds > 15 in palliative care unit, 24 hours visitation policies, delivery of a children leaflet, sending a condolence letter, presence of a support group for relatives, possibility of sleeping on site, authorization for relatives to prepare the body for funerals, presence of a mourning follow-up, organization of an interview after patient's death, delivery of an information leaflet at patient's death. Patients' variables (age), symptoms of admission (pain, respiratory, digestive, psychological suffering), cardiac comorbidity, diagnosis of the type of cancer, single patient, presence of advanced directives, designation of a surrogate, and patient's death after continuous deep sedation. Relatives' variables: gender, age, relation with the patient, primary caregiver, level of education equal or superior to bachelor, presence of anxiety symptoms between Days 3 and 5 after admission diagnosed by a HAS score > 8, presence of depression symptoms diagnosed by a HAD score > 8 between Days 3 and 5 after admission.

studies (Harding et al. 2002; Henriksson et al. 2011; Milberg et al. 2005), our study found that the support group for relatives during palliative care stay provided by some palliative centers was not an effective option as it increased the risk of PG. Actually, relatives may prefer a face-to-face interview with a psychologist instead of sharing their difficulties with other relatives. Differences in study methodology (qualitative vs. quantitative approach) and

<table><caption>**Table 5.** Multivariable analysis of improvement of HADS score in relatives between Day 3 and Day 5 after admission in the palliative care unit and 6 months after patient's death</caption><thead><tr><th>Variables</th><th>OR (95% CI)</th><th>p-value</th></tr></thead><tbody><tr><td><strong>Patients</strong></td><td></td><td></td></tr><tr><td>Anxiety/psychology suffering on admission</td><td>1.59 (1.11-2.28)</td><td>0.01</td></tr><tr><td><strong>Relatives</strong></td><td></td><td></td></tr><tr><td>Patient's surrogate</td><td>1.4 (0.97-2.02)</td><td>0.07</td></tr><tr><td>Admission to the palliative care unit requested by relatives</td><td>0.7 (0.48-1.03)</td><td>0.07</td></tr></tbody></table>

CI = confidence interval; OR = odds ratio.

Variables in the multivariable analysis on the basis of a *p*-value < 0.1 included the following: Center variables: beds > 15 in palliative care unit, 24 hours visitation policies, family on-site sleep in a dedicated room, information of relatives with a formal meeting at patient's death, sending a condolence letter, presence of a grieving support group after death for relatives, presence of a mourning follow-up, and delivery of an information leaflet at patient's death. Patients' variables: single patient, age, duration of the cancer history. Relatives' variables: primary caregiver, relative gender, level of education equal or superior to bachelor, previous palliative care hospitalization for a close relative, presence at home of a health-care worker or a life support person or support hospital service.

in population included (size of the sample) may explain the conflicting results. It seems important to tailor to the relative's needs during illness trajectory, knowing that needs vary according to illness trajectory. Relative's needs were more focused on information, on treatment possibilities and side effects (92.8%), diagnosis (91.6%), testing (91.1%), and physical symptoms (90.9%) following diagnosis of cancer (Ndiok and Ncama 2018). During the late phase of illness, insight into the gravity of the illness, participation in care, knowledge of similar situations in participants, and sense of safety in relation with the patient care became more important needs for relatives (Henriksson and Andershed 2007).

There have been few studies examining the prevalence of post-traumatic stress disorder symptoms in relatives after an expected death in palliative care units (Hirooka et al. 2017a, 2018b). Given that trauma symptoms may be distinct from PG reactions (Horowitz et al. 1997) but may be highly interconnected (Hirooka et al. 2017), we found that 53.2% of relatives had post-traumatic stress disorder symptoms 6 months after patient's death. Young patient age, psychological suffering in patient on admission, being a female partner, or being a patient's child were found to be independent factors at risk of having post-traumatic stress disorder symptoms. Being provided the opportunity as relatives to sleep on site in a dedicated room and to contribute to the physical preparation of the body for funerals were independent factors of decreasing post-traumatic stress disorder symptoms. These two factors explained the importance for relatives to have the opportunity of saying properly goodbye and of staying close to their loved one during the important moment of the transition from life to death. Sending a condolence letter is a matter of debate in palliative care (Hayward et al. 2016; Porter et al. 2021). Half of our units did it. This study showed no benefit of relatives who received a condolence letter contrasting to other study who reported an increase of post-traumatic stress disorder symptoms in different setting (Kentish-Barnes et al. 2017).

