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


In the News
for the Week of 6-8-10


  • Preventive aspirin reasonable for diabetics at high risk, not low
  • Education effort increased thiazide use

Test yourself

  • MKSAP Quiz: lower-extremity pain and 'red knots'


  • Beta-blockers may have benefit in COPD patients


Hormone replacement therapy

  • Route of HRT administration may affect stroke risk

FDA update

  • PPIs get warning on fracture risk
  • Liver injuries found in patients on orlistat

From ACP Internist

  • The next issue of ACP Internist is online and coming to your mailbox

From ACP Hospitalist

From the College

  • Annals editor leads council of science editors
  • ACP awards and Masterships nominations due July 1
  • Recruit-a-Colleague has a winner

Cartoon caption contest

Physician editor: Darren Taichman, FACP


Preventive aspirin reasonable for diabetics at high risk, not low

Guidance on how to use aspirin for primary prevention of cardiovascular events in diabetics was offered in a recent statement from the American Diabetes Association, the American Heart Association and the American College of Cardiology Foundation.

Aspirin use provides a modest (about 10%) reduction in cardiovascular events overall, but its effect as primary prevention in diabetics is unclear, the experts concluded after an evidence review. However, itís reasonable to use low-dose (75 to 162 mg/d) aspirin as prevention in diabetics who have an increased risk of cardiovascular disease (a 10-year risk over 10%), the statement said. That would include most men over 50 and women over 60 who have one or more additional risk factors: smoking, hypertension, dyslipidemia, family history of premature cardiovascular disease or albuminuria.

For patients at intermediate risk (younger patients with one or more of the risk factors, older patients with no risk factors, or anyone with a 10-year risk of 5% to 10%), preventive aspirin might be considered, the experts said. However, patients at low risk (those with a 10-year risk under 5%) should not be advised to take aspirin, as the potential adverse effects from bleeding offset the potential benefits. The statement noted that patients with diabetes are at higher risk for adverse events from aspirin than nondiabetics.

When calculating a patientís risk of cardiovascular disease, physicians should also consider the beneficial effects of other treatments such as statins, blood pressure control and smoking cessation. If these other treatments are adopted first, then there may be less need for aspirin, the statement said. The statement concluded by calling for additional research to better define the effects of aspirin in diabetes, including any sex-specific differences. The statement was published online by Circulation on May 27.


Education effort increased thiazide use

An effort to disseminate evidence-based information on thiazide-type diuretics resulted in a small increase in the use of the medications, a new study found.

Between 2004 and 2007, more than 100 investigator-educators met with more than 18,000 physicians in different parts of the country to educate them about the results of ALLHAT (Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial), which supported the use of thiazides as first-line therapy for hypertension. This study compared use of the drugs in counties where the investigator-educators had been active with use in areas where they hadnít. The results were published in the May 24 Archives of Internal Medicine.

According to a survey of physicians, the percentage of hypertension visits in which the drugs were recorded went up the most in areas where the educators were most active: an increase of 8.6% in active counties compared to 2% or lower increases in other areas. Pharmacy dispensing data showed a similar trend. Thiazide prescriptions went up 8.7% in active counties compared to 3.9% in inactive ones.

Study authors noted that the effect of the program was small, but consistent with the small dose of the intervention that physicians received. In addition, the project had to compete with public questioning of the ALLHAT findings by the pharmaceutical industry and others. Still, they concluded that such efforts, which they described as academic detailing, have the potential to improve prescribing patterns.

Although he praised the effort in an accompanying commentary, Jerry Avorn, MD, noted that it was not actually academic detailing, a concept which he invented. Academic detailing typically involves a one-to-one encounter like that of a pharmaceutical rep visiting a physician, while the ALLHAT dissemination program used group presentations. The difference was probably a major contributor to the projectís small effect, Dr. Avorn noted. More work is needed on how to develop delivery systems for getting evidence-based data into clinical practice, he concluded.


