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

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ACP InternistWeekly



In the News for the Week of July 2, 2013




Highlights

Diabetes meeting features research on prevention, drug effects, complications

CHICAGO—Long-term effects of lifestyle modification and hospitalization rates for complications of diabetes and diabetes treatment were among the research findings presented at the American Diabetes Association's Scientific Sessions last week. More...

Salsalate lowered HbA1c, inflammatory markers but increased LDL, urinary albumin in type 2 diabetics

Salsalate improved glycemic control and showed anti-inflammatory effects compared to placebo in adult patients with type 2 diabetes, a recent study found. More...


Test yourself

MKSAP Quiz: progressive fatigue and dyspnea on exertion

A 38-year-old woman is evaluated for a 6-month history of progressive fatigue and dyspnea on exertion. Over the past 2 years she has noted episodes of hand swelling, joint pain, blue color change of her fingers with cold exposure, and difficulty swallowing. Following a physical exam and lab results, what is the most appropriate next step in management? More...


Infectious disease

New tickborne illness may present as human granulocytic anaplasmosis

Two patients originally diagnosed with human granulocytic anaplasmosis (HGA) were found to have Borrelia miyamotoi infection instead, according to a new case report. More...


Stroke

Clopidogrel plus aspirin may reduce stroke risk better than aspirin alone after TIA, minor stroke

Patients with transient ischemic attack (TIA) or minor stroke who received clopidogrel and aspirin within 24 hours of symptom onset had a lower stroke risk than those who received aspirin alone, with no apparent increase in hemorrhage risk, a new study indicated. More...


CDC update

CDC committee recommends specific flu vaccine as an option for people with egg allergy

The immunization advisory committee at the Centers for Disease Control and Prevention (CDC) last week recommended using the vaccine FluBlok in the 2013-14 flu season for people aged 18 through 49 years with egg allergy. More...


Educational opportunities

Guidelines network conference coming up

ACP members are invited to attend the 10th Guidelines International Network (G-I-N) conference, to be held in San Francisco Aug. 18-21. More...


From ACP Hospitalist

Who's tops at your hospital? Let us know this month!

ACP Hospitalist is seeking candidates for its sixth annual Top Hospitalists issue in November, which will feature the best and brightest in hospital medicine. More...


From the College

ACP announces new chapter in Southeast Asia

Effective July 1, 2013, ACP welcomed its 15th international chapter, the ACP Southeast Asian Chapter. More...

Governance Committee seeks Regent candidates for 2014

The Governance Committee oversees the process for nominating and electing Masters and Fellows of the College to the Board of Regents (BOR) and is beginning the process of seeking Regents to join the Board in May 2014. 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: Daisy Smith, MD, FACP



Highlights


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Diabetes meeting features research on prevention, drug effects, complications

CHICAGO—Long-term effects of lifestyle modification and hospitalization rates for complications of diabetes and diabetes treatment were among the research findings presented at the American Diabetes Association's Scientific Sessions last week.

Final results from the Look AHEAD trial, presented at the meeting and published in the New England Journal of Medicine on June 24, showed that an intensive lifestyle intervention for overweight and obese type 2 diabetics reduced weight, hemoglobin A1c and some cardiovascular risk factors but had no impact on the primary outcome of cardiovascular-related death, myocardial infarction, stroke or angina hospitalization.

An analysis of Medicare fee-for-service beneficiaries with type 2 diabetes between 1999 and 2007 revealed that rates of hospital admission for hyperglycemia have declined (from 114 per 100,000 person-years in 1999 to 70 per 100,000 person-years in 2007) while hospitalizations for hypoglycemia have risen (94 per 100,000 person-years in 1999 up to a peak of 130 per 100,000 in 2007 back down to 105 per 100,000 in 2011). The findings should draw attention to the risks of increasing use of antihyperglycemic medications, said the Yale researchers who conducted the study.

Focusing on similar concerns, CDC researchers presented data on rates of emergency department (ED) visits and hospitalizations for insulin-related adverse events. In 2007-2009, insulin was responsible for 5.1% of all adverse drug event-related ED visits, and hypoglycemia occurred in 91.8% of those cases. Patients age 80 and over were significantly more likely to have an ED visit or hospitalization related to insulin (9.6 ED visits per 100 diabetic patients over 80 vs. 4.3 among younger diabetic patients, and 4.1 hospitalizations vs. 1.0 per 100 younger diabetic patients). The most common causes were not eating when expected and taking the wrong insulin or wrong dose.

