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


In the News
for the Week of 12-21-10


  • Esophageal cancer screening might not be worthwhile for most GERD patients, modeling study finds
  • HIV reduction efforts should target risky behaviors

Test yourself

  • MKSAP Quiz: daily cough without specific triggers

Pain management

  • For arthritis, opioids present increased relative risk compared to NSAIDs
  • Opioids for nonmalignant pain have different adverse event profiles


  • Cystatin C beats creatinine at predicting complications of kidney disease

Regulatory news

  • Are you ready for 5010 and ICD-10?
  • HRSA accepting applications for GME grants program
  • CMS conducting 2011 Medicare Contractor Provider Satisfaction Survey

From the College

  • Depression quality improvement program seeks participants
  • Help choose the best name for ACP’s advocacy program

Cartoon caption contest

Physician editor: Darren Taichman, FACP

Editorial note: ACP InternistWeekly will not be published for the next two weeks due to the Christmas and New Year’s holidays.


Esophageal cancer screening might not be worthwhile for most GERD patients, modeling study finds

Although gastroesophageal reflux increases patients’ relative risk for esophageal adenocarcinoma, the absolute risk is too low to merit screening in most patients, a new study found.

The study used a Markov model to extrapolate based on incidence of gastroesophageal reflux disease (GERD) and its association with esophageal cancer. According to the results, women with GERD have a very low risk of developing esophageal cancer no matter their age. For example, 60-year-old women with weekly GERD have an esophageal cancer incidence rate of 3.9 per 100,000 person-years. Having daily symptoms increases their risk only slightly, the model found.

Men with GERD have a higher risk of esophageal cancer and it increases with age. For example, 70-year-old men have a risk of 60.8 per 100,000 person-years. The study authors compared these risks to those for cancer for which experts have recommended screening. For example, the risk of breast cancer is 100.5 per 100,000 in 40-year-old women and the risk for colorectal cancer is 47.2 per 100,000 in 50-year-old men. The lowest incidence rate at which screening has been recommended was for colorectal cancer in 50-year-old women: 35.6 per 100,000. If the latter rate is taken as a benchmark for cancer screening, the researchers concluded that esophageal cancer screening would be worthwhile only for men over 60 years of age with at least weekly GERD. Because risk increases with more frequent GERD, men with daily GERD would pass the benchmark at age 55.

However, the authors noted, this calculation assumes that esophageal cancer screening effectively reduces mortality, an assumption there is not yet evidence to support. Decisions about the value of screening would also need to consider the cost, accuracy and safety of screening, the authors said. They suggested that identification of additional risk factors for esophageal adenocarcinoma (obesity and tobacco are possibilities) might increase the value of screening, but data on the effects of these factors are still needed. The study was published online Dec. 7 by the American Journal of Gastroenterology.

The findings of this study don’t support current practice of American gastroenterologists, as identified by a recent survey, the authors said. More than 70% of gastroenterologists said they would screen a 35-year-old man with GERD and 42% would screen a 55-year-old woman. The gap between evidence and practice may be due to an inappropriate focus on the relative increase in risk posed by GERD rather than the fairly low absolute risk of esophageal cancer, the authors concluded.


HIV reduction efforts should target risky behaviors

Expanding HIV screening and treatment would help reduce new HIV infections, but prevention efforts should also target risky behaviors to be most effective, a new study indicates.

Approximately 56,000 people become infected with HIV each year in the U.S., and recent clinical guidelines recommend expanding HIV screening to all patients 13 and older regardless of risk factors. Researchers developed a mathematical model and performed a cost-effectiveness analysis to evaluate the effect of expanded screening, antiretroviral therapy (ART) and behavioral counseling on the U.S. HIV epidemic. The goal of the study was to determine whether expanding screening, treatment or both could significantly decrease HIV infections in the U.S., and whether more infections could be prevented by allocating resources to screening or to treatment. Effects of reductions in risky behavior were also evaluated. The study results appear in the Dec. 21 Annals of Internal Medicine.

