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


In the News
for the Week of 6-22-10


  • Diabetes and cancer links evaluated
  • Medicare cuts raised chemotherapy treatments, changed drug choices

Test yourself

  • MKSAP Quiz: Daily, nonproductive cough without hemoptysis

Mental health

  • Anxiety predicts heart disease decades into the future

Men’s health

Infectious diseases

  • MRSA associated with worse survival in patients with cystic fibrosis

Drug alerts

From the College

  • College joins CDC for HIV/AIDS education initiative

Cartoon caption contest

  • Vote for your favorite entry

Physician editor: Darren Taichman, FACP


Diabetes and cancer links evaluated

Links between diabetes and cancer were assessed in a consensus report released last week by experts from the American Diabetes Association and the American Cancer Society.

Epidemiologic data have shown a higher risk for some cancers among diabetes patients, the report found. The risk of liver, pancreas or endometrial cancer is about doubled, while there is a 1.2- to 1.5-fold increased risk of colon/rectal, breast or bladder cancer. Diabetes has actually been associated with a lower risk of prostate cancer. Mortality from cancer may also be higher in diabetics, but it’s not clear if that is true independent of the mortality risk of diabetes in general. The report was published online on June 16 by CA: A Cancer Journal for Clinicians.

It is also unclear whether the association between diabetes and cancer is direct, or whether diabetes is a marker of underlying biologic risk factors, the experts said. The association could also be due to one of the common risk factors between the two diseases, the list of which the experts reviewed in the report. The possible biologic mechanisms that could explain the link include hyperglycemia, hyperinsulinemia and inflammation.

The report also reviewed the association of diabetes therapies with cancer risk. Observational trials have found a reduced risk of cancer and cancer mortality in patients treated with metformin, but sulfonylureas have been associated with an increased risk. The effect of thiazolidinediones on cancer is unclear, with no definitive human data available on these relatively new drugs. Animal studies have found cancer risks with some incretin-based therapies, but no data on human cancer incidence have been reported yet.

The experts noted that the progressive nature of diabetes makes it very difficult to determine the effect of any individual medication on cancer. They called for additional research, particularly observational trials, on this issue, as well as others addressed in the consensus report.


Medicare cuts raised chemotherapy treatments, changed drug choices

Doctors treated more lung cancer patients with chemotherapy and changed which drugs they used to adapt to cuts in Medicare reimbursement, economists found.

Doctors switched from drugs that experienced the largest losses in their profit margin, carboplatin and paclitaxel, to one that didn't, docetaxel, economists reported in a study published in Health Affairs.

Medicare cuts effective January 2005 substantially reduced outpatient chemotherapy reimbursement. Medicare had previously reimbursed chemotherapy drugs at 95% of their average wholesale price, but the drugs were available to physicians much more cheaply than that. So Medicare first lowered reimbursements to 85% of average wholesale price, and then again in January 2005 to the manufacturers' average national sales prices for the previous two fiscal quarters plus 6%.

Economists used Medicare claims data to analyze practice patterns up to 24 months before and 10 months after January 2005 for 222,478 beneficiaries with a confirmed lung cancer diagnosis between 2003 and 2005.

Before the law took effect, 16.5% of patients received chemotherapy within one month of diagnosis. Afterward, chemotherapy within one month increased 2.4% (P<0.001) to 18.9%. This increase came almost entirely from treatment in physicians’ offices. Before the law took effect, 13% of patients received chemotherapy in a physician’s office; afterward, 15.3% did.

Payment rates for carboplatin, paclitaxel, and etoposide declined dramatically in the new reimbursement system. Reimbursement rates for a standard monthly dose declined from $1,845 to $930 for carboplatin and from more than $2,270 to $225 for paclitaxel. Payment rates were relatively flat for docetaxel, a high-price drug at about $2,500 per standardized monthly dose, and gemcitabine HCl, at $1,300 per monthly dose.

