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In the News
for the Week of 11-16-10

Highlights

  • Global risk assessment best for predicting heart failure in asymptomatic patients, panel finds
  • Free, two-minute dementia screen compares well to longer mini-assessments

Test yourself

  • MKSAP Quiz: generalized rash, facial edema, fever, and severe fatigue

Nephrology

Cardiology

  • Intensive statin therapy lowered risk even for low LDL patients

From the College

  • Nominees named for College Officer and Regent positions
  • College awards and Masters of 2011 announced

For the record

Cartoon caption contest

Physician editor: Darren Taichman, FACP


Highlights

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Global risk assessment best for predicting heart failure in asymptomatic patients, panel finds

A global risk assessment rather than extensive testing is the best way to predict heart disease in most asymptomatic patients, according to a new practice guideline from the American College of Cardiology Foundation/American Heart Association.

An expert panel reviewed over 400 studies to arrive at their recommendations, which were released online this week and will appear in the Dec. 14/21 Journal of the American College of Cardiology and the Dec. 21 Circulation: Journal of the American Heart Association. The guideline looked at which diagnostic tests are most helpful in assessing cardiovascular risk in adults 20 years of age and older without obvious signs of heart disease. Tests were evaluated based on whether they added new information that could improve health outcomes by changing physicians’ treatment or patients’ behavior. High risk was defined as a global risk for “hard” coronary heart disease (CHD) events of 20% or higher over 10 years, while intermediate risk was distinguished from low risk by using a lower cutoff value of at least 10% and a higher cutoff value of less than 20%.

The guideline recommended that global risk scoring including factors such as cholesterol, blood pressure, age, sex, diabetes and smoking (e.g., the Framingham Score) should be used to assess cardiovascular risk in all adults, and that family history should always be examined. The expert panel concluded that the following tests are reasonable and may be considered in certain subgroups of asymptomatic patients:

  • C-reactive protein for cardiac risk assessment in intermediate-risk men age 50 and younger and women age 60 and younger, and for determining the appropriateness of statin therapy in certain older people;
  • coronary artery calcium scoring in people with diabetes who are over 40 years old, in intermediate-risk people and possibly in patients at low to intermediate risk;
  • resting electrocardiogram (ECG), especially for patients with high blood pressure or diabetes;
  • ankle-brachial index in those at intermediate risk;
  • carotid intima-media thickness in those at intermediate risk;
  • urinalysis to detect microalbuminuria in patients at intermediate risk or with high blood pressure or diabetes;
  • conventional echocardiography in hypertensive patients;
  • nuclear stress testing in patients who have diabetes or a strong family history of heart disease, if previous tests suggest a high heart disease risk;
  • exercise ECG stress test in those at intermediate risk, for example, previously sedentary adults who are about to start a vigorous exercise program;
  • hemoglobin A1c, regardless of patients’ diabetes status, to assess average blood glucose levels over time; and
  • lipoprotein-associated phospholipase A2 in those at intermediate risk.

The expert panel also concluded that the following lack benefit in asymptomatic patients:

  • genetic testing;
  • lipid parameters besides a standard profile, including lipoproteins, apolipoproteins, particle size and density;
  • natriuretic peptide levels;
  • coronary computed tomography angiography;
  • magnetic resonance imaging for detection of vascular plaque;
  • stress echocardiography;
  • flow-mediated dilation; and
  • measures of arterial stiffness, such as pulse wave velocity.

Research is lacking on the optimal timing and frequency of cardiovascular risk assessment in asymptomatic patients, the panel members noted. More research is also needed on MRIs, genetic testing, environmental risks, and the effect of risk management strategies on outcomes, they wrote.

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Free, two-minute dementia screen compares well to longer mini-assessments

A new, 16-question mental status exam provides quicker cognitive impairment screening in a primary care or hospital setting, according to researchers who developed the test.