The authors' model projected that about 1.23 million new HIV infections would occur in 20 years, 74% in persons at high risk. In the base-case analysis, one-time HIV screening in low-risk persons and annual screening of high-risk persons prevented 6.7% of these infections at a cost per quality-adjusted life-year (QALY) gained of $22,382 when a 20% reduction in sexual activity after screening was assumed. When ART use was expanded to 75% of eligible patients, 10.3% of infections were prevented at a cost of $20,300 QALY gained. A strategy that combined both expanded screening and treatment prevented 17.3% of infections at a cost of $21,580 per QALY gained. The sensitivity analysis, meanwhile, found that expanded screening could prevent 3.7% of infections if sexual activity wasn't reduced, that earlier initiation of ART could prevent 20% to 28% of infections, and that efforts to halve high-risk behavior could reduce new infections by 65%.

The study used a simplified model of disease progression and treatment, did not consider variations in race or ethnicity, and excluded acute HIV screening. Nevertheless, the authors wrote, their results indicate that a multimodal program could markedly affect HIV incidence in the U.S. over the next two decades, with expanded screening and treatment programs leading to a potential 24% reduction. They pointed out that the cost-effectiveness of one-time HIV screening in low-risk persons and annual screening in high-risk persons is comparable to that of screening for type 2 diabetes and mammography screening for breast cancer. "If these [screening and treatment] programs are accompanied by additional interventions that halve risky sexual and needle-sharing behavior, the epidemic could be reduced by 65%, suggesting the need for a comprehensive portfolio of HIV prevention, screening, and treatment," they concluded.


Test yourself

MKSAP Quiz: daily cough without specific triggers

A 52-year-old man is evaluated for a daily cough for the past 6 months. It occurs throughout the day and occasionally at night, but he does not notice any specific triggers. There is occasional production of small amounts of white sputum but no hemoptysis. He does not have any known allergies, has no new pets or exposures, and does not smoke. He does have nasal discharge. He has not noticed any wheezing and has no history of asthma. He has no symptoms of heartburn. He has had no fever, weight loss, or foreign travel, and takes no medications.

Vital signs are normal. There is no cobblestone appearance of the oropharyngeal mucosa or mucus dripping down the oropharynx. Lungs are clear to auscultation. A chest radiograph is normal.

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

A) Antihistamine/decongestant combination
B) CT scan of chest
C) Inhaled fluticasone
D) Proton-pump inhibitor
E) Pulmonary function testing

Click here to see the answer and critique for this question.


Pain management

For arthritis, opioids present increased relative risk compared to NSAIDs

Opioids for arthritis pain control have an increased relative risk for many safety events compared with nonselective, nonsteroidal anti-inflammatory drugs (nsNSAIDs), a new study concluded.

Researchers examined the comparative safety of nsNSAIDs, selective cyclooxygenase 2 inhibitors (coxibs) and opioids. They studied Medicare beneficiaries from Pennsylvania and New Jersey who qualified for pharmaceutical assistance programs for low-income older adults with osteoarthritis or rheumatoid arthritis (RA). Patients had started therapy with an nsNSAID, a coxib, or an opioid in the years from 1999 to 2005. The mean age was 80 years, and almost 85% were female.

Results appeared in the Dec. 13/27 Archives of Internal Medicine alongside a second study derived from the same population and done by many of the same authors. (See the next story, "Opioids for nonmalignant pain have different adverse event profiles.")

Outcome safety events were adverse events related to analgesics: cardiovascular events (myocardial infarction, stroke, heart failure, revascularization and out-of-hospital cardiac death); gastrointestinal effects (upper and lower GI tract bleeding and bowel obstruction); acute kidney injury; hepatic toxic effects; fractures of hip, pelvis, wrist and humerus, but not spine; and trauma from a fall. Patients were matched on propensity scores.