Given the results of this study reporting high distress in most relatives 6 months after patient's death, prevention strategies should be discussed. Although several interventions conducted in outpatient cancer improved relatives' outcomes while the patient was alive (Dionne-Odom et al. 2015a, 2016b), conflicting preventive measures were reported in relatives' bereavement
outcomes. A proactive randomized communication intervention to help patients/relatives to ask questions, express concerns, and help oncologist to address them effectively did not significantly improve mental health, anxiety, depression symptoms, or PG reactions 7 months after patient's death (Duberstein et al. 2019). A randomized trial including bereaved individuals, at risk for PG, 8 months after loss, reported significant efficacy of a cognitive-behavioral therapist-assisted-internet delivered intervention on PG, anxiety, depression, and PTSD (Litz et al. 2014). Research on internet-based grief therapy is ongoing (Hoffmann et al. 2018). This study contributes data that suggest a profile at high-risk relatives of PG. Screening symptoms suggestive of anxiety and depression shortly after patient admission, taking care of relatives of patients with respiratory symptoms, or psychological suffering might alleviate the burden of relatives. The qualitative part of our study, interviewing relatives with PG, should add insights into the improvement of the bereavement process.

This study has several strengths and limitations. The multi-center design and the high number of included relatives and their high response rate at 6 months provide a large overview of post-loss relatives' conditions. We chose to include all relatives willing to participate, providing a potentially broad panel of individual consequences according to their relationship with the patient. This study has several limitations. First, only 24% of invited centers participated in the study, mainly due to fear of physicians to include relatives in a bereavement research project, which contrasts with the reportedly beneficial effects of participating in research for bereaved relatives (Kentish-Barnes et al. 2015). However, participating centers were representative of the current practice for family-centered care in France (Rhondali et al. 2014). Second, grief is a complex phenomenon, and components of psychological distress may not have been sufficiently taken into account in the different statistical models. Third, this study was performed in France and the results may not be generalizable to other European and non-European culture settings (Avidan et al. 2021).

## Conclusions

Six months after the death of a loved one with cancer in palliative care units in France, one-third of relatives were still suffering of complicated grief and half of them had a post-traumatic stress disorder. No recommendations are currently available to prevent these psychological consequences. Thus, this study represents the first step of a potential process of prevention of PG. The next step in our study, the testimony of relatives who have experienced this trauma, will help to define other improvement strategies.

**Supplementary material.** The supplementary material for this article can be found at https://doi.org/10.1017/S1478951523000111.

**Acknowledgments.** This work was supported by the Fondation-de-France (ENG 00089287). The funders did not influence study design, conduct, or reporting. The authors thank Céline Féger, MD (EMIBiotech), for her editorial support. Registration no: NCT03748225.

**Funding.** This study was supported by Fondation-de-France (ENG 0008928).

**Conflict of interest.** The authors declare that there is no conflict of interest.

**Ethical approval.** In accordance with French law, the study (2017-A03440-53) was approved by the "Sud-Ouest et Outremer 1" ethics

committee on 20 March 2018 and 4 March 2019 and the CNIL (Commission Nationale de l'Informatique et des Libertés; number 918120, on 15 June 2018). In accordance with French law, patient's data are collected following the criteria of certificate of conformity MR003.

