Desire for hastened death in patients with advanced disease and the evidence base of clinical guidelines: a systematic review

PURPOSE: Patients' desire for hastened death within the context of advanced disease and palliative care is a controversial topic, frequently discussed in the international literature. Much of the discussion has focused on opinion and debate about ethical matters related to hastened death. Not many research studies seem to have specifically targeted why palliative care patients may desire hastened death, and few have focused on clinical guidelines for responding to such requests. METHODS: Using a systematic literature review process, we evaluated the research evidence related to the reasons patients express a desire for a hastened death, and the quality of clinical guidelines in this area. RESULTS: Thirty-five research studies met the inclusion criteria related to reasons associated with a desire for hastened death. The factors associated with a desire to die were often complex and multifactorial; however, psychological, existential and social reasons seem to be more prominent than those directly related to physical symptoms, such as pain. Much of the evidence supporting the reasons for these statements is based on: (a) patients' perceptions of how they may feel in the future, and (b) health professionals' and families' interpretations of why desire to die statements may have been made. Several publications provided expert opinion for responding to requests for physician-assisted suicide and euthanasia. In keeping with this limited research base, there is a lack of evidence-based guidelines for clinical care that addresses the desire to die among terminally ill patients. Most literature has focused on discipline specific responses, with minimal exploration of how clinicians might respond initially to a statement from a patient regarding a desire to die. CONCLUSIONS: In order to advance understanding of the complex issue of desire for hastened death in the context of palliative care, research should focus on studies with patients who have actually made a desire to die statement and the development of guidelines to help health professionals respond. Direction for research in this area is described.     

Influence of pain and quality of life on desire for hastened death in patients with advanced cancer

OBJECTIVE: to assess the relationship between quality of life, pain and desire for hastened death in advanced cancer patients. METHODS: 120 Greek patients with advanced cancer were interviewed with the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire C30 version 3.0 (EORTC QLQ-C30), the Greek Brief Pain Inventory (G-BPI), the Greek Hospital Anxiety and Depression Scale (G-HADS) and the Greek Schedule of Attitudes toward Hastened Death (G-SAHD). RESULTS: statistically significant associations were found between total G-SAHD scores and scores for the worst level of pain in the previous 24 hours (G-BP13) (r = 0.279, P = 0.002), and between total G-SAHD scores and scores for the level of pain relief obtained in the last 24 hours (G-BP18) (r = -0.326, P = 0.0005). The strongest correlations were found between G-SADH and emotional functioning (r = 0.569, P<0.0001) and global quality of life (r = -0.331, P<0.0001) from EORTC QLQ-C30. In multivariate analyses, emotional functioning, social functioning, financial impact, and the interference of pain in general activity and mood were significant predictors of G-SAHD (all P<0.0001). CONCLUSION: quality of life and pain appeared to have a statistically significant relationship with desire for hastened death. Adequate palliative care should alleviate pain and the desire for hastened death, improving quality of life.     

Pain and desire for hastened death in terminally ill cancer patients

The purpose of this study was to assess the relationship between pain and the desire for hastened death in terminally ill cancer patients. The participants were 120 terminally ill cancer patients under palliative treatment from June 2003 to November 2004. Patients completed a pain assessment tool, the Greek Brief Pain Inventory (G-BPI), and a self-report measure of the desire for hastened death, the Greek Schedule of Attitudes Toward Hastened Death (G-SAHD). Moderate but statistically significant associations were found between some of the severity and interference items of G-BPI and G-SAHD; more specifically, between G-SAHD and G-BPI3, "worst pain in the last 24 hours" (r = 0.279, P = .002); G-SAHD and G-BPI4, "least pain in the last 24 hours" (r = 0.253, P = .005); and G-SAHD and G-BPI5, "average pain in the last 24 hours" (r = 0.283, P = .002). A stronger association was revealed between G-SAHD and G-BPI8, "relief provided by pain treatment and medications in the last 24 hours" (r = -0.326, P = .000). Multiple regression analyses including the enter model and the forward model were conducted. According to the enter model, the strongest predictors of hastened death were items G-BPI6, "current pain"; G-BPI8, "relief provided by pain treatment and medications in the last 24 hours"; G-BPI9i, "interference of pain in general activity"; and G-BPI9iii, "interference of pain in walking." According to the forward model, significant predictors of the desire for death were items G-BPI5, "average pain in the last 24 hours"; G-BPI6, "current pain"; G-BPI9i, "interference of pain in general activity"; and G-BPI9ii, "interference of pain in mood," all of which were statistically significant (P = .000-.042). Pain appeared to have a statistically significant relationship with the desire for hastened death. Effective treatment by healthcare professionals should be provided to reduce pain and cancer-related symptoms as well as the desire for hastened death.     

