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

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ACP InternistWeekly



In the News for the Week of June 18, 2013




Highlights

Some antibiotics taken with statins by older patients may cause more hospitalizations, all-cause mortality

Older people taking statins who were prescribed clarithromycin or erythromycin were hospitalized more frequently for rhabdomyolysis and acute kidney injury and had higher all-cause mortality than people who were prescribed azithromycin, a Canadian study found. More...

DMARD triple therapy noninferior to, but less costly than, TNF inhibitor

In rheumatoid arthritis patients in whom first-line methotrexate therapy has failed, triple therapy with disease-modifying antirheumatic drugs (DMARDs) was noninferior to the tumor necrosis factor (TNF) inhibitor etanercept plus methotrexate, a study found. More...


Test yourself

MKSAP Quiz: sudden onset of severe headache

A 56-year-old woman is evaluated in the emergency department for sudden onset of a severe generalized headache that began 36 hours ago and has not responded to over-the-counter medications. Following laboratory studies and a CT scan, what is the most appropriate next diagnostic test? More...


Mental health

Depression care reduces mortality in elderly patients

Depression care management for elderly patients eliminated the increase in mortality risk associated with major depression, a new study found. More...

Two-step screening appears effective for anxiety, depression in hospitalized cardiac patients

A two-step screening process appears to be effective for detecting generalized anxiety disorder and depression in hospitalized patients with cardiac disease, according to a new study. More...

Autoimmune disorders, infections associated with mood disorders

Autoimmune disorders and infections may increase patients' risk for mood disorders, according to a new study. More...


Cancer survival

Childhood cancer survivors develop many chronic conditions

Adult survivors of childhood cancer have an extraordinarily high rate of chronic health problems, a recent study found. More...


Practice management

Last chance to avoid e-prescribing payment penalty

June 30 is the last day you can report electronic prescriptions to avoid a payment penalty under the Medicare Electronic Prescribing program in 2014. More...

ACP can help you with the new transitional care codes

The Running a Practice section of ACP's website has detailed resources available that can help physician practices figure out the new CPT codes for transitional care management. More...


From the College

Free webinar on 2013 PQRIwizard

The Council of Medical Specialty Societies (CMSS) is offering a free webinar on the Physician Quality Reporting System (PQRS) registry tool PQRIwizard. More...

Governance Committee seeks Regent candidates for 2014

The Governance Committee oversees the process for nominating and electing Masters and Fellows of the College to the Board of Regents (BOR) and is beginning the process of seeking Regents to join the Board in May 2014. More...


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. More...


Physician editor: Philip Masters, MD, FACP



Highlights


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Some antibiotics taken with statins by older patients may cause more hospitalizations, all-cause mortality

Older people taking statins who were prescribed clarithromycin or erythromycin were hospitalized more frequently for rhabdomyolysis and acute kidney injury and had higher all-cause mortality than people who were prescribed azithromycin, a Canadian study found.

annals.jpg

Researchers conducted a population-based cohort study in Ontario, Canada, from 2003 to 2010, among statin users older than 65 who were prescribed clarithromycin (n=72,591) or erythromycin (n=3,267) compared with azithromycin (n=68,478).

Results appeared in the June 18 Annals of Internal Medicine.

The median daily dose was 1,000 mg each for clarithromycin and erythromycin and 300 mg for azithromycin. The median duration of antibiotic therapy was 10 days for clarithromycin or erythromycin and 5 days for azithromycin.

Coprescription of clarithromycin or erythromycin with a CYP3A4-metabolized statin was associated with a higher risk for hospitalization with rhabdomyolysis (relative risk [RR], 2.17; 95% CI, 1.04 to 4.53) and acute kidney injury (RR, 1.78; 95% CI, 1.49 to 2.14) compared to azithromycin. The risk for hospitalization with hyperkalemia was not statistically different (RR, 1.31; 95% CI, 0.89 to 1.94). The risk for all-cause 30-day mortality was higher with clarithromycin or erythromycin (RR, 1.56; 95% CI, 1.36 to 1.80).

