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ACP InternistWeekly



In the News for the Week of 5-10-11




Highlights

Higher-salt diets didn't increase mortality in European study

Higher sodium consumption was associated with increased systolic blood pressure, but not greater mortality or cardiovascular events, in a new prospective analysis of Europeans' sodium excretion. More...

Asthma pill performed similarly to glucocorticoids, LABAs

Leukotriene-receptor antagonists controlled asthma as effectively as more commonly recommended treatments, according to a new report of two pragmatic trials. More...


Test yourself

MKSAP Quiz: Diagnosing amenorrhea

A 26-year-old woman is evaluated for a 4-month history of secondary amenorrhea after stopping her oral contraceptive pill. What is the most appropriate diagnostic test? More...


Prostate cancer

Surgery associated with less prostate cancer mortality than surveillance

Radical prostatectomy was associated with fewer deaths from prostate cancer compared to watchful waiting, a Scandinavian study found. But the results may not apply in the U.S., where more prostate-specific antigen testing occurs. More...


Risk prediction

Growth differentiation factor-15 may help predict mortality in older adults

The biomarker growth differentiation factor-15 may help predict mortality in older community-dwelling adults, a new study indicates. More...


E-prescribing

ACP, others release updated guide to e-prescribing

ACP recently joined other organizations in releasing an updated version of "A Clinician's Guide to Electronic Prescribing," which assists health care professionals in transitioning from paper to e-prescribing systems. More...


CMS update

Are you ready for version 5010?

The Centers for Medicare and Medicaid Services recently announced National Version 5010 Testing Day. More...


From the College

ACP wants your opinion on virtual communities

ACP is investigating whether to provide members with similar interests the opportunity to exchange ideas, information and experiences and to stay connected with one another through online virtual communities and/or live meetings. More...

The Doctors Company announces 2011 dividend for ACP members

The Doctors Company, the nation's largest insurer of physician medical liability, is pleased to announce a 7.5% dividend for ACP members based on strong claims experience and ACP members' commitment to patient care. More...

ACP's John Tooker, MACP, blogs at KevinMD

John Tooker, MACP, ACP's associate executive vice president, continues his monthly column at KevinMD.com, one of the Web's most influential medical blogs. More...

New ACP Online Education & Recertification page

Get a sneak peek at the beta version of ACP's redesigned Education & Recertification web page and send us your feedback. More...


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. More...


Physician editor: Darren Taichman, FACP




Highlights


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Higher-salt diets didn't increase mortality in European study

Higher sodium consumption was associated with increased systolic blood pressure, but not greater mortality or cardiovascular events, in a new prospective analysis of Europeans' sodium excretion.

The study included 3,681 people without cardiovascular disease (CVD) at the start of the trial who were followed for a median of 7.9 years. They were divided into tertiles by their 24-hour urinary sodium excretion, and cardiovascular-related death rates were compared among the tertiles. The results were published in the May 4 Journal of the American Medical Association.

Over the entire course of the study, the patients with the lowest sodium excretion (mean, 107 mmol) had the highest death rate (4.1%), compared to 1.9% in the middle group (mean, 168 mmol) and 0.8% in the highest sodium group (mean, 260 mmol). The inverse association maintained significance, at a P value of 0.02, even when adjusted for multiple variables. The study also found no relationship between baseline sodium excretion and mortality or CVD events. Incident hypertension didn't vary significantly among the tertiles either.

A subset of 1,499 participants also had their blood pressure measured during the study. On average, their systolic blood pressure increased by 0.37 mm Hg per year, but their sodium excretion did not change. However, an adjusted analysis found that every 100-mmol increase in sodium excretion was associated with a 1.71-mm Hg increase in systolic blood pressure, but no change in diastolic blood pressure.

