#214: Prognosis in HIV Associated Malignancies

FAST FACTS AND CONCEPTS #214

PROGNOSIS IN HIV ASSOCIATED MALIGNANCIES

Steven Oppenheim MD

Background Fast Fact #213 introduced prognostic principles in HIV/AIDS, as well as gave survival data for many life-threatening complications of HIV infection. This Fast Fact presents survival data for malignancies commonly arising in the setting of HIV/AIDS. Before applying these data to individual patients, consideration should be given to the prognostic principles in HIV/AIDS discussed in Fast Fact #213.

Prognostic Data

· AIDS related Kaposi’s sarcoma (KS), has become less common since the use of combination antiretroviral therapy (cART). It is a grossly violaeous spindle cell tumor, more common amongst men who have sex with men, and is associated with co-infection with human herpes virus-8. KS can involve the skin, mucous membranes, and viscera. Some patients with mild to moderate KS may have complete resolution of their disease with cART and/or chemotherapy. More extensive disease of the skin or viscera portends a poorer prognosis with a 2 year survival of 58%. A prognostic index has been developed for patients with KS on cART. In this index age > 50 years, developing KS as a later-stage complication of HIV infection (as opposed to KS being a patient’s first AIDS-defining illness), CD4 cell count <100 style=""> Patients with all 4 poor markers had a 1 year survival of ~40%.

· Primary CNS lymphoma is strongly associated with Epstein Barr virus infection. Treatments include cART, whole brain radiation and chemotherapy. Median survival was 3 months before the use of cART, but has improved to16 months for those responding to cART (with ≥ 50 CD4 cell count increase over their baseline count or ≥ 0.5log10* HIV viral load decrease after lymphoma diagnosis).

· Systemic non-Hodgkin’s Lymphoma (Diffuse Large Cell Lymphoma - DLCL) is the most common lymphoma associated with HIV infection. A decreased incidence has not been observed with cART, although survival in HIV patients is now approaching that of DLCL patients without HIV. 5 year survival with current chemotherapy regimens is approximately 50%. A well-validated tool for stratifying DLCL survival is the International Prognostic Index (IPI) which includes age, tumor stage, serum LDH, performance status, and number of extranodal disease sites. Patients with intermediate-risk IPI scores have a 50-64% 3 year survival. However patients with high-risk IPI scores have only a 13% 3 year survival, even in the cART era (see references 3, 9).

· Squamous cell carcinoma (SCC) of the cervix is seen frequently in patients with HIV and is caused by the human papilloma virus. Survival data are limited for HIV infected patients, but it appears to be similar to patients without HIV infection and is unaffected by the use of or response to cART. Five year survival of SCC of the cervix is 86% for locally invasive disease, 43% with regional disease, and 11% with metastatic disease.

· Squamous cell carcinoma (SCC) of the anus, while not officially an AIDS-defining malignancy, is 120 times more common in HIV infected than non-infected patients and is also associated with human papilloma virus infection. Survival does not seem to be affected by HIV status, with overall 2 year survival in the ~75% range.

* 0.5 log10 decrease equals, for instance, a decrease of 4.0 to 3.5 log10, or 10,000 to 3,160 copies HIV-RNA/ml.

References

1. Bernstein WB, Little RF, Wilson WH, Yarchoan R. Acquired Immunodeficiency Syndrome-related malignancies in the era of highly active antiretroviral therapy. Int. J Hematology. 2006; 84:3-11.

2. Biggar RJ, Engles EA, Ly S, et al. Survival after cancer diagnosis in persons with AIDS. JAIDS. 2005; 39:293-299.

3. Bower M, Gazzard B, Mandalia S, et al. A prognostic index for systemic AIDS-related non-Hodgkin lymphoma treated in the era of highly active antiretroviral therapy. Ann Intern Med. 2005; 143:265-273.

4. Cheung MC, Pantanowitz L, Dezube BJ. AIDS Related Malignancies: Emerging challenges in the era of highly active antiretroviral therapy. The Oncologist. 2005; 10:412-426.

