Transcript 1 - RCRMC Family Medicine Residency

AAFP
Which of the following is an appropriate
initial empirical regimen for H. pylori?
A.Triple therapy with a PPI,
clarithromycin, and amoxicillin
B.Concomitant therapy with a PPI,
clarithromycin, amoxicillin, and
metronidazole
C.Quadruple therapy with a PPI,
bismuth, metronidazole, and tetracycline
D.Either B or C
Answer
• D.Either B or C
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The clarithromycin and tetracycline shortages will bring up more questions aboutappropriate drug
regimens for H. pylori.
Triple therapy with a PPI, clarithromycin, and amoxicillin or metronidazole is often used firstline...but usually should NOT be. Efficacy rates are falling due to increasing clarithromycin
resistance.
Start with quadruple or concomitant therapy instead.
Quadruple therapy with bismuth, metronidazole, and tetracycline (Helidac,Pylera) plus a PPI is
making a comeback due to better efficacy.
Many pharmacies can't get tetracycline right now due to manufacturing shortages. If you get a call
asking for a switch, DON'T automatically go to doxycycline. Some experts are trying doxy 100 mg
BID, but there's no evidence that it works as well. Try other alternatives.
For patients willing to pay for the combo packs, use Helidac or Pylera. These are still available and
contain tetracycline.
If you use Helidac, give extra metronidazole to overcome resistance. Give 250 mg TID...with the
three mealtime doses of Helidac.
Concomitant therapy means triple therapy with a PPI, clarithromycin, and amoxicillin...PLUS
metronidazole to help boost efficacy.
This concomitant therapy CAN be used instead of quadruple therapy. It's given BID instead of
QID. And it doesn't contain bismuth...so it avoids the black stools or tongue, constipation, etc.
If your pharmacy can't get plain clarithromycin,
prescribe Prevpac(lansoprazole/amoxicillin/clarithromycin) PLUS metronidazole 500 mg BID.
Don't use another macrolide instead of clarithromycin...the others don't work forH. pylori.
Extended-release clarithromycin (Biaxin XL) will probably work...but this isn't proven.
If necessary, consider whether antibiotics can be delayed until optimal ones are available. Start the
PPI right away to heal the ulcer...and add the antibiotics later to help prevent recurrence.
Which of the following is TRUE about using
chlorthalidone instead of hydrochlorothiazide
for hypertension?
A.Chlorthalidone is longer-acting than
hydrochlorothiazide.
B.Chlorthalidone works better to lower blood
pressure.
C.Chlorthalidone has more evidence that it
improves cardiovascular outcomes.
D.All of the above
Answer
• D.All of the above
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CARDIOLOGY
The new Edarbyclor (eh-DAR-bih-clor) means you'll see more interest in
usingchlorthalidone instead of hydrochlorothiazide for hypertension.
Edarbyclor combines the ARB azilsartan (Edarbi) plus
CHLORTHALIDONE...instead of hydrochlorothiazide like most BP combos.
It's the first new chlorthalidone combo in 20 years. The only others are with atenolol
(Tenoretic, etc) or clonidine (Clorpres).
So why is hydrochlorothiazide used much more? It got a head start years ago due to
concerns about more hypokalemia with chlorthalidone...especially with the high doses
that were initially used with thiazides.
But hypokalemia is much less of a problem with today's lower doses...or when
chlorthalidone is combined with an ACEI or ARB.
Chlorthalidone also has some significant advantages. It's longer-acting...works better
to lower BP...and has more evidence that it improves cardiovascular outcomes and
survival.
Consider using chlorthalidone instead of hydrochlorothiazide...especially for patients
with hard-to-treat BP. When switching, use 12.5 mg of chlorthalidone for 25 mg of
hydrochlorothiazide.
Recommend a pill cutter when prescribing chlorthalidone 12.5 mg...the 25 mg tabs
AREN'T scored and it doesn't come in a 12.5 mg strength.
Don't feel compelled to switch patients with good BP control on
hydrochlorothiazide...it may be more trouble than it's worth.
Save Edarbyclor for patients who need an ARB/chlorthalidone combo tablet. It'll cost
about $100/month...compared to less than $20 for chlorthalidone and a generic ACEI.
Watch for a plethora of ARBs to go generic later this
year...Atacand(candesartan), Avapro (irbesartan), and Diovan (valsartan).
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CARDIOLOGY
You'll hear debate about when it's okay to combine reninangiotensin system blockers...ACEIs, ARBs, or aliskiren (Tekturna,
etc).
Some experts hoped that combining these would improve outcomes.
But there's growing evidence that these combos usually DON'T
provide any additional benefit...and are sometimes harmful.
Aliskiren plus an ACEI or ARB increases the risk of stroke, renal
complications, hyperkalemia, and hypotension in some diabetes
patients.
Don't use this combo...especially in diabetes patients.
ACEI plus ARB combos DON'T improve outcomes for
uncomplicated hypertension, vascular disease, diabetes, or after a heart
attack.
An ACEI plus ARB or aldosterone antagonist (spironolactone, etc)
can improve systolic heart failure...and possibly kidney disease with
proteinuria. But the combo can also cause more serious side effects.
Use an ACEI first in most cases...these have the most evidence for
improving outcomes. Use an ARB if an ACEI isn't tolerated.
Save aliskiren for patients who can't use other first-line BP meds.
There's no proof that aliskiren improves outcomes
Which of the following is TRUE about new
recommendations for hepatitis B and human
papillomavirus (HPV) vaccines?
A.HPV should be given to boys at age 11 or
12 to reduce the risk of genital warts and
some precancerous lesions.
B.Hepatitis B vaccine should be given to all
adults with diabetes under age 60.
C.Hepatitis B vaccine can be given to adults
with diabetes over age 60 if they are at
increased risk for hepatitis B.
D.All of the above
Answer
• D.All of the above
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VACCINES
More people will get hepatitis B (Engerix-B, Recombivax HB) or HPV (Gardasil)
vaccines.
CDC now recommends hepatitis B vaccine for adults with diabetes...and the HPV
(human papillomavirus) vaccine for boys.
Hepatitis B vaccine for diabetes. Recommend hepatitis B immunization for adults with
diabetes under age 60.
Adults with diabetes are more prone to liver disease...have twice the risk of
contracting hepatitis B...and seem more likely to develop a chronic infection than people
without diabetes.
Patients are also at risk for hepatitis B if they're in a group setting that improperly
shares blood glucose monitoring equipment.
Explain that one case of hepatitis B can be prevented for every 124 adults with
diabetes under age 60 who are vaccinated.
Consider hep B vaccination for diabetes patients age 60 and up if they are at increased
risk for hepatitis B. But keep in mind that the vaccine is less effective in these older
patients.
HPV vaccine for boys. Recommend routine HPV vaccination for boys aged 11 to
12...and for those up to 21 who haven't gotten it yet.
Explain that vaccination reduces the risk of genital warts and some precancerous
lesions in males...and will likely reduce HPV transmission to their partner.
Use Gardasil for boys. Cervarix doesn't protect against the appropriate HPV types and
it's not approved for males.
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OPIOIDS
People are often surprised to hear that chronic opioids can lead to
low testosterone and estrogen.
It's more common than you'd think...especially in men.
Opioids can decrease the release of testosterone and estrogen.
Hormone levels drop in up to 86% of chronic opioid users...leading
to low libido, impotence, or irregular menses.
Check hormone levels if patients have symptoms. If levels are low,
consider non-opioid options for pain.
If this isn't possible, consider hormone therapy...but weigh the risks
and benefits carefully.
Combined estrogen and progestin therapy may increase the risk of
cardiovascular disease and breast cancer in postmenopausal
women...andtestosterone might cause edema and worsen BPH in older
men.
Prostate cancer due to testosterone replacement is controversial...and
any risk is likely small. But monitor men on testosterone for prostate
cancer or worsening BPH.
PEDIATRICS
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You'll hear questions about using ciclesonide (Omnaris) or other
corticosteroid nasal sprays instead of antibiotics for ear infections.
Put this in perspective.
This is preliminary...and it's not for ACUTE ear infections.
Nasal steroids are being tried for otitis media WITH
EFFUSION...fluid that persists in the middle ear without signs of an
acute infection. This occurs mostly in kids under age 3.
It usually resolves on its own...but for persistent cases, kids often get
ventilating tubes to drain the fluid and prevent hearing loss.
Drugs are sometimes used to address underlying causes...antibiotics
for an infection or a steroid for inflammation. But drug treatment is
falling out of favor because there's not much benefit.
Don't use nasal steroids for otitis media with effusion. There's not
enough evidence that they're effective.
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PEDIATRICS
New guidelines will help management of constipation in kids.
These are aimed at kids with "functional" constipation...usually due
to a child withholding bowel movements to avoid pain.
If disimpaction is needed, use oral PEG (Miralax, etc) instead of
enemas or digital disimpaction. Oral PEG works as well as enemas and
is better tolerated.
Give 1 to 1.5 g/kg/day of PEG for 3 days.
For maintenance, recommend behavioral modification...dietary
changes...and daily meds to soften stools (PEG, milk of magnesia,
etc).
Use PEG first for maintenance. It works better than lactulose in
kids...and as well as milk of magnesia with fewer side effects.
Start with PEG 0.4 to 1 g/kg/day and titrate as needed. Aim for one
or two soft stools a day.
If needed, go to milk of magnesia or lactulose next. Avoid
docusate...there's no proof that it works for constipation in kids.
Continue meds for at least 6 months to break the cycle of holding
stools out of fear of pain.
Explain that carbohydrates in prune, pear, and apple juices also have
a laxative effect
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STATINS
Do statins benefit very elderly patients?
Providers often wonder if there's an age at which statin benefits are
outweighed by risks, such as myopathy or drug interactions.
But cholesterol is still an important modifiable risk factor...even in patients
over 80. Each 40 mg/dL drop in LDL lowers CV risk by about 20% over one
year...REGARDLESS of age.
Continue to use statins in the elderly if indicated...unless the patient is not
likely to live a year or more. Keep in mind that a patient who survives to 80
will live another 8 years on average.
Watch for drug interactions and side effects. Keep in mind that using a statin
to prevent cardiovascular events may not be worth causing muscle pain or
weakness that leads to a fall and fracture.
Start with a low statin dose and slowly titrate to the patient's LDL goal to
minimize side effects.
Try reducing the dose if patients complain of muscle pain.
Or consider switching to pravastatin or rosuvastatin (Crestor)...they have
fewer drug interactions and might cause less myopathy.
Also check vitamin D status...not enough can also cause muscle pain. Most
adults need 800 to 2000 IU/day to maintain adequate levels.
Many patients and prescribers swear by CoQ10 for myopathy. If you're an
evidence-based type, tell them the evidence is sketchy. If you're comfortable
trying this relatively safe approach, suggest 100 mg once or twice daily
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SUPPLEMENTS
FDA will take some OTC HCG weight loss products off the market.
They're going after homeopathic products promoted for weight loss.
Human chorionic gonadotropin (HCG) isn't an approved homeopathic.
Some weight loss clinics are giving Rx HCG injections...along with a
500 calorie/day diet.
They claim that HCG helps burn fat and maintain muscle...but there's
NO scientific evidence to support this. In fact, FDA requires Rx HCG
labeling to say that it DOESN'T work for weight loss.
Using HCG for weight loss is also linked to serious problems...clots,
depression, heart attacks, and even death.
Explain that any weight loss is likely due to the very low-calorie diet.
And point out that losing weight too rapidly can cause gallstones,
electrolyte imbalances, and arrhythmias.
Keep in mind not all "HCG" supplements will disappear. Some
contain amino acids that are supposed to stimulate HCG production.
But these haven't been shown to help people lose weight either.
Steer patients away from HCG for weight loss. Encourage focusing
on abalanced diet, exercise, and setting realistic goals.
Which of the following is TRUE about
treating latent tuberculosis (TB)?
A.Giving isoniazid (INH) daily for 9
months is no longer recommended.
B.A new alternative is INH plus
rifapentine once a week for 12 weeks.
C.The weekly regimen should be given
as directly observed therapy to ensure
adherence.
D.Both B and C
Answer
• D.Both B and C
INFECTIOUS DISEASES
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You'll hear about a new WEEKLY regimen for latent tuberculosis.