The desire for hastened death in patients with metastatic cancer

A substantial minority of patients in palliative care settings report a high desire for hastened death (DHD), in association with physical and emotional distress, low social support, and impaired spiritual well being. To clarify to what extent DHD emerges in association with suffering prior to the end of life, we determined its prevalence and correlates in ambulatory patients with metastatic cancer, the majority of whom had an expected survival of >6 months. We hypothesized that DHD in this sample would be directly linked to physical and psychological distress, and inversely related to perceived social support, self-esteem, and spiritual well being. Three hundred twenty-six outpatients completed the Schedule of Attitudes Toward Hastened Death (SAHD), Brief Pain Inventory, Memorial Symptom Assessment Scale, Beck Depression Inventory-II (BDI-II), Beck Hopelessness Scale (BHS), Medical Outcomes Study Social Support Survey, FACIT-Spiritual Well-Being Scale, Rosenberg Self-Esteem Scale, and Karnofsky Performance Status. Over 50% of participants reported pain, >20% reported elevated levels of depression (BDI-II ≥ 15) and hopelessness (BHS ≥ 8), but <2% had a high DHD (SAHD ≥ 10). DHD was correlated positively with hopelessness, depression, and physical distress, and negatively with physical functioning, spiritual well being, social support, and self-esteem; it was not associated with treatment status or proximity to death. Over 34% of the variance in predicting SAHD scores was accounted for by hopelessness, depression, and functional status. The relative absence of a strong DHD in this sample suggests that the will to live tends to be preserved in cancer patients prior to the end of life, in spite of significant emotional and physical suffering.     

Cancer-related pain and disability: a longitudinal study

Context

Although the cross-sectional association between cancer-related pain and disability is well established, their longitudinal relationship has been less studied.

Objectives

Data from the Indiana Cancer Pain and Depression (INCPAD) trial were analyzed to determine whether baseline cancer-related pain and changes in pain over time predict disability over 12 months.

Methods

A total of 274 cancer survivors with cancer-related pain were accrued in the INCPAD trial. Data were collected at baseline, one, three, six, and 12 months by interviewers blinded to treatment arm. Disability outcomes included a continuous measure (Sheehan Disability Scale [SDS] score) and a categorical measure (≥14 days in the past four weeks with a ≥50% reduction in usual activities). Predictor variables, operationalized by the Brief Pain Inventory, included baseline pain severity and changes in pain severity scores between each time point. Multivariable analyses were conducted adjusting for treatment group, baseline disability, and selected covariates including depression.

Results

Baseline pain severity did not predict disability outcomes at 12 months. However, improvement in pain severity predicted less disability over 12 months both in terms of SDS scores (b = −0.17, t = −5.33, P < 0.001) and ≥14 disability days in the past month (odds ratio = 0.85; 95% confidence interval, 0.79–0.93; P < 0.001).

Conclusion

Disability over 12 months in patients with cancer-related pain is predicted by changes in pain severity over time. Results suggest that effective pain management may reduce subsequent disability among cancer survivors.     

