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A Comparison of Symptom Prevalence in Far Advanced Cancer, AIDS, Heart Disease, Chronic Obstructive Pulmonary Disease and Renal Disease

  • Joao Paulo Solano
    Affiliations
    Division of Internal Medicine (J.P.S.), Department of Medicine, Federal University of São Paulo, São Paulo, Brazil; and The Cicely Saunders Foundation (B.G., I.J.H.) and Department of Palliative Care and Policy (B.G., I.J.H.), King's College London, London, United Kingdom
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  • Barbara Gomes
    Affiliations
    Division of Internal Medicine (J.P.S.), Department of Medicine, Federal University of São Paulo, São Paulo, Brazil; and The Cicely Saunders Foundation (B.G., I.J.H.) and Department of Palliative Care and Policy (B.G., I.J.H.), King's College London, London, United Kingdom
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  • Irene J. Higginson
    Correspondence
    Address reprint requests to: Prof. Irene J. Higginson, Weston Education Center, 10 Cutcombe Road, London SE5 9PJ, United Kingdom.
    Affiliations
    Division of Internal Medicine (J.P.S.), Department of Medicine, Federal University of São Paulo, São Paulo, Brazil; and The Cicely Saunders Foundation (B.G., I.J.H.) and Department of Palliative Care and Policy (B.G., I.J.H.), King's College London, London, United Kingdom
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      Abstract

      Little attention has been paid to the symptom management needs of patients with life-threatening diseases other than cancer. In this study, we aimed to determine to what extent patients with progressive chronic diseases have similar symptom profiles. A systematic search of medical databases (MEDLINE, EMBASE, and PsycINFO) and textbooks identified 64 original studies reporting the prevalence of 11 common symptoms among end-stage patients with cancer, acquired immunodeficiency syndrome (AIDS), heart disease, chronic obstructive pulmonary disease, or renal disease. Analyzing the data in a comparative table (a grid), we found that the prevalence of the 11 symptoms was often widely but homogeneously spread across the five diseases. Three symptoms—pain, breathlessness, and fatigue—were found among more than 50% of patients, for all five diseases. There appears to be a common pathway toward death for malignant and nonmalignant diseases. The designs of symptom prevalence studies need to be improved because of methodological disparities in symptom assessment and designs.

      Key Words

      Introduction

      Populations are aging all over the world,
      • World Health Organization
      Active aging: A policy framework.
      with those aged 60 and over growing faster than any other age group.
      • World Health Organization
      Active aging: A policy framework.
      By 2025, the percentage of people aged 65 years and over will be almost 30% in developed and almost 15% in less developed regions.
      While this increase in longevity is welcome, as a consequence more and more people are dying from chronic, rather than acute, diseases.
      • Edmonds P.
      • Karlsen S.
      • Khan S.
      • Addington-Hall J.M.
      A comparison of the palliative care needs of patients dying from chronic respiratory disease and lung cancer.
      • Higginson I.J.
      • Jarman B.
      • Astin P.
      • Dolan S.
      Do social factors affect where patients die: an analysis of 10 years of cancer deaths in England.
      • Murray C.J.L.
      • Lopez A.D.
      Mortality by cause for eight regions of the world: global burden of disease study.
      They will usually have endured several symptom complexes for many years. Cartwright,
      • Cartwright A.
      Changes in life and care in the year before death 1969–1987.
      for example, compared reports of the last year of life in 1969 and 1987. In the later study, people died at an increased age, but their longer life was associated with prolonged unpleasant symptoms.
      The symptom management and end-of-life strategies pioneered over the past four decades by hospices and palliative care services have focused mainly on cancer patients.
      • Anderson H.
      • Ward C.
      • Eardley A.
      • et al.
      The concerns of patients under palliative care and a heart failure clinic are not being met.
      • Gibbs L.M.E.
      • Addington-Hall J.
      • Gibbs J.S.
      Dying from heart failure: lessons from palliative care.
      • Higginson I.J.
      Palliative care: a review of past changes and future trends.
      Little attention has been paid to patients with other life-threatening diseases,
      • Gibbs L.M.E.
      • Addington-Hall J.
      • Gibbs J.S.
      Dying from heart failure: lessons from palliative care.
      • Tranmer J.E.
      • Heyland D.
      • Dudgeon D.
      • et al.
      Measuring the symptom experience of seriously ill cancer and noncancer hospitalized patients near the end of life with the Memorial Symptom Assessment Scale.
      even though these cause three of four deaths in developed countries. Some studies have suggested that people with noncancer conditions experience a similar degree of symptom distress as cancer patients, and would benefit from a more holistic, inclusive, and supportive care network.
      • Butters E.
      • Higginson I.J.
      Two HIV/AIDS community support teams: patient characteristics, problems at referral and during the last 6 weeks of life.
      • Gore J.M.
      • Brophy C.J.
      • Greenstone M.A.
      How well do we care for patients with end stage chronic obstructive pulmonary disease (COPD)? A comparison of palliative care and quality of life in COPD and lung cancer.
      • Sepulveda C.
      • Marlin A.
      • Yoshida T.
      • Ullrich A.
      Palliative care: the World Health Organization's global perspective.
      Indeed, one of the first studies on dying, by Hinton
      • Hinton J.
      The physical and mental stress of dying.
      in 1963, described how physical and mental distress were more pronounced in patients dying from heart or renal failure than those with cancer. As a result, governmental and other reports have urged that palliative care be extended to patients with progressive, incurable, nonmalignant conditions.
      • O'Brien T.
      • Welsh J.
      • Dunn F.G.
      ABC of palliative care: non-malignant conditions.
      However, a simple expansion of existing models of care to include all noncancer diseases may not be appropriate. Apart from acquired immunodeficiency syndrome (AIDS), noncancer patients are on average older than cancer patients,
      • Addington-Hall J.
      • Higginson I.J.
      Palliative care for non-cancer patients.
      have different patterns of dependency
      • Addington-Hall J.M.
      • Fakhoury W.
      • McCarthy M.
      Specialist palliative care in non-malignant disease.
      and functional decline, and are likely to be suffering from comorbidities. Little is known about their symptom experiences and, in particular, how these compare with those of cancer patients. For example, do noncancer patients have the same complexity of symptoms as cancer patients? Are there new and different symptoms affecting those with noncancer conditions? What is the relevance of knowledge about symptom management in cancer for noncancer conditions?
      In this study, we sought to determine, from existing studies, the prevalence of 11 symptoms (pain, depression, anxiety, confusion, fatigue, breathlessness, insomnia, nausea, constipation, diarrhea, and anorexia) among end-stage patients suffering from five common, chronic, and progressive conditions—cancer, AIDS, heart disease (HD), chronic obstructive pulmonary disease (COPD), and renal disease (RD). We aimed to determine whether patients with different diseases have different profiles of symptoms.

      Methods

      Search Strategy

      We searched three electronic databases, MEDLINE (1966 to June, 2004), EMBASE (1988 to June, 2004), and PsycINFO (1985 to June, 2004), using three groups of keywords:
      • 1.
        Symptoms, pain, confusion, delirium, cognitive failure, depression, low mood, sadness, anxiety, dyspnoea, dyspnea, breathlessness, fatigue, weakness, anorexia, nausea, diarrhoea, diarrhea, constipation, insomnia, poor sleeping (selected as the most appropriate terms to target the 11 symptoms);
      • 2.
        Dying, end of life, terminally ill, hospice, palliative care, terminal care (terms selected to identify samples of patients at the end of life);
      • 3.
        Terminal disease, advanced cancer, metastatic cancer, AIDS, end stage heart disease, end stage heart failure, end stage respiratory disease, end stage chronic obstructive pulmonary disease, end stage COPD, end stage renal disease (RD), end stage renal failure (terms selected to identify our specified disease groups).
      Within each group the keywords were combined using or. The resultant three groups were then combined using and.
      For the purpose of this review, different ways of assessing symptoms were considered. Given the variety of terms used in articles and textbooks to designate symptoms, we used more than one keyword for most of the symptoms—delirium and cognitive failure were used as alternative search terms for confusion; dyspnoea or dyspnea for breathlessness; low mood and sadness for depression; weakness for fatigue; and poor sleeping for insomnia.
      We also searched relevant chapters in 12 textbooks of palliative care, internal medicine, and oncology: Oxford Textbook of Palliative Medicine; Handbook of Psychiatry in Palliative Medicine; Palliative Care for Non-Cancer Patients; Clinical Audit in Palliative Care; Palliative Medicine Secrets; Managing Terminal Illness; A Guide to Symptom Relief in Palliative Care; Oxford Handbook of Dialysis; Cancer Pain: Assessment and Management; Gastrointestinal Symptoms in Advanced Cancer Patients; Issues in Palliative Care Research; Oncology for Palliative Medicine (Appendix). Reference lists of articles and chapters were checked to refine the search for important previous work on the theme (e.g., articles surrounding large samples, systematic reviews, and/or meta-analysis). Because the majority of studies reported on cancer patients and few on other conditions, more extensive searching and follow-up were undertaken for the four nonmalignant conditions.

