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


In the News
for the Week of 3-4-08

News highlights

  • ACP and AAFP issue guideline on dementia drugs
  • Women who restrict insulin face higher mortality, morbidity
  • Antidepressants not much better than placebo for most patients, study finds

Drug developments

  • More evidence against using anti-anemia drugs for cancer
  • Bevacizumab approved for metastatic breast cancer
  • Tysabri may cause hepatic injury within six days of starting dose

Adolescent medicine

  • New flu vaccine recommendations expand age range
  • Depressed teens may respond to drug switch plus therapy

Disease trends

  • Multi-drug resistant TB on the rise worldwide, says WHO

CMS update

  • Deadline for tamper-resistant prescription pad approaching

Annals of Internal Medicine

  • Annals Audio Summary: new tests for tuberculosis
  • New blood tests and standard test to diagnose TB evaluated
  • New model for predicting breast cancer risk includes breast density

Cartoon caption contest

Call for case studies

  • ACP Internist wants to hear your stories of difficult diagnoses

From the College

  • Next LEAD challenge online
  • Fellow wins HIMSS IT leadership award
  • ACP seeks workshop topics for Internal Medicine '09

News highlights

ACP and AAFP issue guideline on dementia drugs

A new guideline on current pharmacologic treatment of dementia, developed by the College and the American Academy of Family Physicians (AAFP), appears in the March 4 issue of Annals of Internal Medicine.

A committee representing ACP and AAFP reviewed dementia literature for outcomes such as cognition, global function, behavior/mood, and quality of life/activities of daily living and found that high-quality scientific evidence was limited. The committee developed cautious recommendations, including:

  • Clinicians should base the decision to try therapy with FDA-approved drugs for dementia on an individualized assessment of the patient.
  • Clinicians should base the choice of drugs on tolerability, adverse effect profile, ease of use and cost of medication.
  • Further research is urgently needed to address gaps in knowledge about the clinical effectiveness of pharmacologic management of dementia.

Currently five drugs are approved by the FDA for dementia: four acetylcholinesterase inhibitors [donepezil (Aricept), galantamine (Razadyne, Reminyl, Nivalin), rivastigmine (Exelon), and tacrine], and one neuropeptide-modifying agent [memantine (Mamenda)].

The guideline also outlines needed research including:

  • evaluation of the effectiveness of drug therapy for dementia and assessment of whether treatments affect key outcomes, such as institutionalization,
  • evaluation of the appropriate duration of therapy,
  • testing drugs head-to-head, and
  • testing drugs in combination therapy.

One reason for the urgent call for research is the deficiencies found in the existing medical literature. The ACP-AAFP committee found that most of the existing studies focused on statistical significance of changes, but patients with dementia, caregivers and physicians are more interested in clinically important improvement.

“More research is warranted because the available evidence concerning these pharmaceuticals’ effects on quality of life is mixed and the clinical significance of many of the findings is questionable,” said Kenneth G. Schellhase, MD, an AAFP representative on the guideline committee. “In addition, the duration of existing trials was usually less than one year, providing insufficient information to determine the optimal length of treatment, and few trials compare one drug directly with another.”

In summary, no convincing evidence demonstrated that one therapeutic treatment is more effective than another, the committee concluded. The dementia guideline was passed by the ACP Board of Regents on April 16, 2007, and by the American Academy of Family Physicians Board of Directors on June 13, 2007.

The guidelines are online.


Women who restrict insulin face higher mortality, morbidity

Women with type 1 diabetes who restrict their insulin in order to lose weight significantly increase their risk of morbidity and mortality, according to a new study.

The study was an 11-year follow-up of a study of women with type 1 diabetes. The follow-up included 234 women (60% of the original cohort) who had a mean age of 45 years and mean diabetes duration of 28 years. The study looked at self-care behaviors, diabetes-specific and general psychological distress, fear of hypoglycemia, and eating disorder symptoms. The study was published in the March issue of Diabetes Care.

In the original study, 30% of the women had reported insulin restriction, and 26 women died during the follow-up period. Researchers calculated that insulin restriction resulted in a three-fold increased risk of mortality. The insulin restrictors also had increased rates of nephropathy and foot problems, as well as a lower average age of death (45 vs. 58 years).

The study also found an association between mortality and eating disorder symptoms. Other research has shown that women with diabetes are nearly 2.5 times more likely to develop an eating disorder than women without diabetes, noted a study author. Women with this behavior need specialized treatment and awareness needs to be raised among clinicians who treat these patients so that they can make appropriate assessments and referrals to mental health professionals, the author said.