Patients with a recent positive TB test usually get isoniazid (INH) DAILY for 9
months to prevent an active infection.
A new alternative is INH plus rifapentine (Priftin) once a WEEK for only 12 weeks.
This works as well as daily INH and causes less hepatoxicity...BUT stopping drugs early
can lead to resistant TB.
That's why CDC wants a health professional to actually watch each dose get
swallowed...called "directly observed therapy."
This new regimen costs $250 for the drugs plus extra for directly observed
therapy...compared to $20 for 9 months of INH.
Continue to use daily INH for most patients. Add pyridoxine (vitamin B6) to prevent
B6 deficiency and neuropathy.
Go to INH plus rifapentine if there's concern about adherence to INH for 9 months
AND if directly observed therapy is feasible.
Currently there's a shortage of rifapentine. Ask the pharmacy to make sure the patient
can get it for 12 weeks before starting.
Watch for interactions between rifapentine and hormonal contraceptives, warfarin,
phenytoin, antiretrovirals, and others. Rifapentine is an enzyme inducer like rifampin.
See our PL Detail-Document for the regimens recommended for treating latent
tuberculosis.
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WOMEN'S HEALTH
Women often ask what they can use for pain during pregnancy and breastfeeding.
Acetaminophen is usually a good place to start for mild to
moderate pain. Tell women that it's not linked to birth defects...and isn't a problem for breastfed
infants.
NSAIDs (ibuprofen, etc) should usually be avoided during pregnancy.
Explain that they're linked to miscarriage and certain rare birth defects in the first trimester...and
premature closure of the ductus arteriosus in the third trimester.
On the other hand, feel comfortable suggesting ibuprofen during breastfeeding...very little ends up
in breast milk.
Tramadol should be avoided in the first trimester...and used only with caution in the third. It can
cause fetal toxicity in animals...and breathing problems and withdrawal symptoms in newborns.
Tell women that tramadol is usually okay to use during lactation...only small amounts pass into
breast milk.
Opioids (codeine, etc) are associated with an increase in heart defects and spina bifida when used
during the first trimester. But if there's a risk, it's likely very small.
Keep this in perspective. Use an opioid if pain during pregnancy can't be managed with other
options.
Be careful about using codeine, hydrocodone, or oxycodone during breastfeeding. These opioids
are converted to active metabolites by CYP2D6 enzymes. Babies can get an opioid overdose if their
mother is an ultrarapid 2D6 metabolizer.
Ultrarapid 2D6 metabolism occurs in up to 10% of Caucasians...3% of African Americans...and 1%
of Chinese and Hispanics.
If an opioid is necessary during lactation, use a low-dose, short-acting agent...and recommend
taking it AFTER feedings.
Also try to switch to acetaminophen or an NSAID within 4 days after delivery...before infants
begin drinking a lot of milk.
Explain the importance of closely watching the infant for CNS depression or oversedation.
Which of the following is TRUE about
treating ADHD in ADULTS?
A.Most kids with ADHD outgrow it by
the time they are adults.
B.Stimulants can be used in patients
with hypertension if their BP is
controlled and monitored.
C.Stimulants are proven to increase the
risk of substance abuse.
D.Adderall XR is likely to have a longer
duration than Vyvanse.
Answer
• B.Stimulants can be used in patients with
hypertension if their BP is controlled and
monitored.
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ADHD
You'll hear new controversy about whether ADHD stimulants increase cardiovascular
risk or substance abuse in ADULTS.
About 60% of kids with ADHD will have symptoms as adults.
Cardiovascular risk concerns led to updated labeling in 2006.
Now new evidence suggests that ADHD stimulants or Strattera (atomoxetine) DON'T
cause serious CV events in most kids OR adults.
These meds DO increase BP and heart rate...so it's easy to understand why experts
worry about CV risk. But it IS okay to use them in hypertensive patients if BP is
controlled...and monitored.
Avoid these meds in patients with serious arrhythmias, symptomatic heart disease, or a
recent cardiovascular event.
Substance abuse is about 6 times higher in patients with ADHD.
But explain that most evidence suggests that stimulants DON'T increase substance
abuse...and might even DECREASE it.
Watch for signs of diversion...requests for higher doses, refills too soon, lost Rxs, etc.
If necessary, try an extended-release stimulant (Vyvanse, etc)...these are less likely to
be abused than immediate-release products.
Or switch to Strattera or bupropion. These are rarely abused...but are less effective for
ADHD.
Keep in mind some extended-release stimulants work longer than others. Expect about
8 hours with Ritalin LA... 10 hrs with Adderall XR or Focalin XR...and 12 hrs
with Concerta, Daytrana, or Vyvanse.
PERIOPERATIVE CARDIAC
RISK REDUCTION
Which one of the following is
classified as high-risk
surgery? (check one)
A. Prostate surgery.
B. Breast surgery.
C. Aortic surgery.
D. Orthopedic procedures.
Answer
• C. Aortic surgery.
PERIOPERATIVE CARDIAC RISK
REDUCTION
Which of the following statements about drug
therapy to reduce perioperative risk are
correct? (check all that apply)
A. Perioperative statin therapy reduces
cardiovascular risk in patients undergoing vascular
surgery.
B. For most patients, aspirin therapy should be
discontinued before surgery.
C. Patients who are not already taking a beta blocker
should begin therapy immediately before surgery.
D. Beta blockers should be initiated several weeks
before surgery.
Answer
• A. Perioperative statin therapy reduces
cardiovascular risk in patients undergoing
vascular surgery.
D. Beta blockers should be initiated several
weeks before surgery.
Perioperative Cardiac Risk Reduction
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Cardiovascular complications are the most common cause of
perioperative morbidity and mortality.
Noninvasive stress testing is rarely helpful in assessing risk, and for most
patients there is no evidence that coronary revascularization provides
more protection against perioperative cardiovascular events than optimal
medical management.
Patients likely to benefit from perioperative beta blockade include those
with stable coronary artery disease and multiple cardiac risk factors.
Perioperative beta blockers should be initiated weeks before surgery and
titrated to heart rate and blood pressure targets.
The balance of benefits and harms of perioperative beta-blocker therapy
is much less favorable in patients with limited cardiac risk factors and
when initiated in the acute preoperative period.
Perioperative statin therapy is recommended for all patients
undergoing vascular surgery.
When prescribed for the secondary prevention of cardiovascular disease,
aspirin should be continued in the perioperative period.
Clinical recommendation
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Initiation of fixed-dose beta blockers immediately before surgery may be harmful and is not advised.
B
Evidence-based guidelines and a randomized clinical trial
If the decision is made to initiate preoperative beta-blocker therapy, it should begin several weeks
before surgery, allowing time for dose titration and monitoring of adverse events.
B
Evidence-based guidelines
Beta blockers and statins should be continued perioperatively in patients who are already taking these
medications.
A
Evidence-based guidelines
Perioperative statin therapy is recommended for patients undergoing vascular surgery, regardless of
the presence of cardiac risk factors.
A
Evidence-based guidelines and randomized clinical trials
Aspirin therapy for secondary prevention of cardiovascular disease should be continued
perioperatively unless the risk of surgical bleeding is prohibitive.
B
Evidence-based guidelines and meta-analyses
Surgical Risk Categories
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Risk groupCardiac risk* (%)Examples
High
>5
Aortic or other major vascular surgery
Peripheral vascular surgery
Intermediate
1 to 5
Carotid endarterectomy
Head and neck surgery
Intraperitoneal or intrathoracic surgery
Orthopedic surgery
Prostate surgery
Low
<1
Superficial procedures
Breast surgery
Cataract surgery
Endoscopic procedures
Most ambulatory surgeries
• The most challenging patients to evaluate preoperatively are those with
at least one cardiac risk factor and poor or uncertain functional
capacity who are undergoing intermediate- or high-risk surgery.
• Evidence from a randomized trial suggests that preoperative stress
testing is of no value in patients with only one or two cardiac risk
factors.8
• The positive predictive value of stress testing in this population is
about 20 to 40 percent, meaning that most patients with positive test
results will not have an adverse perioperative cardiac event.9
• This is consistent with the finding that with optimal medical therapy,
patients with minimal areas of reversible left ventricular myocardial
ischemia on stress imaging have no greater incidence of perioperative
cardiac events than those with no evidence of ischemia.
• Therefore, noninvasive stress testing is best reserved for patients with
three or more cardiac risk factors in whom preoperative coronary
revascularization is logistically feasible and would have been
considered regardless of the surgical context.
Interventional Myocardial Protection
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PREOPERATIVE CORONARY REVASCULARIZATION
The Coronary Artery Revascularization Prophylaxis (CARP) trial was the first
large (n = 5,859) randomized study designed to determine whether
prophylactic coronary revascularization before major vascular surgery reduced
perioperative cardiac events more than optimal pharmacologic management.
No difference in all-cause mortality was observed at a median follow-up of 2.7
years, and no difference was found in the incidence of postoperative
myocardial infarction (MI).
One criticism of the CARP trial is that the selection criteria excluded too many
high-risk patients.
To address this issue, the Dutch Echocardiographic Cardiac Risk Evaluation
Applying Stress Echocardiography (DECREASE-V) trial included patients
undergoing vascular surgery who had significant cardiac risk factors and
evidence of extensive ischemia.14
Based on the composite end point of all-cause mortality and nonfatal MI,
preoperative revascularization conferred no benefit (Table 4).13–15
These results are consistent with a study that showed no incremental benefit
from prophylactic percutaneous coronary intervention (PCI) when added to
rigorous medical therapy in nonsurgical patients with stable angina.16
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Pharmacologic Intervention
BETA BLOCKERS
The use of perioperative beta blockers is one of the most controversial topics in perioperative medicine.
Most evidence suggests that perioperative beta blockade reduces the risk of MI and cardiac death.
However, enthusiasm for perioperative beta blockade was significantly tempered in 2008 after results of the
Perioperative Ischemic Evaluation (POISE) trial were published.34
This trial randomized more than 8,000 patients to treatment with fixed-dose extended-release metoprolol (Toprol XL)
or placebo initiated immediately before surgery.
Although beta-blocker therapy reduced the risk of nonfatal MI and cardiac death, overall mortality and stroke risk
increased, possibly because of drug-induced hypotension.
These findings caused the ACC and AHA to publish a focused update in which the only class I recommendation for
perioperative beta blockade was that it be continued in patients who were already receiving chronic beta-blocker
therapy.
Although perioperative beta blockade could still be considered in patients with inducible ischemia, coronary artery
disease, or multiple cardiac risk factors, the ACC/ AHA update emphasized the mixed evidence and potential hazards
of rigorous treatment.
New research is beginning to define the safest and most effective use of perioperative beta blockade. A recent cohort
study found that acute preoperative beta blockade in a beta-blocker–naive population resulted in worse cardiac
outcomes compared with a matched cohort receiving chronic beta-blocker therapy.
This effect was not related to an increased stroke risk, but to an increased occurrence of MI and cardiac death. It has
been suggested that in addition to reducing myocardial oxygen demand, beta blockers have anti-inflammatory
properties that contribute to plaque stabilization.
The onset of these effects is delayed, which may be why studies in which beta blockers have been initiated
immediately before surgery have not shown the therapeutic benefit observed when they are started at least two weeks
before surgery.
Early preoperative initiation of beta blockers also allows time for gradual dose adjustments and identification and
management of adverse effects.
A study using a large administrative database found that the effect of perioperative beta blockers differed depending
on the patient's underlying clinical risk profile.
In patients with a Revised Cardiac Risk Index score of at least 3, administration of beta blockers reduced the odds of
in-hospital mortality.
However, in lower-risk patients, administration of beta blockers had no effect or increased the risk of in-hospital
death.
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STATINS
In addition to their lipid-lowering ability, statins reduce vascular inflammation, improve
endothelial function, and stabilize atherosclerotic plaques—so-called pleotropic effects.
The results of several clinical trials and a meta-analysis provide strong evidence that
perioperative statin therapy reduces cardiovascular risk in patients undergoing vascular
surgery.
In the DECREASE-III trial, administration of fluvastatin (Lescol) reduced the incidence
of perioperative MI, in addition to 30-day nonfatal MI and cardiac death.43
The number needed to treat was 13 to prevent one occurrence of myocardial ischemia,
36 to prevent one nonfatal MI, and 42 to prevent one cardiac death. There is no evidence
that perioperative statin use is associated with an increase in adverse events, including
rhabdomyolysis or liver dysfunction.43,45
There is a rebound effect with abrupt cessation of statin therapy, during which the risk
of cardiovascular events sharply increases.46,47
For this reason, the perioperative use of an extended-release formulation is advisable
because no intravenous statin is available.