Compared to azithromycin, clarithromycin or erythromycin was associated with a 0.02% (95% CI, 0.01% to 0.03%) absolute increase in hospitalization with rhabdomyolysis and a 0.25% (95% CI, 0.17% to 0.33%) increase in all-cause mortality, with corresponding numbers needed to harm of 5,870 (95% CI, 3,068 to 67,758) and 399 (95% CI, 304 to 577), respectively.

The researchers wrote, "Given the frequency at which statins are prescribed (atorvastatin is currently the most commonly prescribed drug in Canada), and the high rate of coprescription seen in our study and in other jurisdictions, this preventable drug–drug interaction remains clinically important. The results suggest that many deaths and hospitalizations with acute kidney injury in Ontario may have been attributable to this interaction."


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DMARD triple therapy noninferior to, but less costly than, TNF inhibitor

In rheumatoid arthritis patients in whom first-line methotrexate therapy has failed, triple therapy with disease-modifying antirheumatic drugs (DMARDs) was noninferior to the tumor necrosis factor (TNF) inhibitor etanercept plus methotrexate, a study found.

The study was a 48-week, double-blind, noninferiority trial at 16 Veterans Affairs hospitals, 12 Rheumatoid Arthritis Investigational Network sites, and 8 Canadian medical centers from July 2007 through December 2010. Researchers randomly assigned 353 participants to the triple DMARD regimen of methotrexate, sulfasalazine and hydroxychloroquine or to therapy with etanercept plus methotrexate.

Participants who were assigned to the triple-therapy group received sulfasalazine at a dose of 1 g daily for the first 6 weeks, with the dose increased thereafter to 2 g daily, and also received hydroxychloroquine at a dose of 400 mg daily and an injection of a placebo for etanercept weekly. Participants who were assigned to the etanercept–methotrexate group received a 50-mg injection of etanercept weekly and a placebo of sulfasalazine and hydroxychloroquine tablets daily.

The primary outcome was improvement in the Disease Activity Score for 28-joint counts (DAS28, with scores ranging from 2 to 10 and higher scores indicating more disease activity) at week 48. If the score on the DAS28 improved by 1.2 or more by 24 weeks, the initial therapy continued. If the score on the DAS28 improved by less than 1.2, the patient was switched to the alternative regimen.

Results were published June 11 by the New England Journal of Medicine.

Both groups had significant improvement during the first 24 weeks (P=0.001 for the comparison with baseline). Twenty-seven percent of participants in each group switched treatment at 24 weeks. Participants who switched therapies then improved (P<0.001), and the response after switching did not differ significantly between the two groups (P=0.08). The change in the DAS28 score between baseline and 48 weeks was similar in the two groups (−2.1 with triple therapy and −2.3 with etanercept and methotrexate, P=0.26).

The researchers concluded triple therapy was noninferior to etanercept and methotrexate, since the upper limit of the confidence interval for the difference in change in DAS28 was below the margin for noninferiority (P=0.002). There were no significant differences in secondary outcomes, including radiographic progression, pain, and health-related quality of life, or in major adverse events.

The researchers wrote, "Our findings suggest that a strategy of first administering triple therapy, with a switch to etanercept–methotrexate in patients who do not have an adequate response to triple therapy, will allow a substantial percentage of patients to be treated in a more cost-effective way without adversely affecting the clinical outcomes."

An editorial noted that in current practice, the default for patients with failure of methotrexate alone is a TNF inhibitor. Insurers might pressure physicians to switch to DMARDs due to their lower cost, or the development of new drugs may again change the playing field. "We hope that with the ever-increasing number of effective treatments for rheumatoid arthritis, future recommendations for treatment will be guided by additional comparative-effectiveness studies such as [this study]," the editorial stated.