The study authors also proposed a screening question for clinicians to use: asking patients to answer true or false to the statement, “I take less insulin than I should.” Other warning signs for this problem include unexplained elevations in A1c levels, repeated problems with diabetic ketoacidosis, extreme concerns about weight and body shape, change in eating patterns, unusual patterns of intense exercise (sometimes associated with frequent hypoglycemia), and amenorrhea.

The study is online.

A press release is online.


Antidepressants not much better than placebo for most patients, study finds

Several antidepressants don’t work much better than placebo for most patients, a meta-analysis in the Feb. 25 PLoS Medicine concluded.

British and U.S. researchers collected data on 35 clinical trials submitted to the FDA for the licensing of four selective serotonin reuptake inhibitors (SSRIs): fluoxetine (Prozac), venlafaxine (Effexor), nefazodone (Serzone) and paroxetine (Seroxat/Paxil). The studies involved 5,133 patients, 3,292 of whom had been randomized to medication and 1,841 to placebo. The researchers analyzed the effectiveness of the drugs compared with placebo, and whether the effectiveness differed with the severity of patients’ depression scores. All trials were conducted before 1999.

Patients on both drugs and placebo showed large improvements. Overall, SSRI patients improved 1.8 points more on the Hamilton Depression Rating Scale (HDRS) than did placebo patients--a statistically significant difference--but the improvement didn’t meet the three point drug-placebo difference for clinical significance set by the UK’s National Institute for Clinical Excellence. Patients who scored very high (28 or above) on the HDRS--i.e. extremely depressed patients--did show a clinically significant difference between those who took drugs versus placebo, but this was a result of the placebo being less effective for these patients, not the medication being more effective.

There is little benefit to prescribing antidepressants to patients unless they are severely depressed, the researchers concluded. However, an expert with the American Psychiatric Association countered that since patients often must try several antidepressants before they find one that works, it isn’t surprising that studies that tested a single antidepressant on patients didn’t show much improvement, the Feb. 27 Washington Post reported.

The PLoS Medicine study is online.

The Feb. 27 Washington Post is online.


Drug developments

More evidence against using anti-anemia drugs for cancer

A new review confirms concerns about the risks associated with use of erythropoietin and darbepoetin to treat cancer-associated anemia. The review found that patients taking the drugs had a higher risk of venous thromboembolism (VTE) and mortality compared with controls.

The review, which was based on an overview from the Cochrane Collaboration combined with newer data, included 51 clinical trials of 13,611 patients which looked at survival and 38 trials including 8,172 patients which tracked occurrences of VTE. Researchers found that cancer patients who took the drugs had a 57% higher relative risk of VTE (7.5% vs. 4.9%) and a 10% higher risk of mortality.

The findings are concordant with other recent research which has indicated increased rates of tumor progression, mortality and VTE with use of erthopoiesis-stimulating agents (ESAs), study authors said. The mechanism by which ESAs affect survival may not be understood, but concerns should exist about the possibility that the drugs directly affect tumors, they said. The authors suggested that more research on the topic is necessary, but that combined with basic science, their findings raise concern about the safety of the drugs for cancer patients.

The FDA is currently reviewing data on the drugs, and an advisory panel is scheduled to meet and discuss safety concerns on March 13, the Feb. 26 Washington Post reported. A financial analyst told the Washington Post that the agency is expected to tighten restrictions on the drugs, which currently recommend their use as long as patients’ hemoglobin levels are not raised too high.

Representatives of the drug manufacturers said that the review did not define any new risks and that the researchers’ conclusions do not provide an accurate reflection of the safety profiles of the drugs. The study was published in the Feb. 27 Journal of the American Medical Association.

The study is online.

The Washington Post is online.


Bevacizumab approved for metastatic breast cancer

The FDA said bevacizumab (Avastin) can be used to treat metastatic breast cancer, despite an advisory panel’s recent recommendation against it, several news reports said.

The drug, already approved to treat colon and lung cancer, was approved for breast cancer based on findings that it slowed tumor growth, though it didn’t extend patients’ lives. Overall survival is the usual measure by which the FDA approves drugs, and some experts thought the move might indicate a change in standards, but an FDA official denied this, the Feb. 23 New York Times reported.

Bevacizumab received “accelerated” approval, meaning it can be marketed now, but the approval could be yanked later based on results from ongoing or future trials. A clinical trial found patients who received paclitaxel (Taxol) either died or saw their cancer worsen after 5.8 months, compared with 11.3 months for patients who took bevacizumab plus paclitaxel. The women in both groups lived similar lengths of time overall, however, and those taking bevacizumab had more adverse side effects.