      Inclusion/Exclusion Criteria

      We included studies where the target population encompassed adults with advanced illness suffering from cancer, AIDS, HD, COPD, or RD and for whom the prevalence of specified symptoms had been calculated. For the purpose of this study, advanced illness was taken to include patients who were described as having advanced or terminal illness, were in hospice care, had deteriorated despite treatment, or who were deemed to have a poor prognosis by investigators (i.e., less than one year).
      We excluded articles addressing any restricted population, such as patients with specific cancer types, single cancer sites, children, and drug users; articles reporting symptoms from only the very last hours of life, e.g., the terminal 48 hours; and case reports of single patients. Papers not written in English, Spanish, and Portuguese were excluded due to the investigators' limits of translation.

      Data Extraction

      Data were extracted to predesigned summary tables under the following headings: authors, country of origin, year of publication, aims of the study, number of participants (sample size), study design, measurement methods, and prevalence of individual symptoms.

      Analysis

      Extracted data were transferred to each cell of a “palliative symptom grid” to contrast information about symptom prevalence for the five chosen terminal conditions (Table 1). The number of patients across studies was calculated for each cell—for each of the symptoms under each diagnosis. When no data were found for a specific symptom and condition, “—” was displayed in the grid. Because of variability in assessment tools, samples sizes, and accrual models, it was not possible to reliably combine the findings of different studies. Therefore, we summarized the prevalence ranges for each symptom in each disease category, allowing the findings to be appraised in terms of the minimum and maximum reported prevalences.
      Table 1Symptom Prevalence, Summarized from the Palliative Symptom Grid
      SymptomsCancerAIDSHDCOPDRD
      Pain35–96%
      • Cartwright A.
      Changes in life and care in the year before death 1969–1987.
      • Anderson H.
      • Ward C.
      • Eardley A.
      • et al.
      The concerns of patients under palliative care and a heart failure clinic are not being met.
      • Tranmer J.E.
      • Heyland D.
      • Dudgeon D.
      • et al.
      Measuring the symptom experience of seriously ill cancer and noncancer hospitalized patients near the end of life with the Memorial Symptom Assessment Scale.
      • Addington-Hall J.M.
      • McCarthy M.
      Dying from cancer: results of a national population-based investigation.
      • Addington-Hall J.M.
      • MacDonald M.
      • Anderson H.
      • Freeling P.
      Dying from cancer: the views of bereaved family and friends about the experiences of terminally ill patients.
      • Addington-Hall J.M.
      Heart disease and stroke: lessons from cancer care.
      • Bruera E.
      Research in symptoms other than pain.
      • Chow E.
      • Fung K.
      • Panzarella T.
      • et al.
      A predictive model for survival in metastatic cancer patients attending an outpatient palliative radiotherapy clinic.
      • Cleeland C.S.
      • Gonin R.
      • Hatfield A.K.
      • et al.
      Pain and its treatment in outpatients with metastatic cancer.
      • Hearn J.
      • Higginson I.J.
      Cancer pain epidemiology: a systematic review.
      • Meuser T.
      • Pietruck C.
      • Radbruch L.
      • et al.
      Symptoms during cancer pain treatment following WHO-guidelines: a longitudinal follow-up study of symptom prevalence, severity and etiology.
      • Morita T.
      • Tsunoda J.
      • Inoue S.
      • Chihara S.
      Contributing factors to physical symptoms in terminally-ill cancer patients.
      • Potter J.
      • Hami F.
      • Bryan T.
      • Quigley C.
      Symptoms in 400 patients referred to palliative care services: prevalence and patterns.
      • Vainio A.
      • Auvinen A.
      Prevalence of symptoms among patients with advanced cancer: an international collaborative study.
      • Dunlop G.M.
      A study of the relative frequency and importance of gastrointestinal symptoms and weakness in patients with far advanced cancer.
      • Reuben D.B.
      • Mor V.
      • Hiris J.
      Clinical symptoms and length of survival in patients with terminal cancer.
      • Curtis E.B.
      • Krech R.
      • Walsh T.D.
      Common symptoms in patients with advanced cancer.
      • Brescia F.J.
      • Adler D.
      • Gray G.
      • et al.
      Hospitalized advanced cancer patients: a profile.
      • Ventafridda V.
      • De Conno F.
      • Ripamonti C.
      • Gamba A.
      • Tamburini M.
      Quality-of-life assessment during a palliative care programme.
      N =10,379
      The number of patients is underestimated or unknown because prevalence figures given by textbooks were considered (for which the number of patients was not provided).
      63–80%
      • Breitbart W.
      • McDonald M.V.
      • Rosenfeld B.
      • et al.
      Pain in ambulatory AIDS patients. I: Pain characteristics and medical correlates.
      • Singer E.J.
      • Zorilla C.
      • Fahy-Chandon B.
      • et al.
      Painful symptoms reported by ambulatory HIV-infected men in a longitudinal study.
      • Vogl D.
      • Rosenfeld B.
      • Breitbart W.
      • et al.
      Symptom prevalence, characteristics, and distress in AIDS outpatients.
      N = 942
      41–77%
      • Lynn J.
      • Teno J.M.
      • Phillips R.S.
      • et al.
      Perceptions by family members of the dying experience of older and seriously ill patients.
      • Addington-Hall J.M.
      Heart disease and stroke: lessons from cancer care.
      • Levenson J.W.
      • McCarthy E.P.
      • Lynn J.
      • Davis R.B.
      • Phillips R.S.
      The last six months of life for patients with congestive heart failure.
      • Nordgren L.
      • Sorensen S.
      Symptoms experienced in the last six months of life in patients with end-stage heart failure.
      N = 882
      The number of patients is underestimated or unknown because prevalence figures given by textbooks were considered (for which the number of patients was not provided).
      34–77%
      • Edmonds P.
      • Karlsen S.
      • Khan S.
      • Addington-Hall J.M.
      A comparison of the palliative care needs of patients dying from chronic respiratory disease and lung cancer.
      • Lynn J.
      • Teno J.M.
      • Phillips R.S.
      • et al.
      Perceptions by family members of the dying experience of older and seriously ill patients.
      • Skilbeck J.
      • Mott L.
      • Page H.
      • et al.
      Palliative care in chronic obstructive airways disease: a needs assessment.
      N = 372
      47–50%
      • Davison S.
      Pain in hemodialysis patients: prevalence, cause, severity, and management.
      • Kimmel P.
      • Emont S.
      • Newmann J.
      • Danko H.
      • Moss A.
      ESRD patient quality of life: symptoms, spiritual beliefs, psychosocial factors, and ethnicity.
      N = 370
      Depression3–77%
      • Cartwright A.
      Changes in life and care in the year before death 1969–1987.
      • Tranmer J.E.
      • Heyland D.
      • Dudgeon D.
      • et al.
      Measuring the symptom experience of seriously ill cancer and noncancer hospitalized patients near the end of life with the Memorial Symptom Assessment Scale.
      • Addington-Hall J.M.
      • McCarthy M.
      Dying from cancer: results of a national population-based investigation.
      • Durkin I.
      • Kearney M.
      • O'Siorain L.
      Psychiatric disorder in a palliative care unit.
      • Addington-Hall J.M.
      • MacDonald M.
      • Anderson H.
      • Freeling P.
      Dying from cancer: the views of bereaved family and friends about the experiences of terminally ill patients.
      • Chow E.
      • Fung K.
      • Panzarella T.
      • et al.
      A predictive model for survival in metastatic cancer patients attending an outpatient palliative radiotherapy clinic.
      • Potter J.
      • Hami F.
      • Bryan T.
      • Quigley C.
      Symptoms in 400 patients referred to palliative care services: prevalence and patterns.
      • Dunlop G.M.
      A study of the relative frequency and importance of gastrointestinal symptoms and weakness in patients with far advanced cancer.
      • Curtis E.B.
      • Krech R.
      • Walsh T.D.
      Common symptoms in patients with advanced cancer.
      • Ventafridda V.
      • De Conno F.
      • Ripamonti C.
      • Gamba A.
      • Tamburini M.
      Quality-of-life assessment during a palliative care programme.
      • Akechi T.
      • Okuyama T.
      • Sugawara Y.
      • et al.
      Major depression, adjustment disorders, and post-traumatic stress disorder in terminally ill cancer patients: associated and predictive factors.
      • Breitbart W.
      • Jaramillo J.R.
      • Chochinov H.M.C.
      Palliative and terminal care.
      • Hagerty R.G.
      • Butow P.N.
      • Ellis P.A.
      • et al.
      Cancer patient preferences for communication of prognosis in the metastatic setting.
      • Lloyd-Williams M.
      • Friedman T.
      • Rudd N.
      Criterion validation of the Edinburgh postnatal depression scale as a screening tool for depression in patients with advanced metastatic cancer.
      • Minagawa H.
      • Uchitomi Y.
      • Yamawaki S.
      • Ishitani K.
      Psychiatric morbidity in terminally ill cancer patients: a prospective study.
      • Regnard C.
      • Hockley J.
      A guide to symptom relief in palliative care.
      • Smith E.M.
      • Gomm S.A.
