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

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ACP InternistWeekly



In the News for the Week of March 25, 2014




Highlights

Internal medicine residency match results virtually unchanged from last year

The number of U.S. senior medical students choosing categorical internal medicine residencies increased slightly for the fifth consecutive year. According to the 2014 National Resident Matching Program, 3,167 U.S. medical school seniors matched for residency training in internal medicine. More...

Stool DNA testing more sensitive, less specific than FIT

Multitarget stool DNA testing detected significantly more cancer than fecal immunochemical testing (FIT) but had more false-positive results in asymptomatic persons at average risk for colorectal cancer, a study found. More...


Test yourself

MKSAP Quiz: increasing asthma symptoms

A 24-year-old woman is evaluated for increasing asthma symptoms. Her symptoms now require her to use her as-needed albuterol inhaler two to three times per week, and she has been waking up at night at least once a week with asthma symptoms that require her inhaler. She is still able to perform most of her daily activities, including regular exercise, if she uses albuterol for prevention. She is allergic to house dust mites, ragweed, grass, trees, and cats. Following a physical exam and spirometry, what is the most appropriate treatment? More...


Geriatric medicine

USPSTF finds insufficient evidence to recommend routine screening for cognitive decline

The U.S. Preventive Services Task Force (USPSTF) found insufficient evidence to recommend routine screening with formal screening instruments for cognitive decline in adults over the age of 65 in the primary care setting who have no signs of impairment. More...


Prostate cancer

No mortality benefit associated with primary androgen deprivation therapy in localized prostate cancer

Primary androgen deprivation therapy (PADT) yielded no mortality benefit compared with no PADT in men with clinically localized prostate cancer, according to a new study. More...


Pulmonary embolism

Age-adjusted D-dimer cutoff appears better at ruling out PE

D-dimer cutoffs adjusted for age performed better than a fixed D-dimer cutoff for safely ruling out pulmonary embolism (PE), especially in elderly patients, according to a new study. More...


Rheumatology

Methotrexate monotherapy, combination therapy yield similar 1-year remission rates in early inflammatory arthritis

Patients taking methotrexate monotherapy and those taking methotrexate plus etanercept had similar rates of remission at 1 year, although those on combination therapy responded more quickly, a new study has found. More...


CME

Annals Virtual Patients test physicians' decision-making skills

Annals of Internal Medicine released a new interactive medical education tool designed to test physicians' decision-making skills. Annals Virtual Patients uses a unique "if this, then that" format, so each learner goes down his or her own path through a complex clinical simulation. More...


Internal Medicine 2014

It's not too late to submit a Job Seeker's Profile to the ACP Job Placement Center

Looking for a job? ACP's Job Placement Center offers career opportunities during Internal Medicine 2014, to be held April 10-12 in Orlando, Fla. 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: Daisy Smith, MD, FACP



Highlights


.
Internal medicine residency match results virtually unchanged from last year

The number of U.S. senior medical students choosing categorical internal medicine residencies increased slightly for the fifth consecutive year. According to the 2014 National Resident Matching Program, 3,167 U.S. medical school seniors matched for residency training in internal medicine.

Categorical internal medicine enrollment numbers were 3,135 in 2013, 2,941 in 2012, 2,940 in 2011, and 2,772 in 2010. The 2014 match also showed a slight increase of U.S. medical graduates who matched in internal medicine-primary care (202 in 2014, 200 in 2013, 186 in 2012, 166 in 2011, and 156 in 2010) but a decrease in medicine-pediatrics (284 in 2014, 312 in 2013, 276 in 2012, 309 in 2011, and 299 in 2010).

The 2014 match for internal medicine is still well below the 3,884 U.S. medical school graduates who chose internal medicine residency programs in 1985.

"While the number of U.S. medical students choosing internal medicine residencies continues in an upward trend, the exorbitant cost of medical education with the resulting financial burden on medical students and residents along with problematic payment models and administrative hassles are barriers to a career in general internal medicine and primary care," said Patrick Alguire, MD, FACP, senior vice president for medical education at ACP.

