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


In the News
for the Week of 3-30-10


  • Consider 'pre-CKD' prevalence among pre-diabetics
  • Bisphosphonates not associated with femoral fractures, study suggests

Test yourself

  • MKSAP Quiz: recurrent visual disturbance, headache


  • BNP-guided therapy helps heart failure outcomes, no effect in hospitalizations

Infectious disease

  • Updated C. difficile guidelines address changes in disease strain, drug effectiveness

Smoking cessation

  • Bupropion combined with weight-focused counseling helps women quit

FDA update

  • Don’t use Rotarix vaccine, FDA warns
  • High dose of simvastatin poses muscle injury risk

From the College

  • ACP’s Steven Weinberger, FACP, blogs at KevinMD

Cartoon caption contest

Physician editor: Patrick Alguire, FACP


Consider 'pre-CKD' prevalence among pre-diabetics

About 13 million American adults have undiagnosed or pre-diabetes and chronic kidney disease (CKD), researchers concluded based on national survey data confirmed by lab tests.

Researchers analyzed a sample of 8,188 Americans from the National Health and Nutrition Examination Survey from 1996 to 2006, in a study funded by the Centers for Disease Control and Prevention and reported in the Clinical Journal of the American Society of Nephrology.

The unadjusted CKD prevalence was 39.6% and 41.7% in those with diagnosed and undiagnosed diabetes, respectively. In those with prediabetes, CKD was 17.7%, compared with 10.6% in non-diabetics.

Of those with diagnosed diabetes and CKD, 39% had stage 3 or 4 CKD, and for those with undiagnosed diabetes and CKD, 40.6% had stage 3 or 4 CKD. Among prediabetics, 56.2% had stage 3 or 4 CKD.

Among those with stage 3 or 4 CKD, evidence of albuminuria and reduced kidney function was present in 19.4%, 20.7%, 18.0%, and 14.5% of those with diagnosed diabetes, undiagnosed diabetes, prediabetes, and no diabetes, respectively. Stricter or looser definitions of CKD changed the prevalence, but not the patterns across diabetes categories.

The authors wrote, "A substantial proportion of adults with undiagnosed diabetes had evidence of kidney damage and/or kidney function decline. Current standards of diabetes care recommend annual CKD screening among those with diabetes; however, this screening is unlikely to occur in those with undetected diabetes."

An accompanying editorial called for CKD screening to be extended to patients with prediabetes, and suggested that clinicians consider the concept of "pre-CKD," identifying patients in the early stages of CKD when it's preventable or reversible.


Bisphosphonates not associated with femoral fractures, study suggests

Bisphosphonates do not appear to be associated with atypical fractures of the femur, even after long-term use, according to a new study.

Findings from case reports and case series have indicated that the risk for atypical femoral fractures may be increased in patients taking bisphosphonates. To further investigate this possible association, researchers performed secondary analyses of data from three large randomized trials of bisphosphonate use: the Fracture Intervention Trial (FIT), the FIT Long-Term Extension (FLEX), and the Health Outcomes and Reduced Incidence with Zoledronic Acid Once Yearly (HORIZON) Pivotal Fracture Trial (PFT). They determined the relative hazards for fractures of the subtrochanteric or diaphyseal femur. The industry-funded study was published online March 24 by the New England Journal of Medicine.

Of 284 hip or femur fractures among 14,195 women in the three randomized trials, 12 fractures in 10 patients involved the subtrochanteric or diaphyseal femur. Relative hazards were 1.03 (95% CI, 0.06 to 16.46) for alendronate use in FIT, 1.50 (95% CI, 0.25 to 9.00) for zoledronic acid use in HORIZON-FIT, and 1.33 (95% CI, 0.12 to 14.67) for ongoing alendronate use in FLEX. The combined fracture rate was 2.3 per 10,000 patient-years.

The authors acknowledged that they were not able to examine patients' radiographs, that the number of events examined was small, and that their study "was underpowered for definitive conclusions." However, they wrote, their findings indicate that femoral fractures occur rarely in patients taking bisphosphonates, even after long-term use, and that the drugs were not associated with a significant increase in femoral fracture risk.

An accompanying editorial noted that physicians should not stop prescribing bisphosphonates because of concern about atypical femoral fracture risk. "However, they should reevaluate patients who are receiving long-term bisphosphonate therapy in the context of contemporary guidelines for treatment initiation, progress while receiving therapy, current bone mineral density measurements, and risk factors for fracture," the editorialist wrote.


Test yourself

MKSAP Quiz: recurrent visual disturbance, headache

A 62-year-old man is evaluated for recurrent episodes of visual disturbance followed by headache every 2 to 3 months for the past 5 years. The visual disturbance is described as a shimmering of light that obscures both visual fields and seems to resolve over 25 minutes and that is followed by mild to moderate headache with mild nausea. The headache typically resolves without treatment in 12 to 24 hours. The spells occur without reference to change in bodily position or time of day. He has a distant history of mild headaches with nausea, which he cannot recall clearly. Physical examination is normal.

What is the most likely diagnosis?