      • Dickens C.M.
      Assessing the independent contribution to quality of life from anxiety and depression in patients with advanced cancer.
      • Stone P.
      • Hardy J.
      • Broadley K.
      • et al.
      Fatigue in advanced cancer: a prospective controlled cross-sectional study.
      N = 4378
      The number of patients is underestimated or unknown because prevalence figures given by textbooks were considered (for which the number of patients was not provided).
      10–82%
      • Vogl D.
      • Rosenfeld B.
      • Breitbart W.
      • et al.
      Symptom prevalence, characteristics, and distress in AIDS outpatients.
      • Regnard C.
      • Hockley J.
      A guide to symptom relief in palliative care.
      • Rabkin J.G.
      • Ferrando S.J.
      • Jacobsberg L.B.
      • Fishman B.
      Prevalence of axis I disorders in an AIDS cohort: a cross-sectional, controlled study.
      • Tross S.
      • Hirsch D.A.
      Psychological distress and neuropsychological complications of HIV infection and AIDS.
      N = 616
      The number of patients is underestimated or unknown because prevalence figures given by textbooks were considered (for which the number of patients was not provided).
      9–36%
      • Nordgren L.
      • Sorensen S.
      Symptoms experienced in the last six months of life in patients with end-stage heart failure.
      • Gibbs J.S.R.
      Heart disease.
      N = 80
      The number of patients is underestimated or unknown because prevalence figures given by textbooks were considered (for which the number of patients was not provided).
      37–71%
      • Edmonds P.
      • Karlsen S.
      • Khan S.
      • Addington-Hall J.M.
      A comparison of the palliative care needs of patients dying from chronic respiratory disease and lung cancer.
      • Skilbeck J.
      • Mott L.
      • Page H.
      • et al.
      Palliative care in chronic obstructive airways disease: a needs assessment.
      N = 150
      5–60%
      • Levy J.
      • Morgan J.
      • Brown E.
      Oxford handbook of dialysis.
      • Martin C.R.
      • Thompson D.R.
      Prediction of quality of life in patients with end-stage renal disease.
      • Walters B.
      • Hays R.
      • Spritzer K.
      • Fridman M.
      • Carter W.
      Health-related quality of life, depressive symptoms, anemia, and malnutrition at hemodialysis initiation.
      • Watnick S.
      • Kirwin P.
      • Mahnensmith R.
      • Concato J.
      The prevalence and treatment of depression among patients starting dialysis.
      • Weisbord S.D.
      • Carmody S.S.
      • Bruns F.J.
      • et al.
      Symptom burden, quality of life, advance care planning and the potential value of palliative care in severely ill haemodialysis patients.
      • Wuerth D.
      • Finkelstein S.H.
      • Kliger A.S.
      • Finkelstein F.O.
      Chronic peritoneal dialysis patients diagnosed with clinical depression: results of pharmacologic therapy.
      N = 956
      The number of patients is underestimated or unknown because prevalence figures given by textbooks were considered (for which the number of patients was not provided).
      Anxiety13–79%
      • Addington-Hall J.M.
      • McCarthy M.
      Dying from cancer: results of a national population-based investigation.
      • Addington-Hall J.M.
      • MacDonald M.
      • Anderson H.
      • Freeling P.
      Dying from cancer: the views of bereaved family and friends about the experiences of terminally ill patients.
      • Chow E.
      • Fung K.
      • Panzarella T.
      • et al.
      A predictive model for survival in metastatic cancer patients attending an outpatient palliative radiotherapy clinic.
      • Potter J.
      • Hami F.
      • Bryan T.
      • Quigley C.
      Symptoms in 400 patients referred to palliative care services: prevalence and patterns.
      • Curtis E.B.
      • Krech R.
      • Walsh T.D.
      Common symptoms in patients with advanced cancer.
      • Ventafridda V.
      • De Conno F.
      • Ripamonti C.
      • Gamba A.
      • Tamburini M.
      Quality-of-life assessment during a palliative care programme.
      • Hagerty R.G.
      • Butow P.N.
      • Ellis P.A.
      • et al.
      Cancer patient preferences for communication of prognosis in the metastatic setting.
      • Smith E.M.
      • Gomm S.A.
      • Dickens C.M.
      Assessing the independent contribution to quality of life from anxiety and depression in patients with advanced cancer.
      • Stone P.
      • Hardy J.
      • Broadley K.
      • et al.
      Fatigue in advanced cancer: a prospective controlled cross-sectional study.
      N = 3274
      8–34%
      • Butters E.
      • Higginson I.J.
      Two HIV/AIDS community support teams: patient characteristics, problems at referral and during the last 6 weeks of life.
      • Rabkin J.G.
      • Ferrando S.J.
      • Jacobsberg L.B.
      • Fishman B.
      Prevalence of axis I disorders in an AIDS cohort: a cross-sectional, controlled study.
      • Butters E.
      • George R.
      • Higginson I.J.
      Audit methods: HIV/AIDS care.
      N = 346
      The number of patients is underestimated or unknown because prevalence figures given by textbooks were considered (for which the number of patients was not provided).
      49%
      • Nordgren L.
      • Sorensen S.
      Symptoms experienced in the last six months of life in patients with end-stage heart failure.
      N = 80
      51–75%
      • Claessens M.T.
      • Lynn J.
      • Zhong Z.
      • et al.
      Dying with lung cancer or chronic obstructive respiratory disease: insights from SUPPORT.
      N = 1008
      39–70%
      • Levy J.
      • Morgan J.
      • Brown E.
      Oxford handbook of dialysis.
      • Martin C.R.
      • Thompson D.R.
      Prediction of quality of life in patients with end-stage renal disease.
      N = 72
      The number of patients is underestimated or unknown because prevalence figures given by textbooks were considered (for which the number of patients was not provided).
      Confusion6–93%
      • Cartwright A.
      Changes in life and care in the year before death 1969–1987.
      • Addington-Hall J.M.
      • McCarthy M.
      Dying from cancer: results of a national population-based investigation.
      • Durkin I.
      • Kearney M.
      • O'Siorain L.
      Psychiatric disorder in a palliative care unit.
      • Addington-Hall J.M.
      Heart disease and stroke: lessons from cancer care.
      • Chow E.
      • Fung K.
      • Panzarella T.
      • et al.
      A predictive model for survival in metastatic cancer patients attending an outpatient palliative radiotherapy clinic.
      • Meuser T.
      • Pietruck C.
      • Radbruch L.
      • et al.
      Symptoms during cancer pain treatment following WHO-guidelines: a longitudinal follow-up study of symptom prevalence, severity and etiology.
      • Vainio A.
      • Auvinen A.
      Prevalence of symptoms among patients with advanced cancer: an international collaborative study.
      • Dunlop G.M.
      A study of the relative frequency and importance of gastrointestinal symptoms and weakness in patients with far advanced cancer.
      • Reuben D.B.
      • Mor V.
      • Hiris J.
      Clinical symptoms and length of survival in patients with terminal cancer.
      • Curtis E.B.
      • Krech R.
      • Walsh T.D.
      Common symptoms in patients with advanced cancer.
      • Brescia F.J.
      • Adler D.
      • Gray G.
      • et al.
      Hospitalized advanced cancer patients: a profile.
      • Ventafridda V.
      • De Conno F.
      • Ripamonti C.
      • Gamba A.
      • Tamburini M.
      Quality-of-life assessment during a palliative care programme.
      • Minagawa H.
      • Uchitomi Y.
      • Yamawaki S.
      • Ishitani K.
      Psychiatric morbidity in terminally ill cancer patients: a prospective study.
      • Breitbart W.
      • Chochinov H.
      • Passik S.
      Psychiatric symptoms in palliative medicine.
      • Bruera E.
      • Miller L.
      • McCallion J.
      • et al.
      Cognitive failure in patients with terminal cancer: a prospective study.
      • Caraceni A.
      • Nanni O.
      • Maltoni M.
      • et al.
      Impact of delirium on the short term prognosis of advanced cancer patients.
      • Cobb J.L.
      • Glantz M.J.
      • Nicholas P.K.
      • et al.
      Delirium in patients with cancer at the end of life.
      • Gagnon P.
      • Allard P.
      • Masse B.
      • DeSerres M.
      Delirium in terminal cancer: a prospective study using daily screening, early diagnosis, and continuous monitoring.
      • Lawlor P.G.
      • Gagnon B.
      • Mancini I.L.
      • et al.
      Occurrence, causes, and outcome of delirium in patients with advanced cancer.
      N = 9154
      The number of patients is underestimated or unknown because prevalence figures given by textbooks were considered (for which the number of patients was not provided).
      30–65%
      • Breitbart W.
      • Chochinov H.
      • Passik S.
      Psychiatric symptoms in palliative medicine.
      • Jones K.
      • Breitbart W.
      Palliative care research in human immunodeficiency virus/acquired immunodeficiency syndrome: clinical trials of symptomatic therapies.
      N = ?
      The number of patients is underestimated or unknown because prevalence figures given by textbooks were considered (for which the number of patients was not provided).
      18–32%
      • Lynn J.
      • Teno J.M.
      • Phillips R.S.
      • et al.
      Perceptions by family members of the dying experience of older and seriously ill patients.
      • Addington-Hall J.M.
      Heart disease and stroke: lessons from cancer care.
      • Nordgren L.