Finally, an analysis of hospitalizations for diabetic foot infections from 2001-2010 found that the hospitalizations increased at the same pace as diabetes cases overall. The hospitalizations were associated with an average 8.2-day length of stay and $46,107 in hospital charges, as well as serious complications: Mortality occurred in 2.0% of hospitalizations, sepsis occurred in 9.6%, surgical complications occurred in 8.0% and amputation occurred in 10.5%. The statistics raise questions about whether greater efforts need to be made in the outpatient setting to prevent these hospitalizations, said study authors from the University of Arizona.

By Stacey Butterfield, Associate Editor


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Salsalate lowered HbA1c, inflammatory markers but increased LDL, urinary albumin in type 2 diabetics

Salsalate improved glycemic control and showed anti-inflammatory effects compared to placebo in adult patients with type 2 diabetes, a recent study found.

The randomized trial included 286 patients ages 18 to 75 with hemoglobin A1c (HbA1c) levels of 7.0% to 9.5%, recruited from three private practices and 18 academic centers in the U.S. For 48 weeks, patients added either 3.5 g of salsalate per day or placebo to their current diabetes regimens. Results were published in the July 2 Annals of Internal Medicine.

annals.jpg

The mean HbA1c was 0.37% lower in the salsalate group than in the placebo group over the course of the study (95% CI, −0.53% to −0.21%; P<0.001). This reduction in HbA1c was achieved despite overall reductions in other diabetes medications in the salsalate group and medication increases in the placebo group. The salsalate also showed anti-inflammatory effects: lower circulating leukocyte, neutrophil and lymphocyte counts in patients taking it compared to those on placebo. Salsalate patients also had greater increases in adiponectin and hematocrit levels and decreases in fasting glucose, uric acid and triglycerides.

However, they also had increases in weight, low-density lipoprotein (LDL) cholesterol and urinary albumin levels. The clinical relevance of the albumin increase is unclear, the study authors said, since the increase reversed after discontinuation of the medication and patients' estimated glomerular filtration rates were unchanged. Continued, longer-term evaluation of the effects of salsalate on renal function and LDL cholesterol is warranted before it can be widely recommended for type 2 diabetes patients, the authors said.

The study was limited by its small size and short duration, but salsalate was well tolerated and showed glucose-lowering effects similar to other typical second-line oral diabetes therapies, the study authors concluded.



Test yourself


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MKSAP Quiz: progressive fatigue and dyspnea on exertion

A 38-year-old woman is evaluated for a 6-month history of progressive fatigue and dyspnea on exertion. Over the past 2 years she has noted episodes of hand swelling, joint pain, blue color change of her fingers with cold exposure, and difficulty swallowing. She takes no medications.

mksap.gif

On physical examination, temperature is 36.9 °C (98.4 °F), blood pressure is 126/84 mm Hg, pulse rate is 88/min, and respiration rate is 18/min. Cardiac examination reveals an accentuated pulmonic component of S2 and a grade 2/6 holosystolic murmur. Muscle strength is normal.

Laboratory studies reveal a serum creatine kinase level of 312 units/L, an antinuclear antibody titer of 1:1280 (speckled pattern), and high positive anti-U1-ribonucleoprotein antibodies.

Pulmonary function tests show a DLCO of 55% of predicted with normal FEV1 and lung volumes. Chest radiograph is normal. Electrocardiogram reveals right axis deviation. Echocardiogram shows 2+ tricuspid regurgitation, an enlarged right atrium, normal left and right ventricular function, and an estimated systolic pulmonary artery pressure of 40 mm Hg. High-resolution CT of the chest is normal. Ventilation/perfusion scan results are normal.

Which of the following is the most appropriate next step in management?

A. Muscle biopsy
B. Radionuclide stress test
C. Repeat echocardiography and pulmonary function tests in 1 year
D. Right heart catheterization

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


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Infectious disease


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New tickborne illness may present as human granulocytic anaplasmosis

Two patients originally diagnosed with human granulocytic anaplasmosis (HGA) were found to have Borrelia miyamotoi infection instead, according to a new case report.