The study authors noted that other studies have analyzed the relationship between salt intake and hypertension and CVD, but few have used 24-hour urinary sodium excretion, which is the most accurate measure. They also noted that the inverse association between sodium intake and mortality found in this study is unlikely to result from reverse causality, because patients with existing CVD were excluded. The authors speculated instead that low salt intake may increase mortality because it can negatively impact sympathetic nerve activity, insulin sensitivity, the renin-angiotensin system and aldosterone secretion.

The study was limited by its inclusion of only relatively young, white Europeans, so the results may not apply to other races or to hypertensive patients. However, the authors believe that their results refute commonly publicized estimates of avoidable morbidity and mortality resulting from the general population's salt intake.

"[The results] do also not support the current recommendations of a generalized and indiscriminate reduction of salt intake at the population level," the authors wrote.

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Asthma pill performed similarly to glucocorticoids, LABAs

Leukotriene-receptor antagonists (LTRAs) controlled asthma as effectively as more commonly recommended treatments, according to a new report of two pragmatic trials.

The first of the trials included 300 British primary care patients between 12 and 80 years old who had inadequate asthma control or impaired asthma-related quality of life. The patients were randomized to either an LTRA or an inhaled glucocorticoid as their first-line asthma therapy. The second trial included 350 similar patients who were already taking an inhaled glucocorticoid as first-line therapy, and they were randomized to either an LTRA or a long-acting beta-agonist (LABA) as add-on therapy. The groups' scores on the Mini Asthma Quality of Life Questionnaire (MiniAQLQ) were compared during the following two years of open-label treatment. Results appeared in the May 5 New England Journal of Medicine.

Overall, mean MiniAQLQ scores increased during the two years. After two months of treatment, scores were equivalent between patients taking LTRA or other drugs in both trials. After two years of treatment, the scores were almost equivalent, but they did not meet the study authors' prespecified, and intentionally conservative, criterion for equivalence (mean difference between groups, −0.11), with the other drugs slightly outperforming LTRAs.

Adherence to an LTRA was better than to the other drugs (65% vs. 41% for the first trial, 74% vs. 46% for the second), probably because it's easier to take a pill than use an inhaler, noted an accompanying editorial. The editorialists noted other advantages to LTRAs, including their effects on comorbidities such as rhinitis and ease of use in the developing world.

The study authors urged caution in interpreting their results, since the trials were limited by lack of a placebo control and crossover between treatment groups. However, the pragmatic trial design did allow analysis of adherence, as well as inclusion of patients who would typically be excluded from such research. Almost a quarter of the studied patients were smokers, and 3% may have had chronic pulmonary obstructive disease, making them more like real-world patients than typical study populations.

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Test yourself


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MKSAP Quiz: Diagnosing amenorrhea

A 26-year-old woman is evaluated for a 4-month history of amenorrhea. Menses began at age 13 years. At age 18 years, the patient was placed on an oral contraceptive pill to control heavy bleeding. She discontinued the oral contraceptive pill 4 months ago because she and her husband want to become pregnant, and she has had no menses since then. There is no family history of infertility or premature menopause.

mksap.jpg

On physical examination, vital signs are normal, and BMI is 24. There is no acne, hirsutism, or galactorrhea. Examination of the thyroid gland and visual field testing yield normal findings. Pelvic examination findings are also normal. An office pregnancy test is negative.

Laboratory studies:

Follicle-stimulating hormone 2 mU/mL (2 U/L)
Prolactin 17 ng/mL (17 µg/L)
Thyroid-stimulating hormone 1.1 µU/mL (1.1 mU/L)
Thyroxine (T4), free 1.0 ng/dL (12.9 pmol/L)

Which of the following is the most appropriate next diagnostic test?

A) Measurement of the plasma dehydroepiandrosterone sulfate level
B) Measurement of serum estradiol level
C) MRI of the pituitary gland
D) Progestin withdrawal challenge

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

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Prostate cancer


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Surgery associated with less prostate cancer mortality than surveillance

Radical prostatectomy was associated with fewer deaths from prostate cancer compared to watchful waiting, a Scandinavian study found. But the results may not apply in the U.S., where more prostate-specific antigen (PSA) testing occurs.

