my topic is: the bereaved individual

my topic is: the bereaved individual
NR326 Mental Health Nursing RUA: Scholarly Article Review Guidelines Purpose The student will review, summarize, and critique a scholarly article related to a mental health topic. Course outcomes: This assignment enables the student to meet the following course outcomes. (CO 4) Utilize critical thinking skills in clinical decision-making and implementation of the nursing process for psychiatric/mental health clients. (PO 4) (CO 5) Utilize available resources to meet self-identified goals for personal, professional, and educational development appropriate to the mental health setting. (PO 5) (CO 7) Examine moral, ethical, legal, and professional standards and principles as a basis for clinical decision-making. (PO 6) (CO 9) Utilize research findings as a basis for the development of a group leadership experience. (PO 8) Due date: Your faculty member will inform you when this assignment is due. The Late Assignment Policy applies to this assignment. Total points possible: 100 points Preparing the assignment Follow these guidelines when completing this assignment. Speak with your faculty member if you have questions. Select a scholarly nursing or research article, published within the last five years, related to mental health nursing. The content of the article must relate to evidence-based practice. You may need to evaluate several articles to find one that is appropriate. Ensure that no other member of your clinical group chooses the same article, then submit your choice for faculty approval. The submitted assignment should be 2-3 pages in length, excluding the title and reference pages. Include the following sections (detailed criteria listed below and in the Grading Rubric must match exactly). Introduction (10 points/10%) Establishes purpose of the paper Captures attention of the reader Article Summary (30 points/30%) Statistics to support significance of the topic to mental health care Key points of the article Key evidence presented Examples of how the evidence can be incorporated into your nursing practice Article Critique (30 points/30%) Present strengths of the article Present weaknesses of the article Discuss if you would/would not recommend this article to a colleague Conclusion (15 points/15%) Provides analysis or synthesis of information within the body of the text Supported by ides presented in the body of the paper Is clearly written Article Selection and Approval (5 points/5%) Current (published in last 5 years) Relevant to mental health care Not used by another student within the clinical group Submitted and approved as directed by instructor APA format and Writing Mechanics (10 points/10%) Correct use of standard English grammar and sentence structure No spelling or typographical errors Document includes title and reference pages Citations in the text and reference page For writing assistance (APA, formatting, or grammar) visit the APA Citation and Writing page in the online library. Please note that your instructor may provide you with additional assessments in any form to determine that you fully understand the concepts learned in the review module. Grading Rubric Criteria are met when the student’s application of knowledge demonstrates achievement of the outcomes for this assignment. Assignment Section and Required Criteria (Points possible/% of total points available) Highest Level of Performance High Level of Performance Satisfactory Level of Performance Unsatisfactory Level of Performance Section not present in paper Introduction (10 points/10%) 10 points 8 points 0 points Required criteria Establishes purpose of the paper Captures attention of the reader Includes 2 requirements for section. Includes 1 requirement for section. No requirements for this section presented. Article Summary (30 points/30%) 30 points 25 points 24 points 11 points 0 points Required criteria Statistics to support significance of the topic to mental health care Key points of the article Key evidence presented Examples of how the evidence can be incorporated into your nursing practice Includes 4 requirements for section. Includes 3 requirements for section. Includes 2 requirements for section. Includes 1 requirement for section. No requirements for this section presented. Article Critique (30 points/30%) 30 points 25 points 11 points 0 points Required criteria Present strengths of the article Present weaknesses of the article Discuss if you would/would not recommend this article to a colleague Includes 3 requirements for section. Includes 2 requirements for section. Includes 1 requirement for section. No requirements for this section presented. Conclusion (15 points/15%) 15 points 11 points 6 points 0 points Provides analysis or synthesis of information within the body of the text Supported by ides presented in the body of the paper Is clearly written Includes 3 requirements for section. Includes 2 requirements for section. Includes 1 requirement for section. No requirements for this section presented. Article Selection and Approval (5 points/5%) 5 points 4 points 3 points 2 points 0 points Current (published in last 5 years) Relevant to mental health care Includes 4 Includes 3 Includes 2 Includes 1 No requirements for Not used by another student within the clinical group Submitted and approved as directed by instructor requirements for section. requirements for section. requirements for section. requirement for section. this section presented. APA Format and Writing Mechanics (10 points/10%) 10 points 8 points 7 points 4 points 0 points Correct use of standard English grammar and sentence structure No spelling or typographical errors Document includes title and reference pages Citations in the text and reference page Includes 4 requirements for section. Includes 3 requirements for section. Includes 2 requirements for section. Includes 1 requirement for section. No requirements for this section presented. Total Points Possible = 100 points
my topic is: the bereaved individual
volume 24 number 2 / March 2021 / 15 CLINICIANS OFTEN encounter sleep disturbances in older people who have recently experienced the death of a partner or spouse (Li et al 2018). Bereavement is particularly challenging for those who are physically and emotionally closest to the deceased individual, and studies have found that family carers experience mood and sleep disturbances after the person they were caring for has died (Jonasson et al 2009, Lerdal et al 2016). The reasons for this are numerous and include grief about the loss, departures from daily routine and changes in identity as partner and carer (Tang and Chow 2017). Older people might have spent much of their life with their partner and are then expected to adjust to daily life without that person. Bereavement is different for each individual, with some studies finding that consequences of the loss include symptoms of anxiety, depression and sleep disturbances (Jonasson et al 2009). Although bereavement has been studied thoroughly in the literature, there is still much to understand about this developmental transition and the effect it can have on the body and mind, particularly on sleep. This article offers a systematic review of the literature on sleep disturbances in bereaved older people. Background Biological and social changes Sleep disturbances in older people are well documented and include shorter sleep duration, increased time spent awake at night and an increase in the number of daytime naps (Li et al 2018). Citation Godzik C (2020) Sleep disturbances in bereaved older people: a review of the literature. Mental Health Practice. doi: 10.7748/mhp.2020.e1492 Peer review This article has been subject to external double-blind peer review and has been checked for plagiarism using automated sof tware Correspondence [email protected]. org Conflict of interest None declared Accepted 4 May 2020 Published online October 2020 Why you should read this article: ●To increase your understanding of the physical and mental health consequences of bereavement in old age ●To learn about interventions that may improve sleep in older people before and after the death of a loved one ●To gain awareness of the gaps in the literature on sleep disturbances in bereaved older people Sleep disturbances in bereaved older people: a review of the literature Cassandra Godzik Abstract Sleep disturbances are often seen in older people who have recently experienced the death of a loved one, such as a partner or spouse. Older family carers are particularly at risk of mood and sleep disturbances, not only after the death of the person they were caring for but also beforehand. Sleep disturbances can be treated with psychotropic medicines, but these are not adequate in older people because of the risk of falls, fractures and road accidents. Cognitive behavioural therapy for insomnia is a non-pharmacological intervention that has been found to be beneficial in bereaved older carers. This article offers a systematic review of the literature on sleep disturbances in bereaved older people. One of the main findings is that sleep disturbances may begin before the loved one’s death, during the caregiving period. More research is needed on sleep disturbances in bereaved older people – notably in those aged ≥85 years, in partners or spouses from same-sex couples, into long-term symptoms post-bereavement, and into sleep interventions provided before the loved one’s death. Author details Cassandra Godzik, Geisel School of Medicine, Dartmouth Centers for Health and Aging, Hanover, New Hampshire, US; and Department of Psychiatry, Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire, US Keywords bereavement, bereavement support, carers, clinical, end of life care, grief, patient experience, patients, professional, sleep mentalhealthpractice.com | PEER≥REVIEWED | evidence & practice / bereavement PermissionTo reuse this article or for information about reprints and permissions, please contact [email protected] 16 / March 2021 / volume 24 number 2 Older people are unique in terms of their sleep for several reasons. In advanced age, the circadian rhythm (temporal body clock) shifts to a new schedule (Chen et al 2016). Why this occurs is still not known, but it appears that the sleep-wake cycle biologically changes with age. Beyond this biological shift, sleep may also be affected by life events that occur in old age. For example, older people no longer have the daytime work requirements that warrant getting up early in the morning and staying awake for the whole day (Ohayon and Vecchierini 2005). They can take daytime naps that reduce their sleep pressure ( time needed to rest) during the night hours (Häusler et al 2019). Sleep practices in older people can affect markers of inflammation (Okun et al 2011) and this can be an issue in those who are bereaved (Seiler et al 2018). Seiler et al (2018) found that fatigued individuals who had recently been bereaved had increased levels of C-reactive protein (CRP) compared with non-fatigued bereaved individuals. Similarly, Chirinos et al (2019) found an association between elevated CRP levels and sleep disturbances in those who had been recently bereaved. Effects on physical and mental health Research has found that inadequate sleep can have an adverse effect on people’s health (Cappuccio and Miller 2017, Itani et al 2017). For example, people who report chronically sleeping less than required experience more complications from diabetes and coronary issues (Cappuccio and Miller 2017). This could be explained by the metabolic processes that are thought to take place during sleeping hours (Chirinos et al 2019). Quality and amount of sleep are associated with mood symptoms. Research has indicated that people with impaired sleep – which includes being unable to fall asleep and/or remain asleep through the night – report more depressive symptoms (Tanimukai et al 2015). Seiler et al (2018) found that fatigued bereaved individuals reported higher levels of stress and depressive symptoms than non-fatigued bereaved individuals. Bereavement has been shown to affect people’s physical and mental health. One study in 389,316 bereaved individuals found that they had excess mortality and an increased number of physical diseases compared with non-bereaved individuals (Prior et al 2018). Spousal bereavement has been associated with higher rates of conditions such as cirrhosis (Erlangsen et al 2017). In a study that looked at 432 bereaved carers, researchers found that sleep and mood disturbances were significant in that population (Chiu et al 2011). Effects on cognition It is recognised that cognitive issues can be present in individuals who are unable to obtain adequate sleep. The process of memory consolidation has been shown to be related to sleep (Gildner et al 2014) and a review of observational studies found that, among older people, those with extreme sleep durations, whether long or short, had worse cognition (Devore et al 2016). Cognition has also been researched in bereaved people, for example by Pérez et al (2018), who found that prolonged grief disorder was associated with reduced cognitive function. Another study found changes in memory consolidation related to sleep fragmentation in older people (Pace- Schott and Spencer 2015), while widowhood has been found to be associated with cognitive decline (Lyu et al 2018). Treatments for sleep disturbances Short-term insomnia, defined as sleep disturbances lasting between a few days and a few weeks, can lead to chronic or long-term insomnia (Griffiths and Peerson 2005). Sleep disturbances are often treated, and may be temporarily resolved, with prescribed psychotropic medicines, notably benzodiazepines such as temazepam or zolpidem tartrate (Pillai et al 2017). However, the long-term risks associated with these medicines are well documented, particularly in older people (Kaufmann et al 2018, Kim et al 2019). Studies have found an increased risk of falls and fractures with benzodiazepines (Tinetti and Kumar 2010, Bakken et al 2014), which can also cause morning drowsiness and reduce co-ordination, with a potential risk of road accidents if patients are still driving (Booth et al 2016). Even over-the-counter medicines used for sleep contain ingredients that may increase the risk of falls, cognitive impairment and dizziness. Common over-the-counter sleeping aids include diphenhydramine and doxylamine, which are both listed as potentially inappropriate medicines in the Beers Criteria for Potentially Inappropriate Medication Use in Older Adults (American Geriatrics Society Beers Criteria Update Expert Panel 2019). Sleep disturbances can also be managed with non-pharmacological methods, such as sleep hygiene strategies and cognitive behavioural therapy (CBT). Sleep hygiene strategies usually involve education about lifestyle and how the environment affects sleep, including information about fluid intake, exercise restrictions, night- time routines and adherence to a predetermined bedtime (Irish et al 2015). CBT for insomnia (CBT-I) is a psychotherapy programme designed mentalhealthpractice.com | PEER≥REVIEWED | evidence & practice / bereavement volume 24 number 2 / March 2021 / 17 to support individuals who struggle to initiate and maintain sleep, and has been delivered in a variety of ways ranging from