Christie H. Izutsu, MD, of UC San Diego, presents "End of Life Care: Discussions and Medical Decision Making"

1. End of Life Care:
Discussions & Medical
Decision Making
Christie Izutsu
Resident Physician, PGY-2
Department of Internal Medicine
University of California, San Diego

2. Case Discussion
23 M born prematurely at 24-28 wks gestation
• Birth complicated by intraventricular hemorrhage
resulting in developmental delay
• Received several blood transfusions resulting in
contraction of HIV at 6 months of age
First visit to Owen adolescent clinic, 1/31/06
• M184V, D67N, & T689D
• K103N, Y188L
• No PI mutations

3. Case Discussion:
Continued
1/17/07 – clinic visit:
• Labs indicate probable development of resistance
(CD4 103, VL 53892) – repeat resistance testing
more consistent with not taking meds
• Meds:
Epzicom/abacavir/3TC
Norvir/ritonavir
Viread/tenofovir
TMP/SMX DS
Reyataz/atazanavir

4. Case Discussion:
Continued
December 2009 – clinic visit:
• Hospitalized for seizures
• Per brother was diagnosed with progressive
multifocal leukoencephalopathy (PML, +JC virus in
CSF)
• Urine tox +amphetamines, +benzodiazepines
• EEG without seizure activity
• Serum CrAg negative

5. Case Discussion:
Continued
2009-2011 – ongoing medication adherence issues:
• Moving back & forth between Northern California
• Intermittent substance abuse (meth, marijuana)
• Insurance problems (ADAP & Ryan White funding
lapsed 3/2010)
• Misplaced prescriptions
• Patient perspective - “did not have a clear
understanding of risks associated with his non-
compliance to meds”

6. Case Discussion:
Continued
2009-2011 – ongoing medication adherence issues:
• Discontinued ARVS 1/2011 due to nonadherence
and increasing resistance pattern
• Resistance testing:
– 12/2008 (on Atripla): Resistant 3TC, FTC, DLV, EFV, NVP
• NRTI: D67N, T69D, M184V; NNRTI: K103N, Y188L; PI:
none
– 2007 (not on meds): pan-sensitive
– 5/23/2002 (on Trizivir): Resistant 3TC, ddC, AZT, DLV, EFV,
NVP
• restarted Atripla 7/2011, realized he had “AIDS”

7. Case Discussion:
Continued
Social history – complicated family dynamics:
• mother passed due to ruptured aneurysm peri-
partum; “misses the mom he never knew”
• Moved to San Diego 2/2010 from Bakersfield;
previously living with uncle who passed (diabetic
on dialysis)
• Moved in with GM, father, two uncles (Guillermo &
Juan), one of whom assisted with meds
• Father s/p CVA and recent coma, now “like a baby”
• Education up to 11th grade, wanting to get GED

8. Case Discussion:
Continued
Progression through 2012:
• Started on new ARV regimen
• Developed anemia of chronic disease & worsening
of thrush
• Hospitalized for pneumonia at end of 2011
• Hospitalized 7/2012 for GI bleed, coagulopathy
and duodenal obstruction; persistent vomiting –
started on MAC therapy
• Admitted to Hillcrest next week, 7/23-7/25, for
emesis, dehydration; thought to be due to MAC

9. Case Discussion:
Continued
8/2-8/11/12 – clinic to hospitalization:
• Readmitted for tachycardia, bloody diarrhea;
ARVs discontinued
• Stool AFB positive, likely disseminated MAC
• Also diagnosed with:
– severe malnutrition (188  87 lb over 2 yrs)
– hypogonadism
– peridontitis

10. Case Discussion:
Continued
Progression through 1/2013 – clinic visits:
• Worsening diarrhea, now in diapers
• More weight loss – now 83 lb
• requiring assistance to shower
• new abdominal distention & lower
extremity/scrotal edema
• uncles note worsening functional decline
– using walker for ambulation due to leg weakness
– R>L UE tremor which makes feeding himself difficult