Researchers in Massachusetts and New Jersey detailed their findings on two patients, one from each state, who presented to primary care outpatient facilities with fever and were subsequently diagnosed with HGA, a tickborne illness. Both patients were eventually hospitalized due to the severity of their symptoms but failed to respond to doxycycline therapy after 24 hours. In addition, no molecular evidence of Anaplasma phagocytophilum, the causative agent of HGA, or of seroconversion to its antibodies was found in either patient. These findings led to further investigation with polymerase chain reaction (PCR), which identified B. miyamotoi. The case report was published in the July 2 Annals of Internal Medicine.

The authors cautioned that co-infection with B. burgdorferi could not be ruled out in one of the patients. However, they concluded that B. miyamotoi infection should be considered in patients who are thought to have HGA but do not respond to treatment with doxycycline, and they noted that such cases involving fever, myalgia, and elevated aminotransferase levels are probably being misdiagnosed and erroneously reported to the Department of Public Health.

"In North American sites, and indeed globally across the Holarctic where Lyme disease and HGA are commonly zoonotic, clinicians need to be aware of this newly recognized pathogen and include B. miyamotoi infection in the differential diagnosis of tick-exposed patients presenting with fever, myalgia, and elevated aminotransferase levels," they wrote.

The authors of an accompanying editorial urged caution in transitioning agent-specific PCR and serologic tests from the research setting to the clinical laboratory, noting that it seemed most appropriate for public health laboratories, both local and regional, to first work with investigators to develop and offer diagnostic testing to study the disease. However, they said, "In the meantime, B. miyamotoi infection should be included in the differential diagnosis of patients presenting in Lyme disease-endemic areas with unexplained fever, headache, myalgia, elevated hepatic aminotransferase levels, and leukopenia or thrombocytopenia during the summer months, and empirical doxycycline should be considered in severely ill patients."



Stroke


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Clopidogrel plus aspirin may reduce stroke risk better than aspirin alone after TIA, minor stroke

Patients with transient ischemic attack (TIA) or minor stroke who received clopidogrel and aspirin within 24 hours of symptom onset had a lower stroke risk than those who received aspirin alone, with no apparent increase in hemorrhage risk, a new study indicated.

Researchers performed a randomized, double-blind, placebo-controlled trial at 114 centers in China involving patients who had had minor ischemic stroke or TIA. The study included patients who were at least 40 years or age or older, had been diagnosed with an acute minor ischemic stroke or TIA, and were able to start taking the study drug within 24 hours of symptom onset. Patients were randomly assigned to receive clopidogrel, 300 mg initially followed by 75 mg/d for 90 days, plus aspirin, 75 mg/d for the first 21 days, or placebo plus aspirin, 75 mg/d for 90 days. All patients received open-label aspirin, 75 to 300 mg as determined by their clinicians, on day 1. The study's primary outcome was ischemic or hemorrhagic stroke over 90 days in an intention-to-treat analysis. Results were published online June 26 by the New England Journal of Medicine.

A total of 42,561 patients were screened for the study between October 2009 and July 2012, and 5,170 were randomly assigned, 2,584 to the clopidogrel-aspirin group and 2,586 to the aspirin-alone group. Almost 34% of patients were women, and the median patient age was 62 years. Overall, 8.2% of patients in the clopidogrel-aspirin group and 11.7% of those in the aspirin-only group had a stroke during follow-up (hazard ratio, 0.68; P<0.001). Seven patients in the clopidogrel-aspirin group and eight patients in the aspirin-only group developed moderate or severe hemorrhage (0.3% per group; P=0.73). In addition, the hemorrhagic stroke rate was also 0.3% in each group.

The authors noted that their study was conducted in China, where access to stroke therapies, availability of secondary prevention practices, and distribution of stroke subtypes can differ from the U.S. and Europe, and that their results may not be generalizable to other patient populations with ischemic events. However, they concluded that 21 days of clopidogrel plus aspirin followed by 90 days of clopidogrel alone reduces subsequent stroke risk better than aspirin alone in patients with high-risk TIA or minor ischemic stroke who are first seen within 24 hours of symptom onset.