The great majority of current internal medicine residents will ultimately enter a subspecialty of internal medicine, such as cardiology or gastroenterology. Only about 20% to 25% of internal medicine residents eventually choose to specialize in general internal medicine, compared with 54% in 1998, according to an ACP press release.


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Stool DNA testing more sensitive, less specific than FIT

Multitarget stool DNA testing detected significantly more cancer than fecal immunochemical testing (FIT) but had more false-positive results in asymptomatic persons at average risk for colorectal cancer, a study found.

Researchers in North America enrolled asymptomatic persons between the ages of 50 and 84 years who were considered to be at average risk for colorectal cancer and who were scheduled to undergo screening colonoscopy from June 2011 through November 2012 in a cross-sectional study at 90 sites. Enrollment was weighted toward persons 65 years of age or older in order to increase the prevalence of cancer. All participants provided a stool specimen and underwent screening colonoscopy within 90 days.

The study was funded by the manufacturer of a stool DNA test and was designed by the authors. Data were gathered by a contract research organization.

The DNA test includes quantitative molecular assays for KRAS mutations, aberrant NDRG4 and BMP3 methylation, and β-actin, plus a hemoglobin immunoassay. An algorithm was used to generate results, with values of 183 or more considered to be positive. FIT values of more than 100 ng Hg/mL of buffer were considered to be positive.

Results appeared in the March 19 New England Journal of Medicine.

Of 9,989 participants, 65 (0.7%) had colorectal cancer and 757 (7.6%) had advanced precancerous lesions, defined as advanced adenomas or sessile serrated polyps measuring 1 cm or more in the greatest dimension. The sensitivity for detecting colorectal cancer was 92.3% with DNA testing and 73.8% with FIT (P=0.002), a difference of nearly 20 percentage points, the authors noted.

DNA testing detected 42.4% of advanced precancerous lesions and FIT detected 23.8% (P<0.001). DNA testing detected 69.2% of high-grade dysplasia and FIT detected 46.2% (P=0.004). DNA detected 42.4% of serrated sessile polyps measuring 1 cm or more and FIT detected 5.1% (P<0.001).

Specificity with DNA testing was 86.6% of participants with nonadvanced or negative findings, and FIT was 94.9% (P<0.001). Specificity with DNA testing was 89.8% among those with negative results on colonoscopy and 96.4% among those with negative results on FIT (P<0.001).

The numbers of persons who would need to be screened to detect 1 cancer were 154 with colonoscopy, 166 with DNA testing, and 208 with FIT.

The researchers noted that sensitivity of the DNA test exceeded the performance of the FIT overall and in important subsets of lesions, including adenomas measuring 2 cm or more and large, sessile serrated polyps that may account for up to one-third of colorectal cancers. DNA testing was associated with a relative increase of 27% in the rate of detection of stage I to III colorectal cancers and a relative increase of 78% in the rate of detection of advanced precancerous lesions compared to FIT. But, the authors continued, the specificity of FIT (94.9% to 96.4%) was superior to that of the DNA test (86.6% to 89.8%), with false-positive rates of 3.6% to 5.1% and 10.2% to 13.4%, respectively.

An editorial commented that the stool DNA test is clearly an improvement over its predecessors and that the results of this study will help the U.S. Preventive Services Task Force reevaluate screening tests.

"Only through a better understanding of other key factors, such as the screening interval, adherence, cost, and diagnostic evaluation of positive results, can we determine the appropriate place for stool DNA testing on the screening menu," the editorial noted.



