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


In the News
for the Week of 5-4-10


  • Growth hormones improve sprint times in recreational athletes, but safety is unclear
  • B vitamins harmful, not helpful, for diabetic nephropathy

Test yourself with MKSAP 15

  • MKSAP Quiz: aching knee pain and stiffness

Infectious disease

  • Herpes zoster vaccine safe and effective, but cost may hinder its use
  • HPV testing more sensitive than conventional screen

Breast cancer

  • Biomarkers may aid treatment decisions in DCIS

Care transitions

  • Many stent patients delay taking clopidogrel with adverse results

From ACP Internist

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

Professional development

  • ABIM offers module on caring for the medically underserved
  • Upcoming survey on injection practices

From the College

  • ACP signs on to ethics code for interactions with companies

Cartoon caption contest

Physician editor: Darren Taichman, FACP


Growth hormones improve sprint times in recreational athletes, but safety is unclear

Growth hormones increased sprint capacity in recreational athletes when used alone and in combination with testosterone, according to the first trial to demonstrate that the hormones do affect athletic performance.

Australian researchers in a blinded study followed 96 recreationally trained athletes (63 men and 33 women) with a mean age of 27.9 years (SD, 5.7). Men received either placebo or a hormone (somatropin, Novo Nordisk) in a dose of 2 mg/d subcutaneously, testosterone (Sustanon, Organon) in a dose of 250 mg/wk intramuscularly, or combined treatments. Women received placebo or hormone (2 mg/d).

After eight weeks, researchers assessed fat mass, lean body mass, extracellular water mass and body cell mass and their correlation to endurance (maximum oxygen consumption), strength (dead lift), power (jump height) and sprint capacity on a bicycle (Wingate value). Results appeared in the May 4 issue of Annals of Internal Medicine. Video of the report is available online.

Growth hormone significantly reduced fat mass, increased lean body mass through an increase in extracellular water, and increased body cell mass in men when combined with testosterone. Growth hormone significantly increased sprint capacity, by 0.71 kJ (95% CI, 0.1 to 1.3 kJ; relative increase, 3.9% [CI, 0.0% to 7.7%]) in men and women combined. In men co-administered with testosterone, hormone increased sprint capacity by 1.7 kJ (CI, 0.5 to 3.0 kJ; relative increase, 8.3% [CI, 3.0% to 13.6%]). Endurance, strength and power did not significantly change. The increased sprint capacity was not maintained after a six-week washout period.

The improvement in sprint capacity in men who also received testosterone injections would correlate to a 0.4-second improvement over 10 seconds in a 100-meter dash, according to lead author Ken K. Y. Ho, MD. “This improvement could turn the last-place finisher in the Olympic finals into a gold medal winner,” he said.

Growth hormone dosage may have been lower than that used covertly by competitive athletes, who might see bigger gains but also may experience greater side effects. While the study was too small to draw conclusions about safety, patients in all treatment arms reported swelling, joint and muscle pain, paresthesia and acne.


B vitamins harmful, not helpful, for diabetic nephropathy

Taking B vitamins reduces hyperhomocysteinemia in patients with diabetic nephropathy but increases their risk of vascular events, a new study found.

The randomized controlled trial included 238 Canadians with type 1 or 2 diabetes and nephropathy. The patients were given a daily tablet that included 2.5 mg of folic acid, 25 mg of B6 and 1 mg of B12 or placebo and were followed for 36 months. At the conclusion of the study, patients in the B-vitamin group had a mean decrease in their radionuclide glomerular filtration rate (GFR) of 16.5 mL/min/1.73 m2 compared to only 10.7 mL/min/1.73 m2 in the placebo group.

Those who took B vitamins also had double the risk of myocardial infarction, stroke, revascularization and all-cause mortality compared with the placebo group. The groups required dialysis at similar rates, but the B-vitamin group did see a decrease in plasma total homocysteine, while the placebo group had an increase. The study was published in the April 28 Journal of the American Medical Association.

While other trials have suggested no benefit and potential harm from pharmacologic doses of B vitamins, this is the first to show significant detrimental effects, the study authors said. It’s possible that homocysteine-lowering would be protective against vascular disease, but that the benefits were outweighed by toxicity of B vitamins. If that is the case, alternate methods of lowering homocysteine may be needed, the authors said.

Given that patients with renal impairment would be less able to excrete the vitamins, it’s not certain that these results would be generalizable to other populations, the authors noted. Still, they concluded that the use of high-dose B vitamins to lower homocysteine levels should be discouraged based on their results and other large-scale trials finding no benefit.


Test yourself with MKSAP 15

MKSAP Quiz: aching knee pain and stiffness

EDITOR'S NOTE: ACP InternistWeekly now features questions from MKSAP 15. See the Answer and Critique for this question for important information about MKSAP 15.