The author of an accompanying editorial called the results "impressive" but noted that they may not apply to many groups of patients, including those with major ischemic stroke, non-Chinese patients, patients with lower absolute risk for recurrent stroke, and patients who can take advantage of effective secondary stroke prevention. He also pointed out that the results apply only to the first 90 days after ischemic stroke and cannot be generalized beyond that.

"The implication of this trial is that Chinese patients with acute TIA or minor ischemic stroke (onset within the previous 24 hours) who are at high risk for recurrence should be regarded as a medical emergency," the editorialist wrote. He said such patients should immediately receive clopidogrel plus aspirin for 21 days, then clopidogrel alone until 90 days, then long-term clopidogrel, aspirin, or aspirin plus extended-release dipyridamole. He recommended a bolus loading dose of 162 mg for aspirin and 300 mg for clopidogrel on day 1 in order to rapidly inhibit platelet aggression and stressed that dual antiplatelet therapy has the greatest effect soon after TIA and ischemic stroke.

The editorialist also called for continued enrollment of non-Chinese patients in large clinical trials examining the safety and efficacy of dual and triple antiplatelet therapy after acute TIA and minor ischemic stroke. "Moreover, I hope that researchers will evaluate new antiplatelet agents (e.g., ticagrelor and prasugrel) and new anticoagulant agents (e.g., rivaroxaban) that are effective in atherothrombotic acute coronary syndrome in patients with acute TIA and minor ischemic stroke due to arterial thromboembolism," he concluded.



CDC update


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CDC committee recommends specific flu vaccine as an option for people with egg allergy

The immunization advisory committee at the Centers for Disease Control and Prevention (CDC) last week recommended using the vaccine FluBlok in the 2013-14 flu season for people aged 18 through 49 years with egg allergy.

Unlike other available seasonal flu vaccines, FluBlok does not use the influenza virus or chicken eggs in its manufacturing process and can be used in adults with an egg allergy of any severity, the CDC said in a release. FluBlok was licensed by the Food and Drug Administration (FDA) in January 2013. The most common side effects are pain at the injection site, headache, fatigue, and muscle aches.

FluBlok has a shorter shelf life than other influenza vaccines, so clinicians should be sure to check the expiration date before administering it, the CDC said.



Educational opportunities


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Guidelines network conference coming up

ACP members are invited to attend the 10th Guidelines International Network (G-I-N) conference, to be held in San Francisco Aug. 18-21.

Long-term participants as well as new professionals who are passionate about high-quality guidelines will gather for the meeting. ACP is an active member of G-I-N and will be supporting the conference. Amir Qaseem, MD, PhD, MHA, FACP, director of clinical policy for ACP, is the current chair of G-I-N.

The conference features plenary speakers from all over the world, with an opening address by Joe V. Selby, MD, MPH, the first executive director of the Patient-Centered Outcomes Research Institute (PCORI). There is also a full day of educational courses on Sunday, Aug. 18, covering various guideline-related topics, including GRADE, developing guidelines to include lay expertise and health economics, and a master class in guideline implementation, as well as a two-hour AGREE II workshop. Registration for both the conference and the courses is available online.



From ACP Hospitalist


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Who's tops at your hospital? Let us know this month!

ACP Hospitalist is seeking candidates for its sixth annual Top Hospitalists issue in November, which will feature the best and brightest in hospital medicine. Let us know what your colleagues have accomplished in 2013. Did they take charge of a key quality or safety initiative? Do they always go out of their way to educate patients or help new physicians? Maybe they are amazing at tricky diagnoses, or selfless about volunteer outreach. Whatever the contribution, if it helped further hospital medicine, we'd like to hear about it.

Recommending a physician is easy: Just visit our online form and tell us which physician you think we should feature and why. The deadline is July 24, 2013. We look forward to receiving your suggestions!

Note: ACP Hospitalist's Top Hospitalist issue is not part of the ACP National Awards Program. Self-nomination is not permitted. Candidates need not be ACP members. The selection process is not scientific. Editorial board members are solely responsible for determining those profiled in the Top Hospitalists issue.



From the College


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ACP announces new chapter in Southeast Asia

Effective July 1, 2013, ACP welcomed its 15th international chapter, the ACP Southeast Asian Chapter.