Test yourself


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MKSAP Quiz: sudden onset of severe headache

A 56-year-old woman is evaluated in the emergency department for sudden onset of a severe generalized headache that began 36 hours ago and has not responded to over-the-counter medications. The patient has a history of hypertension treated with lifestyle modifications. She has a 30-pack-year smoking history.

mksap.gif

On physical examination, blood pressure is 148/68 mm Hg, pulse rate is 96/min and regular, and respiration rate is 16/min. Nuchal rigidity is noted. Other general examination findings are normal.

Results of laboratory studies are notable for a platelet count of 190,000/µL (190 × 109/L), an INR of 0.9, and a serum creatinine level of 0.9 mg/dL (79.6 µmol/L).

A CT scan of the head without contrast is normal.

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

A: CT of the head with contrast
B: Lumbar puncture
C: Magnetic resonance angiography of the head and neck
D: MRI of the brain without contrast

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


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Mental health


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Depression care reduces mortality in elderly patients

Depression care management for elderly patients eliminated the increase in mortality risk associated with major depression, a new study found.

Researchers screened patients age 60 and over for depression at 20 primary care practices in New York City, Philadelphia and Pittsburgh between May 1999 and August 2001. They selected 1,226 patients (396 with major depression, 203 with clinically significant minor depression and 627 not depressed) to follow through 2008 (a median follow-up of 8 years). Results were published by BMJ on June 5.

Patients with depression were randomized to usual care (educational sessions for primary care physicians and notification to the physicians of patients' depression status) or usual care plus an intervention. The intervention added education of patients' families and a depression care manager who worked in the primary care practices for two years. The care managers (social workers, nurses and psychologists) worked with physicians to recommend treatment (psychotherapy and/or antidepressants) and interacted with patients in person or by phone at scheduled intervals and as needed.

At the conclusion of follow-up, 405 patients had died. The patients with major depression who had been randomized to usual care were significantly more likely to have died than the patients without depression (hazard ratio [HR], 1.90; 95% CI, 1.57 to 2.31). However, patients with major depression who received the intervention had about the same mortality risk as patients without depression (HR, 1.09; 95% CI, 0.83 to 1.44). The study found no significant effect on mortality in patients with minor depression.

This study provides the first evidence from a randomized clinical trial that treatment of major depression can extend life, the study authors concluded. Patients in the intervention group received more antidepressant and psychotherapy treatment than those in usual care. The effects of the care manager's presence may have continued after the intervention ended, with clinicians being more sensitive to symptoms and skillful at managing depression, the authors suggested.

The study authors concluded that treatment of depression probably works on multiple pathways to interrupt the link between depression and mortality and that this study shows the importance of integrating depression care into chronic care management. Policy changes to facilitate this integration in a way that's acceptable to older patients and families are urgently needed, the authors concluded.


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Two-step screening appears effective for anxiety, depression in hospitalized cardiac patients

A two-step screening process appears to be effective for detecting generalized anxiety disorder (GAD) and depression in hospitalized patients with cardiac disease, according to a new study.

In a care management trial, researchers screened hospitalized cardiac disease patients using a four-item tool in nursing data sets (Coping Screen), a five-item screening tool for patients who tested positive on the Coping Screen (Patient Health Questionnaire-2 [PHQ-2], GAD-2, plus an item on panic attacks), and diagnostic evaluation with PHQ-9 and the anxiety disorder modules from the Primary Care Evaluation of Mental Disorders.

The aim of the study was to see how well this three-step approach identified cardiac inpatients with depression, GAD, or panic disorder, as well as to assess prevalence and to ascertain the predictive value of individual screening items. Results were published early online June 11 by Circulation: Cardiovascular Quality and Outcomes.

A total of 6,210 patients completed the Coping Screen, and 581 completed all three of the screening components. Of the 6,210 patients, 63.7% were men and the average age was 66.5 years. Two hundred ten patients (30% of those who had the five-item screen and 36% of those who had disorder-specific screening) were diagnosed, 143 with depression, 129 with GAD, and 30 with panic disorder.

