American College of Physicians: Internal Medicine — Doctors for Adults ®

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ACP InternistWeekly



In the News for the Week of June 12, 2012




Highlights

Insulin doesn't appear to increase cancer or cardiovascular risk

Using basal insulin to normalize glucose levels in patients with early diabetes and pre-diabetes doesn't affect cardiovascular event or cancer rates, a new study found. More...

Viscosupplementation for knee osteoarthritis has little benefit, analysis finds

Viscosupplementation for knee osteoarthritis offers little clinical benefit and increases risk for adverse events, a new study has found. More...


Test yourself

MKSAP Quiz: Emergency evaluation of severe chest pain

This week's quiz asks readers to evaluate a 68-year-old woman who visits the emergency department for sudden onset of severe chest pain, which began 3 hours ago. More...


Preventive medicine

Low-dose aspirin associated with bleeding events

Daily use of low-dose aspirin was associated with an increased risk of major gastrointestinal or cerebral bleeding, a study found. More...


Perioperative care

Elevated troponin T may help predict 30-day mortality

Troponin T levels accurately predict 30-day mortality after noncardiac surgery, a new study found. More...


Deep venous thrombosis

Age-adapted D-dimer cutoffs in older patients may help exclude DVT in primary care

Using age-adapted D-dimer cutoffs in older patients may help rule out deep venous thrombosis (DVT) in primary care, according to a new study. More...


Resources

Physician re-entry resources available

The issue of physician re-entry into the workforce is growing in importance, and a number of organizations and individuals have collaborated to examine re-entry and create guidelines, recommendations, and strategies to assist physicians and ensure access to care for patients. More...


Cartoon caption contest

Put words in our mouth

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


Physician editor: Philip Masters, MD, FACP



Highlights


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Insulin doesn't appear to increase cancer or cardiovascular risk

Using basal insulin to normalize glucose levels in patients with early diabetes and pre-diabetes doesn't affect cardiovascular event or cancer rates, a new study found.

The trial randomized more than 12,000 people with a mean age of 63.5 years who had cardiovascular risk factors plus impaired fasting glucose, impaired glucose tolerance or type 2 diabetes to receive daily basal insulin glargine or standard care, defined as treatment based on local guidelines or the investigator's best judgment. Insulin was titrated to a target fasting blood glucose level of ≤95 mg/dL in the glargine treatment group; in the standard care group, only 11% were treated with insulin, with a majority of patients (60%) being treated with metformin, and 19% not receiving any glucose-lowering agents. Median length of follow-up was 6.2 years. The study was presented at the American Diabetes Association annual meeting and published online by the New England Journal of Medicine on June 11.

The insulin and control groups had similar rates of myocardial infarction, stroke or death from cardiovascular causes (2.94 with insulin vs. 2.85 without per 100 person-years) and of a combined outcome of those events plus revascularization or hospitalization for heart failure (5.52 vs. 5.28 per 100 person-years). The incidence of new diabetes in the pre-diabetic patients, measured about three months after insulin was discontinued, was lower in the insulin group (30% vs. 35%; odds ratio, 0.80; P=0.05). However, insulin was associated with more weight gain (1.6 kg vs. −0.5 kg) and severe hypoglycemia (1.00 vs. 0.31 per 100 person-years). The rate of cancer did not differ between groups.

Researchers concluded that insulin glargine had a neutral effect on cardiovascular outcomes and cancer but increased hypoglycemia and weight. As the largest and longest study of its kind, this trial provides reassurance about previously suspected links between insulin and cardiovascular problems and cancer, the authors said. They attributed the extended benefit of diabetes reduction after insulin was discontinued to resting of the pancreas, although they noted that the durability of the effect is unknown.

The study also randomized patients to receive n-3 fatty acids or placebo, and results of that investigation, also published in the New England Journal of Medicine, showed no benefit or harm from the supplementation.


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Viscosupplementation for knee osteoarthritis has little benefit, analysis finds

Viscosupplementation for knee osteoarthritis offers little clinical benefit and increases risk for adverse events, a new study has found.

annals.jpg

Researchers performed a systematic review and meta-analysis to determine the risks and benefits of viscosupplementation, a treatment involving intra-articular injection of hyaluronic acid, for knee osteoarthritis. Randomized or quasi-randomized, controlled trials comparing viscosupplementation with a sham or nonintervention control in adults with symptomatic knee osteoarthritis were included. The primary outcomes of the review and meta-analysis were pain intensity and flareups; the secondary outcomes were function and severe adverse events. The study results were published online June 12 by Annals of Internal Medicine.