Compared with nsNSAIDs, coxibs (hazard ratio [HR], 1.28; 95% CI, 1.01 to 1.62) and opioids (HR, 1.77; 95% CI, 1.39 to 2.24) had elevated relative risk for cardiovascular events. Gastrointestinal tract bleeding risk was reduced in patients on coxibs (HR, 0.60; 95% CI, 0.35 to 1.00) and similar for opioids. Coxibs and nsNSAIDs posed similar fracture risk. Fracture risk was elevated with opioid use (HR, 4.47; 95% CI, 3.12 to 6.41). Opioids (HR, 1.68; 95% CI, 1.37 to 2.07) but not coxibs, were associated with an increased risk for events requiring hospitalization compared with nsNSAIDs. Opioids (HR, 1.87; 95 CI, 1.39 to 2.53) but not coxibs raised the risk of all-cause mortality compared with nsNSAIDs.

The authors wrote, "Although nsNSAIDs pose certain risks, these analyses support the safety of these agents compared with other analgesics. The recent concerns raised about opioid use in nonmalignant pain syndromes appear warranted on the basis of these data."

An editorialist commented that, for a practicing internist, treating the underlying condition is as important as treating the pain. While there was likely some residual bias in which sicker patients were more likely to take opioids, "many clinicians use opioids in their patients, including the elderly, precisely for the reason that this class is perceived to be less toxic, whether out of concern for the gastrointestinal toxicity or nephrotoxicity of nsNSAIDs or the cardiovascular toxicity of coxibs, for example," the editorialist wrote. "However, the results of this study, as well as others, suggest that those assumptions may no longer hold up under more rigorous scrutiny from systematic comparative safety analyses such as this."


Opioids for nonmalignant pain have different adverse event profiles

Adverse events among older adults using opioids for nonmalignant pain vary significantly by agent, contrary to the commonly held belief that all opioids are associated with a similar risk, a study found.

Researchers devised a propensity-matched cohort analysis that used health care utilization data collected from the years 1996 to 2005 among Medicare beneficiaries from Pennsylvania and New Jersey who started opioid therapy for nonmalignant pain. The five studied opioids were codeine phosphate, hydrocodone bitartrate, oxycodone hydrochloride, propoxyphene hydrochloride and tramadol hydrochloride. No patients had a cancer diagnosis, and none were using hospice or nursing home care.

Main outcome measures were incidence rates and rate ratios (RRs) with 95% CIs for cardiovascular events, fractures, gastrointestinal events, and several composite end points. Results appeared in the Dec. 13/27 Archives of Internal Medicine alongside a study derived from the same population and done by many of the same authors. (See the previous story, "For arthritis, opioids present increased relative risk compared to NSAIDs.")

In the study, 143,482 (26.5%) potentially eligible subjects were available for matching. The study looked at 6,275 subjects in each of the five opioid groups. Their mean age was 79 years; 80.9% were women; 91.0% were white.

Researchers looked at fractures (including hip, pelvis, wrist, and humerus fractures, but not spine fractures), cardiovascular events (myocardial infarction, stroke, heart failure, revascularization and out-of-hospital cardiac death) and gastrointestinal bleeding or bowel obstruction.

Results showed that the risk of cardiovascular events was elevated for codeine (RR, 1.62; 95% CI, 1.27 to 2.06) after 180 days. Compared with hydrocodone, after 30 days of opioid exposure, the risk of fracture was significantly reduced for tramadol (RR, 0.21; 95% CI, 0.16 to 0.28) and propoxyphene (RR, 0.54; 95% CI, 0.44 to 0.66) users. Gastrointestinal safety events did not differ across opioid groups. All-cause mortality was elevated after 30 days for oxycodone (RR, 2.43; 95% CI, 1.47 to 4.00) and codeine (RR, 2.05; 95% CI, 1.22 to 3.45) users compared with hydrocodone users.

Limitations include that the study analyzed typical, nonrandomized practice data, leading to potential residual confounding, and the study was unable to assess causality. Secondly, the study database consisted of health care and pharmacy data without corroboration from death certificates, or other details such as pain levels, functional status, aspirin or tobacco use, or over-the-counter medication use. Third, the study occurred among older, low-income adults, limiting generalizability, and fourth, the study looked at a limited number of events in several outcome-exposure relationships, limiting the ability to prove the safety of an opioid for a specific outcome.

Editorialists commented that there is now a need to re-examine the widespread use of codeine. "If codeine is of middling efficacy for pain and is more risky than other opioids, there would be little reason to use it. ... [T]his large observational study revealing a previously unknown risk makes further research imperative," they wrote.

