Transcript 1 - RCRMC Family Medicine Residency

Paliative Care and Cholestrol
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Obesity
July 8, 2011 (Washington DC) — A new report illustrates in stark terms how the obesity epidemic in the US has
spiraled in the past two decades and pinpoints, on a state-by-state basis, where the largest increases have occurred [1].
The authors stress, however, that ranking the states in this way is not a reproof; rather, "we want to raise awareness,
drive action, identify solutions, and reverse the epidemic."
"F as in fat: How obesity threatens American's future 2011," a report from the Trust for America's Health (TFAH)
and the Robert Wood Johnson Foundation (RWJF), shows that the problem is greatest in the South, which has nine
of the 10 states with the highest adult obesity rates. Mississippi holds the dubious title of state with the highest adult
obesity rate, for the seventh year in a row, and obesity has grown fastest in Alabama, Oklahoma, and Tennessee.
For the first time, the report looks at how obesity levels have altered over the past 20 years; two decades ago, no state
had an obesity rate above 15%, whereas now, 12 states have rates above 30% (even just four years ago, only one state
had a rate above 30%). Two out of three states have obesity rates over 25%; just one, Colorado, has a rate lower than
20%.
"Today, the state with the lowest obesity rate would have had the highest rate in 1995," says Dr Jeff Levi (executive
director, TFAH) in a statement [2]. "There was a clear tipping point in our national weight gain over the past 20 years,
and we can't afford to ignore the impact obesity has on our health."
In terms of childhood and adolescent obesity, more than one-third of children aged 10 to 17 are obese (16.4%) or
overweight (18.2%), and Mississippi again tops the poll, with a rate of 21.9%, with nine other states, plus DC, having
childhood obesity rates >20%.
The report points out the inverse relationship between educational attainment and income and obesity and invites
readers to "imagine what it is like to live in a neighborhood where there are no supermarkets, sidewalks, or
community playgrounds, where being outside may not be safe, and joining a gym is not an option."
The aim is to help promote change by advocating a number of policies that are backed by scientific research and
likely to make an impact quickly, particularly for those people whose options have been most limited. These include
initiatives aimed at improving access to affordable healthy foods and safe places for children to walk, bike, and play
in the communities hardest hit by the epidemic and with the fewest resources.
Late Thursday, the American Heart Association issued a statement highlighting the TFAH report, calling the rise in
obesity rates "astonishing" and calling on Americans "to recognize the severity of the obesity crisis" and "the need for
collective action among food manufacturers, restaurants, government and consumers to change the direction we are
headed."
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NSAID’s
July 14, 2011 (Gainesville, Florida) — Older patients with hypertension and coronary artery disease who use nonsteroidal antiinflammatory drugs (NSAIDs) chronically for pain are at significantly increased risk of cardiovascular events, a new post hoc analysis
from the International Verapamil-Trandolapril Study (INVEST) demonstrates [1]. The research is published in the July 2011 issue
of the American Journal of Medicine.
"We found a significant increase in adverse cardiovascular outcomes, primary driven by an increase in cardiovascular mortality," lead
author Dr Anthony A Bavry (University of Florida, Gainesville) told heartwire. "This is not the first study to show there is potential
harm with these agents, but I think it further solidifies that concern."
He says the observational study, conducted within the hypertension trial INVEST, is particularly relevant to everyday practice because
the patients included were typical of those seen in internal-medicine, geriatric, and cardiology clinics--they were older, with
hypertension and clinically stable CAD.
Bavry and colleagues were not able to differentiate between NSAIDs in the study--most people were taking ibuprofen, naproxen, or
celecoxib--and he says until further work is done, he considers the risks of NSAIDs "a class effect," and their use should be avoided
wherever possible.
I try to get them to switch to an alternative agent, such as acetaminophen.
However, "Patients should not terminate these medicines on their own," he says. "They should have a discussion with their physician.
When I see patients like these taking NSAIDs I will have an informed discussion with them and tell them there is evidence that these
agents may be associated with harm. I try to get them to switch to an alternative agent, such as acetaminophen, or if that's not possible
I at least try to get them to reduce the dose of NSAID or the frequency of dosing. But ultimately, it's up to them if this potential risk is
worth taking depending upon the indication for their use."
Chronic NSAID Use More Than Doubles CV Mortality
Within the large cohort of more than 22 000 patients in INVEST, Bavry and colleagues identified patients who reported taking NSAIDs
at every follow-up visit and termed them chronic users (n=882). Most often, patients were taking these agents for conditions such as
rheumatoid arthritis, osteoarthritis, and lower back pain, Bavry said.
They compared the chronic NSAID users with those who only intermittently (n=7286) or never (n=14 408) used NSAIDs over an
average of 2.7 years and adjusted the findings for potential confounders.
The primary outcome--a composite of all-cause death, nonfatal MI, or nonfatal stroke--occurred at a rate of 4.4 events per 100 patientyears in the chronic-NSAID group vs 3.7 events per 100 patient-years in the nonchronic group (adjusted hazard ratio 1.47; p=0.0003).
As noted by Bavry, the end point was primarily driven by a more than doubling in the risk of death from CV causes in the chronicNSAID group compared with never or infrequent users (adjusted HR 2.26; p<0.0001).