in-person group sessions to individual online sessions (Taylor and Pruiksma 2014). Research has found the treatment to be acceptable and to reduce sleep disturbances and depressive symptoms in bereaved older carers (Carter et al 2009). Findings about CBT-I have generally been positive, with one study (Currie et al 2004) showing that participants recovering from alcohol dependence who received a CBT-I intervention had a significantly improved sleep efficiency compared with controls. However, the number of CBT-I therapists is limited. Method For this systematic literature review, four major health and psychology online databases were searched: PubMed, Cumulative Index of Nursing and Allied Health Literature, OVID with PsychInfo, and Scopus. Medical subject headings (MeSH) used included: ‘ bereavement’, ‘sleep initiation and maintenance disorders’, ‘spousal’, ‘caregivers’, ‘aged’ and ‘middle aged’. Search strings using these MeSH were used to locate relevant articles. Once relevant articles had been identified, their abstracts were examined by the author. Articles deemed to be of interest were retrieved in their entirety for further reading. Those meeting the inclusion criteria were retained for inclusion in the literature review. The inclusion criteria were: »Peer-reviewed content. »Original research. »Articles published between 2008 and 2018. »Articles written in English. »Study participants aged ≥50 years and bereaved in the previous decade. »Measurement of sleep disturbances. The database search produced a total of 153 non-duplicate articles. Reviewing the abstracts left 59 articles, which were read in their entirety; 51 of them were excluded because they did not fulfil all inclusion criteria. Eight articles were therefore included in the literature review. They are described in detail in Table 1. All eight articles reported quantitative studies, two of which were behavioural interventions; the remaining six were descriptive studies. The quality of the eight articles was evaluated using the Quality Assessment Tool for Quantitative Studies (Effective Public Health Practice Project 1998) and rated. The ratings are shown in Table 1. Findings The findings of the literature review are summarised under four themes: »Gender differences in symptomatology. »Carer versus non-carer responsibilities and dying process experience. »Sleep disturbances beginning during the caregiving period. »Benefits of sleep interventions. Gender differences in symptomatology Women made up the largest group of study participants in four of the eight studies (Monk et al 2008, Carter et al 2009, Pfoff et al 2014, Lerdal et al 2016). In one study, only widowers had been recruited (Jonasson et al 2009). In Tanimukai et al (2015), no statistically significant differences between genders were found for insomnia symptoms, but women had significantly more depressive symptoms than men during the bereavement period. The age of the bereaved played a role in the number of insomnia symptoms reported. Insomnia symptoms significantly increased in women aged 50-59 years and in men aged 65-70 years in the first year of bereavement (Simpson et al 2014). None of the studies had collected longitudinal data beyond a year for women. In their study population of widowers, Jonasson et al (2009) determined that sleep disturbances continued for four to five years after the death of the spouse (Jonasson et al 2009). Carer versus non-carer responsibilities and dying process experience The involvement of the surviving partner or spouse in the care of their partner or spouse before death appears to be a critical component in understanding sleep disturbances in bereaved older people. The role of the surviving spouse can be categorised as either ‘carer’ or ‘non- carer’ (Carter et al 2009). A spousal carer is the person who primarily supports their partner at the end of life; the care provided typically involves dressing, cleaning, feeding and administering medicines. A spousal non-carer may still provide some care to their partner but they are not the sole or main carer; there may be a round-the-clock paid carer in the home, or the partner may live in a hospice or be hospitalised. Spousal carers had high levels of depression in bereavement. Carter et al (2009) found that primary carers had scores ranging from 4 to 45 (mean 17) on the Center for Epidemiologic Studies – Depression scale. The spousal carer is a witness to the dying process of their spouse or partner, which can be life-altering. In Jonasson et al (2009), men who had witnessed their wives experiencing unresolved pain had an increased risk of sleep-related issues for four to five years after their loss; men whose wives had experienced anxiety in Key points ●Sleep disturbances are often seen in older people who have recently experienced the death of a loved one, such as a partner or spouse ●Among bereaved older people, those who were the main carers of the deceased are particularly at risk of mood and sleep disturbances ●Sleep disturbances in older carers may start before the death of their loved one, during the caregiving period ●Psychotropic medicines such as benzodiazepines are not adequate to treat long- term insomnia in older people because of the risk of falls, fractures and road accidents ●Cognitive behavioural therapy for insomnia has been shown to reduce sleep disturbances and depressive symptoms in bereaved older carers mentalhealthpractice.com | PEER≥REVIEWED | Table 1. Detailed description of the eight studies included in the systematic literature review Citation Purpose Measurement of variables Population Primary findings Strengths and limitations Rating* Carter P, Mikan S, Simpson C (2009) A feasibility study of a two-session home-based cognitive behavioral therapy-insomnia intervention for bereaved family caregivers. Palliative and Supportive Care. 7, 2, 197-206. doi: 10.1017/S147895150900025X To investigate the implementation of a cognitive behavioural therapy for insomnia (CBT-I) intervention for treating insomnia and depressive symptoms in bereaved family carers »Sleep quality: –19-item Pittsburgh Sleep Quality Index –Sleep diaries –Actigraph worn for three 72-hour periods »Goal attainment: Goal Attainment Scaling Measure »Depression: 20-item Center for Epidemiologic Studies – Depression scale 11 bereaved primary carers recruited through flyers at oncology centres in Texas Statistically significant improvement in sleep disturbance from baseline to five weeks (total length of study). No statistically significant improvement in depressive symptoms »Strengths: minimal resources needed for the intervention, optimal participant retention »Limitations: no control group, small sample size, heterogeneity of sample 1 Jonasson J, Hauksdóttir A, Valdimarsdóttir U et al (2009) Unrelieved symptoms of female cancer patients during their last months of life and long-term psychological morbidity in their widowers: a nationwide population- based study. European Journal of Cancer. 45, 10, 1839- 1845. doi: 10.1016/j.ejca.2009.02.008 To examine surviving widowers’ mental health and sleep status four to five years after their wives’ deaths from cancer »Depression and anxiety: Hospital Anxiety and Depression Scale »Wife’s death and other information: 69-item survey developed by the research team 691 men enrolled through Sweden national registries participated in the final study Men who had observed their wives having depression in the last three months of life had an increased risk of waking up at night with anxiety. Men who had observed their wives experiencing unrelieved pain were at increased risk of being unable to fall asleep »Strengths: large databases used, three periods of participants’ lives captured »Limitations: recall biases, no significant difference in the demographic characteristics between participants and non-participants 2 Lerdal A, Slåtten K, Saghaug E et al (2016) Sleep among bereaved caregivers of patients admitted to hospice: a 1-year longitudinal pilot study. BMJ Open. 6, 1, e009345. doi: 10.1136/bmjopen-2015-009345 To measure sleep changes in bereaved family members before and after the death of a relative »Sleep quality: »19-item Pittsburgh Sleep Quality Index »Actigraph worn for four nights and three days »Sleep diaries Sixteen family members recruited in a hospice centre Bereaved spousal carers experienced significantly worse sleep quality than bereaved carers who were not the deceased person’s partner or spouse. Older carers (>65 years) had longer sleep durations than younger carers (<65 years) »Strengths: objective and subjective measures of sleep, sleep measures collected before and after death »Limitations: small sample size, 20% attrition rate, relatives were in a hospice and not at home 1 Monk T, Begley A, Billy B et al (2008) Sleep and circadian rhythms in spousally bereaved seniors. Chronobiology International. 25, 1, 83-98. doi: 10.1080/07420520801909320 To examine circadian rhythms in partners experiencing spousal bereavement »Sleep quality: –Pittsburgh Sleep Quality Index –Sleep diaries –17-item Social Rhythm Metric –Actigraph worn for two weeks »Grief: –Composite Scale of Mourningness –Texas Revised Inventory of Grief –Index of Complicated Grief »Biomarkers: core body temperature 28 spousally bereaved older people recruited via word of mouth and advertisements Higher levels of grief were associated with less sleep. All other associations with sleep were not statistically significant »Strengths: objective and subjective measures of sleep »Limitations: small sample size, mean age of participants (72.3 years) younger compared with other studies, older people aged ≥85 years not represented 1 Monk T, Germain A, Buysse D (2009) The sleep of the bereaved. Sleep and Hypnosis. 11, 1, 219 To compare self-reported sleep measures in a group of bereaved partners, a group of non-bereaved adults with insomnia, and a group of controls »Sleep quality: »18-item Pittsburgh Sleep Quality Index »Two-week Pittsburgh Sleep Diary »Actigraph worn for two weeks 47 bereaved partners recruited by advertisements, oral presentations, and word of mouth Sleep quality of bereaved partners found to be somewhere between the sleep qualities of ‘good sleeper ’ controls and of non-bereaved adults with insomnia. In diaries, sleep latency values were similar for bereaved partners and non-bereaved adults with insomnia »Strengths: bereavement period clearly defined as being between four and 19 months »Limitations: objective data collected using an actigraph but no effect size observed, which could be due to the fact that actigraphy is less reliable in older people 2 Pfoff M, Zarotney J, Monk T (2014) Can a function- based therapy for spousally bereaved seniors accrue benefits in both functional and emotional domains? Death Studies. 38, 6-10, 381-386. doi: 10.1080/07481187.2013.766658 To compare the effectiveness of functional therapy versus control therapy for sleep and mood »Grief: 21-item Texas Revised Inventory of Grief »Depression: 21-item Hamilton Rating Scale for Depression »Objective sleep: Pittsburgh Sleep Diary »Sleep quality: 18-item Pittsburgh Sleep Quality Index 38 participants at least two months after loss of a partner, recruited from senior centres, funeral homes and churches Grief, mood and sleep improved in both the functional therapy group and the control therapy group. The functional therapy group, who received sleep education, showed greater improvements »Strengths: significant health screenings to rule out organic sleep disorders, long period of intervention (ten weeks) »Limitations: small sample size, no blinding of participants 2 Simpson C, Allegra J, Ezeamama A et al (2014) The impact of mid- and late-life loss on insomnia: findings from the Health and Retirement Study, 2010 cohort. Family and Community Health. 37, 4, 317-326. doi: 10.1097/FCH.0000000000000039 To examine the association between loss and insomnia symptoms in different age cohorts and genders »Insomnia: four-question insomnia measure »Depression: eight-item Center for Epidemiologic Studies – Depression scale »Losses: number of losses in participant’s life »Lifestyle: physical activity, body mass index, smoking, alcohol consumption Data from 12,759 participants in the Health and Retirement Study There was a positive relationship between the number of insomnia symptoms and the number of losses experienced. Loss was associated with predictive increase of insomnia symptoms in women aged 50-59 years and men aged 65-70 years »Strengths: large sample size »Limitations: many potential covariates not explored, including the amount of time that had passed since the loss and the relationship of participants with the person who had died (for example, participants could have lost a partner or a child) 2 Tanimukai H, Adachi H, Hirai K et al (2015) Association between depressive symptoms and changes in sleep condition in the grieving process. Supportive Care in Cancer. 23, 7, 1925-1931. doi: 10.1007/s00520-014-2548-x To clarify the prevalence of insomnia symptoms and to explore associations between present depressive state and changes in sleep condition in the grieving process in bereaved Japanese families »Insomnia: four-question insomnia measure »Psychological status: 11-item Center for Epidemiologic Studies – Depression scale »Attribution of symptoms to bereavement: one-item question 561 bereaved families recruited from 103 certified palliative care units in Japan Depressive symptoms were highest in women and in spouses. Insomnia symptoms were highest in participants aged ≥65 years and in spouses. 81% of all participants experienced insomnia symptoms »Strengths: large sample size »Limitations: self-reported questionnaires, recalling past sleep conditions, simpler version of insomnia questionnaire than is typically used in research, treatment interventions possible but not evaluated 2 * Ratings obtained by using the Quality Assessment Tool for Quantitative Studies: 1 = strong; 2 = moderate; 3 = weak 18 / March 2021 / volume 24 number 2 mentalhealthpractice.com | PEER≥REVIEWED | evidence & practice / bereavement Table 1. Detailed description of the eight studies included in the systematic literature review Citation Purpose Measurement of variables Population Primary findings Strengths and limitations Rating* Carter P, Mikan S, Simpson C (2009) A feasibility study of a two-session home-based cognitive behavioral therapy-insomnia intervention for bereaved family caregivers. Palliative and Supportive Care. 7, 2, 197-206. doi: 10.1017/S147895150900025X To investigate the implementation of a cognitive behavioural therapy for insomnia (CBT-I) intervention for treating insomnia and depressive symptoms in bereaved family carers »Sleep quality: –19-item Pittsburgh Sleep Quality Index –Sleep diaries –Actigraph worn for three 72-hour periods »Goal attainment: Goal Attainment Scaling Measure »Depression: 20-item Center for Epidemiologic Studies – Depression scale 11 bereaved primary carers recruited through flyers at oncology centres in Texas Statistically significant improvement in sleep disturbance from baseline to five weeks (total length of study). No statistically significant improvement in depressive symptoms »Strengths: minimal resources needed for the intervention, optimal participant retention »Limitations: no control group, small sample size, heterogeneity of sample 1 Jonasson J, Hauksdóttir A, Valdimarsdóttir U et al (2009) Unrelieved symptoms of female cancer patients during their last months of life and long-term psychological morbidity in their widowers: a nationwide population- based study. European Journal of Cancer. 