Also, the editorial said, elevated fracture risk with opioid use is suspected from increased fall risk and the drugs' effects on bone metabolism. Starting opioids at low doses, monitoring for side effects, and avoiding polypharmacy have been used to prevent adverse events. But, said the editorial, "[T]hese studies strongly suggest that implementation of these basic safety measures is suboptimal for patients taking opioids."



Cystatin C beats creatinine at predicting complications of kidney disease

Testing for cystatin C, a protease inhibitor made by most cells and a biomarker of renal function, more accurately identifies chronic kidney disease (CKD) patients who are at high risk for complications than creatinine testing does, according to a new study.

The study included more than 11,000 participants of the Multi-Ethnic Study of Atherosclerosis (MESA) and the Cardiovascular Health Study (CHS). Patients were assessed for chronic kidney disease (defined as estimated glomerular filtration rate [GFR] <60 mL/min per 1.73 m2) using creatinine testing and cystatin C testing. The researchers used CKD-EPI equations to estimate GFR based on the biomarkers. In the MESA study, 9% of participants had CKD based on the creatinine test, 2% had it based on cystatin C and 4% had it according to both measures. In the other study, the percentages were 12%, 4% and 13% respectively. The results were published by the Journal of the American Society of Nephrology on Dec. 16.

The study also assessed the risk of death, cardiovascular events, heart failure and end-stage renal disease among the patients found to have CKD. In the MESA group, patients diagnosed by creatinine had no higher mortality risk than those without CKD (hazard ratio, 0.80; 95% CI, 0.50 to 1.26), while patients who were diagnosed by cystatin C had a significantly increased risk of death (hazard ratio, 3.23; 95% CI, 1.84 to 5.67). Those who tested positive on both had an increased risk with a hazard ratio of 1.93 (95% CI, 1.27 to 2.92). Trends were similar in the CHS study and for the other outcomes tracked by the study.

Recent efforts to improve detection of CKD have promoted the use of creatinine testing, the study authors noted. Given that this study found that patients whose creatinine indicated CKD had no greater risk than average, creatinine-based equations may be leading patients to receive unnecessary nephrology referrals, testing and treatments, the authors said. Cystatin C testing would offer greater specificity and therefore may be useful as either a confirmatory test for patients who’ve been identified with possible CKD by creatinine testing or, in high-risk groups, as a screening test.

The two tests could also be combined with albuminuria testing, the authors suggested. Future research should evaluate the cost-effectiveness of such a triple screening process. Cystatin C testing—which is becoming more readily available in U.S. labs, the authors noted—could be used in a stepwise system to identify CKD patients who are higher risk for complications. The end result could be more specific screening and less unneeded care, the authors concluded.


Regulatory news

Are you ready for 5010 and ICD-10?

It’s only a little over a year until the deadline for practices to convert their coding to 5010 electronic transactions.

As part of preparation for the ICD-10-CM code set, which must be used starting Oct. 1, 2013, all electronic transactions must be using 5010 standards by Jan. 1, 2012. To make sure that your practice is ready, you need to begin testing the upgraded electronic administrative transactions with your trading partners during 2011. To help you prepare, CMS maintains a resource that provides guidance on talking to vendors about 5010 readiness. In addition, you can visit the AMA’s website to access additional resources and view a free archived webinar to help your practice prepare for these approaching deadlines.


HRSA accepting applications for GME grants program

The Health Resources and Services Administration is now accepting applications for the new Teaching Health Center Graduate Medical Education program.

Established as part of the health care reform legislation, this program is designed to encourage resident education in ambulatory care sites and can be used to fund new positions for primary care training. The deadline for submitting a grant application is Dec. 30. Additional information can be found in the announcement on the HRSA website.


CMS conducting 2011 Medicare Contractor Provider Satisfaction Survey

The Centers for Medicare and Medicaid Services (CMS) is now conducting its annual satisfaction survey for Medicare fee-for-service contractors responsible for processing and paying Medicare claims.