Physicians were already using bevacizumab off-label to treat breast cancer, but the approval might spur more insurance companies to cover the drug, which costs about $92,000 annually for breast cancer treatment, the New York Times said.

The New York Times is online.

The Associated Press is online.


Tysabri may cause hepatic injury within six days of starting dose

Markedly elevated serum hepatic enzymes and elevated total bilirubin--signs of potentially severe liver injury--may appear as early as six days after starting natalizumab (brand: Tysabri), an integrin receptor antagonist approved for treatment of multiple sclerosis and Crohn’s disease, the FDA and the drug’s manufacturers warned last week.

In a February 2008 letter to physicians posted on the FDA's Web site, manufacturers Biogen Edec and Elan Pharmaceuticals said that it had received reports of signs of liver injury for the first time after multiple doses, and in some cases liver injury recurred upon rechallenge, indicating that the damage was caused by natalizumab.

The letter continued that the combination of transaminase elevations and elevated bilirubin without evidence of obstruction is generally recognized as an important predictor of severe liver injury that may lead to death or the need for a liver transplant in some patients. Also, Tysabri should be discontinued in patients with jaundice or other evidence of significant liver injury.

Serious adverse events associated with the use of Tysabri can be reported to the manufacturer at 800-456-2255 or to the FDA’s MedWatch reporting system by phone 800-332-0178 or via the Web at

The manufacturers' letter and prescribing information are online.


Adolescent medicine

New flu vaccine recommendations expand age range

All children, from age 6 months through 18 years, should be vaccinated against influenza, the CDC announced last week.

The new recommendation, which comes from the CDC’s Advisory Committee on Immunization Practices, replaces previous advice that children between age 6 and 59 months should be vaccinated. The new recommendation increases the number of children recommended for vaccination by approximately 30 million, and is to take effect no later than the 2009-2010 flu season.

Immunization providers should begin offering vaccination to all children in the 2008-2009 season, if feasible, but vaccination of children under age 5 should continue to be a priority because they are at higher risk for more severe complications. Those who live in households with children younger than age 6 months also should be vaccinated because infants, who are at high risk of complications, cannot receive the vaccine, the CDC said.

During the meeting at which the recommendation was issued, the advisory committee also reviewed data on vaccine efficacy among children receiving their first influenza vaccinations. They found that the children who received only one dose did not receive statistically significant protection, underscoring the importance of current recommendations which call for children under age 9 who are receiving the vaccine for the first time to get two doses.

The CDC press release is online.


Depressed teens may respond to drug switch plus therapy

. Adolescents who don’t respond to an initial antidepressant may improve if they switch to another drug, or switch drugs and add cognitive behavioral therapy (CBT), a new study found.

The randomized controlled trial involved 334 patients age 12 to 18 years who had a primary diagnosis of major depressive disorder and who hadn’t responded to two months of initial treatment with a selective serotonin reuptake inhibitor (SSRI). The patients were assigned to one of four treatments for 12 weeks: switching to a different SSRI [either paroxetine (Paxil), citalopram (Celexa), or fluoxetine (Prozac)]; switching to a different SSRI plus CBT; switching to venlafaxine (Effexor); or switching to venlafaxine plus CBT. The study was published in the Feb. 27 Journal of the American Medical Association.

Switching to a different medication and adding CBT showed a higher response rate than switching medications alone (55% response vs. 41%, P= .009). The effect was seen in a median of nine CBT sessions. It didn’t matter if patients switched to venlafaxine (48% response) or another SSRI (47% response), but those on venlafaxine had a greater increase in diastolic blood pressure and pulse, and more frequent occurrence of skin problems. There were no significant differences in response among the three SSRIs.

Researchers didn’t control for the greater attention that patients in the CBT group received, and the study design didn’t allow them to determine if CBT might have been effective without switching drugs. Given that only about 60% of adolescents will respond to an initial SSRI, however, the study should give hope to patients and families that other treatments may work, the authors said.

The Journal of the American Medical Association is online.


Disease trends

Multi-drug resistant TB on the rise worldwide, says WHO

Multi-drug resistant tuberculosis is more widespread than ever with nearly half-a-million known new cases a year worldwide, accounting for about 5% of the 9 million new TB cases recorded annually, according to a report from World Health Organization.

The survey, based on data collected between 2002 and 2006 on 90,000 patients in 81 countries, found drug-resistant TB in 45 countries, said a Feb. 26 WHO news release. The rate was highest in Baku, capital of Azerbaijan, where almost one-quarter of new TB cases were multi-drug resistant. In the U.S., 1.2% of TB cases were multi-drug resistant and, of those, 1.9% were extensively drug-resistant, said the Feb. 26 Washington Post.