The percentage of patients receiving carboplatin declined from almost 56% to 54%, while the percentage of those receiving paclitaxel declined from 30% to 26%. Prescriptions for docetaxel increased 1.2% to 1.8%. The absolute change was small, involving a base of 9.2% of patients who were receiving docetaxel before 2005, but represented a 13% to 20% relative increase.

The timing of the changes preceded the cut in reimbursement by several months, suggesting physicians knew the law's impending impact and were changing their prescribing patterns ahead of time. Docetaxel's increase preceded the change in reimbursement by about a month, further suggesting that physicians were changing their existing stock in anticipation of the new law, the authors wrote.


Test yourself

MKSAP Quiz: Daily, nonproductive cough without hemoptysis

A 48-year-old woman is evaluated for a cough that has lasted for 3 months. She describes the cough as occurring daily, nonproductive, and without hemoptysis. She has experienced no associated dyspnea, wheezing, fever, weight loss, night sweats, or recent illness. She has not traveled recently or been exposed to anyone else who has been ill. She has never smoked. She was diagnosed with essential hypertension 6 months ago and has taken lisinopril daily since her diagnosis.

Physical examination is unremarkable. She has no oral or pharyngeal exudates or drainage. A chest radiograph is normal.

Which of the following is the most appropriate management option for this patient at this time?

A) Discontinue the lisinopril
B) Order a chest CT
C) Order spirometry
D) Start an antihistamine/decongestant combination
E) Start a proton-pump inhibitor

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


Mental health

Anxiety predicts heart disease decades into the future

Two studies link anxiety but not depression to cardiovascular risk for coronary heart disease later in life.

In the studies, anxiety disorders predicted heart disease even after controlling for baseline differences in blood pressure, smoking, and other potential risk factors for coronary heart disease (CHD). Both studies appear in the June 29 Journal of the American College of Cardiology.

In one of the studies, a meta-analysis combined 20 prospective studies reporting on incident cardiac events and included 249,846 persons with a mean follow-up period of 11.2 years.

Anxious persons were at risk of CHD (hazard ratio [HR] random, 1.26; 95% CI, 1.15 to 1.38; P<0.0001) and cardiac death (HR, 1.48; 95% CI, 1.14 to 1.92; P=0.003), independent of demographic variables, biological risk factors and health behaviors. Subgroup analyses did not show any significant differences regarding study characteristics, with significant associations for different types of anxiety, short- and long-term follow-up, and both men and women.

A second study confirmed the role of anxiety as a strong predictor of future cardiac events. This 37-year follow-up involved 49,321 young Swedish men who were medically examined for military service in 1969 and 1970, when they were 18 to 20 years of age. Psychologists interviewed all men, and psychiatrists saw all men reporting or presenting any symptoms. Data on well-established CHD risk factors and potential confounders were also collected, including smoking, alcohol consumption, body mass index, family history of heart disease, diabetes, blood pressure and physical activity.

Multiadjusted HRs for anxiety were 2.17 (95% CI, 1.28 to 3.67) for CHD and 2.51 (95% CI, 1.38 to 4.55) for acute myocardial infarction. Multiadjusted HRs associated with depression were 1.04 (95% CI, 0.70 to 1.54) for CHD and 1.03 (95% CI, 0.65 to 1.65) for acute myocardial infarction.

An editorial noted how the two studies should guide clinical practice currently: "... By the time patients with symptoms of CHD present themselves to a cardiologist, early-life anxiety might have already taken its toll."

Assessment tools are readily available, have easy-to-ask questions and might be relevant for diagnosing and preventing CHD. But, the editorialist continued, "Physicians are frequently timid about assessing emotional symptoms. It is odd that we thread catheters, ablate lesions, and give rectal exams but are uncomfortable asking our patients about their lives."


Men’s health

Three sexual symptoms indicate hypogonadism in older men

A new study has identified three sexual symptoms that, when combined with measurement of testosterone levels, can be used to diagnose late-onset hypogonadism.