      • Sorensen S.
      Symptoms experienced in the last six months of life in patients with end-stage heart failure.
      N = 343
      The number of patients is underestimated or unknown because prevalence figures given by textbooks were considered (for which the number of patients was not provided).
      18–33%
      • Edmonds P.
      • Karlsen S.
      • Khan S.
      • Addington-Hall J.M.
      A comparison of the palliative care needs of patients dying from chronic respiratory disease and lung cancer.
      • Lynn J.
      • Teno J.M.
      • Phillips R.S.
      • et al.
      Perceptions by family members of the dying experience of older and seriously ill patients.
      N = 309
      Fatigue32–90%
      • Anderson H.
      • Ward C.
      • Eardley A.
      • et al.
      The concerns of patients under palliative care and a heart failure clinic are not being met.
      • Portenoy R.K.
      Cancer-related fatigue: an immense problem.
      • Bruera E.
      Research in symptoms other than pain.
      • Potter J.
      • Hami F.
      • Bryan T.
      • Quigley C.
      Symptoms in 400 patients referred to palliative care services: prevalence and patterns.
      • Vainio A.
      • Auvinen A.
      Prevalence of symptoms among patients with advanced cancer: an international collaborative study.
      • Dunlop G.M.
      A study of the relative frequency and importance of gastrointestinal symptoms and weakness in patients with far advanced cancer.
      • Curtis E.B.
      • Krech R.
      • Walsh T.D.
      Common symptoms in patients with advanced cancer.
      • Ventafridda V.
      • De Conno F.
      • Ripamonti C.
      • Gamba A.
      • Tamburini M.
      Quality-of-life assessment during a palliative care programme.
      • Stone P.
      • Hardy J.
      • Broadley K.
      • et al.
      Fatigue in advanced cancer: a prospective controlled cross-sectional study.
      • Neuenschwander H.
      • Bruera E.
      Asthenia.
      N = 2888
      The number of patients is underestimated or unknown because prevalence figures given by textbooks were considered (for which the number of patients was not provided).
      54–85%
      • Vogl D.
      • Rosenfeld B.
      • Breitbart W.
      • et al.
      Symptom prevalence, characteristics, and distress in AIDS outpatients.
      • Breitbart W.
      • McDonald M.V.
      • Rosenfeld B.
      • Monkman N.D.
      • Passik S.
      Fatigue in ambulatory AIDS patients.
      N = 1435
      69–82%
      • Anderson H.
      • Ward C.
      • Eardley A.
      • et al.
      The concerns of patients under palliative care and a heart failure clinic are not being met.
      • Lynn J.
      • Teno J.M.
      • Phillips R.S.
      • et al.
      Perceptions by family members of the dying experience of older and seriously ill patients.
      • Nordgren L.
      • Sorensen S.
      Symptoms experienced in the last six months of life in patients with end-stage heart failure.
      N = 409
      68–80%
      • Lynn J.
      • Teno J.M.
      • Phillips R.S.
      • et al.
      Perceptions by family members of the dying experience of older and seriously ill patients.
      • Skilbeck J.
      • Mott L.
      • Page H.
      • et al.
      Palliative care in chronic obstructive airways disease: a needs assessment.
      N = 285
      73–87%
      • Weisbord S.D.
      • Carmody S.S.
      • Bruns F.J.
      • et al.
      Symptom burden, quality of life, advance care planning and the potential value of palliative care in severely ill haemodialysis patients.
      • Parfrey P.S.
      • Vavasour H.M.
      • Henry S.
      • Bullock M.
      • Gault M.H.
      Clinical features and severity of nonspecific symptoms in dialysis patients.
      N = 116
      Breathlessness10–70%
      • Cartwright A.
      Changes in life and care in the year before death 1969–1987.
      • Anderson H.
      • Ward C.
      • Eardley A.
      • et al.
      The concerns of patients under palliative care and a heart failure clinic are not being met.
      • Tranmer J.E.
      • Heyland D.
      • Dudgeon D.
      • et al.
      Measuring the symptom experience of seriously ill cancer and noncancer hospitalized patients near the end of life with the Memorial Symptom Assessment Scale.
      • Addington-Hall J.M.
      • McCarthy M.
      Dying from cancer: results of a national population-based investigation.
      • Addington-Hall J.M.
      • MacDonald M.
      • Anderson H.
      • Freeling P.
      Dying from cancer: the views of bereaved family and friends about the experiences of terminally ill patients.
      • Addington-Hall J.M.
      Heart disease and stroke: lessons from cancer care.
      • Bruera E.
      Research in symptoms other than pain.
      • Chow E.
      • Fung K.
      • Panzarella T.
      • et al.
      A predictive model for survival in metastatic cancer patients attending an outpatient palliative radiotherapy clinic.
      • Meuser T.
      • Pietruck C.
      • Radbruch L.
      • et al.
      Symptoms during cancer pain treatment following WHO-guidelines: a longitudinal follow-up study of symptom prevalence, severity and etiology.
      • Morita T.
      • Tsunoda J.
      • Inoue S.
      • Chihara S.
      Contributing factors to physical symptoms in terminally-ill cancer patients.
      • Potter J.
      • Hami F.
      • Bryan T.
      • Quigley C.
      Symptoms in 400 patients referred to palliative care services: prevalence and patterns.
      • Vainio A.
      • Auvinen A.
      Prevalence of symptoms among patients with advanced cancer: an international collaborative study.
      • Dunlop G.M.
      A study of the relative frequency and importance of gastrointestinal symptoms and weakness in patients with far advanced cancer.
      • Reuben D.B.
      • Mor V.
      • Hiris J.
      Clinical symptoms and length of survival in patients with terminal cancer.
      • Curtis E.B.
      • Krech R.
      • Walsh T.D.
      Common symptoms in patients with advanced cancer.
      • Brescia F.J.
      • Adler D.
      • Gray G.
      • et al.
      Hospitalized advanced cancer patients: a profile.
      • Ventafridda V.
      • De Conno F.
      • Ripamonti C.
      • Gamba A.
      • Tamburini M.
      Quality-of-life assessment during a palliative care programme.
      • Regnard C.
      • Hockley J.
      A guide to symptom relief in palliative care.
      • Dudgeon D.
      Multidimensional assessment of dyspnea.
      • Dudgeon D.J.
      • Kristjanson L.
      • Sloan J.A.
      • Lertzman M.
      • Clement K.
      Dyspnea in cancer patients: prevalence and associated factors.
      • Ross D.D.
      • Alexander C.S.
      Management of common symptoms in terminally ill patients: part II. Constipation, delirium and dyspnea.
      N = 10,029
      The number of patients is underestimated or unknown because prevalence figures given by textbooks were considered (for which the number of patients was not provided).
      11–62%
      • Vogl D.
      • Rosenfeld B.
      • Breitbart W.
      • et al.
      Symptom prevalence, characteristics, and distress in AIDS outpatients.
      • Ross D.D.
      • Alexander C.S.
      Management of common symptoms in terminally ill patients: part II. Constipation, delirium and dyspnea.
      N = 504
      60–88%
      • Anderson H.
      • Ward C.
      • Eardley A.
      • et al.
      The concerns of patients under palliative care and a heart failure clinic are not being met.
      • Lynn J.
      • Teno J.M.
      • Phillips R.S.
      • et al.
      Perceptions by family members of the dying experience of older and seriously ill patients.
      • Addington-Hall J.M.
      Heart disease and stroke: lessons from cancer care.
      • Levenson J.W.
      • McCarthy E.P.
      • Lynn J.
      • Davis R.B.
      • Phillips R.S.
      The last six months of life for patients with congestive heart failure.
      • Nordgren L.
      • Sorensen S.
      Symptoms experienced in the last six months of life in patients with end-stage heart failure.
      • Regnard C.
      • Hockley J.
      A guide to symptom relief in palliative care.
      N = 948
      The number of patients is underestimated or unknown because prevalence figures given by textbooks were considered (for which the number of patients was not provided).
      90–95%
      • Edmonds P.
      • Karlsen S.
      • Khan S.
      • Addington-Hall J.M.
      A comparison of the palliative care needs of patients dying from chronic respiratory disease and lung cancer.
      • Lynn J.
      • Teno J.M.
      • Phillips R.S.
      • et al.
      Perceptions by family members of the dying experience of older and seriously ill patients.
      • Skilbeck J.
      • Mott L.
      • Page H.
      • et al.
      Palliative care in chronic obstructive airways disease: a needs assessment.
      • Regnard C.
      • Hockley J.
      A guide to symptom relief in palliative care.
      N = 372
      The number of patients is underestimated or unknown because prevalence figures given by textbooks were considered (for which the number of patients was not provided).
      11–62%
      • Kimmel P.
      • Emont S.
      • Newmann J.
      • Danko H.
      • Moss A.
      ESRD patient quality of life: symptoms, spiritual beliefs, psychosocial factors, and ethnicity.
      • Loos C.
      • Briancon S.
      • Frimat L.
      • Hanesse B.
      • Kessler M.
      Effect of end-stage renal disease on the quality of life of older patients.
      N = 334
      Insomnia9–69%
      • Cartwright A.
      Changes in life and care in the year before death 1969–1987.
      • Anderson H.
      • Ward C.
      • Eardley A.
      • et al.
      The concerns of patients under palliative care and a heart failure clinic are not being met.