The survey will be sent to a random sample of 30,000 Medicare providers and suppliers. If you are contacted, please take the time to complete the survey. It should take no more than 20 minutes. More information about the survey can be found on the CMS website.


From the College

Depression quality improvement program seeks participants

Physicians are invited to participate in ACP’s new quality improvement program on depression.

This free Web-based program offers physicians the chance to earn up to 30 performance improvement CME credits and credit toward American Board of Internal Medicine Part 4 Maintenance of Certification. This program will help physicians to analyze their own practice patterns, evaluate actual practice data in identifying gaps, and learn how to implement clinical quality improvement tools and techniques.

Participants will also communicate with national experts via conference call to interact and receive guidance on practice improvement. The program is done for free without leaving the office. Physicians will be asked to complete both a survey and a set of chart abstractions twice during the program and will be given access to a Web-based educational module on depression. The first 50 physicians to enroll in the program will be entered into a raffle to win either MKSAP 15 or Internal Medicine 2011 registration. If you are interested in participating in this program, please contact Meghan Gannon at


Help choose the best name for ACP’s advocacy program

The College is looking for a new name for its federal advocacy grassroots program.

ACP's grassroots advocates e-mail, call and meet with their members of Congress on issues of importance to medical students, internists and their patients. ACP gives these physicians the tools necessary to develop and maintain relationships with their representatives.

Please take a minute to fill out this short survey and help us determine our new name.


Cartoon caption contest

Put words in our mouth

ACP InternistWeekly wants readers to create captions for this cartoon and help choose the winner. Pen the winning caption and win a $50 gift certificate good toward any ACP product, program or service.

E-mail all entries to ACP staff will choose finalists and post them online for an online vote by readers. The winner will appear in an upcoming edition.


MKSAP answer and critique

The correct answer is A) Antihistamine/decongestant combination. This item is available to MKSAP 15 subscribers as item 9 in the General Internal Medicine section.

The most appropriate treatment for this patient is a trial of an antihistamine/decongestant combination. The initial approach in patients with chronic cough (>8 weeks in duration) is to conduct a history and physical examination looking for identifiable causes, determine whether the patient is taking an angiotensin-converting enzyme (ACE) inhibitor, and obtain a chest radiograph. In the population of patients who do not smoke, do not take an ACE inhibitor, and have a normal chest radiograph, upper airway cough syndrome (UACS) (previously termed postnasal drip), asthma, and gastroesophageal reflux disease (GERD) are responsible for approximately 99% of cases of chronic cough. When the etiology of a chronic cough is unclear, the American College of Chest Physicians recommends initial treatment with a first-generation antihistamine/decongestant combination to treat UACS. This is true even in the absence of evidence of a postnasal drip. The diagnosis of chronic cough is often based upon the patient’s response to empiric therapy, and it may take weeks or even months for the cough to resolve with appropriate therapy.

In a nonsmoking patient with a normal chest radiograph and no systemic symptoms, CT scan of the chest is not indicated.

Asthma is a common cause for a chronic cough and may present only with a cough (cough-variant asthma). However, pursuing pulmonary function testing or initiating empiric β-agonist therapy for asthma is premature unless the patient fails to respond to empiric treatment of UACS.

In the absence of GERD symptoms, proton-pump inhibitors should be reserved for patients with chronic cough who have a normal chest radiograph, are not taking an ACE inhibitor, do not smoke, and have failed to improve with treatment for UACS, asthma, and nonallergic eosinophilic bronchitis.

Key Point

  • Empiric treatment of chronic cough in a nonsmoking patient not taking an angiotensin-converting enzyme inhibitor who has a normal chest radiograph begins with treatment for upper airway cough syndrome.

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Test yourself

A 38-year-old woman is evaluated during a follow-up visit. She has a history of well-controlled hypertension and type 1 diabetes mellitus. She is at 16 weeks' gestation with her first pregnancy. Prior to conception she was taking lisinopril, which was discontinued in anticipation of the pregnancy, and labetalol was initiated. Other medications are insulin glargine, insulin lispro, and a prenatal vitamin. Following a physical exam and lab studies, what is the most appropriate step in the management of this patient's hypertension? .

Find the answer

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