Researchers in the Scandinavian Prostate Cancer Group Study Number 4 (SPCG-4) randomized 695 men with early prostate cancer to watchful waiting or radical prostatectomy from October 1989 to February 1999. Follow-up occurred through December 2009. Researchers presented results in the May 5 New England Journal of Medicine. The study follows up on the group's 2008 report with an additional three years of data to present 15-year results.

Upon study enrollment, 12% of the patients had nonpalpable T1c tumors. The mean PSA level was approximately 13 ng/mL. During a median follow-up of 12.8 years, 367 of the 695 men enrolled in the study had died from all causes—166 of the 347 men in the radical-prostatectomy group and 201 of the 348 in the watchful-waiting group (P=0.007).

The cumulative incidence of death from prostate cancer at 15 years of follow-up was 14.6% in the surgical group and 20.7% in the surveillance group (relative risk with surgery, 0.62; P=0.01). The number needed to treat to avert one death was 15 overall and 7 for men younger than 65 years of age. Among men who underwent surgery, those with extracapsular tumor growth had a risk of death from prostate cancer 7 times more than men without it. Cumulative incidence of local progression at 15 years was 21.5% in the surgical group and 49.3% in the surveillance group. Cumulative incidence of distant metastases at 15 years was 21.7% in the surgical group and 33.4% in the surveillance group.

A total of 124 men in the surgical group and 139 in the surveillance group had a PSA level of less than 10 ng/mL and a tumor with a Gleason score of less than 7 or a WHO of grade 1. Among them, 42 in the surgical group and 68 in the surveillance group died. In men with low-risk disease, the absolute benefit of surgery with respect to death from prostate cancer and the risk of metastases was similar to that in the whole cohort.

But researchers noted that the study's low-risk group cannot be compared directly with other studies because few of them had a tumor found by a PSA screening test. The biopsy protocol for the SPCG-4 study also had a lower sensitivity for diagnosing high-risk disease than other studies. More follow-up may identify prognostic markers in men assigned to surveillance that can serve as trigger points for active treatment, the study authors said.

"The benefit of radical prostatectomy continued to be seen beyond 9 years, which contradicts the notion that there is only a distinct subpopulation that responds to radical surgery with an early reduction in risk," the researchers wrote. "The finding that some low-risk tumors will progress and become lethal emphasizes the importance of protocols with well-defined end points at which men in active surveillance switch to curative treatment."

An editorialist commented that the survival benefit of radical prostatectomy in men with low-risk disease is the most important new finding of SPCG-4, but that it may not apply to low-risk, early-stage prostate cancers identified by PSA screening. Compared to SPCG-4 patients, American men newly diagnosed with prostate cancer have far fewer palpable tumors and are far more likely to have tumors identified by PSA. Two large, randomized, controlled trials are under way to determine whether treatment will reduce mortality in men with prostate cancer identified through PSA screening.

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Risk prediction


.
Growth differentiation factor-15 may help predict mortality in older adults

The biomarker growth differentiation factor-15 (GDF-15) may help predict mortality in older community-dwelling adults, a new study indicates.

GDF-15, previously known as macrophage-inhibitory cytokine-1, is part of the superfamily of growth factor-β cytokines. It is usually expressed by activated macrophages in low levels but is upregulated in massive myocardial infarction and is expressed by atherosclerotic plaques and overexpressed in several types of malignancies. The authors noted that in previous studies, GDF-15 has added prognostic information to more standard cardiovascular biomarkers and risk factors in patients who had acute coronary syndromes and chronic heart failure.

In the current study, the researchers measured levels of plasma GDF-15, N-terminal pro-B-type natriuretic peptide (NT-proBNP) and C-reactive protein in stored samples of blood from 1,391 patients who participated in the Rancho Bernardo Study, a population-based epidemiologic study performed in Southern California between 1972 and 1974. Patients included in the study had no history of cardiovascular disease (CVD) at a follow-up visit that took place between 1992 and 1996. The objective of the current study was to determine whether GDF-15 independently predicted increased risk for death in this population. The primary outcome was all-cause mortality, and the secondary outcomes were fatal CVD and noncardiovascular death. The study was published online May 2 by Circulation.