5. Chiao EY, Giordano TP, Richardson P, El-Serag HB. Human Immunodeficiency Virus-associated squamous cell cancer of the anus: Epidemiology and outcomes in the highly active antiretroviral therpy era. J Clin Onc. 2008; 26:474-479.

6. Hentrich M, Maretta L, Chow KU, et al. Highly active antiretroviral therapy (HAART) improves survival in HIV-associated Hodgkin’s disease: results of a multicenter study. Ann Oncology. 2006; 17:914-919.

7. Hoffmann C, Tabrizian S, Wolf E. Survival of AIDS patients with primary central nervous system lymphoma is dramatically improved by HAART-induced immune recovery. AIDS. 2001; 15:2119-2127.

8. Goldie SJ, Weinstein MC, Kuntz KM, Freedberg KA. The costs, clinical benefits and cost-effectiveness of screening for cervical cancer in HIV-infected women. Ann Intern Med. 1999; 130:97-107.

9. Lim ST, Karim R, Tulpule A, Nathwani BN, Levine AM. Prognostic factors in HIV-related diffuse large-cell lymphoma: before versus after highly active antiretroviral therapy. J Clin Oncol. 2005; 23:8477-8482.

10. Mounier N, Spina M, Gisselbreght C. Modern management of non-Hodgkin lymphoma in HIV-infected patients. Br J Haem. 2007; 136:685-698.

11. Oehler-Janne C, Huguet F, Provencher S, et al. HIV specific differences in outcome of squamous cell carcinoma of the anal canal: a multicentric cohort study of HIV-positive patients receiving highly active antiretroviral therapy. J Clin Onc. 2008; 26:2550-2557.

12. Skiest DJ, Crosby C. Survival is prolonged by highly active antiretroviral therapy in AIDS patients with primary central nervous system lymphoma. AIDS. 2003; 17:1787-1793.

13. Stebbing J, Sanitt A, Nelson M, Gazzard B, Bower M. A prognostic index for AIDS-associated Kaposi’s sarcoma in the era of highly active antiretroviral therapy. Lancet. 2006; 367:1495-1502.

14. Uronis HE, Bendell JC. Anal cancer: an overview. The Oncologist. 2007; 12:524-534.

Author Affiliation: San Diego Hospice at the Institute for Palliative Care, San Diego, California.

FAST FACTS AND CONCEPTS #213

PROGNOSIS IN HIV AND AIDS

Steven Oppenheim MD

Introduction The prognosis of patients with HIV/AIDS (Human Immunodeficiency Virus infection/Acquired Immune Deficiency Syndrome) has improved dramatically since 1996 for those who have access to appropriate treatment. Due to the success of combination antiretroviral therapy (cART) since 1996 as well as improvements in the prevention and treatment HIV complications, over 80% of patients are now alive 10 years after sero-conversion,. Deaths from opportunistic infections (OI) have declined while mortality from other co-morbidities has become more common (e.g. hepatitis B and C infection, renal failure, non-HIV-related cancers, cardiovascular disease, suicide, and complications of substance abuse). In fact, patients with CD4 counts >200 cells/mm3 are more likely to die from non-HIV-related illnesses than they are from complications of AIDS, at least over a time-frame of one decade. This Fast Fact discusses prognostication in patients who are suffering life-threatening complications related to HIV infection using data where cART was available. Fast Fact #214 will discuss prognosis specifically for malignancies arising in the setting of HIV infection.

Prognostic Principles

· Numerous factors affect prognosis such as age, remaining antiviral treatment options, opportunistic infections’ response to therapy, the development of untreatable complications, functional status, nutritional status, CD4 cell count, and HIV viral load.

· In the pre-cART era median survival for people with a CD4 count <>

· Due to the rapidly changing field of HIV medicine, close collaboration with the patient’s HIV provider is mandatory. While the following data are the best available they remain incomplete, may become outdated as therapies evolve, and should be applied to individual patients cautiously.