Researchers controlled for age, sex and other screening items and found that the PHQ-2 items independently predicted clinical depression (odds ratios [OR], 6.65 for little interest/pleasure [P<0.001] and 5.24 for depressed mood [P=0.001]). In addition, the panic item (having experienced an anxiety attack) predicted panic disorder (OR, 49.61 [P<0.001]) and GAD-2 items predicted GAD (ORs, 4.09 for anxiety [P=0.003] and 10.46 for unable to control worrying [P<0.001]).

The authors noted that they could not determine true prevalence rates of any of the disorders they screened for and that their results may not be generalizable, among other limitations. They called the performance of the three-step screening process "suboptimal," in part because many patients were discharged before all three steps were completed, but said that the GAD-2 was "an effective screening tool."

Based on their results, which suggested that GAD and depression were equally prevalent in this population but panic disorder occurred relatively rarely, they recommended using the similarly scored PHQ-2 plus GAD-2 to screen inpatients with cardiac disease for anxiety and depression. "When scoring the frequency of each item on a scale of 0 to 3 (0=not at all, 1=several days, 2=more than half the days, 3=nearly every day), a total score of ≥6 should signal clinicians to investigate the symptoms further," the authors wrote.


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Autoimmune disorders, infections associated with mood disorders

Autoimmune disorders and infections may increase patients' risk for mood disorders, according to a new study.

Researchers performed a nationwide population-based prospective cohort study to evaluate the relationship between risk for mood disorders and autoimmune diseases and infections. Data encompassing 78 million person-years of follow-up were obtained from longitudinal registers in Denmark. Survival analysis techniques were used for analysis, and data were adjusted for calendar year, age and sex. The study's main outcome measure was the risk for first lifetime diagnosis of a mood disorder from a psychiatrist at a hospital, outpatient clinic or emergency department.

Mood disorders were classified as bipolar affective disorder, unipolar depression, psychotic depression, or a group of any of the remaining mood disorders. Results were published early online June 12 by JAMA Psychiatry.

Overall, 3.56 million people born between 1945 and 1996 were followed from Jan. 1, 1977, through Dec. 31, 2010. Of these, 91,637 (55,677 women and 35,960 men) were diagnosed with a mood disorder.

Previous hospital contact because of autoimmune disease appeared to increase the subsequent risk for mood disorder diagnosis (incidence rate ratio [IRR], 1.45; 95% CI, 1.39 to 1.52), as did history of hospitalization for infection (IRR, 1.62; 95% CI, 1.60 to 1.64). When both of these risk factors were present, the mood disorder risk appeared even higher (IRR, 2.35; 95% CI, 2.25 to 2.46), and a dose-response relationship was noted. Thirty-two percent and 5% of patients with mood disorders had previous hospital contact for infection and autoimmune disease, respectively.

The authors acknowledged that recording of the time of disease onset may have been biased and that their study did not include less severe cases of any of the disorders studied. However, they wrote, "The associations found in this study suggest that autoimmune diseases and infections are important etiologic factors in the development of mood disorders in subgroups of the patients possibly because of the effects of inflammatory activity." It's still unclear, they said, how the brain is affected by the immunologic process and whether there is a causal relationship.



Cancer survival


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Childhood cancer survivors develop many chronic conditions

Adult survivors of childhood cancer have an extraordinarily high rate of chronic health problems, a recent study found.

Beginning in October 2007, researchers conducted systematic exposure-based medical assessments of 1,713 adult survivors of childhood cancer who were enrolled in the St. Jude Lifetime Cohort Study. The patients had a median age of 32 and a median time from diagnosis of their cancer of 25 years. Results were published in the June 12 Journal of the American Medical Association.