The researchers developed the "Sweet 16" exam, which comprises 16 scored items worth one point each and takes about two minutes to complete. The exam includes eight items that assess orientation in time and space; three registration items involving immediate repetition; two practice and two scored digit span items (practice items count forward, scored items count backward); and three recall items. The items were chosen based on widely used cognitive assessment measures that test areas most likely to be impaired, such as memory. The exam doesn't require pen and paper to complete and can be administered by clinical or lay staff in different settings, according to an article in the Nov. 8 Archives of Internal Medicine.

Current screening tests take about 15 minutes, require the patient to write or copy patterns with pen and paper, or may be affected by poor vision or lower educational levels. Also, the Mini-Mental State Exam is copyrighted, requiring fees to use.

In the development cohort, the Sweet 16 highly correlated with the MMSE (Spearman r, 0.94; P<0.001). The overall agreement between the Sweet 16 and the MMSE at clinically relevant thresholds (<14 for Sweet 16 and <24 for MMSE) was a weighted κ of 0.60 (P<0.001). Equipercentile equating, defined as “a procedure that creates the same percentile distributions across both scales,” identified Sweet 16 cut points that correlated with MMSE cut points, as follows:

MMSE Sweet 16
24 13.1
20 10.9
18 9.7
10 4.6

An MMSE score of 24 is widely used to indicate cognitive impairment. Because the equivalent value on the Sweet 16 falls between integers, researchers opted for a Sweet 16 value less than 14 as the cutoff for cognitive impairment, as it maximizes sensitivity compared to the MMSE (80% vs. 70%). The Sweet 16 is also more able to exclude disease. The likelihood ratio for a negative test result was 0.29 for the Sweet 16 compared with 0.42 for the MMSE. And across a range of education levels, the area under the curve for higher education (>12 years) was 0.90 for the Sweet 16 and 0.84 for the MMSE (P=0.03).

The Sweet 16 is a screening exam that requires follow-up with a more comprehensive exam, researchers noted. "[T]he Sweet 16 may be preferred over the MMSE in frail older or medically ill hospitalized or institutionalized patients in whom the ability to write and manipulate props may be limited for reasons other than cognitive impairment (eg, intravenous tubing, positioning in bed) and in situations such as a busy clinical practice or a large study cohort in which the ability to quickly complete a cognitive assessment is essential," they wrote.

The Sweet 16 tool is available online.

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Test yourself

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MKSAP Quiz: generalized rash, facial edema, fever, and severe fatigue

A 51-year-old woman is evaluated for generalized rash, facial edema, fever, and severe fatigue that have developed over the past week. She was recently diagnosed with rheumatoid arthritis. She currently takes prednisone, hydroxychloroquine, and sulfasalazine. She has no previously known allergies.

On physical examination, temperature is 39.1 °C (102.3 °F), blood pressure is 110/78 mm Hg, pulse rate is 108/min, and respiration rate is 25/min. The face is edematous. Skin examination reveals a generalized morbilliform eruption. The skin is not painful, and no blisters are present. There is no ocular or mucosal involvement. Lymphadenopathy is noted in the cervical and axillary regions. Laboratory studies show a serum alanine aminotransferase level of 330 U/L and a serum aspartate aminotransferase level of 355 U/L. Results of a complete blood count are normal except for 16% eosinophils.

Which of the following is the most likely diagnosis?

A) Drug reaction with eosinophilia and systemic symptoms (DRESS)
B) Erythema multiforme
C) Stevens-Johnson syndrome
D) Toxic epidermal necrolysis

Click here or scroll to the bottom of the page for the answer and critique.

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Nephrology

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Early hemodialysis initiation may be harmful to patients

Guidelines and current practice have been leading patients to begin hemodialysis at higher estimated glomerular filtration rates (eGFRs) but the earlier initiation may actually be increasing mortality, according to a new study.

The observational study included more than 80,000 nondiabetic hemodialysis patients who had no comorbidities other than hypertension and were relatively young—between 20 and 64 years old. The patients were divided by their eGFR at initiation of dialysis. Among patients with a eGFR below 5.0 mL/min/1.73 m2, one-year mortality was 6.8%. In the highest eGFR group (>15.0 mL/min/1.73 m2), the mortality rate was 20.1%. After adjustment and compared with the lowest eGFR group, patients starting with a eGFR of 5.0 to 9.9 mL/min/1.73 m2 had a 23% increased risk for mortality over two years, while those with an eGFR between 10 and 15 mL/min/1.73 m2 had a 47% increased risk and those with an eGFR over 15 mL/min/1.73 m2 had a 74% risk.