The association did not appear to be due to elevated blood pressure, the researchers say, because chronic NSAID users actually had
slightly lower on-treatment BP over the follow-up period.
They note that a recent American Geriatrics Society panel on the treatment of chronic pain in the elderly recommends acetaminophen
as a first-line agent and suggests that nonselective NSAIDs or COX-2 inhibitors be used only with extreme caution. "Our findings
support this recommendation," they state.
Bavry added: "We do need more studies to further characterize the risks of these agents, which are widely used and widely available,
and perhaps the risks are underappreciated. We are working on the next level of studies to try to identify which are the most harmful
agents."
Algorithm for Treatment of Hypertension in the Elderly
ACEI indicates angiotensin-converting enzyme inhibitor; ALDO ANT, aldosterone antagonist; ARB, aldosterone receptor
blocker; BB, beta blocker; CA, calcium antagonist; CAD, coronary artery disease; CVD, cardiovascular disease; DBP,
diastolic blood pressure; RAS, renin-angiotensin system; SBP, systolic blood pressure; and THIAZ, thiazide diuretic.
Breast Cancer and OCs: Still Worried
After All These Years?
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Two studies confirm that oral contraceptives are not associated with breast
cancer–specific or all-cause mortality.
Epidemiologic studies have yielded reassuring findings that oral
contraceptives (OCs) do not raise risk for developing breast cancer (JW
Womens Health Aug 20 2002). To evaluate risk for all-cause or breast cancer–
related death in women with invasive breast cancer who used OCs,
investigators assessed mortality of 4565 participants in the Women's
Contraceptive and Reproductive Experiences (CARE) Study (a populationbased case-control study) and 3929 participants in the California Teachers
Study (CTS; a cohort study).
No associations were observed between OC use and breast cancer–specific
mortality in the CARE study (828 breast cancer deaths; median follow-up, 8.6
years) or the CTS (261 breast cancer deaths; median follow-up, 6.1 years). In
addition, no association was observed between OC use and all-cause mortality
(CARE relative risk, 1.01; CTS RR, 0.84). Lower risk for all-cause death (but
not breast cancer–related death) was observed in those CTS participants who
used OCs for 10 years (RR, 0.67); however, no trend for decreasing risk with
increasing OC duration was observed (P for trend, 0.22).
Don't Miss the New AHA
Recommendations on Triglycerides
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A new scientific statement raises the threshold for pharmacologic treatment of hypertriglyceridemia.
The following was published as a "Voices" blog on CardioExchange, an online forum for cardiology
news and discussion. The blog prompted a lively conversation, which you can access and join by
registering for CardioExchange.
I've been surprised at the lack of fanfare surrounding the American Heart Association's recently
published scientific statement on triglycerides and cardiovascular disease (CVD). The attention it did
receive focused on the lower fasting triglyceride level that is now considered optimal: <100 mg/dL.
In my opinion, the real headline was the committee's important statements in support of less drug
treatment — in particular, the recommendation for a substantial increase in the triglyceride level that
should trigger consideration of pharmacologic therapy.
After a careful review of the recent literature, the committee concluded that pharmacologic therapy
should not be started until a patient's fasting triglyceride level is 500 mg/dL (in contrast to the Adult
Treatment Panel's recommendation of 200 mg/dL). See the figure, which also appears on page 2308
of the AHA statement.
The AHA committee also explicitly acknowledges (on page 2297) that "the independence of
triglyceride level as a causal factor in promoting CVD remains debatable. Rather, triglyceride levels
appear to provide unique information as a biomarker of risk, especially when combined with low
HDL-C and elevated LDL-C." This clear statement — together with the new, higher threshold for
initiating drug treatment — represents a remarkable change.
Meanwhile, on April 20, Abbott announced that sales of its flagship fenofibrate drugs increased by
28% in the first quarter.
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Cumulative Antibiotic Exposure Is Associated
with Risk for C. difficile Infection
In a retrospective study among hospitalized patients, higher cumulative dose, number,
and duration of antibiotics were independently associated with greater risk.
Antibiotic therapy is a major risk factor for Clostridium difficile infection (CDI), but
little is known about the effect of cumulative exposure. To explore this issue,
researchers performed a retrospective cohort study involving adults who were
hospitalized at a Rochester, New York, medical center in 2005 and received antibiotics
for 2 consecutive days during their stay.
For each day of antibiotic exposure, the total dose of each agent was calculated. Daily
doses were standardized according to the WHO Defined Daily Dose system. The
number of different antibiotics and the duration of exposure were also calculated.
A total of 10,154 hospitalizations involving 7792 unique patients met study criteria. The
incidence of CDI in this group was 4.3 per 10,000 patient-days. Factors significantly
associated with increased CDI risk included older age, gastrointestinal procedures, HIV
infection, history of CDI, higher chronic disease score, longer length of stay, and receipt
of antacid therapy, including proton-pump or histamine-2 inhibitors. In addition, CDI
risk rose, in a dose-dependent manner, with increases in cumulative dose, number, and
days of antibiotics. Risk was 7.8-fold higher in patients with >18 antibiotic days than in
those with <4 days and 9.6-fold higher in patients who received five or more antibiotics
than in those who received only one. Intravenous cephalosporins, β-lactamase inhibitor
combinations, sulfa drugs, fluoroquinolones, and vancomycin were all associated with
an increased risk for CDI.
