• 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 for H. 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.

•
The new Edarbyclor (eh-DAR-bih-clor) means you'll see more interest in using chlorthalidone 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).

• 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

•
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.

• 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...and
testosterone 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.

• 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.

• 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

•
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

• 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 a balanced diet , exercise, and setting realistic goals.

•
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.

•
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.

•
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 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.

•
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.

• 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

•
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.

•
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

•
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.

•
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

•
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.

(check one)

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.

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

•
InjuryIndicationAmerican College of Radiology criteria 5 Ottawa Knee Rule 6 Pittsburgh Knee Rule 7
•
Age < 12 years or > 50 years
• X P
• Age ≥ 55 years
• X O
•
Altered mental status
•
X
•
Fall or blunt trauma
•
X P
•
Inability to bear weight for four steps (unable to transfer weight twice) immediately after injury or in the emergency setting
• X O P
• X
• X
•
Inability to flex knee to 90 degrees
•
X O
•
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
•
X O
•
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 test 3
• 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.

3

3

3

3

15

16

• Positive likelihood ratio*
•
Negative likelihood ratio*
• Probability of injury if maneuver is†Positive (%)
• Negative (%)
• Anterior cruciate ligament tear
•
Pivot shift test 3
•
20.3 0.4 69 4
• Lachman test 3
• 12.4 0.14 58 2
•
Anterior drawer test 3
•
3.7 0.6 29 6
• Effusion
• Ballottement test; noticeable swelling 16
•
3.6 0.4 NA NA
•
Meniscal tear
• Thessaly test 15
• 39.3 0.09 81 1
•
McMurray test 3
•
17.3 0.5 66 5
• Age > 40 years, continuation of activity not possible, weight bearing during trauma, and pain with passive flexion 17
•
5.8 0.9 39 9
•
Joint line tenderness 3
• 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
•
History
•
Physical examination
•
Diagnosis to consider
Physical Examination
•
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

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.

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.

• 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.

• 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

•
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 .

• 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

• 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

• 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)

• 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 of
Haemophilus 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

•
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 trachomatis serotype 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

• 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

• 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 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

•
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. ducreyi infection, 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

•
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) , and adults , 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 diabetes mellitus, 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.

•
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.

•
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.
4 Autoantibodies 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.
7 Treatment 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.

•
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.

(check one)

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.

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.

• 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.

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
•
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
•
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
•
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.

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.

•
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
•
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 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

• 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.

•
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

•
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

•
•
•
•
•
•
•
•
•
•
•
•
•
•
•
•
•
•
•
•
•
•
•
•
•
•
•
•
•
•
•
•
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

•
DSM-IV Criteria for Major Depressive Episode A. 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.

(check one)

(check all that apply)

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.

•
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.

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

• 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.

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.

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.

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.

•
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 (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
•
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

• 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
.

• 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

•
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.

Breslow depthMargins

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.

•
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 stopping abruptly.
•
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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•
•
•
•
•
•
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•
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•
•
•
•
•
•
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 between benefits 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.

• 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.

•
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).

(check one)

(check all that apply)