      • Tranmer J.E.
      • Heyland D.
      • Dudgeon D.
      • et al.
      Measuring the symptom experience of seriously ill cancer and noncancer hospitalized patients near the end of life with the Memorial Symptom Assessment Scale.
      • Addington-Hall J.M.
      • McCarthy M.
      Dying from cancer: results of a national population-based investigation.
      • Addington-Hall J.M.
      • MacDonald M.
      • Anderson H.
      • Freeling P.
      Dying from cancer: the views of bereaved family and friends about the experiences of terminally ill patients.
      • Meuser T.
      • Pietruck C.
      • Radbruch L.
      • et al.
      Symptoms during cancer pain treatment following WHO-guidelines: a longitudinal follow-up study of symptom prevalence, severity and etiology.
      • Potter J.
      • Hami F.
      • Bryan T.
      • Quigley C.
      Symptoms in 400 patients referred to palliative care services: prevalence and patterns.
      • Vainio A.
      • Auvinen A.
      Prevalence of symptoms among patients with advanced cancer: an international collaborative study.
      • Dunlop G.M.
      A study of the relative frequency and importance of gastrointestinal symptoms and weakness in patients with far advanced cancer.
      • Curtis E.B.
      • Krech R.
      • Walsh T.D.
      Common symptoms in patients with advanced cancer.
      • Ventafridda V.
      • De Conno F.
      • Ripamonti C.
      • Gamba A.
      • Tamburini M.
      Quality-of-life assessment during a palliative care programme.
      N = 5606
      74%
      • Vogl D.
      • Rosenfeld B.
      • Breitbart W.
      • et al.
      Symptom prevalence, characteristics, and distress in AIDS outpatients.
      N = 504
      36–48%
      • Anderson H.
      • Ward C.
      • Eardley A.
      • et al.
      The concerns of patients under palliative care and a heart failure clinic are not being met.
      • Nordgren L.
      • Sorensen S.
      Symptoms experienced in the last six months of life in patients with end-stage heart failure.
      N = 146
      55–65%
      • Edmonds P.
      • Karlsen S.
      • Khan S.
      • Addington-Hall J.M.
      A comparison of the palliative care needs of patients dying from chronic respiratory disease and lung cancer.
      • Skilbeck J.
      • Mott L.
      • Page H.
      • et al.
      Palliative care in chronic obstructive airways disease: a needs assessment.
      N = 150
      31–71%
      • Kimmel P.
      • Emont S.
      • Newmann J.
      • Danko H.
      • Moss A.
      ESRD patient quality of life: symptoms, spiritual beliefs, psychosocial factors, and ethnicity.
      • Parfrey P.S.
      • Vavasour H.M.
      • Henry S.
      • Bullock M.
      • Gault M.H.
      Clinical features and severity of nonspecific symptoms in dialysis patients.
      • Iliescu E.A.
      • Coo H.
      • McMurray M.H.
      • et al.
      Quality of sleep and health-related quality of life in haemodialysis patients.
      N = 351
      Nausea6–68%
      • Anderson H.
      • Ward C.
      • Eardley A.
      • et al.
      The concerns of patients under palliative care and a heart failure clinic are not being met.
      • Tranmer J.E.
      • Heyland D.
      • Dudgeon D.
      • et al.
      Measuring the symptom experience of seriously ill cancer and noncancer hospitalized patients near the end of life with the Memorial Symptom Assessment Scale.
      • Addington-Hall J.M.
      • McCarthy M.
      Dying from cancer: results of a national population-based investigation.
      • Addington-Hall J.M.
      • MacDonald M.
      • Anderson H.
      • Freeling P.
      Dying from cancer: the views of bereaved family and friends about the experiences of terminally ill patients.
      • Addington-Hall J.M.
      Heart disease and stroke: lessons from cancer care.
      • Bruera E.
      Research in symptoms other than pain.
      • Chow E.
      • Fung K.
      • Panzarella T.
      • et al.
      A predictive model for survival in metastatic cancer patients attending an outpatient palliative radiotherapy clinic.
      • Meuser T.
      • Pietruck C.
      • Radbruch L.
      • et al.
      Symptoms during cancer pain treatment following WHO-guidelines: a longitudinal follow-up study of symptom prevalence, severity and etiology.
      • Morita T.
      • Tsunoda J.
      • Inoue S.
      • Chihara S.
      Contributing factors to physical symptoms in terminally-ill cancer patients.
      • Potter J.
      • Hami F.
      • Bryan T.
      • Quigley C.
      Symptoms in 400 patients referred to palliative care services: prevalence and patterns.
      • Vainio A.
      • Auvinen A.
      Prevalence of symptoms among patients with advanced cancer: an international collaborative study.
      • Dunlop G.M.
      A study of the relative frequency and importance of gastrointestinal symptoms and weakness in patients with far advanced cancer.
      • Reuben D.B.
      • Mor V.
      • Hiris J.
      Clinical symptoms and length of survival in patients with terminal cancer.
      • Curtis E.B.
      • Krech R.
      • Walsh T.D.
      Common symptoms in patients with advanced cancer.
      • Brescia F.J.
      • Adler D.
      • Gray G.
      • et al.
      Hospitalized advanced cancer patients: a profile.
      • Ventafridda V.
      • De Conno F.
      • Ripamonti C.
      • Gamba A.
      • Tamburini M.
      Quality-of-life assessment during a palliative care programme.
      • Regnard C.
      • Hockley J.
      A guide to symptom relief in palliative care.
      • Bruera E.
      • Seifert L.
      • Watanabe S.
      • et al.
      Chronic nausea in advanced cancer patients: a retrospective assessment of a metoclopramide-based antiemetic regimen.
      • Potter J.
      • Higginson I.
      Frequency and severity of gastrointestinal symptoms in advanced cancer.
      • Sarhill N.
      • Mahmoud F.
      • Walsh D.
      • et al.
      Evaluation of nutritional status in advanced metastatic cancer.
      N = 9140
      The number of patients is underestimated or unknown because prevalence figures given by textbooks were considered (for which the number of patients was not provided).
      43–49%
      • Vogl D.
      • Rosenfeld B.
      • Breitbart W.
      • et al.
      Symptom prevalence, characteristics, and distress in AIDS outpatients.
      • Radin Kimball L.
      • McCormick W.C.
      The pharmacologic management of pain and discomport in persons with AIDS near the end of life: use of opioid analgesia in the hospice setting.
      N = 689
      17–48%
      • Anderson H.
      • Ward C.
      • Eardley A.
      • et al.
      The concerns of patients under palliative care and a heart failure clinic are not being met.
      • Addington-Hall J.M.
      Heart disease and stroke: lessons from cancer care.
      • Nordgren L.
      • Sorensen S.
      Symptoms experienced in the last six months of life in patients with end-stage heart failure.
      N = 146
      The number of patients is underestimated or unknown because prevalence figures given by textbooks were considered (for which the number of patients was not provided).
      30–43%
      • Parfrey P.S.
      • Vavasour H.M.
      • Henry S.
      • Bullock M.
      • Gault M.H.
      Clinical features and severity of nonspecific symptoms in dialysis patients.
      • McCann K.
      • Boore J.R.P.
      Fatigue in persons with renal failure who require maintenance haemodialysis.
      • Merkus M.
      • Jager K.
      • Dekker F.
      • et al.
      Physical symptoms and quality of life in patients on chronic dialysis: results of The Netherlands cooperative study on adequacy of dialysis (NECOSAD).
      N = 362
      Constipation23–65%
      • Cartwright A.
      Changes in life and care in the year before death 1969–1987.
      • Tranmer J.E.
      • Heyland D.
      • Dudgeon D.
      • et al.
      Measuring the symptom experience of seriously ill cancer and noncancer hospitalized patients near the end of life with the Memorial Symptom Assessment Scale.
      • Addington-Hall J.M.
      • McCarthy M.
      Dying from cancer: results of a national population-based investigation.
      • Addington-Hall J.M.
      • MacDonald M.
      • Anderson H.
      • Freeling P.
      Dying from cancer: the views of bereaved family and friends about the experiences of terminally ill patients.
      • Addington-Hall J.M.
      Heart disease and stroke: lessons from cancer care.
      • Bruera E.
      Research in symptoms other than pain.
      • Meuser T.
      • Pietruck C.
      • Radbruch L.
      • et al.
      Symptoms during cancer pain treatment following WHO-guidelines: a longitudinal follow-up study of symptom prevalence, severity and etiology.
      • Morita T.
      • Tsunoda J.
      • Inoue S.
      • Chihara S.
      Contributing factors to physical symptoms in terminally-ill cancer patients.
      • Potter J.
      • Hami F.
      • Bryan T.
      • Quigley C.
      Symptoms in 400 patients referred to palliative care services: prevalence and patterns.
      • Vainio A.
      • Auvinen A.
      Prevalence of symptoms among patients with advanced cancer: an international collaborative study.
      • Dunlop G.M.
      A study of the relative frequency and importance of gastrointestinal symptoms and weakness in patients with far advanced cancer.
      • Reuben D.B.
      • Mor V.
      • Hiris J.
      Clinical symptoms and length of survival in patients with terminal cancer.
      • Curtis E.B.
      • Krech R.
      • Walsh T.D.
      Common symptoms in patients with advanced cancer.
      • Ventafridda V.
      • De Conno F.
      • Ripamonti C.
      • Gamba A.
      • Tamburini M.
      Quality-of-life assessment during a palliative care programme.