Extended-release versions of lovastatin (Altoprev) and fluvastatin are available.
Ideally, statins should be initiated several weeks before surgery for maximal antiinflammatory and plaque-stabilizing benefits.29,30
However, benefits have been observed from statin initiation in the immediate
preprocedural period.48
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ASPIRIN
Aspirin causes irreversible inactivation of cyclooxygenase 1 and 2, which reduces
prostaglandin and thromboxane production and results in antiplatelet and antiinflammatory effects.
Unstable coronary plaques are associated with inflammatory mediators and platelet
accumulation, hence the benefit of aspirin in the treatment of acute coronary syndrome
and secondary prevention of coronary artery disease.
In a meta-analysis of patients receiving aspirin as secondary prevention, discontinuation
resulted in a threefold increase in the risk of adverse cardiac events.49
Among patients with coronary stents, cessation of aspirin therapy resulted in a 90-fold
increase in complications.49
Aspirin withdrawal has been implicated as a causal factor in up to 10 percent of adverse
perioperative cardiovascular events occurring an average of 10 days after aspirin
cessation.50,51
Aspirin increases surgical bleeding by approximately 20 percent.33 However, concern
over hemorrhagic complications is not supported by evidence from clinical trials.
A meta-analysis of studies comparing surgical bleeding in patients taking low-dose
aspirin with that of patients who were not taking aspirin found no difference in severity
of bleeding events (with the exception of intracranial surgery and possibly transurethral
prostatectomy) or mortality.50
Therefore, in most cases, aspirin therapy should be continued in the perioperative
period.
Communication between the primary care physician and surgeon is essential in
weighing the cardiovascular risks of aspirin cessation against the bleeding risks of
aspirin continuation.
EVALUATING ACUTELY INJURED
PATIENTS FOR INTERNAL
DERANGEMENT OF THE KNEE
Which one of the following is the most
accurate diagnostic test for meniscal
injury? (check one)
A. Evaluation for joint line tenderness.
B. McMurray test.
C. Anterior drawer test.
D. Thessaly test.
Answer
• D. Thessaly test.
EVALUATING ACUTELY INJURED
PATIENTS FOR INTERNAL DERANGEMENT
OF THE KNEE
Which one of the following historical and physical
examination findings would require radiography in a
patient with acute knee pain? (check one)
A. Inability to flex knee to 90 degrees.
B. Age between 12 and 50 years.
C. Ability to bear weight for at least four steps
immediately after injury or in the emergency setting.
D. Joint effusion 48 hours after a fall.
Answer
• A. Inability to flex knee to 90 degrees.
Evaluating Acutely Injured Patients for Internal Derangement of the Knee
• Although historical findings have some value in
diagnosing internal derangement of the knee, a
thorough physical examination can often rule out
fracture and ligamentous and meniscal injuries.
• The Ottawa Knee Rule can help physicians determine
which patients require radiography.
• Positive physical examination tests and findings of
acute effusion suggest internal derangement.
• An abnormal McMurray or Thessaly test strongly
suggests meniscal injury, whereas a normal Thessaly
test may rule out meniscal injury.
• Absence of evidence of joint effusion significantly
decreases the probability of internal derangement.
• Magnetic resonance imaging should be reserved for
ruling out internal derangement in patients with
suggestive historical and physical examination findings.
• Nearly one-half of adults will experience knee
pain at some point in their lives.1
• Primary care physicians in the United States
evaluate knee pain during approximately 4 million
office visits each year, and knee symptoms are the
10th most common reason for outpatient visits.2
• Although most episodes of knee pain in primary
care patients are caused by osteoarthritis, many
patients have acute injuries.
• Approximately 9 to 10 percent of patients with
acute knee pain who are treated by family
physicians have meniscal tears, 7 percent have
collateral ligament injury, and about 4 percent
have a cruciate ligament injury
Clinical recommendation
• The Ottawa Knee Rule should be used to determine which
patients with acute knee injury require radiography.
• A
• Further testing is not immediately needed in patients with
knee injury who have negative physical examination
findings, although close clinical follow-up is required.
• C
• In patients with suspected meniscal injury, the Thessaly
test is preferred over the McMurray test and evaluation for
joint line tenderness.
• C
• Internal derangement should be suspected in patients with
knee trauma and effusion.
• C
Indications for Radiography in Patients
with Acute Knee
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InjuryIndicationAmerican College of Radiology criteria5Ottawa Knee Rule6Pittsburgh Knee Rule7
Age < 12 years or > 50 years
XP
Age ≥ 55 years
XO
Altered mental status
X
Fall or blunt trauma
XP
Inability to bear weight for four steps (unable to transfer weight twice) immediately after injury or in the emergency
setting
X OP
X
X
Inability to flex knee to 90 degrees
XO
X
Joint effusion within 24 hours of a direct blow or fall
X
Tenderness over head of fibula or isolated to patella without other bony tenderness
XO
X
Information from references 5 through 7.
• The American College of Radiology has published
recommendations for use of knee radiography in patients
who have acute knee trauma.5
• Although the recommendations have not been
prospectively validated, they are similar to the Ottawa
Knee Rule criteria.
• They recommend against radiography in patients
(excluding infants) who can walk without a limp or who
have a twisting injury and no effusion.
• The Pittsburgh Knee Rule criteria include blunt trauma or
fall as the mechanism of injury, age younger than 12 years
or older than 50 years, and inability to walk as independent
predictors of fracture.7
• A prospective validation trial comparing the Ottawa and
Pittsburgh criteria showed that each rule is sensitive (97 to
100 percent of fractures found), but that the Pittsburgh rule
is more specific (60 versus 27 percent for the Ottawa
rule).12
• Anterior cruciate ligament tear
• Anterior drawer test3
• With the patient supine on the examining table,
flex the hip to 45 degrees and the knee to 90
degrees. Sit on the dorsum of the foot, wrap hands
around the hamstrings (ensuring that these
muscles are relaxed), then pull and push the
proximal part of the leg, testing the movement of
the tibia on the femur. Do these maneuvers in
three positions of tibial rotation: neutral, 30
degrees externally rotated, and 30 degrees
internally rotated. A normal test result is no more
than 6 to 8 mm of laxity.
• Lachman test3
• With the patient supine on the examining
table and the leg at the examiner's side,
slightly externally rotated and flexed (20 to
30 degrees), stabilize the femur with one
hand and apply pressure to the back of the
knee with the other hand, with the thumb on
the joint line. A positive test result is
movement of the knee with a soft or mushy
end point.
• Pivot shift
• Fully extend the knee and rotate
the foot internally. Apply a
valgus (abduction) force while
progressively flexing the knee,
watching and feeling for
translation of the tibia on the
femur.
3
test
• Meniscal tear
• Joint line tenderness3
• Palpate medially or laterally
along the knee to the joint line
between the femur and tibial
condyles. Pain on palpation is a
positive finding.
• McMurray test3
• Flex the hip and knee maximally.
Apply a valgus (abduction) force to the
knee while externally rotating the foot
and passively extending the knee. An
audible or palpable snap during
extension suggests a tear of the medial
meniscus. For the lateral meniscus,
apply a varus (adduction) stress during
internal rotation of the foot and passive
extension of the knee.
• Thessaly
• Hold patient's outstretched
hands while he or she stands
flat-footed on the floor,
internally and externally
rotating three times with the
knee flexed 20 degrees.
15
test
• Effusion
• Ballottement test16
• Push the patella posteriorly with two or
three fingers using a quick, sharp
motion. In the presence of a large
effusion, the patella descends to the
trochlea, strikes it with a distinct
impact, and flows back to its former
position.
Maneuver or clinical findings
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Positive likelihood ratio*
Negative likelihood ratio*
Probability of injury if maneuver is†Positive (%)
Negative (%)
Anterior cruciate ligament tear
Pivot shift test3
20.3 0.4 69 4
Lachman test3
12.4 0.14 58 2
Anterior drawer test3
3.7 0.6 29 6
Effusion
Ballottement test; noticeable swelling16
3.6 0.4 NA NA
Meniscal tear
Thessaly test15
39.3 0.09 81 1
McMurray test3
17.3 0.5 66 5
Age > 40 years, continuation of activity not possible, weight bearing during trauma, and pain with
passive flexion17
5.8 0.9 39 9
Joint line tenderness3
1.1 0.8 11 8
• Magnetic resonance imaging (MRI) is highly accurate in
diagnosing injury to the ACL and posterior cruciate
ligament.18
• It can be used when historical and physical examination
findings are equivocal.
• Although the use of MRI has been advocated to confirm
clinical suspicions before proceeding to arthroscopy,13 the
American Academy of Orthopaedic Surgeons states that it
is usually not required to diagnose an ACL tear.19
• It has been suggested that MRI is better used to rule out
internal derangement than to rule it in, because clinical
findings are often sufficient for diagnosis.20
• Internal derangement is unlikely (less than 2 percent) and
MRI typically unnecessary if physical examination
maneuvers are negative.3
Knee Injury: Diagnostic Clues from History and
Physical Examination
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History
Physical examination
Diagnosis to consider
Direct injury to anterior tibia; forced hyperflexion or hyperextension injury; posterior
pain; pain with kneeling
Positive sag or posterior drawer test; mild swelling or slow onset; posterior swelling;
painful limitation (10 to 20 degrees flexion)
Posterior cruciate ligament tear
Pivoting or leaping injury; sense of disruption; audible pop; instability; early swelling
(one to two hours)
Positive Lachman, anterior drawer, or pivot shift test; loss of hyperextension
Anterior cruciate ligament tear
Squatting, cutting, or twisting injury; trivial twisting injury in older persons; giving way;
locking and catching
Joint line tenderness; positive McMurray test; joint effusion; loss of extension (locked
knee)
Meniscal tear
Thessaly test
DIAGNOSIS AND MANAGEMENT OF GENITAL
ULCERS
Which one of the following statements about acyclovir
(Zovirax) therapy for genital ulcers caused by herpes simplex
virus infection is correct? (check one)
A. Initial episodes should be treated for no more than five
days.
B. Both initial and recurrent episodes should be treated for
five days.
C. Both initial and recurrent episodes should be treated for
seven to 10 days.
D. Initial episodes should be treated for seven to 10 days.
Answer
• D. Initial episodes should be treated for
seven to 10 days.
DIAGNOSIS AND MANAGEMENT OF
GENITAL ULCERS
Which one of the following may be prescribed for
treatment of chancroid? (check one)
A. Oral azithromycin (Zithromax), one 500-mg
dose.
B. Oral ciprofloxacin (Cipro), 250 mg twice daily
for two days.
C. Oral erythromycin, 250 mg twice daily for seven
days.
D. Intramuscular ceftriaxone (Rocephin), one 250mg dose.
Answer
• D. Intramuscular ceftriaxone (Rocephin),
one 250-mg dose.
Diagnosis and Management of
Genital Ulcers
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Herpes simplex virus infection and syphilis are the most common causes of genital ulcers in the
United States.
Other infectious causes include chancroid, lymphogranuloma venereum, granuloma inguinale
(donovanosis), secondary bacterial infections, and fungi.
Noninfectious etiologies, including sexual trauma, psoriasis, Behçet syndrome, and fixed drug
eruptions, can also lead to genital ulcers.
Although initial treatment of genital ulcers is generally based on clinical presentation, the
following tests should be considered in all patients: serologic tests for syphilis and darkfield
microscopy or direct fluorescent antibody testing for Treponema pallidum, culture or
polymerase chain reaction test for herpes simplex virus, and culture for Haemophilus ducreyi in
settings with a high prevalence of chancroid.
No pathogen is identified in up to 25 percent of patients with genital ulcers. The first episode of
herpes simplex virus infection is usually treated with seven to 10 days of oral acyclovir (five
days for recurrent episodes). Famciclovir and valacyclovir are alternative therapies.
One dose of intramuscular penicillin G benzathine is recommended to treat genital ulcers
caused by primary syphilis.
Treatment options for chancroid include a single dose of intramuscular ceftriaxone or oral
azithromycin, ciprofloxacin, or erythromycin.