A 37-year-old woman is evaluated for a 2-week history of bilateral anterior knee pain. The pain is described as aching in nature; it worsens when she descends steps or kneels, and requires her get up from her chair at work every few hours to relieve stiffness and discomfort. The patient runs several times a week but has not had any traumatic injury to the knees. She has no other medical problems.

On physical examination, there is no swelling, warmth, redness, or instability of the knees. Pressing the patella against the femur and moving it inferiorly and superiorly reproduces the pain.

Which of the following is the most likely cause of this patient’s knee pain?

A) Osteoarthritis
B) Patellofemoral pain syndrome
C) Pes anserine bursitis
D) Prepatellar bursitis

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


Infectious disease

Herpes zoster vaccine safe and effective, but cost may hinder its use

The herpes zoster vaccine is safe and effective, but financial considerations may keep clinicians from administering it, according to studies in today's Annals of Internal Medicine.

Researchers for the Shingles Prevention Study Group studied 38,546 adults 60 years and older who had a history of chickenpox but not shingles (of these, 6,616 also participated in an adverse events substudy that gathered more detailed information about early adverse events). Participants were randomly assigned to receive either the herpes zoster vaccine or a placebo and were followed for approximately three years. Adverse events were assessed at 42 days after vaccination and at three years.

Only 1.4% of both the vaccine and placebo recipients reported serious adverse events. More vaccine recipients than placebo recipients in the substudy (48% vs. 16%) reported local side effects, such as redness, swelling and tenderness. Seven participants in the vaccine group developed herpes zoster compared with 24 participants in the placebo group. Over a mean follow-up of 3.39 years, hospitalization rates and mortality rates did not differ between groups. Although the participants in the substudy were not randomly selected and serious adverse events were not always confirmed in the medical record, the authors concluded that herpes zoster vaccine is well tolerated in older, immunocompetent adults.

However, despite the vaccine's safety and effectiveness, fewer than 10% of those eligible for it actually receive it. The vaccine costs about $200, making it one of the most expensive available for adults, and is covered under Medicare Part D instead of Medicare Part B. In a second study, researchers performed a national mail and Internet-based survey of 301 general internists and 297 family medicine physicians to assess current knowledge, vaccination practices and barriers to vaccination. Of the 72% who responded to the survey, 93% reported that they make the vaccine available to their patients, 49% by stocking and administering the vaccine in their offices, 36% by asking the patient to purchase the vaccine in a pharmacy and then visit the office for vaccine administration, and 33% by referring patients to a pharmacy for vaccine administration.

Both internists and family practitioners most frequently cited financial reasons as the main barriers to vaccination. Twelve percent of respondents initially administered the vaccine in their offices but had stopped doing so because of cost and reimbursement issues. Only 45% of respondents knew how vaccine administration is reimbursed. The authors noted that the survey results might not accurately affect practice and may not represent all clinicians. However, they concluded that although physicians are trying to make herpes zoster available to their patients, they face substantial barriers, mainly financial. "Efforts to facilitate the financing of herpes zoster vaccine could help increase its use," they wrote.


HPV testing more sensitive than conventional screen

Testing for human papillomavirus (HPV) DNA was a more sensitive means of detecting cervical cancer and pre-cancerous lesions than conventional Pap testing, a Finnish screening program found.

The population-based program invited more than 50,000 women between 30 and 60 to be screened and then randomized them to conventional testing or HPV testing. The outcomes were cervical cancer and a composite of cervical intraepithelial neoplasia grade III and adenocarcinoma in situ (referred to as CIN III+). The study was published online by BMJ last week.

The women who got the HPV tests had an increased rate of diagnosis with CIN III+ (77% higher than women screened conventionally). The differences in cervical cancer between the groups were not statistically significant (6 in the HPV group vs. 8 in the conventional group if all women invited to screening were included, 6 vs. 3 among those who attended the screening).

Of the women who were referred for additional screening after an HPV test, 794 had a negative result on cytology triage (of whom 11 were subsequently found to have CIN III+), 353 women had at least a borderline result on cytological triage (15 eventually diagnosed with CIN III+) and four women remained with an inadequate screening result because of inadequate cytological triage.

The study authors concluded that HPV testing compared well with conventional testing and didn’t cause too much burden to patients, at least in women age 35 or older. They noted that the high rate of positive HPV tests among women under 35 makes HPV screening challenging and indicates the need for better triage tests. They recommended that primary HPV screening be piloted in additional programs, in Finland as well as elsewhere in the world.


Breast cancer

Biomarkers may aid treatment decisions in DCIS

Certain biomarkers may help predict risk for and severity of recurrent disease in women with ductal carcinoma in situ (DCIS), according to a new study.

