Download 1 - RCRMC Family Medicine Residency

Aging Patient and AAFP
Which of the following statements
about dementia and depression is
true?
A) Dementia is an etiology but
depression is a syndrome
B) Dementia is a syndrome but
depression is an etiology
C) Dementia and depression are
syndromes, not etiologies
D) Dementia and depression are
etiologies, not syndromes
Answer
• C) Dementia and depression are syndromes,
not etiologies
Cognitive impairment can be a
feature of a depressive episode. It
_______ fully remit(s) with
treatment.
A) Always
B) May not
Answer
• B) May not
Frontotemporal dementia
tends to occur at a younger
age than Alzheimer
disease.
A) True
B) False
Answer
• A) True
All the following are clinical
clues to depression in an older
patient who denies sadness or
depression, except:
A) Memory complaints
B) Hopelessness
C) Anxiety
D) Increased sexual interest
Answer
• D) Increased sexual interest
If unsure whether an older patient has
depression, dementia, or both, it is
recommended to treat depression first and
monitor for a response, and to start treatment
with:
A) Serotonin-norepinephrine reuptake
inhibitors (SNRIs)
B) Selective serotonin reuptake inhibitors
(SSRIs)
C) Tricyclic antidepressants
D) Benzodiazepines
Answer
• B) Selective serotonin reuptake inhibitors
(SSRIs)
It is estimated that by 2020,
approximately _______ of
drivers will be >65 yr of age.
A) 25%
B) 40%
C) 50%
D) 66%
Answer
• A) 25%
Elderly adults have the ______
crash rate per driver of any age
group but the _______ rate per
miles driven.
A) Highest; lowest
B) Lowest; second lowest
C) Lowest; second highest
D) Highest; second highest
Answer
• C) Lowest; second highest
Tests for dementia
________ good
predictors of driving
performance.
A) Are
B) Are not
Answer
• B) Are not
Choose the incorrect statement about the
Assessment of Driving-Related Skills
(ADReS) instrument.
A) Structured series of in-office tests for
evaluating drivers at risk
B) Assesses vision, cognition, and
motor strength
C) Functions as a guide but is not
predictive
D) Both extremely sensitive and specific
Answer
• D) Both extremely sensitive and specific
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Trail A and B
Trail Making Test (TMT) Parts A & B
Instructions:
Both parts of the Trail Making Test consist of 25 circles distributed over a sheet of paper. In Part
A, the circles are numbered 1 – 25, and the patient should draw lines to connect the numbers in
ascending order. In Part B, the circles include both numbers (1 – 13) and letters (A – L); as in
Part A, the patient draws lines to connect the circles in an ascending pattern, but with the added
task of alternating between the numbers and letters (i.e., 1-A-2-B-3-C, etc.). The patient should
be instructed to connect the circles as quickly as possible, without lifting the pen or pencil from
the paper. Time the patient as he or she connects the "trail." If the patient makes an error, point
it out immediately and allow the patient to correct it. Errors affect the patient's score only in that
the correction of errors is included in the completion time for the task. It is unnecessary to
continue the test if the patient has not completed both parts after five minutes have elapsed.
Step 1: Give the patient a copy of the Trail Making Test Part A worksheet and a pen or
pencil.
Step 2: Demonstrate the test to the patient using the sample sheet (Trail Making Part A –
SAMPLE).
Step 3: Time the patient as he or she follows the “trail” made by the numbers on the test.
Step 4: Record the time.
Step 5: Repeat the procedure for Trail Making Test Part B.
Scoring:
Results for both TMT A and B are reported as the number of seconds required to complete the
task; therefore, higher scores reveal greater impairment.
Average Deficient Rule of Thumb
Trail A 29 seconds > 78 seconds Most in 90 seconds
Trail B 75 seconds > 273 seconds Most in 3 minutes
Timed get up and go test
• Begin timing
• Rise from a standard arm chair
• Walk to a line on the floor approximately
10 feet away from the chair
• Turn and return to the chair
• Sin in the chair again
• End Timing
Timed bet up and Go test
• Precautions and Rules
• May use a cane or walker
• Test is valid only for a person able to walk
unassisted
• Patient should be given one practice trial
and timed 3 times and average times
Scoring in Seconds
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< 10
< 20
20-29
>20
Freely mobile
Mostly independent
Variable mobility
Impaired mobility
Most people eventually
have to retire their
driver's license.
A) True
B) False
Answer
• A) True
The State of California requires
manditory reporting of all
patients diagnosed with dementia
to the DMV?
• A. Yes
• B. No
Answer
• A. Yes
A MMSE of around _____ has
been shown to have some
correlation with reduced driving
skills?
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A. 24
B. 22
C. 20
D. Less than 20
E. 18
Answer
• D. Less than 20
TREATMENT OF ALZHEIMER DISEASE
1. Which one of the following statements about the
use of acetylcholinesterase inhibitors for the
treatment of Alzheimer disease is correct?
A. Donepezil (Aricept) is more effective than other
acetylcholinesterase inhibitors for the treatment of
mild to moderate dementia.
B. The benefit may be statistically significant, but
the clinical significance is unclear.
C. It increases mortality by prolonging the QT
interval and causing sedation.
D. Memantine (Namenda) is more effective than
acetylcholinesterase inhibitors in patients with mild
Alzheimer disease.
Answer
• B. The benefit may be statistically
significant, but the clinical significance is
unclear.
Which one of the following
treatment options is appropriate
for patients with moderate to
severe Alzheimer disease?
A. Selegiline (Eldepryl).
B. An insulin sensitizer plus a
statin.
C. Vitamin E.
D. Memantine.
Answer
• D. Memantine.
Which of the following
interventions are considered
promising for the prevention of
Alzheimer disease?
A. Treatment of hypertension.
B. Vitamin E.
C. Exercise.
D. Statins.
Answer
• A. Treatment of hypertension.
• C. Exercise.
Potential Foods/Supplements
• Potential Foods/Supplements
• Axona (Accera)
• Medical food that targets metabolic
deficiencies
• Resveratrol (red wine)
• Anti-oxidant, “anti-aging”
• Curcumin (curry spice)
• Anti-inflammatory and anti-amyloid
• Caffeine
• Associated with lower risk for Parkinson’s
• Alcohol in moderation
Keeping Your Brain
Young
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Risk for brain aging
1/3 genetics
2/3 lifestyle choices
Preventing brain cell loss more effective
than repairing
Brain Healthy
Lifestyle Strategies
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Associated with a Lower Risk for
Dementia
Physical conditioning
Stress reduction
Healthy diet
Mental challenge/cognitive training
Healthy Brain Diet*
• Moderate caloric intake to avoid illnesses
associated
• with obesity
• Antioxidants
• Dietary sources
• Vitamin supplements
• Omega-3 fatty acids
• Mediterranean diet: fish, olive oil
• Avoiding animal fats
• Low glycemic index carbohydrates
Alzheimer’s Disease
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Alzheimer disease is the most common form of dementia, affecting more than one-third of Americans older
than 85 years.
It is characterized by progressive memory loss and cognitive decline. Amyloid plaque accumulation,
neurofibrillary tau tangles, and depletion of acetylcholine are among the pathologic manifestations of
Alzheimer disease.
Although there are no proven modalities for preventing Alzheimer disease, hypertension treatment, omega-3
fatty acid supplementation, physical activity, and cognitive engagement demonstrate modest potential.
Acetylcholinesterase inhibitors are first-line medications for the treatment of Alzheimer disease, and are
associated with mild improvements in cognitive function, behavior, and activities of daily living; however, the
clinical relevance of these effects is unclear.
The most common adverse effects of acetylcholinesterase inhibitors are nausea, vomiting, diarrhea, dizziness,
confusion, and cardiac arrhythmias.
Short-term use of the N-methyl-D-aspartate receptor antagonist memantine can modestly improve measures of
cognition, behavior, and activities of daily living in patients with moderate to severe Alzheimer disease.
Memantine can also be used in combination with acetylcholinesterase inhibitors.
Memantine is generally well tolerated, but whether its benefits produce clinically meaningful improvement is
controversial.
Although N-methyl-D-aspartate receptor antagonists and acetylcholinesterase inhibitors can slow the
progression of Alzheimer disease, no pharmacologic agents can reverse the progression.
Atypical antipsychotics can improve some behavioral symptoms, but have been associated with increased
mortality rates in older patients with dementia.
There is conflicting evidence about the benefit of selegiline, testosterone, and ginkgo for the treatment of
Alzheimer disease.
There is no evidence supporting the beneficial effects of vitamin E, estrogen, or nonsteroidal anti-inflammatory
drug therapy.
Recomendations
• Acetylcholinesterase inhibitors should be considered first-line therapy
for patients with mild to moderate Alzheimer disease.
• A
• Combination therapy with an acetylcholinesterase inhibitor and
memantine (Namenda) should be considered in patients with moderate
to severe Alzheimer disease.