Test yourself


.
MKSAP Quiz: increasing asthma symptoms

A 24-year-old woman is evaluated for increasing asthma symptoms. Her symptoms now require her to use her as-needed albuterol inhaler two to three times per week, and she has been waking up at night at least once a week with asthma symptoms that require her inhaler. She is still able to perform most of her daily activities, including regular exercise, if she uses albuterol for prevention. She is allergic to house dust mites, ragweed, grass, trees, and cats.

mksap.gif

On physical examination, vital signs are normal. Pulmonary examination is normal with no wheezing. Spirometry shows an FEV1 of 85% of predicted and an FEV1/FVC ratio of 80% of predicted.

Which of the following is the most appropriate treatment?

A: Add a long-acting β2-agonist
B: Add a long-acting β2-agonist and a low-dose inhaled corticosteroid
C: Add a low-dose inhaled corticosteroid
D: Advise scheduled use of albuterol
E: Refer for allergen immunotherapy

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


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Geriatric medicine


.
USPSTF finds insufficient evidence to recommend routine screening for cognitive decline

The U.S. Preventive Services Task Force (USPSTF) found insufficient evidence to recommend routine screening with formal screening instruments for cognitive decline in adults over the age of 65 in the primary care setting who have no signs of impairment.

annals.jpg

To update its recommendations, the USPSTF commissioned a systematic review of the evidence on screening for cognitive impairment, including dementia and mild cognitive impairment. The Task Force findings appear in the March 25 Annals of Internal Medicine.

Although the Task Force found details on routine screening insufficient, they also identified important reasons to identify early cognitive impairment:

  • to help patients make diagnostic and treatment decisions, such as treatment of reversible causes and management of comorbid conditions;
  • to allow clinicians to anticipate problems patients may have in understanding and adhering to recommended therapy; and
  • to allow patients and their caregivers and family members to anticipate and plan for future problems.

Despite the insufficient evidence, clinicians should remain alert to early signs or symptoms of cognitive impairment (for example, problems with memory or language) and evaluate them, the review stated. The National Institute on Aging has information on the detection and management of cognitive impairment for patients and clinicians, including a database of tools to detect cognitive impairment online.

In 2003, the USPSTF concluded that the evidence was insufficient to recommend for or against routine screening for dementia in older adults. The current evidence review found much more information on the test performance of screening instruments than in 2003, and the Task Force concluded that there is now adequate information on the test performance of some screening tools, the report stated.

The Mini-Mental State Examination was the most widely published, with 25 studies. It is a 30-point instrument with 11 items. For the most tool's commonly reported cut points (23/24 or 24/25 [score considered "positive"/"negative"]), the pooled sensitivity from 14 studies involving 10,185 participants was 88.3% (95% CI, 81.3% to 92.9%) and specificity was 86.2% (95% CI, 81.8% to 89.7%). Other instruments, such as the Clock Drawing Test, verbal fluency tests, or Informant Questionnaire on Cognitive Decline in the Elderly, were reviewed by 4 to 7 studies each, had limited reproducibility in primary care-relevant populations, and had unknown optimum cut points. Sensitivity and specificity ranged widely, the report stated.

Similar to the findings of the 2003 evidence review and recommendation, the USPSTF found that pharmacologic treatments result in small benefits of unknown clinical significance. The review identified more than 130 studies on several interventions for managing or treating mild to moderate dementia, including pharmacologic and nonpharmacological interventions.

Pharmacologic interventions included FDA-approved medications for the treatment of Alzheimer's disease with the purpose of preventing or delaying cognitive impairment. Acetylcholinesterase inhibitors and memantine improved global cognitive function by approximately 1- to 3-point differences on the Alzheimer's Disease Assessment Scale–Cognitive Subscale (ADAS-cog). A meta-analysis of 7 rivastigmine trials reported a 3-point difference on the ADAS-cog (−3.06; [95% CI, −4.48 to −1.65]; I2=92.6%).

Only 4 trials were done in patients with mild cognitive impairment and reported global cognitive function. Trials of donepezil and galantamine generally showed a small but unclear clinical effect on global cognitive function, the report stated.