Baseline for the current study was defined as the visit that took place between 1992 and 1996. Patients were followed for a mean of 11 years. The mean age of the study population at baseline was 70 years, and 36% of patients were men. The median level of GDF-15 was 1,268 ng/mL, with higher levels in men than in women (1,349 ng/L vs. 1,229 ng/L; P=0.001). After adjustment for traditional CVD risk factors, GDF-15 predicted all-cause, cardiovascular and noncardiovascular death and was a better predictor of all-cause mortality than NT-proBNP or C-reactive protein, the latter of which was not a significant predictor. GDF-15 was the only biomarker studied that predicted noncardiovascular death (hazard ratio, 1.6; P<0.0001). Elevated levels of both GDF-15 and NT-proBNP conferred a greater risk for death than did elevated NT-proBNP levels alone (hazard ratio, 1.5; P=0.01).

The authors acknowledged that most of the study participants were white and of similar socioeconomic status, limiting generalizability. They also pointed out that existing CVD could have been misclassified and that blood samples were stored for over a decade before GDF-15 levels were measured. However, they concluded that GDF-15 appears to be a strong predictor of all-cause, cardiovascular and noncardiovascular death in community-dwelling older adults without known CVD.

"This emerging biomarker may be a useful addition to current tools for risk stratification if results are confirmed in other cohorts," the authors wrote.

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E-prescribing


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ACP, others release updated guide to e-prescribing

ACP recently joined other organizations in releasing an updated version of "A Clinician's Guide to Electronic Prescribing," which assists health care professionals in transitioning from paper to e-prescribing systems.

The new edition of the guide, which was first created in 2008, addresses the changing health care information technology environment, including e-prescribing, the Health Information Technology for Economic and Clinical Health (HITECH) Act and health care reform. Along with ACP, the American Medical Association, the American Academy of Family Physicians, the Medical Group Management Association, e-Health Initiative, and The Center for Improving Medication Management were also involved in creating the guide. The 2011 edition is available online.

Beginning in 2011, physicians and practices that are not e-prescribing will be subject to a 1% penalty on total allowed charges under Medicare Part B. To avoid this penalty, physicians must have implemented a qualified system by the end of June. Additional information on the Medicare e-prescribing program is available on the Running a Practice section of the College's website.

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CMS update


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Are you ready for version 5010?

The Centers for Medicare and Medicaid Services (CMS) recently announced National Version 5010 Testing Day.

On June 15, CMS will encourage trading partners (clinicians, clearinghouses and vendors) to come together to test their compliance with the version 5010 standards. More information will be coming from CMS and Medicare Administrative Contractors about real-time help desk support available that day.

Version 5010 is a new set of standards for electronic transactions that must be in use for all health care transmissions by Jan. 1, 2012. To ensure that the transition proceeds smoothly and no practices experience a lapse in payments, CMS has been stressing the importance of early testing of practice systems. More information on version 5010 is available on the CMS website. Additional guidance is also available from ACP.

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From the College


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ACP wants your opinion on virtual communities

ACP is investigating whether to provide members with similar interests the opportunity to exchange ideas, information and experiences and to stay connected with one another through online virtual communities and/or live meetings. Answer seven questions and tell us what you think by taking a short survey.

Top


.
The Doctors Company announces 2011 dividend for ACP members

The Doctors Company, the nation's largest insurer of physician medical liability, is pleased to announce a 7.5% dividend for ACP members based on strong claims experience and ACP members' commitment to patient care.

The 2011 dividend credit, approved by The Doctors Company's Board of Governors, will be applied as a 7.5% premium reduction for ACP members on policy renewals on or after July 1, 2011. More information on The Doctors Company's benefit programs is online.