Overall, 89 trials involving 12,667 adults were included. The average patient age ranged from 50 to 72 years. Sixty-eight trials had a sham control, 22 trials used cross-linked forms of hyaluronic acid, and 40 trials had more than three months' follow-up. Seventy-one trials involving 9,617 patients found that viscosupplementation resulted in a moderate decrease in pain (effect size, −0.37 [95% CI, −0.46 to −0.28]). In five unpublished trials involving 1,149 patients, the effect size was −0.03 (95% CI, −0.14 to 0.09), while 18 large trials with blinded outcome assessment involving 5,094 patients showed an effect size of −0.11 (95% CI, −0.18 to −0.04), which was clinically irrelevant. Six trials involving 811 patients showed a nonstatistically significant increase in risk for flareups with viscosupplementation (relative risk, 1.51 [95% CI, 0.84 to 2.72]), while 14 trials in 3,667 patients showed that viscosupplementation increased risk for serious adverse events (relative risk, 1.41 [95% CI, 1.02 to 1.97]). The authors noted important between-trial heterogeneity and an asymmetrical funnel plot, writing that "Trial size, blinded outcome assessment, and publication status were associated with effect size."

The authors acknowledged that most of the included trials were of low quality and many did not report safety data. However, they concluded that viscosupplementation offers "minimal or nonexistent" benefit for pain and function in patients with knee osteoarthritis. "Because of increased risks for serious adverse events and local adverse events, the administration of these preparations should be discouraged," they wrote.



Test yourself


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MKSAP Quiz: Emergency evaluation of severe chest pain

A 68-year-old woman is evaluated in the emergency department for the sudden onset of severe pain, which began 3 hours ago. The pain is in the middle of her chest and radiates to her back. Medical history includes hypertension treated with hydrochlorothiazide and lisinopril.

mksap.jpg

On physical examination, the patient is afebrile. Her blood pressure is 190/110 mm Hg, pulse is 108/min and regular, and respiration rate is 18/min. An S4 gallop is auscultated. No pericardial rub or murmur is present. Distal pulses are equal, full, and symmetric. Neurologic examination is normal. Laboratory results include normal serum cardiac troponin and serum creatinine levels. Oxygen saturation is 99% while breathing ambient air.

Electrocardiogram shows tachycardia but is otherwise normal. CT scan of the chest with intravenous contrast demonstrates a crescent-shaped density within the media of the aorta, arising just distal to the origin of the left subclavian artery and extending to just above the celiac axis. Contrast dye is not present within this crescent.

In addition to analgesia and intravenous β-blockade, which of the following is the most appropriate treatment?

A) Endovascular repair
B) Intravenous sodium nitroprusside
C) Intravenous unfractionated heparin
D) Urgent surgical repair

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


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Preventive medicine


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Low-dose aspirin associated with bleeding events

Daily use of low-dose aspirin was associated with an increased risk of major gastrointestinal or cerebral bleeding, a study found.

Researchers used administrative data from 4.1 million citizens in 12 local health authorities in Italy to identify a cohort of 186,425 individuals taking aspirin (daily doses of 300 mg or less) from January 2003 to December 2008 and 186,425 matched controls who didn't take aspirin.

Results appeared in the June 6 Journal of the American Medical Association. During a median follow-up of 5.7 years, there were 6,907 first episodes of major bleeding requiring hospitalization. There were 4,487 episodes of gastrointestinal bleeding and 2,464 episodes of intracranial hemorrhage.

The incidence rates of total hemorrhagic events were 5.58 (95% CI, 5.39 to 5.77) per 1,000 person-years for those on aspirin and 3.60 (95% CI, 3.48 to 3.72) per 1,000 person-years for those without aspirin use (incidence rate ratio [IRR], 1.55; 95% CI, 1.48 to 1.63). Aspirin was associated with an excess risk of gastrointestinal bleeding (IRR, 1.55; 95% CI, 1.46 to 1.65) and intracranial bleeding (IRR, 1.54; 95% CI, 1.43 to 1.67). Regardless of aspirin use, diabetes was independently associated with an increased risk of major bleeding episodes (IRR, 1.36; 95% CI, 1.28 to 1.44).