Researchers performed a nested case-control study of 1,162 women diagnosed with DCIS and treated with lumpectomy alone from 1983 to 1994. The study looked at clinical characteristics of DCIS, subsequent disease (invasive breast cancer, DCIS in the ipsilateral breast or DCIS at a regional or distant site more than six months after initial DCIS treatment), and data from pathology reviews and immunohistochemical staining. The authors examined factors related to subsequent invasive cancer and subsequent DCIS and calculated patients' eight-year risk. The study results were published early online April 28 by the Journal of the National Cancer Institute.

Eight-year risk for subsequent invasive cancer was higher in women whose DCIS was detected on palpation or whose lesions were positive for p16, cyclooxygenase-2 (COX-2) and Ki67 antigen (19.6%; 95% CI, 19.0% to 21.3%) than in women whose DCIS was detected on mammography and in which the same three biomarkers were negative (4.1%; 95% CI, 3.4% to 5.0%) (P=0.018). Eight-year risk for subsequent DCIS, meanwhile, was greatest for women whose DCIS lesions had disease-free margins of at least 1 mm and one of the following biomarker profiles: estrogen-receptor negative, epidermal growth factor receptor-2 positive, Ki67 antigen positive or p16 positive, COX-2 negative and Ki67 antigen positive. Five- and eight-year risk for subsequent DCIS was lowest in women whose disease-free margins were 10 mm or more. Nuclear grade was not associated with future invasive cancer.

The study had several potential limitations, including retrospective assessment of clinical factors and possible over- or underestimation of subsequent tumor risk. However, the authors concluded that biomarkers can be useful in helping to quantify future cancer risk in women with DCIS. "We show that the mode of detection and the biomarkers p16, COX-2, and Ki67 may be used to help stratify a woman's risk of subsequent invasive cancer and to help her decide whether she should undergo adjuvant therapies," the authors wrote.

Another study released last week reported that established breast cancer risk factors in non-Hispanic white women do not necessarily apply to Hispanic populations. Using data from the population-based, case-controlled 4-Corners Breast Study, the authors found that Hispanic women with breast cancer were more likely to have characteristics usually associated with lower breast cancer risk, such as earlier age at first childbirth and less hormone use. Overall, 62% to 75% of breast cancer cases could be attributed to established risk factors in non-Hispanic white women versus 7% to 36% of breast cancer cases in Hispanic women. The study was published online April 26 by Cancer.


Care transitions

Many stent patients delay taking clopidogrel with adverse results

Patients who delay filling their clopidogrel prescription for even a day after discharge post-implantation of a drug-eluting stent (DES) have a higher risk of death or myocardial infarction (MI).

A retrospective cohort study included 7,402 patients who received a DES at one of three large integrated health centers. According to pharmacy records, 16% of the patients did not fill their prescriptions for clopidogrel on the day of discharge. Patients who did fill the scripts had a 7.9% risk of death or myocardial infarction compared to 14.2% among those who didn’t, with a large proportion of the adverse events occurring within the first 30 days after discharge. Patients were less likely to fill the prescription if they were older or had more comorbidities. The study appears in the May issue of Circulation: Cardiovascular Quality and Outcomes.

Whether patients delayed by only one day or more than five had no significant impact on their increased risk, which may be due to the loading dose, patients metabolizing clopidogrel differently or the possibility that they don’t start taking the drug the day they pick it up. The study also found that delay in filling prescriptions for statins did not increase risk, although they could not collect data on compliance with aspirin therapy. The researchers also noted that patients who delayed filling the initial clopidogrel prescription were more likely to have gaps between subsequent refills.

The study’s results may actually underestimate the degree of the problem, the authors noted, because all patients in the study had prescription drug coverage. The findings highlight the importance of ensuring that patients take clopidogrel as prescribed and thereby reduce their risk of stent thrombosis. In order to accomplish this goal, the lead author of the study said in a press release that hospitals should ensure that patients receive a follow-up phone call from a pharmacist or nurse soon after discharge, in addition to general efforts to improve the quality of discharge transitions.


From ACP Internist

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

The May issue of ACP Internist features the following articles:

Volunteer internists help to rebuild HaitiVolunteer internists help to rebuild Haiti. Physicians in Haiti face a new set of challenges as they stem the spread of infectious diseases and restore medical care to a country that had little before a devastating earthquake struck.

Getting to quality and safety by 'degrees'. Programs in quality and patient safety initiatives have come to the fore as graduate-level degrees, adding prestige to a new body of knowledge that has emerged in the past decade.

Summit covers myths and evidence of competing with retail clinics. Providers and administrators of retail medical clinics try to assess the evidence base behind the care delivered at these facilities. Office-based practitioners ignore the increasing number and expanding capabilities of storefront medicine clinics at their peril.