· Survival for all the HIV associated complications discussed in this Fast Fact has improved due to the use of cART.

Common causes of death in patients with HIV/AIDS with available survival data

· Disseminated mycobacterium avium complex infection: median survival is ~10 months with optimal therapy.

· Pneumocystis pneumonia: survival for all patients presenting is 80-90%. Short-term ICU survival is 75% in patients on cART and 37% not on cART.

· Disseminated cytomegalovirus infection (including retinitis): the largest prospective cohort study demonstrated a median survival of 35 months for all patients on cART compared with 8 months for those not using cART. Six month survival is 61-73% for patients not taking or not responding to cART, but 98% for patients with low CD4 counts who initiate and respond well to cART (CD4 count increases to over 50 cells/mm3).

· Toxoplasma encephalitis: 77-90% of patients are alive after 12 months if on cART, and most who die do so within 6 months of diagnosis. Persistence of altered mental status after initiation of therapy is a strong predictor of early death.

· Progressive multifocal leukoencephalopathy: median survival is ~11 months on cART, 4 months without cART. If cART is started after PML is diagnosed 1 year survival is 58% vs. 24% for those who develop PML already cART.

· AIDS Dementia complex: is caused by HIV and results in progressive cognitive, motor, and behavioral decline. The median survival is 40-81 months from the time of diagnosis; shorter if the CD4 cell count remains <200>5,000 copies/ml.

· AIDS wasting syndrome: is defined by the involuntary loss of >10% body weight along with fever not associated with an OI or neoplasm, and either chronic diarrhea or weakness. Patients with very low lean body mass index (mass in kilograms/height in meters squared) – less than 14.5kg/m2 – have a median survival of ~16 months. These data are from the mid-1990s and it is unclear if the prognosis has changed in the last decade. With unintentional weight loss which does not meet the syndrome definition (loss of 5-10% body weight) there is still a four-fold increased risk of death over 6 months.

References

1. Antinori A, Cingolani A, Lorenzini P, et al. Clinical epidemiology and survival of progressive multifocal leukoencephalopathy in the era of highly active antiretroviral therapy: Data from the Italian Registry Investigative Neuro AIDS (IRINA). J Neurovirol. 2003; 9(suppl 1):47-53.

2. Antinori A, Larussa D, Cingolani A et al. Prevalence, associated factors and prognostic determinants of AIDS-related Toxoplasmic encephalitis in the era of advanced highly active antiretroviral therapy. Clin Infect Dis. 2004; 39:1681-1691.

3. Bhaskaran K, Hamouda O, Sannes M, et al. Changes in the Risk of Death After HIV Seroconversion Compared With Mortality in the General Population. JAMA. 2008; 300(1):51-59.

4. Clifford DB, Yiannoutsos C, Glicksman M, et al. HAART improves prognosis in HIV-associated progressive multifocal leykoencephalopathy. Neurology. 1999; 52:623-625.

5. Coakley E, Samore M, Gillis J, et. Al. The values of quantitative serum HIV-1 RNA levels and CD4 cell counts of <50 x 10 6 cells/L. AIDS. 2000; 14:1147-1153.

6. D’Avignon LC, Schofield CM, Hospenthal DR. Pneumocystis Pneumonia. Semin Respir Crit Care Med. 2008; 29(2):132-40.

7. Dore GJ, MvDonald A, Yueming L, et al. Marked improvement in survival following AIDS dementia complex in the era of highly active antiretroviral therapy. AIDS. 2003; 17:1539-1545.

8. Dworkin MS, Wan PC, Hanson DL, Jones JL. Progressive Multifocal leukoencephalopathy: Improved survival of human immunodeficiency virus-infected patients in the protease-inhibitor era. J Infect Dis. 1999; 180:621-625.

9. Gasnault J, Taoufik Y, Goujard C et al. Prolonged survival without neurological improvement in patients with AIDS-related progressive multifocal leukoencephalopathy on potent combined antiretroviral therapy. J Neurovirol. 1999; 13:1426-1428.