Prostate cancer


.
No mortality benefit associated with primary androgen deprivation therapy in localized prostate cancer

Primary androgen deprivation therapy (PADT) yielded no mortality benefit compared with no PADT in men with clinically localized prostate cancer, according to a new study.

Researchers performed a retrospective cohort study with comprehensive utilization and cancer registry data obtained from 3 health plans: Kaiser Permanente Northern California, Kaiser Permanente Southern California, and Henry Ford Health System in Detroit. Included patients were men who received a new diagnosis of clinically localized prostate cancer between 1995 and 2008, who were followed through December 2010, and who did not receive curative-intent therapy. PADT was defined as gonadotropin-releasing hormone analogue or a gonadotropin-release hormone antagonist with or without an oral antiandrogen received for localized disease in the first 12 months after diagnosis, with no receipt of radiation or radical prostatectomy. The study's main outcomes were all-cause and prostate cancer-specific mortality. The results were published online March 17 by the Journal of Clinical Oncology.

The study included data from 15,170 men, 23% of whom received PADT. Men who received PADT had higher PSA levels and higher Gleason scores than those who did not, such that 58% of the PADT group were considered high-risk by American Urological Association criteria compared with 18% of the no-PADT group. A total of 4,921 men died, 1,049 of causes related to prostate cancer. Median follow-up time was 54 months in the PADT group and 64 months in the no-PADT group. After adjusting for sociodemographic and clinical characteristics, researchers found no association between PADT and risk for all-cause mortality (hazard ratio [HR], 1.04; 95% CI, 0.97 to 1.11) or prostate cancer-specific mortality (HR, 1.03; 95% CI, 0.89 to 1.19). Lower risk for all-cause mortality was associated with PADT only in men who had a high risk for progressive disease (HR, 0.99; 95% CI, 0.78 to 0.97).

The authors noted that residual confounding might have affected their results and that the findings may have limited generalizability, among other limitations. However, they concluded that PADT conferred no mortality benefit when compared with no PADT in most men who had clinically localized prostate cancer and who did not receive therapy intended to cure the disease. PADT may confer a small clinical benefit in men whose risk for progressive disease is high, the authors found.

"Our main conclusion is that PADT does not seem to be an effective strategy as an alternative to no therapy among men diagnosed with clinical localized [prostate cancer] who are not receiving curative-intent therapy," the authors wrote. "The risks of serious adverse events and the high costs associated with its use mitigate against any clinical or policy rationale for PADT use in these men." Although the study did find a possible benefit for all-cause mortality in men at high risk for progressive disease, the authors cautioned that prescribing PADT in this population should be done only after careful consideration of the possible harms.



Pulmonary embolism


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Age-adjusted D-dimer cutoff appears better at ruling out PE

D-dimer cutoffs adjusted for age performed better than a fixed D-dimer cutoff for safely ruling out pulmonary embolism (PE), especially in elderly patients, according to a new study.

Researchers performed a multicenter prospective management outcome study in 19 centers in Europe from Jan. 1, 2010, to Feb. 28, 2010. The study's objective was to prospectively validate whether an age-adjusted D-dimer cutoff (age × 10 in patients ≥50 years of age) had better diagnostic yield than the conventional D-dimer cutoff in patients in whom PE was suspected. The study involved consecutive outpatients who presented to EDs with clinically suspected PE, defined as acute-onset or worsening shortness of breath or chest pain without another obvious cause.

Patients were evaluated by a sequential diagnostic strategy that was based on clinical probability according to the simplified revised Geneva score or the 2-level Wells score; highly sensitive D-dimer measurement; and CT pulmonary angiography (CTPA). Patients whose D-dimer value fell between the usual cutoff (500 μg/L) and their age-adjusted cutoff didn't receive CPTA or treatment but were formally followed for 3 months. The study's primary outcome was the diagnostic strategy's failure rate, as defined by thromboembolic events during the 3 months of follow-up in patients who didn't receive anticoagulants because of a negative age-adjusted D-dimer result. Three independent experts who were blinded to the criteria for ruling out PE at study inclusion adjudicated all suspected venous thromboembolic events and deaths. The study results appeared in the March 19 Journal of the American Medical Association.