Overall, by age 45, the survivors had an estimated cumulative presence of 95.5% for any chronic health condition and 80.5% for chronic problems that were serious, disabling or life-threatening. Abnormal pulmonary function was the most common problem, affecting 65.2% of study participants, followed by hearing loss (62.1%), endocrine disorders (62.0%), cardiac conditions (56.4%) and neurocognitive impairment (48%). Hepatic, skeletal, renal and hematopoietic dysfunctions were less common (liver dysfunction, 13%; osteoporosis, 9.6%; kidney dysfunction, 5%; abnormal blood cell counts, 3%).

This study differs from most previous analyses in its use of comprehensive assessments to identify undiagnosed conditions, rather than relying on patient self-reports. Such assessments are helpful to identify conditions that may be remediated (such as low-stage occult breast cancer in women treated with chest radiation or cardiomyopathy in patients exposed to anthracyclines and chest radiation) or at least monitored (reduced cognitive status and memory in patients who had 24-Gy cranial irradiation), the authors said.

Many of the problems found during the assessments are more typical of older patients, and therefore concerning in a population with a median age of only 32. It may indicate a pattern of accelerated or premature aging in these patients, who will continue to be followed for future research. The observation of differences in rates of various chronic conditions may be helpful to refine screening recommendations, the authors noted.

The study was limited by only 60% participation in the follow-up screening, but still the findings underscore the need for ongoing monitoring in these patients, especially focused on conditions that have significant morbidity if not detected early (such as malignancies) and those that can be remediated (such as hearing loss).



Practice management


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Last chance to avoid e-prescribing payment penalty

June 30 is the last day you can report electronic prescriptions to avoid a payment penalty under the Medicare Electronic Prescribing program in 2014.

If you do not successfully e-prescribe, or successfully file a hardship exemption, you will receive a 2% penalty on all Medicare Part B claims in 2014. If you still need to complete your e-Rx submissions, or if you're not sure whether you've satisfied the program, please check out the eRx page on the Running a Practice section of the College website.


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ACP can help you with the new transitional care codes

The Running a Practice section of ACP's website has detailed resources available that can help physician practices figure out the new CPT codes for transitional care management.

Visit the College's Running a Practice website to find a list of articles with discussion about the care components of the codes, the time constructs for the postdischarge contact with the patient, the face-to-face visit, and the 30-day care period.



From the College


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Free webinar on 2013 PQRIwizard

The Council of Medical Specialty Societies (CMSS) is offering a free webinar on the Physician Quality Reporting System (PQRS) registry tool PQRIwizard. This informational webinar will be held on June 25, 2013, at noon Eastern Standard Time.

PQRIwizard is ACP's online registry tool designed to help physicians and other eligible professionals quickly and easily participate in the PQRS program. ACP members can purchase PQRIwizard at a discounted rate.

Physician members and practice managers are encouraged to participate in this webinar. Those who report in 2013 will receive a 0.5% bonus from Medicare.

The webinar is free, but registration is required.


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Governance Committee seeks Regent candidates for 2014

The Governance Committee oversees the process for nominating and electing Masters and Fellows of the College to the Board of Regents (BOR) and is beginning the process of seeking Regents to join the Board in May 2014.

The Governance Committee will strive to represent the diversity within internal medicine on ACP's Board of Regents. Important general qualifications include commitment to ACP, dependability, leadership qualities, and the ability to represent the College in numerous and diverse arenas. Regent nominees must be Fellows or Masters of the College.

All candidates for Regent must submit a letter of nomination (not from the candidate) and two letters of support (from two individuals other than the nominator) by Aug. 1, 2013.

Letters of nomination should include the following sections:

  • brief description of the nominee's current activities,
  • special attributes the candidate would bring to the BOR in terms of the desired characteristics outlined above,
  • previous and current service in College-related activities,
  • service in organizations other than the College (medical and nonmedical) and
  • identification of two individuals who will write letters of support for the candidate.

Letters of support do not need to have specific content or format but will be most useful if they focus on the candidate's qualifications and how he or she would contribute to the BOR and the College.