45, 10, 1839- 1845. doi: 10.1016/j.ejca.2009.02.008 To examine surviving widowers’ mental health and sleep status four to five years after their wives’ deaths from cancer »Depression and anxiety: Hospital Anxiety and Depression Scale »Wife’s death and other information: 69-item survey developed by the research team 691 men enrolled through Sweden national registries participated in the final study Men who had observed their wives having depression in the last three months of life had an increased risk of waking up at night with anxiety. Men who had observed their wives experiencing unrelieved pain were at increased risk of being unable to fall asleep »Strengths: large databases used, three periods of participants’ lives captured »Limitations: recall biases, no significant difference in the demographic characteristics between participants and non-participants 2 Lerdal A, Slåtten K, Saghaug E et al (2016) Sleep among bereaved caregivers of patients admitted to hospice: a 1-year longitudinal pilot study. BMJ Open. 6, 1, e009345. doi: 10.1136/bmjopen-2015-009345 To measure sleep changes in bereaved family members before and after the death of a relative »Sleep quality: »19-item Pittsburgh Sleep Quality Index »Actigraph worn for four nights and three days »Sleep diaries Sixteen family members recruited in a hospice centre Bereaved spousal carers experienced significantly worse sleep quality than bereaved carers who were not the deceased person’s partner or spouse. Older carers (>65 years) had longer sleep durations than younger carers (<65 years) »Strengths: objective and subjective measures of sleep, sleep measures collected before and after death »Limitations: small sample size, 20% attrition rate, relatives were in a hospice and not at home 1 Monk T, Begley A, Billy B et al (2008) Sleep and circadian rhythms in spousally bereaved seniors. Chronobiology International. 25, 1, 83-98. doi: 10.1080/07420520801909320 To examine circadian rhythms in partners experiencing spousal bereavement »Sleep quality: –Pittsburgh Sleep Quality Index –Sleep diaries –17-item Social Rhythm Metric –Actigraph worn for two weeks »Grief: –Composite Scale of Mourningness –Texas Revised Inventory of Grief –Index of Complicated Grief »Biomarkers: core body temperature 28 spousally bereaved older people recruited via word of mouth and advertisements Higher levels of grief were associated with less sleep. All other associations with sleep were not statistically significant »Strengths: objective and subjective measures of sleep »Limitations: small sample size, mean age of participants (72.3 years) younger compared with other studies, older people aged ≥85 years not represented 1 Monk T, Germain A, Buysse D (2009) The sleep of the bereaved. Sleep and Hypnosis. 11, 1, 219 To compare self-reported sleep measures in a group of bereaved partners, a group of non-bereaved adults with insomnia, and a group of controls »Sleep quality: »18-item Pittsburgh Sleep Quality Index »Two-week Pittsburgh Sleep Diary »Actigraph worn for two weeks 47 bereaved partners recruited by advertisements, oral presentations, and word of mouth Sleep quality of bereaved partners found to be somewhere between the sleep qualities of ‘good sleeper ’ controls and of non-bereaved adults with insomnia. In diaries, sleep latency values were similar for bereaved partners and non-bereaved adults with insomnia »Strengths: bereavement period clearly defined as being between four and 19 months »Limitations: objective data collected using an actigraph but no effect size observed, which could be due to the fact that actigraphy is less reliable in older people 2 Pfoff M, Zarotney J, Monk T (2014) Can a function- based therapy for spousally bereaved seniors accrue benefits in both functional and emotional domains? Death Studies. 38, 6-10, 381-386. doi: 10.1080/07481187.2013.766658 To compare the effectiveness of functional therapy versus control therapy for sleep and mood »Grief: 21-item Texas Revised Inventory of Grief »Depression: 21-item Hamilton Rating Scale for Depression »Objective sleep: Pittsburgh Sleep Diary »Sleep quality: 18-item Pittsburgh Sleep Quality Index 38 participants at least two months after loss of a partner, recruited from senior centres, funeral homes and churches Grief, mood and sleep improved in both the functional therapy group and the control therapy group. The functional therapy group, who received sleep education, showed greater improvements »Strengths: significant health screenings to rule out organic sleep disorders, long period of intervention (ten weeks) »Limitations: small sample size, no blinding of participants 2 Simpson C, Allegra J, Ezeamama A et al (2014) The impact of mid- and late-life loss on insomnia: findings from the Health and Retirement Study, 2010 cohort. Family and Community Health. 37, 4, 317-326. doi: 10.1097/FCH.0000000000000039 To examine the association between loss and insomnia symptoms in different age cohorts and genders »Insomnia: four-question insomnia measure »Depression: eight-item Center for Epidemiologic Studies – Depression scale »Losses: number of losses in participant’s life »Lifestyle: physical activity, body mass index, smoking, alcohol consumption Data from 12,759 participants in the Health and Retirement Study There was a positive relationship between the number of insomnia symptoms and the number of losses experienced. Loss was associated with predictive increase of insomnia symptoms in women aged 50-59 years and men aged 65-70 years »Strengths: large sample size »Limitations: many potential covariates not explored, including the amount of time that had passed since the loss and the relationship of participants with the person who had died (for example, participants could have lost a partner or a child) 2 Tanimukai H, Adachi H, Hirai K et al (2015) Association between depressive symptoms and changes in sleep condition in the grieving process. Supportive Care in Cancer. 23, 7, 1925-1931. doi: 10.1007/s00520-014-2548-x To clarify the prevalence of insomnia symptoms and to explore associations between present depressive state and changes in sleep condition in the grieving process in bereaved Japanese families »Insomnia: four-question insomnia measure »Psychological status: 11-item Center for Epidemiologic Studies – Depression scale »Attribution of symptoms to bereavement: one-item question 561 bereaved families recruited from 103 certified palliative care units in Japan Depressive symptoms were highest in women and in spouses. Insomnia symptoms were highest in participants aged ≥65 years and in spouses. 81% of all participants experienced insomnia symptoms »Strengths: large sample size »Limitations: self-reported questionnaires, recalling past sleep conditions, simpler version of insomnia questionnaire than is typically used in research, treatment interventions possible but not evaluated 2 * Ratings obtained by using the Quality Assessment Tool for Quantitative Studies: 1 = strong; 2 = moderate; 3 = weak volume 24 number 2 / March 2021 / 19 mentalhealthpractice.com | PEER≥REVIEWED | 20 / March 2021 / volume 24 number 2 the three months before death had unresolved issues falling asleep and frequent night-time awakenings with anxiety during bereavement (Jonasson et al 2009). These various findings could indicate that more contact with one’s partner at the end of life may result in worse outcomes for the surviving partner. When sleep was assessed using objective measures, such as an actigraph – a wearable device that detects activity through light and movement (Scarlett et al 2020) – it did not appear to be affected by spousal death. However, subjective measures of sleep, obtained for example through sleep diaries, were significantly different in the bereaved, who reported more sleep disturbances than controls (Monk et al 2009). Even when no sleep disturbances were recorded by the actigraph, participants continued to report suboptimal sleep quality. Sleep disturbances beginning during the caregiving period Several studies found that sleep disturbances had begun before the death of the loved one. Stressors associated with death and dying begin once death starts to be anticipated and can therefore start to affect carers’ sleep during the caregiving period (Tanimukai et al 2015, Lerdal et al 2016). Sleep quality may remain stable during the transition period into bereavement, so when sleep quality is suboptimal before the relative’s death, it remains suboptimal after their death. Tanimukai et al (2015) found that the prevalence of insomnia in bereaved families was stable between six weeks before and six months after the death of their relative. In the weeks before death, the prevalence of insomnia was 86.5% and after death it was 84.5% (Tanimukai et al 2015). Benefits of sleep interventions Two out of the eight studies included in the literature review had tested interventions, including CBT-I and sleep hygiene strategies, to manage sleep disturbances in their respective populations. Their findings suggest that sleep interventions in the bereavement period are possible and can be beneficial. Carter et al (2009) used a CBT-I intervention administered over two sessions in the home of participants (who were bereaved family carers). When comparing baseline and five- week measurements, sleep measures had significantly improved in terms of self-reported duration, sleep efficiency and Pittsburgh Sleep Quality Index (PSQI) scores (Carter et al 2009). Pfoff et al (2014) used a function-based therapy modality intervention over ten individual sessions. The intervention comprised teaching healthy sleep practices and education about factors that can affect sleep. Sleep and mood improved between baseline and end-of-study assessment in both the treatment group and the control group, but improvements were greater in the treatment group (Pfoff et al 2014). Discussion Sleep disturbances in bereaved older people are an important clinical problem that has not been studied thoroughly. Not adequately addressing this health concern has individual and societal consequences. Medicines such as benzodiazepines are not adequate to treat long-term insomnia in older people because of the risk of falls, fractures and road accidents (Tinetti and Kumar 2010, Bakken et al 2014, Booth et al 2016). Studies in this literature review suggest that sleep disturbances may start before the death of the loved one, so there may be scope in researching the risk characteristics of those vulnerable to sleep disturbances (Lerdal et al 2016), as well as sleep interventions provided during the caregiving period. Clinicians and relatives need to be aware that older carers need support before and after the death of their loved one. The findings of this literature review emphasise that more research is needed in the field of sleep disturbances in bereaved older people. Specific gaps in the literature identified are described below. »Long-term symptoms such as insomnia and low mood in both genders at two, three and four years after the death of a loved one and beyond are not thoroughly understood. Data about the long-term experiences of older men post-bereavement are limited, while the long-term experiences of older women post- bereavement have not yet been explored. »Sleep disturbances among bereaved partners or spouses from same-sex couples have not yet been explored. »Older people aged ≥85 years are rarely represented in study samples, so more research is needed in that age group. »Sleep interventions provided during the caregiving period need be further explored – for example, there is scope for investigating whether sleep disturbances can be prevented or limited by early CBT-I. Limitations This systematic literature review was limited to research published between 2008 and 2018 and retrieved from four databases. The included articles had important limitations. While the measures used in the studies were reliable and valid, no consistent set of measures was used mentalhealthpractice.com | PEER≥REVIEWED | evidence & practice / bereavement References American Geriatrics Society Beers Criteria Update Expert Panel (2019) American Geriatrics Society 2019 Updated AGS beers criteria for potentially inappropriate medication use in older adults. Journal of the American Geriatrics Society. 67, 4, 674-694. doi: 10.1111/jgs.15767 Bakken M, Engeland A, Engesæter L et al (2014) Risk of hip fracture among older people using anxiolytic and hypnotic drugs: a nationwide prospective cohort study. European Journal of Clinical Pharmacology. 70, 7, 873-880. doi: 10.1007/s00228-014-1684-z Booth J, Behring M, Cantor R et al (2016) Zolpidem use and motor vehicle collisions in older drivers. Sleep Medicine. 20, 98-102. doi: 10.1016/j.sleep.2015.12.004 Cappuccio F, Miller M (2017) Sleep and cardio-metabolic disease. Current Cardiology Reports. 19, 11, 110. doi: 10.1007/s11886-017-0916-0 Carter P, Mikan S, Simpson C (2009) A feasibility study of a two-session home-based cognitive behavioral therapy-insomnia intervention for bereaved family caregivers. Palliative and Supportive Care. 7, 2, 197-206. doi: 10.1017/S147895150900025X Chen C, Logan R, Ma T et al (2016) Effects of aging on circadian patterns of gene expression in the human prefrontal cortex. Proceedings of the National Academy of Sciences. 113, 1, 206-211. doi: 10.1073/pnas.1508249112 Chiu Y, Yin S, Hsieh H et al (2011) Bereaved females are more likely to suffer from mood problems even if they do not meet the criteria for prolonged grief. Psycho-Oncology. 20, 10, 1061-1068. doi: 10.1002/pon.1811 Chirinos D, Ong J, Garcini L et al (2019) Bereavement, self-reported sleep disturbances, and inflammation. Psychosomatic Medicine. 81, 1, 67-73. doi: 10.1097/PSY.0000000000000645 Currie S, Clark S, Hodgins D et al (2004) Randomized controlled trial of brief cognitive-behavioural interventions for insomnia in recovering alcoholics. Addiction. 99, 9, 1121-1132. doi: 10.1111/j.1360-0443.2004.00835.x Devore E, Grodstein F, Schernhammer E (2016) Sleep duration in relation to cognitive function among older adults: a systematic review of observational studies. Neuroepidemiology. 46, 1, 57-78. doi: 10.1159/000442418 Effective Public Health Practice Project (1998) Quality Assessment Tool for Quantitative Studies. McMaster University, Hamilton ON. Erlangsen A, Runeson B, Bolton J et al (2017) Association between spousal suicide and mental, physical, and social health outcomes. JAMA Psychiatry. 74, 5, 456-464. doi: 10.1001/jamapsychiatry.2017.0226 Gildner T, Liebert M, Kowal P et al (2014) Associations between sleep duration, sleep quality, and cognitive test performance among older adults from six middle income countries: results from the Study on Global Ageing and Adult Health (SAGE). Journal of Clinical Sleep Medicine. 10, 6, 613-621. doi: 10.5664/jcsm.3782 Griffiths M, Peerson A (2005) Risk factors for chronic insomnia following hospitalization. Journal of Advanced Nursing. 49, 3, 245-253. doi: 10.1111/j.1365-2648.2004.03283.x Häusler N, Marques-Vidal P, Haba-Rubio J et al (2019) Does sleep predict next-day napping or does napping influence same-day nocturnal sleep? Results of a population-based ecological momentary assessment study. Sleep Medicine. 