Lymphogranuloma venereum and donovanosis are treated with 21 days of oral doxycycline.
Treatment of noninfectious causes of genital ulcers varies by etiology, and ranges from topical
wound care for ulcers caused by sexual trauma to consideration of subcutaneous pegylated
interferon alfa-2a for ulcers caused by Behçet syndrome.
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Clinical recommendation
Treatment
Oral acyclovir (Zovirax), valacyclovir (Valtrex), and famciclovir (Famvir) are effective treatments
for initial or recurrent episodes of HSV by decreasing symptom duration and viral shedding.
A
Lymphogranuloma venereum and granuloma inguinale (donovanosis) should be treated with oral
doxycycline, 100 mg twice daily for 21 days. The patient should be followed until resolution of signs
and symptoms. For patients with donovanosis, antibiotics should be continued if necessary.
C
In patient's with Behçet syndrome, subcutaneous pegylated interferon alfa-2a (Pegasys), 6 million
units three times weekly for three months, reduces duration and pain of oral ulcers and frequency of
genital ulcers.
B
There is insufficient evidence for the use of oral acyclovir, oral colchicine, and topical interferon to
treat ulcers caused by Behçet syndrome.
B
Topical and vaginal sucralfate (not available in the United States) do not significantly reduce the
average frequency, healing time, or pain of genital ulcers caused by Behçet syndrome.
B
Extensive genital ulcers may be treated with cool water or saline, topical antimicrobials, topical or
oral analgesics, perineal baths, topical or oral anti-inflammatory agents, or cool compresses with
Burow solution to decrease surrounding edema, inflammation, and pain.
C
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Prevention
Avoiding sexual intercourse during outbreaks does not prevent transmission of HSV
infection.
B
Couples in which one partner has HSV infection should be counseled that consistent
condom and dental dam use may decrease, but does not eliminate, risk of transmission.
C
In patients with symptomatic HSV outbreaks, daily acyclovir or valacyclovir should be
considered to reduce transmission to seronegative partners. Famciclovir is less effective
for reducing viral shedding and HSV transmission.
B
Follow-up testing
Screening for HIV should be performed in all patients with previously negative results
who have genital ulcers caused by Treponema pallidum or Haemophilus
ducreyi infection, and should be strongly considered for those who have genital ulcers
caused by HSV infection.
C
Patients treated for chancroid should be retested for syphilis and HIV three months after
diagnosis.
C
Women who have partners with HSV infection should be offered type-specific serologic
testing to assess their risk.
C
HIV = human immunodeficiency virus; HSV = herpes simplex virus.
Epidemiology
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The global incidence of genital ulcer disease is estimated to be more than 20 million cases annually. 4
HSV types 1 and 2 are the most common causes of genital ulcers in the United States, followed by
syphilis and chancroid.5
One in five women and one in nine men 14 to 49 years of age has genital HSV type 2 infection. 6
In 2009, the rate of syphilis was highest in men and women 20 to 24 years of age (20.7 and 5.6 cases
per 100,000 persons, respectively).
However, syphilis rates increased in persons 15 to 19 years of age between 2002 and 2009 (1.3
versus 6.0 cases per 100,000 males and 1.5 versus 3.3 cases per 100,000 females). 7,8
In 2006, most cases of primary and secondary syphilis occurred in men who have sex with men. 7,8
Chancroid usually occurs in discrete outbreaks, but the disease may be endemic in some regions.
The incidence of chancroid has been declining in the United States, with only 28 cases reported to
state health departments in 2009.9
However, H. ducreyi infection is challenging to confirm, likely leading to underreporting. 9
Approximately 10 percent of patients with chancroid are coinfected with syphilis or HSV; these are
even more common coinfections for patients who acquired chancroid outside the United States. 5
Lymphogranuloma venereum primarily occurs in men who have sex with men. 10
Behçet syndrome is most common in young adults in the Eastern Mediterranean and in men in the
Far East, whereas women are predominantly affected in the United States.2
Herpes simplex virus infection
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Usually multiple vesicular lesions that rupture and become painful, shallow ulcers (Figure
1)Constitutional symptoms, lymphadenopathy in first-time infections
Definitive: herpes simplex virus identified on culture or polymerase chain reaction testing of ulcer
scraping or vesicle fluid aspiratePresumptive: typical lesions and any of the following factors
Previously known outbreak
Positive Tzanck smear of ulcer scraping
Exclusion of other causes of ulcers
Fourfold increase in acute and convalescent antibody titer results (in a first-time infection)
First episode
Acyclovir (Zovirax), 400 mg orally three times daily for seven to 10 days, or 200 mg orally five
times daily for seven to 10 days
Famciclovir (Famvir), 250 mg orally three times daily for seven to 10 days
Valacyclovir (Valtrex), 1,000 mg orally twice daily for seven to 10 days
Recurrent episode
Acyclovir, 400 mg orally three times daily for five days, 800 mg orally twice daily for five days, 800
mg orally three times daily for two days, or 200 mg orally five times daily for five days
Famciclovir, 1,000 mg twice daily for one day, 500 mg orally once then 250 mg twice daily for two
days, or 125 mg orally twice daily for five days
Valacyclovir, 500 mg orally twice daily for three days or 1,000 mg orally once daily for five days
Suppressive therapy
Acyclovir, 400 mg orally twice daily or 200 mg orally three to five times daily
Famciclovir, 250 mg orally twice daily
Valacyclovir, 1,000 mg orally once daily
Valacyclovir, 500 mg orally once daily, if fewer than 10 outbreaks per year
Syphilis (primary)
• Single, painless, well-demarcated ulcer (chancre) with a
clean base and indurated border (Figure 2)Mild or
minimally tender inguinal lymphadenopathy
• Treponema pallidum identified on darkfield microscopy or
direct fluorescent antibody testing of a chancre or lymph
node aspirate
• Penicillin G benzathine, 2.4 million units intramuscularly
in a single dose
• or
• Positive result on serologic nontreponemal testing (i.e.,
Venereal Disease Research Laboratories or rapid plasma
reagin) that is confirmed with a positive result on serologic
treponemal testing (i.e., fluorescent treponemal antibody
absorption or T. pallidum passive agglutination)
Chancroid
• Nonindurated, painful with serpiginous border and
friable base; covered with a necrotic, often
purulent exudate (Figure 3)Tender, suppurative,
unilateral inguinal lymphadenopathy or adenitis
• Gram stain suggestive ofHaemophilus
ducreyi (gram-negative, slender rod or
coccobacillus in a “school of fish”
pattern)Definitive: H. ducreyi identified on
culturePresumptive: painful genital ulcer or ulcers
with regional lymphadenopathy and no evidence
of T. pallidum infection at least seven days after
ulcer onset, and testing negative for herpes
simplex virus
Lymphogranuloma venereum
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Small, shallow, painless, genital or rectal papule or ulcer; no
indurationUnilateral, tender inguinal or femoral lymphadenopathyRectal
bleeding, pain, or discharge; ulcerative proctitis; constipation or tenesmus
Definitive:
Chlamydia trachomatisserotype L1, L2, or L3 culture, identified from clinical
specimen
or
Immunofluorescence demonstrating inclusion bodies in leukocytes of an
inguinal lymph node (bubo) aspirate
or
Microimmunofluorescence positive for lymphogranuloma venereum strain
of C. trachomatis
Doxycycline, 100 mg orally twice daily for 21 daysErythromycin base, 500
mg orally four times daily for 21 daysPregnant or lactating women:
erythromycin, 500 mg orally four times daily for 21 days
Presumptive:
Clinical suspicion
Community prevalence
Exclusion of other causes of proctocolitis, inguinal lymphadenopathy, or
genital ulcers
Granuloma inguinale (donovanosis)
• Persistent, painless, beefy-red (highly vascular) papules or ulcers
(Figure 4)May be hypertrophic, necrotic, or scleroticNo
lymphadenopathyMay have subcutaneous granulomas
• Definitive:
• Intracytoplasmic Donovan bodies on Wright stain
• or
• Positive result with Giemsa stain or biopsy of granulation tissue
• Treatment should continue until lesions have healed
• Doxycycline, 100 mg orally twice daily for at least 21 days
• Azithromycin, 1 g orally once weekly for at least 21 days
• Ciprofloxacin, 750 mg orally twice daily for at least 21 days
• Erythromycin base, 500 mg orally four times daily for 21 days
• Trimethoprim/sulfamethoxazole (Bactrim, Septra) double strength,
160/800 mg orally twice daily for at least 21 days
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Noninfectious
Behçet syndrome
Aphthous oral ulcers (100 percent of cases); genital ulcers (70 to 90 percent of cases)
Consider rheumatoid factor, antinuclear antibody testingMay have positive antibodies to
carboxyterminal subunit of SIP1Biopsy may show diffuse arteritis with
venulitisDiagnostic criteria: recurrent aphthous oral ulcers (more than three per year)
and any two of the following
Recurrent genital ulcers
Eye lesions (e.g., uveitis)
Cutaneous lesions (e.g., erythema nodosum)
Positive pathergy test (2 mm erythema appears 24 to 48 hours after skin prick test)
Biopsy may show diffuse arteritis with venulitis
Spontaneous regression is possiblePegylated interferon alfa-2a (Pegasys), 6 million
units subcutaneously three times weekly for three months for mucocutaneous
involvement
Fixed drug eruptions
Varied ulcerations that resolve with withdrawal of offending agent
Diagnosis of exclusion when ulcers resolve after drug withdrawal
Self-limited
Topical analgesics or anti-inflammatory agents, as needed
Consider treating exacerbation of underlying inflammatory disease if applicable
LABORATORY EVALUATION
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Laboratory evaluation of an initial genital ulcer outbreak should include culture or polymerase chain reaction testing
for HSV infection, HSV type-specific serology, serologic testing for syphilis, and culture for H. ducreyi in settings
with a high prevalence of chancroid. For the diagnosis of HSV infection, polymerase chain reaction testing is 96 to
100 percent sensitive and 97 to 98 percent specific (positive likelihood ratio = 49, negative likelihood ratio = 0.02),
much more sensitive than culture.25,26 Among adults who report that they have never had genital herpes, the
seroprevalence of HSV type 2 antibodies is 21.6 percent, suggesting the disease is underdiagnosed.27
Darkfield microscopy and direct fluorescent antibody tests of exudate or tissue material are the definitive methods for
diagnosing primary syphilis.3,4,28 However, in patients presenting with genital ulcers, a presumptive diagnosis of
syphilis can be made with a serologic nontreponemal test (i.e., Venereal Disease Research Laboratories or rapid
plasma reagin). But, because of possible false-positive results, positive nontreponemal test results should be
confirmed with serologic treponemal testing (i.e., fluorescent treponemal antibody absorption or T. pallidum passive
agglutination).3,4,28 Nontreponemal titers typically decline and may become nonreactive after treatment, but most
positive treponemal test results tend to remain persistently active. If primary syphilis is treated, up to 25 percent of
patients may have nonreactive treponemal results in two to three years; however, treponemal titers are not
recommended to evaluate response to treatment.3
Although a definitive diagnosis of chancroid requires identification of H. ducreyi, testing with special culture media is
less than 80 percent sensitive and polymerase chain reaction testing for H. ducreyi is not available in the United
States.4 A presumptive diagnosis is possible with a painful genital ulcer, regional lymphadenopathy, no evidence of T.
pallidum infection, and negative HSV test results.3
To diagnose lymphogranuloma venereum, genital swabs or bubo aspirate may be tested for C. trachomatis serotypes
L1, L2, and L3 by culture, direct immunofluorescence, or nucleic acid amplification.3 Nucleic acid amplification tests
for lymphogranuloma venereum are not approved by the U.S. Food and Drug Administration for rectal specimens.
Health care professionals may collect and send rectal specimens to state health departments for referral to the Centers
for Disease Control and Prevention for testing and validating diagnostic methods for lymphogranuloma venereum.3
Even with appropriate laboratory testing, no pathogen is identified in up to 25 percent of patients with genital
ulcers.4 Biopsy is rarely needed to diagnose the cause of genital ulcers, but it may be considered if an ulcer persists
after treatment.3
What is it?
Answer
• Genital Herpies
What is it?
Answer
• Primary syphilus
What is it?
Answer
• Chabcriod
What is it?