The authors noted, "[W]eighing the benefits of aspirin therapy against the potential harms is of particular relevance in the primary prevention setting, in which benefits seem to be lower than expected based on results in high-risk populations. In this population-based cohort, aspirin use was significantly associated with an increased risk of major bleeding, but this association was not observed for patients with diabetes. In this respect, diabetes might represent a different population in terms of both expected benefits and risks associated with antiplatelet therapy."

An editorial noted that guidelines advocating the routine use of aspirin for primary prevention for individuals above a moderate level of risk of coronary heart disease should be carefully considered as this approach may not be advisable for all patients.



Perioperative care


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Elevated troponin T may help predict 30-day mortality

Troponin T levels accurately predict 30-day mortality after noncardiac surgery, a new study found.

The prospective, international cohort study involved more than 15,000 patients age 45 and older who had noncardiac surgery requiring at least overnight hospital admission. Fourth-generation troponin T (TnT) measurements were taken six to 12 hours after surgery and on postsurgery days 1, 2 and 3. The patients' peak troponin T measurements were collected and compared with 30-day mortality rates.

Overall, 30-day mortality among the patients was 1.9%. In multivariable analysis, the study authors found that troponin T levels of 0.02 ng/mL or higher predicted increased risk of 30-day mortality. Compared to patients whose TnT never went above 0.01 ng/mL, those with a peak of 0.02 ng/mL had a adjusted hazard ratio of death of 2.41. The risk was even higher for patients with peaks of 0.03 to 0.29 ng/mL (hazard ratio, 5.00) and 0.30 ng/mL or above (hazard ratio, 10.48). Within the 30 days after surgery, mortality rates were 1.0%, 4.0%, 9.3% and 16.9% for patients with TnT peaks of 0.01 or greater, 0.02, 0.03 to 0.29, and 0.30 or greater, respectively.

Based on these findings, elevated TnT levels may have predicted 41.8% of the deaths in the study population, researchers calculated. They noted that this multicenter study had consistent results across sites, indicating that the observed TnT thresholds could be relevant worldwide. They also observed that while many laboratories consider TnT values below 0.04 ng/mL to be normal, because of the nearly absolute specificity of troponins for myocardial tissue, levels below this threshold following noncardiac surgery may reflect cardiac injury and are strongly associated with 30-day mortality.

The next step in this research would be to determine whether interventions in the immediate post-surgical period (74.2% of patients with elevated TnT had it in the first 24 hours after surgery) could reduce the risk of mortality, the authors said. Aspirin and statin therapy show promise, but large, randomized clinical trials of interventions are needed, they concluded. The study was published in the June 6 Journal of the American Medical Association.



Deep venous thrombosis


.
Age-adapted D-dimer cutoffs in older patients may help exclude DVT in primary care

Using age-adapted D-dimer cutoffs in older patients may help rule out deep venous thrombosis (DVT) in primary care, according to a new study.

Researchers in the Netherlands conducted a retrospective, cross-sectional diagnostic study involving patients of 110 primary care doctors affiliated with three hospitals. Patients were evaluated for clinical suspicion of DVT between Jan. 1, 2002, and Jan. 1, 2006. The study's main objective was to determine whether age-adjusted D-dimer values could be used to safely exclude suspected DVT in primary care patients. All patients were assessed using both the Wells score for clinical probability of DVT and D-dimer levels. The primary outcome measures were the proportion of patients whose D-dimer levels were below two proposed age-adapted cutoffs and in whom DVT could be safely excluded, as well as the number of false-positive results. The two proposed D-dimer cutoffs were age in years × 10 μg/L in patients older than 50 or 750 μg/L in patients 60 or older. The study results were published online June 6 by BMJ.

A total of 1,374 consecutive patients with clinically suspected DVT were included in the study. Of these, 936 (68.1%) were older than 50. Six hundred forty-seven patients had a low clinical likelihood of DVT according to the Wells score. In this group, the age-dependent cutoff value safely excluded DVT in 309 patients (47.8%) compared with 272 patients (42.0%) when the cutoff of 500 μg/L, the conventional value, was used (increase, 5.7% [95% CI, 4.1% to 7.8%]). The false-negative rates were 0.5% and 0.3%, respectively (increase, 0.2% [95% CI, 0.004% to 8.6%]). In patients older than 80 years, the age-dependent cutoff value safely excluded DVT in 22 patients (35.5%) compared with 13 patients (21.0%) using the conventional cutoff value (increase, 14.5% [95% CI, 6.8% to 25.8%]). The cutoff value of 750 μg/L had similar exclusion and false-negative rates when compared with the age-dependent cutoff value (47.4% [307 patients] and 0.3%, respectively).