Does the HbA1c Criterion for
Prediabetes Predict Incident Diabetes?
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Measuring both fasting glucose and glycosylated hemoglobin levels might be the best
method.
The American Diabetes Association recently added a new criterion for diagnosis of
prediabetes — glycosylated hemoglobin (HbA1c) level of 5.7% to 6.4%. To evaluate this
new criterion, Japanese investigators studied 6241 people who had five or six
consecutive annual health examinations that included measurements of fasting glucose
and HbA1c levels.
At their baseline examinations, 2092 patients were identified as prediabetic: 60% by
impaired fasting glucose (IFG; 100–125 mg/dL) alone, 20% by HbA1c alone, and 20%
by both tests. During a mean 4.7-year follow-up, 338 patients progressed to diabetes, of
whom 292 (86%) had been identified as prediabetic at baseline: 32% by IFG alone, 9%
by HbA1c alone, and 46% by both tests. Both IFG alone and HbA1c alone predicted
incident diabetes equally strongly, with multivariate-adjusted hazard ratios of about 6,
compared with that for baseline normoglycemia. Patients who were prediabetic by both
criteria at baseline were 32 times more likely to progress to diabetes than those who
were normoglycemic.
Comment: These results are similar to those from a U.S. data set (Diabetes Care 2010;
33:2190). Impaired fasting glucose and HbA1c measure different aspects of dysglycemia
and, together, provide more sensitive and specific prediction of excess risk for diabetes
than does either one alone. However, whether this accuracy improves clinically
meaningful long-term outcomes remains unclear.
The Latest Word on Pot and
Susceptibility to Psychosis
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A meta-analysis indicates a specific association between cannabis use and earlier onset of psychosis.
Marijuana evokes psychotic-like symptoms in susceptible individuals (see JW Psychiatry Mar 14
2011), and cannabis use may be associated with an earlier age of onset of psychotic illness. But does
marijuana cause psychosis, or are the people who are destined to become psychotic more likely to
use the drug? With more than 16 million regular pot smokers in the U.S., the question is important.
This meta-analysis of 83 studies of the age at onset of psychosis involved 8167 psychosis patients
who used psychoactive substances and 14,352 nonusing psychosis patients.
The results confirmed that the age at onset of psychosis was almost 3 years earlier in cannabis users
than in nonusers. Alcohol use was not significantly associated with earlier onset of psychosis. Studies
with a higher percentage of cannabis users reported an earlier mean age at psychosis onset. The
association was not explained by sex, schizophrenia versus affective psychosis, study methodology,
or, to a lesser extent, patient age at the time of the study.
Comment: Because alcohol use was not associated with a younger age at onset of psychosis, the
results do not suggest that people who are going to develop psychosis just start using drugs earlier
than people who are less vulnerable to psychosis. Still, it is not known whether people who would
not otherwise become psychotic might develop a chronic psychosis after prolonged cannabis use, as
has been noted with amphetamine use. Also unknown is whether the risk results from a primary toxic
effect, from an interaction of cannabis with dopamine metabolism or with an intracellular signal, or
from an effect of the drug on brain maturation in adolescents. Regardless of pathogenesis, even if a
psychotic illness is to develop anyway, avoiding marijuana may delay its onset or reduce its severity.
Parenteral Nutrition in ICU
Patients: What's the Rush?
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Delaying intravenous nutrition for 1 week led to fewer infectious complications, shorter length of
stay, and lower hospital costs than did early initiation.
Guidelines differ substantially in their recommendations about when to start parenteral nutrition in
critically ill patients; these guidelines are based primarily on expert opinion. To evaluate
prospectively the optimal timing of nutritional support, investigators in Belgium randomized 4640
nutritionally at-risk patients in the intensive care unit (ICU; ~85% surgical patients, including 60%
who underwent cardiac surgery) to receive early initiation (ICU day 3) or late initiation (ICU day 8)
of parenteral nutrition. The study was not blinded, but allocation was concealed.
Although no differences were noted in mortality (ICU, in-hospital, or 90-day) between the groups,
the late-initiation group had significantly shorter lengths of stay (LOS) in the ICU (3 vs. 4 days) and
in the hospital (14 vs. 16 days); fewer infections, including fewer lung, bloodstream, and wound
infections (22.8% vs. 26.2%, number needed to treat [NNT], 29); shorter mean duration of
mechanical ventilation; and lower costs (~US$1600 less per patient). Surprisingly, surgical patients
in the late-initiation group for whom early enteral nutrition was contraindicated benefited
substantially in lower infection rate (30% vs. 40% for similar early-initiation patients; NNT, 10) and
shorter ICU LOS.
Comment: This well-designed study reveals that the early routine administration of parenteral
nutrition in critically ill, nutritionally at-risk patients leads to worse outcomes. Delaying parenteral
nutrition for at least 1 week should be standard practice for surgical ICU patients. Although this
study included relatively few medical ICU patients (~500), this conclusion also can be reasonably
applied to such patients, unless new evidence becomes available.