Overall, 3,346 patients with suspected PE were initially included in the study. Of these, 22 did not have a D-dimer test performed and 1 withdrew consent. The prevalence of PE was 19%. A total of 2,898 patients had a nonhigh or unlikely clinical probability of PE, and of these, 817 (28.2%) had a D-dimer level below 500 μg/L and 337 had a D-dimer level that fell between the conventional cutoff and their age-adjusted cutoff. Patients with a D-dimer level higher than 500 μg/dL but lower than their age-adjusted cutoff had a 3-month diagnostic failure rate of 0.3% (95% CI, 0.1% to 1.7%).

Seven hundred seventy-six patients were at least 75 years old, and of these, 673 had a nonhigh clinical probability of PE. In this group of older patients, the age-adjusted cutoff versus the 500 μg/L cutoff allowed more patients to have PE excluded based on D-dimer testing (200 of 673 vs. 43 of 673, or 29.7% vs. 6.4%). No additional false-negative findings were noted with use of the age-adjusted cutoff in this group.

The authors noted that their study was not randomized and that the different institutions involved used different tools to assess pretest probability, as well as different commercial D-dimer assays, among other limitations. However, they concluded that age-adjusted D-dimer cutoffs, when combined with probability assessment, ruled out PE in more ED patients than the conventional cutoff and were associated with a low risk for subsequent symptomatic venous thromboembolism, especially in patients at least 75 years of age.

"Future studies should assess the clinical usefulness of the age-adjusted D-dimer cutoff in clinical practice," the authors wrote. "Whether the age-adjusted cutoff can result in improved cost-effectiveness or quality of care remains to be demonstrated."



Rheumatology


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Methotrexate monotherapy, combination therapy yield similar 1-year remission rates in early inflammatory arthritis

Patients taking methotrexate monotherapy and those taking methotrexate plus etanercept had similar rates of remission at 1 year, although those on combination therapy responded more quickly, a new study has found.

U.K. researchers conducted a 78-week multicenter, randomized, placebo-controlled superiority trial in patients 18 to 80 years of age with early inflammatory arthritis who had not previously taken disease-modifying antirheumatic drugs (DMARDs). Patients were randomly assigned to receive methotrexate plus etanercept or methotrexate plus placebo for 52 weeks. All patients had injections stopped at week 52, but injections were stopped early in patients who had no tender or swollen joints for more than 26 weeks. Methotrexate was weaned in patients who had no tender or swollen joints more than 12 weeks after injections were stopped. The study's primary end point was lack of tender or swollen joints at week 52. The results were published online March 13 by Annals of Rheumatic Diseases.

One hundred ten patients were included in the study. At week 52, no statistically significant difference was observed in the primary end point. The percentage of patients with no tender or swollen joints was 32.5% in the combination group and 28.1% in the monotherapy group (adjusted odds ratio, 1.32 [95% CI, 0.56 to 3.09]; P=0.522). In addition, secondary end points, including remission as defined by the 2011 American College of Rheumatology/European League Against Rheumatism criteria, did not differ between groups at week 52 or at week 78. More people in the combination group had a clinical response to treatment at week 2 and week 12 compared with the monotherapy group (adjusted odds ratios, 8.87 [95% CI, 2.53 to 31.17] and 2.49 [95% CI, 1.12 to 5.54]; P=0.001 and 0.026, respectively).

The authors noted that their study did not examine other available therapies and that some data were missing. However, they concluded that although patients receiving methotrexate plus etanercept had a faster response to treatment than those receiving methotrexate alone, the two therapies achieved similar effects at 1 year. The authors said their results confirm the benefit of early methotrexate treatment and dose escalation in patients with inflammatory arthritis.