10. Hoffmann C, Ernst M, Wolf E, et al. Evolving characteristics of toxoplasmosis in patients infected with human immunodeficiency virus-1: clinical course and Toxoplasma gondii-specific immune responses. Clin Microbiol Infect. 2007; 13:510-515.

11. Karakousis PC, Moore RD, Chaisson RE. Mycobacterium avium complex in patients with HIV infection in the era of highly active antiretroviral therapy. Lancet Infectious Diseases. 2004; 4:557-565.

12. Kempen JH, Jabs DA, Wilson LA, et al. Mortality risk for patients with cytomegalovirus retinitis and acquired immune deficiency syndrome. Clin Infect Dis. 2003; 37:1365-1373.

13. Krentz HB, Kliewer G and Gill MJ. Changing mortality rates and causes of death for HIV-infected individuals living in Southern Alberta, Canada from 1998 to 2003. HIV Medicine. 2005; 6:99-106.

14. MacArthur RD, et.al. Comparison of prognostic significance of latest CD4 cell count and HIV RNA levels in patients with advanced HIV infection on highly active antiretroviral therapy. HIV Clin Trials. 2005; 6:127-135.

15. Melchior JC, Niyongabo T, Henzel D, Durack-Bown J, Boulier A. Malnutrition and wasting, immunodepression, and chronic inflammation as independent predictors of survival in HIV-infected patients. Nutrition. 1999; 15:865-869.

16. Mikaelsson L, Jacobson G, Andersson R. Pneumocystis pneumonia: a retrospective study 1991-2001 in Gothenburg, Sweden. J Infect. 2006; 53:260-265.

17. Moore RD, CHaisson RE. Natural history of opportunistic disease in an HIV infected urban clinical cohort. Ann Intern Med. 1996; 124:633-642.

18. Morris A, Wachter RM, Luce J, Turner J and Huang L. Improved survival with highly active antiretroviral therapy in HIV-infected patients with severe Pneumocystis carinii pneumonia. AIDS. 2003; 17:73-80.

19. Selwyn PA, Forstein M. Overcoming the False Dichotomy of Curative vs Palliative for Late-Stage HIV/AIDS “Let me live the way I want to live, until I can’t”: JAMA. 2003; 290:806-814.

20. Shen JM, Blank A, Selwyn PA: Predictors of Mortality for Patients with Advanced Disease in an HIV Palliative Care Program: J AIDS. 2005; 40:445-447.

21. Shetty SM, Vanston VJ, Alexander C. The Hospice and Palliative Medicine Approach to Caring for Patients with HIV/AIDS. UNIPAC-7, 3^rd Ed. American Academy of Hospice and Palliative Medicine. 2008.

22. Tang AM, Forrester J, Spieglman D, et al. Weight loss and survival in HIV-positive patients in the era of highly active antiretroviral therapy. JAIDS. 2002; 31:230-236.

23. Tozzi V, Balestra P, Serraino D, et al. Neurocognitive impairment and survival in a cohort of HIV-infected patients treated with HAART. AIDS Res Human Retrov. 2005; 21:706-713.

24. The Antiretroviral Therapy (ART) Cohort Collaboration. Prognosis of HIV-1-infected patients up to 5 years after initiation of HAART: collaborative analysis of prospective studies. AIDS. 2007; 21:1185-1197.

25. The CASCADE Collaboration. Effective Therapy has altered the spectrum of cause-specific mortality following HIV-seroconversion. AIDS. 2006; 20: 741-749.

26. Welch K, Morse A, et al. The clinical profile of end-stage AIDS in the era of highly active antiretroviral therapy. AIDS Pt Care and STDs. 2002; 16:75-81.

Author Affiliation: San Diego Hospice at the Institute for Palliative Care, San Diego, California.