Test yourself

MKSAP Quiz: lower-extremity pain and 'red knots'

A 25-year-old woman is evaluated for a 2-week history of bilateral lower-extremity pain and skin lesions that she describes as ďred knots.Ē Ibuprofen has not alleviated her discomfort, and she has continued to develop new skin lesions. Six months ago, she developed vulvar ulcers that were negative for herpes simplex virus on a polymerase chain reaction assay; these lesions healed within 3 weeks. Two years ago, she developed uveitis that was treated with prednisolone drops. She also has a 7-year history of Raynaud phenomenon and a long-standing history of recurrent oral ulcers. She has had no recent infections and currently has no vulvar ulcers.

On physical examination, vital signs and cardiopulmonary and abdominal examinations are normal. There is no conjunctival injection. There are two ulcers on her tongue. Cutaneous examination reveals several subcutaneous reddish-colored nodules that are tender to palpation located on the lower extremities bilaterally. There is no synovitis, and range of motion of all joints is full.

Laboratory studies:

Complete blood count Normal
Erythrocyte sedimentation rate 95 mm/h
Metabolic panel Normal
Rheumatoid factor Negative
Antinuclear antibodies Negative
ANCA Negative
Urinalysis Normal

A chest radiograph is normal.

Which of the following is the most appropriate treatment for this patient?

A) Leflunomide
B) Penicillin
C) Prednisone
D) Sulfasalazine

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



Beta-blockers may have benefit in COPD patients

Beta-blockers may help reduce exacerbation risk and improve survival in patients with chronic obstructive pulmonary disease (COPD), according to a new study.

Physicians often avoid beta-blockers in COPD patients with cardiovascular disease because of potential pulmonary complications. However, some research has indicated that beta-blockers may in fact be helpful in this population. To further examine this question, researchers performed an observational cohort study of data from 23 Dutch general medicine practices. The goal of the study, which appeared in the May 24 Archives of Internal Medicine, was to determine whether long-term use of beta-blockers improves outcomes in COPD patients with and without cardiovascular disease.

A total of 2,230 patients who had prevalent COPD at the start of the study (25%) or were diagnosed with incident COPD during follow-up (75%) were included. Fifty-three percent of patients were men, and the mean age at the beginning of the study was 64.8 years. Six hundred eighty-six patients (30.8%) died and 1,055 (47.3%) had one or more COPD exacerbations over a mean of 7.2 years of follow-up. Overall crude and adjusted hazard ratios with beta-blocker use, respectively, were 0.70 (95% CI, 0.59 to 0.84) and 0.68 (95% CI, 0.56 to 0.83) for mortality and 0.73 (95% CI, 0.63 to 0.83) and 0.71 (95% CI, 0.60 to 0.83) for exacerbations. Results were similar in patients with COPD but no evident cardiovascular disease.

The authors noted that COPD could have been incorrectly diagnosed in some study patients who actually had cardiovascular disease, among other limitations. However, they concluded that beta-blockers may reduce mortality rates and COPD exacerbations in patients with both COPD and cardiovascular disease. An accompanying editorial emphasized the need for a randomized, controlled trial to confirm the findings but said that the current study "provide[s] a rationale for the practicing clinicians to use Ŗ-blockers (even noncardioselective ones such as carvedilol) cautiously in their patients with COPD who also have a coexisting cardiovascular condition for which a Ŗ-blocker is required."



SSRIs linked to cataract development

Researchers found a possible association between current use of selective serotonin reuptake inhibitors (SSRIs), especially fluvoxamine and venlafaxine, and a future diagnosis of cataracts.

Researchers conducted a nested, case-control study of subjects within a previous study of patients who had received a coronary revascularization procedure between 1995 through 2004 in Quebec, Canada. Linked administrative databases of the health insurance system provided the data for all residents 65 years or older who are part of Canada's universal health care plan. Results appeared in the June issue of Ophthalmology.

Available SSRIs included citalopram, fluoxetine, fluvoxamine, paroxetine, and sertraline, and researchers also looked at venlafaxine, a serotonin and norepinephrine reuptake inhibitor (SNRI). Researchers identified patients prescribed SSRIs or venlafaxine one year before the index date. Current users had received an SSRI or venlafaxine within 30 days of the index date, or were defined as past users. Cataracts were identified by an ophthalmologist.