61, 31-36. doi: 10.1016/j.sleep.2019.04.014 Irish L, Kline C, Gunn H et al (2015) The role of sleep hygiene in promoting public health: a review of empirical evidence. Sleep Medicine Reviews. 22, 23-36. doi: 10.1016/j.smrv.2014.10.001 Itani O, Jike M, Watanabe N et al (2017) Short sleep duration and health outcomes: a systematic review, meta-analysis, and meta-regression. Sleep Medicine. 32, 246-256. doi: 10.1016/j.sleep.2016.08.006 Jonasson J, Hauksdóttir A, Valdimarsdóttir U et al (2009) Unrelieved symptoms of female cancer patients during their last months of life and long-term psychological morbidity in their widowers: a nationwide population-based study. European Journal of Cancer. 45, 10, 1839-1845. doi: 10.1016/j.ejca.2009.02.008 Kaufmann C, Spira A, Depp C et al (2018) Long-term use of benzodiazepines and nonbenzodiazepine hypnotics, 1999-2014. Psychiatric Services. 69, 2, 235-238. doi: 10.1176/appi.ps.201700095 Kim H, Gerlach L, Van RT et al (2019) Predictors of long-term and high-dose use of zolpidem in veterans. Journal of Clinical Psychiatry. 80, 2, 18m12149. doi: 10.4088/JCP.18m12149 Lerdal A, Slåtten K, Saghaug E et al (2016) Sleep among bereaved caregivers of patients admitted to hospice: a 1-year longitudinal pilot study. BMJ Open. 6, 1, e009345. doi: 10.1136/bmjopen-2015-009345 Li J, Vitiello M, Gooneratne N (2018) Sleep in normal aging. Sleep Medicine Clinics. 13, 1, 1-11. doi: 10.1016/j.jsmc.2017.09.001 Lyu J, Min J, Kim G (2018) Widowhood status as a risk for cognitive decline among Korean older adults. Innovation in Aging. 2, Suppl 1, 255-256. doi: 10.1093/geroni/igy023.951 Monk T, Begley A, Billy B et al (2008) Sleep and circadian rhythms in spousally bereaved seniors. Chronobiology International. 25, 1, 83-98. doi: 10.1080/07420520801909320 Monk T, Germain A, Buysse D (2009) The sleep of the bereaved. Sleep and Hypnosis. 11, 1, 219. Ohayon M, Vecchierini MF (2005) Normative sleep data, cognitive function and daily living activities in older adults in the community. Sleep. 28, 8, 981-989. Okun M, Reynolds C, Buysse D et al (2011) Sleep variability, health-related practices, and inflammatory markers in a community dwelling sample of older adults. Psychosomatic Medicine. 73, 2, 142-150. doi: 10.1097/PSY.0b013e3182020d08 Pace-Schott E, Spencer R (2015) Sleep-dependent memory consolidation in healthy aging and mild cognitive impairment. Current Topics in Behavioral Neurosciences. 25, 307-330. doi: 10.1007/7854_2014_300 Pérez H, Saavedra M, Ikram A et al (2018) Prolonged grief and cognitive decline: a prospective population-based study in middle-aged and older persons. American Journal of Geriatric Psychiatry. 26, 4, 451-460. doi: 10.1016/j.jagp.2017.12.003 Pfoff M, Zarotney J, Monk T (2014) Can a function-based therapy for spousally bereaved seniors accrue benefits in both functional and emotional domains? Death Studies. 38, 6-10, 381-386. doi: 10.1080/07481187.2013.766658 Pillai V, Roth T, Roehrs T et al (2017) Effectiveness of benzodiazepine receptor agonists in the treatment of insomnia: an examination of response and remission rates. Sleep. 40, 2, zsw044. doi: 10.1093/sleep/zsw044 Prior A, Fenger-Grøn D, Davydow J et al (2018) Bereavement multimorbidity and mortality: a population-based study using bereavement as an indicator of mental stress. Psychological Medicine. 48, 9, 1437-1443. doi: 10.1017/S0033291717002380 Scarlett S, Nolan HN, Kenny RA et al (2020) Discrepancies in self-reported and actigraphy-based sleep duration are associated with self-reported insomnia symptoms in community-dwelling older adults. Sleep Health. S2352-7218(20)30173-X. doi: 10.1016/j.sleh.2020.06.003 Seiler A, Murdock K, Fagundes C (2018) Impaired mental health and low-grade inflammation among fatigued bereaved individuals. Journal of Psychosomatic Research. 112, 40-46. doi: 10.1016/j.jpsychores.2018.06.010 Simpson C, Allegra J, Ezeamama A et al (2014) The impact of mid- and late-life loss on insomnia: findings from the Health and Retirement Study, 2010 cohort. Family and Community Health. 37, 4, 317-326. doi: 10.1097/FCH.0000000000000039 Tanimukai H, Adachi H, Hirai K et al (2015) Association between depressive symptoms and changes in sleep condition in the grieving process. Supportive Care in Cancer. 23, 7, 1925-1931. doi: 10.1007/s00520-014-2548-x Tang S, Chow A (2017) How do risk factors affect bereavement outcomes in later life? An exploration of the mediating role of dual process coping. Psychiatry Research. 255, 297-303. doi: 10.1016/j.psychres.2017.06.001 Taylor D, Pruiksma K (2014) Cognitive and behavioural therapy for insomnia (CBT-I) in psychiatric populations: a systematic review. International Review of Psychiatry. 26, 2, 205-213. doi: 10.3109/09540261.2014.902808 Tinetti M, Kumar C (2010) The patient who falls. JAMA. 303, 3, 258-266. doi: 10.1001/jama.2009.2024 volume 24 number 2 / March 2021 / 21 across studies. Most studies used the PSQI to measure sleep, but the actual questions asked to participants varied: some studies used the 19-item PSQI, others used the 18-item PSQI and others did not specify the number of PSQI items used. Depressive symptoms were measured using a variety of tools, including various forms of the Center for Epidemiologic Studies – Depression scale and the 21-item Hamilton Rating Scale for Depression. This means that it is challenging to compare findings between studies and to discuss mental health conditions other than depression, such as anxiety disorders. Sampling was also quite different between the studies. Lastly, only five of the eight articles described the use of a theoretical framework as part of their design. Conclusion Older people who have recently been bereaved are likely to experience sleep disturbances, and sleep disturbances can start before the loved one’s death. Sleep interventions such as CBT-I have been found to be beneficial, but more research is needed to identify ways to improve sleep in the period before the loved one’s death, especially for those who act as the main carer for their partner or spouse, who are particularly at risk. Future studies will need to be more inclusive and extend their populations to partners or spouses of same-sex couples and to older people aged ≥85 years. Finally, few studies have explored the long-term effects of bereavement on sleep in older people, which will need to be addressed in future research. mentalhealthpractice.com | PEERREVIEWED | Reproduced with permission of copyright owner. Further reproductionprohibited without permission.
my topic is: the bereaved individual
Palliative and Supportive Care cambridge.org/pax Guest Editorial Cite this article:Lichtenthal WG (2018). Supporting the bereaved in greatest need: We can do better.Palliative and Supportive Care 16,371–374. https://doi.org/10.1017/ S1478951518000585 Received: 28 June 2018 Revised: 2 July 2018 Accepted: 2 July 2018 Author for correspondence: Wendy G. Lichtenthal, Department of Psychiatry & Behavioral Sciences, Memorial Sloan Kettering Cancer Center, 641 Lexington Avenue, 7th Floor, New York, New York 10022. E-mail:[email protected] © Cambridge University Press 2018 Supporting the bereaved in greatest need: We can do better Wendy G. Lichtenthal, PH.D. Department of Psychiatry & Behavioral Sciences, Memorial Sloan Kettering Cancer Center, New York, NY Introduction The disturbing truth is that following the loss of someone significant in their lives, those who struggle, those who may benefit from professional support the most, are often the ones who do not end up getting help. This is not unique to the context of bereavement, but given the increased risk of downstream physical and mental health challenges that grieving individuals face (Kirby et al.,2018; Marziliano et al.,2018; Prigerson et al.,2009) and the importance of continuity of palliative care through bereavement, the bereaved demand our attention. It is well-established that many individuals find their way through the pain of loss without the need for intervention (Bonanno and Kaltman,2001; Jordan and Neimeyer,2003). For an important group of individuals, though, the challenges are debilitating and persistent (Prigerson et al.,2009). And yet, for several reasons, many of which are touched on in the cur- rent issue ofPalliative & Supportive Care, too many of those who are struggling ultimately do not access professional support (Aoun et al.,2015; Breen et al.,2014a; Cherlin et al.,2007; Lichtenthal et al.,2015a). The reasons for this are multifactorial, and several of these are touched on in the articles by Kirby et al. (2018) and Hudson et al. (2018), both in this issue. There are characteristics of the patients or clients themselves that play a role, there are factors related to professionals and our approaches that may play a role, and there are, sadly, innumerable systems factors at play (Lichtenthal,2017). Hudson et al. (2018) do an outstanding job of addressing several of the challenges that impede sound bereavement aftercare through their proposed standards for bereavement sup- port and their recommendations for implementation of these standards. They do so with humility, highlighting that their proposal is a work in progress and pointing to the areas in need of additional research. Indeed, there are numerous ways that I agree the field needs to advance in order to“do better”in supporting the bereaved and to give the implementation of such standards a fighting chance. Namely, we need to improve screening efforts, reduce bar- riers to accessing support, improve our ability to assess the bereaved, improve the fit and effi- cacy of therapies, disseminate and implement empirically supported grief interventions, establish standards of care (as Hudson et al., in this issue propose), increase the workforce of grief specialists, and minimize burnout of these providers (Lichtenthal,2017). Improve screening First, we need to figure out how to better and more systematically identify those who will be in the greatest need of support, capitalizing on family members’accessibility while patients are receiving care, a point Hudson et al. (2018) emphasized. Doing so will allow providers to triage the limited resources and time that most organizations have available to dedicate to bereave- ment aftercare. Screening family members for their risk of bereavement-related mental health challenges both before and after the patient’s death can help reduce the many instances of fam- ily members falling through the cracks. Implementing a screening process in healthcare set- tings also allows an initial connection to mental health providers, offering an entrée into the system, should grievers feel the need for further support. Furthermore, screening can min- imize overdiagnosing and underdiagnosing bereavement-related mental health challenges, because understanding an individual’s risk profile can help a clinician better interpret present- ing symptoms and determine whether additional support is indicated (Roberts et al.,2017a). Our group’s efforts in this area have focused on developing a brief, clinically useful, self‐report measure that is transdiagnostic, not only assessing predictors of prolonged grief, as is often the focus (Hudson et al.,2018; Patel et al.,2018), but also of bereavement-related depression and post- traumatic stress (Roberts et al.,2017a). We have used patient-reported outcome measure develop- ment methods to obtain feedback on this tool, referred to as the Bereavement Risk Inventory and Screening Questionnaire (BRISQ), because of the need for sensitively-worded and comprehensible screening items when approaching those whose loved one is seriously ill or who are grieving (Roberts et al.,2017a,2017b). Examining the validity and reliability of the BRISQ as well as those instruments described by Hudson et al. (2018) through large-scale psychometric studies will be essential. And, it would be helpful to consider these screening tools as living documents that can revised as we learn more about prospective risk factors through other investigations (Burke and Neimeyer,2013; Roberts et al.,2017a). Once more rigorous studies of screening tools establish those that are psychometrically sound, the field will need to determine how to best implement such assess- ments in various clinical settings to ensure their uptake and to better understand when to screen and how frequently (as some risk factors are dynamic; Roberts et al.,2017b). Finally, we should be mindful of the fact that our estimates of risk (and of the prevalence of clinically significant symptoms) and frankly, most bereavement studies, are likely biased, because those who are struggling the most often decline research participation. For example, a healthy selection bias was suggested in the study described by Kirbyet al.(2018). Bereaved caregivers’perceptions of bereavement support, which was characterized as appropriate for those who were“falling apart,”seemed to reflect that partici- pants in their study were generally coping adaptively with their respective losses (Kirby et al.,2018). Though not without their struggles, by and large, participants in that study did not appear to represent those in greatest need. In contrast to their findings, in a study of parents bereaved by cancer, we found that nearly 50% of parents indicated a desire for coping assistance and 22% had clinically significant levels of depression, anxiety, or prolonged grief symptoms (Lichtenthal et al.,2015a). Unfortunately, a sub- stantial proportion of these parents—around 40% of parents in both cases—were not being met. In other words, around 40% of parents said they wanted services but were not using them, and around 40% were clinically symptomatic and were not using services. Reduce barriers to accessing care This brings us to the next area in need of more clinical and research attention: the reduction of access-to-care barriers. So let us imagine that we have identified a grieving individual who seems at risk for mental health challenges in the wake of her loss. We inform her about available resources, inviting her to use both universal and specialized services. What happens next to this intensely distressed, debilitated individual who may have lost her main source of sup- port—perhaps the person who helped schedule her medical appointments? Is she likely to make an appointment with a coun- selor? The bereaved face similar barriers to accessing mental health services that all individuals may face, such as transportation, time, and finances (depending on their country’s healthcare system). What we recognize clinically, and something for which our group has found some empirical support, is that the pain of grief itself is also a significant barrier to accessing care. In our study of bereaved parents, in fact, it was the number one barrier: 64% of bereaved parents who wanted or needed services but were not accessing such support reported it being“too painful”as a barrier to service use (Lichtenthal et al.,2015a). Kushner and Sher (1991) described this phenomenon as“treatment fearfulness,”defined as apprehension related to expectations about engaging in treatment and being exposed to“the very things that they fear most” ( p. 198). In line with this, we found that bereaved parents with ele- vated