## References

Avidan A, Sprung CL, Schefold JC, et al. (2021) Variations in end-of-life practices in intensive care units worldwide (Ethicus-2): A prospective observational study. *The Lancet Respiratory Medicine* 9(10), 1101–1110. doi:10.1016/S2213-2600(21)00261-7

Bui E, Simon NM, Robinaugh DJ, et al. (2013) Periloss dissociation, symptom severity, and treatment response in complicated grief. *Depression and Anxiety* 30(2), 123–128. doi:10.1002/da.22029

Chan KS, Aronson Friedman L, Bienvenu OJ, et al. (2016) Distribution-based estimates of minimal important difference for hospital anxiety and depression scale and impact of event scale-revised in survivors of acute respiratory failure. *General Hospital Psychiatry* 42, 32–35. doi:10.1016/j.genhosppsych. 2016.07.004

Chiu YW, Huang CT, Yin SM, et al. (2010) Determinants of complicated grief in caregivers who cared for terminal cancer patients. *supportive Care in Cancer* 18(10), 1321–1327. doi:10.1007/s00520-009-0756-6

Coelho A and Barbosa A (2017) Family anticipatory grief: An integrative literature review. *American Journal of Hospice and Palliative Medicine* 34(8), 774–785. doi:10.1177/1049909116647960

Coelho A, Delalibera M, Barbosa A, et al. (2015) Prolonged grief in palliative family caregivers: A pilot study in a Portuguese sample. *OMEGA – Journal of Death and Dying* 72(2), 151–164. doi:10.1177/003022281557 4833

de Miranda S, Pochard F, Chaize M, et al. (2011) Postintensive care unit psychological burden in patients with chronic obstructive pulmonary disease and informal caregivers: A multicenter study. *Critical Care Medicine* 39(1), 112–118. doi:10.1097/CCM.0b013e3181feb824

Dionne-Odom JN, Azuero A, Lyons KD, et al. (2015a) Benefits of early versus delayed palliative care to informal family caregivers of patients with advanced cancer: Outcomes from the ENABLE III randomized controlled trial. *Journal of Clinical Oncology* 33(13), 1446–1452. doi:10.1200/JCO.2014. 58.7824

Dionne-Odom JN, Azuero A, Lyons KD, et al. (2016b) Family caregiver depressive symptom and grief outcomes from the ENABLE III randomized controlled trial. *Journal of Pain and Symptom Management* 52(3), 378–385. doi:10.1016/j.jpainsymman.2016.03.014

Huberstein PR, Maciejewski PK, Epstein RM, et al. (2019) Effects of the values and options in cancer care communication intervention on personal caregiver experiences of cancer care and bereavement outcomes. *Journal of Palliative Medicine* 22(11), 1394–1400. doi:10.1089/jpm.2019.0078

Fagundes CP, Brown RL, Chen MA, et al. (2019) Grief, depressive symptoms, and inflammation in the spousally bereaved. *Psychoneuroendocrinology* 100, 190–197. doi:10.1016/j.psyneuen.2018.10.006

Fasse L, Flahault C, Bredart A, et al. (2015) Describing and understanding depression in spouses of cancer patients in palliative phase. *Psycho-Oncology* 24(9), 1131–1137. doi:10.1002/pon.3777

Fasse L, Sultan S, Flahault C, et al. (2014) How do researchers conceive of spousal grief after cancer? A systematic review of models used by researchers to study spousal grief in the cancer context. *Psycho-Oncology* 23(2), 131–142. doi:10.1002/pon.3412

Fujisawa D, Miyashita M, Nakajima S, et al. (2010) Prevalence and determinants of complicated grief in general population. *Journal of Affective Disorders* 127(1–3), 352–358. doi:10.1016/j.jad.2010.06.008

Garrourste-Orgeas M, Flahault C, Poulain E, et al. (2019a) The Fami-Life Study: Protocol of a prospective observational multicenter mixed study of psychological consequences of grieving relatives in French palliative care units on behalf of the Family Research in Palliative Care (F.R.I.P.C research network). *BMC Palliative Care* 18(1), 111. doi:10.1186/s12904-019- 0496-4

Garrourste-Orgeas M, Flahault C, Vinatier I, et al. (2019b) Effect of an ICU diary on posttraumatic stress disorder symptoms among patients receiving
mechanical ventilation: A randomized clinical trial. *Journal of the American Association* **322**(3), 229-239. doi:10.1001/jama.2019.9058