• B
• Atypical antipsychotic agents can improve some behavioral
manifestations of Alzheimer disease but are associated with increased
mortality in older patients.
• B
• Nonsteroidal anti-inflammatory drugs, vitamin E, testosterone,
estrogen, statins, and insulin sensitizers are not recommended for the
treatment of Alzheimer disease.
• B
• Physicians should consider discontinuing treatment for Alzheimer
disease in patients who continue to decline despite maximal therapy.
• C
Prevention
• Numerous studies have assessed factors that may affect the incidence
of Alzheimer disease, such as the use of dietary supplements and
pharmacologic agents, diet, socioeconomic factors, medical conditions,
and environmental exposures.
• Although many studies have found an association, they have not
proven that the relationship is causal or that modification of these
factors reduces the risk of Alzheimer disease.
• Of the prevention strategies studied, treatment of hypertension,
consumption of omega-3 fatty acids, physical activity, and cognitive
engagement demonstrate some promise.
• However, larger randomized controlled trials are needed to further
assess these results.6–10
• A recent consensus statement from the National Institutes of Health's
State-of-the-Science Conference on Preventing Alzheimer's Disease
and Cognitive Decline concluded that the current evidence is
insufficient to support the association of any modifiable factor,
pharmacologic agent, or dietary supplement with a reduction in the risk
of Alzheimer disease
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Medications
Acetylcholinesterase inhibitors reversibly bind and inactivate the enzyme that degrades
acetylcholine, which is involved in memory.12
Donepezil (Aricept) is the only acetylcholinesterase inhibitor approved for use in all stages of the
disease.
The N-methyl-D-aspartate receptor antagonist memantine (Namenda) is approved for treating
moderate to severe disease, and is thought to prevent excitatory amino acid neurotoxicity without
interfering with the physiologic actions of glutamate, a neurotransmitter necessary for learning and
memory.
Studies of these drugs have usually assessed effectiveness using one of several scales, such as the
Alzheimer's Disease Assessment Scale for Cognition (ADAS-cog; a 70-point scale), the Alzheimer's
Disease Cooperative Study Activities of Daily Living inventory (ADCS-ADL; a 54-point scale), or
the Severe Impairment Battery (SIB; a 100-point scale).
In general, to be clinically significant (defined as a noticeable improvement by the patient or
caregiver), an increase should be at least 10 percent of the scale length (i.e., 7 points on the ADAScog, 5 points on the ADCS-ADL, or 10 points on the SIB).
ACETYLCHOLINESTERASE INHIBITORS
Acetylcholinesterase inhibitors are first-line agents for the treatment of mild to moderate Alzheimer
disease, according to existing guidelines.
Most randomized controlled trials and systematic reviews have found no notable differences in
effectiveness among the various acetylcholinesterase inhibitors.
Despite small variations in mechanisms of action, these agents have varying adverse effect profiles.
The most common adverse effects are nausea, vomiting, and diarrhea; cardiovascular and neurologic
adverse effects are comparable.
The incidence of adverse effects is directly related to the dose administered.
Rivastigmine (Exelon) patches may be better tolerated than oral rivastigmine.
Tacrine is no longer available because of safety and tolerability concerns.
Acetylcholinesterase inhibitors
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A Cochrane review concluded that in patients with Alzheimer disease,
treatment with donepezil, galantamine (Razadyne), or rivastigmine for six
months to one year resulted in slightly improved cognitive function by an
average of −2.7 points on the ADAS-cog.
Improvements in behavior and activities of daily living also have been noted
in patients treated with one of these three agents; however, none of the
medications has a large treatment effect, and the clinical significance of these
effects is questionable.
Another systematic review concluded that, despite statistical significance, the
improvement in patients with dementia taking acetylcholinesterase inhibitors
was clinically marginal (−0.1 to −5.3 points on the ADAS-cog).
Additional trials are needed to determine the benefits of long-term therapy and
whether these agents are effective in patients with moderate to severe
Alzheimer disease.
It is reasonable to discontinue treatment if there is no improvement within six
to eight weeks.
Therapy may be restarted if symptoms worsen after the medication is tapered,
because acetylcholinesterase inhibitors may be more effective for symptomatic
control than previously recognized.
MEMANTINE
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Memantine prevents excessive glutamatergic activity.
A Cochrane review concluded that memantine at a dosage of 20 mg per day over six months slightly improved
cognition (3 points on the SIB) and ability to do activities of daily living (1.3 points on the ADCS-ADL) in patients
with moderate to severe Alzheimer disease.
The effect on cognition was statistically significant in patients with mild to moderate dementia (1 point on the ADAScog) but is unlikely to have clinical significance.
A small reduction in agitation was seen in patients taking memantine.
Seventeen patients with moderate to severe Alzheimer disease would need to be treated for six months to prevent one
episode of agitation.
A meta-analysis concluded that memantine was ineffective for patients with mild Alzheimer disease, and the benefits
for patients with moderate Alzheimer disease were inconsistent.
Memantine is generally well tolerated and is often used with acetylcholinesterase inhibitors. One study randomized
patients taking donepezil for moderate to severe Alzheimer disease to receive 20 mg of memantine or placebo every
day for 24 weeks.
Patients taking memantine showed mild improvement in cognition (+0.9 points versus −2.5 points with placebo on the
SIB) and activities of daily living (−2.0 points versus −3.4 points with placebo on the ADCS-ADL). Another study
evaluated the effectiveness and safety of 20 mg of memantine per day for 24 weeks in patients already taking
donepezil, rivastigmine, or galantamine for mild to moderate Alzheimer disease.28
Adding memantine was not associated with a statistically significant improvement compared with placebo. The lack
of adverse effects was consistent with findings in other memantine monotherapy studies.13,28
Guidelines from the National Institute for Health and Clinical Excellence cite a study that found no improvement with
memantine compared with placebo in patients who had moderate to severe Alzheimer disease.
Patients taking memantine may have problems with adherence because it is typically taken twice per day. A oncedaily extended-release formulation of memantine was approved by the U.S. Food and Drug Administration in June
2010
SELEGILINE
• Selegiline (Eldepryl) is a monoamine oxidase type B
inhibitor with minimal anticholinergic effects.
• A Cochrane review analyzed 17 double-blind, randomized,
placebo-controlled trials evaluating selegiline at a dosage
of 10 mg per day for the treatment of Alzheimer disease.
• The authors concluded that cognition improved at four to
six weeks in some trials; however, there were no
differences after six weeks.
• The benefits were found primarily in two studies; other
trials did not support these findings.
• No differences in adverse effects were noted compared
with placebo.
• Currently, there is not enough evidence to recommend
selegiline for the treatment of Alzheimer disease.
ANTIPSYCHOTICS
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Antipsychotics are not approved by the U.S. Food and Drug Administration for the
treatment of Alzheimer disease, although they are commonly used to treat behavioral
symptoms.
Evidence suggests that olanzapine (Zyprexa) and risperidone (Risperdal) reduce
aggression, and risperidone reduces psychosis in patients with Alzheimer disease.
The Clinical Antipsychotic Trials of Intervention Effectiveness protocol for Alzheimer
disease assessed the effects of atypical antipsychotics on psychiatric and behavioral
symptoms.
It included 421 outpatients with Alzheimer disease and psychosis or agitated/aggressive
behavior.
Patients were randomized to receive olanzapine, quetiapine (Seroquel), risperidone, or
placebo for up to 36 weeks.
There were no clinically or statistically significant differences in functioning, care
needs, or quality of life between patients taking antipsychotics and those taking placebo.
Some clinical symptoms improved, such as anger, aggression, and paranoia.
Patients taking olanzapine experienced worsening functional ability at week 12
compared with those taking placebo.
A small randomized, double-blind, placebo-controlled trial failed to demonstrate
effectiveness of quetiapine or rivastigmine for treatment of agitation in patients with
Alzheimer disease in care facilities after 26 weeks.
At six weeks, a statistically significant decline in cognition was noted in patients taking
quetiapine compared with those taking placebo.
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ANTIPSYCHOTICS
Older patients with dementia who are treated with atypical
antipsychotics have a twofold higher mortality rate than those taking
placebo.
One study found that new use of atypical antipsychotics was
associated with an increased risk of death at 30 days both in
community-dwelling patients (hazard ratio = 1.31; 95% confidence
interval, 1.02 to 1.70) and in those living in long-term care facilities
(hazard ratio = 1.55; 95% confidence interval, 1.15 to 2.07).33
Most of those deaths were related to cardiovascular or infectious
causes, possibly because antipsychotics can prolong QT interval and
cause sedation, which may increase the risk of aspiration.
Other common adverse effects of antipsychotics include gait
disturbances and extrapyramidal effects.
Using atypical antipsychotics to treat behavioral symptoms such as
agitation in patients with Alzheimer disease generally should be
avoided because of adverse effects, although these agents may be
appropriate in some situations.