The ACP Board of Regents approved the proposal to establish a chapter, and Oscar T. Cabahug, MD, FACP, immediate past president of the Philippine College of Physicians, was appointed Interim Governor. The new chapter includes the countries of Thailand, Indonesia, Malaysia, the Philippines, and Singapore.

In addition to the Southeast Asian Chapter, ACP has international chapters in Brazil, Canada (six chapters), Central America, Chile, Colombia, Japan, Mexico, Saudi Arabia, and Venezuela. ACP's total international membership now exceeds 10,000.


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Governance Committee seeks Regent candidates for 2014

The Governance Committee oversees the process for nominating and electing Masters and Fellows of the College to the Board of Regents (BOR) and is beginning the process of seeking Regents to join the Board in May 2014.

The Governance Committee will strive to represent the diversity within internal medicine on ACP's Board of Regents. Important general qualifications include commitment to ACP, dependability, leadership qualities, and the ability to represent the College in numerous and diverse arenas. Regent nominees must be Fellows or Masters of the College.

All candidates for Regent must submit a letter of nomination (not from the candidate) and two letters of support (from two individuals other than the nominator) by Aug. 1, 2013.

Letters of nomination should include the following sections:

  • brief description of the nominee's current activities,
  • special attributes the candidate would bring to the BOR in terms of the desired characteristics outlined above,
  • previous and current service in College-related activities,
  • service in organizations other than the College (medical and nonmedical) and
  • identification of two individuals who will write letters of support for the candidate.

Letters of support do not need to have specific content or format but will be most useful if they focus on the candidate's qualifications and how he or she would contribute to the BOR and the College.

Please send your confidential nominations, no later than Aug. 1, 2013, to:

Governance Committee

ATTN: Mrs. Florence Moore

American College of Physicians

190 N. Independence Mall West

Philadelphia, PA 19106-1572

Fax: 215-351-2829

e-mail: fmoore@acponline.org

Only candidates who submit a letter of nomination and two letters of support by Aug. 1, 2013, will be advanced to the Governance Committee for review.



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-20130702-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 D. Right heart catheterization. This item is available to MKSAP 16 subscribers as item 26 in the Rheumatology section. More information is available online.

Right heart catheterization is appropriate for this patient to evaluate for pulmonary arterial hypertension (PAH). She has symptoms and signs suggestive of an underlying diagnosis of mixed connective tissue disease (MCTD), which is characterized by overlapping clinical features of systemic lupus erythematosus, polymyositis, and systemic sclerosis, with high titers of antinuclear and anti-U1-ribonucleoprotein (RNP) antibodies. PAH may also occur, which is the most common disease-related cause of death in patients with MCTD.

This patient has Raynaud phenomenon, hand swelling, joint pain, dysphagia, high-titer speckled antinuclear antibodies, and high-titer RNP antibodies, all of which are typical findings of MCTD. This patient's symptoms of dyspnea on exertion, isolated low DLCO, and elevated estimated systolic pulmonary artery pressure on echocardiogram all suggest PAH. Therefore, right heart catheterization is indicated.

Despite the patient's mildly elevated serum creatine kinase level, muscle biopsy is not necessary, because her muscle strength is normal. Patients with MCTD may have subclinical myositis, but respiratory muscle weakness causing dyspnea would be a late finding associated with more profound myositis.

Radionuclide stress test is not indicated for this patient, whose abnormal DLCO and systolic pulmonary artery pressure on echocardiogram are not suggestive of ischemic cardiac disease as the cause for her dyspnea.

In patients with confirmed MCTD without cardiopulmonary symptoms and with normal baseline pulmonary function testing and echocardiogram, yearly repeat tests are appropriate for routine monitoring. It is an inappropriate choice for this symptomatic patient with findings highly suggestive of PAH.

Key Point

  • Pulmonary arterial hypertension is the most common disease-related cause of death in patients with mixed connective tissue disease.

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Test yourself

A 19-year-old man is evaluated for a sore throat, daily fever, frontal headache, myalgia, and arthralgia of 5 days' duration. He also has severe discomfort in the lower spine and a rash on his trunk and extremities. He returned from a 7-day trip to the Caribbean 8 days ago. The remainder of the history is noncontributory. Following a physical exam and lab studies, what is the most likely diagnosis?

Find the answer

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