First-Trimester SSRI Exposure
and Congenital Anomalies
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Specific antidepressants are associated with risk for cardiovascular or neural-tube defects in a
population-based study.
Studies have only inconsistently linked cardiovascular anomalies with first-trimester exposure to
selective serotonin reuptake inhibitors (SSRIs). The very low base rates of these anomalies require
researchers to use large samples to detect statistically significant differences. The current researchers
examined the issue in a retrospective study using Finnish national registries.
Data included pregnancies ending in live birth, stillbirth, or termination due to severe fetal anomaly
between 1996 and 2006. SSRI exposure was defined as at least one purchase of an SSRI in the month
before pregnancy or in the first trimester. SSRI-exposed women were less likely to be married than
nonexposed women, twice as likely to smoke or to have a chronic medical condition, and 20 times
more likely to have purchased other psychiatric medications.
Overall, after adjustment for confounders such as maternal age, diabetes, and purchase of other
psychiatric drugs, major anomalies were not more common among the 6976 offspring exposed to
SSRIs than among the 628,607 nonexposed offspring. In adjusted analyses, significant associations
existed between fluoxetine and both overall cardiovascular anomalies (2.04% vs. 1.29% without
SSRI exposure) and ventricular septal defects (1.43% vs. 0.87%); between paroxetine and right
ventricular outflow defects (0.31% vs. 0.07%); and between citalopram and neural tube defects
(0.29% vs. 0.09%). Prevalence of fetal alcohol spectrum disorders was higher with SSRI exposure
than with no exposure (0.12% vs. 0.012%).
Comment: Even in this large, population-based study, anomalies were rare, making it difficult to
reach definite conclusions. Still, the study gives further evidence of associations between SSRIs and
at least cardiovascular anomalies, and clinicians must inform patients of these potential risks. Within
the informed consent process, weighing these risks against those of untreated depression is essential.
Clinicians should also address their patients' smoking and alcohol use and should avoid multiple
psychiatric prescriptions during pregnancy.
A 2008 study in JAMA found that
cancer patients who had end-oflife discussion with a health care
professional were less likely to
be:
A) Resuscitated
B) On a ventilator
C) In the intensive care unit
D) All the above
Answer
• D) All the above
Which of the following is the
more effective interview structure
for eliciting patients' end-of-life
concerns?
A) Tell-ask-tell
B) Ask-tell-ask
Answer
• B) Ask-tell-ask
When interviewing a patient
during an end-of-life
conversation, it is recommended
that the physician not allow more
than 5 to 7 sec of silence between
questions and responses.
A) True
B) False
Answer
• B) False
Which of the following is not one
of the criteria for a major
depressive episode?
A) Feeling of helplessness
B) Weight loss or gain
C) Anger
D) Decreased energy
Answer
• C) Anger
Which of the following statements about
depressive symptoms is true?
A) Not considered the norm for
terminally ill patients
B) Occur in the majority of patients
receiving palliative care
C) Occur in >75% of patients with
advanced cancer
D) None of the above
Answer
• A) Not considered the norm for terminally
ill patients
Depression is often _______ at
the end of life.
A) Overdiagnosed and
overtreated
B) Underrecognized and underor untreated
Answer
• B) Underrecognized and under- or untreated
Which of the following is not
considered a risk factor for
depression at the end of life?
A) Poorly controlled pain
B) Treatment with corticosteroids
C) Older age
D) History of substance abuse
Answer
• C) Older age
All the following are
characteristics of grief and not of
depression, except:
A) Focus on loss
B) Having specific guilt or regret
C) Emotions that come in waves
D) Preference for isolation
Answer
• D) Preference for isolation
Choose the incorrect statement about dignity
therapy for treatment of depression in patients
receiving palliative care.
A) Targets psychosocial and existential
distress
B) In a recent study, achieved high patient
satisfaction rating
C) Shown to be effective in improving sense
of dignity, but had no effect on depressive
symptoms
D) Shown to improve sense of purpose and
meaning
Answer
• C) Shown to be effective in improving
sense of dignity, but had no effect on
depressive symptoms
Which of the following statements about
psychostimulant therapy for the
treatment of depression in hospice
patients is incorrect?
A) Often poorly tolerated in this
population
B) Has rapid effect
C) Can counteract opioid-induced
sedation
D) May provide adjuvant analgesia
Answer
• A) Often poorly tolerated in this population
The measurement of which of the
following cardiac biomarkers is
recommended as part of the early risk
stratification of a patient with suspected
acute coronary syndrome (ACS)?
A) Creatine kinase-myocardial band
B) Brain natriuretic peptide
C) Troponin I or T
D) Myoglobin
Answer
• C) Troponin I or T
The 2007 American College of
Cardiology/American Heart Association
(ACC/AHA) Class I recommendations for
initial management and anti-ischemic therapy
for ACS include all the following, except:
A) Bed rest
B) Continuous electrocardiography (ECG)
monitoring
C) Intravenous (IV) nitroglycerine
D) Supplemental oxygen (O2) in all patients
Answer
• D) Supplemental oxygen (O2) in all patients
Which glycoprotein (GP) IIb/IIIa
inhibitor is generally
contraindicated as upstream
therapy for ACS and indicated
only if there is no delay in taking
the patient to the cardiac
catheterization laboratory?