Patient experiences of anxiety, depression and acute pain after surgery: a longitudinal perspective

This study sought to explore the impact of the psychological variables anxiety and depression, on pain experience over time following surgery. Eighty-five women having major gynaecological surgery were assessed for anxiety, depression and pain after surgery. To gain further understanding, 37 patients participated in a semi-structured taped telephone interview 4-6 weeks post-operatively. Pre-operative anxiety was found to be predictive of post-operative anxiety on Day 2, with patients who experienced high levels of anxiety before surgery continuing to feel anxious afterwards. By Day 4 both anxiety and depression scores increased as pain increased and one-third of the sample experienced levels of anxiety in psychiatric proportions whilst under one-third experienced similar levels of depression. These findings have significant implications for the provision of acute pain management after surgery. Future research and those managing acute pain services need to consider the multidimensional effect of acute pain and the interface between primary and secondary care.     

Personality traits,depression and migraine in women: a longitudinal study

Our purpose was to examine the association between personality traits, depression and migraine in the long term. In 56 women with migraine a psychological assessment was carried out to assess the presence of major depression, and the Minnesota Multiphasic Personality Inventory (MMPI) and the State and Trait Anxiety Inventory (STAI) were administered at baseline (T0) and after 6-7 years (T2). Frequency, severity and duration of migraine were recorded at T0, after treatment (T1) and at T2, and their relation to the prevalence of depression and to the MMPI and STAI data was examined (ANOVA, Student's t-test, chi2 analysis, and multiple regression analysis). Pain parameters improved in all patients in T0-T1, but at T2 were higher in patients with depression at T0. The patients whose migraine improved at T2 had, at T0 and T2, significantly lower MMPI and STAI scores. Multiple regression analysis showed a correlation of the MMPI depression score and STAI 1,2 scores at T0 with headache frequency at T2. We conclude that the co-occurrence of migraine, personality changes and depression in women does not appear to influence the results of treatment at short-term, but it seems to be influential on headache history in the long term.     

Multidisciplinary management of cancer pain: a longitudinal retrospective study on a cohort of end-stage cancer patients

The epidemiology of cancer pain and the outcomes associated with pain treatments were investigated through a retrospective survey of 772 patients with advanced cancer. The cumulative prevalence of pain was 87%, including all types of cancer. Mean duration of pain was 6.9+/-8.1 months. The prevalence of pain was 28%, 46%, 67%, 75%, and 79% at 6 months, 3 months, 1 month, 1 week, and 1 day before the time of death, respectively. The so-called "strong" opioids had been used in 85% of the 669 patients with pain. Seventy-nine percent of patients with pain received nonsurgical antineoplastic treatment for pain control. No more than 11% of patients ultimately experienced substantial pain in the last 6 months of life (defined as pain score 5-10 on a 0-10 numeric rating scale). We conclude that the application of a multidisciplinary approach to pain management offers effective pain control for most patients with advanced cancer.     

Risk factors at pretreatment predicting treatment-induced nausea and vomiting in Australian cancer patients: a prospective, longitudinal, observational study

Purpose  

Despite significant advances in antiemetic management, almost 50% of cancer patients still experience nausea and vomiting during treatment. The goal of antiemetic therapy is complete prevention of treatment-induced nausea and/or vomiting (TINV); however, realisation of this goal remains elusive, thus supplementary strategies identifying patients at high risk must be employed in the interim. Consequently, we examined TINV incidence and its risk factors, including patient, clinical and pretreatment quality of life (QOL)/psychological factors.     

Anxiety, depression, and pain: differences by primary cancer

Goals of work  

Disease-related cancer pain is a multidimensional phenomenon. Psychological factors that may alter pain perception in cancer patients have not been well studied. The study purpose was to explore differences in pain, anxiety, and depression by type of primary cancer.     

Symptoms during cancer pain treatment following WHO-guidelines: a longitudinal follow-up study of symptom prevalence, severity and etiology