A) Vertebral-basilar transient ischemic attack
B) Cluster headache
C) Migraine without aura
D) Thunderclap headache
E) Migraine with aura

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



BNP-guided therapy helps heart failure outcomes, no effect in hospitalizations

Therapy guided by B-type natriuretic peptide (BNP) reduces all-cause mortality in patients with chronic heart failure compared with usual clinical care, especially in patients younger than 75 years, even if it doesn't reduce hospitalizations or increase hospital-free survival.

To examine the overall effect of BNP-guided drug therapy on outcomes in patients with chronic heart failure, researchers did a meta-analysis of eight prospective randomized, controlled trials of 1,726 outpatients with a history of heart failure. Eligible trials (mean duration, 16 months; range, 3 to 24 months) enrolled more than 20 patients and compared BNP-guided drug therapy versus usual clinical care in an outpatient setting. Results were reported in the March 22 Archives of Internal Medicine.

There was a significantly lower risk of all-cause mortality (relative risk [RR], 0.76; 95% CI, 0.63 to 0.91; P=0.003) in the BNP-guided therapy group compared with the control group. Patients younger than 75 years in the BNP-guided group had significantly lower all-cause mortality (RR, 0.52; 95% CI, 0.33 to 0.82; P=0.005). However, patients 75 years or older had no reduction in mortality with BNP-guided therapy (RR, 0.94; 95% CI, 0.71 to 1.25; P=0.70).

Risk of all-cause hospitalization and survival free of any hospitalization was not significantly different between groups (RR, 0.82; 95% CI, 0.64 to 1.05; P=0.12 and RR, 1.07; 95% CI, 0.85 to 1.34; P=0.58, respectively). More patients in the BNP groups had their doses of angiotensin-converting enzyme inhibitors and β-blockers titrated up to reach target levels (21% and 22% in the BNP group vs. 11.7% and 12.5% in the control group, respectively).

The authors noted that while BNP-guided therapy can decrease all-cause mortality, a major study limitation was that they were not able to examine key clinical end points, such as hospitalization for heart failure, where BNP-guided therapy should theoretically improve outcomes.


Infectious disease

Updated C. difficile guidelines address changes in disease strain, drug effectiveness

Two professional societies have issued updated Clostridium difficile guidelines to address epidemiologic and treatment changes since guidelines were first released in 1995.

In the last 15 years, researchers have identified a more virulent strain of C. difficile and have published data on the decreased effectiveness of metronidazole in severe disease, said the update by the Society for Healthcare Epidemiology of America and the Infectious Diseases Society of America. The update was published in the May Infection Control and Hospital Epidemiology. Recommendations include:

  • While stool culture is the most sensitive test, it is not clinically practical due to slow turnaround time. Toxin testing is most important clinically, but lacks sensitivity. A potential strategy is to employ a two-step method that uses enzyme immunoassay testing of glutamate dehydrogenase (GDH) as initial screening, and then uses the cell cytotoxicity assay or toxigenic culture as the confirmatory test for GDH-positive stool specimens. Results seem to differ based on the GDH kit used, so this is an interim recommendation.
  • Polymerase chain reaction (PCR) testing seems to be rapid, sensitive and specific, but more data are needed before it can be recommended for routine testing.
  • Repeat testing during the same episode of diarrhea is discouraged, as it has limited value.
  • Use metronidazole for an initial episode of mild-to-moderate C. difficile infection (CDI). The dosage is 500 mg orally three times per day for 10 to 14 days.
  • For an initial episode of severe CDI, use vancomycin. The dosage is 125 mg orally four times per day for 10 to 14 days.
  • For the first recurrence of CDI, usually use the same regimen as the initial episode, though stratify by disease severity. For the second or later recurrence, use vancomycin with a tapered and/or pulse regimen. Don't use metronidazole after the first recurrence or for long-term chronic therapy, due to the potential for cumulative neurotoxicity.


Smoking cessation

Bupropion combined with weight-focused counseling helps women quit

Women who are worried about gaining weight if they quit smoking may benefit from a combination of cognitive behavioral therapy (CBT) and treatment with bupropion, according to a new study.

The randomized trial included 349 women who were concerned about their weight and received smoking cessation counseling. The women were divided into four groups: one that received CBT targeted at their smoking-related weight concerns and bupropion hydrochloride sustained release, one that received standard cessation treatment with discussion of smoking but not weight and bupropion, one that received the weight counseling and placebo, and one that received standard counseling with placebo.

After six months of treatment, 34% of the women in the weight counseling plus bupropion group were nonsmoking, compared to 21% in the standard treatment plus bupropion group and 11.5% in the weight counseling with placebo group. However, at 12 months, the study found no difference in abstinence rates associated with the different counseling methods. There was also no difference in weight gain among the abstinent women, or in the study’s measurement of women’s weight concerns. Women who received the standard counseling did have reduced nicotine withdrawal and depressive symptoms if they took the active drug.