11. Case Discussion:
Continued
ARV Clinic, 1/5/12 – ARV history:
• 7/11-present: Atripla
• 2/09-4/10: EPZ+RAL+ETR
(continued viremia, questionable adherence)
• 10/07-2/09: Off ARVs
• 3/05-10/07: EPZ+TDF+ATV/r
(persistent viremia, likely non-compliant)
• 3/04-1/05: FTC+TDF+ABC+ATV/r
• 10/01-1/04: Trizivir
(undetectable, then rebound viremia)
• 11/98-3/99: D4T+NFV+EFV (continued viremia)
• 5/96-7/98: 3TC+d4T
• 12/94-1/96: Ddi+AZT+NVP
• 8/93-3/94: AZT

12. Case Discussion:
Continued
2/1/12 – ARV Clinic:
• “understands why he can no longer use Atripla and understands
he has developed resistance to certain medications due to non-
compliance”
• “based on his genotype, Complera, Prezista/Norvir appears to be
a reasonable option for this patient which will help with
adherence and this regimen should have full antiretroviral activity
based on the past genotype resistance test.”
• “MedAction plan should help the patient stay adherent with his
regimen”
• “Expect a 1-2 log reduction in VL after 2-4 weeks on this new
regimen, and should provide an excellent long-term virologic
response, as long as patient continues to be adherent to the
regimen.”

13. CD4 count, 3/2010-1/2013

14. CD4 Percent, 3/2010-1/2013

15. Viral load

16. Case Discussion:
Continued
1/15-1/28/13 – hospitalization:
• Admitted following posturing of arms and nonresponsiveness
• Emesis during LP, intubated for airway protection
• 1/17: bronchoscopy revealed exophytic lesion of right main
stem bronchus; galactomannan (+), cytology (-)
• 1/19: evaluated by neuro, thought to have HAND (HIV
associated neurocognitive disorder)
• Started on empiric meningitis coverage; all cultures (-)
• CT abdomen/pelvis with new and enlarging hypoattenutating
lesions in the liver & spleen, diffuse colitis and
lymphadenopathy; broadened to vancomycin & pip/tazo
• continued on ARVs, MAC coverage and OI prophylaxis
• 1/21: amphotericin added, discontinued 1/23

17. Case Discussion:
Continued
1/15-1/28/13 – hospitalization:
• Developed new thrombocytopenia
• Noted to have ongoing aspiration events – per speech
eval, unsuitable for oral intake; NG placed temporarily
• 1/23: family meeting to discuss goals of care
– Discussed severity of condition
– Liver lesions suspicious for malignancy, unable to biopsy
– Believe it is time to consider other options to minimize
“suffering”
– Current options included prolongation of life v providing
quality of life measures to improve comfort and enjoyment in
last phase of life

18. Case Discussion:
Continued
1/15-1/28/13 – hospitalization:
• 1/24/13 – DNR/DNI order placed
• Over the next few days, Howell consulted; priest
present
• 1/28/13 – noted to have agonal breathing, passed at
3am
• Autopsy declined by father – previously permitted by
sister who “wanted to help advance medicine for her
children”

19. Dealing with End-of-Life: Pre-ARV era
• Number 1 cause of death of Americans aged 25-
44 in 1997
CDC “Mortality Slide Series”

20. Dealing with End-of-Life: Pre-ARV era
• Number 1 cause of death of Americans aged 25-
44 in 1997
• Death often before knowing diagnosis
• Focus on quality, rather than quantity of life
• Eventually shifted to emphasis on the quality of
one’s death
– Due to increased acceptance of death in young
healthy individuals
– “Sharing a common fate”
– Desire to control how one dies
Kobayashi JS. Bulletin of the Menninger Clinic. 1997;61(2):146-188.

21. A Different Death Experience
• Multiple losses – friends, partners,
employment, future, independence, self-
esteem, meaningfulness in life
• Often results in complicated grief
• High rates of depression
• “Hidden grievers”

22. Death in the era of Treatment
Advancements
CDC “Mortality Slide Series”

23. Death in the era of Treatment
Advancements
CDC “Mortality Slide Series”

24. Death in the era of Treatment
Advancements
CDC “Mortality Slide Series”

25. Death in the era of Treatment
Advancements
CDC “Mortality Slide Series”

26. Death in the era of Treatment
Advancements
Death still exists
• Treatment failures
– Declining benefits of treatment with time
– Intolerable side effects
– Inability to adhere due to demands & complexity
(significant portion of patients not 100% adherent)
• 75% adherence rates in 2011 (UCSF study)
• 46-88% in 2001
• Inaccessible treatments (economic, social –
providers may not prescribe due to concern for
adherence)