The researchers also stratified patients based on serum albumin concentrations, and found the same increased mortality risk even in the healthiest patients, who had serum albumin above 3.5 g/dL. The study authors offered several possible mechanisms for the effect, including myocardial ischemia and “stunning” and changes resulting from fixed systolic dysfunction induced by hemodialysis. They concluded that initiation of hemodialysis “should not be based on an arbitrary level of eGFR or serum creatinine level unless this measure is accompanied by definitive end-stage renal failure-related indications.”

Current guidelines recommend that dialysis be started when eGFR falls below 10.5 mL/min/1.73 m2, and the average eGFR and serum creatinine of patients initiating dialysis have increased substantially over the last 15 years, noted an accompanying editorial. The current study, and the recent IDEAL trial, do not support that practice, the editorialist concluded. She called for changing practice and starting dialysis only when patients’ symptoms are worse than the side effects of dialysis are likely to be. The study and editorial were published online by Archives of Internal Medicine on Nov. 8.

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Cardiology

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Intensive statin therapy lowered risk even for low LDL patients

A new meta-analysis of intensive statin therapy found that as patients’ LDL cholesterol decreased further, their risk of heart attack, revascularization and ischemic stroke also decreased, with no bottom threshold or significant increase in adverse events.

The analysis included data from 170,000 patients in 26 randomized trials comparing either more intensive against less intensive statin regimens or statins against controls. In the trials comparing more and less intensive regimens, the more intensive regimens reduced major vascular events by 15% more than the less intensive regimens (95% CI, 11% to 18%). For every 1 mmol/L (about 39 mg/dL) that statins lowered patients’ LDL cholesterol, all-cause mortality was reduced by about 10%. The benefits were similar in all types of patients, including those with LDL lower than 2 mmol/L (about 77 mg/dL). The greatest reductions were seen in CHD deaths (rate ratio, 0.80; 99% CI, 0.74 to 0.87) and death from other cardiac causes (rate ratio, 0.89; 99% CI, 0.81 to 0.98).

The study authors concluded that reductions in LDL cholesterol safely produce reductions in the incidence of heart attack, revascularization and ischemic stroke, with no evidence of any lower threshold. Although current guidelines emphasize treating cholesterol to a target, the authors suggested that for high-risk patients, additional benefits may be achieved by lowering LDL even further.

The analysis, which was published by The Lancet on Nov. 13, also looked at potential negative effects of intensive therapy. There was a nonsignificant increase in hemorrhagic strokes associated with lowering LDL. However, the overall effect of reduced LDL on deaths from stroke or other vascular causes was not significant. The study also found no evidence of an increase in cancer associated with the use of statins.

Results from one study within the meta-analysis were also published in the same issue. The trial randomized myocardial infarction survivors to 80 mg or 20 mg of simvastatin per day and found about a 6% decrease in major vascular events (risk ratio, 0.94; 95% CI, 0.88-1.01) associated with the higher dose, but a significant increase in myopathy, greatest during the first year of treatment. Two (or 0.03%) of the patients in the low-dose group had myopathy compared to 53 (0.9%) in the higher-dose group. Based on these results, blood monitoring should be considered for any patients placed on an 80-mg dose of simvastatin, the study authors concluded.

A more appropriate strategy—and one also advocated in the meta-analysis—may be to achieve LDL reductions using a newer, more potent statin or a combination of a generic statin and another medication, the author said. A comment article accompanying the studies offered some caveats. Although the studies present relative risk reductions, clinicians should focus more on the absolute risk reductions for individual patients. The results of the meta-analysis should also not be understood to suggest that statin therapy should target an LDL of less than 2 mmol/L (77 mg/dL) but that high-risk patients whose baseline is below that level may still benefit from intensive therapy, the comment said.

