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

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In the News
for the Week of 2-24-09

Highlights

  • Stroke 2009: Research highlights tPA, gender differences
  • BP therapy helps even non-hypertensive diabetics

Test yourself

  • MKSAP quiz: herpes zoster

Therapeutics

  • Anti-TNF drugs increase herpes zoster risk
  • Genetic algorithm more accurate than fixed-dose for initial warfarin dosing

FDA update

Insurance update

  • Another insurer settles allegations of under-reimbursement

From ACP Internist's blog

  • Stroke 2009 and surgeries on twitter

From the College

Cartoon caption contest

  • Vote for your favorite entry

Physician editor: John Tooker, FACP


Highlights

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Stroke 2009: Research highlights tPA, gender differences

SAN DIEGO—Studies on tPA administration timing and gender differences in treatment were among the new research presented last week at International Stroke Conference 2009, sponsored by the American Heart Association/American Stroke Association.

One study examined whether women are less likely than men to be treated with tissue plasminogen activator (tPA) for acute stroke. The meta-analysis of 18 studies and 2.3 million acute stroke patients found that women’s odds of getting tPA treatment in the hospital were 30% lower than men's—a statistically significant difference. Yet a subgroup analysis of four studies, in which all patients had arrived at the hospital within the three-hour window for getting tPA, found that women were 19% less likely to get treatment—a difference that was no longer statistically significant.

Meanwhile, a retrospective study of 445 patients found that while women arrived at the emergency department of a tertiary stroke center later than men, they were treated just as quickly and often as men once they got there. Perhaps, then, observed gender differences in tPA treatment can be explained in part by women’s later arrival to the ED—when physicians may be more reluctant to use tPA for fear of missing the treatment window, the study’s coauthor suggested. It’s not known why women take longer getting to the ED, but the topic merits further study, she said.

Patients who arrive at hospitals within an hour of stroke symptom onset are more than twice as likely to get tPA as those who arrive in the second or third hour, a registry study of more than 100,000 patients found. Specifically, 27% who arrived within an hour of symptom onset got tPA, compared to 13% who arrived between one and three hours after onset. However, physicians took 15 minutes longer to treat first-hour patients than those who arrived later, perhaps thinking they had more of a time cushion to ensure that treatment was the right decision, the study’s coauthor said. Current guidelines recommend a "door to needle" time for tPA of 60 minutes from hospital arrival; for the study patients, the door to needle time was 90 minutes, on average. The study also revealed that 28% of ischemic stroke patients arrive within 60 minutes of symptom onset, 31.7% arrive in one to three hours, and 40% arrive more than three hours after symptoms start.

Up-to-the-minute updates are available on ACP Internist's blog.

—By Jessica Berthold

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BP therapy helps even non-hypertensive diabetics

Prescribing an ACE inhibitor together with a diuretic can reduce the risk of kidney disease in type 2 diabetics, even if they don't have high blood pressure, according to a new analysis from the ADVANCE study.

In the study of 11,140 diabetics, patients were randomly assigned to take either perindopril and indapamide or a placebo. Most of the patients were hypertensive, but 20% had normal blood pressure (under 130/80 mm Hg). At the follow-up of about four years, patients on the drugs had a 21% lower risk of renal events than controls. The active treatment group also had reduced risks of developing microalbuminuria and macroalbuminuria.

The findings held true even for patients who did not meet the criteria for high blood pressure. The lower the blood pressure level, the lower the risk of kidney disease found; the study could not identify a threshold below which the benefit was lost. Study authors called for more research on the topic, but also suggested that the new evidence may justify lowering the threshold at which type 2 diabetics are considered for antihypertensive treatment.

One limitation of the study was that it was not large enough to assess the impact of the drugs on kidney failure, a study author noted in a
press release. It was also not possible to determine the impact of the specific drug combination used or to prove whether the renal effects were due entirely to the reduction in blood pressure. The study was published online by the Journal of the American Society of Nephrology on Feb. 18.

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Test yourself

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MKSAP quiz: herpes zoster

A 70-year-old man is evaluated for an episode of herpes zoster. Two months ago, he developed a painful rash over the right trunk and was examined after symptoms persisted for 1 week. He was advised to use acetaminophen for pain and was given a prescription for acetaminophen with codeine. He continues to experience sharp pain, particularly when trying to sleep, and he has not found the pain medications to be effective. His history is significant for benign prostatic hyperplasia and hypertension for which he takes doxazosin and hydrochlorothiazide. On physical examination, vital signs are normal. Examination of the right posterior trunk reveals scattered areas of hypopigmentation in a dermatomal distribution. The patient notes tingling and pain with light touch.