A) Abciximab
B) Eptifibatide
C) Tirofiban
Answer
• A) Abciximab
The antithrombotic agent
_______is associated with a
lower rate of bleeding but
requires that patients be
pretreated with clopidogrel.
A) Enoxaparin
B) Fondaparinux
C) Bivalrudin
D) Unfractionated heparin
Answer
• C) Bivalrudin
A conservative treatment strategy
for ACS is recommended for:
A) All men with low-risk features
B) All women with low-risk
features
C) Almost all women, whether
low or high risk
Answer
• B) All women with low-risk features
There is a huge overlap of
cholesterol levels in people with
and without coronary heart
disease (CHD).
A) True
B) False
Answer
• A) True
The National Cholesterol Education
Program (NCEP) Adult Treatment Panel
(ATP) III 2004 update recommends a
therapeutic goal of LDL<70 mg/dL for
"very high risk patients," defined as
those with:
A) Established coronary artery disease
plus multiple risk factors
B) Severe and poorly controlled risk
factors
C) ACS
D) All the above
Answer
• D) All the above
In a recent cost analysis of lipidlowering therapy, which statin
regimen was found to achieve the
greatest reduction in LDL?
A) Atorvastatin 80 mg/day
B) Simvastatin 80 mg/day
C) Rosuvastatin 40 mg/day
D) Simvastatin 40 mg/day
Answer
• C) Rosuvastatin 40 mg/day
Choose the incorrect statement about
statin intolerance.
A) Patient complaints about statins in
clinical practice higher than reported in
clinical trials
B) Muscle aches usually due to statin
toxicity
C) Rhabdomyolysis extremely rare
D) True toxicity greater at higher doses
Answer
• B) Muscle aches usually due to statin
toxicity
After the starting dose, each time
a patient's statin dose is doubled,
it provides an additional _______
reduction in LDL.
A) 3% to 4%
B) 6%
C) 10% to 12%
D) 18%
Answer
• B) 6%
Introductory remarks:
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physicians generally make sense of situations through biomedical or scientific approach
however, most people make sense of situations and handle major decision making through narrative
having patients relate their “stories” and express desired outcomes represents different approach to
medicine
physician’s role often involves giving patients information
particularly in area of severe end-stage illness (where medical options limited), information relayed
often includes facts patients would rather not hear (least effective way to share information)
more effective to engage in dialogue that helps patient and family understand where treatment of
disease ends and natural fate of all human beings (ie, death) begins; having ongoing relationship
with patient provides trust and intimacy necessary for this conversation
end-of-life conversations known to have tremendous effect on patient choices (2008 study in JAMA
found cancer patients who had end-of-life discussion with health care professional 8 times less likely
to be resuscitated
7 times less likely to be on ventilator
3 times less likely to be in intensive care unit [ICU], and in hospice longer and
Earlier
bereavement of surviving caregivers much less severe)
taking on responsibility of having discussion takes considerable courage and involves sharing both
positive and
negative emotions with patients and their families
Determining when to have discussion
• see patient and read his or her chart
• perform physical examination
• if, in your opinion, it would not be
surprising for patient to die within 1 yr,
professional responsibility requires that you
discuss type of care patient would want if
he or she became diminished
Essential Conversation Skills
• Set up “safe space” for discussion
• studies of physician-patient communication have shown patients
commonly do not take lead in discussing preferences
• Talking within concept of paradox
• paradox—facts that appear contradictory although actually compatible
• Paradoxes in medicine—life and death (ie, cells start deteriorating at
35 yr of age
• after that, “living and dying at same time”)
• certainty and uncertainty (physicians try to limit uncertainty through
accumulation of information
• however, when dealing with severely ill people, more information not
necessarily more helpful)
• explain state of uncertainty and palliative care physician’s role in
determining family’s important concerns, needs for information, and
preferences
Setting up structure of interview
• most common interview structure for physicians is “tell-ask-tell”
• in biomedically decision-based discussion, patient typically asks
questions about biomedicine and decisions only
• instead of telling patient, ask how patient sees his or her situation
• patient’s reply provides clues to questions that will elicit “deeper”
issues
• speaker generally finds that he has information necessary to best serve
patient as physician by third question and response
• silence—average physician can tolerate silence from patient for more
than 7 sec before “rescuing” him or her;
• however, speaker suggests that longer interval (eg, up to 60 sec)
• appropriate when asking patient facing mortality about his or her
greatest fears
• in this type of interviewing, silence is powerful tool
Patient cues
• shown to be elicited in interviews lasting
>15 min
• represent powerful emotional statements
(either verbal or nonverbal)
• can be followed by “continuer” or
“terminator” (eg, terminator attempts to
move crying patient toward decision)