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From the College

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Nominees named for College Officer and Regent positions

The Governance Committee of the American College of Physicians places in nomination candidates for College officers and the Board of Regents.

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College awards and Masters of 2011 announced

The Board of Regents recently approved the 2011 ACP Masters and national award winners. The list of winners is available on ACP Online. The new Masters and award winners will be honored at Convocation at Internal Medicine 2011 in San Diego.

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For the record

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Clarification to a previous issue

In last week's ACP InternistWeekly, the first sentence of the item on reimbursement cuts and prostate drugs should have read "Medicare reimbursement cuts were associated with reduced use of androgen-deprivation therapy for prostate cancer, particularly among men for whom the benefits of such therapy were unclear." The item has been updated.

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Cartoon caption contest

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Put words in our mouth

ACP InternistWeekly wants readers to create captions for this cartoon and help choose the winner. Pen the winning caption and win a $50 gift certificate good toward any ACP product, program or service.

E-mail all entries to acpinternist@acponline.org. ACP staff will choose finalists and post them online for an online vote by readers. The winner will appear in an upcoming edition.

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MKSAP answer and critique

The correct answer is A) Drug reaction with eosinophilia and systemic symptoms (DRESS). This item is available to MKSAP 15 subscribers as item 4 in the Dermatology module.

This patient has a drug reaction characterized by a generalized papular eruption, eosinophilia, and systemic symptoms and is consistent with drug reaction with eosinophilia and systemic symptoms (DRESS). With cessation of the causative drug, most likely sulfasalazine, the skin reaction rapidly subsides along with lymphadenopathy, fever, elevated aminotransferase levels, and eosinophilia. Patients with DRESS may develop severe hepatitis, and fulminant hepatic necrosis may occur if the condition is unrecognized.

Erythema multiforme (EM) is an acute, often recurrent mucocutaneous eruption that usually follows an acute infection, most frequently recurrent herpes simplex virus infection, but it may also be drug related or idiopathic. Lesions range in size from several millimeters to several centimeters and consist of erythematous plaques with concentric rings of color. Patients may have low-grade fever during an EM outbreak. However, this patient’s skin lesions are not consistent with EM, and EM does not cause lymphadenopathy, aminotransferase elevations, or eosinophilia.

The reactions that are generally classified within the spectrum of severe cutaneous adverse reactions include acute generalized exanthematous pustulosis, Stevens-Johnson syndrome/toxic epidermal necrolysis, DRESS, and vasculitis. Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are characterized by fever, skin pain, and mucocutaneous lesions resulting in epidermal death and sloughing. The clinical difference between SJS and TEN is the severity and percentage of body surface involved. SJS involves less than 10% of body surface area, SJS/TEN overlap involves 10% to 30%, and TEN involves greater than 30%. This patient’s skin lesions are not compatible with SJS or TEN, and these conditions cannot explain the patient’s other systemic findings.

Key Point

  • Drug reaction with eosinophilia and systemic symptoms (DRESS) is a serious cutaneous adverse reaction characterized by a generalized papular eruption, facial edema, fever, arthralgia, and generalized lymphadenopathy and is commonly associated with elevated aminotransferase levels, eosinophilia, and lymphocytosis.

Click here to return to the rest of ACP InternistWeekly.

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Copyright 2010 by the American College of Physicians.

Test yourself

A 48-year-old man is evaluated during a follow-up visit for urinary frequency. He reports no hesitancy, urgency, dysuria, or change in urine color. He has not experienced fevers, chills, sweats, nausea, vomiting, diarrhea, or other gastrointestinal symptoms. He feels thirsty very often; drinking water and using lemon drops seem to help. He has a 33-pack-year history of smoking. He has hypertension, chronic kidney disease, and bipolar disorder. Medications are amlodipine, lisinopril, and lithium. He has tried other agents in place of lithium for his bipolar disorder, but none has controlled his symptoms as well as lithium. What is the most appropriate treatment intervention for this patient?

Find the answer

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