Answer
• Genital ulcer with hypertrophic borders,
caused by donovanosis.
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Prevention and Screening
The U.S. Preventive Services Task Force recommends screening for syphilis in persons at increased risk,34 and
recommends against routinely screening for HSV in asymptomatic patients.35
There are no current screening recommendations for chancroid, lymphogranuloma venereum, or donovanosis.
Patients with genital ulcers should be counseled on reducing risk factors for STIs, including limiting the number of
sex partners, using a condom with each sexual encounter, and regularly being screened for STIs if recommended by
evidence-based guidelines.
HIV testing should be performed in all patients with previously negative HIV test results who have genital ulcers
caused by T. pallidum or H. ducreyiinfection, and should be strongly considered for those who have genital ulcers
caused by HSV infection.3
Avoiding sexual intercourse during outbreaks does not prevent HSV transmission.36 Although condom use can
effectively prevent transmission, the infection can be spread through skin-to-skin contact in genital areas unprotected
by a condom.37,38
The American College of Obstetricians and Gynecologists recommends that women who have partners with HSV
infection be offered type-specific serologic testing to assess their risk, and these couples should be advised on condom
and dental dam use, including a warning about incomplete protection.39
Chemoprophylaxis is available for severe or recurrent outbreaks of genital HSV infection in the form of daily
suppressive medication. Suppressive therapy reduces the frequency and severity of outbreaks, reduces asymptomatic
viral shedding by 90 percent, and reduces the risk of transmission to a seronegative partner.40
Options for suppressive therapy include acyclovir, 400 mg twice daily; famciclovir, 250 mg twice daily; or
valacyclovir, 1,000 mg daily.29,41,42
If a patient has fewer than 10 outbreaks per year, 500 mg of oral valacyclovir daily is an appropriate
option.3 Famciclovir is equally effective for suppression but less effective for the prevention of viral shedding and
transmission to sex partners.43
The American College of Obstetricians and Gynecologists recommends that pregnant patients with HSV infection
begin suppressive therapy at 34 to 36 weeks' gestation to reduce the likelihood of lesions during labor.44
Suppressive therapy reduces the risk of recurrence by 75 percent and the rate of cesarean delivery because of HSV
lesions by 40 percent.45
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This issue of American Family Physician introduces the 2012 immunization schedules for young children (birth
through six years of age), older children and adolescents (seven through 18 years of age), andadults, as well as
the catch-up immunization schedule for persons who have not received a recommended vaccination on time or at the
appropriate intervals. A few changes this year are especially pertinent to family physicians.
With regard to pertussis, the Advisory Committee on Immunization Practices (ACIP) of the Centers for Disease
Control and Prevention now recommends that health care professionals and pregnant women receive a single dose of
the tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis (Tdap) vaccine—regardless of the time since the
previous tetanus and diphtheria vaccine—if they have not received a dose of Tdap previously.
In pregnant women, the preferred time for Tdap administration is during the late second or early third trimester.
Based on studies that have shown an increased incidence of hepatitis B infection in persons with diabetesmellitus, the
ACIP now recommends routine hepatitis B vaccination for all adults younger than 60 years who have diabetes. For
older adults with diabetes, the ACIP agreed to a
Category B recommendation (formerly known as a permissive recommendation) for hepatitis B vaccination, which
allows for individualized decision-making by the physician and patient about the appropriateness of the vaccine.
The most complicated recommendations from the ACIP this year involve the administration of quadrivalent human
papillomavirus (HPV4) vaccine (Gardasil) for boys and young men.
These recommendations are specific to the quadrivalent vaccine, and do not apply to the bivalent vaccine (Cervarix).
The ACIP now recommends routine HPV4 vaccination in boys 11 to 12 years of age, with catch-up vaccinations at 13
to 21 years of age. It is acceptable to begin HPV4 vaccination as young as nine years of age. HPV4 vaccination is also
recommended at 22 to 26 years of age in men who have human immunodeficiency virus infection and in men who
have sex with men. For other men 22 to 26 years of age, the ACIP makes a Category B recommendation for HPV4
vaccination.
Finally, the ACIP recommends that children six months to eight years of age receive two doses of influenza vaccine
during the current season if they did not receive at least one dose of the vaccine during the 2010–2011 season. This is
a departure from past recommendations, which stated that two doses in any previous season meant the child needed
only one dose for the current season.
Photo Quiz
Generalized Red Rash
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A 50-year-old woman presented to the emergency department with a diffuse
rash that appeared four months earlier. The rash began on the upper
extremities and gradually spread to her entire body. It was pruritic and
associated with subjective fever and chills. Some of the lesions were pustular
and crusting. She did not have a history of skin problems, and she had not been
exposed to any new body creams, medications, detergents, or foods. The
patient also noted a lump in her right breast at the same time the rash appeared.
She had not seen a physician previously for the lump. She had a significant
history of tobacco use and a family history of breast cancer in an aunt.
On examination, her blood pressure was 176/84 mm Hg, and her pulse was
113 beats per minute. The breast examination revealed a 3-cm, firm mass in
the right outer quadrant that was fixed to underlying structures. There were
peau d'orange changes surrounding the areola and a single palpable right
axillary lymph node. She had generalized erythema and desquamation of the
scalp, face, chest, back, and extremities with crusting and weeping of the skin
surface (see accompanying figure). No lesions were noted on the palms or
soles.
What is it? A. Erythroderma (exfoliative dermatitis).
B. Pemphigus foliaceus.
C. Staphylococcal scalded skin syndrome.
D. Toxic epidermal necrolysis.
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Discussion
The answer is A: Erythroderma (exfoliative dermatitis). Exfoliative dermatitis is a diffuse erythema and scaling of the
skin involving more than 90 percent of the total body skin surface. Common underlying etiologies include drug
hypersensitivity reactions, psoriasis, atopic dermatitis, and malignancy. Drug hypersensitivity reactions account for
approximately 15 percent of exfoliative dermatitis cases.1 The most commonly implicated drugs are calcium channel
blockers, antiepileptics (phenytoin [Dilantin], carbamazepine [Tegretol], lamotrigine [Lamictal]), antibiotics
(vancomycin, sulfonamides, penicillins), cimetidine (Tagamet), dapsone, and allopurinol (Zyloprim). Cutaneous Tcell lymphoma is the most common malignancy associated with exfoliative dermatitis.2 This patient had a more
unusual presentation associated with a solid organ tumor (breast cancer).
Patients with exfoliative dermatitis initially present with pruritic, erythematous patches that progress to generalized
erythema, possibly with fever and chills. Physical examination may reveal lymphadenopathy, pretibial edema, and
alopecia. Laboratory findings are generally nonspecific.3 Because of the diffuse skin involvement, the condition may
be complicated by fluid and electrolyte imbalances, hypothermia, staphylococcal infection, and high-output heart
failure.
Treatment is supportive and includes wound care with emollients, and low-dose topical steroids plus oral
antihistamines and antibiotics for superinfections. A dermatology consultation may be helpful if there is inadequate
response to initial therapy. Second-line treatment includes oral corticosteroids and immunosuppressive agents, such as
cyclophosphamide and methotrexate.
Pemphigus foliaceus is an autoimmune disorder characterized by acantholysis and superficial
blistering.4Autoantibodies against desmoglein 1 lead to the formation of blisters. Patients with typical pemphigus may
present with scaly, crusted lesions on a red base without mucosal involvement. The lesions are confined to the face,
scalp, and upper trunk. Initial treatment involves topical antibiotics and corticosteroids.
Staphylococcal scalded skin syndrome is a toxin-mediated form of exfoliative dermatitis that usually occurs in
children.5 Patients present with fever, malaise, and skin tenderness. The condition begins as a burning, erythematous,
sandpaper-like rash that is worse in flexor creases. The rash progresses to wrinkled, desquamative, bullous
lesions.5 Treatment involves supportive care with antipyretics, intravenous fluids, and parenteral antibiotics.
Toxic epidermal necrolysis is a clinical syndrome related to Stevens-Johnson syndrome and involves greater than 30
percent epidermal skin detachment.6 Like erythroderma, toxic epidermal necrolysis is often related to medication use;
80 percent of cases occur one to three weeks after initiation of the medication.7 Medications associated with toxic
epidermal necrolysis include allopurinol, anticonvulsants, nonsteroidal anti-inflammatory drugs, and sulfonamide
antibiotics. Patients often present following an influenza-like illness with fever, sore throat, and myalgias. Skin
examination reveals desquamative, atypical, purpuric, targetoid lesions that coalesce into dusky, poorly demarcated,
confluent patches.7Treatment involves immediate discontinuation of the offending medication, as well as supportive
therapy and aggressive wound care.
COCHRANE FOR CLINICIANS
STEROIDS FOR THE TREATMENT OF
OTITIS MEDIA WITH EFFUSION IN
CHILDREN
Oral steroids have been shown to improve which one
of the following outcomes in children who have
otitis media with effusion? (check one)
A. Symptoms.
B. Time to effusion resolution.
C. Hearing loss.
D. Hyperactivity.
Answer
• B. Time to effusion resolution.
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Practice Pointers
Otitis media with effusion, a noninflammatory condition characterized by fluid in the middle ear, is common in young
children. About 50 percent of children will have at least one episode in the first year of life.1 Otitis media with
effusion is the most common cause of transient hearing loss in children and can impact the development of speech.
Although it usually resolves spontaneously, physicians sometimes use medical treatment in an attempt to hasten the
course.2
One potential etiologic factor for otitis media with effusion is inflammation, which may be reduced with steroids.
Other potential mechanisms of action include directly shrinking tissue around the eustachian tube, improving
eustachian tube surfactant secretion, and reducing middle ear effusion viscosity.3 Oral and topical nasal steroids have
been used to treat otitis media with effusion. Use of oral steroids is associated with behavioral changes, increased
appetite, weight gain, adrenal suppression, and avascular necrosis of the femoral head. Topical steroids have fewer
adverse effects because of minimal systemic absorption.1
Twelve randomized controlled trials comparing oral or topical nasal steroids (with or without antibiotics) with
placebo were included in this analysis.3 Nine studies evaluated oral steroids, and three studies evaluated topical nasal
steroids. Children up to 12 years of age were included. Hearing loss was the primary outcome of interest; secondary
outcomes included time to resolution of effusion and symptoms.
Three studies reported audiometry data from follow-up visits. One study compared oral steroids with placebo, and
another compared oral steroids plus antibiotics with placebo. Neither study showed statistically significant differences
between groups with regard to hearing loss. A third study comparing topical steroids with placebo showed no
significant difference in the median number of days of hearing loss.
All 12 studies evaluated resolution of effusion. Two studies comparing oral steroids with placebo did not show a
significant effect at short-term or intermediate-term follow-up. In five of six studies evaluating oral steroids plus
antibiotics versus antibiotics alone, the children in the steroid group showed significantly greater resolution of
effusion at follow-up visits after seven to 28 days. Studies of topical nasal steroids showed no improvement in
resolution of effusion versus the control group.
Adverse effects, including diarrhea, increased appetite, and hyperactivity, were reported in five of the oral steroid
studies and three of the topical nasal steroid studies. In one study that compared oral steroids with antibiotics and
placebo with antibiotics, five of 144 children dropped out of the study because of adverse effects; none of the adverse
effects appeared to be related to steroid use.4
Oral steroids lead to faster resolution of otitis media with effusion but do not affect symptoms or hearing outcomes.
Topical nasal steroids have no effect on otitis media with effusion. Given the cost and potential adverse effects of
steroids, their use in otitis media with effusion is not warranted.
CURRENT CONCEPTS IN
CONCUSSION: EVALUATION AND
MANAGEMENT
If initial neuroimaging is warranted in a
patient with suspected concussion, which one
of the following modalities is
preferred? (check one)
A. Computed tomography.
B. Magnetic resonance imaging.
C. Functional magnetic resonance imaging.
D. Plain radiography of the head.
Answer
• A. Computed tomography.
CURRENT CONCEPTS IN CONCUSSION:
EVALUATION AND MANAGEMENT
A 16-year-old athlete sustains a concussion during a football
game. It is determined that he does not have a more serious
injury. Which one of the following management approaches
is appropriate? (check one)
A. If symptoms resolve, he can return to play and finish the
game.
B. A graded return-to-play protocol should be implemented
after rest and full recovery.