For each case, 10 controls were selected and matched by index date, age and cohort entry. Crude and adjusted rate ratios (RRs) and corresponding confidence intervals (CIs) were computed for current SSRI use. Rate ratios were adjusted for gender, corticosteroid use, statins, high blood pressure, antihypertensives and antidiabetics.

From the data, 18,784 cases and 187,840 controls met inclusion criteria. The adjusted RR for cataracts among current users of SSRIs was 1.15 (95% CI, 1.08 to 1.23). The risk of cataracts was highest with fluvoxamine (RR, 1.39; 95% CI, 1.07 to 1.80), followed by venlafaxine (RR, 1.33; 95% CI, 1.14 to 1.55) and paroxetine for cataract surgery (RR, 1.23; 95% CI, 1.05 to 1.45).

The average time to diagnosis of cataracts while on SSRI therapy was 656 days for the first analysis and 690 days for a second analysis. The two analyses were generally concordant, except when cases were restricted to outpatient surgery. Then, paroxetine was associated with cataracts (RR, 1.23; 95% CI, 1.05 to 1.45). Past use did not pose a risk (RR, 1.06; 95% CI, 0.97 to 1.17).

The strength of this study is the large sample size and the detailed prescription drug information, which allowed researchers to look at the time of onset of cataracts, as well as the risk of individual SSRIs. Limitations include cataract diagnosis by ICD-9 codes, which does not confirm surgery. Detailed work-ups for cataract diagnosis were not available. Not all confounders, including smoking, could be assessed. Finally, because cataracts may take years to develop, subjects could have had undiagnosed cataracts.

Up to 10% of U.S. residents take an antidepressant, mainly SSRIs and SNRIs. Using a relative risk of 1.15 for SSRI users, a population attributable risk of 1.5%, and a 10% prevalence of use, researchers estimated 22,000 cases of cataracts may be avoided secondary to SSRI use. However, more study is needed to confirm the link in other populations, authors wrote.


Hormone replacement therapy

Route of HRT administration may affect stroke risk

Risk for stroke may be lower with transdermal versus oral hormone replacement therapy (HRT) in postmenopausal women, according to a new study.

Canadian and German researchers performed a population-based, nested case-control study to determine whether route of HRT administration affected stroke risk in postmenopausal women. Data from approximately 400 general practices in the United Kingdom reporting to the General Practice Research Database were examined. Women who were 50 to 79 years of age between Jan. 1, 1987 and Oct. 31, 2006 were included. HRT exposure was classified as estrogens only, estrogens plus progestogen, progestogen only, and tibolone. Estrogens were further classified by oral or transdermal route of administration and high or low dose. The study's main outcome measures were rate ratio of stroke with current oral and transdermal HRT use versus no use. Results were published online June 4 by BMJ.

Overall, 15,710 stroke cases were matched to 59,958 controls over the study period. One thousand two hundred fourteen cases (7.7%) and 4,124 controls (6.9%) received at least one HRT prescription in the year preceding the index date (i.e., the date of the first recorded stroke). The adjusted rate ratio of stroke associated with current transdermal HRT use was 0.95 (95% CI, 0.75 to 1.20) compared with no use. Patches with low estrogen doses did not increase stroke risk compared with no use, while patches with high estrogen doses did (rate ratio, 0.81 [95% CI, 0.62 to 1.05] vs. 1.89 [95% CI, 1.15 to 3.11]). Stroke rate was higher in current low- and high-dose HRT users than in nonusers (rate ratio, 1.28 [95% CI, 1.15 to 1.42]).

The data used in the study were not validated by chart review, and the authors were unable to distinguish between ischemic and hemorrhagic stroke, among other limitations. However, the authors concluded that transdermal HRT with low doses of estrogen does not appear to increase stroke risk among postmenopausal women.

"Although these results alone do not represent definitive evidence to promote the use of the transdermal route over oral administration of oestrogen replacement therapy, this study should encourage further research on the importance of the route of administration to define the role of transdermal oestrogens in the therapeutic arsenal for the treatment of menopausal symptoms," the authors wrote.


FDA update

PPIs get warning on fracture risk

High doses or long-term use of proton-pump inhibitors may increase the risk of certain fractures, the FDA recently warned health care professionals and patients.