Ineffective Therapies
• Estrogen has been studied for the prevention and treatment of
dementia.
• A Cochrane review found no beneficial effect of long-term estrogen
use on cognitive function in patients with Alzheimer disease.
• Estrogen does not enhance the effects of acetylcholinesterase
inhibitors; no benefit was found when it was used in combination with
rivastigmine.
• An updated Cochrane review concluded that there is no evidence
supporting the use of vitamin E for the prevention or treatment of
Alzheimer disease, and it may be harmful in higher doses.
• Studies have demonstrated no beneficial effect of nonsteroidal antiinflammatory drugs for the treatment of Alzheimer disease.
• Statins and insulin sensitizers have not demonstrated benefit in
clinical trials in patients with Alzheimer disease.
• Systematic reviews have found no clear benefit of lecithin or acetyl-Lcarnitine
Therapies with Conflicting Evidence
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TESTOSTERONE
There is conflicting evidence on the benefit of testosterone in men with
Alzheimer disease.
Two randomized, double-blind, placebo-controlled studies demonstrated
benefit in visuospatial cognition, but it is unclear if this effect is clinically
meaningful.
A randomized, placebo-controlled trial examined the effect of 1% testosterone
gel supplementation (75 mg per day) in men with mild to moderate Alzheimer
disease over a period of six months.
No statistically significant benefits were detected, although testosterone
treatment mildly improved patients' quality of life.
A randomized, double-blind, placebo-controlled trial of men older than 65
years with limited mobility and low testosterone levels evaluated treatment
with testosterone gel or placebo.
The results showed a significantly increased incidence of adverse
cardiovascular effects in the treatment group over six months (22 versus 5
percent in the placebo group; P = .05; number needed to harm = 6).
Because of the risk of serious adverse effects and the paucity of clinically
helpful effects, testosterone therapy in men with Alzheimer disease is not
recommended.
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GINKGO
A Cochrane Review evaluated 36 studies of ginkgo for the treatment of cognitive
impairment and dementia.
All but one study used the standard ginkgo extract EGb 761, at a dosage of 80 to 600 mg
per day.
Ginkgo was not associated with a consistent, clinically significant benefit in persons
with Alzheimer disease.
A European study of 96 patients with Alzheimer disease demonstrated equal
effectiveness among a prescription ginkgo extract (240 mg per day), donepezil (5 to 10
mg per day), and a combination of the two agents.
Because ginkgo is not available as a regulated prescription product in the United States,
it is possible that the variability in dietary supplement quality may account for the
difference in findings.
Clinical evidence appears to support the safety of ginkgo, with no additional adverse
effects reported compared with placebo.
However, possible drug-supplement interactions must be considered in patients with
Alzheimer disease who use ginkgo, especially the risk of bleeding with the use of
aspirin, nonsteroidal anti-inflammatory drugs, or anticoagulants.
This is noteworthy because many patients with Alzheimer disease take aspirin for
cardiovascular health.
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Approach to the Patient
Guidelines on the treatment of Alzheimer disease are available from a number
of organizations, including one developed by the American Academy of
Family Physicians, in conjunction with the American College of Physicians.15
All guidelines emphasize the importance of educating patients and their
families about the disease process and its expected course.
Early referral to local support groups is recommended, and medicolegal issues
such as driving and end-of-life planning should be addressed.
The decision to treat with medication should be shared with the patient and
caregivers, including a discussion of the modest clinical benefit, adverse
effects, and cost.
Physicians should consider discontinuing therapy in patients who continue to
decline despite maximal therapy.
The National Institute on Aging and the Alzheimer's Association have released
recommendations on the diagnosis of dementia and mild cognitive impairment
from Alzheimer disease; however, these guidelines do not address the
treatment of Alzheimer disease and do not recommend the clinical use of
biomarkers.
Possible Future Treatments
• Many potential therapeutic agents are currently under investigation for
the treatment of Alzheimer disease.
• Amyloid precursor protein and enzymes involved in β-amyloid
formation are thought to contribute to genetic forms of Alzheimer
disease; therefore, interventions to reduce amyloid plaque burden by
altering amyloid metabolism are being evaluated.
• Immunotherapy to promote clearance of β-amyloid from the central
nervous system is being assessed.
• Advanced glycation end products are associated with aging.
• The advanced glycation end products receptor is a potential target to
decrease plaque formation and inflammation.
• Other potential treatments include resveratrol, a compound from the
skin of red grapes that may have beneficial effects on aging in mice,
and latrepirdine, a N-methyl-D-aspartate receptor antagonist that may
also weakly inhibit acetylcholinesterase, which may improve cognitive
performance and is currently in phase 3 trials. Agents targeted against
tau are other possible options
UPDATE ON VITAMIN B12 DEFICIENCY
4. A patient with paresthesias, weakness, and gait
abnormalities is found to have a vitamin B12 level of
100 pg per mL (73.78 pmol per L). Which one of the
following is indicated before starting treatment?
A. Measurement of serum methylmalonic acid.
B. Measurement of serum homocysteine.
C. Measurement of serum holotranscobalamin.
D. Use of Schilling test.
E. No confirmatory testing is generally needed
before starting treatment.
Answer
• E. No confirmatory testing is generally
needed before starting treatment.
A patient with pernicious anemia is starting
treatment. Which one of the following
statements about vitamin B12 supplementation
is correct?
A. The patient should not breastfeed while
undergoing treatment.
B. The patient must continue treatment
indefinitely.
C. Intramuscular preparations are more
effective than oral treatments.
D. Oral dosages in excess of 1 mg daily are
considered unsafe.
Answer
• B. The patient must continue treatment
indefinitely.
Which of the following patients require
vitamin B12 supplementation?
A. Patients on a strict vegetarian diet.
B. Patients with coronary artery disease
and high homocysteine levels.
C. Patients with normal vitamin
B12 levels who want to prevent dementia.
D. Pregnant women at high risk of
vitamin B12 deficiency.
Answer
• A. Patients on a strict vegetarian diet.
• D. Pregnant women at high risk of vitamin
B12 deficiency
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Vitamin B12 (cobalamin) deficiency
Vitamin B12 (cobalamin) deficiency is a common cause of megaloblastic anemia, a variety of
neuropsychiatric symptoms, and elevated serum homocysteine levels, especially in older
persons.
There are a number of risk factors for vitamin B12 deficiency, including prolonged use of
metformin and proton pump inhibitors.
No major medical organizations, including the U.S. Preventive Services Task Force, have
published guidelines on screening asymptomatic or low-risk adults for vitamin B12 deficiency,
but high-risk patients, such as those with malabsorptive disorders, may warrant screening.
The initial laboratory assessment of a patient with suspected vitamin B12 deficiency should
include a complete blood count and a serum vitamin B12 level.
Measurements of serum vitamin B12 may not reliably detect deficiency, and measurement of
serum homocysteine and/or methylmalonic acid should be used to confirm deficiency in
asymptomatic high-risk patients with low normal levels of vitamin B12. Oral administration of
high-dose vitamin B12 (1 to 2 mg daily) is as effective as intramuscular administration in
correcting the deficiency, regardless of etiology.
Because crystalline formulations are better absorbed than naturally occurring vitamin B12,
patients older than 50 years and strict vegetarians should consume foods fortified with vitamin
B12 and vitamin B12 supplements, rather than attempting to get vitamin B12 strictly from
dietary sources.
Administration of vitamin B12 to patients with elevated serum homocysteine levels has not been
shown to reduce cardiovascular outcomes in high-risk patients or alter the cognitive decline of
patients with mild to moderate Alzheimer disease.
Recommendations
• Because it is as effective as intramuscular vitamin
B12 injections, high-dose oral vitamin B12 might be a
reasonable choice for replacement in many patients with
vitamin B12 deficiency, regardless of the etiology.
• B
• Vitamin B12 supplementation to reduce elevated serum
homocysteine levels in patients with mild to moderate
Alzheimer disease should not be given because it does not
alter the rate of cognitive decline.
• B
• Vitamin B12 supplementation to reduce levels of serum
homocysteine in high-risk patients is not recommended
because it does not reduce cardiovascular mortality.
• A
B12
• Pernicious anemia, which is characterized by an
autoimmune-mediated chronic atrophic gastritis, is a
classically described cause of vitamin B12 deficiency
• other common causes include postsurgical malabsorption,
dietary deficiencies, and vitamin B12 malabsorption from
food.
• Because of extensive hepatic stores of vitamin B12, there
may be a five- to 10-year delay between the onset of
deficiency and the appearance of clinical symptoms.4
• In asymptomatic patients with low-normal levels of
vitamin B12 (200 to 350 pg per mL [147.56 to 258.23 pmol
per L]), elevated levels of the precursor compounds
homocysteine and methylmalonic acid may prompt a
decision to supplement patients with vitamin B12
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B12
The true prevalence of vitamin B
deficiency is difficult to
estimate because reports are based on values that vary
because of inclusion criteria and individual laboratory
methodology.