Geng HM, Chuang DM, Yang F, et al. (2018) Prevalence and determinants of depression in caregivers of cancer patients: A systematic review and meta-analysis. *Medicine (Baltimore)* **97**(3), e11863. doi:10.1097/MD. 00000000000011863

Ghesquiere A, Haidar YM and Shear MK (2011) Risks for complicated grief in family caregivers. *Journal of Social Work in End-Of-Life & Palliative Care* **7**(2-3), 216-240. doi:10.1080/15524256.2011.593158

Ghesquiere A, Shear MK and Duan N (2013) Outcomes of bereavement care among widowed older adults with complicated grief and depression. *Journal of Primary Care & Community Health* **4**(4), 256-264. doi:10.1177/ 2150131913481231

Grassi L (2007) Bereavement in families with relatives dying of cancer *Current Opinions Support Palliative Care*. **1**(1), 43-49. doi:10.1097/SPC. 0b013e32813a3276

Grosse J, Treml J and Kersting A (2018) Impact of caregiver burden on mental health in bereaved caregivers of cancer patients: A systematic review. *Psycho-Oncology* **27**(3), 757-767. doi:10.1002/pon.4529

Guldin MB, Vedsted P, Zachariae R, et al. (2012) Complicated grief and need for professional support in family caregivers of cancer patients in palliative care: A longitudinal cohort study. *Supportive Care in Cancer* **20**(8), 1679-1685. doi:10.1007/s00520-011-1260-3

Harding R, Leam C, Pearce A, et al. (2002) A multi-professional short-term group intervention for informal caregivers of patients using a home palliative care service. *Journal of Palliative Care* **18**(4), 275-281. doi:10.1177/ 082585970201800405

Hargrave PA, Leathem JM and Long NR (2012) Peritraumatic distress: Its relationship to posttraumatic stress and complicated grief symptoms in sudden death survivors. *Journal of Traumatic Stress* **25**(3), 344-347. doi:10.1002/jts. 21703

Hayward JS, Makinde O and Vasudev NS (2016) Letters of condolence: Assessing attitudes and variability in practice amongst oncologists and palliative care doctors in Yorkshire. *Ecan cancer*. doi:10.3332/ ecancer.2016.642

Henriksson A and Andershed B (2007) A support group programme for relatives during the late palliative phase. *International Journal of Palliative Nursing* **13**(4), 175-183. doi:10.12968/ijpn.2007.13.4.23484

Henriksson A, Benzein E, Ternestedt BM, et al. (2011) Meeting needs of family members of persons with life-threatening illness: A support group program during ongoing palliative care. *Palliative & Supportive Care* **9**(3), 263-271. doi:10.1017/S1478951511000216

Hirooka K, Fukahori H, Ozawa M, et al. (2017) Differences in posttraumatic growth and grief reactions among adolescents by relationship with the deceased. *Journal of Advanced Nursing* **73**(4), 955-965. doi:10.1111/jan. 13196

Hirooka K, Fukahori H, Taku K, et al. (2017a) Quality of death, rumination, and posttraumatic growth among bereaved family members of cancer patients in home palliative care. *Psycho-Oncology* **26**(12), 2168-2174. doi:10.1002/pon.4446

Hirooka K, Fukahori H, Taku K, et al. (2018b) Examining posttraumatic growth among bereaved family members of patients with cancer who received palliative care at home. *American Journal of Hospice and Palliative Medicine* **35**(2), 211-217. doi:10.1177/104990917703358

Hoffmann R, Grosse J, Nagl M, et al. (2018) Internet-based grief therapy for bereaved individuals after loss due to Haematological cancer: Study protocol of a randomized controlled trial. *BMC Psychiatry* **18**(1), 52. doi:10.1186/ s12888-018-1633-y

Horowitz MJ, Siegel B, Holen A, et al. (1997) Diagnostic criteria for complicated grief disorder. *American Journal of Psychiatry* **154**(7), 904-910.