Data from Latvia and Ukraine revealed a link between HIV infection and multi-drug resistant TB, said the release. In those countries, the resistant strain was twice as common among patients with HIV as among patients without HIV.

The survey found widespread multi-drug resistant TB in China as well as parts of Moldova, the Russian Federation and Uzbekistan, said the release. The report was limited in scope, however, the WHO noted, because many countries lack the resources needed to collect data. In Africa, for example, which has the highest incidence of TB in the world, only six countries provided drug-resistance data.

The data highlight the need for more funding to stop the spread of TB globally, said the report's authors, in order to find new diagnostics and more effective drugs and vaccines.

The WHO news release is online.

The Washington Post is online.


CMS update

Deadline for tamper resistant prescription pad approaching

On April 1, a new regulation from CMS will require that prescriptions for Medicaid beneficiaries be written on tamper-resistant prescription pads. The April 1 deadline reflects an extension that Congress passed last fall to delay the program by six months.

The new law requires that all written, non-electronic prescriptions for Medicaid patients must be written on tamper-resistant prescription pads to qualify for federal reimbursement. This requirement applies to all prescriptions for Medicaid patients, not just controlled substances.

Because Medicaid is administered by individual states, each state may interpret the guidelines differently. However, CMS has specified that a tamper-resistant prescription:

  • prevents unauthorized copying of prescriptions,
  • prevents the erasure or modification of information written on a prescription, and
  • makes it difficult for counterfeit forms to be created.

If you have not already received the specific requirements of a tamper-resistant prescription pad for your state, contact your state Medicaid director. The director also should be able to tell you whether there are preferred vendors for these pads in your state, and whether your state has plans to purchase these pads and provide them to Medicaid participating physicians at no cost or at a discounted rate.

A list of state Medicaid directors and related contact information is online.

Further guidance is also available from CMS.


Annals of Internal Medicine

Annals Audio Summary: new tests for tuberculosis

In this week's Annals audio summary, Dick Menzies, MD, of McGill University discusses the role of interferon-gamma release assays in the diagnosis of tuberculosis. Also, in the first of a two part series, former CMS Director Mark McClellan, MD, and others discuss the state of the art and future directions of comparative effectiveness studies in excerpts from an Institute of Medicine panel discussion. The podcast, which also includes a summary of all the articles in the current issue, is available at or on iTunes.


New blood tests and standard test to diagnose TB evaluated

New T-cell blood tests, with fast turnaround time, are recommended for diagnosis of latent tuberculosis. A study involving 389 adults with moderate to high clinical suspicion of active tuberculosis evaluated two T- cell assays and tuberculin skin testing individually and in combination with each other. Researchers found the ELISpot(plus) more sensitive than the ELISpot and tuberculin skin testing. Almost all patients with active tuberculosis had positive results on either tuberculin skin testing or ELISpot(plus). If both tests are negative, active tuberculosis is very unlikely to be the diagnosis. An editorial writer discusses the issues of specificity and sensitivity raised by the combination tests and says “the search for a rapid, accurate test must go on.”


New model for predicting breast cancer risk includes breast density

Researchers developed a new risk-prediction model that uses breast density in addition to other, better known predictors of breast cancer risk. Breast density seemed to be a useful addition to the model, and low breast density was associated with a low breast cancer risk regardless of family history of breast cancer and other factors. However, like older models, the new risk-prediction model had only modest ability to discriminate between women who will develop breast cancer and those who will not. Although the model is easy to use, its accuracy needs further study before it can be recommended for routine clinical practice.

Annals of Internal Medicine is online.


Cartoon caption contest

Put words in our mouth

ACP InternistWeekly wants readers to create captions for this cartoon--and help choose the winner.

Put words in our mouth

E-mail all entries to by March 14. ACP staff will choose three finalists and post them in the March 18 issue of ACP InternistWeekly for an online vote by readers. The winner will appear in the March 25 issue.

Pen the winning caption and win a $50 gift certificate good toward any ACP product, program or service.


Call for case studies

ACP Internist wants to hear your stories of difficult diagnoses

ACP Internist columnists Jerome Groopman, FACP, and Pamela Hartzband, FACP, would like to hear about your stories of difficult or missed diagnoses for possible use in their next 'Mindful Medicine' column.

Dr. Groopoman, a hematologist/oncologist and author of the bestselling "How Doctors Think," and Dr. Hartzband, an endocrinologist, are on the Harvard Medical School faculty and serve as staff physicians at Boston's Beth Israel Deaconess Medical Center. Every other issue, they present a case study from an ACP Internist reader describing a difficult or missed diagnosis, and provide commentary on how a mistake was, or might have been, avoided.