• In 1994, the Framingham Heart Study reported the
prevalence of vitamin B12 deficiency, as defined by a
serum vitamin B12 level less than 200 pg per mL and
elevated levels of serum homocysteine, methylmalonic
acid, or both, to be 12 percent among 548 communitydwelling older patients.
• However, most deficient patients did not have hematologic
manifestations, and neurologic manifestations were not
assessed
• According to unpublished data from the National Health
and Nutrition Examination Survey, 3.2 percent of U.S.
adults older than 50 years are estimated to have a serum
vitamin B level less than 200 pg per mL
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B12
• Of particular interest to family physicians, an association between
metformin (Glucophage) use and vitamin B12 deficiency has been
observed.
• A multicenter trial of 390 patients with diabetes mellitus receiving
insulin therapy who were randomized to receive metformin, 850 mg
three times daily, or placebo assessed the risk of vitamin
B12 deficiency and low vitamin B12 levels over four years.7
• Compared with placebo, patients taking metformin had an increased
risk of vitamin B12 deficiency (number needed to harm = 14 per 4.3
years) and low vitamin B12 levels (number needed to harm = 9 per 4.3
years).
• The effect increased with the duration of therapy.
• Although it is not known if prophylactic vitamin B12 supplementation
prevents deficiency, it seems prudent to monitor vitamin B12 levels
periodically in patients taking metformin
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B12
Although the classic hematologic expression of vitamin B 12 deficiency is a megaloblastic macrocytic
anemia characterized by an elevated mean corpuscular volume and mean corpuscular hemoglobin,
and a peripheral smear containing macroovalocytes and hypersegmented neutrophils, up to 28
percent of affected patients may have a normal hemoglobin level, and up to 17 percent may have a
normal mean corpuscular volume.
Although folate deficiency may also produce a megaloblastic anemia, it is less common in the United
States because of required folate fortification of enriched grain and cereal products.
Clinical manifestations of megaloblastic anemia include pallor, tachycardia, weakness, fatigue, and
palpitations. The evaluation and management of macrocytosis has been recently reviewed
inAmerican Family Physician (http://www.aafp.org/afp/2009/0201/p203.html).
Unlike hematologic manifestations, the specific mechanism by which vitamin B 12 deficiency affects
the neurologic system is unknown.
Common neurologic manifestations include paresthesias, weakness, gait abnormalities, and cognitive
or behavioral changes.
Vitamin B12 crosses the placenta and is present in breast milk.
Pregnant women with low or marginal levels of vitamin B 12 are at increased risk of having children
with neural tube defects.
Exclusively breastfed children of mothers with vitamin B 12 deficiency are at increased risk of failure
to thrive, hypotonia, ataxia, developmental delays, anemia, and general weakness.
Women at high risk of or with known vitamin B12 deficiency should supplement with vitamin
B12 while pregnant or breastfeeding.1
Screening and Laboratory Assessment
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Currently, the U.S. Preventive Services Task Force does not have published guidelines on screening asymptomatic
adults for vitamin B12 deficiency.
Other major medical organizations do not have any recommendations for screening low-risk patients.
Family physicians should consider screening patients who have any risk factors listed in Table 1.1–3,6,7
The initial laboratory assessment of a patient with suspected vitamin B12 deficiency should include a complete blood
count and a serum vitamin B12 level.
Several coexisting conditions may falsely lower serum B12 levels, including oral contraceptive use, multiple
myeloma, pregnancy, and folate deficiency.
In contrast, falsely normal levels may be seen in patients with liver disease, myeloproliferative disorders, or renal
disease.
Although many research studies and clinical laboratories define vitamin B12 deficiency at a level of less than 150 pg
per mL (110.67 pmol per L), or in some cases 200 pg per mL, patients with values above these levels may be
symptomatic and benefit from treatment.
Vitamin B12 levels greater than 350 pg per mL seem to be protective against symptoms of vitamin B12 deficiency.
In patients with clinical symptoms of vitamin B12 deficiency and low levels of serum vitamin B12, no further
confirmatory testing is generally needed before treatment is initiated.
Verification with serum methylmalonic acid and/or serum homocysteine level may be necessary in asymptomatic
patients with high-risk conditions, symptomatic patients with low-normal levels of vitamin B12 (200 to 350 pg per
mL), or symptomatic patients in whom vitamin B12 deficiency is unlikely but must be excluded.
Elevated levels of serum homocysteine and methylmalonic acid have been shown to be highly sensitive markers for
vitamin B12 deficiency.
Testing is widely available,5,8 but expensive, and multiple conditions may falsely elevate serum homocysteine and
methylmalonic acid levels (Table 3).15 Because serum methylmalonic acid level is as sensitive as, but more specific
than, serum homocysteine level for vitamin B12 deficiency, it is the confirmatory test of choice.8,15 Serum
holotranscobalamin level, which is reduced in vitamin B12deficiency, compared favorably with homocysteine and
methylmalonic acid levels as a confirmatory test in one study, but further trials are needed before its widespread use
for this purpose can be recommended
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Treatment
Treatment of clinical vitamin B12 deficiency has traditionally been accomplished by intramuscular
injection of crystalline vitamin B12 at a dosage of 1 mg weekly for eight weeks, followed by 1 mg
monthly for life.
In a 2005 Cochrane review, patients who received high dosages of oral vitamin B 12 (1 to 2 mg daily)
for 90 to 120 days had an improvement in serum vitamin B 12 similar to patients who received
intramuscular injections of vitamin B12.
These results were consistent in patients regardless of the etiology of their vitamin B 12 deficiency,
including malabsorption states and pernicious anemia.
Given the lower cost and ease of administration of oral vitamin B 12, this might be a reasonable choice
for replacement in many patients.
In cases of megaloblastic anemia, reticulocytosis generally occurs within a few days, and the
hematocrit generally normalizes over several weeks.
Advanced neurologic symptoms may not respond to replacement.
Vitamin B12 has been demonstrated to be safe in doses up to 1,000 times the recommended dietary
allowance and is safe in pregnancy.
The bioavailability of sublingual vitamin B12 appears to be equivalent to oral vitamin B12, but there is
no evidence that sublingual delivery offers any advantage over oral preparations. 22
There are no clinical guidelines for the treatment of subclinical vitamin B 12 deficiency (asymptomatic
patients with decreased levels of vitamin B12 and elevated levels of homocysteine and/or
methylmalonic acid). Physicians may opt to treat these patients and monitor for improvement of
metabolic markers, particularly in populations at high risk of clinical vitamin B 12 deficiency, or
observe these patients and periodically reassess their levels of vitamin B 12, homocysteine, and/or
methylmalonic acid.
Patients with subclinical vitamin B12 deficiency will need at least 1 mg of vitamin B12 daily
HERPES ZOSTER AND
POSTHERPETIC NEURALGIA:
PREVENTION AND MANAGEMENT
7. Which one of the following statements
about the clinical features of acute herpes
zoster (shingles) is correct?
A. The prodrome may include abnormal skin
sensation.
B. The ophthalmic area is the most common
site of eruption.
C. The rash is usually bilateral.
D. Lesions typically heal within seven to 10
days.
Answer
• A. The prodrome may include abnormal
skin sensation.
Which one of the following statements about the
management of acute herpes zoster is correct?
A. Antiviral therapy during the acute phase has been
proven to prevent postherpetic neuralgia.
B. Topical antiviral agents reduce the severity and
duration of symptoms.
C. Antiviral therapy alone is usually sufficient to
control pain in patients with acute herpes zoster.
D. Adding corticosteroids to antiviral therapy
decreases the pain associated with acute herpes
zoster.
Answer
• D. Adding corticosteroids to antiviral
therapy decreases the pain associated with
acute herpes zoster.
Which of the following increase
the risk of developing neuralgia
after acute herpes zoster?
A. Male sex.
B. History of prodromal pain.
C. Mild pain during the acute
phase.
D. Older age.
Answer
• B. History of prodromal pain.
• D. Older age.
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Herpes Zoster and Postherpetic Neuralgia:
Prevention and Management
Herpes zoster (shingles) is diagnosed clinically by recognition of the distinctive,
painful vesicular rash appearing in a unilateral, dermatomal distribution.
An estimated 1 million cases occur in the United States each year, and increasing
age is the primary risk factor.
Laboratory testing, including polymerase chain reaction, can confirm atypical
cases.
Treatment with acyclovir, famciclovir, or valacyclovir decreases the duration of the
rash.
Adjunct medications, including opioid analgesics, tricyclic antidepressants, or
corticosteroids, may relieve the pain associated with acute herpes zoster.
There is conflicting evidence that antiviral therapy during the acute phase prevents
postherpetic neuralgia.