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

A) Oral famciclovir
B) Oral prednisone
C) Oral gabapentin
D) Oral oxycodone

Click here for the answer and critique for this question.

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Therapeutics

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Anti-TNF drugs increase herpes zoster risk

Treatment with anti-TNF drugs increases the risk of herpes zoster infection, according to a new study of rheumatoid arthritis patients.

Using data from a German biologics registry, researchers tracked cases of zoster in 5,040 patients who were receiving either TNF inhibitors or conventional disease-modifying antirheumatic drugs (DMARDs). Overall, there were 86 zoster episodes in 82 patients, 39 of which occurred in the anti-TNF recipients, 23 in the group taking entanercept, and 24 in the conventional DMARD group. After adjusting for age, arthritis severity and glucocorticoid use (all factors that have been found to increase risk), the researchers concluded that monoclonal antibodies increase risk of developing zoster by 82%, but the difference did not meet the study's threshold for clinical significance.

The study indicates that the increase in risk posed by anti-TNF drugs is fairly moderate compared to that in other immunocompromised groups, noted an accompanying editorial. The drugs elevate patients' risk to about the level observed in people over age 80. The arthritis patients were found to have more severe cases of zoster than would be typical, although they reported less postherpetic neuralgia—possibly due to the anti-inflammatory effects of the drugs. The study was published in the Feb. 18 Journal of the American Medical Association.

Because the herpes zoster vaccine is made from a live virus, it is not recommended for patients currently receiving anti-TNF therapy, both the article and editorial noted. For patients who have not yet initiated therapy, however, vaccination is a reasonable, although not clinically tested, option. Anti-TNF drugs continue to provide great benefits to patients with inflammatory diseases, but clinicians should be aware of the risk of infectious complications, such as zoster, the editorial concluded.

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Genetic algorithm more accurate than fixed-dose for initial warfarin dosing

Using a pharmacogenetic algorithm for estimating the appropriate initial dosing of warfarin was more accurate for some patients than the traditional method of starting with a fixed dose and making adjustments, a study found.

In the study, 3 researchers gathered clinical and genetic data from more than 4,000 patients in order to create two algorithms: one based only on clinical variables and another that also included genetic information. The pharmacogenetic algorithm was more accurate than the clinical algorithm in identifying patients who required 21 mg or 49 mg per week of warfarin (49.4% vs. 33.3%, P<0.001, and 24.8% vs. 7.2%, P<0.001, respectively). However, the genetic formula performed no better than the fixed-dose for people in the middle of the dosage range. The results appear in the Feb. 19 New England Journal of Medicine.

An accompanying editorial noted that, because the traditional fixed-dose was derived for the “average patient,” the genetic algorithm worked better for patients who required lower- or higher-than-average doses. Thus, using genetic information has the potential to lower risks for people who do not have an average response to drugs such as warfarin. “A better understanding of individual differences in the response, either positive or negative, to medicines should be an overarching goal for pharmacotherapy over the next decade,” the editorial concluded.

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FDA update

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Advisory on psoriasis drug

The FDA last week issued an advisory about possible serious adverse events connected with the psoriasis drug efalizumab (Raptiva).

The agency said it had received three confirmed and one possible report of progressive multifocal leukoencephalopathy (PML) in patients using efalizumab, which is taken as a once-weekly injection for moderate to severe plaque psoriasis. The affected patients had been taking the drug for more than three years and were not receiving any other immunosuppressive treatments. None of the patients have died.

The FDA advised physicians to carefully monitor patients taking efalizumab, as well as those who have discontinued the drug, for signs of PML, which has no known effective treatment. Drugmaker Genentech added a boxed warning to the drug's label in October 2008 about risks of life-threatening infections, including PML, the FDA said. Reports of serious adverse events should be made to the FDA's MedWatch adverse event reporting program.

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Insurance update

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Another insurer settles allegations of under-reimbursement

CIGNA agreed to drop its use of a database used to set reimbursement for out-of-network services, following a lawsuit from the American Medical Association and another action by New York's attorney general. CIGNA will give $10 million to a new not-for-profit that will administer a new database to determine reasonable and customary charges for out-of-network services. CIGNA will also provide relevant billing and claims data to the project.

The AMA said it commended the action but will continue its class action suit against CIGNA, citing "serious damages"—a decade of alleged under-reimbursement—based on the insurer's use of a database that set out-of-network reimbursement rates.

Another insurer, WellPoint, also agreed with New York's attorney general to give another $10 million toward the same nonprofit system and to stop using the existing database.