      • Vogl D.
      • Rosenfeld B.
      • Breitbart W.
      • et al.
      Symptom prevalence, characteristics, and distress in AIDS outpatients.
      • Sarhill N.
      • Mahmoud F.
      • Walsh D.
      • et al.
      Evaluation of nutritional status in advanced metastatic cancer.
      N = 7602
      The number of patients is underestimated or unknown because prevalence figures given by textbooks were considered (for which the number of patients was not provided).
      34–35%
      • Vogl D.
      • Rosenfeld B.
      • Breitbart W.
      • et al.
      Symptom prevalence, characteristics, and distress in AIDS outpatients.
      • Radin Kimball L.
      • McCormick W.C.
      The pharmacologic management of pain and discomport in persons with AIDS near the end of life: use of opioid analgesia in the hospice setting.
      N = 689
      38–42%
      • Addington-Hall J.M.
      Heart disease and stroke: lessons from cancer care.
      • Nordgren L.
      • Sorensen S.
      Symptoms experienced in the last six months of life in patients with end-stage heart failure.
      N = 80
      The number of patients is underestimated or unknown because prevalence figures given by textbooks were considered (for which the number of patients was not provided).
      27–44%
      • Edmonds P.
      • Karlsen S.
      • Khan S.
      • Addington-Hall J.M.
      A comparison of the palliative care needs of patients dying from chronic respiratory disease and lung cancer.
      • Skilbeck J.
      • Mott L.
      • Page H.
      • et al.
      Palliative care in chronic obstructive airways disease: a needs assessment.
      N = 150
      29–70%
      • Yasuda G.
      • Shibata K.
      • Takizawa T.
      • et al.
      Prevalence of constipation in continuous ambulatory peritoneal dialysis patients and comparison with hemodialysis patients.
      N = 483
      Diarrhea3–29%
      • Tranmer J.E.
      • Heyland D.
      • Dudgeon D.
      • et al.
      Measuring the symptom experience of seriously ill cancer and noncancer hospitalized patients near the end of life with the Memorial Symptom Assessment Scale.
      • Addington-Hall J.M.
      • MacDonald M.
      • Anderson H.
      • Freeling P.
      Dying from cancer: the views of bereaved family and friends about the experiences of terminally ill patients.
      • Meuser T.
      • Pietruck C.
      • Radbruch L.
      • et al.
      Symptoms during cancer pain treatment following WHO-guidelines: a longitudinal follow-up study of symptom prevalence, severity and etiology.
      • Morita T.
      • Tsunoda J.
      • Inoue S.
      • Chihara S.
      Contributing factors to physical symptoms in terminally-ill cancer patients.
      • Potter J.
      • Hami F.
      • Bryan T.
      • Quigley C.
      Symptoms in 400 patients referred to palliative care services: prevalence and patterns.
      • Dunlop G.M.
      A study of the relative frequency and importance of gastrointestinal symptoms and weakness in patients with far advanced cancer.
      • Reuben D.B.
      • Mor V.
      • Hiris J.
      Clinical symptoms and length of survival in patients with terminal cancer.
      • Ventafridda V.
      • De Conno F.
      • Ripamonti C.
      • Gamba A.
      • Tamburini M.
      Quality-of-life assessment during a palliative care programme.
      • Regnard C.
      • Hockley J.
      A guide to symptom relief in palliative care.
      • Potter J.
      • Higginson I.
      Frequency and severity of gastrointestinal symptoms in advanced cancer.
      • Sarhill N.
      • Mahmoud F.
      • Walsh D.
      • et al.
      Evaluation of nutritional status in advanced metastatic cancer.
      • Mercadante S.
      Diarrhea in terminally ill patients: pathophysiology and treatment.
      N = 3392
      The number of patients is underestimated or unknown because prevalence figures given by textbooks were considered (for which the number of patients was not provided).
      30–90%
      • Vogl D.
      • Rosenfeld B.
      • Breitbart W.
      • et al.
      Symptom prevalence, characteristics, and distress in AIDS outpatients.
      • Regnard C.
      • Hockley J.
      A guide to symptom relief in palliative care.
      • Mercadante S.
      Diarrhea in terminally ill patients: pathophysiology and treatment.
      • Meyer M.
      Palliative care and AIDS: 2. Gastrointestinal symptoms.
      N = 504
      The number of patients is underestimated or unknown because prevalence figures given by textbooks were considered (for which the number of patients was not provided).
      12%
      • Nordgren L.
      • Sorensen S.
      Symptoms experienced in the last six months of life in patients with end-stage heart failure.
      N = 80
      21%
      • Weisbord S.D.
      • Carmody S.S.
      • Bruns F.J.
      • et al.
      Symptom burden, quality of life, advance care planning and the potential value of palliative care in severely ill haemodialysis patients.
      N = 19
      Anorexia30–92%
      • Cartwright A.
      Changes in life and care in the year before death 1969–1987.
      • Anderson H.
      • Ward C.
      • Eardley A.
      • et al.
      The concerns of patients under palliative care and a heart failure clinic are not being met.
      • Tranmer J.E.
      • Heyland D.
      • Dudgeon D.
      • et al.
      Measuring the symptom experience of seriously ill cancer and noncancer hospitalized patients near the end of life with the Memorial Symptom Assessment Scale.
      • Addington-Hall J.M.
      • McCarthy M.
      Dying from cancer: results of a national population-based investigation.
      • Addington-Hall J.M.
      • MacDonald M.
      • Anderson H.
      • Freeling P.
      Dying from cancer: the views of bereaved family and friends about the experiences of terminally ill patients.
      • Bruera E.
      Research in symptoms other than pain.
      • Meuser T.
      • Pietruck C.
      • Radbruch L.
      • et al.
      Symptoms during cancer pain treatment following WHO-guidelines: a longitudinal follow-up study of symptom prevalence, severity and etiology.
      • Morita T.
      • Tsunoda J.
      • Inoue S.
      • Chihara S.
      Contributing factors to physical symptoms in terminally-ill cancer patients.
      • Potter J.
      • Hami F.
      • Bryan T.
      • Quigley C.
      Symptoms in 400 patients referred to palliative care services: prevalence and patterns.
      • Vainio A.
      • Auvinen A.
      Prevalence of symptoms among patients with advanced cancer: an international collaborative study.
      • Dunlop G.M.
      A study of the relative frequency and importance of gastrointestinal symptoms and weakness in patients with far advanced cancer.
      • Reuben D.B.
      • Mor V.
      • Hiris J.
      Clinical symptoms and length of survival in patients with terminal cancer.
      • Curtis E.B.
      • Krech R.
      • Walsh T.D.
      Common symptoms in patients with advanced cancer.
      • Brescia F.J.
      • Adler D.
      • Gray G.
      • et al.
      Hospitalized advanced cancer patients: a profile.
      • Potter J.
      • Higginson I.
      Frequency and severity of gastrointestinal symptoms in advanced cancer.
      • Sarhill N.
      • Mahmoud F.
      • Walsh D.
      • et al.
      Evaluation of nutritional status in advanced metastatic cancer.
      • Hawkins C.
      Anorexia and anxiety in advanced malignancy: the relative problem.
      N = 9113
      51%
      • Vogl D.
      • Rosenfeld B.
      • Breitbart W.
      • et al.
      Symptom prevalence, characteristics, and distress in AIDS outpatients.
      N = 504
      21–41%
      • Anderson H.
      • Ward C.
      • Eardley A.
      • et al.
      The concerns of patients under palliative care and a heart failure clinic are not being met.
      • Nordgren L.
      • Sorensen S.
      Symptoms experienced in the last six months of life in patients with end-stage heart failure.
      N = 146
      35–67%
      • Edmonds P.
      • Karlsen S.
      • Khan S.
      • Addington-Hall J.M.
      A comparison of the palliative care needs of patients dying from chronic respiratory disease and lung cancer.
      • Skilbeck J.
      • Mott L.
      • Page H.
      • et al.
      Palliative care in chronic obstructive airways disease: a needs assessment.
      N = 150
      25–64%
      • Loos C.
      • Briancon S.
      • Frimat L.
      • Hanesse B.
      • Kessler M.
      Effect of end-stage renal disease on the quality of life of older patients.
      • Merkus M.
      • Jager K.
      • Dekker F.
      • et al.
      Physical symptoms and quality of life in patients on chronic dialysis: results of The Netherlands cooperative study on adequacy of dialysis (NECOSAD).
      N = 395
      1. Minimum-maximum range of prevalence (%) is shown.
      2. HD = heart disease; COPD = chronic obstructive pulmonary disease; RD = renal disease.
      3. N refer to the total number of patients involved in the studies found for each symptom in a given disease (e.g., there are 372 patients involved in the three studies on pain prevalence in COPD).
      4. Superscripted numbers relate to the reference source and indicate the number of studies for each symptom in a given disease (e.g., there are three studies on pain prevalence in COPD patients). In two occasions, a single study reported a prevalence range rather than a single point prevalence—anxiety for COPD and constipation for renal failure. “—” was displayed when no data were found for a specific symptom and condition (e.g., confusion for renal failure).
      a The number of patients is underestimated or unknown because prevalence figures given by textbooks were considered (for which the number of patients was not provided).