Postherpetic neuralgia in the cutaneous nerve distribution may last from 30 days to
more than six months after the lesions have healed.
Evidence supports treating postherpetic neuralgia with tricyclic antidepressants,
gabapentin, pregabalin, long-acting opioids, or tramadol; moderate evidence
supports the use of capsaicin cream or a lidocaine patch as a second-line agent.
Immunization to prevent herpes zoster and postherpetic neuralgia is recommended
for most adults 60 years and older.
Herpes Zoster
• Antiviral therapy should be initiated within 72 hours of onset of the
rash in patients with acute herpes zoster to increase the rate of healing
and decrease pain.
• A
• Based on individual patient characteristics, a tricyclic antidepressant,
tramadol (Ultram), long-acting opioid, or anticonvulsant (i.e.,
gabapentin [Neurontin] or pregabalin [Lyrica]) should be selected to
decrease the pain of postherpetic neuralgia.
• A
• If topical therapy is indicated, capsaicin cream (Zostrix) or a lidocaine
patch (Lidoderm) may decrease pain in patients with postherpetic
neuralgia.
• B
• Herpes zoster vaccine (Zostavax) should be given to most persons 60
years and older to prevent herpes zoster and postherpetic neuralgia.
• B
Clinical Presentation
• Prodromal symptoms include malaise, headache, photophobia,
abnormal skin sensations, and occasionally fever.
• These symptoms may occur one to five days before the appearance of
the rash.
• Abnormal skin sensations range from itching and burning to
hyperesthesia and severe pain.
• The intensity of the pain may lead to a misdiagnosis, such as renal
colic or myocardial infarction, depending on location.
• The rash (Figure 1) begins as maculopapular lesions in a unilateral,
dermatomal distribution that rarely crosses the midline.
• Lesions progress to clear vesicles that become cloudy within three to
five days, then crust and heal within two to four weeks.
• Scarring and changes in pigmentation may occur. Dermatomes of the
back and face are most often affected, although multiple dermatome
involvement is possible.
Diagnosis
• The diagnosis of herpes zoster is usually clinical,
based on recognition of the distinctive
presentation and rash.
• Cases of herpes zoster without a rash (zoster sine
herpete) are difficult to diagnose and require
laboratory confirmation of varicella-zoster virus
reactivation.
• Fluid obtained from vesicles may be evaluated
with polymerase chain reaction testing, viral
culture, or direct immunofluorescent antigen
staining.
• lists the accuracy of diagnostic testing for herpes
zoster
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Complications
Postherpetic neuralgia is the most common complication of herpes zoster.
It occurs in approximately 30 percent of patients older than 80 years and in
approximately 20 percent of patients 60 to 65 years; it is rare in patients younger than 50
years.
Replication of the varicella-zoster virus in the basal ganglia destroys the nerves, leading
to pain in the affected dermatome.
Postherpetic pain may take several forms, including allodynia (nonpainful stimulus
perceived as painful), hyperpathia (slightly painful stimulus perceived as very painful),
and dysesthesia (abnormal sensation with no stimuli).
Women are at greater risk of postherpetic neuralgia.
Additional risk factors include older age, moderate to severe rash, moderate to severe
acute pain during the rash, ophthalmic involvement, and history of prodromal pain.
Postherpetic neuralgia may persist from 30 days to more than six months after the
lesions have healed, and most cases resolve spontaneously.
Herpes zoster ophthalmicus (ophthalmic zoster) occurs in 5 to 10 percent of patients
with herpes zoster and may lead to permanent vision loss and cranial nerve palsies.
Urgent ophthalmology referral is recommended in these patients. Superimposed
bacterial skin infections with streptococci and staphylococci should be treated with
appropriate oral antibiotics.
Encephalitis, meningitis, myelitis, and disseminated cutaneous and visceral disease may
occur in patients with severe immunosuppression.
Management of Acute Herpes Zoster
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Antiviral therapy is first-line treatment and should be initiated within 72 hours
of rash onset to increase the rate of healing and decrease pain.
No study has investigated the effectiveness of later initiation of antiviral
therapy, but it is believed to benefit patients with active vesicle eruptions.
Acyclovir (Zovirax), famciclovir (Famvir), and valacyclovir (Valtrex) are
approved by the U.S. Food and Drug Administration (FDA) for the treatment
of acute herpes zoster. These agents are considered safe and are well tolerated
with minimal adverse effects (e.g., headache, nausea).
All three drugs are available in a generic form, although acyclovir is
significantly less expensive than famciclovir or valacyclovir.
These antiviral agents decrease the severity and duration of acute herpes
zoster.
In one randomized controlled trial, valacyclovir led to complete pain
resolution sooner than acyclovir (44 versus 51 days) and required less frequent
dosing
Famciclovir has shown similar effectiveness to valacyclovir.
Topical antiviral agents are not effective
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Herpes Zoster
Although antiviral medications slow the production of the virus and decrease the viral load in the
dorsal root ganglia, evidence showing that these medications alter the incidence and course of
postherpetic neuralgia is inconsistent.
Some studies suggest that no antiviral agent prevents postherpetic neuralgia, whereas others report
reduced duration of symptoms.
Famciclovir and valacyclovir are associated with better outcomes than placebo or acyclovir.
Antivirals alone are usually insufficient to relieve the often debilitating pain of acute herpes zoster.
Mild to moderate pain may be controlled with acetaminophen or nonsteroidal anti-inflammatory
drugs, alone or in combination with a weak opioid or tramadol (Ultram).
Moderate to severe pain requires scheduled opioids (e.g., oxycodone, morphine).
The intensity of pain during the acute attack is an important predictor for the development of
postherpetic neuralgia, and medications given during this phase may influence the outcome of later
interventions for postherpetic neuralgia.
If pain does not rapidly respond to opioid analgesics or if opioids are not tolerated, the prompt
addition of an adjunctive therapy should be considered.3 Nortriptyline (Pamelor), gabapentin
(Neurontin), and pregabalin (Lyrica) have been recommended, but they have not been extensively
studied for pain relief in patients with acute herpes zoster.
The addition of corticosteroids to acyclovir decreases the pain of acute herpes zoster and speeds
lesion healing and return to daily activities.
Combination therapy with corticosteroids and antivirals should be considered in older patients with
no contraindications.
Although corticosteroids have anti-inflammatory effects that could be expected to decrease nerve
damage and the risk of postherpetic neuralgia, a Cochrane review found no significant difference
between corticosteroids and placebo in preventing postherpetic neuralgia six months after onset of
the rash.
Management of Postherpetic
Neuralgia
• Theoretical models suggest that reducing pain during the
acute phase of herpes zoster may stop the initiation of the
mechanisms that cause chronic pain, thus reducing the risk
of postherpetic neuralgia.
• If the condition develops, treatment focuses on preventing
a chronic pain syndrome.
• Several medications have proved effective for postherpetic
neuralgia and should be selected based on individual
patient characteristics.
• Many of these medications require dosing adjustment in
older patients and in those with reduced creatinine
clearance.
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Treatment PHN
Tricyclic antidepressants, such as amitriptyline, desipramine (Norpramin), and nortriptyline, have pain-modulating effects in
neuropathic and other chronic pain states.
They are the mainstay of treatment for postherpetic neuralgia, and evidence supports their effectiveness.
In older patients, tricyclic antidepressants should be started at lower doses given at bedtime, and the patient should be monitored
for adverse effects, including interactions with other medications.
Opioid medications have analgesic effects and are helpful for postherpetic neuralgia.
Studies have shown that patients taking oxycodone, morphine, or methadone have better pain relief than those taking placebo.
Opioids should be carefully adjusted in all patients for clinical response.
Oxycodone is of special concern because of a 50 percent higher serum concentration when creatinine clearance is less than 60
mL per minute per 1.73 m2 (1.00 mL per second per m2).
Morphine and methadone have been shown to provide better pain relief than tricyclic antidepressants.
A Cochrane review of seven trials found tramadol to be effective for neuropathic pain, including postherpetic neuralgia.
Studies involving anticonvulsants showed that gabapentin and pregabalin reduce pain from postherpetic neuralgia by
approximately 50 percent.
Another study comparing the maximum tolerated dosages of gabapentin and nortriptyline found that both reduced pain scores,
but gabapentin was associated with fewer adverse effects.
The FDA has approved two topical medications for treatment of postherpetic neuralgia. A Cochrane review that included a few
small studies of topical lidocaine patches (Lidoderm) reported benefit in some patients, but found insufficient evidence to
recommend them as first-line therapy
Based on poor-quality studies, capsaicin cream (Zostrix), which is derived from peppers, provides limited reduction in
postherpetic neuralgia.
Topical antiviral agents, such as idoxuridine (not available in the United States), may reduce the prevalence of postherpetic
neuralgia in immunocompetent patients, but the evidence is low-quality.
Intrathecal preservative-free methylprednisolone (not available in the United States) is effective for intractable postherpetic
neuralgia.