• speaker advocates being continuer (show
patience and ask patient to share his or her
thoughts and feelings)
Case example
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68-yr-old man with advanced lung cancer
had just been transferred from intensive care unit (ICU)
family informed of patient’s dire prognosis
patient and family initially in denial
through conversation interview techniques previously
described, speaker able to engage in narrative with family
and allow them to express hidden concerns and fears
• this enabled family to move from denial
• to understanding, which allowed resolution of fears and
gave direction to patient’s end-of-life care, based on his
stated desires (using evidence-based best practice
approach)
Cultural variations in physician-patient communication
• ask patients whether they would prefer that
information be given to them or to their
families
• have family members share important
values and cultural beliefs about disease
and/or death before starting discussion and
interview process
Depression end of life
• symptom, episode, or disorder; Diagnostic and
Statistical Manual of Mental Disorders, 4th Edition
(DSMIV)
• criteria for major depressive episode (MDE)—
• depressed mood or diminished interest or pleasure, plus 4
of following (feeling helpless, hopeless, worthless, or
• Guilty
• indecision or poor concentration
• suicidal ideation
• weight loss or gain
• insomnia or hypersomnia
• Decreased energy
• psychomotor retardation or agitation) during significant
portion of day over 2-wk period
Case example
• 89-yr-old white man
• prostate cancer diagnosed 14 yr
previously
• had metastasis to spine and lost ability to
walk, with debulking surgery performed 6
mo before visit
• Symptoms at presentation—depressed mood
• feeling hopeless and helpless
• decreased appetite and energy (symptoms
confounded by patient’s physical issues)
• suicidal ideation
Depression in palliative care
• somatic symptoms often not helpful when assessing for depression in
this setting
• Focus on cognitive and emotional symptoms (dysphoria, despair,
and/or sadness
• Anhedonia
• worthlessness, helplessness, and/or hopelessness
• excessive guilt
• loss of self-esteem
• desire for hastened death)
• paranoia does not necessarily indicate depression (possibly delirium)
• depression represents treatable form of suffering
• anger not criterion for MDE, but can be psychologic symptom
requiring intervention
• prevalence—depressive symptoms occur in 42% of patients receiving
palliative care and 58% of patients with advanced cancer (ie, not
“normal” for these patients
• 15% meet criteria for MDE)
Recognition
• depression often misdiagnosed or
underrecognized (in study of 2700 hospice
patients, depression recognized in only 10%
of home-care patients and 14% of
inpatients)
• often mis-, under-, or untreated at end of life
Consequences
• untreated, depression associated with
poor prognosis and causes suffering
• can undermine self-esteem, worsen medical
illness and quality of life, lengthen inpatient
stays, and interfere with preparations for
death (ability to make decisions, understand
situation, interact with caregivers and loved
ones, or reach final goals)
Assessment for depression
• typical medical assessment
• Requires good interview, family observations, review of risk factors,
and thorough medical examination
• if assessment difficult, consult with mental health professional
• Initial assessment
• determine desired outcomes for patient and context of symptoms (eg,
medical illness, sudden loss, anniversary of spouse’s death)
• Screening for depression
• 2 questions to ask—over past 2 wk, has patient 1) ever felt “down,”
depressed, or hopeless, or 2) felt little pleasure or interest in doing
things
• positive answer to either or both questions has 96% to 100% sensitivity
and 57% to 100% specificity
• Study showed depression screening not burdensome for either staff
administering questions or for patients
Risk Factors
• Risk factors for depression at end of life or in palliative
care
• poorly controlled pain or other symptoms
• progressive physical impairment
• advanced disease
• medications (steroids; chemotherapeutics;
• benzodiazepines)
• particular diseases (eg, pancreatic, breast, or lung cancer,
metastases to nervous system)
• younger age
• spiritual pain
• risk factors in general population (previous or family
history of depression; social stressors; suicide attempts;
substance use)
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Differentiate depression from
delirium and dementia
delirium (particularly hypoactive)
dementia (characterized by changes in cognitive function
depression not typically associated with cognitive impairment)
adjustment disorders (occur within 3 mo of stressor and resolve within 6 mo if stressor removed)
Grief, Grief vs depression
grief—identifiable loss
focus on loss; emotions come in waves
fluctuating ability to feel pleasure
closeness of others reassuring
relatively stable self-esteem
specific guilt or regret
thoughts of wanting to be with deceased
“nonbizarre” hallucinations
depression—loss may or may not be identifiable
focus on self
emotions chronic
inability to feel pleasure
isolation preferred
loss of self-esteem or feelings of worthlessness
guilt out of proportion
Active thoughts of suicide
both—hallucinations and/or delusions