"While earlier clinical responses were seen with [methotrexate plus etanercept], with maintenance of clinical and imaging responses in the majority of patients when stopping [etanercept], the value of this combination, particularly in the context of cost effectiveness, needs to be considered," the authors wrote. "Ideally, determining which patients would benefit significantly and in the longer term with initial intensive induction therapy with a biological DMARD with the possibility of biologic or even drug-free remission would be of importance."



CME


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Annals Virtual Patients test physicians' decision-making skills

Annals of Internal Medicine released a new interactive medical education tool designed to test physicians' decision-making skills. Annals Virtual Patients uses a unique "if this, then that" format, so each learner goes down his or her own path through a complex clinical simulation. Each simulation covers the examination, diagnosis, and treatment of a virtual patient. Upon completion of each case, physicians may earn Continuing Medical Education (CME) and Maintenance of Certification (MOC) credits.

Annals Virtual Patients is uniquely formatted to allow physicians to learn from mistakes as they proceed through the simulations. Selecting a response prompts a detailed explanation of the medical consequences based on the answer chosen. At the end of each case, the physician is presented with a complete summary of the clinical problem and solution.

The cases were developed by Annals of Internal Medicine editors in collaboration with faculty of the Division of General Internal Medicine at the University of Pittsburgh.



Internal Medicine 2014


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It's not too late to submit a Job Seeker's Profile to the ACP Job Placement Center

Looking for a job? ACP's Job Placement Center offers career opportunities during Internal Medicine 2014, to be held April 10-12 in Orlando, Fla. Submit a Job Seeker's Profile (mini-CV) to be included in 1 of 2 booklets based on your criteria. Your profile is guaranteed to be distributed to participating employers who submit a job posting to the center. You do not have to attend the meeting to submit a profile.

All physicians who submit a Job Seeker's Profile (limit, 1 mini-CV per physician) will be eligible for a drawing for a $100 Amazon gift card on April 12. Winners will be contacted by e-mail.

The Job Placement Center, located in the Orange County Convention Center, Exhibit Hall B2, Booth #1075, provides physicians with tools to assist in job searches, as well as the opportunity to meet with potential employers.

Submit your profile online today.



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-20140325-cartoon.jpg

"Another case of Peyronie's disease causing a reptile dysfunction."

This issue's winning cartoon caption was submitted by John A. Tenini, MD, ACP Resident/Fellow Member. Thanks to all who voted! The winning entry captured 61.8% of the votes.

The runners-up were:

"I keep telling you, Mr. S, you are OK. That's not a 'death rattle' that you are hearing."

"I hope your employer provided you with tail coverage."


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MKSAP Answer and Critique



The correct answer is C: Add a low-dose inhaled corticosteroid. This item is available to MKSAP 16 subscribers as item 54 in the Pulmonology and Critical Care section. More information is available online.

The most appropriate treatment is to add a low-dose inhaled corticosteroid (ICS). This patient has mild persistent asthma; she has symptoms more than 2 days per week but not daily and she wakes up once a week but not nightly. The preferred therapy for this patient is a low-dose ICS added to an as-needed short-acting β2-agonist. Alternatives to ICS include a leukotriene receptor antagonist or theophylline.

Adding a long-acting β2-agonist is not recommended for patients with asthma who are not already receiving ICS therapy.

Providing combination long-acting β2-agonist and ICS therapy is not indicated at this point. Based on the Expert Panel Report 3 guidelines and an FDA black box warning, patients should be started on ICS first. Long-acting β2-agonists should be added only if medium-dose ICS therapy fails to control symptoms.

Scheduled use of albuterol is not recommended, because it might mask ongoing airway inflammation and the need to provide anti-inflammatory therapy with ICS.

Allergen immunotherapy is an option for some patients, but its benefits are mostly for those with allergic rhinitis and would not be recommended for patients with mild persistent asthma.

Key Point

  • The preferred therapy for mild persistent asthma is a low-dose inhaled corticosteroid added to an as-needed short-acting β2-agonist.

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