#212: Phantom Limb Pain

FAST FACTS AND CONCEPTS #212

PHANTOM LIMB PAIN

Kavitha Ramchandran MD and Joshua Hauser MD

Background Phantom limb pain (PLP) can be a painful and debilitating consequence of limb amputation from any cause including trauma, cancer, and vascular diseases. This Fast Fact will review the evaluation and management of PLP.

Definition and Characteristics PLP describes pain which patients perceive as coming from an amputated limb as if it were still contiguous with the body. It is distinct from pain at the actual site of the amputation (‘stump pain’). Patients usually experience PLP as occurring in the distal part of the phantom limb and can describe it as feeling ‘burning,’ ‘tingling,’ ‘sharp,’ and ‘cramping.’ Uncomfortable perceptions of limb distortion (such as retraction into the stump) are also reported. PLP is most commonly seen after limb amputation, but similar syndromes can occur with the removal of other body parts including breasts, testicles, eyes, and tongue.

Epidemiology PLP occurs in 50-80% of patients after amputation, but is severe in 5-10% of cases. Risk factors for developing PLP include: tumor-related amputations, chronic limb pain prior to amputation, and significant pain the day of amputation. Despite this, meticulous peri-operative analgesia with epidural anesthesia has not been clearly shown to prevent PLP.

Pathophysiology Both central and peripheral mechanisms are believed to mediate PLP and are incompletely understood. Amputation can lead to reorganization of the somatosensory cortex with ‘remapping’ of the location of amputated limb into the mouth and chin areas. For these patients stimulation of the mouth or ipsilateral face can cause sensations, including pain, that seem be originating from the phantom limb. Central sensitization from preexisting chronic limb pain as well as ectopic discharges from the stump neuroma are also implicated.

Therapy While both drug and non-drug therapies have been investigated, treatment of phantom limb pain remains poorly studied and is largely empiric. Due to the complex nature of PLP and its therapies, a multi-disciplinary approach to treatment is mandatory including pain specialists, physiatrists, physical and occupational therapists, and psychologists.

· Drug treatment: Most clinicians approach PLP as a neuropathic pain syndrome. A few small controlled trials have shown positive results with gabapentin, ketamine, and opioids, but not with tricyclic antidepressants. Despite this, there is insufficient evidence to judge the superiority or inferiority of any drug therapy for PLP, and most clinicians empirically use the full range of adjuvant analgesics along with opioid therapy if needed in its management.

· Non-drug treatments: Non-pharmacologic therapies have also been investigated. These include myoelectrical prostheses, transelectrical nerve stimulation, and mirror therapy. In small studies, the regular use of a myoelectric prosthesis (a prosthesis with electrodes embedded in the socket which stimulate nerves in the stump), has been demonstrated to alter cortical re-organization and reduce pain. For those patients for whom a myoelectric prosthesis is not possible, transelectrical nerve stimulation (a TENS unit) to the stump can have a similar affect. A newly investigated approach is mirror therapy. Mirror therapy involves the placement of mirrors to create the illusion of an intact limb (patients visually perceive that they have an intact limb where their stump is). Patients are taught to move both the real and the illusory limb with the hypothesis that this increases control of the brain over the phantom limb and leads to a decrease in PLP. In one small controlled study 100% of patients who underwent mirror therapy had a decrease in pain.

References

1. Devor M and Seltzer Z. Pathophysiology of damaged nerves in relation to chronic pain. In: Wall PD and Melzack RA, Editors. Textbook of Pain (4th Ed). Churchill-Livingstone, New York (1999), pp. 128–164.

2. Bone M, Critchley P, Buggy D. Gabapentin in postamputation phantom limb pain: A randomized, double-blind, placebo-controlled, cross-over study. Reg Anesth Pain Med. 2002; 27:481-486.

3. Robinson LR, Czerniecki JM, Ehde DM, et al. Trial of amitriptyline for relief of pain in amputees: results of a randomized controlled study. Arch Phys Med Rehabil. 2004; 85:1-6.