C. He should be given a sedative.
D. He can return to the same level of play after rest and full
recovery.
Answer
• B. A graded return-to-play protocol should
be implemented after rest and full recovery.
CURRENT CONCEPTS IN CONCUSSION:
EVALUATION AND MANAGEMENT
Which of the following statements about the
diagnosis of concussion are correct? (check all that
apply)
A. Headache is the most common symptom.
B. Loss of consciousness is necessary to make the
diagnosis.
C. Neurologic examination results are normal
except for mental status and balance deficits.
D. Evaluation should include a physical
examination and use of available concussion
assessment tools.
Answer
• A. Headache is the most common
symptom.
C. Neurologic examination results are
normal except for mental status and balance
deficits.
D. Evaluation should include a physical
examination and use of available
concussion assessment tools.
Current Concepts in Concussion:
Evaluation and Management
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Concussion is a disturbance in brain function caused by direct or indirect force to the head.
It is a functional rather than structural injury that results from shear stress to brain tissue
caused by rotational or angular forces—direct impact to the head is not required.
Initial evaluation involves eliminating cervical spine injury and serious traumatic brain injury.
Headache is the most common symptom of concussion, although a variety of clinical domains
(e.g., somatic, cognitive, affective) can be affected.
Signs and symptoms are nonspecific; therefore, a temporal relationship between an
appropriate mechanism of injury and symptoms must be determined.
There are numerous assessment tools to aid diagnosis, including symptom checklists,
neuropsychological tests, postural stability tests, and sideline assessment tools.
These tools are also used to monitor recovery.
Cognitive and physical rest are the cornerstones of initial management.
There are no specific treatments for concussion; therefore, focus is on managing symptoms and
return to play.
Because concussion recovery is variable, rigid classification systems have mostly been
abandoned in favor of an individualized approach.
A graded return-to-play protocol can be implemented once a patient has recovered in all
affected domains.
Children, adolescents, and those with a history of concussions may require a longer recovery
period.
There is limited research on the management of concussions in children and adolescents, but
concern for potential consequences of injury to the developing brain suggests that a more
conservative approach to management is appropriate in these patients.
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Clinical recommendation
Evaluation of a possible concussion should include a physical examination in addition to use of available concussion
assessment tools.
C
Imaging studies are sometimes used to rule out serious injuries, but are not indicated in the evaluation of
uncomplicated concussion.
C
Complete cognitive and physical rest are key components in the initial management of concussion.
C
After concussion symptoms resolve, postural stability testing should be performed to ensure complete recovery.
C
Concussion should be managed based on the individual patient, with a graded return-to-play protocol.
C
After sustaining a concussion, athletes should not return to play until they have completely recovered.
C
Medical treatment of concussion focuses on symptom management, including the same medications appropriate in
patients without a concussion.
C
Athletes should not return to play on the same day of sustaining a concussion.
C
A more conservative approach, including a longer asymptomatic period before return to play, should be considered
for the management of concussion in children.
C
Protective gear has not been shown to reduce the incidence of concussion, but should be used to prevent other
injuries.
C
Definition of Concussion from the Third International
Conference on Concussion in Sport
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A complex pathophysiologic process affecting the brain, induced by traumatic
biomechanical forces
Several common features that incorporate clinical, pathologic, and
biomechanical injury constructs that may be used in defining the nature of a
concussive head injury include the following:
Concussion may be caused by a direct blow to the head, face, neck, or
elsewhere on the body with an “impulsive” force transmitted to the head
Concussion typically results in the rapid onset of short-lived impairment of
neurologic function that resolves spontaneously
Concussion may result in neuropathologic changes, but the acute clinical
symptoms largely reflect a functional disturbance rather than a structural
injury
Concussion results in a graded set of clinical symptoms that may or may not
involve loss of consciousness; resolution of the clinical and cognitive
symptoms typically follows a sequential course; however, it is important to
note that in a small percentage of cases, postconcussive symptoms may be
prolonged
No abnormality on standard structural neuroimaging studies is seen in
concussion
Assessment Tools for Concussion Diagnosis and
Management
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Symptom checklists
Postconcussion Symptom ScaleGraded Symptom ChecklistHead Injury ScaleMcGill Abbreviated Concussion
Evaluation (ACE) postconcussion symptom scaleHeadMinderConcussion Symptom Inventory
The most commonly used type of concussion assessment tool
Quick, easy, cost-effective tool with good sensitivity; allows athletes to self-report symptoms
Cautions: symptoms may be delayed, may not be reported, or were already present at baseline
Most checklists developed using clinical judgment; the Concussion Symptom Inventory is the only empirically
derived symptom checklist
Neuropsychological tests
Written
Trail Making Test
Digit Symbol Substitution Test
Controlled Oral Word Association Test
Hopkins Verbal Learning Test
Stroop Color and Word Test
Computer-basedHeadMinder
CogSport
ImPACT
Automated Neuropsychological Assessment Metrics
Designed to identify subtle cognitive deficits
Written tests are labor intensive and must be interpreted, whereas computer-based tests can be administered rapidly
and to multiple patients simultaneously
Results best interpreted when compared with baseline data; affected by psychiatric disorders, physical symptoms,
cultural factors, and motivation/effort
These tests are not validated, and no data demonstrate that they affect outcomes when used to guide return to play
There are limited baseline data in children younger than 12 years; child-specific computerized tests are under
development
Definition of Concussion from the Third International
Conference on Concussion in Sport
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Postural stability testing
BESS (and modified version)SOT
Very sensitive for concussion diagnosis, but there are limited data regarding its
use in monitoring recovery
SOT is the preferred test, but it is not portable; BESS is inexpensive and easy
to administer on the sideline of a sporting event
Instability usually lasts three to five days after a concussion occurs
Sideline assessment tools
SACSCATSCAT2
A single, simple tool to assess a variety of domains in the initial concussion
assessment
Often used to monitor the recovery process
SAC can be used immediately after injury to evaluate orientation, memory,
concentration, and delayed recall; validated as a sideline tool for athletes
junior high school–aged and older; emergency department version is validated
in adults
SCAT2 combines multiple assessment tools (symptom checklist, concentration
and memory tasks [Maddock's questions], SAC, BESS, and Glasgow Coma
Scale); it is not validated but is widely used and the most sophisticated sideline
tool available
SCREENING FOR DEPRESSION
Which one of the following statements is correct
based on recommendations from the U.S. Preventive
Services Task Force? (check one)
A. Adolescents should be screened for depression,
but there is insufficient evidence to support
screening children.
B. Children should be screened for depression, but
there is insufficient evidence to support screening
adolescents.
C. Both children and adolescents should be screened
for depression.
D. There is insufficient evidence to support
screening children or adolescents for depression.
Answer
• A. Adolescents should be screened for
depression, but there is insufficient
evidence to support screening children.
SCREENING FOR DEPRESSION
Which of the following are effective
screening instruments for
depression? (check all that apply)
A. Patient Health Questionnaire (PHQ)9.
B. PHQ-2.
C. Geriatric Depression Scales.
D. Mood Disorder Questionnaire.
Answer
• A. Patient Health Questionnaire (PHQ)-9.
B. PHQ-2.
C. Geriatric Depression Scales.
SCREENING FOR DEPRESSION
According to recommendations from the American
Geriatrics Society, if a PHQ-2 is positive for
depression in an 82-year-old patient, follow-up using
which of the following would be indicated? (check
all that apply)
A. Diagnostic and Statistical Manual of Mental
Disorders, 4th ed., criteria for depression.
B. 15-item Geriatric Depression Scale.
C. Mood Disorder Questionnaire.
D. PHQ-9.
Answer
• B. 15-item Geriatric Depression Scale.
D. PHQ-9.
Screening for Depression
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In the United States, depression affects up to 9 percent of patients and
accounts for more than $43 billion in medical care costs.
The U.S. Preventive Services Task Force recommends screening in
adolescents and adults in clinical practices that have systems in place to
ensure accurate diagnosis, effective treatment, and follow-up.
It does not recommend for or against screening for depression in children
seven to 11 years of age or screening for suicide risk in the general
population.
The Patient Health Questionnaire (PHQ)-2 and PHQ-9 are commonly
used and validated screening tools.
The PHQ-2 has a 97 percent sensitivity and 67 percent specificity in
adults, whereas the PHQ-9 has a 61 percent sensitivity and 94 percent
specificity in adults.
If the PHQ-2 is positive for depression, the PHQ-9 should be
administered; in older adults, the 15-item Geriatric Depression Scale is
also an appropriate follow-up test.
If these screening tests are positive for depression, further evaluation is
needed to confirm that the patient's symptoms meet the Diagnostic and
Statistical Manual of Mental Disorders' criteria for diagnosis.
Clinical recommendation
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Because there is no significant difference in performance among the different depression
screening instruments, the most practical tool for the clinical setting should be used.
C
Adults and adolescents 12 to 18 years of age should be screened for depression in
clinical practices that have systems to ensure effective diagnosis, treatment, and followup.
B
There is insufficient evidence to balance the benefits and harms of screening children
seven to 11 years of age for depression.
C
There is insufficient evidence to recommend for or against screening for suicide risk in
the general population.
C
The PHQ-2 is accurate for depression screening in adolescents, adults, and older adults.
B
The PHQ-9 is a valid, quick screening instrument for depression that also can be used as
a follow-up to a positive PHQ-2 result and to monitor treatment response.
C
Depression screening in older adults can be accomplished with multiple instruments,
including the PHQ-2, PHQ-9, and various Geriatric Depression Scales.
B
Depression
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Depression is often not adequately treated.5 Even when treated appropriately,
more than 75 percent of patients with depression have recurrent episodes and
10 to 30 percent have residual symptoms.6,7
Depression has been associated with poorer outcomes in patients with a variety
of medical conditions, such as coronary artery disease, diabetes mellitus, and
stroke.8–10
Treatment of depression may reduce mortality from these conditions, as well
as help prevent suicide.11–13
Therefore, accurately identifying patients who have depression is important so
that appropriate treatment can be initiated.
Symptoms and Risk Factors
Classically, patients with depression present with psychological symptoms of
depressed mood, loss of interest in activities, impaired concentration, feelings
of worthlessness or guilt, and suicidal ideation.
However, some patients may instead report nonspecific symptoms (Table 1).
One study found that 45 to 95 percent of patients with depression worldwide
have only somatic symptoms.14
Screening for Depression
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A 2005 Cochrane review found that routine depression screening had minimal effect on the
management or outcomes of depression after six or 12 months of follow-up.15
However, the U.S. Preventive Services Task Force (USPSTF) has published more recent reviews on
depression screening. This article focuses on the recommendations and findings of the USPSTF.
ADULTS
The USPSTF found good evidence that treatment with antidepressants, psychotherapy, or both
decreases clinical morbidity and improves outcomes in adults with depression identified through
screening in primary care settings.
Screening adults for depression is recommended in clinical practices that have systems in place to
ensure accurate diagnosis, effective treatment, and follow-up.
Screening for depression in clinical practices without these systems is of minimal benefit.
Furthermore, the USPSTF found no evidence of harms of screening for depression in adults. 16
The USPSTF found insufficient evidence to recommend for or against screening for suicide risk in
the general population, compared with screening only those with depression. 17
ADOLESCENTS AND CHILDREN
The USPSTF recommends screening adolescents 12 to 18 years of age for depression in clinical
practices that have systems (or referral systems) in place to ensure accurate diagnosis, psychotherapy
(cognitive behavioral or interpersonal therapy), and follow-up.
There is insufficient evidence to balance the benefits and harms of depression screening in children
seven to 11 years of age.
There is adequate evidence that treatment with selective serotonin reuptake inhibitors,
psychotherapy, or both decreases depression symptoms in adolescents. Similar evidence is lacking in
children.
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SCREENING INSTRUMENTS
Many instruments have been developed for depression screening.
Although the USPSTF found little evidence that one is superior, the most practical tool
for the clinical setting should be used.16,18
Positive results on a screening test should trigger full diagnostic interviews that use
standard diagnostic criteria from the Diagnostic and Statistical Manual of Mental
Disorders, 4th ed. (DSM-IV).
PHQ-2. Ultrashort screening instruments, such as the Patient Health Questionnaire
(PHQ)-2 (Table 3)may rule out, but not definitively diagnose, depression.19
However, the PHQ-2, which asks two simple questions about mood and anhedonia, has
strengths.