Go to for more, including online-only features.


Professional development

ABIM offers module on caring for the medically underserved

The American Board of Internal Medicine (ABIM) will offer internists and subspecialists in the Maintenance of Certification (MOC) program a new knowledge assessment option focused on improving health care for medically underserved populations and closing well-documented disparities in care. The first MOC tool of its kind developed by any American Board of Medical Specialties member board, the ABIM module "Care for the Underserved" was developed by internationally recognized experts in the disparities arena.

The module focuses on the evidence base around caring for diverse populations. The module comprises 25 multiple-choice questions, many of which present patient-based clinical vignettes and ask respondents to select a correct diagnosis, treatment or management approach. The vignettes are based on the latest research and examine:

  • concepts of health disparities and health care disparities, as well as their underlying causes;
  • effective communication with patients of diverse socioeconomic, racial and ethnic backgrounds and varying literacy levels;
  • issues related to underserved populations that must be considered when making clinical and administrative decisions; and
  • new research on patient preferences, legal issues, cultural competency, health literacy and practice systems as well as national position statements and clinical practice guidelines.

Upon successful completion of the module, physicians are provided with evidence-based rationales for the correct answers as well as bibliographic references for further study. The module has been approved for AMA PRA Category 1 Credits™.


Upcoming survey on injection practices

The Premier Safety Institute, in conjunction with the FDA and the CDC, is conducting a survey to gather information on current injection practices among health care professionals. The survey will focus primarily on injection practices with just a few items on propofol use, and is currently being pilot tested in a large health care system and its associated departments, medical offices, and clinics. Results will be shared with the CDC, the FDA, and professional groups to guide research, outreach and education related to reducing risks to patients.

The survey launches around May 10 and will be live until June 18. The results of the survey will be posted online.


From the College

ACP signs on to ethics code for interactions with companies

ACP signed on to the Code for Interactions with Companies, released April 21 by the Council of Medical Specialty Societies (CMSS). The code guides medical societies in developing policies and procedures that safeguard the independence and transparency of their programs, policies and advocacy positions in relationships with industry.

The rules suggest that medical societies:

  • publicly post industry support,
  • decline industry funding for developing medical practice guidelines,
  • require most members of a guidelines panel be free of industry ties,
  • disclose the financial ties board members and journal editors have with companies, and
  • ban company or product names and logos from conference giveaways.

ACP, a founding member of CMSS, is the largest of the 32 medical specialty societies represented by CMSS, and one of 14 original signers of the CMSS Code.


Cartoon caption contest

And the winner is …

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.

"I guess we've got some bad news for each other. Do you want yours first?"

This issue's winning cartoon caption was submitted by David A. Cooke, FACP, who will receive a $50 gift certificate good toward any ACP product, program or service. Readers cast 118 ballots online to choose the winning entry. Thanks to all who voted!

The winning entry captured 54.2% of the votes.

The runners-up were:
“OK, OK, I admit it. I should have called hospice sooner.”
“You drug reps will do just about anything to get my attention.”

ACP Internist continues its cartoon caption contest next week.


MKSAP 15 answer and critique

The correct answer is B) Patellofemoral pain syndrome. This item is available online to MKSAP 15 subscribers in the General Internal Medicine section, Item 132.

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’s history and physical examination are typical of the patellofemoral pain syndrome (chondromalacia patellae), the most common cause of knee pain in active adults younger than 45 years. The exacerbation of the pain by going down steps and the development of knee stiffness and pain at rest when the knee is flexed for an extended period are clues to the diagnosis. Reproducing the pain by firmly moving the patella along the femur confirms the diagnosis. Patellofemoral pain syndrome is self-limited and responds to rest and NSAIDs.

The patient has no history of worsening pain over the course of the day that is typical for osteoarthritis. Patients with knee osteoarthritis may have crepitus with joint movement and bone tenderness and enlargement. The absence of these signs and symptoms excludes the diagnosis of osteoarthritis in this patient.

Pes anserine bursitis is another common overuse injury characterized by tenderness directly over the pes anserine bursa on the medial aspect of the leg just below the knee. This patient’s presentation is consistent with patellofemoral pain syndrome rather than anserine bursitis.

Prepatellar bursitis is nearly always unilateral and often asymptomatic. Typically, there is a history of knee trauma or repetitive or extended kneeling preceding the knee pain. On palpation, there is tenderness over the entire bursal sac and a collection of fluid directly over the patella; these findings are absent in this patient, excluding this diagnosis.

Key Point

  • The typical patient with patellofemoral pain syndrome is an active young woman with anterior knee pain worsened by going down steps.

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Copyright 2010 by the American College of Physicians.


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