Researchers randomly surveyed more than 3,000 European men between the ages of 40 and 79. They measured the men’s total and free testosterone, and asked them about their general, sexual, physical and psychological health. The study found nine symptoms that were associated with lower testosterone levels: three sexual symptoms (decreased frequency of morning erection, decreased frequency of sexual thoughts and erectile dysfunction), three physical symptoms (an inability to engage in vigorous activity, an inability to walk more than 1 km and an inability to bend, kneel or stoop), and three psychological symptoms (loss of energy, sadness and fatigue).

Although the symptoms were all associated with low testosterone, they were also common among men with normal levels, and only the three sexual symptoms had a syndromic association with decreased testosterone levels. Having more sexual symptoms was associated with lower testosterone. Overall, 2.1% of the study population had at least the three sexual symptoms as well as total testosterone less than 11 nmol/L and free testosterone less than 220 pmol/L.

Based on the results, the study authors recommend that the three sexual symptoms, along with testosterone measurement, be used as the diagnostic criteria for late-onset hypogonadism. Total testosterone should be used as the primary measurement, with the addition of free testosterone in borderline cases, they noted. Physicians should also remember that, given the overlap of conditions in aging patients, there could be alternate causes of the patients’ symptoms and a comprehensive general assessment should be done.

The study is not intended to set criteria for initiating testosterone treatment, the authors wrote. They suggested that further clinical trials are required to resolve that issue, but noted that their findings could reduce excessive diagnoses of hypogonadism and curb injudicious use of testosterone therapy. The study was published in the June 16 New England Journal of Medicine.


Infectious diseases

MRSA associated with worse survival in patients with cystic fibrosis

Presence of methicillin-resistant Staphylococcus aureus (MRSA) in the respiratory tract is associated with worse survival in patients with cystic fibrosis, a new study has shown.

Researchers performed a cohort study of patients with cystic fibrosis seen at U.S. Cystic Fibrosis Foundation-accredited centers from January 1996 to December 2006. Patients were 6 to 45 years of age at study entry and were followed until December 2008. Data were obtained from the Cystic Fibrosis Foundation Patient Registry, which began specifically collecting information on the presence or absence of respiratory-tract MRSA in 1996. The main outcome measure was time from age at study entry to age at death from any cause. Study results appeared in the June 16 Journal of the American Medical Association.

Overall, 19,833 patients were included, accounting for 137,819 patient-years of observation (median, 7.3 years per patient). During this time, 2,537 patients died and 5,759 were found to have respiratory-tract MRSA. Patients with MRSA had a higher mortality rate (27.7 deaths per 1,000 patient-years; 95% CI, 25.3 to 30.4) than those without (18.3 deaths per 1,000 patient-years; 95% CI, 17.5 to 19.1), and a 34.0% (95% CI, 26.7% to 40.4%) attributable risk percentage of death associated with MRSA. MRSA was associated with a higher risk for death in unadjusted analysis (hazard ratio, 1.47; 95% CI, 1.32 to 1.62) and after adjustment for illness severity (hazard ratio, 1.27; 95% CI, 1.11 to 1.45). The median estimated age of survival was higher in the non-MRSA group than in the MRSA group (36.9 years vs. 30.7 years).

The authors noted that their study had several important potential limitations, including misclassification of patients, sampling bias, and lack of analysis of whether MRSA treatment would have affected outcome. However, they concluded that patients with cystic fibrosis and respiratory-tract MRSA are at greater risk for death than cystic fibrosis patients without MRSA. Their study, taken together with previous data, "further establish MRSA as a significant CF pathogen and provide impetus for more aggressive treatment of CF patients who are persistently MRSA positive," they wrote. They also noted the need to emphasize infection control guidelines in patients with cystic fibrosis to minimize MRSA transmission.


Drug alerts

Tylenol recall expanded

Benadryl Allergy Ultratab tablets and Extra Strength Tylenol rapid release gels were added to the large January recall by McNeil Consumer Healthcare.