The authors noted that some data on D-dimer levels were missing and that two different assays were used, among other limitations. They also suggested caution when interpreting their results in patients older than 80, since that subgroup was small. However, they concluded that when combined with a low clinical probability of DVT, the age-dependent D-dimer cutoff in patients older than 50 and the higher cutoff of 750 μg/L in patients 60 and older significantly increased safe exclusion of DVT compared with the conventional cutoff value in primary care. They called for further study to assess the potential benefits of this approach in daily practice before widespread implementation.



Resources


.
Physician re-entry resources available

The issue of physician re-entry into the workforce is growing in importance, and a number of organizations and individuals have collaborated to examine re-entry and create guidelines, recommendations, and strategies to assist physicians and ensure access to care for patients.

Physician re-entry is defined as "a return to clinical practice in the discipline in which one has been trained or certified following an extended period of clinical inactivity not resulting from discipline or impairment." Resources on the subject can be accessed from the American Medical Association's Council on Medical Education and The Physician Reentry into the Workforce Project.



Cartoon caption contest


.
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.

acpi-20120612-cartoon.jpg

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 B) Intravenous sodium nitroprusside. This item is available to MKSAP 15 subscribers as item 30 in the Cardiology section. MKSAP 16 will release Part A on July 31. More information is available online.

The abrupt onset of severe chest pain is consistent with acute aortic disease. The CT scan findings for this patient are characteristic of an acute distal (type B) intramural hematoma. Analgesia is imperative in the treatment of acute aortic syndromes, as pain control is integral in management of blood pressure and heart rate. Medical management, consisting of control of heart rate with intravenous β-blockade, followed by intravenous administration of a rapidly titratable parenteral arterial vasodilator (such as sodium nitroprusside, fenoldopam, or enalaprilat), is the preferred therapy. Heart rate should be reduced to 60 to 80/min with the use of a parenteral β-blocking agent, such as esmolol, labetalol, or metoprolol. Blood pressure should be lowered to a systolic pressure of 100 to 120 mm Hg, mean arterial pressure of 60 to 75 mm Hg, or the lowest blood pressure commensurate with vital end-organ perfusion.

Certain findings on physical examination, including unequal upper-extremity blood pressures and a pulse deficit, increase the likelihood of acute aortic disease (including dissection and intramural hematoma); however, the absence of these findings, as in this patient, should not influence the decision to pursue further diagnostic testing.

Surgical therapy together with medical hemodynamic control would be appropriate for an ascending aortic (type A) hematoma. Whereas endovascular repair has been used for treatment of aortic dissection, there is no current role for endovascular treatment of isolated acute intramural hematoma. Surgical therapy of type B aortic syndromes is associated with significant morbidity and mortality. Endovascular repair or surgical intervention should be considered when distal intramural hematoma arises in association with a deep (≥10 mm) and wide (≥20 mm) penetrating atherosclerotic ulcer.

Aortic hematoma is caused by acute bleeding, possibly from rupture of the vasa vasorum, contained within the media of the aorta. There is no role for anticoagulation as part of management.

With treatment, patients with type B acute intramural hematomas fare as well as, or better than, patients with type B aortic dissection. Over time, intramural hematomas may follow one of three courses: resorption and normalization, aneurysmal dilation, or conversion to typical dissection. Because of this, follow-up surveillance by CT is reasonable.

Key Point

  • Medical management of pain, heart rate, and blood pressure is the preferred treatment for type B (distal) acute intramural hematoma.

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Test yourself

A 59-year-old woman is evaluated for a 1-week history of increasing pain of the right foot. She recalls stepping on a nail about 1 month before her symptoms began. The patient has a 5-year history of heart failure secondary to idiopathic dilated cardiomyopathy. She has an implantable cardioverter-defibrillator, and her current medications are carvedilol, lisinopril, furosemide, and spironolactone. Following a physical examination and radiograph of the foot, what is the most appropriate next step to establish the diagnosis?

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