Jacobs S and Ostfeld A (1997) An epidemiological review of the mortality of bereavement. *Psychosomatic Medicine* **39**(5), 344-357. doi:10.1097/ 00006842-197709000-00006

Kentish-Barnes N, Chevret S, Champigneulle B, et al. (2017) Effect of a con-
dolence letter on grief symptoms among relatives of patients who died in the
ICU: A randomized clinical trial. *Intensive Care Medicine* **43**(4), 473-484.
doi:10.1007/s00134-016-4669-9

Kentish-Barnes N, McAdam JL, Kouki S, et al. (2015) Research participation for bereaved family members: Experience and insights from a qualitative study. *Critical Care Medicine* **43**(9), 1839-1845. doi:10.1097/CCM. 00000000000001092

Kersting A, Brahler E, Glaesmer H, et al. (2011) Prevalence of complicated grief in a representative population-based sample. *Journal of Affective Disorders* **131**(1-3), 339-343. doi:10.1016/j.jad.2010.11.032

Litz BT, Schorr Y, Delaney E, et al. (2014) A randomized controlled trial of an internet-based therapist-assisted indicated preventive intervention for prolonged grief disorder. *Behaviour Research and Therapy* **61**, 23-34. doi:10.1016/j.brat.2014.07.005

Lobb EA, Kristjanson LJ, Aoun SM, et al. (2010) Predictors of complicated grief: A systematic review of empirical studies. *Death Studies* **34**(8), 673-698. doi:10.1080/07481187.2010.496686

Marwit SJ, Chibnall JT, Dougherty R, et al. (2008) Assessing pre-death grief in cancer caregivers using the Marwit-Meuser Caregiver Grief Inventory (MM-CGI). *Psycho-Oncology* **17**(3), 300-303. doi:10.1002/pon. 1218

Milberg A, Rydstrand K, Helander L, et al. (2005) Participants’ experiences of a support group intervention for family members during ongoing palliative home care. *Journal of Palliative Care* **21**(4), 277-284. doi:10.1177/ 082585970502100407

Miller LM, Utz RL, Supiano K, et al. (2020) Health profiles of spouse caregivers: The role of active coping and the risk for developing prolonged grief symptoms. *Social Science & Medicine* **266**, 113455. doi:10.1016/j.socscimed. 2020.113455

Morita T, Akechi T, Ikenaga M, et al. (2007) Terminal delirium: Recommendations from bereaved families’ experiences. *Journal of Pain and Symptom Management* **34**(6), 579-589. doi:10.1016/j.jpainsymman.2007.01. 012

Mutabaruka J, Sejourne N, Bui E, et al. (2012) Traumatic grief and traumatic stress in survivors 12 years after the genocide in Rwanda. *Stress and Health* **28**(4), 289-296. doi:10.1002/smi.1429

Ndiok A and Ncama B (2018) Assessment of palliative care needs of patients/families living with cancer in a developing country. *Scandinavian Journal of Caring Sciences* **32**(3), 1215-1226. doi:10.1111/scs.12568

Neria Y, Gross R, Litz B, et al. (2007) Prevalence and psychological correlates of complicated grief among bereaved adults 2.5-3.5 years after September 11th attacks. *Journal of Traumatic Stress* **20**(3), 251-262. doi:10.1002/jts. 20223

Newson RS, Boelen PA, Hek K, et al. (2011) The prevalence and characteristics of complicated grief in older adults. *Journal of Affective Disorders* **132**(1-2), 231-238. doi:10.1016/j.jad.2011.02.021

Nielsen MK, Neergaard MA, Jensen AB, et al. (2017) Predictors of complicated grief and depression in bereaved caregivers: A Nationwide Prospective Cohort Study. *Journal of Pain and Symptom management* **53**(3), 540-550. doi:10.1016/j.jpainsymman.2016.09.013

Pochard F, Darmon M, Fassier T, et al. (2005) Symptoms of anxiety and depression in family members of intensive care unit patients before discharge or death. A prospective multicenter study. *Journal of Critical Care* **20**(1), 90-96. doi:10.1016/j.jcrc.2004.11.004