The products were inadvertently omitted from the initial recall action, according to a press release. The original recall was motivated by consumers reporting a moldy, musty or mildew-like odor, which was eventually linked to trace amounts of a chemical called 2,4,6-tribromoanisole (TBA) in wooden pallets that transport and store product packaging materials.

Anyone who purchased product from the five newly recalled lots or other lots included in the January recall should stop using the product and contact McNeil Consumer Healthcare for instructions on a refund or replacement.


From the College

College joins CDC for HIV/AIDS education initiative

The Centers for Disease Control and Prevention (CDC) has launched “HIV Screening. Standard Care.” a new initiative encouraging physicians to make HIV testing a standard part of the medical care they provide to their patients.

The initiative is the latest component of CDC’s Act Against AIDS Campaign, a large patient education outreach about HIV that uses ACP's HIV guidance statement as part of the educational outreach for primary care physicians and patients.

Amir Qaseem, FACP, ACP’s Clinical Programs and Quality of Care senior medical associate, is a member of the initiative’s clinical workgroup. "It is critical that we adopt routine HIV testing for our patients," said Dr. Qaseem. "As physicians, we play a crucial role in identifying those who are HIV-infected, providing timely treatment and care to extend their lives and helping them prevent transmission."

More information is available online.


Cartoon caption contest

Vote for your favorite entry

ACP InternistWeekly's cartoon caption contest continues. Readers can vote for their favorite caption to determine the winner.









".sessalg deen yam uoY"
"In a world of no drug reps, no standardized eye charts."
"No, you don't have situs inversus; you have 'sighted inversus.'"

Go online to pick the winner, who receives a $50 gift certificate good toward any ACP program, product or service. Voting continues through Monday, June 28, with the winner announced in the June 29 issue.


MKSAP answer and critique

The correct answer is A) Discontinue the lisinopril. This item is available online to MKSAP 15 subscribers in the General Internal Medicine section, Item 4.

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 most appropriate management option for this patient is to discontinue the angiotensin-converting enzyme (ACE) inhibitor lisinopril. This patient presents with a cough of longer than 8 weeks’ duration and thus meets the definition for chronic cough. According to American College of Chest Physicians guidelines, the initial evaluation of all patients with a chronic cough involves a history and physical examination to determine likely etiologies, followed by a chest radiograph to identify obvious abnormalities. If the chest radiograph is normal, one should recommend discontinuing ACE inhibitors and smoking, if these factors are identified in the history, or pursue empiric management of chronic cough if the patient is a nonsmoker and is not taking an ACE inhibitor. There may be no obvious temporal relationship between the initiation of ACE inhibitor therapy and the onset of cough. The median time to resolution is 26 days from withdrawal of the ACE inhibitor.

In patients with chronic cough and a normal chest radiograph, a chest CT is only indicated for those at high risk for lung cancer. A chest CT is not indicated in this young, otherwise healthy, nonsmoking patient.

Asthma and nonallergic eosinophilic bronchitis may present without any symptoms other than cough. Spirometry would be indicated in the evaluation of chronic cough that has not resolved after the initial management measures (history, physical examination, chest radiograph, cessation of ACE inhibitor, treatment for upper-airway cough syndrome).

Upper-airway cough syndrome (UACS) is a common cause of chronic cough. A trial of a first-generation antihistamine/decongestant combination for several weeks is appropriate treatment for UACS. In a nonsmoking patient who is taking an ACE inhibitor, however, the ACE inhibitor should be discontinued for several weeks before treating for UACS. Similarly, although empiric therapy for gastroesophageal reflux disease (GERD) is appropriate if prominent symptoms of GERD accompany the cough or if initial management measures fail, discontinuing the ACE inhibitor always should precede empiric therapy for either UACS or GERD.

Key point

  • In patients taking an angiotensin-converting enzyme inhibitor who present with a chronic cough and a normal chest radiograph, discontinuing the angiotensin-converting enzyme inhibitor may be both diagnostic and therapeutic.

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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?

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