However, it should be used only if other agents have been ineffective.
Other treatments for postherpetic neuralgia have been investigated, but not all are effective.
Aspirin cream has been helpful in a few small studies, but the benefit is not considered significant.
No recommendations can be made for the anticonvulsants valproate (Depakote)19 and carbamazepine (Tegretol)20 because of
limited data. Anesthetic agents such as N-methyl-D-aspartate receptor antagonists play a role in processing pain signals and could
potentially benefit patients with postherpetic neuralgia. Ketamine (Ketalar), dextromethorphan, and memantine (Namenda) have
not been shown to improve pain compared with placebo
Prevention
• Herpes zoster and postherpetic neuralgia are preventable
conditions.
• The Centers for Disease Control and Prevention
recommends one dose of the herpes zoster vaccine
(Zostavax) for persons 60 years and older.
• The FDA recently approved the herpes zoster vaccine for
healthy patients between 50 and 59 years of age, and the
Advisory Committee on Immunization Practices is
expected to vote on recommending the vaccine for this
population in late 2011.
• Patients may be immunized without serologic testing and
regardless of any history of varicella virus infection or
herpes zoster.
• Coadministration with other inactivated vaccines common
in this age group is considered safe
Prevention
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The Shingles Prevention Study found the herpes zoster vaccine to be 51.3 percent
effective in preventing herpes zoster and 66.5 percent effective in preventing
postherpetic neuralgia (when defined as pain rated as at least a 3 out of 10 on a severity
scale that persisted for at least 90 days after rash onset).
Vaccination has also been shown to reduce the incidence of postherpetic neuralgia by 39
percent among patients who develop herpes zoster.
The number needed to treat to prevent one case over three years is 58 for herpes zoster
and 364 for postherpetic neuralgia.
Fewer than 10 percent of eligible persons receive the herpes zoster vaccine.
Patient surveys show that many do not know about it or believe it is not needed.
Cost is a significant issue with the vaccine. The average wholesale cost of Zostavax is
$194 per dose, and many insurance plans do not cover it.
Another concern is storage. The vaccine must be frozen, and in-office administration
requires a monitored, temperature-controlled freezer.
Patients may be referred to a pharmacy for immunization or given a prescription for the
vaccine, which must be kept cold and administered within 30 minutes.
Physicians can play a key role in overcoming these barriers and should encourage
vaccination to prevent herpes zoster and postherpetic neuralgia
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Food
allergy
Food allergy can be difficult to diagnose. Currently, there is no treatment, and
it can be managed only by avoidance of allergens and treatment of symptoms.
Because diagnosis and management options vary, the National Institute of
Allergy and Infectious Diseases (NIAID) helped develop guidelines to provide
physicians with “best practices” for diagnosing and treating patients with food
allergy.
This summary guideline will review some of the diagnostic recommendations.
Specific clinical syndromes may occur as a result of food allergy. These
include:
Food-induced anaphylaxis (a serious allergic reaction with a rapid onset that
may cause death)
Gastrointestinal food allergies (i.e., immediate gastrointestinal
hypersensitivity, eosinophilic esophagitis, eosinophilic gastroenteritis, food
protein–induced allergic proctocolitis, food protein–induced enterocolitis
syndrome, and oral allergy syndrome)
Cutaneous reactions (i.e., acute urticaria, angioedema, atopic dermatitis,
allergic contact dermatitis, and contact urticaria)
Respiratory manifestations of immunoglobulin E (IgE)-mediated food allergy
Heiner syndrome (a rare disease in infants and young children caused
primarily by the ingestion of milk)
COMMON ADVERSE EFFECTS OF
ANTIRETROVIRAL THERAPY FOR HIV
DISEASE
10. Which one of the following statements about
antiretroviral therapy (ART) is correct?
A. Lipid disorders associated with ART can be
managed with lipid-lowering medications.
B. When a rash occurs in patients taking the nonnucleoside reverse transcriptase inhibitor etravirine
(Intelence), the medication generally can be
continued safely.
C. Heavy alcohol use can offset ART-induced
cardiovascular risk.
D. Treatment for patients with ART-induced
proteinuria includes dietary protein restriction.
Answer
• A. Lipid disorders associated with ART can
be managed with lipid-lowering
medications.
Which one of the following types
of medications generally should
not be used in combination with
ART?
A. Most psychiatric medications.
B. Most antiemetics.
C. Herbal medications.
D. Oral contraceptives.
Answer
• C. Herbal medications.
Which of the following should be
recommended in patients with human
immunodeficiency virus infection?
A. Initiating ART in patients with CD4 cell
counts of 500 per mm3 or less.
B. Screening for dyslipidemia at least
annually in patients taking ART.
C. Annual or biannual calculation of
glomerular filtration rate.
D. Dual-energy x-ray absorptiometry in select
patients taking ART.
Answer
• A. Initiating ART in patients with CD4 cell
counts of 500 per mm3 or less.
• B. Screening for dyslipidemia at least
annually in patients taking ART.
• C. Annual or biannual calculation of
glomerular filtration rate.
• D. Dual-energy x-ray absorptiometry in
select patients taking ART.
PUTTING PREVENTION INTO PRACTICE: AN
EVIDENCE-BASED APPROACH
ASPIRIN FOR THE PREVENTION OF
CARDIOVASCULAR DISEASE
13. Which one of the following statements about aspirin use
and cardiovascular disease (CVD) is correct?
A. The optimal dosage of aspirin for preventing CVD is 75
mg per day.
B. The optimal dosage of aspirin for preventing CVD is not
known, but 75 mg per day seems to be as effective as a higher
dosage.
C. Nonsteroidal anti-inflammatory drug therapy combined
with aspirin use neither increases nor decreases the risk of
serious gastrointestinal bleeding.
D. The U.S. Preventive Services Task Force recommends
against the use of aspirin for CVD prevention in men and
women 80 years and older.
Answer
• B. The optimal dosage of aspirin for
preventing CVD is not known, but 75 mg
per day seems to be as effective as a higher
dosage.
CLINICAL EVIDENCE HANDBOOK
CROHN DISEASE
14. A 28-year-old man with Crohn disease
presents to the emergency department with
abdominal pain and decreased bowel sounds
on auscultation. Evaluation confirms an acute
exacerbation. Which of the following
treatments have been shown to induce
remission in patients with Crohn disease?
A. Oral corticosteroids.
B. Infliximab.
C. Antibiotics.
D. Probiotics.
Answer
• A. Oral corticosteroids.
• B. Infliximab.
Prevalence
• The prevalence of peanut and tree nut allergies in the United States is
0.6 percent and 0.4 to 0.5 percent, respectively.
• Approximately 0.6 percent of children and 2.8 percent of adults in the
United States have a seafood allergy.
• A Danish cohort study of children followed from birth to three years of
age determined that 2.2 percent of children had confirmed milk
allergy.
• Guidelines
• Food allergy should be suspected in the following persons: those with
anaphylaxis or any combination of symptoms in that occur within
minutes to hours of ingesting food, especially in young children; those
with symptoms that have occurred more than once with the ingestion
of a particular food; children with certain conditions, including
moderate to severe atopic dermatitis, eosinophilic esophagitis,
enterocolitis, enteropathy, and allergic proctocolitis; and adults with
eosinophilic esophagitis.
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History is useful for identifying foods that may be responsible for IgE-mediated allergic reactions, but when used
alone, it lacks sensitivity and specificity.
It may be more useful for diagnosing immediate food-induced allergic reactions versus delayed reactions.
Further assessment (e.g., laboratory studies, food challenges) is needed to confirm a diagnosis.
Physical examination alone also cannot be considered diagnostic for food allergy, but it can provide signs consistent
with an allergic reaction or disorder associated with food allergy.
History and physical examination should be used in combination to help with the diagnosis of food allergy.
Studies have shown that 50 to 90 percent of presumed food allergies are not actually allergies; therefore parent- and
patient-reported food allergy must be confirmed by appropriate evaluation.
A skin prick test should be used to help determine which foods could be causing IgE-mediated food-induced allergic
reactions; however, when used alone, a skin prick test cannot be considered diagnostic.
Insufficient evidence exists to support the use of intradermal testing or total serum IgE measurements for diagnosing
food allergy; therefore, neither test should be used.
Allergen-specific IgE tests can be useful for identifying foods that are thought to provoke IgE-mediated food-induced
allergic reactions, and specified cutoff levels (defined as 95 percent predictive values) may be more predictive than
skin prick tests in certain patients, but are not diagnostic of food allergy when used alone.
There is insufficient evidence to support the use of the atopy patch test for the evaluation of food allergy; therefore, it
should not be routinely used in the evaluation of non-contact food allergy.
The literature does not support the idea that using skin prick tests, allergen-specific IgE tests, and atopy patch tests in
combination provides any significant advantage over the use of skin prick tests or allergen-specific IgE tests alone;
therefore, routinely using these tests in combination for diagnosis of food allergy is not recommended.