It is as effective as longer screening instruments, such as the Beck Depression Inventory
or Zung Depression Scale.15,20,21
The PHQ-2 has been found to be up to 97 percent sensitive and 67 percent specific in
adults, with a 38 percent positive predictive value and 93 percent negative predictive
value.21
It is reported to have a 74 percent sensitivity and 75 percent specificity in adolescents
Over the past two weeks, how often have you been bothered by any of the following
problems?
Little interest or pleasure in doing things
Feeling down, depressed, or hopeless
SCREENING INSTRUMENTS
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PHQ-9. The PHQ-9 (Table 4) is one of the most common instruments used for
depression screening.
Although it can be used on its own as a screening test or to monitor treatment,
it is increasingly administered for confirmation of a positive PHQ-2 result.
The PHQ-9 is valid, takes two to five minutes to complete, and has
demonstrated 61 percent sensitivity and 94 percent specificity for mood
disorders in adults, and 89.5 percent sensitivity and 77.5 percent specificity in
adolescents
Screening Instruments for Older Adults. A systematic review of 18 studies
evaluating nine screening instruments in patients older than 65 years
demonstrated sensitivities of 74 to 100 percent, and specificities of 53 to 98
percent.24
The PHQ-2 has a sensitivity of 100 percent and specificity of 77 percent in
these patients,25 whereas the 30-item and the 15-item Geriatric Depression
Scales have a sensitivity of 74 to 100 percent and a specificity of 53 to 98
percent.24
A five-item Geriatric Depression Scale (Table 5) was found to be as effective
as the 15-item scale, with 97 percent sensitivity and 85 percent specificity.26
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The American Geriatrics Society recommends using the PHQ-2 as an initial screening test for depression in older adults. If
positive, the 15-item Geriatric Depression Scale (Table 6 27) or the PHQ-9 is recommended as a follow-up test.
15-Item Geriatric Depression ScaleChoose the best answer for how you have felt over the past week:1. Are you basically
satisfied with your life?
Yes/No
2. Have you dropped many of your activities and interests?
Yes/No
3. Do you feel that your life is empty?
Yes/No
4. Do you often get bored?
Yes/No
5. Are you in good spirits most of the time?
Yes/No
6. Are you afraid that something bad is going to happen to you?
Yes/No
7. Do you feel happy most of the time?
Yes/No
8. Do you often feel helpless?
Yes/No
9. Do you prefer to stay at home, rather than going out and doing new things?
Yes/No
10. Do you feel you have more problems with memory than most?
Yes/No
11. Do you think it is wonderful to be alive now?
Yes/No
12. Do you feel pretty worthless the way you are now?
Yes/No
13. Do you feel full of energy?
Yes/No
14. Do you feel that your situation is hopeless?
Yes/No
15. Do you think that most people are better off than you are?
Yes/No
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DSM-IV Criteria for Major Depressive EpisodeA. Five (or more) of the following symptoms have been present
during the same 2-week period and represent a change from previous functioning; at least one of the symptoms is
either 1) depressed mood or 2) loss of interest or pleasure.
Note: Do not include symptoms that are clearly due to a general medical condition, or mood-incongruent delusions or
hallucinations.
1) depressed mood most of the day, nearly every day, as indicated by either subjective report (e.g., feels sad or empty)
or observation made by others (e.g., appears tearful). Note: In children and adolescents, can be irritable mood
2) markedly diminished interest or pleasure in all, or almost all, activities most of the day, nearly every day (as
indicated by either subjective account or observation made by others)
3) significant weight loss when not dieting or weight gain (e.g., a change of more than 5% of body weight in a
month), or decrease or increase in appetite nearly every day. Note: In children, consider failure to make expected
weight gains
4) insomnia or hypersomnia nearly every day
5) psychomotor agitation or retardation nearly every day (observable by others, not merely subjective feelings of
restlessness or being slowed down)
6) fatigue or loss of energy nearly every day
7) feelings of worthlessness or excessive or inappropriate guilt (which may be delusional) nearly every day (not
merely self-reproach or guilt about being sick)
8) diminished ability to think or concentrate, or indecisiveness, nearly every day (either by subjective account or as
observed by others)
9) recurrent thoughts of death (not just fear of dying), recurrent suicidal ideation without a specific plan, or a suicide
attempt or a specific plan for committing suicide
B. The symptoms do not meet criteria for a Mixed Episode.
C. The symptoms cause clinically significant distress or impairment in social, occupational, or other important areas
of functioning.
D. The symptoms are not due to the direct physiological effects of a substance (e.g., a drug of abuse, a medication) or
a general medical condition (e.g., hypothyroidism).
E. The symptoms are not better accounted for by Bereavement, i.e., after the loss of a loved one, the symptoms persist
for longer than 2 months or are characterized by marked functional impairment, morbid preoccupation with
worthlessness, suicidal ideation, psychotic symptoms, or psychomotor retardation.
FEBRILE SEIZURES: RISKS,
EVALUATION, AND PROGNOSIS
Patients with simple febrile seizures have an
increased risk of which one of the
following? (check one)
A. Academic problems.
B. Mortality.
C. Subsequent febrile seizures.
D. Behavioral problems.
Answer
• C. Subsequent febrile seizures.
FEBRILE SEIZURES: RISKS,
EVALUATION, AND PROGNOSIS
Which of the following features must be
present for a febrile seizure to be classified as
simple? (check all that apply)
A. Duration of less than 15 minutes.
B. Generalized.
C. Occurring no more than once in a 24-hour
period.
D. Patient has no history of neurologic
problems.
Answer
• A. Duration of less than 15 minutes.
B. Generalized.
C. Occurring no more than once in a 24hour period.
D. Patient has no history of neurologic
problems.
FEBRILE SEIZURES: RISKS, EVALUATION,
AND PROGNOSIS
Which of the following factors increase the risk of
recurrence of a febrile seizure? (check all that
apply)
A. Age older than 18 months.
B. Temperature of less than 104°F (40°C) during
the first febrile seizure.
C. First-degree relative with febrile seizure.
D. Duration of fever more than two hours before the
first febrile seizure.
Answer
• B. Temperature of less than 104°F (40°C)
during the first febrile seizure.
C. First-degree relative with febrile seizure
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Febrile Seizures: Risks, Evaluation,
and Prognosis
Febrile seizures are common in the first five years of life, and many factors that
increase seizure risk have been identified.
Initial evaluation should determine whether features of a complex seizure are
present and identify the source of fever.
Routine blood tests, neuroimaging, and electroencephalography are not
recommended, and lumbar puncture is no longer recommended in patients with
uncomplicated febrile seizures.
In the unusual case of febrile status epilepticus, intravenous lorazepam and buccal
midazolam are first-line agents.
After an initial febrile seizure, physicians should reassure parents about the low
risk of long-term effects, including neurologic sequelae, epilepsy, and death.
However, there is a 15 to 70 percent risk of recurrence in the first two years after
an initial febrile seizure.
This risk is increased in patients younger than 18 months and those with a lower
fever, short duration of fever before seizure onset, or a family history of febrile
seizures.
Continuous or intermittent antiepileptic or antipyretic medication is not
recommended for the prevention of recurrent febrile seizures.
Classification of Febrile Seizures
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Simple (all of the following)
Duration of less than 15 minutes
Generalized
No previous neurologic problems
Occur once in 24 hours
Complex (any of the following)
Duration of more than 15 minutes
Focal
Recurs within 24 hours
Clinical recommendation
• Routine laboratory tests, electroencephalography, and
neuroimaging are not recommended in patients with simple
febrile seizures.
• C
• Parents should be reassured after a simple febrile seizure
that there is no negative impact on intellect or behavior,
and no increased risk of death.
• B
• Use of long-term continuous or intermittent antiepileptic
medication after a first simple febrile seizure is not
recommended because of potential adverse effects.
• B
• Use of antipyretic agents at the onset of fever is not
effective at reducing simple febrile seizure recurrence
• A
Acute Treatment
• Although most febrile seizures have resolved by the time
of presentation, physicians should be prepared to treat
patients with febrile status epilepticus.
• In the acute setting, intravenous lorazepam (Ativan) in a
dose of 0.1 mg per kg is the treatment of choice for acute
tonicclonic pediatric seizures.
• A Cochrane review found lorazepam to be as effective as
diazepam (Valium), with fewer adverse effects and less
need for additional antiepileptic agents.27
• The same study found buccal midazolam to be superior to
rectal diazepam (Diastat) when intravenous administration
is not possible.
Risk of Recurrence After an Initial Febrile
Seizure
• Risk factors
• Age < 18 months
• Duration of fever < 1 hour before seizure
onset
• First-degree relative with febrile seizure
• Temperature < 104°F (40°C)
CUTANEOUS MALIGNANT MELANOMA: A
PRIMARY CARE PERSPECTIVE
Which one of the following statements refers to the "ugly
duckling" sign? (check one)
A. Different shades of tan, brown, and black, and sometimes
red, white, or blue within the same lesion are suggestive of
melanoma.
B. A melanoma may look different compared with
surrounding moles.
C. Lentigo maligna generally begins as an irregularly shaped
tan spot that slowly grows to form a larger spot.
D. New-onset pigmented lines on a single nail require a
biopsy into the nail matrix to properly evaluate for
melanoma.
Answer
• B. A melanoma may look different
compared with surrounding moles.
CUTANEOUS MALIGNANT MELANOMA: A
PRIMARY CARE PERSPECTIVE
A patient has a superficial spreading melanoma with
a Breslow depth classified as in situ. Which one of
the following is the most appropriate next
step? (check one)
A. Surgical excision with wide margins (3 to 5 cm).
B. Evaluation with complete blood count, chemistry
panel, and lactate dehydrogenase level.
C. Sentinel node biopsy.
D. Surgical excision with 5-mm margins.
Answer
• D. Surgical excision with 5-mm margins.
CUTANEOUS MALIGNANT MELANOMA: A
PRIMARY CARE PERSPECTIVE
A patient presents with a suspicious pigmented lesion that is 8
mm in diameter. Which of the following statements about
biopsy of the lesion are correct? (check all that apply)
A. A superficial shave biopsy is the best way to obtain an
adequate specimen.
B. If excisional biopsy is not practical, a punch biopsy is
appropriate if the entire lesion can be removed.
C. A small margin of normal-appearing skin (approximately
3 mm) is acceptable.
D. Complete elliptical excision is the generally preferred
method.
Answer
• B. If excisional biopsy is not practical, a
punch biopsy is appropriate if the entire
lesion can be removed.
C. A small margin of normal-appearing
skin (approximately 3 mm) is acceptable.
D. Complete elliptical excision is the
generally preferred method.
Cutaneous Malignant Melanoma: A
Primary Care Perspective
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Cutaneous malignant melanoma accounts for 3 to 5 percent of all skin cancers and
is responsible for approximately 75 percent of all deaths from skin cancer.
Persons with an increased number of moles, dysplastic (also called atypical) nevi,
or a family history of the disease are at increased risk compared with the general
population.
An important tool to assist in the evaluation of potential melanomas for patients
and health care professionals is the ABCDE mnemonic, which takes into account
asymmetry, border irregularities, color variation, diameter, and evolution.
Any suspicious pigmented lesion should be biopsied. Appropriate methods of
biopsy can vary, and include deep shave, punch, and excisional biopsy.
Regardless of the procedure selected, it is essential that the size of the specimen be
adequate to determine the histologic depth of lesion penetration, which is known as
the Breslow depth. The Breslow depth is the most important prognostic parameter
in evaluating the primary tumor.
Because early detection and treatment can lead to identification of thinner lesions,
which may increase survival, it is critical that physicians be comfortable with
evaluating suspicious pigmented lesions and providing treatment or referral as
necessary.
Cutaneous Malignant Melanoma
• Cutaneous malignant melanoma (CMM) is a potentially
lethal form of skin cancer.
• Although it comprises only 3 to 5 percent of all skin
cancers, it is responsible for approximately 75 percent of
all deaths from skin cancers.1,2
• CMM results from the malignant transformation of
melanocytes, which are the pigment-producing cells
responsible for the color of skin.
• The key triggers leading to malignant transformation of
melanocytes have yet to be fully elucidated, but are
multifactorial and include UV radiation damage and
genetic susceptibility.