4. Flor H. Phantom limb pain: characteristics, causes, treatment. Lancet Neurol. 2002; 1:182-189.

5. Dworkin RH et al. Pharmacologic management of neuropathic pain: evidenced-based recommendations. Pain 2007. 132:237-251.

6. Chan BL, Witt R. Mirror therapy for phantom limb pain. N Engl J Med. 2007; 357:2206-7.

Author Affiliations Northwestern University Feinberg School of Medicine Palliative Care and Home Hospice Program.

#211 Guided Imagery For Anxiety

FAST FACTS AND CONCEPTS #211

GUIDED IMAGERY FOR ANXIETY

Karen Cooper LCSW, OSW-C and Susan Stollings PhD

Background Anxiety occurs in hospitalized patients for many reasons including fear of specific procedures, worry about the future, and lack of control. Guided imagery is an intervention that can be delivered at the bedside in 10-15 minutes by a wide range of trained health care providers at a low cost (1).This Fast Fact will discuss guided imagery as an anxiety reduction technique.

The Technique Guided imagery is a mind-body exercise based on prompting patients to formulate meaningful mental pictures to achieve relaxation and reduce anxiety. Many guided imagery scripts include common elements such as asking the patient to sit or lie in a comfortable position, quieting the mind, removing negative thoughts and images, and calling to mind a vivid image or scenario that is calming and relaxing (a ‘safe place’). The content of a guided imagery script can include quiet and peaceful music with focus on a “safe place” where one feels secure and relaxed or it may involve more active, physical sensations such as playing and winning a tennis match. It can be performed by trained professionals or with the use of audio recordings, and can be performed daily or as needed by the patient. An example of language used in a guided imagery exercise is: “Position yourself as comfortably as you can, shifting your weight so that you’re allowing your body to be fully supported by your chair or couch…. Take a deep, full, cleansing breath…inhaling as fully as you can…breathing deep into the belly if you can…and breathing all the way out…. Imagine a place where you feel safe and peaceful and easy…a place either make-believe or real….” See reference (2) for an example of a full script. Information about further training in the use of guided imagery can be found at http://academyforguidedimagery.com.

Research Outcomes

Guided imagery has been shown to reduce anxiety and use of anxiolytics, and to improve patient satisfaction in a variety of medical settings (1, 3, 7). In separate studies it was shown to significantly reduce anxiety and worry among patients facing abdominal surgery or cardiac catheterization compared to usual care (3, 4). In a group of patients who had been hospitalized for more than two days, use of anxiolytic medication and heart rate were lower in the guided imagery group than in a control group (5). A combination of diaphragmatic breathing and guided imagery was used with a group of breast and gynecological cancer brachytherapy patients using 10 minutes of face to face training and a follow-up taped script via audiocassette. Patients in the intervention group had significantly less anxiety at follow-up several weeks later than those in the control group (6). Clinical experience and expert opinion support its helpfulness for advanced cancer patients, although there is little research yet in this population (8).

Limits and Cautions

While a safe technique, guided imagery can rarely elicit negative emotional reactions, as well as create situations of patient vulnerability and susceptibility. Due to this, guided imagery should be initiated in health care settings by a clinician who is trained in its proper use, who is comfortable with professional therapeutic boundaries, and who can respond appropriately to negative emotional reactions. In particular, guided imagery may trigger flashbacks in patients with post-traumatic stress disorder, and it is relatively contraindicated in these patients. It is also contraindicated in patients who have hallucinations or delusions, delirium, or severe obsessive compulsive disorder. As with any intervention, there are some patients who do not benefit from this technique or who are unable to call to mind a relaxing image.

References

1. Miller R. Nurses at community hospital welcome guided imagery tool. Dimensions Crit Care Nursing. 2003; 22(5):225-226.

2. Naparstek B. Staying Well with Guided Imagery. New York: Warner Books. 1994: pp. 76-79.

3. Tusek D, Church JM, Fazio V W. Guided imagery as a coping strategy for perioperative patients. AORN Journal. 1997; 66(4):644-649.