Elimination of at least one specific food from the diet may be useful in diagnosing food allergy, especially foods that
may cause some non–IgE-mediated (e.g., food protein–induced enterocolitis syndrome, allergic proctocolitis, Heiner
syndrome) and some mixed IgE- and non–IgE-mediated (e.g., eosinophilic esophagitis) food-induced allergic
disorders.
Treatment for food allergies consists of dietary avoidance of certain allergens. For more information on treatments for
specific food allergies, please refer to the full guidelines.
ASA
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Cardiovascular disease (CVD) is the leading cause of death in adults, accounting for one out of every 2.8 deaths in the United States.
Daily use of low-dose (75 to 325 mg) aspirin as a secondary preventive measure reduces all-cause mortality by 18 percent, and subsequent
myocardial infarctions by 30 percent in persons with known CVD.
Aspirin use prevents CVD by inhibiting cyclooxygenase, which blocks the formation of thromboxane A2 and thus disrupts platelet
aggregation and prevents vasoconstriction.
The American Heart Association recommends that daily aspirin be used indefinitely in all patients with known CVD, unless contraindicated,
for secondary prevention.
There is interest in and controversy over daily use of aspirin for primary prevention of CVD in persons who have yet to demonstrate clinical
evidence of CVD.
Several major randomized clinical trials and subsequent meta-analyses involving more than 96,000 participants have demonstrated that daily
aspirin use in persons at moderate to high risk of CVD can reduce the risk of a first-time CVD event by at least 28 percent.
However, recent studies have questioned whether the benefits of daily aspirin for primary cardioprevention outweigh the risks of
gastrointestinal (GI) and intracerebral hemorrhage.
In addition, a recent randomized controlled trial involving 39,876 relatively healthy women 45 years and older suggested that daily aspirin
therapy may not decrease the risk of acute myocardial infarction in women, although there was a 17 percent decreased risk of stroke.
Currently, two large, international randomized controlled trials (n > 10,000) are investigating the benefit of daily aspirin therapy for primary
cardioprevention in select populations: the ASCEND trial (a study of cardiovascular events in diabetes) and the ASPREE trial (aspirin in
reducing events in the elderly). Results from these trials should be available within the next five years.
After critically analyzing the evidence of potential benefits and harms of aspirin therapy, the U.S. Preventive Services Task Force (USPSTF)
reaffirmed and clarified its position in 2009, concluding that aspirin is effective for primary CVD prevention. 11 Aspirin should be
recommended when benefits outweigh risks. The USPSTF found good evidence that aspirin use decreases myocardial infarctions in men 45
to 79 years of age, and strokes in women 55 to 79 years of age who are at increased risk of, but have not yet experienced, these events.
Compared with its 2002 recommendation,6 the USPSTF's 2009 recommendation differentiates CVD risk by age group and sex, complicating
physicians' task of determining patients' CVD risk.
Physicians must now consider the 10-year myocardial infarction risk for men and 10-year stroke risk for women.
Aspirin therapy should be considered in men with a 10-year CVD risk of at least 4 percent in those 45 to 59 years of age, 9 percent in those
60 to 69 years of age, and 12 percent in those 70 to 79 years of age.
Aspirin therapy should be considered in women with a 10-year stroke risk of at least 3 percent in those 50 to 59 years of age, 8 percent in
those 60 to 69 years of age, and 11 percent in those 70 to 79 years of age. Several online calculators are available to help physicians
determine these risks.
To assist physicians in better identifying patients who potentially would benefit from aspirin therapy, the American College of Preventive
Medicine is studying the use of a patient-friendly decision table.
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ASA
When advising aspirin use, the USPSTF recommends considering the risk of GI
bleeding.
The most widely recognized adverse effect of aspirin therapy is a modestly increased
risk of GI bleeding; 769 persons need to be treated with aspirin to cause one additional
major bleeding episode annually.
Aspirin-induced GI toxicity appears to be dose-dependent; higher aspirin doses increase
the risk of bleeding.
It appears that in most persons, low-dose aspirin (81 mg) is best.
Increasing the dose to 325 mg does not increase the effectiveness, but does increase the
risk of GI bleeding.
Aspirin for primary cardioprevention should be avoided in persons who have had a GI
or cerebral bleeding episode, and in those who are at risk of bleeding problems (e.g.,
bleeding disorder, severe liver disease, thrombocytopenia, concomitant anticoagulant
therapy).
For persons with an aspirin- induced bleeding ulcer, aspirin use in combination with a
proton pump inhibitor may be safely restarted after the ulcer has healed.
A randomized controlled trial found that in those taking low-dose aspirin who had GI
bleeding, continuous aspirin therapy may increase the risk of recurrent GI bleeding, but
potentially reduces cardiovascular and cerebrovascular mortality rates.
Eradication of Helicobacter pyloridecreases the risk of recurrent GI bleeding in those
taking low-dose aspirin.
Enteric-coated or buffered aspirin does not decrease the risk of GI toxicity.
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ASA
As with any medication, the key to aspirin therapy for CVD prevention is appropriate use.
A study evaluating 24 clinical preventive services considered effective by the USPSTF found that
advising at-risk adults to consider taking daily aspirin was the most cost-effective preventive measure
available for physicians.
If 90 percent of those who should be taking aspirin were doing so, it is estimated that an additional
45,000 lives would be saved each year.
Despite this benefit, less than one-half of those who should be taking aspirin regularly are actually
taking it.
Although not reported, there are also persons taking daily aspirin for primary cardioprevention in
whom the benefit is negligible or the risk is high.
These persons should be cautioned against this practice until the benefit outweighs the risk.
The factor most strongly associated with appropriate aspirin use is a conversation between the patient
and physician.
The National Committee for Quality Assurance has proposed that health plans measure their
members' use of aspirin, as well as the extent to which physicians discuss aspirin use with their
patients.
Determining patients' CVD risk and discussing appropriate aspirin use with them should be a priority
for all family physicians.
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Syndrome vs etiology
dementia and depression syndromes, not
etiologies
Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV)
definitions
dementia—impairment in memory and 1 of following (aphasia; apraxia; agnosia;
impaired executive function)
functional impairment
deficits not due to delirium
major depressive episode—5 of following
within 2-wk period (depressed or sad mood
diminished interest or pleasure
weight loss or gain
insomnia or hypersomnia
psychomotor agitation or retardation
fatigue or loss of energy
feelings of worthlessness or excessive or inappropriate guilt
poor concentration or indecisiveness
recurrent thoughts of death or suicidality)
not bipolar mixed episode
functional impairment
not better accounted for by another condition
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Etiologies
dementia—Alzheimer disease (AD)
Cerebrovascular disease (CVD)
Lewy body disease
other brain diseases (eg, HIV)
Depression
depression—AD CVD
substance induced
genetic predisposition
reaction to psychosocial stress
Relationship between depression and dementia
• cognitive impairment can be feature of depressive
episode (may not always fully remit with treatment)
• in late-life depression, often see slowed information
processing that affects all cognitive domains
• depression occurs in 50% of patients with dementia
• recent meta-analysis showed depression doubles chance of
developing AD
• unclear if depression first symptom (prodrome) or
independent risk factor for dementia
• evidence exists for both explanations
• risk factor—more plaques tangles seen in brains of people
with AD who had lifelong depression
• prodrome—most people who had depression with cognitive
features never recovered and went on to develop dementia
Pathways linking depression to persistent cognitive impairment
and dementia:
• patient who has some depression-associated
neuropathology (eg, hippocampal volume loss)
may develop mild cognitive impairment (MCI),
and this may remain stable over time
• patient with depression and underlying AD
neuropathology can progress to frank dementia
(AD)
• Patients with CVD develop frontal lobe damage,
and often get depression with MCI (ie, vascular
depression), which can progress over time to
vascular dementia (VaD)
Frontotemporal
dementia (FTD)
• tends to occur at younger age than AD
(incidence peaks in 60s)
• earliest symptoms can resemble depression
or mood disorder
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Clinical clues to depression in older patient who denies sadness
or depression
unexplained somatic complaints
hopelessness
Helplessness
Anxiety
memory complaints
Anhedonia
Slowed movement
Irritability
lack of interest in personal care
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Evaluation of older patient
presenting with depression
look for red flags for dementia
detailed patient history—personality changes
risk factors (RFs) for dementia
thorough review of systems
complete physical and neurologic examination—look for focal neurologic findings
Parkinsonism
gait abnormalities
cognitive evaluation—at minimum, Mini-Mental State Examination (MMSE) in all patients
consider more extensive evaluation if dementia red flags present (options include modified MMSE
clock-drawing test
trail-making test
Montreal Cognitive Assessment )
laboratory evaluation—routine screening tests
Consider erythrocyte sedimentation rate or C-reactive protein
Antinuclear antibody or rheumatoid factor
HIV
Lyme disease
Lumbar puncture
Electroencephalography
neuroimaging—head computed tomography or (preferably) brain magnetic resonance imaging
positron emission tomography or single-photon emission