Most patients with advanced cancer develop diverse symptoms that can limit the efficacy of pain treatment and undermine their quality of life. The present study surveys symptom prevalence, etiology and severity in 593 cancer patients treated by a pain service. Non-opioid analgesics, opioids and adjuvants were administered following the WHO-guidelines for cancer pain relief. Other symptoms were systematically treated by appropriate adjuvant drugs. Pain and symptom severity was measured daily by patient self-assessment; the physicians of the pain service assessed symptom etiology and the severity of confusion, coma and gastrointestinal obstruction at each visit. The patients were treated for an average period of 51 days. Efficacy of pain treatment was good in 70%, satisfactory in 16% and inadequate in 14% of patients. The initial treatment caused a significant reduction in the average number of symptoms from four to three. Prevalence and severity of anorexia, impaired activity, confusion, mood changes, insomnia, constipation, dyspepsia, dyspnoea, coughing, dysphagia and urinary symptoms were significantly reduced, those of sedation, other neuropsychiatric symptoms and dry mouth were significantly increased and those of coma, vertigo, diarrhea, nausea, vomiting, intestinal obstruction, erythema, pruritus and sweating remained unchanged. The most frequent symptoms were impaired activity (74% of days), mood changes (22%), constipation (23%), nausea (23%) and dry mouth (20%). The highest severity scores were associated with impaired activity, sedation, coma, intestinal obstruction, dysphagia and urinary symptoms. Of all 23 symptoms, only constipation, erythema and dry mouth were assessed as being most frequently caused by the analgesic regimen. In conclusion, the high prevalence and severity of many symptoms in far advanced cancer can be reduced, if pain treatment is combined with systematic symptom control. Nevertheless, general, neuropsychiatric and gastrointestinal symptoms are experienced during a major part of treatment time and pain relief was inadequate in 14% of patients. Cancer pain management has to be embedded in a frame of palliative care, taking all the possibilities of symptom management into consideration.     

Diabetes mellitus and risk of subsequent depression: a longitudinal study

BackgroundFindings of previous studies on the association between diabetes and the risk of depression are contradictory. Furthermore, much less is known concerning the association among young adults.ObjectiveTo investigate whether diabetes is associated with an increased risk of subsequent development of depression, with emphasis on age-specific variations.DesignA cohort study.SettingClaims data of one million subjects randomly selected from 23 million people covered by the Taiwan National Health Insurance program.ParticipantsFrom the claims data, we identified 14,048 patients aged ≥20 years with newly diagnosed diabetes in 2000–2002 and randomly selected 55,608 non-diabetic subjects for comparison, that were frequency-matched by calendar year, age, and gender. Incidence rates of depression to the end of 2007 were identified, and risks were compared between the two groups.ResultsThe incidence of depression was 1.80-times higher in the diabetic group than in nondiabetic subjects over a median follow-up of 6.5 years (adjusted hazard ratio [HR] = 1.46, 95% confidence interval [CI]: 1.24–1.71). Age-specific HRs for incidence of depression in relation to diabetes were not statistically different between the patient subgroups aged 20–39, 40–49, 50–59, 60–69 and ≥70 years (p value for age-diabetes interaction = 0.33). Stratified analyses showed that the association was much stronger for subjects without comorbid cardiovascular disease than for those with this comorbidity. Insulin treatment was associated with a 43% reduced risk of depression in diabetic patients.ConclusionsIn this population-based study, diabetic patients were at a higher risk for subsequent depression. Adequate treatment reduced the risk.     

Pain and pain treatment in AIDS patients: a longitudinal study

To determine the prevalence, incidence, and characteristics of pain connected with AIDS, 95 AIDS patients were enrolled in a prospective longitudinal study and interviewed every six months during a 2-year period or until death. The overall incidence of pain was 88%, and 69% of the patients suffered from constant pain interfering with daily living to a degree described as moderate or severe. The most common pain localizations were: extremities (32%), head (24%), upper gastrointestinal tract (23%) and lower gastrointestinal tract (22%). Pain conditions were connected to various opportunistic infections, Kaposi's sarcoma, or lymphoma. Pain in the extremities was predominantly of neuropathic origin (21%). The number of pain localizations increased significantly as death approached (0.8 +/- 1. 0 vs. 1.4 +/- 0.8, p = 0.03). The survival rate for patients without pain at entry was significantly higher than the survival rate of patients in pain, probably related to differences in the duration of AIDS at the time of inclusion. Sustained-release morphine preparations were prescribed in 29% of the patients. Of 39 patients (41%) who died in the department, 7 patients were prescribed continuous intravenous morphine infusion for pain treatment in the terminal phase and 20 patients received short-acting opioids. According to the Pain Management Index (PMI), the patients were insufficiently treated at the beginning of the study. Although the PMI improved significantly during the observation period, the patients felt that pain was not taken seriously by the physicians. However, the patients were convinced that treatment was optimal and, therefore, only 9% of the patients were dissatisfied. Patients were reluctant to take analgesics, primarily because of fear of addiction.     