27. Death in the era of Treatment
Advancements
Feelings surrounding death:
• Seems “more unusual” – avoidance and disbelief
when death occurs
– AIDS now a “chronic illness”
• Death anxiety
– “longer period of uncertainty and anticipatory grief”
(Demmer)
– Greater variability in course of illness
– Treatment can fail at any time
• Caregivers – more emotional & physical exhaustion

28. What do you feel is the largest barrier
to discussions about end-of-life care?
a) Timing – not sure when to bring this up
b) Patient discomfort
c) Clinic appointment constraints
d) Lack of training

29. Difficulties Discussing Death
Clinician perspectives:
• Unsure when to discuss end-of-life issues
• Not ready for patients to die (Curtis et al) due to
treatment advancements
• Still with feelings of helplessness, frustration
– Close relationships with long-term pts so more intense
feelings of loss
– Advancements = new challenges, don’t know how to deal
with them
• Lack of training for paraprofessionals

30. Difficulties Discussing Death
Patient perspectives:
• Physician and patient not on same “page”
– Not wanting to face reality
– Complicated process
– Family opinion
• Lack of knowledge
– Understanding what actually happens
– Statistics surrounding resuscitation

31. “Barriers to communication”
Curtis et al, 1996:
• Focus groups of 47 AIDS patients and 19 physicians
• Physician issues – discomfort, time pressures
during appt, fear of undermine hope, role to make
patients feel better, young age of patients
• Patient issues –having AD meant no further
discussions were needed, didn’t want preferences
“set in stone”, felt discriminated against
Curtis et al. J Gen Intern Med. 1997;12:736-41.

32. “Barriers to communication”
Curtis et al, 1996:
One major concern was that “discussing end-of-life care may be
harmful to the patient and may even hasten death”
Curtis et al. J Gen Intern Med. 1997;12:736-41.

33. SUPPORT Study
• “timely provision of prognostic information
by trained nurse”
• Less than 50% of physicians knew when
patients changed their code status to DNR
• Caveat – did not include HIV positive
patients

34. What percentage of your patients have
advance planning documents written up
prior to actually needing end-of-life care?
a) More than 95%
b) 75-95%
c) 50-75%
d) 25-50%
e) Less than 25%

35. Improving Communication:
HIV-Specific Advance Directive
Singer et al. at University of Toronto, 1995
•203 individuals randomized to generic v HIV-specific
living will (50 v 52)
•101 received both
•77.2% v 22.8% preferred the HIV-specific document,
(p<0.001)
•ADAQ (Adv Directive Assessment Questionnaire)
compared the two –mean ADAQ score slightly higher for
HIV document (68.5% v 66.2%, p=0.051
•May not be document itself, but translates to point that
advanced planning should be tailored to patient

36. Creating an Advance Directive:
HIV-specific documents
Singer et al. J Gen Intern Med 1997;12:729-735

37. Creating an Advance Directive:
HIV-specific documents
Singer et al. J Gen Intern Med 1997;12:729-735

38. Advance directive:
disease-specific study
Figure 1: Treatment preferences based on Centre for Bioethics Living Will (Singer et al)

39. Advance directive:
disease-specific study
Figure 2: Treatment preferences based on the HIV Living Will (Singer et al)

40. Advance directive:
disease-specific study
• Generally, prefer less aggressive treatment if
illness more advanced
• Within specific illness scenarios, little
variation in preferences for different
therapies
• Advanced directives are NOT meant to be a
substitute for end-of-life discussions

41. Improving Discussions
What clinicians can do:
• Act as “fellow travelers who can help grievers
make sense of issues that may impact their grief”
– Information and warnings about what to expect
• Open communication
• Active coping strategies
• Structured deliberation – (Emanuel LL) small
choices rather than large ones all at once