As reported in the Feb. 17 issue of ACP InternistWeekly, the AMA had previously sued and settled with UnitedHealth, which developed the database, and with Aetna, another licensee of the database. The AMA alleges that for more than a decade health insurance companies underpaid physicians for out-of-network medical services and forced patients to pay an excessive portion of the costs.

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From ACP Internist's blog

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Stroke '09 and surgeries on twitter

Visit ACP Internist's blog for more coverage of Stroke 2009, including San Diego's emergency stroke response system in which a 9-1-1 call summons not only the ambulance but pages an entire team that clears imaging machines and bed space for when the ambulance pulls up. Also, read up on the new trend of medical twittering, and get a chuckle from the latest installment of Medical News of the Obvious. Stay up to date by signing up for our RSS Feed.

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From the College

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College to hold series of practice-related webinars

Over the next three weeks ACP is hosting a series of webinars to let members know about the latest happenings in practice innovations and health care reform. The first presentation will be Wednesday, Feb. 25 at 7 p.m. EST. The hour-long presentation, given by the College’s Vice President of Practice Advocacy and Improvement, Michael Barr, FACP, will be an overview of the Patient-Centered Medical Home and answer the question of how a practice becomes a medical home. Upcoming sessions will cover the Physician Quality Reporting Initiative, which allows physicians to earn a bonus payment for reporting quality data to Medicare, and what the real chance is for major health care reforms in 2009.

Further information and registration instructions are available online. Click on the "upcoming" tab.

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ACP leaders honored

Several of the College’s current and past leadership have recently received honors of distinction and achievement.

  • ACP Board of Regents Chair William Applegate, FACP, has been named president of Wake Forest University of Health Sciences.
  • Former Regent and current ACP Foundation Board member Barbara L. Schuster, MACP, has been named campus dean of the Medical College of Georgia/University of Georgia Medical Partnership Campus in Athens, Ga.
  • Regent Phyllis A. Guze, FACP, of Riverside, Calif., was recently named acting vice chancellor for medical sciences and dean of the school of medicine at the University of California at Riverside.
  • Rowen K. Zetterman, MACP, has been named dean of the Creighton University School of Medicine in Omaha.

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Cartoon caption contest

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Vote for your favorite entry

ACP InternistWeekly's cartoon caption contest continues. ACP staff has selected three finalists for the latest contest and is now asking readers to vote for their favorite caption to determine the winner.

Go online to view the cartoon and pick the winner, who receives a $50 gift certificate good toward any ACP program, product or service. Voting continues through March 2, with the winner announced in the March 3 issue.

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MKSAP Answer and Critique

This topic is available to subscribers in the General Internal Medicine section, item 66.

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.

The correct answer is C) = Oral gabapentin.

This patient's diagnosis is postherpetic neuralgia from herpes zoster. Postherpetic neuralgia, causing pain after the rash heals, occurs in about 9% to 34% of patients with herpes zoster, and the incidence increases with age. Spontaneous resolution of postherpetic neuralgia is common, particularly during the first 6 months of the episode, but medical treatment may be indicated for pain that is interfering with functioning or sleep. Gabapentin, approved by the Food and Drug Administration for treatment of postherpetic neuralgia, has been shown to reduce pain and improve sleep in randomized controlled trials. Side effects of treatment include dizziness, somnolence, and peripheral edema.

Although acute treatment of herpes zoster with antiviral agents such as famciclovir can reduce the incidence of postherpetic neuralgia, the agents do not provide symptomatic relief for this condition. Prednisone is also not effective for relieving symptoms in patients with postherpetic neuralgia. Most studies evaluating other treatments for postherpetic neuralgia, including opioids, lidocaine patch, and capsaicin, are small and heterogeneous. Better-designed trials are needed.

This patient's age and history of bladder outlet obstruction from benign prostatic hyperplasia require cautious use of opioids such as oral oxycodone. Tricyclic antidepressants (off-label use) can reduce severity, duration, and prevalence of postherpetic neuralgia, especially when initiated early in the course of the illness, but side effects can limit their use.

Key Point

Gabapentin, approved by the Food and Drug Administration for treatment of postherpetic neuralgia, has been shown to reduce pain and improve sleep in randomized controlled trials.

Click here to return to the rest of ACP InternistWeekly.

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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.

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Copyright 2008 by the American College of Physicians.

Test yourself

A 50-year-old man is evaluated in follow-up for a recent diagnosis of cirrhosis secondary to nonalcoholic steatohepatitis. He has a history of asthma, type 2 diabetes mellitus, hyperlipidemia, and obesity. His current medications are inhaled fluticasone, montelukast, insulin glargine, insulin lispro, simvastatin, and lisinopril. Following a physical exam, lab studies, and upper endoscopy, what is the most appropriate treatment?

Find the answer

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