prolonged grief symptoms were nearly seven times more likely to indicate that a barrier to getting help is that it is just too painful to talk about their loss (Lichtenthal et al.,2015a). To address this barrier, whenever possible, enlisting the help of those who have been in a similar position can be invaluable. For example, our group has used video-recorded testimonials to assistin outreach for a grief intervention trial targeting parents bereaved by cancer (Lichtenthal et al.,2017). Having someone who has suf- fered the same loss engaging in outreach efforts may also be a pow- erful way to help address the fearful bereaved individual’s concerns. Given the emotional and logistical barriers of returning to the institution where their child was treated, we also deliver counsel- ing via videoconferencing to bereaved parents, doing our best to ensure that we are conveying the warmth, presence, compassion, and attunement that is necessary for effective grief counseling (Lichtenthal et al.,2017). In fact, telemedicine may have a variety of applications in maintaining continuity of palliative care of fam- ilies through bereavement, from screening, to connecting bereaved individuals with one another, to individual counseling. The qualitative study by Kirby et al. (2018) noted that another barrier to service use is the public image of grief support, suggest- ing that we can do better“PR”for bereavement aftercare. We also realize that many people who are interested in bereavement ser- vices struggle to find competent specialized support. Palliative care services should of course provide this kind of specialized sup- port, but it is not always logistically feasible for family members to access the care that is offered. The identification of local special- ized referrals can be facilitated by pooling knowledge in shared databases of trained providers and widely publicizing these data- bases or search engines (Lichtenthal,2017). We need to know who has grief specialty training and where we can find them. Improve assessment Once a person is willing to meeting with a grief specialist, how do we understand what she needs? Does she need anything at all? What do clinicians perceive when they assess psychological symptoms in the context of a significant loss (Dodd et al.,2017; Lichtenthal et al., in press)? We recently conducted a study of mental health clinicians and found that those who received a brief tutorial on prolonged grief disorder (PGD) were over four times more likely to correctly diagnose the individuals who depicted PGD (Lichtenthal et al., in press). We further observed that educating clinicians about PGD result did not result in them pathologizing normative grief, a com- mon concern about establishing bereavement-related diagnoses in existing diagnostic manuals (Davis et al.,2018). That is, clinicians who received the PGD tutorial were not more likely to diagnose nor- mative grief as PGD (Lichtenthal et al.,in press). This suggests that training really can help. If we help clinicians in training programs and through continuing education opportunities learn how to dis- tinguish different types of reactions in bereavement, they will know how to better help. If we do not get the assessment right, then we do not get the treatment right, and that is how the belief that“no one can help”is cultivated (Lichtenthal et al.,2015a). That is when we see individuals drop out of treatment. ‘We also would do well to more carefully consider assessment issues in our research. Participants in our grief investigations have anecdotally shared how variable their grief experiences are, and how their answers to our questions—whether through self-report or through clinical interview—are highly dependent on when you “catch them.”This has important implications for our basic science investigations of grief phenomena as well as our interpretations of treatment outcome studies. Contemporary theories of grief acknowl- edge this movement and variability (Stroebe & Schut,2010). Thus, we need to begin to think outside of the box with our use and timing of standardized questionnaires that ask participants to recall how they have been recently feeling, perhaps revising instructions, or including ecological momentary assessment or diary approaches (Eisma et al., 372Guest Editorial 2017; Monk et al.,2006; Myin-Germeys et al.,2018), so that our assessment tools account for these assessment challenges. Improving therapeutic fit What else can we do to make sure those who need help get it? Well, we can improve the fit of the treatments available. We have found that the most frequently cited reason bereaved parents discontinued therapy was because they felt it was not working, with 36% of parents indicated this was an issue in one study of bereaved parents (Lichtenthal,2017). To improve fit, stakeholder input is key (Lichtenthal et al.,2017; Snaman et al.,2017). Although research has demonstrated the efficacy of several thera- peutic approaches, including pharmacotherapy interventions, none are universally efficacious (Boelen,2016; Boelen et al., 2011; Bryant et al.,2017; Kissane et al.,2006; Mancini et al., 2012; Sandler et al.,2010; Shear et al.,2016). We realize one size surely does not fit all. We need to have thoughtful adaptations for different populations and different clinical issues. For example, at the Weill Cornell Medicine Center for Research on End-of-Life Care directed by Drs. Holly Prigerson and Paul Maciejewski, our group is now adapting established cognitive-behavioral and acceptance-based approaches into a brief intervention for caregiv- ers of noncommunicative patients in intensive care units (Kentish-Barnes & Prigerson,2016; Marziliano et al.,2018). We also need more moderator analyses conducted to determine for whom a given grief intervention approach is most beneficial. Disseminate and implement empirically supported interventions Research to date has focused on intervention development and estab- lishment of treatment efficacy. Many pilots and smaller scale studies have been conducted. But we need more large-scale trials and repli- cation studies. And as the evidence base of efficacious grief interven- tions grows, we need to get the word out. Bereavement intervention researchers will need to develop expertise in dissemination and implementation research methods. Palliative care and bereavement professional organizations can promote use of and training in these approaches. Existing treatments need to be disseminated, fol- lowing training models for grief interventions that have garnered empirical support (e.g., the Family Bereavement Program through the Arizona State University REACH Institute, The Center for Complicated Grief at the Columbia School of Social Work). Establish standards The establishment of standards and guidelines helps us raise the bar. If we aim higher, we may still experience misses, but we will do better than we are doing now. Standards should be realis- tic, taking into account the state of the science and reasonable resources (Hudson et al.,2018). For example, we proposed a set of standards for bereavement follow-up following the death of a child to cancer; it suggests a bare minimum of a single contact by the healthcare team to the grieving parents (Lichtenthal et al.,2015b). Although we would ideally like to see more follow-up than that, it is a practical start. But how can we ensure such standards are accepted and imple- mented? Hudson et al. (2018) offer a model for doing so by incor- porating a pathway to implementation that accompanies their proposed guidelines. We have to be mindful of the gaps between guidelines and actual practice and think carefully about what might make compliance with the standards more challenging(Aoun et al.,2017). We also need to appeal to institutions and organizations for the needed resources (e.g., funding, training). Increase the workforce and minimize burnout At least one reason for the gap between standards and practice is related to staffing. Who is going to carry out the work suggested by the standards (e.g., regular bereavement outreach)? We need to increase the workforce, and importantly, we need to increase the trained workforce (Hudson et al.,2018). A simple search of gene- ral therapist databases will reveal a surprising number of clini- cians who list“grief”as a topic area in which they are expert. Although there is no denying the value of clinical experience, there is an expectation that clinicians who include grief among their specialty areas have specialized training in this field (Ober et al.,2012), and trained grief specialists are at a premium. It is imperative to create a culture that helps individuals feel that if they go to someone with presumed expertise in grief and loss, those individuals are trained and competent providers. This goes hand-in-hand with establishing standards-standards that not only mandate training for all palliative care and bereave- ment support providers (Hudson et al.,2018), but that also spec- ify what this training should be ( per discipline) and that establish the need for an accrediting body that can oversee the quality of training programs. As mentioned earlier, obtaining grief support is often a person’s first experience with psychotherapy, and we often get one shot to demonstrate that psychotherapy can be help- ful. If a griever meets with someone lacking the training to work with the bereaved, she may become disenchanted with therapy and decide not to return for help in other times of need. This may be especially important for those struggling more; we found that parents who lost a child to cancer and who reported higher levels of prolonged grief symptoms were three times more likely to indicate that feeling that no one could help was a barrier to actually getting help (Lichtenthal et al.,2015a). Another way to increase the workforce is to train volunteers, which Kirby et al. (2018) suggested to enlarge the capacity of the community to support the bereaved. As we know, for many bereaved individuals, supporting others who have experienced similar losses is a way to make meaning of their pain and struggles (Lichtenthal et al., 2010). We recognize how meaningful it can be for a bereaved indi- viduals to support others in need of support, and how helpful it can be to connect to others who“get it”(Snaman et al.,2017). As others have done, our group developed a parent ‐to‐parent program that involves training bereaved parents further out from their loss to sup- port those more recently bereaved (Lichtenthal et al.,2013). Extending reach in this way can be invaluable. Finally, it is important to do what we can to minimize burnout in the workforce and to promote self-care (Breen et al.,2014b). Sadly, the amount of space dedicated here may parallel the amount of time dedicated to such efforts. Yet its significance can- not be understated. It is a relatively small and select group of indi- viduals who chooses a career in palliative care and bereavement support, and these individuals need to be nurtured and should have protected time and resources for self-care (Boerner et al., 2017; Breen et al.,2014b; Chan et al.,2015). Hudson et al. (2018) characterized bereavement support as“the forgotten child”of palliative care. One could argue that this reflects the lack of a single discipline championing advances in bereavement clinical care, research, and policy. Perhaps advancements in the field have been slowed because bereavement care is so multidisciplinary and diffuse, even more so than the broad field of palliative care, Palliative and Supportive Care373 with no one group devoting resources to moving the field forward. The waters may have also been muddied as different professional groups—including but not limited to social work, psychology, psy- chiatry, palliative medicine, chaplaincy, and nursing—learn one another’slanguages.Itistimetotransformthecomplexitiesofour subfield into its greatest strength. It is time to synthesize varying per- spectives and use them to advance bereavement support, learning from one another so that we can, indeed, do better. Acknowledgments.The research referenced has been supported by National Cancer Institute grants R03CA139944 (W.G.L.), K07CA172216 (W.G.L.), P30CA008748 (Thompson), T32CA009461 (Ostroff ), R21CA218313 (Prigerson/W.G.L.), and F31CA192447 (Roberts); National Institute of Mental Health grant R21MH095378 (W.G.L./Prigerson); the American Cancer Society (Prigerson/W.G.L.); and the Seth Sprague Foundation (Holland). Those of others listed lent support to the work described. References Aoun SM, Breen LJ, Howting DA,et al.(2015) Who needs bereavement sup- port? A population based survey of bereavement risk and support need. PLoS One10, e0121101. Aoun SM, Rumbold B, Howting D,et al.(2017) Bereavement support for family caregivers: The gap between guidelines and practice in palliative care.PLoS One12, e0184750. Boelen PA(2016) Improving the understanding and treatment of complex grief: An important issue for psychotraumatology.European Journal of Psychotraumatology7, 32609. Boelen PA, de Keijser J, van den Hout MA,et al.(2011) Factors associated with outcome of cognitive-behavioural therapy for complicated grief: A pre- liminary study.Clinical Psychology & Psychotherapy18, 284–291. Boerner K, Gleason H, and Jopp DS(2017) Burnout after patient death: Challenges for direct care workers.Journal of Pain and Symptom Management54, 317–325. Bonanno GA. and Kaltman S(2001) The varieties of grief experience.Clinical Psychology Review21, 705–734. Breen LJ, Aoun SM, O’Connor M,et al.(2014a) Bridging the gaps in palliative care bereavement support: An international perspective.Death Studies38,54–61. Breen LJ, O’Connor M, Hewitt LY,et al.(2014b). The“specter”of cancer: Exploring secondary trauma for health professionals providing cancer sup- port and counseling.Psychological Services11,60–67. Bryant RA, Kenny L, Joscelyne A,et al.(2017) Treating prolonged grief dis- order: A 2-year follow-up of a randomized controlled trial.Journal of Clinical Psychiatry78, 1363–1368. Burke LA and Neimeyer RA(2013) Prospective risk factors for complicated grief: A review of the empirical literatureComplicated Grief: Scientific Foundations for Health Care Professionals. New York, NY: Routledge/ Taylor & Francis Group, pp. 145–161. Chan WC, Tin AF and Wong KL(2015) Coping with existential and emo- tional challenges: Development and validation of the self-competence in death work scale.Journal of Pain and Symptom Management50,99–107. Cherlin EJ, Barry CL, Prigerson HG,et al.(2007) Bereavement services for family caregivers: How often used, why, and why not.Journal of Palliative Medicine10, 148–158. Davis EL, Deane FP, Barclay GD,et al.(2018). Attitudes of palliative care clinical staff toward prolonged grief disorder diagnosis and grief interven- tions.Palliative and Supportive Care. doi: 10.1017/S1478951517000505. Dodd A, Guerin S, Delaney S,et al.(2017) Complicated grief: Knowledge, attitudes, skills and training of mental health professionals: A systematic review.Patient Education and Counseling100, 1447–1458. Eisma MC, Boelen PA, Schut HA,et al.(2017) Does worry affect adjustment to bereavement? A longitudinal investigation.Anxiety Stress Coping,30(3), 243–252. Hudson P, Hall C, Boughey A,et al.