42. Improving Discussions
Ongoing discussions:
• “Learn why patients express certain preferences
rather than what those preferences are” (Forrow
L.)
– Outcomes may drive preferences (Rosenfeld, et al)
– Similar concept as Singer study
• Realize that some patients will continue to resist
despite our best efforts

43. President’s Emergency Plan for
AIDS relief
HIV Palliative Care:
• Palliative care begins at time of diagnosis
• Clinical, psychological, social and spiritual
care

44. Children/Youth and HIV
New York Times, Feb 26, 2008

45. What do you feel is the most important
aspect of HIV care in children/youth?
a) Medication adherence
b) Understanding the disease & its progression
c) How the child feels about the disease
d) How the disease impacts their relationships
with others

46. Children/Youth and HIV
• How could we explain children/youth that they
are different, and unless they take multiple
pills every day they would die?
• Common terminology among clinicians
treating for growing and youth living with HIV
are: treatment experienced, HIV resistance
• Not very often stated or address are: stigma
and isolation felt by these patients

47. Children/Youth & HIV: Statistics
Children/youth living with HIV:
• WHO – 3.4 million as of 2011
• UNAIDS – as of 12/2003, children < 15 yrs of age:
– 700,000 newly diagnosed = 13% of all new cases
– 500,000 died that year alone
• Older stats: through 2002, 9300 Americans < 13
– 92 new cases of pediatric AIDS in 2002
– 3x as many HIV cases
• Death rates declined 68% from 1998-2002 in
number of children/youth who died from AIDS

48. Children/Youth & HIV: Progression
Two general patterns:
• 20% - serious disease in first 12 months
– Death usually by age 4
• 80% - slow rate of progression
– May not see serious symptoms until adolescence
– Often with delayed growth & milestones
– Opportunistic infections:
• PCP is the leading cause of death in children
• CMV – primary infection rather than reactivation
• LIP (lymphocytic interstitial pneumonia)
• Severe candidiasis

49. Children/Youth and HIV: Discussions
Talking to children/youth about their disease:
• Tailor to age & development
• May not be a “right” age

50. Children/Youth and HIV: Discussions
Factors influencing disclosure:
Figure 2 (Vaz et al.)

51. Children/Youth and HIV: Concerns
Issues that affect children/youth with HIV:
• Medications – who to tell at school
• Friends
– Psychosocial variables & immune response
• Increase in CD4% by ~5.55% with recent disclosure
(Sherman et al, 2000)
• Being “different”
– Anger, withdrawal, rebelliousness
– Refusal to take medications
• Socially isolated & restricted in activities

52. Children/Youth and HIV:
Medication Adherence
Barriers to medication use:
• Insurance and financial
concerns less prominent
• Otherwise similar to
adults
• Results in complications
and resistance
Table 2. Barriers to Medication Adherence for full Study Sample & By Route of Infection (MacDonell et al.)

53. Spirituality
• Spirituality is part of comprehensive palliative
care
• Associated with health outcomes
– McClain C et al (2003) Lancet 361:1603 – spiritual
well-being correlated with less depression,
hopelessness, SI; higher social support
– Existential well-being and HIV symptoms correlate
with psychological well-being

54. What percentage of your patients have
discussed spirituality with you and the
role this plays in their healthcare?
a) Greater than 95%
b) 75-95%
c) 50-75%
d) 25-50%
e) Less than 25%

55. Spiritual Distress
• Distress comes from fear of dying, conflict of
beliefs and same reasons make addressing
death difficult

56. Suggestions for Discussing
Spirituality
Lo, et al. JAMA. 2002;287:749-754.

57. Suggestions for Discussing
Spirituality
Lo et al:
• Clarifying religious statements
• Responding to statements that may indicate
spiritual concerns
• Responding to religious reasons for rejecting
medical recommendations
• Listening – nonjudgmentally
• Recognizing rituals, symbols, icons

58. Addressing Spiritual Needs
Puchalski et al – FICA format:
• F – faith (belief, meaning)
• I – importance (influence on life)
• C – community (who they belong to)
• A – address/action in care (how we
address)