The labeling of both prescription and over-the-counter PPIs will be revised to reflect this risk, according to an FDA news release. The warning is based on an FDA review of several epidemiological studies that reported an increased risk of fractures of the hip, wrist and spine in patients using PPIs.

Physicians should weigh the known benefits against the potential risks of proton-pump inhibitors when determining if these medications are appropriate for treatment, the FDA advised. ďWhen prescribing proton-pump inhibitors, health care professionals should consider whether a lower dose or shorter duration of therapy would adequately treat the patient's condition,Ē said an FDA official.

Any side effects or other product problems with PPIs should be reported via the FDAís MedWatch Adverse Event Reporting program or by calling 800-332-1088.


Liver injuries found in patients on orlistat

Cases of severe liver injury with hepatocellular necrosis or acute hepatic failure have been reported in patients taking the weight-loss medication orlistat, the FDA recently announced.

Warnings will be added to the labeling for Xenical (the 120-mg prescription form of orlistat) and Alli (60 mg, available over the counter). The injuries have been reported only rarely (12 foreign reports with Xenical and 1 U.S. report with Alli) and a cause-and-effect relationship has not been established, according to an FDA news release. However, because of the seriousness of severe liver injury, the FDA added information to the labels to educate the public.

Prescribing physicians should weigh the benefits of weight loss against the potential risks when determining if these medications are appropriate for patients and instruct patients to report any symptoms of hepatic dysfunction (anorexia, pruritus, jaundice, dark urine, light colored stools, or right upper quadrant pain) when using these medications. If liver injury is suspected, orlistat and other suspect medications should be discontinued immediately and liver function tests and ALT and AST levels obtained. Any adverse events associated with the medications should be reported to FDA's MedWatch program.


From ACP Internist

The next issue of ACP Internist is online

The June issue of ACP Internist features the following articles:

ACP Internist Internal Medicine 2010 coverage: Pearls aid treatment of opioid dependence
An expert reviews the benefits of agonist treatments over ďgoing cold turkey,Ē how to foil abuse of oral medications, and the best way to nail inpatient diagnoses.

More conference coverage: Hospital medicine meeting offers advice for all internists
In addition to complete coverage of the American College of Physiciansí Internal Medicine meeting, readers can find coverage from the Society of Hospital Medicineís annual meeting, including a digest of palliative care, consulting as a career and infectious disease control.

Practice Rx: DEA to ease burden, allow e-prescribing for controlled substances
The Drug Enforcement Administration has released an interim final rule allowing doctors to transmit prescriptions for controlled substances electronically. ACPís practice management staff members outline how physicians can begin the process.


From ACP Hospitalist

Suggest a colleague as a Top Hospitalist

ACP Hospitalist is seeking candidates for its third annual Top Hospitalists issue. The magazine is looking for hospitalists who made notable contributions to the field in 2010, whether through exceptional clinical skills, improved work flow, patient safety, cost savings, leadership, mentorship or quality improvement.

Do you know a colleague who might qualify? Fill out the form and tell ACP Hospitalist who and why. All recommendations must be received by July 16, 2010, when the editorial advisory board will pick the winners. Top Hospitalists will be profiled in the magazine's November 2010 issue.


From the College

Annals editor leads council of science editors

Annals of Internal Medicine editor Christine Laine, FACP, recently took office as president of the Council of Science Editors (CSE).

CSE is an organization composed of editorial professionals dedicated to the responsible and effective communication of science. A nationally renowned academic general internist, Dr. Laine is the youngest editor in the history of Annals of Internal Medicine. Dr. Laine is a clinical associate professor of medicine in the Division of Internal Medicine at Jefferson Medical College in Philadelphia where she continues to teach and see patients.


ACP awards and Masterships nominations due July 1

The deadline is fast approaching for nominations for ACPís 2010-2011 awards and Masterships. All nominations are welcome, particularly those for awards recognizing:

  • Science as related to medicine (ACP Science Award)
  • Diabetes (Eichold Award)
  • Care of patients (Claypoole Award)
  • Lay contributions to the health field (Loveland Award)
  • Science of mental health (Menninger Award)
  • Clinical care (Rosenthal Award #1)
  • Delivery of health care (Rosenthal Award #2)
  • Medical student education (Waxman Award)

The 2010-2011 Awards and Mastership Booklet, available online, contains criteria for the College's awards and Masterships plus detailed instructions for writing and submitting nominating and supporting letters. More information is available online.