(2018) Bereavement support standards and bereavement care pathway for quality palliative care.Palliative and Supportive Care. doi: 10.1017/S1478951517000451. Jordan JR and Neimeyer RA (2003) Does grief counseling work?Death Studies27, 765–786.Kentish-Barnes N and Prigerson HG(2016) Is this bereaved relative at risk of prolonged grief ?Intensive Care Medicine42, 1279–1281. Kirby E, Kenny K, Broom A,et al.(2018) The meaning and experience of bereavement support: A qualitative interview study of bereaved family care- givers.Palliative and Supportive Care. doi: 10.1017/S1478951517000475. Kissane DW, McKenzie M, Bloch S,et al.(2006) Family focused grief ther- apy: A randomized, controlled trial in palliative care and bereavement. American Journal of Psychiatry163, 1208–1218. Kushner MG and Sher KJ(1991) The relation of treatment fearfulness and psychological service utilization: An overview.Professional Psychology: Research and Practice22 , 196–203. Lichtenthal W, Davis M and Pickett N(2013) A mentoring program for par- ents bereaved by cancer.Psychooncology22(Suppl. 2), 72. Lichtenthal WG(2017)When those who need it most use it least: Facilitating grief support for those at greatest risk. Keynote address presented at the Association for Death Education and Counseling 39th Annual Conference, Portland, OR. Lichtenthal WG, Corner GW, Sweeney CR,et al.(2015a) Mental health ser- vices for parents who lost a child to cancer: If we build them, will they come?Journal of Clinical Oncology33, 2246–2253. Lichtenthal WG, Currier JM, Neimeyer RA.et al.(2010) Sense and signifi- cance: A mixed methods examination of meaning making after the loss of one’s child.Journal of Clinical Psychology66, 791–812. Lichtenthal WG, Lacey S, Roberts K,et al.(2017) Meaning-centered grief therapy. InMeaning-centered psychotherapy in the cancer setting. WS Breitbart (ed.), pp. 88–99. New York, NY: Oxford University Press. Lichtenthal WG, Maciejewski PK, Craig Demirjian C,et al.(In press). Evidence of the clinical utility of a prolonged grief disorder diagnosis [Letter to the Editor].World Psychiatry. Lichtenthal WG, Sweeney CR, Roberts KE,et al.(2015b) Bereavement follow-up after the death of a child as a standard of care in pediatric oncol- ogy.Pediatric Blood Cancer62(Suppl. 5), S834–S869. Mancini AD, Griffin P and Bonanno GA(2012) Recent trends in the treat- ment of prolonged grief.Current Opinions in Psychiatry25,46–51. Marziliano AM, Lichtenthal WG and Prigerson HG(2018) Diagnosis of prolonged grief disorder (PGD). InPsychosocial issues in palliative care: A community based approach for life limiting illness, 3rd ed. M LLoyd-Williams (ed.), pp. 210–226. New York: Oxford University Press. Monk TH, Houck PR and Shear MK(2006) The daily life of complicated grief patients–what gets missed, what gets added?Death Studies30,77–85. Myin-Germeys I, Kasanova Z, Vaessen T,et al.(2018) Experience sampling methodology in mental health research: new insights and technical develop- ments.World Psychiatry17, 123 –132. Ober AM, Granello DH. and Wheaton JE(2012) Grief counseling: An inves- tigation of counselors’training, experience, and competencies.Journal of Counseling & Development90. Patel SR, Cole A, Little V,et al.(2018) Acceptability, feasibility and outcome of a screening programme for complicated grief in integrated primary and behav- ioural health care clinics.Family Practice. doi: 10.1093/fampra/cmy050. Prigerson HG, Horowitz MJ, Jacobs SC,et al.(2009) Prolonged grief disor- der: Psychometric validation of criteria proposed for DSM-V and ICD-11. PLoS Medicine6, e1000121. Roberts K, Holland J, Prigerson HG,et al.(2017a) Development of the Bereavement Risk Inventory and Screening Questionnaire (BRISQ): Item generation and expert panel feedback.Palliative and Supportive Care 15,57–66. Roberts KE, Jankauskaite G, Slivjak E,et al.(2017b) Using family member feed- back to improve bereavement screening. Poster presented at the Association for Death Education and Counseling 39th Annual Conference, Portland, OR. Sandler IN, Ma Y, Tein JY,et al.(2010) Long-term effects of the family bereave- ment program on multiple indicators of grief in parentally bereaved children and adolescents.Journal of Consulting Clinical Psychology78,131–143. Shear MK, Reynolds 3rd CF, Simon NM,et al.(2016) Optimizing treatment of complicated grief: A randomized clinical trial.JAMA Psychiatry73, 685–694. Snaman JM, Kaye EC, Levine DR,et al.(2017) Empowering bereaved parents through the development of a comprehensive bereavement program. Journal of Pain and Symptom Management53, 767–775. Stroebe M and Schut H(2010) The dual process model of coping with bereavement: A decade on.Omega(Westport)61, 273–289. 374Guest Editorial Copyright © Cambridge University Press 2018 
my topic is: the bereaved individual
The effect of metoprolol and aspirin on cardiovascular risk in bereavement: A randomized controlled trial Geoffrey H. Tofler, MD, a,b Marie-Christine Morel-Kopp, PhD, a,b,c Monica Spinaze, RN, a,b Jill Dent, RN, a,b Christopher Ward, MD, a,b Sharon McKinley, PhD, dAnastasia S. Mihailidou, PhD, a,c,e Jennifer Havyatt, BSocStud, a,b Victoria Whitfield, BSW, a,b Roger Bartrop, MD, a,b Judith Fethney, BA, bHolly G. Prigerson, PhD, eand Thomas Buckley, PhD a,b,f Royal North Shore Hospital; University of Sydney; Kolling Institute; Deakin University; Macquarie University; and Weill Cornell Medicine Background Bereavement is associated with an increased risk of cardiovascular disease; however, no reports exist of interventions to reduce risk. In a randomized, double-blind, placebo-controlled trial of 85 recently bereaved participants, we determined whetherβ-blocker (metoprolol 25 mg) and aspirin (100 mg) reduce cardiovascular risk markers and anxiety, without adversely affecting bereavement intensity. Methods Participants were spouses (n = 73) or parents (n = 12) of deceased from 5 hospitals in Sydney, Australia, 55 females, 30 males, aged 66.1 ± 9.4 years. After assessment within 2 weeks of bereavement, subjects were randomized to 6 weeks of daily treatment or placebo, and the effect evaluated using ANCOVA, adjusted for baseline values (primary analysis). Results Participants on metoprolol and aspirin had lower levels of home systolic pressure (P= .03), 24-hour average heart rate (Pb.001) and anxiety (P= .01) platelet response to arachidonic acid (Pb.001) and depression symptoms (P= .046) than placebo with no difference in standard deviation of NN intervals index (SDNNi), von Willebrand Factor antigen, platelet- granulocyte aggregates or bereavement intensity. No significant adverse safety impact was observed. Conclusions In early bereavement, low dose metoprolol and aspirin for 6 weeks reduces physiological and psychological surrogate measures of cardiovascular risk. Although further research is needed, results suggest a potential preventive benefit of this approach during heightened cardiovascular risk associated with early bereavement. (Am Heart J 2020;220:264-72.) The importance of psychosocial factors in cardiovascular disease is increasingly recognized. 1-4 Bereavement due to the death of a loved one is one of the most stressful experiences to which almost every human is exposed, and is associated with symptoms of depression, anxiety, anger and grief 5,6 that often persist for weeks and months and for some may become prolonged. 7,8 While most people adjust to the loss, there is a heightened risk of mortality up to 6 months with cardiovascular disease accounting for up to half of the excess deaths during spousal bereavement. 6,9 In the Determinants of Myocardial Infarction Onset Study, the relative risk of non-fatal infarction peaked in the first dayfollowing bereavement and remained 4-fold increased between 7 days to 1 month following bereavement. 10 The mechanism of the increased cardiovascular risk in bereavement has not been well studied; however potential contributors include increased systolic blood pressure and heart rate, reduced heart rate variability, prothrombotic and immune changes, and anxiety, depression and anger. 6,11-15 Considering the large numbers of bereaved individuals at increased risk for cardiovascular disease, it is important to identify strategies that reduce risk without having a deleterious impact on the bereavement process. Prior studies suggest that beta adrenergic blocking drugs and/or aspirin modify pathways activated in bereavement. 16-20 In this trial, we therefore tested the hypothesis that the combination of low dose metoprolol and aspirin would reduce cardiovascular risk markers, including symptoms of anxiety, without an adverse impact on bereavement intensity. Methods The present study was a prospective, double-blind, placebo-controlled trial. The protocol was approved by From the aRoyal North Shore Hospital, St Leonards, NSW, Autralia, bUniversity of Sydney, Sydney, NSW, Autralia, cKolling Institute, St Leonards, NSW, Autralia, dDeakin University, Melbourne, Victoria, Autralia, eMacquarie University, Sydney, NSW, Autralia, and fWeill Cornell Medicine, New York, NY, U.S.A.. Funding support was received from Heart Research Australia. Submitted January 10, 2019; accepted November 10, 2019. Reprint requests: Geoffrey H Tofler MD, Cardiology Department, Royal North Shore Hospital, St Leonards, NSW 2065, Australia. E-mail:Geoffrey.Tofl[email protected] 0002-8703 © 2019 Published by Elsevier Inc. https://doi.org/10.1016/j.ahj.2019.11.003 Clinical Investigation the Institutional Review Board of Northern Sydney Health Ethics Committee, Australia, and all participants signed informed consent. An independent data and safety monitoring committee reviewed safety and efficacy data. Trial registration was with the Australia and New Zealand Clinical Trials Registry, Registration Number ACTRN12618001387213, Registry URL ttp://www. anzctr.org.au/BasicSearch.aspx. Funding support was provided by a grant from Heart Research Australia. The authors are solely responsible for the design and conduct of this study, all study analyses, and drafting and editing of the manuscript. Participants We recruited spouses, partners or parents of patients who died in hospital wards, intensive care units and emergency departments of 5 participating hospitals in Northern Sydney, Australia. Exclusions were any severe illness, current use of beta blockers, other heart rate lowering drugs, aspirin or other antiplatelet or antithrombotic medication, or having a contra-indication to their use, heart rateb60 bpm, systolic blood pressureb120 mmHg at screening or first assessment, nursing home resident, or cannot speak or read English. Participants lived within 60 minutes driving time from the Core Hematology Laboratory to allow standardization of blood collection and transport to the laboratory. Assess- ments were conducted in participants’ homes between 8 am and noon. Withdrawal was allowed at any time at subject request, or investigator discretion if participation was considered to be causing undue psychological distress or adverse physiological change. Study design (Figure 1) At enrolment, data were obtained on sociodemographic and clinical history, cardiovascular risk factors, body mass index, prior illness, medications, smoking, alcohol use,social support 21and the specifics of the bereavement. After satisfactory review of the enrolment assessment (Assess- ment 1) by investigators, subjects were randomized to active therapy or placebo using a randomization code (See Figures 1 and 2). Intervention Theactivetherapywasmetoprololtartrate(25mgmane Metohexal) and low dose immediate release aspirin (100 mg mane DBR). Blinding was assured by the provision of placebos identical to the active treatment. Assessment 2 was after 6 weeks on study treatment, following which the medication was ceased. Assessment 3 was 6 weeks following assessment 2 (and cessation of medication). At 6 months, a questionnaire was mailed, and if needed, followed up by telephone or visit. Questionnaires and surrogate measures of cardiovascular risk At each assessment, including at 6 months, question- naires were administered for symptoms of anxiety and anger (Spielberg State–trait Anxiety and Anger question- naires), 22,23 depression (Centre for Epidemiological Studies-Depression (CES-D) Scale), 24 and bereavement intensity (Core Bereavement Items Questionnaire, CBI- 17). 25Internal consistency reliability (Cronbach’s alpha) of the questionnaires were as follows: State Anxiety (0.90, 0.92, 0.93), State Anger (0.88, 0.93, 0.90), CES-D (0.76, 0.91, 0.89), and CBI-17 (0.95, 0.95, 0.95). For blood pressure recordings, we used a UA 787 Digital monitor (Grade A/A). The study investigator obtained blood pressure measure- ments for eligibility (mean of 3 measurements). Then the participant was instructed by the investigator in obtaining duplicate measurements at 3 time points (morning, afternoon and evening) over a 24-hour period during each assessment. Adequate subject technique was verified Figure 1 Study design.Tofler et al265 American Heart Journal Volume 220 by the investigator. For 24-hour ECG Holter monitor, we used the Medtel Digital System, and the Medilog Optima system (Oxford Instruments Medical Systems Division) for analysis. Average, minimum and maximum heart rate was obtained. Autonomic data were obtained on the 24-hour Holter tracings, for standard deviation of the NN intervals index (SDNNi) and the square root of the mean squared differences of successive intervals. (rMSSD). 12 For blood sampling, a 21-gauge butterfly needle with a Vacutainer system was used. Blood analyses were performed in Core Hematology and pathology laborato- ries at Royal North Shore Hospital. Platelet-granulocyte aggregates were measured using flow cytometry, 26 von Willebrand Factor antigen using immunoturbidimetric method, 13and Multiplate ASPI test with Arachidonic Acid Stimulation 0.5 mM. 27 Statistical analysis Differences between treatment groups in sociodemo- graphic data were analyzed using Student’s t-test for interval data and Chi Square test of Independence for categorical data using intention-to-treat analysis. The primary physiological outcome variables were hemody- namic: home systolic blood pressure (mean of morning, afternoon and evening levels) and 24-hour average heart rate; heart rate variability: SDNNi; and thrombotic: von Willebrand factor antigen and platelet-granulocyte aggre- gates. Secondary physiological outcomes were morning, afternoon and evening systolic and diastolic pressures considered separately, minimum and maximum heart rates, rMSSD and platelet response to arachidonic acid (Multiplate ASPI test). The primary psychological outcomes were symptoms of anxiety and bereavement intensity, and Figure 2 Screening, recruitment and flow of participants throughout study. 