computer tomography for distinguishing AD from FTD
Beware of delirium
• sad mood does not equal depression
• Delirium common in acute care settings
and may present with depressive symptoms
Prevention of dementia
• potentially modifiable RFs for dementia
vascular RFs (smoking; hypertension
[HTN], high body mass index and/or high
cholesterol in midlife; diabetes)
• Steps to reduce vascular RFs—control of
HTN and cholesterol
• smoking cessation
• weight loss
• Mediterranean diet
• Cognitive protective factors—education
• exercise
Treatment
• if unsure whether patient has depression, dementia, or
both— treat depression first and monitor for response
• In general, antidepressants effective and have favorable
risk-benefit profiles
• start with selective serotonin reuptake inhibitors (SSRIs)
• avoid those that have many drug-drug interactions, eg,
paroxetine, fluoxetine
• if ineffective, serotonin–norepinephrine reuptake inhibitors
(SNRIs; eg, duloxetine, venlafaxine, and mirtazapine) also
good for depression and anxiety
• avoid tricyclic antidepressants
• use benzodiazepines with caution
Driving in the Elderly
• Introductory remarks
• driving important medical, social, and public health
issue
• normal aging and associated conditions may compromise
ability to drive safely
• most older drivers self-adjust driving habits
• growing apprehension about older drivers, and evidence
suggests families and patients increasingly turn to health
care providers (HCPs) for guidance
• Issue requires balancing public safety vs individual
autonomy, and currently no clear guidelines
Older
drivers
• by 2020, 25% of drivers will be >65 yr of age
• older adults see driving as key to independence,
self-esteem, and socialization
• loss of license can be devastating and may result
in depression, isolation, and sometimes loss of
home
• 33% of people >90 yr of age still driving
• study of patients referred to geriatric assessment
clinic found 25% still driving
• (>50% had MMSE scores <24/30; 33% to 50%
had problems with activities of daily living [ADLs
and instrumental ADLs )
Performance of older drivers
• elderly have lowest crash rate
• per driver of any age group (in context of low-risk driving)
but
• have second highest rate per miles driven; motor vehicle
• crashes by older adults more often due to inattention and
difficulty
• with visual processing; much more likely to result in
injury,
• hospitalization, and death; much of morbidity and
mortality attributed to drivers’ poor physical condition
• Also related to cars driven
• crashes usually low impact
Violations by older drivers
• occur at complicated traffic patterns that
require quick response, full peripheral
vision, and interaction with other drivers
(typically occur in merging and yielding
right of way)
Types of crashes
• typically multiple-vehicle at intersections
• left-hand turn significant cause of crashes
by older adults (requires judgment of speed
and distance, which becomes impaired with
aging)
Impact of aging on driving skills
• driving complex but highly practiced skill
(and older people can drive safely despite
significant losses)
• primary areas of concern when assessing
older driver for safety visual problems,
effect of chronic medical conditions and
associated medications, mobility, and
cognition
Age-related visual changes
• decreased visual acuity
• restriction of horizontal peripheral field of vision
• lens changes and problems with glare (result in decreased
ability to see low-contrast items at night)
• useful field of view (UFOV)—area over which driver can
absorb visual information and make rapid decisions
• UFOV test assesses dynamic visual acuity and cognitive
processing
• Strong correlation between size of UFOV and risk for
crashes
Chronic medical conditions
• affect driving skills and increase crash
rates (true in any age group)
• medications associated with conditions (eg,
benzodiazepines, narcotics) can also
influence crash rates
• Alcohol
• contribution of alcohol to crashes well
known
• More common problem in elderly than
realized
• important to recognize risk and ask patients
about alcohol use
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Mobility and function
driving physical activity requiring muscle strength and endurance
osteoarthritis (OA)—prevalent problem in older adults
affects joints involved in driving
driving ability impaired by aches, pain, and weakness caused by OA
and by effects of medications
Dementia and driving
controversial issue
long assumed cognitive deficits associated with dementia impact
driving
People with dementia often do not self-restrict (1-2 yr after diagnosis,
50% continue to drive [50% get lost and/or crash on regular basis
yet 50% of caregivers consider them safe drivers])
Tests for dementia not good predictors of driving performance
Physician’s Guide to Assessing and
Counseling Older Drivers
• developed by American Medical Association (AMA) in
cooperation with National Highway Traffic Safety
Administration
• available online at www.ama-assn.org/go/olderdrivers;
provides
• algorithm for office-based assessment of medical fitness to
drive
• Reporting laws: vary from state to state
• important to know state law regarding older drivers
• eg, in Maryland, no mandatory reporting by HCPs for
medical concerns
• immunity given if report made in good faith; anonymity
granted if requested
Assessment of DrivingRelated Skills (ADReS)
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structured series of office tests for evaluating drivers at risk
assesses vision, cognition, and motor strength
functions as guide (not predictive)
when discussing tests with patient, be straightforward, kind, but tactful and clear
explain goal to keep patient driving and that tests may help identify areas that need to be
worked on to keep him or her safely on road as long as possible
Vision: tested with Snellen E chart
based on last full row patient can read clearly
assessment of visual fields done by confrontation
Cognition: evaluated with trail-making test, Part B (assesses working memory and
selective and divided attention; correlates well with ability to drive safely) and clockdrawing test
Mobility and motor strength: assessed with 20-ft rapid-pace walk (measures strength,
endurance, and balance) and manual test of motor strength (on 5/5 scale)
in addition, ask patient to demonstrate what it looks like when he or she tries to back up,
brake, and grip steering wheel (for evaluation of range of motion and grip strength)
What to do with ADReS score
• score (as well as any red flags, eg, crash history, concern of family
members) directs intervention
• intervention requires tactful, candid discussion and may involve
counseling patient on driving restrictions, physical therapy, or car
adaptations
• observing driver provides critical information for deciding appropriate
intervention
• gold standard is observation by driver rehabilitation specialist
• driving schools, American Automobile Association, or American
Association of Retired Persons may also offer resources for skills
assessment
• second best alternative to ask family member or other person patient
trusts to drive with him or her and provide feedback
• recommended that any abnormal ADReS score should trigger
intervention
• however, keep in mind ADReS extremely sensitive but not very
specific (>33% of patients who fail ADReS still pass driving test with
ease)
If driving needs to stop
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most people eventually have to retire driver’s license (on average, women
go for 10 yr at end of life without driving, and men 7 yr)
recommended to talk to patient and involve family if possible
goal to reach collaborative agreement where all agree best thing to retire
patient’s license
Transportation options available
best if it does not require that patient move
how to start discussion—depends on physician’s style and relationship with
patient
focus on safety (risk to self and others)
Economic arguments have not proven successful
make sure patient understands what is being said
write prescription that says “do not drive”
may want to inform patient about state reporting laws and how they affect
decision making
be sure to follow up for adherence to recommendations and for evidence of
impact of cessation of driving
do not put responsibility on patient’s family
If patient refuses to cooperate
with assessment
• Guidelines and booklets available that can help patient and
family deal with driving issues
• encourage patient to drive with family member or friend to
get feedback on driving abilities
• Dealing with patient who lacks decision-making
capacity
• Involve family/guardian/surrogate decision makers
• goals to re- tire driver and avoid conflict
• helpful interventions include hiding car, changing or
hiding keys, or disabling car
Society’s role in controlling older
adults’ ability to drive
• HCPs will get better tools for assessment and may
get more involved and take on more responsibility
• governments have role in how they build roads
and left-hand turn signs, and how they focus on
age-based licensing
• insurance companies may limit ability to drive
simply by raising rates for older drivers
• automobile industry can make smart cars that may
help keep patients safe on road
Questions and Answers
• Are there pieces of driving assessment
algorithm more highyield than others
that could be used when physician has
only few minutes to see patient?
• many components of algorithm can be
done by person in office other than
physician, and may interface with other
assessments being done
• hard for speaker to say to not do trailmaking test, Part B, because it has highest
correlation with crash rates
• Any questions that can be added to review of systems that have
higher predictability for identifying patients who need to undergo
all parts of assessment algorithm?
• Other than general assessment of cognition, patient who has crashed
once has high risk of crashing again (problem patient not always
willing to offer that information or accept fault for crash)
• people who have fallen also at higher risk for crashes
• Is there any data on 33% of patients who fail ADReS but go on to
pass driving test—are they more likely to crash than people who
pass both?
• no studies on this subset of patients
• If patient disagrees with assessment that he or she should not
drive, does reporting him or her to Motor Vehicle Department run
afoul of Health Insurance Portability and Accountability Act law?
• no, it should not
• most states provide immunity if report made in good faith