The researchers concluded that bupropion therapy improves cessation rates when used with weight counseling, but not with standard treatment. The weight counseling also appears to improve cessation rates and abstinence duration, at least during active treatment. Although the effect sizes were small, the study’s results are noteworthy, the authors said, because the intervention may help women smokers concerned about weight gain, who have been shown to have particularly difficulty with quitting.

The authors noted that some subgroups of the study had quite small sample sizes, and called for future research into the possible mechanisms of action in the studied interventions. The practicality of wider dissemination of the weight counseling program should also be investigated, they said. The study appeared in the March 22 Archives of Internal Medicine.


FDA update

Don’t use Rotarix vaccine, FDA warns

Health care professionals should temporarily suspend the use of Rotarix, one of the vaccines used to prevent rotavirus disease, the FDA recommended last week.

The suspension is being taken as a precaution after DNA from porcine circovirus type 1 (PCV1) was found in Rotarix. PCV1 is not known to cause disease in humans and the FDA reports no evidence of a safety risk. No medical follow-up is recommended for patients who have been vaccinated with Rotarix, according to the FDA safety alert.

However, use of the other licensed rotavirus vaccine, RotaTeq, is currently advised. In children who have received one dose of Rotarix, clinicians can complete the series with RotaTeq for the next two doses, according to the CDC.


High dose of simvastatin poses muscle injury risk

Patients taking high doses of simvastatin (Zocor) face an increased risk of myopathy, according to a new warning from the FDA.

Although muscle injury is a known side effect with all statins, the warning highlights the greater risk of developing muscle injury, including rhabdomyolysis, for patients who take the 80-mg dose of this drug, the FDA said. Rhabdomyolysis is the most serious form of myopathy and can lead to severe kidney damage, kidney failure, and sometimes death.

The FDA’s data on simvastatin were derived from observational studies, adverse event reports, prescription use data, and clinical trials, including the SEARCH (Study of the Effectiveness of Additional Reductions in Cholesterol and Homocysteine) trial, which evaluated patients taking 80 mg compared to 20 mg of simvastatin.

In addition to being sold as a single-ingredient generic medication and as the brand name Zocor, simvastatin is sold in combination with ezetimibe as Vytorin and in combination with niacin as Simcor.


From the College

ACP’s Steven Weinberger, FACP, blogs at KevinMD

Steven Weinberger, FACP, ACP's deputy executive vice president and senior vice president for medical education and publishing, continues his monthly column at, one of the Web's most influential medical blogs. This month's column looks at physician accountability.


Cartoon caption contest

And the winner is …

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

"We had to clone our interns to meet the latest work hour rules."

This issue's winning cartoon caption was submitted by Ami Shah, ACP Member, a rheumatologist at Johns Hopkins University in Baltimore, who will receive a $50 gift certificate good toward any ACP product, program or service. Readers cast 168 ballots online to choose the winning entry. Thanks to all who voted!

The winning entry captured 37.5% of the votes.

The runners-up were:

"We had a rough year in the Match."
"So, what's alien you?"
"They thought I was discussing a problem with Uranus."

ACP Internist continues its cartoon caption contest next week.


MKSAP answer and critique

The correct answer is E) Migraine with aura. This item is available online to MKSAP 14 subscribers in the Neurology section, Item 18.

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 patient has a distant history of migraine without aura, but his current headache meets the criteria for migraine with aura. Although vertebral-basilar transient ischemic attack could produce episodes of visual disturbance and headache, the episodes tend to be of shorter duration and worsen in frequency and severity over time. In addition, such episodes may be associated with postural change and should also be associated with other posterior circulation deficits, such as diplopia, vertigo, and dyscoordination. This patient has had the same frequency and severity of attacks over 5 years and does not relate other features consistent with posterior circulation disease. However, if this patient had presented without the 5-year history of similar events, then an evaluation for vertebral-basilar insufficiency should be considered.

Cluster headache is a brief headache and is generally not associated with visual disturbance. Thunderclap headache comes without warning and is a severe-intensity headache of sudden onset and remission, which does not fit this patient's description. This patient has a description of migraine with aura. It is not unusual for patients with distant migraine histories to change in later years to other forms of migraine, including the remission or initiation of migraine aura.

Key Point

  • Approximately 20% of patients with migraine have headache with aura, that is, neurologic problems such as visual hallucinations or numbness or tingling before or during headache.

Click here to return to the rest of ACP InternistWeekly.


About ACP InternistWeekly

ACP InternistWeekly is a weekly newsletter produced by the staff of ACP Internist. It is automatically sent to all College members who have an e-mail address on file with ACP.

To add your e-mail address to your member record and to begin receiving ACP InternistWeekly, please click here.

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

Not an ACP Member?

Join today and discover the benefits waiting for you.

Not an ACP Member? Join today and discover the benefits waiting for you

ACP offers different categories of membership depending on your career stage and professional status. View options, pricing and benefits.

A New Way to Ace the Boards!

A New Way to Ace the Boards!

Ensure you're board-exam ready with ACP's Board Prep Ace - a multifaceted, self-study program that prepares you to pass the ABIM Certification Exam in internal medicine. Learn more.