266Tofler et al American Heart Journal February 2020 secondary psychological outcomes were symptoms of depression and anger. The primary analysis of the primary and secondary outcomes compared the effect of 6 weeks of daily therapy or placebo, using analysis of covariance (ANCOVA) on the post-treatment scores (assessment 2), with pre-treatment score as a covariate and treatment as an independent variable. Secondary analyses of the primary and secondary outcomes compared active and placebo scores at baseline and at 6 weeks following cessation of therapy (assessment 3), and psychological outcomes at 6 months. We calculated that a total sample size of 80participants (40 completed participants per group) would provideN80% power to identify a between-group differ- ence in systolic pressure of 8 mm Hg and heart rate of 5 bpm. SPSS Version 24, (IBM Corporation Armonk, NYI, USA) was used for all analyses, with two-sided alpha set to Pb.05. There was no adjustment for multiple testing as all outcomes were pre-specified. Because the baseline data showed a statistically significant difference in sex distribu- tion, a post hoc analysis was conducted using analysis of covariance (ANCOVA) on the post-treatment scores, with pre-treatment scores as covariate, and sex and treatment as independent variables. Subjects were analyzed based on intention to treat. Data from participants who did not complete the 6-week assessment, were not included in the primary analysis. Results Study population Between 2011 and 2015, we screened 5183 hospital deaths (Figure 2). The main study exclusion was the absence of a spouse or partner. Of the 598 patients who were eligible by screening, 485 declined to participate, and 28 were excluded due to a low resting heart rate or blood pressure, resulting in 85 subjects who were randomized to active or placebo treatment. Participant characteristics are shown inTable I. The participants comprised spouses (n = 73) or parents (n = 12) of deceased from 5 hospitals in Northern Sydney, Australia. Participants were aged 66.1 ± 9.4 years (SD) (range 36–85 years), and comprised 55 females and 30 males. The average duration from bereavement to enrol- ment did not differ between groups, 12.7 (SD 3.2) in the Table I.Characteristics of study participants at baseline assessment Intervention group N=42Placebo group N=43 Characteristic Age, mean (SD) 65.3 ± 8.8 67.0 ± 10.0 Females, n (%) 32 (76%) 23 (53%)⁎ BMI (kg/m2) mean (±SD) 27.0 ± 6.7 27.0 ± 6.0 Waist circumference cm mean (±SD) 92.8 ± 15.3 95.4 ± 13.9 History of Hypertension 20 (48%) 18 (42%) History of Diabetes 4 (9%) 6 (14%) History of High Cholesterol 12 (29%) 12 (28%) Family history heart disease 11 (26%) 11 (25%) History of acute myocardial infarction 0 0 History of anxiety disorder 4 (9%) 5 (11%) History of depression 5 (12%) 8 (19%) Social support+ availability mean (±SD) 5.2 (2.4) 4.7 (2.2) Social support+ satisfaction mean (±SD) 5.5 (0.7) 5.3 (0.9) Days from death to enrolment mean (±SD) 12.7 ± 3.2 11.9 ± 3.2 Standard drinks past week mean (±SD) 8.2 ± 7.3 10.2 ± 8.0 Reported sleep duration per night past week mean (±SD) hours5.8 ± 1.3 5.9 ± 1.2 ⁎P= .02, +Social Support Scale (SSQ-6). Table II.Physiological outcomes at baseline (prior to randomization), on treatment and 6 weeks off treatment Intervention group Control group Baseline6-weeks on treatment12-weeks off treatmentBaseline6-weeks on placebo12-weeks off placebo Primary Outcomes Systolic BP home+ (mmHg) 135.8 ± 1.9 129.0 ± 2.1* 129.95 ± 1.7 136.0 ± 2.3 135.4 ± 2.1 134.5 ± 1.7 Heart rate average 24 hours (bpm) 75.4 ± 1.0 67.1 ± 0.8*** 75.4 ± 0.9 73.1 ± 1.0 73.6 ± 0.8 74.1 ± 0.9 SDNNi 24 hours (ms) 38.9 ± 2.0 45.5 ± 2.5 38.4 ± 2.9 41.7 ± 3.0 44.3 ± 2.4 46.8 ± 2.7 Platelet granulocyte aggregates (x 10 6/ l) 484.4 ± 58.0 378.5 ± 38.9 384.6 ± 37.6 410.0 ± 31.0 420.0 ± 37.0 403.9 ± 35.2 Von Willebrand Factor (%) 130.9 ± 7.5 129.2 ± 3.0 129.4 ± 3.5 135.7 ± 6.5 131.3 ± 2.8 131.8 ± 3.3 Secondary Outcomes Systolic BP morning (mmHg) 137.2 ± 2.2 132.1 ± 2.6* 132.2 ± 2.1* 136.5 ± 2.1 139.5 ± 2.4 141.6 ± 2.0 Systolic BP afternoon (mmHg) 138.0 ± 2.6 130.0 ± 2.6 134.6 ± 2.3 140.7 ± 2.8 135.2 ± 2.4 136.2 ± 2.1 Systolic BP evening (mmHg) 131.9 ± 2.3 129.2 ± 2.6 131.4 ± 2.3 134.8 ± 2.9 131.8 ± 2.6 136.4 ± 2.3 Diastolic BP home+ (mmHg) 86.1 ± 1.3 81.6 ± 1.0 81.5 ± 0.9 83.3 ± 1.2 83.2 ± 1.1 82.1 ± 0.9 Heart rate–minimum (bpm) 54.4 ± 0.9 50.0 ± 0.7** 53.0 ± 0.8 52.4 ± 0.9 53.23 ± 0.7 53.2 ± 0.7 Heart rate–maximum (bpm) 123.2 ± 2.0 110.4 ± 1.8** 119.5 ± 2.1 117.0 ± 2.7 118.3 ± 1.7 119.5 ± 2.0 RMSSD 24 hours (ms) 42.0 ± 3.8 54.1 ± 5.1 42.6 ± 5.1 46.1 ± 5.9 51.3 ± 4.9 56.4 ± 4.9 Multiplate ASPI test 78.5 ± 3.4 10.6 ± 2.5*** 73.5 ± 3.7 79.1 ± 2.9 77.4 ± 2.4 79.6 ± 3.5 All values mean ± SE. Between-group differences adjusted for baseline values at *Pb.05, **Pb.01, ***Pb.001. Follow-up means are estimated marginal means ± standard error (SE). Multiplate ASPI test – platelet response to arachidonic acid. +Average of morning, afternoon, evening home BP levels. Tofler et al267 American Heart Journal Volume 220 treatment group and 11.86 11.9 (3.2) in controls,P=.20. There was no difference between groups in the duration of the intervention (mean ± SD 42.3 ± 7.8 vs 43,2 43.2 ± 4.35 4.4 days or in the number of medications taken from post intervention pill count (0 = 0.47). The earliest enrolment was at day 5, with the Holter monitor being placed prior to the funeral service. The groups were well matched for risk factors other than more women in the active treatment group. There was no significant difference between women and men in baseline measures of anxiety (48.0 ± 11.4 versus 56.0 ± 10.9) or depression (27.5 ± 11.3 versus 33.7 ± 10.0). There was also no difference in proportion of spouses and parents within the two groups (intervention group: spouses n = 37, parents n = 5 versus control group: spouses n = 34, parents n = 9. Although the number of bereaved parents was small, there were no significant differences between parents and spouses in baseline measures of anxiety (53.6 ± 14.6 versus 49.4 ± 11.4) or depression (30.8 ± 11.5 versus 28.7 ± 11.3). There were no significant differences between the active versus placebo groups in whether the death occurred suddenly (73.8 vs 88.4%), how prepared they felt for the death (possible score 1–7) (3.3 ± 2.0 vs 2.7 ± 1.8) or whether the participant was the primary carer (78.6 vs 81.4%). Adherence, which was verified by the counting of medication returned at the conclusion of the study period, showed no significant difference between the treatment and control groups. Outcomes Mean levels and between-group ANCOVA results adjusted for baseline values for the physiological and psychological variables are shown inTables II and III. After 6 weeks on treatment Blood pressure.The intervention group had lower levels of the primary outcome of mean home systolic blood pressure (P= .03) and morning systolic pressure (P=.04) adjusted for baseline. There were no differences for afternoon or evening systolic or diastolic pressures. Heart rate.The intervention group had lower levels of the primary outcome of average 24-hour heart rate(Pb.001), as well as minimum (P= .002) and maximum heart rate (P = .002). Autonomic Function.Therewerenostatistically significant between-group differences for SDNNi (P=.44) or rMSSD (P= .60). Thrombotic.There were no significant differences for the primary thrombotic outcomes of platelet-granulocyte aggregates (P= .44) or von Willebrand Factor (P= .63). The platelet response to Arachidonic Acid was reduced in the active treatment group (Pb.001). Psychological outcomes.The intervention group had lower levels of anxiety (P= .01) and depression symptoms (P= .046), adjusted for baseline (Table III) whereas there were no between-group differences in bereavement intensity (P= .52) or anger (P= .98). Change scores for treatment versus placebo are shown inFigure 3. Off treatment.After 6 weeks off treatment, the morning systolic pressure and anxiety levels remained lower in the treatment group compared to placebo, adjusted for baseline, although there were no other persisting between-group differences (Table II and III). At 6 months, the anxiety level remained lower in the treatment group, with no other between-group differences in psychosocial outcomes (Table III). Post hoc analysis additionally adjusted for gender The findings with the additional adjustment for sex were not different in interpretation from the primary analyses that did not include sex. Thus, after 6 weeks on treatment, the sex-adjusted mean home systolic blood pressure was lower with active treatment (P= .03) as was morning systolic pressure (P = .03), average 24-hour heart rate (Pb.001), minimum (P= .002) and maximum heart rate (P= .001), platelet response to Arachidonic Acid (Pb.001), and anxiety (P= .009). The sex-adjusted depression level treatment statistical comparison p value was 0.08, (0.046 when unadjusted for sex). Safety during the study There were no major adverse events. Our predetermined protocol to deal with severe grief reactions was not needed by any participant. One subject on active treatment became Table III.Psychological outcomes at baseline (prior to randomization), on treatment, 6 weeks off treatment and at 6 months. Intervention group Control group Baseline6 weeks on treatment12 weeks off treatment6-months Baseline6 weeks on placebo12 weeks off treatment6-months State Anxiety 49.9 ± 1.8 38.1 ± 1.2** 37.7 ± 1.4* 36.4 ± 1.5* 45.5 ± 1.7 42.4 ± 1.2 41.1 ± 1.4 40.8 ± 1.5 Depression 29.1 ± 1.7 16.4 ± 1.4* 15.1 ± 1.3 13.6 ± 1.5 25.1 ± 1.5 20.3 ± 1.3 17.8 ± 1.2 17.0 ± 1.4 State Anger 20.5 ± 1.0 18.5 ± 0.7 17.7 ± 0.5 17.1 ± 0.5 19.1 ± 0.8 18.5 ± 0.7 18.3 ± 0.5 17.5 ± 0.4 Bereavement intensity 44.3 ± 1.8 41.0 ± 1.1 39.5 ± 1.0 38.9 ± 1.2 43.7 ± 1.5 42.0 ± 1.1 41.2 ± 1.0 39.5 ± 1.1 All values mean ± SE. Significant difference between groups adjusted for baseline values at *Pb.05, **Pb.01. All follow-up means are estimated marginal means ± standard error (SE). 268Tofler et al American Heart Journal February 2020 dizzy and hypotensive after the first dose, and was withdrawn. On review by the data and safety monitoring committee, this participant was a protocol violation, with a pre-randomization systolic pressure measure below entry criteria. One participant receiving placebo was hospitalized on the day after the second assessment with an episode of chest pain and hypertension (systolic pressure of 210 mmHg) and suspected unstable angina. This subject (unblinded only to the chief investigator) responded well to metoprolol with a fall in pressure to 130 mmHg. Two other subjects on active treatment withdrew for non-medical reasons. There was no difference between intervention and control groups in reported health related behaviors at 6 weeks: sleep duration (mean ± SD 6.4 ± 1.6 vs 6.4 ± 1.3 hours,P=.81) and alcohol consumption (mean ± SD standard drinks in the week prior 5.8 ± 6.2 vs 7.9 ± 8.1,P=.19)orat12weeks: sleep duration (6.5 ± 1.2 vs 6.5 ± 1.2,P=.90)andalcohol intake (6.8 ± 6.6 vs 8.9 ± 7.7,P=.19). Discussion In this prospective, randomized, placebo-controlled trial, low dose metoprolol (25 mg morning) and aspirin (100 mg) reduced home systolic blood pressure, 24-hour average heart rate, platelet response to arachidonic acid, and symptoms of anxiety and depression. Heart rate variability, platelet granulocyte aggregates and von Will- ebrand factor were not altered by the intervention. The 6 weeks of daily medication commenced an average of 12 days following bereavement of partners or children,was well tolerated with no adverse effect on bereavement intensity up to 6 months. Low dose metoprolol and aspirin were chosen as the interventions for several reasons. Beta-adrenergic blocking drugs may provide protection against emotional triggers of acute coronary syndrome 28,29 and their effect is pronounced during the morning increase in adrenergic activity and peak in CVD. 30β-Blockers also attenuate stress- related surges in heart rate, blood pressure and ischemia, decrease arrhythmia, improve autonomic function and may reduce coagulability. 17,31,32 Low dose metoprolol (25 mg daily) has been shown to reduce plaque progression, improves plaque stability while lowering intermediate outcomes of heart rate by 3.2 bpm and systolic blood pressure by 3.1 mmHg compared with placebo. 16 The hemodynamic effects seen with the dose of metoprolol used in the present study, are similar to differences in mean heart rate and blood pressure previously observed between bereaved and non-bereaved controls. 11 The clinical utility of low dose therapy is supported by Barron who showed that patients post MI treated with low doses of beta blockers had reduced cardiovascular mortality compared with those not receiving beta blockers. 33 There is also evidence that aspirin may reduce the relative risk of MI triggered by anger, 29,34 and modify the link between inflammation and depression. 20 Aspirin preferentially reduces morning MI concurrent with peak platelet reactivity. 30,35 Catecholamine surges associated with stressors increase platelet activation. 36 Aspirin inhibits epinephrine-induced aggregation and thromboxane Figure 3 Change scores for treatment (metoprolol 25 mg/aspirin 100 mg versus placebo. (All between-group differences depicted are statistically significant (Pb.05) for 6 weeks versus baseline. Home BP = Average of morning, afternoon, evening home measurements).Tofler et al269 American Heart Journal Volume 220 production, 37although in an animal model, an epinephrine infusion overcame the aspirin inhibition of thrombogen- esis. 38While our findings on heart rate and blood pressure support the hypothesis that the physiologic effects of low dose metoprolol and aspirin in bereavement are similar to those reported in non-bereaved populations, it was important to determine efficacy and tolerability in be- reaved subjects, with their fluctuating symptoms of depression, anxiety and anger. While beta blockers do not in general have a negative impact on depression, 39- 42 this has not been previously evaluated in bereave- ment. It is reassuring that we in fact found a reduction in anxiety and depressive symptoms. There are conflicting data on the effect of aspirin orβ-blocker on von Willebrand factor and platelet aggregates, markers that have been shown to be elevated in bereaved individuals. 13 While we found no significant effect on these markers in the present trial, it is reassuring that aspirin had its expected significant effect on arachidonic acid-induced platelet aggrega- tion, as assessed by the Multiplate ASPI test. A morning dose of short-acting metoprolol was used, to ensure maximal drug effect in the daytime hours where we previously found the bereaved to have a higher heart rate than bereaved. 11 An evening dose of metoprolol was not given, since we had not previ- ously seen a higher heart rate in the bereaved at that time 11 and it enabled a low daily dose (25 mg daily) to be used to minimize the potential for side effects in individuals not used to taking this medication. Our regimen was consistent with current guidelines that recommend beta blockers without stipulating dosage, and ongoing daily aspirin therapy of 75–162 mg. 43 The reductions in systolic blood pressure and heart rate that we found, are consistent with the known effects ofβ- blockers that contribute to their cardioprotective effect. 16 The greatest reduction in systolic pressure with treatment occurred in the morning, corresponding to the circadian time of greatest cardiovascular risk, 30 and greatest separa- tion in systolic pressure between bereaved and non- bereaved in our prior study. 11 The morning systolic pressure remained lower in the active arm 6 weeks following treatment cessation, raising the possibility of a legacy effect. Because higher heart rates are associated with increased cardiovascular risk, and are present in bereaved individuals, the reduced average and maximal heart rate seen with treatment represents a potential protective effect. 