      Results

      In total, 1900 articles were found from the electronic searches. Of these and follow-up of the reference lists, 64 eligible articles were identified (33 cancer, 9 AIDS, 2 HD, 3 COPD, 13 RD, and 4 considered more than one disease) and reference lists were searched. In addition, information was extracted from 18 book chapters.
      Table 1 shows the results extracted from our palliative care grid, in terms of minimum and maximum prevalences for each symptom within the five selected clinical conditions. Most studies, particularly large-scale studies, describe symptoms for cancer patients. For this reason, the prevalences of symptoms in cancer are related to a much higher number of patients (ranging from 2,888 to 10,379 patients, for each symptom), when compared with all the other four diseases (ranging from 19 to 1,435 patients). No data were obtained for the prevalence of nausea and diarrhea among COPD patients, nor for confusion among RD patients. Hence, “—” is displayed for such cases. For some symptoms and conditions, we found only one eligible data source, and thus can only report a single prevalence. That was the case for insomnia and anorexia among AIDS patients; anxiety and diarrhea among HD patients; and diarrhea among renal patients.
      There were wide variations in symptom prevalence. Fig. 1, Fig. 2 illustrate this in more detail and plot the symptom prevalence results for all included studies for depression and breathlessness.
      Figure thumbnail gr1
      Fig. 1Depression: Prevalences found in 33 studies for the five conditions. For most studies, a simple point prevalence was given. When studies reported a range (five studies), both maximum and minimum points in the range are shown.
      Figure thumbnail gr2
      Fig. 2Breathlessness: Prevalences found in 35 studies for the five conditions. For most studies, a simple point prevalence was given. When studies reported a range (three studies), both maximum and minimum points in the range are shown.
      Appraisal of the study methods identified variables that may account for the wide range of prevalence found. These are illustrated in Table 2 for the symptom of depression. Many of these factors were also noted for other symptoms, where ranges were narrower but still present. Nevertheless, our findings highlighted that depression is common not only among cancer patients, but also nearly equally among AIDS, HD, COPD, and renal patients (77% against 82%, 36%, 71%, and 60%, respectively, if maximum prevalences are considered). In contrast, anxiety seemed to be less prevalent among AIDS patients (8%–34%) in comparison to the other four diseases (13%–79%).
      Table 2Factors Contributing to the Variation in Symptom Prevalence: Depression as an Example
      (A) Factors relating to the definition of the symptom
      • Hotopf M.
      • Chidgey J.
      • Addington-Hall J.M.
      • Ly K.L.
      Depression in advanced disease: a systematic review. Part 1: prevalence and case finding.
      • Breitbart W.
      • Bruera E.
      • Chochinov H.
      • Lynch M.
      Neuropsychiatric syndromes and psychological symptoms in patients with advanced cancer.
       • Some authors defined depression as a symptom, others, as a subjective complaint (e.g., feeling depressed, in a low mood), others, as a psychiatric disorder as defined by DSM
      • American Psychiatric Association
      Diagnostic and statistical manual of mental disorders.
      or ICD
      • World Health Organization
      The tenth revision of the International Classification of Diseases and Related Health Problems (ICD-10).
      (e.g., major depression).
       • Some studies used the substitution criteria of Endicott,
      • Endicott J.
      Measurement of depression in patients with cancer.
      e.g., replacing weight loss with depressive appearance in terminally ill patients, others did not.
       • Some authors raised the threshold during the assessment to allow for signs of depression, sadness, or low mood expected to be present in terminally ill patients, others did not.
      (B) Factors relating to the methods to detect “cases” of depression
      • Hotopf M.
      • Chidgey J.
      • Addington-Hall J.M.
      • Ly K.L.
      Depression in advanced disease: a systematic review. Part 1: prevalence and case finding.
      • Breitbart W.
      • Bruera E.
      • Chochinov H.
      • Lynch M.
      Neuropsychiatric syndromes and psychological symptoms in patients with advanced cancer.
       • Some studies refer to clinically recognized depression.
       • Some studies used single-item questionnaires to screen.
       • Some studies used screening questionnaires (e.g., HADS,
      • Zigmond A.
      • Snaith R.
      The Hospital Anxiety and Depression Scale.
      BDI
      • Beck A.
      • Ward C.
      • Mendelson M.
      An inventory for measuring depression.
      ).
       • Some studies used diagnostic interviews (e.g., SADS,
      • Endicott J.
      • Spitzer A.
      A diagnostic interview: the schedule for affective disorders and schizophrenia.
      SCID
      • Spitzer A.
      • Williams J.
      • Gibbon M.
      • First M.
      The Structured Clinical Interview for DSM-III-R (SCID): 1. History, rationale, and description.
      ).
      (C) Factors relating to the design
       • Some authors sought point prevalence, others period prevalence (with a range of time periods), and others mixed both.
      • Potter J.
      • Higginson I.
      Frequency and severity of gastrointestinal symptoms in advanced cancer.
       • Studies have different length of follow-up.
      (D) Factors relating to the sample
       • Studies had varied sample sizes.
       • Studies included terminally ill patients at different stages of disease (e.g., according to predefined life expectancy, excluding patients who died after a predefined terminal phase period).
      (E) Factors relating to the setting of the study and to the accrual model
       • Studies recruited patients from hospital wards, hospital acute wards, hospices, community-based units, outpatients clinics, etc.
       • Some studies attempted to avoid biased samples (e.g., patients from the mental health system, when assessing depression), others did not.
      (F) Factors relating to the method of data collection
       • Some studies were based on recorded data (e.g., hospital records).
       • Some studies were based on recorded data about drugs prescribed (e.g., antidepressants).
       • Some studies interviewed the patient, others a carer, others a bereaved carer, and others interviewed staff members.
      (G) Miscellaneous
       • Some studies only included symptoms if they had been severe and/or present according to a predefined frequency.
       • Some approaches accounted for the possibility of preexisting symptoms, others did not.
       • Some studies referred to new symptoms, others to symptoms as a result of treatment, others combined both.
       • Some studies did not recruit patients who were continuing curative treatment, others did.
      Note: Superscripted numbers relate to the reference source.
      Despite these variations within diseases, some patterns emerged. The results consistently show high prevalence for almost all considered symptoms. Most symptoms were found in one-third or more patients. Multiple symptoms occurred for all five diseases. However, two symptoms, pain and fatigue, were common in all five diseases, occurring in 34%–96% and 32%–90%, respectively. Breathlessness was common in most conditions, with a wide range of experience. However, it was most consistently found among patients with COPD and HD; the minimum values of prevalence was 90% and 60%, respectively, and the maximum values were prevalence was 95% and 88%, respectively. Insomnia was most common among AIDS patients (although this is based on only one study). Nausea was present in at least 43% of AIDS patients (compared with at least 6% of cancer patients, 17% of heart disease patients, and 30% of renal patients). Constipation seemed to be more frequent among cancer and renal patients (65% and 70%, respectively; maximum prevalence). Diarrhea was highly prevalent among AIDS patients, with a prevalence as high as 90%, against 29% in cancer, 12% in HD, and 21% in renal patients (though just single values were found for the latter two conditions). Anorexia was most common among cancer patients—present in up to 92% of the patients (against 41%, 67%, 64%, and 51% among HD, COPD, RD, and AIDS patients, respectively, though just a single value was found for the last).