Email your ideas to Drs. Groopman and Hartzband at The authors will contact physicians whose cases they would like to use in the column.


From the College

Next LEAD challenge online

The next online leadership challenge for LEAD, ACP’s Leadership Enhancement and Development Program, is now available. For the challenge, “Developing a Medical Student Ambulatory Care Rotation,” participants will discuss how to develop a rotational curriculum in a small private practice. Strategies for getting practice members to agree on how to evaluate student progress will be examined , as well as how to make a medical student ambulatory care rotation an overall meaningful experience for learners.

LEAD was created for members looking to develop their leadership skills and offers an online discussion group for members to discuss a variety of challenges with experienced ACP leaders. Ongoing challenges will be announced every two weeks in Internist Weekly. The CME portion of the LEAD program officially debuts at Internal Medicine 2008 with the pre-course, “Essential Competencies for the Emerging Leader,” on May 14.

In addition to the pre-course, other courses offered at IM 2008 will count toward the LEAD Certificate of Completion. Registration for the LEAD pre-course is offered with other IM 2008 courses online.


Fellow wins HIMSS IT leadership award

Peter Basch, FACP, received the Healthcare Information and Management Systems Society's (HIMSS) Physician IT Leadership Award for his work applying information technology to the needs of physicians. Dr. Basch, a general internist in Washington, D.C., is the medical director for ambulatory clinical systems at MedStar Health, a nonprofit health system with eight hospitals in the Baltimore-Washington corridor.

Dr. Basch, clinical leader of MedStar's ambulatory electronic health record (EHR) implementation, serves on ACP's Medical Informatics Subcommittee and Medical Services Committee. He also chairs the Maryland Task Force on EHRs, co-chairs the Physicians' EHR Coalition, and serves on the board of the eHealth Initiative.

Dr. Basch was honored at the annual HIMSS awards and recognition banquet on Feb. 26, in Orlando, Fla. More information on the awards is on the HIMSS Web site.

The HIMSS news release is online.


ACP seeks workshop topics for 2009

The Clinical Skills Subcommittee (CSSC) and Medical Informatics Subcommittee (MISC) are accepting workshop proposals for Internal Medicine 2009.

The CSSC welcomes all proposals but places a priority on interactive workshops that focus on the acquisition or improvement of physical examination skills, communication skills, and procedural skills. The CSSC is most interested in workshops that have a high likelihood of changing physician behavior using proven teaching techniques or new and innovative teaching strategies that have yet to be tested. ACP can offer a variety of time slots including 60, 90 and 120 minutes, as well as a one or two day pre-session workshops.

MISC welcomes all proposals but places a priority on interactive workshops that focus on the use of technology and computer applications in the care of patients and the management of medical practice. The MISC is most interested in workshops that have a high likelihood of encouraging use of technology and computer applications shown to improve quality of care, patient safety, and practice management efficiency. ACP Internal Medicine offers a variety of learning formats including interactive computer workshops, lectures, and panel presentations. ACP supplies each computer workshop with 12 computers with internet connection; each computer is shared by two learners.

Resources permitting, ACP will assist course directors in the acquisition of necessary equipment (beyond audiovisual equipment) and follow-up evaluations of learners. CSSC and MISC workshop faculty receive financial support for travel to the meeting, a per diem (hotel and food), meeting registration, and a small honorarium. Final selections of workshops are made at the annual program planning meeting in June 2008.

To suggest a workshop, complete this online application and attach a copy of your curriculum vitae and mail (or e-mail) these to the address below by June 1, 2008.

Patrick C. Alguire, FACP
Director, Education and Career Development
American College of Physicians
190 N. Independence Mall West
Philadelphia, PA 19106-1572


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 2008 by the American College of Physicians.


Test yourself

A 30-year-old woman is evaluated for a 1-year history of fatigue, headaches, poor sleep, depression, intermittently blurred vision, and weakness when climbing stairs. She takes no medication.

Find the answer

What will you learn from your Annals Virtual Patient?

Annals Virtual Patient

Annals Virtual Patients is a unique patient care simulator that mirrors real patient care decisions and consequences. CME Credit and MOC Points are available. Start off with a FREE sample case. Start your journey now.

Internal Medicine Meeting 2015 Live Simulcast!

Internal Medicine Meeting 2015 Live Simulcast

Unable to attend the meeting this year? On Saturday, May 2, seven sessions will be streamed live from the meeting. Register for the simulcast and earn CME credit after watching each session. Watch it live or download for later viewing.