Clinical recommendation
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Some organizations recommend including a skin examination during periodic
health examinations for adults; however, the U.S. Preventive Services Task
Force found insufficient evidence to recommend for or against annual
screening for skin cancer.
C
There is no statistically significant difference in survival for narrow vs. wide
surgical margins for treatment of cutaneous malignant melanoma.
B
Statistically insignificant benefit for wide margins
Sentinel node biopsy in persons with melanoma with a Breslow depth of 1.0
mm or greater is useful for determining staging and prognosis.
C
Sentinel node biopsy is effective for determining staging and prognosis; no
increase in survival has been proven
Diagnosis
• CMM can occur de novo or in a preexisting nevus; therefore, close
examination of all nevi on a patient is necessary.7
• This may be a daunting task in a busy primary care environment,
particularly given the other myriad problems that require evaluation at
any particular visit.
• Some organizations recommend including a skin examination during
periodic health examinations for adults; however, the U.S. Preventive
Services Task Force concluded that there is not enough evidence to
recommend for or against annual whole-body skin examination by a
primary care physician or patient for early detection of skin cancers in
the adult general population.2,8,9
• This recommendation was directed toward patients without a history of
premalignant or malignant lesions.
• Although it makes intuitive sense to counsel patients on disease
prevention and to screen them periodically, there is not yet strong
evidence to support these practices.
• The Web site FamilyDoctor.org presents a guideline for patients on
skin cancer prevention and self-screening
at http://familydoctor.org/614.xml.
ABCDE Mnemonic for
Evaluating Melanoma
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Asymmetry
One-half of lesion is different than the other half
Border
Irregular or poorly defined border
Color
Varied from one area to another; different shades of tan, brown, black;
sometimes red, white, or blue within the same lesion
Diameter
Larger than 6 mm (bigger than the size of a pencil eraser)
Evolving
A mole that looks different compared with surrounding moles (“ugly
duckling” sign), or the mole is changing in size, shape, or color
Maligant Melanoma Insitu
Superficial spreading melanoma
with a Breslow depth of 0.45
mm.
Nodular melanoma with a
Breslow depth of 0.6 mm.
Lentigo maligna melanoma.
Acral-lentiginous amelanotic
melanoma.
Acral-lentiginous melanoma with
a Breslow depth of 4.0 mm.
Subungual melanoma.
Surgical Treatment
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Surgical removal is the primary treatment for CMM.
The Breslow depth of the lesion determines definitive surgical margins (Table
4).30
The purpose of the surgical margin is to ensure complete removal of the
primary lesion and any residual melanoma cells that may have spread into the
surrounding skin to definitively treat the lesion and reduce the chance of
recurrence.
A 2009 Cochrane review involving 3,297 patients examined the association
between surgical margins and survival.
No statistically significant difference in survival was identified between wide
(3 to 5 cm) and narrow (1 to 2 cm) surgical margins.1
This has allowed for narrower surgical margin recommendations, with less
morbidity associated with the traditionally wide margins used in the past. If the
physician who performed the biopsy is not providing the surgical treatment,
then appropriate referral is necessary as soon as possible.
Although there is no literature to identify the optimal time from diagnosis to
treatment, definitive surgical treatment should usually occur no later than three
to four weeks after receipt of the biopsy report.
• Recommended Surgical Margins for
Melanoma Based on Breslow Depth
• Breslow depthMarginsIn situ
• 5 mm
• ≤ 2.0 mm
• 1 cm
• > 2.0 mm
• 2 cm
CLINICAL EVIDENCE HANDBOOK
THROMBOEMBOLISM
A 60-year-old man develops acute left lower
extremity edema after an international flight.
Ultrasonography reveals proximal deep venous
thrombosis. Which of the following treatments are
known to be beneficial? (check all that apply)
A. Low-molecular-weight heparin.
B. High-intensity oral anticoagulation.
C. Compression stockings.
D. Home treatment.
Answer
• A. Low-molecular-weight heparin.
C. Compression stockings.
D. Home treatment.
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Thromboembolism
Deep venous thrombosis (DVT) or pulmonary embolism may occur in almost two in 1,000 persons each year, with up
to 25 percent of those having a recurrence.
About 5 to 15 percent of persons with untreated DVT may die from pulmonary embolism.
The risk of recurrence of thromboembolism falls over time, but the risk of bleeding from anticoagulation remains
constant.
Oral anticoagulants are considered effective in persons with proximal DVT compared with no treatment, although we
found few trials.
In persons with proximal DVT or pulmonary embolism, long-term anticoagulation reduces the risk of recurrence, but
high-intensity treatment has shown no benefit. Both approaches increase the risk of major bleeding.
Low-molecular-weight heparin (LMWH) is more effective than unfractionated heparin, and may be as effective as
oral anticoagulants, although all are associated with some adverse effects.
We do not know how effective tapering of oral anticoagulant agents is compared with stoppingabruptly.
We do not know whether once-daily LMWH is as effective as twice-daily administration at preventing recurrence.
Home treatment may be more effective than hospital-based treatment at preventing recurrence, and equally effective
at reducing mortality.
Vena cava filters reduce the short-term rate of pulmonary embolism, but they may increase the long-term risk of
recurrent DVT.
Elastic compression stockings reduce the incidence of postthrombotic syndrome after DVT compared with placebo or
no treatment.
In persons with isolated calf DVT, anticoagulation with warfarin may reduce the risk of proximal extension, although
prolonged treatment seems no more beneficial than short-term treatment.
Anticoagulation may reduce mortality compared with no anticoagulation in persons with a pulmonary embolus, but it
increases the risk of bleeding. We found few studies that evaluated treatments for pulmonary embolism.
LMWH may be as effective and safe as unfractionated heparin.
Thrombolysis seems as effective as heparin in treating major pulmonary embolism, but it is also associated with
adverse effects.
The use of computerized decision support may increase the time spent in target international normalized ratio range
and reduce thromboembolic events or major hemorrhage, compared with manual dosage calculation.
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Clinical Questions
What are the effects of treatments for proximal DVT?
Beneficial
Compression stockings
LMWH (reduced mortality, recurrence, and risk of major hemorrhage compared with unfractionated heparin)
Likely to be beneficial
Home treatment with short-term LMWH
Oral anticoagulants
Trade-off between benefits and harms
Long-term LMWH vs. long-term anticoagulation (both showed similar levels of benefits but with important adverse effects)
Long-term vs. short-term oral anticoagulation
Vena cava filters (reduce short-term rate of pulmonary embolism, but may increase the long-term risk of recurrent DVT)
Unknown effectiveness
Abrupt discontinuation of oral anticoagulation
Once-daily vs. twice-daily LMWH
Unlikely to be beneficial
High-intensity oral anticoagulation
What are the effects of treatments for isolated calf DVT?
Likely to be beneficial
Warfarin (reduced rate of proximal extension compared with no further treatment in persons who had received initial heparin and wore compression
stockings)
Unlikely to be beneficial
Prolonged duration of anticoagulation
What are the effects of treatments for pulmonary embolism?
Likely to be beneficial
Anticoagulants (warfarin and heparin)*
Thrombolysis
Trade-off betweenbenefits and harms
Prolonged duration of anticoagulation
Unknown effectiveness
LMWH (no clear evidence of a difference in mortality, new episodes of thromboembolism, or in risk of major hemorrhage compared with unfractionated
heparin)
Unlikely to be beneficial
High-intensity anticoagulation (extrapolated data from persons with proximal DVT)
What are the effects of interventions on oral anticoagulation management in persons with thromboembolism?
Unknown effectiveness
Computerized decision support in oral anticoagulation (increased time spent in target international normalized ratio range)
Self-testing and self-management of oral anticoagulation
PUTTING PREVENTION INTO PRACTICE:
AN EVIDENCE-BASED APPROACH
OCULAR PROPHYLAXIS FOR
GONOCOCCAL OPHTHALMIA
NEONATORUM
What are the potential complications of untreated
gonococcal ophthalmia neonatorum? (check all that
apply)
A. Ocular perforation.
B. Amblyopia.
C. Corneal scarring.
D. Blindness.
Answer
• A. Ocular perforation.
C. Corneal scarring.
D. Blindness.
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Case Study
You are called to an emergent but uncomplicated spontaneous vaginal delivery at 38 weeks'
gestation. The mother is 19 years of age, with a history of heroin use and multiple sex partners. She
has not received medical care for the past few years.
Case Study Questions
According to the U.S. Preventive Services Task Force (USPSTF), what is the primary indication for
providing this newborn with prophylaxis for gonococcal ophthalmia neonatorum?
– A. Lack of prenatal care.
– B. Maternal risk of sexually transmitted infection.
– C. Maternal history of heroin use.
– D. Maternal age.
– E. All newborns should receive prophylaxis for gonococcal ophthalmia neonatorum.
Which one of the following ocular regimens is approved by the U.S. Food and Drug Administration
for the prevention of gonococcal ophthalmia neonatorum?
– A. Erythromycin 0.5% ophthalmic ointment.
– B. Tetracycline 1.0% ophthalmic ointment.
– C. Silver nitrate 1.0% drops.
– D. Ciprofloxacin 0.3% solution.
– E. Povidone-iodine 2.5% solution.
What are the potential complications of untreated gonococcal ophthalmia neonatorum?
– A. Ocular perforation.
– B. Amblyopia.
– C. Corneal scarring.
– D. Blindness.
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Answers
1. The correct answer is E. The USPSTF recommends universal prophylaxis for
gonococcal ophthalmia neonatorum in newborns. There is high certainty that the net
benefit is substantial. There is convincing evidence that blindness due to gonococcal
ophthalmia neonatorum has become rare in the United States since the implementation
of universal prophylaxis, and that universal prophylaxis of newborns is not associated
with serious harms. Some newborns are at increased risk of gonococcal ophthalmia
neonatorum, including those with a maternal history of sexually transmitted
infections,substance abuse, or lack of prenatal care. Maternal age is not an independent
risk factor.
2. The correct answer is A. Prophylactic regimens using tetracycline 1.0% or
erythromycin 0.5% ophthalmic ointment are equally effective in the prevention of
gonococcal ophthalmia neonatorum; however, the only drug approved by the U.S. Food
and Drug Administration for this indication is erythromycin 0.5% ophthalmic ointment.
Prophylaxis should be provided within 24 hours after birth. Tetracycline ophthalmic
ointment and silver nitrate drops are no longer available in the United States.
Ciprofloxacin is not indicated for the treatment of gonococcal ophthalmia neonatorum.
A 2.5% solution of povidone-iodine may be useful in preventing ophthalmia
neonatorum, but it has not been approved for use in the United States.
3. The correct answers are A, C, and D. Gonococcal ophthalmia neonatorum develops
in approximately 28 percent of newborns delivered to women with gonorrheal disease in
the United States. Identifying and treating the infection are important because
gonococcal ophthalmia neonatorum can result in corneal scarring, ocular perforation,
and blindness. Amblyopia is not associated with gonococcal ophthalmia neonatorum.
OUTPATIENT BURNS: PREVENTION AND
CARE
A 22-year-old woman presents with an
erythematous, dry, painful burn covering her upper
shoulders bilaterally. Yesterday she participated in a
four-hour hike and did not apply sunscreen. Which
one of the following is an appropriate initial
therapy? (check one)
A. Twice-daily application of ice to the affected
area.
B. Topical bacitracin.
C. Topical corticosteroids.
D. Silver sulfadiazine (Silvadene).
Answer
• B. Topical bacitracin.
OUTPATIENT BURNS: PREVENTION
AND CARE
Which one of the following is a criterion for
referral to a burn center? (check one)
A. A first-degree burn on an arm.
B. A painful sunburn on the shoulders.
C. A burn that covers less than 10 percent of
the total body surface area, but has blisters
and is weeping clear fluid.
D. Inhalation burns.
Answer
• D. Inhalation burns.
OUTPATIENT BURNS: PREVENTION
AND CARE
Which of the following are appropriate pieces
of advice for burn counseling during a wellchild visit? (check all that apply)
A. Do not leave a child unattended near a
fireplace.
B. Check smoke alarms on a regular basis.
C. Set the hot water heater to 140°F (60°C).
D. Use the back burner on the stove when
children are present.
Answer
• A. Do not leave a child unattended near a
fireplace.
B. Check smoke alarms on a regular basis.
D. Use the back burner on the stove when
children are present.