59. Community Resources for
Addressing Spiritual Needs/Distress
“Heart of Medicine”

60. Books on Life & Death:
Recommended by Rev Kovach, MD

61. At the end:
Medical Decision Making
Decisions at end-of-life:
• Can be difficult if poor communication ahead of
time
• Most times left to family (Kelly B et al)
– Involved 60-80% of the time
– Unfortunately family often unsure of patient wants
• Difficult to decide when to stop pursuing active
measures in hospitalized patients
– Stepwise process (Stroud)

62. Figure 1, Thelen M

63. At the end:
Medical Decision Making
Table 1, Thelen M

64. Closing Thoughts & Reflections
• Medicine is a balance of science & art
• Our compassion and caring connections with
patients can have an immense impact on patient
perceptions & influence the ultimate outcome of
one of the biggest events in life

65. Resources
Demmer, C. “Dealing with AIDS-related loss and grief in a time of treatment advances.” Am J of Hospice & Palliative Care. Vol 18, No
1, Jan/Feb 2001.
Singer et al “The HIV-Specific Advance Directive.” J Gen Intern Med 1997;12:729-735
http://www.slideshare.net/ucsdavrc/addressing-the-spiritual-and-emotional-needs-of-hiv-patients
Wilson, I. “End of Life Care in HIV Disease.” JGIM. Vol 12, Dec 1997.
Forrow L. “The green eggs and ham phenomena. Hastings Cent Rep. 1997;24:S29-32.
Rosenfeld, et al. “End-of-Life Decision Making. A Qualitative Study of Elderly Individuals.” J Gen Intern Med. 2000; 15:620-625.
http://www.state.gov/documents/organization/64416.pdf
“Spiritual Issues in HIV/AIDS Palliative Care.” The Center for Palliative Care Education.
Curtis JR, Patrick DL. “Barriers to Communication About End-of-Life Care in AIDS Patients.” J Gen Intern Med. 1997;12:736-741.
Lo et al. JAMA. 2002;287:749-754.
Puchalski CM, Romer AL. Taking a spiritual history allows clinicians to understand patients more fully. J Pall Med 2000;3:129-37.
CDC Mortality Slide Series. “HIV Mortality Slides.”
WHO. “Antiretroviral therapy for HIV infection in infants and children: Towards universal access. Recommendations for a public
health approach: 2010 revision”
Vaz et al. “Telling Children They Have HIV: Lessons Learned from Findings of a Qualitative Study in Sub-Saharan Africa.” AIDS
Patient Care and STDs. Vol 24, Num 4. 2010.
MacDonell et al. “Barriers to Medication Adherence in Behaviorally and Perinatally Infected Youth Living with HIV.” AIDS Behav.
(2013) 17:86-93.
Kovach, DA. “Caring for the whole person with HIV: Mind, Body and Spirit.” The Permanente Journal. Spring 2008. Volume 12,
Number 2.
Sherman et al. “When Children Tell Their Friends They Have AIDS: Possible Consequences for Psychological Well-Being and Disease
“Please Talk to Kids About AIDS”. Hennessey et al. (documentary, vineeta.org)
Womenshealth.gov “AIDS”

66. Resources
“Talking with Children about Sex & AIDS: At What Age to Start?” New York Times. Feb 26, 2008.
Childrennow.org “Talking with Kids About Tough Issues: HIV/AIDS”
Kelly B, et al. “Systematic Review: Individuals’ Goals for Surrogate Decision Making.” JAGS. 60: 884–895
National Institute of Allergy and Infectious Disease (NIAID) website. “HIV/AIDS: HIV infection in infants and children”
http://www.niaid.nih.gov/topics/HIVAIDS/Understanding/Population%20Specific%20Information/Pages/children.aspx
Okonsky, J. “Problems taking pills: understanding HIV medication adherence from a new perspective.” AIDS Care. Vol 23, Issue 12.
2011.
Univ of Toronto Joint Centre for Bioethics. “HIV Living Will.”
http://www.jointcentreforbioethics.ca/tools/documents/jcb_livingwill_hiv.pdf
“The SUPPORT Principal Investigators. A Controlled trial to improve care for seriously ill hospitalized patients: The Study to
Understand Prognoses and Preferences for Outcomes and Risks of Treatments (SUPPORT).” JAMA. 1996;274:1591-8.
http://theologyforum.files.wordpress.com/2012/12/light-shining.jpg