For questions or information about the status of nominations submitted previously, please email the staff liaison for the Awards Committee at


Recruit-a-Colleague has a winner

Japan Chapter member Hidetaka Yanagi, FACP, was selected as the winner in the 2009-2010 Recruit-a-Colleague Program. Dr. Yanagi has won the grand prize of a trip to Internal Medicine 2011 in San Diego, Calif. For more information about the Recruit-a-Colleague program, visit the program website.


Cartoon caption contest

And the winner is Ö

ACP InternistWeekly has tallied the voting from its latest cartoon contest, where readers are invited to match wits against their peers to provide the most original and amusing caption.









"Odd ... it says here that your co-pay is an arm and a leg."

This issue's winning cartoon caption was submitted by Zac Erekson, a student member who will begin residency training in Internal Medicine at the University of Iowa in July. Readers cast 142 ballots online to choose the winning entry. Thanks to all who voted!

The winning entry captured 53% of the votes.

The runners-up were:
"My HMO says I can be capitated here."
"You've lost weight, but that didn't really change your BMI."

ACP Internist continues its cartoon caption contest this week. Pen the winning caption and win a $50 gift certificate good toward any ACP product, program or service.

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






MKSAP 15 answer and critique

The correct answer is C) Prednisone. This item is available online to MKSAP 15 subscribers in the Rheumatology section, Item 6.

ACP's Medical Knowledge Self-Assessment Program (MKSAP) allows you to:

  • Update your knowledge in all areas of internal medicine
  • Prepare for ABIM certification or recertification
  • Support your clinical decisions in practice
  • Assess your medical knowledge with 1,200 multiple-choice questions

To order the latest edition of MKSAP, go online.

This patientís lower-extremity lesions are consistent with erythema nodosum. She also has oral ulcers, an elevated erythrocyte sedimentation rate, and a history of genital mucosal ulcers and uveitis. This clinical presentation strongly suggests a diagnosis of BehÁet disease, and the most appropriate management for this patient is prednisone.

Diagnostic criteria for BehÁet disease consist of the presence of oral ulcerations that recur at least three times in 1 year and at least two of the following manifestations: recurrent genital ulcerations, inflammatory eye disease, cutaneous lesions, and positive results on a pathergy test (characterized by a papule developing 48 hours after insertion of a 20-gauge needle intradermally). Patients with BehÁet disease also may have central nervous system vasculitis; a nonerosive arthritis that involves the medium and large joints; and elevated markers of inflammation, such as the erythrocyte sedimentation rate. Other manifestations include arterial and venous thromboses, and patients with BehÁet disease have a high mortality rate associated with arterial aneurysm rupture.

Treatment of BehÁet disease is directed toward the involved organ system. Although erythema nodosum can be treated with NSAIDs, use of these agents has not alleviated this patientís symptoms. Treatment with a corticosteroid such as prednisone is therefore reasonable.

Leflunomide and sulfasalazine are indicated to treat rheumatoid arthritis but are not useful in patients with erythema nodosum or BehÁet disease. Rheumatoid arthritis may present with Raynaud phenomenon and subcutaneous nodules. However, rheumatoid nodules typically develop on pressure points and are not tender or erythematous. Rheumatoid arthritis also is characterized by swelling and tenderness in and around the joints and may manifest as joint stiffness, synovial hypertrophy, synovitis, joint effusion, and loss of normal range of motion. These findings are absent in this patient.

Sulfasalazine also is used to treat inflammatory bowel disease, which may be associated with erythema nodosum. However, this patient has no gastrointestinal manifestations.

Key Point

  • Treatment in patients with BehÁet disease is directed toward the involved organ system.

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Copyright 2010 by the American College of Physicians.


Test yourself

A 67-year-old man is evaluated for a recent diagnosis of primary hyperparathyroidism after an elevated serum calcium level was incidentally detected on laboratory testing. Medical history is significant only for hypertension, and his only medication is ramipril. Following a physical exam and lab studies, what is the most appropriate management of this patient?

Find the answer

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