4. McCaffrey R, Taylor N. Effective anxiety treatment prior to diagnostic cardiac catheterization. Holistic Nursing Practice. 2005; 19(2):70-73.

5. Toth M, Wolsko PM, Foreman J, Davis RB, Delbanco T, Phillips RS. A pilot study for a randomized, controlled trial on the effects of guided imagery in hospitalized medical patients. Journal of Alternative and Complementary Medicine. 2007; 13(2):194-197.

6. Leon-Pizarro C, Gich I, Barthe E, et al. A randomized trial of the effect of training in relaxation and guided imagery techniques in improving psychological and quality of life indices for gynecologic and breast brachytherapy patients. Psycho-Oncology. 2007; 16:971-979.

7. Halpin LS, Speir AM, CapoBianco P, Barnett SD. Guided imagery in cardiac surgery. Outcomes Management. 2002; 6(3):132-137.

8. Foley KM, Back A, Bruera E, et al. (Eds). When the Focus is on Care: Palliative Care and Cancer. Atlanta: American Cancer Society. 2005: p. 176.

Author Affiliations: University of Pittsburgh Medical Center, Pittsburgh, PA.

The original version of this Fast Fact is available at EPERC.

210: Suicide Attempts in the Terminally Ill

FAST FACTS AND CONCEPTS #210
SUICIDE ATTEMPTS IN THE TERMINALLY ILL
Sean Marks MD and Drew Rosielle MD

Background Chronic or advanced medical illness is a significant risk factor for suicidality (1). This Fast Fact discusses evaluating and responding to suicidality in patients with life-limiting diseases. Note: this Fast Fact does not address cases of ‘physician assisted suicide’ which have occurred after a deliberative process including psychiatric screening such as in Oregon in the US (2).

Ethics
• Core Principles: It is a core obligation of physicians to prevent a patient from initiating suicide and to intervene medically to prevent a patient from dying after a suicide attempt (3). This obligation can include detaining and restraining patients against their will and the use of invasive medical interventions such as mechanical ventilation if needed, although such restrictions to a patient’s liberty should be kept to the minimum necessary. Most suicidal patients are considered impaired by depression or other mental illnesses and their actions are not considered autonomous, thus justifying detaining patients and providing medical interventions against their will (4). Such interventions can create further opportunities to treat the patient’s psychiatric condition, and only 20% of people who are prevented from committing suicide subsequently complete another attempt.

• Exceptions at life’s end: The above logic is less compelling in terminally ill patients who have attempted suicide, particularly with short prognoses (e.g. less than 1 month). In these patients most medical interventions are unlikely to restore health or significantly alter the dying process in a way that would materially benefit the patient. Clinicians may opt to forgo certain interventions (e.g. mechanical ventilation), particularly if family/proxy decision makers consider such interventions inappropriate in their dying loved ones. In these situations clinicians are advised to 1) verify the certainty of the very short prognosis, utilizing consultants liberally, 2) discuss with proxy decision makers all possible treatment plans including, when feasible, less-invasive supportive care options with treatment limitations (e.g. ICU monitoring, gastric lavage and charcoal administration for an overdose, but establishing a do-not-resuscitate/do-not-intubate order even if the patient deteriorates), and 3) seek ethics consultation.

• Advance Directives: Advance directives such as living wills stating a patient’s wish to not be mechanically ventilated are not binding in the setting of a suicide attempt. However, they should be honored in patients with short prognoses per the discussion above. Advanced directives specifying treatment limitations should be re-evaluated if it is suspected those statements were made during a period of undetected depression (5,6).

Epidemiology and Risk Factors The actual rate of suicide attempts in terminally ill patients is unknown, and there has been limited research into specifically ‘terminally ill’ populations. What is clear is that advancing age and psychiatric comorbidity are risk factors for suicide (along with male sex, AIDS diagnosis, a family history of suicide, and uncontrolled pain) (7,8). Cancer patients have nearly twice the incidence of suicide than the general population (rate of 31.4/100,000 vs. 16.7/100,000 patient-years) (6). Lung, stomach, and head and neck cancers have the highest suicide rates among all cancer types (9). Up to 8.5% of terminally ill cancer patients express a sustained and pervasive wish for an early death, and in one survey of terminally ill patients, 10% of patients reported “seriously pursuing” physician assisted suicide (10,11). Rates of actual suicide attempts are presumably lower.