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Treatment
review desired outcomes
provide nonpharmacologic and pharmacologic relief
consult mental heath professional for assistance
Psychotherapy
all physicians provide supportive psychotherapy
group therapy shown to reduce stress and mood
symptoms at end of life
existential group therapy focuses
on value and meaning as well
Dignity therapy: targets psychosocial and existential distress;
protocol of semistructured questions; transcript made of patient’s
responses (document edited, title and summary added,
and given to patient and family); in study of 100 patients,
achieved 91% satisfaction rate; patients experienced heightened
sense of dignity (76%), purpose (68%), and meaning
(67%), and increased will to live (47%), and had significantly
reduced depressive symptoms and sense of suffering
Complementary therapies
guided imagery
muscle relaxation
Hypnosis
Meditation
Massage
aromatherapy
avoidance of caffeine and alcohol
treatment of insomnia
exercise (if possible)
exposure to bright light
Pharmacologic options
• consist of usual armamentarium of >24
antidepressants with 7 different mechanisms of
action
• tricyclic antidepressants [TCAs]
• monoamine oxidase inhibitors (MAOIs)
• selective serotonin reuptake inhibitors [SSRIs]
• serotonin–norepinephrine reuptake inhibitors
[SNRIs]
• bupropion [Wellbutrin; Zyban; Aplenzin]
• mirtazapine
• trazodone
Current depression treatment guidelines (American
Psychiatric Association)
• moderate to severe depression— psychotherapy plus antidepressants
• titrate dose over weeks
• if no moderate improvement by 6 to 8 wk, adjust treatment and
monitor another 6 to 8 wk
• continue after remission for 16 to 20 wk, followed by maintenance for
1 yr
• partial response associated with poor outcomes
• Poor outcomes in hospice patients
• Sequenced Treatment Alternatives to Relieve Depression (STAR*D)
trial demonstrated 14 wk of SSRI monotherapy produces only 50%
response and 30 remission rates
• average time on hospice in United States <9 wk (median <3 wk)
• 33% of patients at speaker’s hospice die within 1 wk (insufficient time
to achieve response)
Psychostimulants
• much anecdotal and small amount of
controlled data on use in medically ill and
geriatric populations and in palliative care
• benefits—rapid effect in hours to days
• minimal adverse effects
• can be continued indefinitely
• can titrate to effect or until side effect
• Tolerance seems not to be factor
• diminish opioid-induced sedation
• may provide adjuvant analgesia
Methylphenidate (Ritalin;
Concerta; Metadate)
• starts with 5 mg in morning and if no adverse effects within 1 hr,
repeats dose at noon
• next day, increases dose to 10 mg
• in rare instances, dose increased to 15 mg, to 20 mg in extremely rare
cases (if no effect seen at this dose, response unlikely)
• response to methylphenidate—in recent study patients diagnosed with
MDE randomized to receive methylphenidate, SSRI, “other”
medication (eg, bupropion,
• mirtazapine, SNRI), or usual care
• 95% of patients who received methylphenidate responded (vs 44% of
those who received SSRI and 0% who received usual care)
• time to response—methylphenidate proved significantly faster than
SSRIs or other therapies
Selective serotonin reuptake inhibitors
• if patient already on SSRI, maximize or possibly
augment it
• prescribes SSRI if patient (or family member) has
had good response to drug in past
• can take 3 to 6 wk to produce response
• only 30% effective
• well tolerated
• requires once-daily dosing
• lower doses may be effective, but should still
titrate to effect
• check for drug-drug interactions
Other antidepressants might be helpful for
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sedation (mirtazapine or trazodone)
energy (SNRIs, bupropion)
Appetite stimulation (mirtazapine)
pain (several have data supporting use for
treatment of pain and as analgesic adjuvant)
• effects still being studied in this population
Comments
• all SSRIs approximately equally effective
• Must try 3 before finding drug that works
for patient
• Choose based on drug-drug interactions or
other side effects
Management of patient
in case example
• treated with psychotherapy and 5 mg methylphenidate in
morning and at noon
• within 24 hr, no longer met criteria for MDE (patient
engaging with family, taking phone calls from friends, and
sitting outside)
• did not change goals for end-of-life care
• (ie, no antibiotic treatment for aspiration pneumonias)
• 7 day later, patient developed pneumonia and died
• conclusion—treatment worthwhile despite short period
during which patient enjoyed benefits
• returning patient to more typical mental state before death
has lasting beneficial effect on surviving family members
and caregivers
“Normal” cholesterol
• average total cholesterol for Americans 208 mg/dL
• average low-density lipoprotein (LDL) 130 mg/dL
• modern humans only adult mammals with mean LDL >80
mg/dL (and total cholesterol level double that of many
species)
• population studies have shown life expectancy 4 to 9 yr
longer if total cholesterol <200 mg/dL
• huge overlap of cholesterol levels in people with and
without coronary heart disease (CHD), received aspirin
within range of 150 to 300 mg/dL (>300 mg/dL
synonymous with CHD, but seen in 10% of that patient
population)
Can LDL be too low?