44 Although HRV is reduced in bereavement, 12,14 and some studies suggest beta blockers and to a lesser extent aspirin may increase HRV, 17,19 we found no treatment effect on autonomic endpoints. Anxiety, depression and anger, which are commonly foundinbereavedindividuals,havebeenlinkedtoincreased cardiovascular risk. 1-6 It was therefore important to evaluate whether the medication had favorable or deleteriouspsychological effects. The reduced anxiety we found with the active treatment is consistent with limited studies that support beta blocker use for acute anxiety and panic attacks. 18 Of note, the reduction in anxiety persisted post- therapy to the 6-month time point. In some studies, beta blockers have resulted in reduced incidence of post- traumatic stress disorder, although data are not conclu- sive. 45 The reduction in depressive symptoms was reassuring for the safety of the strategy. Aspirin may possibly have improved depressive symptoms, since inflammation and depression have been linked, and some studies, although not all, suggest reduced depres- sive symptoms with aspirin. 20 A feasibility study in 10 bereaved individuals reported encouraging data for a benefit of aspirin on HRV, attenuated physiological reactivity to a grief-related stress task and a beneficial effect on depressive symptoms. 46In our study, there was no treatment effect on grief intensity or symptoms of anger either on treatment or at 6 months, and no evidence of a withdrawal effect. Several limitations of our study should be considered. We only evaluated the medication response after 6 weeks, and a different and possibly greater treatment impact may have been observed had we evaluated the participants after a shorter period, such as after 1 week, when physiological and psychological activation would be greater than at 6 weeks, or if medication had been commenced earlier that our average of day 12 post- bereavement. However, even though stress-related physiologic and psychological changes would likely be higher closer to the bereavement, our time window fitted within the logistics of a randomized study and sensitivity to the bereavement needs of the participants, and was well within the 6-month period of increased cardiovascular risk with bereavement, with similar timing to our prior case–control study which demon- strated increases in physiological and psychosocial risk factors. 15 Thesamplesizewassmallalthoughitwas based on our prior power calculations. Since both metoprolol and aspirin were used as an active strategy versus two matched placebos, we cannot separate the effects of the individual drugs, especially because beta blockers may have antithrombotic effects, and aspirin may modify HRV and depression. Further research is needed to separate out the actions of these two therapies. Other viable pathways were not assessed in this analysis including physical inactivity, poor eating habits and other maladaptive changes in health behavior, although there was no difference in sleep duration or alcohol use. Although the average age of our participants is less than that of the overall bereaved population, the age range was broad, including a participant aged 85 years, and the increased cardiovascular risk with bereavement is seen in men and women of all ages. 6 The recruitment rate of 19% of eligible subjects raises a question regarding generalizability, however we 270Tofler et al American Heart Journal February 2020 consider this rate to be reasonable, since the trial was at the sensitive time of early bereavement, and included randomization to medication, which had not been previously evaluated in this population. Since we enrolled participants where the deaths occurred in hospital, the reactions may have been greater than when deaths occurred at home or in a nursing home. However, while the stress of hospitalization of a relative is independently associated with increased cardiovascular events, 47 epidemiologic studies of bereavement have not been restricted to hospitalized patients. 5,6,9,10 Implications and future studies Thefindingthatlowdosemetoprololandaspirinhasa positive impact on several surrogate cardiovascular risk markers including anxiety, and is well tolerated in early bereavement with no negative impact on bereavement intensity up to 6 months, enables clinicians to consider this treatment in their patients. While clinicians need to be wary of appearing to medicalize an almost universal stressful experience, reducing heart attacks among bereaved people is a worthy goal. At a time when the deceased is the focus of attention, our findings remind clinicians to consider the well-being of bereaved individuals more broadly, including encouraging ade- quate diet and sleep, ensuring medication adherence and reminding the bereaved to seek help for symptoms that may be cardiac. A large randomized trial would be required to see differences in hard endpoints 10 and to identify which individuals would derive particular benefit. Our study was not designed to evaluate prolonged bereavement intensity, however the reduced anxiety seen at 6 months, suggests that the impact may persist beyond the period of treatment, and provides encouragement for further evaluation. While the present study focused on bereavement due to the death of partners and children, our findings are relevant to other causes of bereavement, including job loss, relationship breakdown, trauma and deaths of other loved ones, including pets. The findings also provide encouragement for the evaluation of the beta blocker/aspirin combination in acute stress situations as triggered acute risk prevention (TARP) therapy. 48 Further research is needed into timing and duration of the intervention, possibly beginning earlier in bereavement. Our encouraging findings in bereavement also suggest that this metoprolol and aspirin treatment combination could be considered in other acute stress situations. Conclusion In early bereavement, low dose metoprolol (25 mg morning) and aspirin (100 mg morning) lowered blood pressure and heart rate and platelet responsiveness, and safely reduced anxiety and depressive symptoms. There is a paucity of proven interventions preventing adverse physical health during bereavement, which is a uniquelife stress with a complex combination of psychological symptoms. This study, the first randomized trial to investigate cardiac risk reduction in early bereavement, suggests that low dose metoprolol and aspirin may have a positive effect on reducing cardiovascular risk. Acknowledgement Data and Safety Monitoring Committee: Andrea Marshall PhD, Anthony Delaney MD and Peter Caspari MD. Funding support was received from Heart Research Australia References 1.Yusuf S, Hawken S, Ounpuu S, et al. Effect of potentially modifiable risk factors associated with myocardial infarction in 52 countries (the INTERHEART study): case-control study. Lancet2004;364:937-52. 2.Wassertheil-Smoller S, Shumaker S,OckeneJ,etal.Depressionand cardiovascular sequelae in postmenopausal women. The Women’s Health Initiative (WHI). Arch Intern Med2004;164:289-98. 3. Watkins LL, Koch GG, Sherwood A, et al. Association of anxiety and depression with all-cause mortality in individuals with coronary heart disease. J Am Heart Assoc2013;2, e000068.https://doi.org/10. 1161/JAHA.112.000068. 4.Glozier N, Tofler GH, Colquhoun DM, et al. Psychosocial risk factors for coronary heart disease. Med J Aust2013;199:179-80. 5.Stroebe M, Stroebe W, Schut H, et al. Grief is not a disease but bereavement merits medical awareness. Lancet2017;389:347-9. 6.Buckley T, McKinley S, Tofler G, et al. Cardiovascular risk in early bereavement: A literature review and proposed mechanisms. Int J Nurs Studies2010;47:229-38. 7.Maciejewski PK, Maercker A, Boelen PA, et al. “Prolonged grief disorder” and “persistent complex bereavement disorder”, but not “complicated grief”, are one and the same diagnostic entity: an analysis of data from the Yale Bereavement Study. World Psychiatry2016;15:266-75. 8.Bodnar JC, Kiecolt-Glaser JK. Caregiver depression after bereavement: Chronic stress isn’t over when it’s over. Psychol Aging1994;9:372-80. 9.Carey IM, Shah SM, DeWilde S, et al. Increased risk of acute cardiovascular events after partner bereavement. A matched cohort study. JAMA Int Med2014;174:598-605. 10.Mostofsky E, Maclure M, Sherwood JB, et al. Risk of Acute Myocardial Infarction After the Death of a Significant Person in One’s Life: The Determinants of Myocardial Infarction Onset Study. Circulation 2012;125:491-6. 11.Buckley T, Mihailidou A, Bartrop R, et al. Haemodynamic changes during early bereavement: potential contribution to increased cardiovascular risk. Heart. Lung & Circ2011;20:91-8. 12.Buckley T, Stannard A, Bartrop R, et al. Early bereavement is associated with increased heart rate and reduced heart rate variability. Am J Cardiol2012;110:1378-83. 13.Buckley T, Morel-Kopp MC, Ward C, et al. Inflammatory and thrombotic changes in early bereavement: a prospective evaluation. Eur J Cardiovasc Prev Rehab2012;19:1145-52. 14.Faguendes CP, Murdock KW, LeRoy A, et al. Spousal bereavement is associated with more pronounced ex vivo cytokine production and lower heart rate variability: Mechanisms underlying cardiovascular risk? Psychoneuroendocrinology2018;93:65-71. 15.Buckley T, Bartrop R, McKinley S, et al. Prospective study of early bereavement on psychological and behavioural cardiac risk factors. Int Med J2009;39:370-8. Tofler et al271 American Heart Journal Volume 220 16.Ostling G, Goncalves I, Wikstrand J, et al. Long-term treatment with low-dose metoprolol cr/xl is associated with increased plaque echogenicity: The beta-blocker cholesterol-lowering asymptomatic plaque study (BCAPS). Atherosclerosis2011;215:440-5. 17.Niemela MJ, Airaksinen KE, Huikuri HV. Effect of beta-blockade on heart rate variability in patients with coronary artery disease. J Am Coll Cardiol1994;23:1370-7. 18.Steenen SA, van Wijk AJ, van der Heijden GJ, et al. Propranolol for the treatment of anxiety disorders: Systematic review and meta- analysis. J Psychopharmacol2016;30:128-39. 19.Siepmann M, Rauh R, Spanos E, et al. The effects of acetylic salicylic acid on heart rate variability in healthy subjects. Clin Auton Res2007;17:115-7. 20.Berk M, Dean O, Drexhage H, et al. Aspirin: a review of its neurobiological properties and therapeutic potential for mental illness. BMC Med2013;11:74. 21.Sarason IG, Levine HM, Basham RB, et al. Assessing social support: The Social Support Questionnaire. J Pers Soc Psychol1983;44:127-39. 22.Spielberger CD.Manual for the State-Trait Anxiety Inventory (STAI). PaloAlto, CA: Consulting Psychologists Press. 1983. 23.Spielberger CD.State-Trait Anger Expression Inventory (STAXI) manual. Tampa, FL: Psychological Assessment Resources, Inc.. 1988. 24.Radloff LS. The CES-D scale: A self-report depression scale for research in the general population. Appl Psych Measurement1977;1:385-401. 25.Burnett P, Middleton W, Raphael B, et al. Measuring core bereavement phenomena. Psychol Med1997;27:49-57. 26.Morel-Kopp MC, McLean L, Chen Q, et al. The association of depression with platelet activation: evidence for a treatment effect. J Thromb Haemost2009;7:573-81. 27.Jámbor C, Weber CF, Gerhardt K, et al. Whole blood multiple electrode aggregometry is a reliable point-of-care test of aspirin- induced platelet dysfunction. Anesth Analg2009;109:25-31. 28.Mostofsky E, Maclure M, Tofler GH, et al. Relations of outbursts of anger and risk of acute myocardial infarction. Am J Cardiol2013;112:343-8. 29.Buckley T, Soo Hoo S, Fethney J, et al. Triggering of acute coronary occlusion by episodes of anger. Eur Heart J: Acute Cardiovascular Care2015;4:493-8. 30.Muller JE, Tofler GH, Stone PH. Circadian variation and triggers of onset of acute cardiovascular disease. Circulation1989;79:733-43. 31.Malfatto G, Facchini M, Sala L, et al. Effects of cardiac rehabilitation and beta-blocker therapy on heart rate variability after first acute myocardial infarction. Am J Cardiol1998;81:834-40. 32.Spencer CG, Felmeden DC, Blann AD, et al. Effects of “newer” and “older” antihypertensive drugs on hemorrheological, platelet, and endothelial factors. A substudy of the anglo-scandinavian cardiac outcomes trial. Am J Hypertens2007;20:699-704. 33.Barron HV, Viskin S, Lundstrom RJ, et al. Beta-blocker dosages and mortality after myocardial infarction: Data from a large health maintenance organization. Arch Intern Med1998;158:449-53.34.Mittleman MA, Maclure M, Sherwood JB, et al. Triggering of acute myocardial infarction onset by episodes of anger. Determinants of Myocardial Infarction Onset Investigators. Circulation1995;92: 1720-5. 35.Ridker PM, Manson JE, Buring JE, et al. Circadian variation of acute myocardial infarction and the effect of low-dose aspirin in a randomized trial of physicians. Circulation1990;82:897-902. 36.Haft JI, Arkel YS. Effect of emotional stress on platelet aggregation in humans. Chest1976;70:501-5. 37.Vanags D, Rodgers SE, Lloyd JV, et al. The antiplatelet effect of daily low dose enteric-coated aspirin in man: A time course of onset and recovery. Thromb Res1990;59:995-1005. 38.Folts JD, Rowe GG. Epinephrine potentiation of in vivo stimuli reverses aspirin inhibition of platelet thrombus formation in stenosed canine coronary arteries. Thromb Res1988;50:507-16. 39.RanchordAM,SpertusJA,BuchananDM,etal.Initiationofβ-blocker therapy and depression after acute myocardial infarction. Am Heart J 2016;174:37-42. 40.Battes Linda C, LC Susanne S, et al. Beta blocker therapy is associated with reduced depressive symptoms 12 months post percutaneous coronary intervention. J Affective Disorders2012;136:751-7. 41.van Melle JP, Verbeek DE, van den Berg MP, et al. Beta-blockers and depression after myocardial infarction: a multicenter prospective study. J Am Coll Cardiol2006;48:2209-14. 42.Ringoir L, Pedersen SS, Widdershoven JW, et al. Beta-blockers and depression in elderly hypertension patients in primary care. Fam Med 2014;46:447-53. 43.Qaseem A, Fihn SD, Dallas P, et al. Management of stable ischemic heart disease: Summary of a clinical practice guideline from the American College of Physicians/American College of Cardiology Foundation/American Heart Association/American Association for Thoracic Surgery/Preventive Cardiovascular Nurses Associa- tion/Society of Thoracic Surgeons. Ann Intern Med2012;157: 735-43. 44.Custodis F, Reil JC, Laufs U, et al. Heart rate: a global target for cardiovascular disease and therapy along the cardiovascular disease continuum. J Cardiol2013;62:183-7. 45.Giustino TF, Fitzgerald PJ, Maren S. Revisiting propranolol and PTSD: Memory erasure or extinction enhancement? Neurobiol Learn Mem 2016;130:26-33. 46.Karl S, Fallon M, Palitsky R, et al. Low-dose aspirin for prevention of cardiovascular risk in bereavement: results from a feasibility study. Psychother Psychosom2018;87:112-3. 47.Christakis NA, Allison PD. Mortality after the hospitalisation of a spouse. N Engl J Med2006;354:719-30. 48.Tofler GH, Spinaze M, Shaw E, et al. Therapy for triggered acute risk prevention in subjects at increased cardiovascular risk. Am J Cardiol 2013;111:1755-8. 272Tofler et al American Heart Journal February 2020 Reproduced with permission of copyright owner. Further reproductionprohibited without permission.