Please send your confidential nominations, no later than Aug. 1, 2013, to:

Governance Committee

ATTN: Mrs. Florence Moore

American College of Physicians

190 N. Independence Mall West

Philadelphia, PA 19106-1572

Fax: 215-351-2829

e-mail: fmoore@acponline.org

Only candidates who submit a letter of nomination and two letters of support by Aug. 1, 2013, will be advanced to the Governance Committee for review.



Cartoon caption contest


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Vote for your favorite entry

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

acpi-20130618-cartoon.jpg

"Oh great, another super bug."

"You must be the new stool culture testing technician."

"... and make sure you stay off the Web."

Go online to pick the winner, who receives a $50 gift certificate good toward any ACP program, product or service. Voting ends on July 24, with the winner announced in the July 25 issue.


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MKSAP Answer and Critique



The correct answer is B: Lumbar puncture. This item is available to MKSAP 16 subscribers as item 24 in the Neurology section. More information is available online.

This patient should have a lumbar puncture. At presentation, she has sudden onset of a severe headache, which is most concerning for subarachnoid hemorrhage. In a minority of patients with a small amount of blood in the subarachnoid space, a head CT may initially be normal. When this occurs, a lumbar puncture is required to detect erythrocytes or xanthochromia (a yellowish discoloration caused by the breakdown of erythrocytes) in the cerebrospinal fluid (CSF). Because xanthochromia may not develop for 6 hours or longer after the initial event, the presence of erythrocytes in the CSF should prompt consideration of a subarachnoid hemorrhage. A lumbar puncture is also helpful for excluding other diagnoses, such as meningitis, and for measuring the opening pressure.

Because the initial CT of the head without contrast was normal, a CT with contrast is unlikely to show a mass lesion sufficient in size to cause headache. CT angiography or venography may eventually be used to rule out aneurysms or dural sinus thrombosis, but subarachnoid hemorrhage first needs to be ruled out in the acute setting.

Although magnetic resonance angiography (MRA) eventually may be necessary to exclude dissection or aneurysms as the cause of this patient's symptoms, it is inappropriate at this time. Unless the presence of a subarachnoid hemorrhage is first established, an aneurysm detected on MRA or other vascular imaging may be an incidental finding that does not require surgical intervention.

The effectiveness of MRI for diagnosing subarachnoid hemorrhage remains under investigation. Additionally, MRI is time consuming and may not differentiate subarachnoid hemorrhage from other diagnoses well enough. Unlike CSF analysis, MRI does not afford the additional benefit of measuring the CSF opening pressure.

Of note, clinical examination findings, including those from funduscopy, have insufficient sensitivity and specificity to establish the diagnosis of subarachnoid hemorrhage.

Key Point

  • In a patient with a suspected subarachnoid hemorrhage and normal results on a head CT scan, a lumbar puncture is the most appropriate next step in evaluation.

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Test yourself

A 38-year-old man is evaluated for a mass in his right neck that he first noticed 2 weeks ago while shaving. The patient also reports experiencing a pressure sensation when swallowing solid foods for the past year and daily diarrhea for the past 2 months. His personal medical history is unremarkable. His younger brother has nephrolithiasis, and his father died of a hypertensive crisis and cardiac arrest at age 62 years while undergoing anesthesia induction to repair a hip fracture. Following a physical exam, lab studies, and a chest radiograph, what is the most likely diagnosis?

Find the answer

MKSAP 16 Holiday Special: Save 10%

MKSAP 16 Holiday Special:  Save 10%

Use MKSAP 16 to earn MOC points, prepare for ABIM exams and assess your clinical knowledge. For a limited time save 10% when you use priority code MKPROMO! Order now.

Maintenance of Certification:

What if I Still Don't Know Where to Start?

Maintenance of Certification: What if I Still Don't Know Where to Start?

Because the rules are complex and may apply differently depending on when you last certified, ACP has developed a MOC Navigator. This FREE tool can help you understand the impact of MOC, review requirements, guide you in selecting ways to meet the requirements, show you how to enroll, and more. Start navigating now.