      Discussion

      A first concern raised by this study is the wide range of symptom prevalences for individual diseases. This can be at least partially explained by the fact that studies differed regarding methodological procedures. Due to such heterogeneity, we felt it was not possible to aggregate the data using meta-analytic techniques. Therefore, we have displayed the results in terms of minimum and maximum prevalences. We identified eight clusters of different factors that contributed to this heterogeneity. First, there were factors relating to the definition of the symptom with different criteria and interpretation of the symptom across studies. Second, there were variations in the methods to detect cases of the symptom, with different questionnaires and screening methods used. Third, there were variations in study design, with a mix of point prevalence, period prevalence, and length of follow-up. Fourth, there were variations in the sample. In addition to variations in sample size, different authors defined the terminal or advanced stage of illnesses differently. Defining when a slowly progressive disease reaches advanced stages is difficult. Heart failure, renal failure, and especially AIDS have a fluctuating trajectory. This difficulty in prognostication may be one of the reasons why patients with noncancer conditions are not referred to palliative care services in some settings. Lack of a clear definition is also likely to have contributed to the variation in prevalence among both cancer and noncancer patients. Prognostic uncertainty suggests that palliative care should be made available on the basis of need, e.g., symptoms, rather than prognosis. Fifth, variation resulted from differences in study setting (hospital wards, hospice, community) and the method of recruitment and accrual. There were particular difficulties in some studies with biased samples—for example, patients with pain in pain clinics or patients from the mental health system when assessing mental depression. This fails to give a true population-based perspective. Six, there were variations in the methods of data collection. Some studies were based on recorded data, for example from routine hospital records; some directly interviewed patients' families. Other studies used proxies, either professionals or carers, and in some instances, bereaved carers. Probably least reliably, some studies relied on presence of symptoms by assessing whether drugs were prescribed or not. In particular, these studies may under-report the prevalence of symptoms. Seventh, some studies only included symptoms if they were severe or present according to predefined frequencies, whereas other studies included symptoms if they were simply present. Eighth, there was a great variety in the approaches to including patients with particular groups of symptoms. Some studies accounted for possible preexisting symptoms, some studies referred only to new symptoms, some studies looked at symptoms as a result of treatment but excluded preexisting symptoms, and some studies did not include patients who were continuing curative treatment.
      In this study, we sought to compare symptom prevalence among people with five far advanced, life-limiting diseases. We did find eight comparative studies encompassing people in such conditions. However, three compared cancer with a mixed noncancer group (included several diseases),
      • Tranmer J.E.
      • Heyland D.
      • Dudgeon D.
      • et al.
      Measuring the symptom experience of seriously ill cancer and noncancer hospitalized patients near the end of life with the Memorial Symptom Assessment Scale.
      • Addington-Hall J.M.
      • Fakhoury W.
      • McCarthy M.
      Specialist palliative care in non-malignant disease.
      • Addington-Hall J.M.
      • McCarthy M.
      Dying from cancer: results of a national population-based investigation.
      two had few noncancer patients in the comparison,
      • Durkin I.
      • Kearney M.
      • O'Siorain L.
      Psychiatric disorder in a palliative care unit.
      • Hugel H.
      • Ellershaw J.E.
      • Cook L.
      • Skinner J.
      • Irvine C.
      The prevalence, key causes and management of insomnia in palliative care patients.
      and all compared no more than two conditions.
      • Edmonds P.
      • Karlsen S.
      • Khan S.
      • Addington-Hall J.M.
      A comparison of the palliative care needs of patients dying from chronic respiratory disease and lung cancer.
      • Tranmer J.E.
      • Heyland D.
      • Dudgeon D.
      • et al.
      Measuring the symptom experience of seriously ill cancer and noncancer hospitalized patients near the end of life with the Memorial Symptom Assessment Scale.
      • Addington-Hall J.M.
      • Fakhoury W.
      • McCarthy M.
      Specialist palliative care in non-malignant disease.
      • Addington-Hall J.M.
      • McCarthy M.
      Dying from cancer: results of a national population-based investigation.
      • Durkin I.
      • Kearney M.
      • O'Siorain L.
      Psychiatric disorder in a palliative care unit.
      • Hugel H.
      • Ellershaw J.E.
      • Cook L.
      • Skinner J.
      • Irvine C.
      The prevalence, key causes and management of insomnia in palliative care patients.
      • Lynn J.
      • Teno J.M.
      • Phillips R.S.
      • et al.
      Perceptions by family members of the dying experience of older and seriously ill patients.
      • Murray S.A.
      • Boyd K.
      • Kendall M.
      • et al.
      Dying of lung cancer or cardiac failure: prospective qualitative interview study of patients and their carers in the community.
      Thus, our comparisons had to be made between articles, limiting the comparability.
      Nevertheless, our findings shed some light on what may constitute the core of the common pathway toward the end of life in terms of symptomatology. Three symptoms are particularly universal and frequent—pain, fatigue, and breathlessness—with prevalences often well above 50% in all five conditions. Insomnia and anorexia are also recurrent symptoms in all conditions. Despite their high prevalence, these symptoms face underassessment and undertreatment, each of which occurs for different reasons. This poses different challenges for the management of each symptom.
      Methods of pain relief have improved considerably in the past two decades, especially for cancer-related pain.
      • Portenoy R.K.
      Cancer-related fatigue: an immense problem.
      Yet, there is evidence in some settings that pain control falls far short of the recommendations of the World Health Organization (WHO).
      • Bernabei R.
      • Gambassi G.
      • Lapane K.
      • et al.
      Management of pain in elderly patients with cancer.
      Wide dissemination and adoption of effective methods of pain control are required if pain relief is to be accessible to more people. Fatigue has not had the same scientific evolution as pain and effective treatments have not yet been identified. Underassessment is common, as this symptom is rarely discussed by physicians and patients,
      • Vogelzang N.J.
      • Breitbart W.
      • Cella D.
      • et al.
      Patient, caregiver, and oncologist perceptions of cancer-related fatigue: results of a tripart assessment survey. The Fatigue Coalition.
      although a consensus is emerging among patients, caregivers, and oncologists about the importance of fatigue in many progressive diseases.
      • Curt G.A.
      Fatigue in cancer.
      Breathlessness is also a difficult symptom to control with limited treatments.
      • Andrewes T.
      The management of breathlessness in palliative care.
      Early intervention and teaching practical skills to patients and carers might be priorities given that this symptom tends to occur in acute episodes of crisis.
      • Andrewes T.
      The management of breathlessness in palliative care.
      • Higginson I.
      • McCarthy M.
      Measuring symptoms in terminal cancer: are pain and dyspnoea controlled?.
      Although terminal patients with different conditions would benefit from better management of breathlessness, COPD patients are a particular group in need. Since insomnia is often caused by inadequate symptom control, attempts to optimize symptom control should be a priority in its treatment.
      • Hugel H.
      • Ellershaw J.E.
      • Cook L.
      • Skinner J.
      • Irvine C.
      The prevalence, key causes and management of insomnia in palliative care patients.
      Because anorexia is not always an obvious condition, comprehensive and individualized routine screening is necessary.
      • Strasser F.
      • Bruera E.D.
      Update on anorexia and cachexia.
      There were some situations in which there were few data available, and research is needed to determine whether symptoms such as diarrhea are found among patients with COPD, advanced heart failure, or renal failure; nausea in COPD patients; and confusion in patients with advanced renal failure.
      Our analysis showed that for patients with each of four diseases—AIDS, HD, COPD, and RD—11 symptoms are often as prevalent in advanced disease as among advanced cancer patients. Thus, there seems to be a common pathway that people with far advanced progressive diseases have to face. This suggests that palliative care is relevant for people with all five conditions, although aspects of assessment and management may need modification. Over the past decade, mutual cooperation among the WHO, governments, charitable initiatives, and palliative care policy makers has led to the recognition of need and subsequent inclusion of AIDS patients in palliative care services.
      • Sepulveda C.
      • Marlin A.
      • Yoshida T.
      • Ullrich A.
      Palliative care: the World Health Organization's global perspective.
      Cheap, effective, and culturally appropriate palliative care initiatives, such as the home-based palliative care program in Uganda, where palliative care is part of the national health plan, are to be pursued worldwide.
      The untapped potential of palliative care for AIDS.
      • Ramsay S.
      Leading the way in African home-based palliative care. Free oral morphine has allowed expansion of model home-based palliative care in Uganda.
      It would be a reasonable step forward to accurately plan how patients with other chronic, life-threatening illnesses, such as HD, COPD, and RD, could be embraced by such a benefit.

      Acknowledgments

      The authors thank The Cicely Saunders Foundation, which funded this project, and its International Scientific Expert Panel, which suggested that this enquiry be undertaken. The authors also thank Dr. Richard Harding for comment on an earlier draft.

      Appendix. List of Texts Included in Search

      • Addington-Hall J, Higginson IJ, eds. Palliative care for non-cancer patients. New York: Oxford University Press, 2001.
      • Bruera E, Portenoy RK, eds. Cancer pain: Assessment and management. Cambridge: Cambridge University Press, 2003.
      • Chochinov HM, Breitbart W, eds. Handbook of psychiatry in palliative medicine. Oxford: Oxford University Press, 2000.
      • Doyle D, Hanks GWC, MacDonald M, eds. Oxford textbook of palliative medicine. Oxford: Oxford University Press, 2004.
      • Doyle D, Hanks GWC, MacDonald M, eds Oxford textbook of palliative medicine. Oxford: Oxford University Press, 1998.
      • Ford G, Lewin I, eds. Managing terminal illness. London: Royal College of Physicians of London, 1996.
      • Higginson IJ, ed. Clinical audit in palliative care. Abingdon: Radcliffe Medical Press, 1993.
      • Hoskin P, Makin W, eds. Oncology for palliative medicine. New York: Oxford University Press, 1998.
      • Joishy SK, ed. Palliative medicine secrets. Philadelphia: Hanley & Belfus, 1999.
      • Levy J, Morgan J, Brown E. Oxford handbook of dialysis. New York: Oxford University Press, 2001.
      • Portenoy RK, Bruera E, eds. Issues in palliative care research. Oxford: Oxford University Press, 2003.
      • Regnard C, Hockley J. A guide to symptom relief in palliative care. Abingdon: Radcliffe Medical Press, 2004.
      • Ripamonti C, Bruera E, eds. Gastrointestinal symptoms in advanced cancer patients. Oxford: Oxford University Press, 2002.

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