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ACP's John Tooker, MACP, blogs at KevinMD

John Tooker, MACP, ACP's associate executive vice president, continues his monthly column at KevinMD.com, one of the Web's most influential medical blogs. This month's column looks at immigration and health care.

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New ACP Online Education & Recertification page

Get a sneak peek at the beta version of ACP's redesigned Education & Recertification web page and send us your feedback.

The newly reorganized page offers one-click access for certification, recertification and CME content, plus a great new way to quickly search through ACP's products and events for exactly what you're looking for. Offer feedback on the page through an online survey.

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Cartoon caption contest


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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.

acpi-20110510-cartoon.jpg

"If you suddenly get the urge to kick it, press the call button immediately."

This issue's winning cartoon caption was submitted by Fred Bromberg, FACP, from Livingston, N.J. Readers cast 90 ballots online to choose the winning entry. Thanks to all who voted! The winning entry captured 54.4% of the votes.

The runners-up were:

"That's a 'pay-for-performance' jar."

"It's for your bucket list."

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MKSAP Answer and Critique



The correct answer is D) Progestin withdrawal challenge. This item is available to MKSAP 15 subscribers as item 5 in the Endocrinology and Metabolism section.

The next step in the evaluation of this patient with secondary amenorrhea after stopping her oral contraceptive pill is a progestin withdrawal challenge. At one time, the use of oral contraceptives was thought to be associated with an increased risk of developing amenorrhea once the oral contraceptive pill was discontinued. Studies have since shown that the incidence of amenorrhea and other endocrinologic findings in women who discontinue oral contraceptive use is no different from that in women with spontaneous amenorrhea. Therefore, women who stop oral contraceptive use are evaluated in the same way as women who have secondary amenorrhea and have never used oral contraceptives.

This patient has an unremarkable personal and family medical history and no evidence of androgen excess. Results of her screening laboratory studies are negative for thyroid disorders, ovarian dysfunction, and hyperprolactinemia. Given these data, the differential diagnosis of this patient's secondary amenorrhea includes anatomic defects and chronic anovulation, with or without estrogen. The differential diagnosis can be narrowed most effectively with a progestin withdrawal challenge. Menses after challenge excludes anatomic defects and chronic anovulation without estrogen. Therefore, a progestin withdrawal challenge is the most appropriate next step.

Polycystic ovary syndrome (PCOS) affects 6% of women of child-bearing age and typically presents with oligomenorrhea and signs of androgen excess (hirsutism, acne, and, occasionally, alopecia). Insulin resistance is a major feature of the disorder, as is overweight and obesity (although only 50% of women with PCOS are obese). Typically, testosterone and dehydroepiandrosterone sulfate levels are mildly elevated, and the luteinizing hormone to follicle-stimulating hormone ratio is greater than 2:1.

Measurement of dehydroepiandrosterone sulfate is rarely clinically useful. Positive withdrawal bleeding after the progestin withdrawal challenge suggests an estradiol level of greater than 40 pg/mL (146.8 pmol/L) and thus obviates the need for measurement of serum estradiol levels. An MRI of the pituitary gland is unnecessary at this point because her follicle-stimulating hormone, prolactin, and thyroid levels are all normal.

Key Point

  • Menstrual flow on progestin withdrawal indicates relatively normal estrogen production and a patent outflow tract, which limits the differential diagnosis of secondary amenorrhea to chronic anovulation with estrogen present.

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A 72-year-old woman is evaluated during a routine examination. She has very severe COPD with multiple exacerbations. She has dyspnea at all times with decreased exercise capacity. She does not have cough or any change in baseline sputum production. She is adherent to her medication regimen, and she completed pulmonary rehabilitation 1 year ago. She quit smoking 1 year ago. Her medications are a budesonide/formoterol inhaler, tiotropium, and an albuterol inhaler as needed. Following a physical and pulmonary exam, what is the most appropriate next step in management?

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