• no cholesterol treatment trials have demonstrated
levels can get too low
• Results of trials on lowering LDL with statin therapy
• Data from primary prevention trials show rate of CHD
events drops to 0% when LDL lowered to 57 mg/dL, while
data extrapolated from secondary prevention trials show
rate drops to 0% when LDL lowered to 30 mg/dL
(suggesting secondary prevention requires even lower
LDL)
• in primary and secondary prevention trials, subgroup of
patients with DM had higher risk for CHD events if
untreated, but greater reduction in risk with statin
intervention than patients without DM
Study of the Effectiveness of Additional Reductions in
Cholesterol
and Homocysteine (SEARCH) trial
• 12,000 patients with history of MI
randomized to 80 or 20 mg/day simvastatin;
during
• 6.5-yr follow up, 80-mg therapy achieved
• mean LDL of 83 mg/dL vs 97 mg/dL with
20-mg therapy
• rate of major vascular events 24.5% vs
25.7% (6% reduction in relative risk and
1.2% reduction in absolute risk)
2010 meta-analysis of cholesterol treatment trial
participants
170,000 participants from statin trials that included
1000 patients and had 2 yr follow up; focused on
more vs less intensive statin treatment
conclusions—every 38 to 39 mg/dL lowering of LDL
associated with 14% to 15% reduction in vascular
mortality (with no difference in nonvascular death
or risk for cancers)
LDL reduction achieved through more intensive
statin regimen produces significant further
reduction in risk for major vascular events
LDL goal recommendations
• National Cholesterol Education Program (NCEP) Adult
Treatment Panel (ATP) III 2004 update—
• LDL <100 mg/dL overall therapeutic goal
• for very high-risk patients (defined as having established
CAD plus multiple risk factors [RFs], or severe and poorly
controlled RFs, or multiple RFs of metabolic syndrome, or
ACS), therapeutic goal LDL<70 mg/dL
• Intensity of drug therapy should be sufficient to achieve
30% to 40% reduction in LDL
• 2006 AHA/ACC update—similar recommendations for
high-risk patients, but states intensity of therapy should be
sufficient to achieve 50% reduction in LDL
• 2011 AHA recommendations for CAD prevention in
women—LDL<100 mg/dL overall goal
• LDL <70 mg/dL for very high-risk women
Economics of statin therapy
• recent cost-effectiveness analysis suggests
atorvastatin 80 mg/day will become most
cost-effective therapy once drug becomes
generic
• percentage of LDL reduction—atorvastatin
80 mg/day achieves 50% reduction
• rosuvastatin 40 mg/day, 56% reduction
• simvastatin 80 mg/day, 45% reduction
• simvastatin 40 mg/day, 37% reduction
Statin intolerance and/or
nonadherence
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many complaints from patients (incidence 5%-10% in clinical practice; higher than
reported in clinical trials)
however, studies show muscle aches usually not due to statin toxicity
rhabdomyolysis extremely rare
true toxicity greater at higher doses
Management strategies
clarify whether symptom truly began and sustained on new drug
identify barriers to adherence (eg, cost; lack of education about necessity of continuous intervention)
If patient complains of muscle soreness—measure creatine kinase (CK)
if not elevated, myopathy not statin-related
if <5 times ULN, continue therapy and monitor patient
modify other RFs (eg, physical activity; hypothyroidism, alcohol consumption)
change to less lipophilic drug
try lower dose, alternate-day or weekly dosing
can combine lower-dose statin with another lipid-lowering agent (eg, bile acid binding agents,
niacin, fibrates)
insist on lifestyle management
can consider vitamin D or coenzyme Q10 to help manage complaints (no strong supporting data)
stop statin if patient refuses to continue, symptoms intolerable, or CK >10 times ULN
Can LDL of 70 mg/dL
be achieved
• with 1 exception, no clinical trial on lowering LDL has achieved 70
mg/dL (in early 2000s, very few patients on treatment lowered LDL to
<100 mg/dL)
• first-dose effect (bulk of lowering with initial dose of whatever statin
used)
• need higher-efficacy statins
• may need higher doses (but be careful of toxicity)
• might want to shift goal to 30% to 50% reduction in LDL rather than
actual target number
• “rule of 6”—after starting dose, each time statin doubled, only
additional 6% reduction in LDL
• even with 22% reduction in relative risk for cardiovascular (CV)
events seen in Treating to New Targets (TNT) study with atorvastatin,
much greater residual risk remained
Steps for lowering residual risk
• ongoing emphasis on lifestyle
Modification
• improve all lipid targets (pay particular
attention to high-density lipoproteins [HDL]
and triglycerides)
• combination therapy useful with good
monitoring
• Improve other RFs (eg, glycemic and blood
pressure control)
Who needs LDL of 70
mg/dL?
• 55-yr-old who has just experienced STEMI
(yes)
• 60-yr-old with hypertension and DM (not
• Necessarily would need overt CHD and
uncontrolled RFs)
• 25-yr-old with familial hypercholesterolemia
(patient at extremely high risk, multiple drug
treatment indicated to lower LDL as much as
possible, but will not be able to achieve 70 mg/dL)
• 80-yr-old with stroke (yes)
Questions and Answers
• Should LDL be lowered to 70 mg/dL regardless of patient’s HDL
level? Yes
• this is about targeting LDL
• HDL should also be evaluated
• any patient being considered for statin intervention must have baseline
lipid profile, so will know HDL level as well
• Role for ezetimibe (Zetia)? Unclear
• in combination with statins, does achieve additional lowering of LDL
• however, current clinical trials have not demonstrated additional
benefit
• Advantage to testing for apolipoprotein E (ApoE)4 genotype (less
responsive to statins)?
• not yet ready for use in clinical practice
• Is there role for measuring small particles? advocates claim
additional benefit
• however, speaker usually does not do submolecular assessments
(expensive and do not alter treatment in most cases)