Porter AS, Weaver MS, Snaman JM, et al. (2021) “Still caring for the fam-
ily”: Condolence expression training for pediatric residents. *Journal of Pain
Symptom Management* **62**(6), 1188-1197. doi:10.1016/j.jpainsymman.2021.
05.019

Prigerson HG, Bierhals AJ, Kasl SV, et al. (1997) Traumatic grief as a risk fac-
tor for mental and physical morbidity. *American Journal of Psychiatry* **154**(5),
616-623. doi:10.1176/ajp.154.5.616

Prigerson HG, Bridge J, Maciejewski PK, et al. (1999) Influence of trau-
matic grief on suicidal ideation among young adults. *American Journal of
Psychiatry* **156**(12), 1994-1995. doi:10.1176/ajp.156.12.1994

Prigerson HG, Horowitz MJ, Jacobs SC, et al. (2009) Prolonged grief disorder: Psychometric validation of criteria proposed for DSM-V and ICD-11. *PLoS Medicine* **6**(8), e1000121. doi:10.1371/journal.pmed.1000121

Rash CJ, Coffey SF, Baschnagel JS, et al. (2008) Psychometric properties of the IES-R in traumatized substance dependent individuals with and without PTSD. *Addictive Behaviors* **33**(8), 1039-1047. doi:10.1016/j.addbeh.2008. 04.006
Rhondali W, Dev R, Barbaret C, et al. (2014) Family conferences in palliative care: A survey of health care providers in France. *Journal of Pain and Symptom Management* 48(6), 1117-1124. doi:10.1016/j.jpainsymman.2014.03.007

Shear K, Frank E, Houck PR, et al. (2005) Treatment of complicated grief: A randomized controlled trial. *Journal of American Association* 293(21), 2601-2608. doi:10.1001/jama.293.21.2601

Shear MK, Ghesquiere A and Glickman K (2013) Bereavement and complicated grief. *Current Psychiatry Reports* 15(11), 406. doi:10.1007/s11920-013-0406-z

Simon NM (2013) Treating complicated grief. *Journal of American Association* 310(4), 416-423. doi:10.1001/jama.2013.8614

Thomas K, Hudson P, Trauer T, et al. (2014) Risk factors for developing prolonged grief during bereavement in family carers of cancer patients in palliative care: A longitudinal study. *Journal of Pain and Symptom Management* 47(3), 531-541. doi:10.1016/j.jpainsymman.2013.05.022

Tsai WI, Prigerson HG, Li CY, et al. (2016) Longitudinal changes and predictors of prolonged grief for bereaved family caregivers over the first 2 years

after the terminally ill cancer patient's death. *Palliative Medicine* 30(5), 495-503. doi:10.1177/0269216315603261

van Doorn C, Kasl SV, Beery LC, et al. (1998) The influence of marital quality and attachment styles on traumatic grief and depressive symptoms. *The Journal of Nervous & Mental Disease* 186(9), 566-573. doi:10.1097/00005053-199809000-00008

Wiese CH, Morgenthal HC, Bartels UE, et al. (2010) Post-mortal bereavement of family caregivers in Germany: A prospective interview-based investigation. *Wiener Klinische Wochenschrift* 122(13-14), 384-389. doi:10.1007/s00508-010-1396-z

Zigmond AS and Snaith RP (1983) The Hospital Anxiety and Depression scale. *Acta Psychiatrica Scandinavica* 67(6), 361-370. doi:10.1111/j.1600-0447.1983.tb09716.x

Zisook S, Reynolds CF, Pies R, et al. (2010a) Bereavement, complicated grief, and DSM, part 1: Depression. *Journal of Clinical Psychiatry* 71(7), 955-956. doi:10.4088/JCP.10ac06303blu

Zisook S, Simon NM, Reynolds CF, et al. (2010b) Bereavement, complicated grief, and DSM, part 2: Complicated grief. *The Journal of Clinical Psychiatry* 71(8), 1097-1098. doi:10.4088/JCP.10ac06391blu