Assessment All patients with life-limiting illnesses should be routinely assessed for depression and mood disorders (see Fast Facts #7, 43); depressed patients should be screened for suicidal thoughts. Patients who admit to suicidal thoughts or a desire for hastened death should be asked about specific plans for self-harm, past history of suicide attempts, access to firearms or other lethal means to carry out a suicidal act, and level of support/supervision available in the home (e.g. family caregivers). Although some clinicians may be concerned that exploring suicidal thoughts may make suicide more likely, there is no evidence that this occurs. Many ill patients who express a desire for death are simply communicating unresolved emotional and existential concerns about dying: see Fast Facts #156 & 159.


Responding to Suicidal Intent All patients who are seriously threatening self-harm, or who have pervasive thoughts of ending their life, should be evaluated urgently by a psychiatrist (12). Immediate resources depend on local availability and can include prompt evaluation by an established psychiatrist, medical or psychiatric urgent care clinics or emergency departments, or even voluntary hospital admission. Options include voluntary psychiatric treatment, arranging 24 hour safety monitoring from the patient’s family and friends, introducing home hospice or home nursing support, removing means to carry out a suicidal act, and imposing emergency detention. For disabled patients close to death, removing the means of self-harm (e.g. limit access to pain medications as long as a reliable family member can administer them) and providing close supervision through, for instance, hospice services are often sufficient and minimally restrictive.

References
1. Hendin H. Suicide, assisted suicide and medical illness. J of Clin Psychiatry. 1999; 60 Suppl 2:46-50.
2. Death With Dignity Act Report 2007. State of Oregon Department of Human Services. Available at: http://www.oregon.gov/DHS/ph/pas/index.shtml. Accessed November 10, 2008.
3. Lo B. Resolving ethical dilemmas: a guide for clinicians – 3rd Edition. Lippincott Williams & Wilkins, 2005: 256-9.
4. Miller RD. Need-for-treatment criteria for involuntary civil commitment: impact in practice. Am J Psychiatry. 1992; 149:1380-4.
5. Ganzini L, Lee MA, Heinz RT, et al. The effect of depression treatment on elderly patients’ preferences for life sustaining medical therapy. Am J of Psychiatry. 1994; 151:1631-6.
6. Sontheimer D. Suicide by advance directive. J Med Ethics. 2008; 34:e4; doi:10.1136/jme.2008.025619.
7. Farberow NL, Banzler S, Cutter F, Reynolds D. An eight-year survey of hospital suicides. Suicide and Life-Threatening Behavior. 1971; 1:184-201.
8. Rabins PV. Prevention of mental disorder in the elderly: current perspectives and future prospects. J Am Geriatric Soc. 1992; 40:727-33.
9. Misono S, Weiss NS, Fann JR, Redman M, Yueh B. Incidence of suicide in persons with cancer. J Clin Oncol. 2008; 26:4731-4738.
10. Chochinov HM, Wilson KG, Enns M, Mowchun N, Lander S, Levitt M, et al. Desire for death in the terminally ill. Am J Psychiatry. 1995; 152:1185-91.
11. Emanuel EJ, Fairclough DL, Emanuel LL. Attitudes and desires related to euthanasia and physician-assisted suicide among terminally ill patients and their caregivers. JAMA. 2000; 284:2460-2468.
12. Block SD. Chapter 6: Assessing and managing depression in the terminally ill patient. Physician’s Guide to End of Life Care. Snyder, Lois ACP Press, 2001.

Author Affiliations: Medical College of Wisconsin, Milwaukee, Wisconsin.


The original version of this Fast Fact can be found at EPERC.