Dimensions of depression: A comparative longitudinal study

A study was conducted to examine the factor structure of a set of commonly employed depression-related measures and to determine whether higher-order composite variables based on factor loadings would be differentially related to changes in depression status. Five cognitive and two behaviorally oriented measures were administered to 66 hospitalized depressives at pretreatment, 4 to 8 weeks later at the end of an initial phase of pharmacological treatment, and at 2- to 4-month intervals during an 8-month follow-up period. A principal-components analysis performed on nine variables produced three interpretable factors that differed systematically with respect to amount of differentiation between responders and nonresponders, as well as magnitude of change associated with successful treatment. Analyses performed on individual measures to track maintainers versus relapsers across three time points likewise yielded results consistent with predictions based on factor membership.This research was supported in part by National Institute of Mental Health Grant MH37664. The authors would gratefully like to acknowledge Margo Hurwitz, Donna Richard, Michelle Thrush, and Abe Wolf for assistance in data preparation.     

Acupuncture for chronic low back pain in routine care: a multicenter observational study

OBJECTIVE: To investigate patient characteristics and outcomes after undergoing acupuncture treatment for chronic low back pain (cLBP) in Germany and to analyze chronification, pain grading, and depression as predictors for treatment outcomes. PATIENTS AND METHODS: Patients with cLBP (ICD-10 diagnoses M54.4 or M54.5) who underwent acupuncture therapy (mean number of sessions 8.7+/-2.9) within the framework of a reimbursement and research program sponsored by German statutory sickness funds were included in an observational study. Patients were asked to complete detailed questionnaires that included questions on intensity and frequency of pain and instruments measuring functional ability, depression, and quality of life (SF-36) before and after treatment and 6 months after beginning acupuncture. Participating physicians assessed pain chronification in patients. RESULTS: A total of 2564 patients (mean age 57.7+/-14.0 y, 78.7% female), who were treated by 1607 physicians, were included in the main analysis. After 6 months (6-mo follow-up), 45.5% of patients demonstrated clinically significant improvements in their functional ability scores. The mean number of days with pain was decreased by half (from 21 to 10 d/mo). Employed patients (employed patient subgroup analysis) reported a 30% decrease from baseline in days of work lost. In all, 8.1% of patients reported adverse events, the majority of which were minor. Subgroup analyses focusing on pain severity, stage of chronification, and depression revealed statistically significant relationships both to baseline measures and to reduction of pain after acupuncture. CONCLUSIONS: Acupuncture treatment is associated with clinically relevant improvements in patients suffering from cLBP of varying degrees of chronification and/or severity.     

Risk factors for neck pain: a longitudinal study in the general population

The objective of the study was to examine the 1-year cumulative incidence of episodic neck pain and to explore its associations with individual risk factors, including a history of previous neck injury. A baseline cross-sectional survey of an adult general population sample made up of all 7669 adults aged 18-75 years, registered with two family practices in South Manchester, United Kingdom, identified the study population of adults with no current neck pain. This study population was surveyed again 12 months later to identify all those who had experienced neck pain during the follow-up period. At follow-up, cumulative 1-year episode incidence of neck pain was estimated at 17.9% (95% confidence interval 16.0-19.7%). Incidence was independent of age, but was more common in women. A history of previous neck injury at baseline was a significant risk factor for subsequent neck pain in the follow-up year (risk ratio 1.7, 95% confidence interval 1.2-2.5), independent of gender and psychological status. Other independent baseline risk factors for subsequent neck pain included number of children, poor self-assessed health, poor psychological status and a past history of low back pain. We have carried out a prospective study in a general population sample and demonstrated that established risk factors for chronic pain predict future episodes of neck pain, and shown that in addition a history of neck injury is an independent and distinct risk factor. This finding may have major public health and medicolegal implications.