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

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ACP InternistWeekly



In the News for the Week of June 10, 2014




Highlights

Higher-potency statins associated with more new diabetes cases

Patients taking higher-potency statins for secondary prevention are more likely to develop diabetes than those on lower-potency statins, a new study found. More...

Lifetime risks of hypertension quantified by large U.K. database

Blood pressure affects cardiovascular risk differently across different diseases and age ranges, according to a large, new study. More...


Test yourself

MKSAP Quiz: 1-year history of cough

A 38-year-old man is evaluated for a 1-year history of cough with mucoid sputum and a 6-month history of mildly progressive dyspnea. He has a 12-pack-year history of smoking. He has no history of asthma, allergies, skin disease, or liver disease. Following physical and pulmonary exams and lab studies, what is the most appropriate next step in management? More...


Infectious disease

CDC issues health advisory on polio vaccination for international travelers

The CDC issued a health advisory last week on polio vaccination for international travelers. More...

Two drugs may make skin structure infections easier to manage

Two new drugs may make acute bacterial skin and skin-structure infections easier to manage, including on an outpatient basis, according to 2 new studies. More...


Anticoagulation

Rivaroxaban has similar safety, efficacy versus warfarin in older and younger nonvalvular afib patients

Rivaroxaban appears to have similar safety and efficacy compared with warfarin in both older and younger patients with nonvalvular atrial fibrillation, although stroke and major bleeding rates were higher in the former group, a new study found. More...


Maintenance of certification

ACP provides update about ABIM's MOC program

In response to numerous concerns and complaints expressed by ACP members about the Maintenance of Certification (MOC) requirements from the American Board of Internal Medicine (ABIM), ACP leaders have made the MOC issue their number-one priority and outlined recent steps taken by the College to address members' concerns. More...


From Annals of Internal Medicine

Annals calls for Personae photographs in celebration of ACP's centennial

In recognition of the American College of Physicians' 100th anniversary, Annals of Internal Medicine is seeking photographs of internal medicine physicians to feature on each issue of the journal during 2015, ACP's centennial year. More...


CMS update

Reminder: CMS Open Payment registration began June 1

On June 1, physicians and teaching hospital representatives could begin registering to participate in the Physician Payments Sunshine Act/Open Payment Program. More...


From the College

Governance Committee seeks Regent candidates for 2015

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 2015. More...


Cartoon caption contest

Put words in our mouth

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


Physician editor: Philip Masters, MD, FACP



Highlights


.
Higher-potency statins associated with more new diabetes cases

Patients taking higher-potency statins for secondary prevention are more likely to develop diabetes than those on lower-potency statins, a new study found.

The multicenter observational study included more than 130,000 U.S., Canadian, and British patients who were started on a statin after hospitalization for a major cardiovascular event or procedure. They were all 40 years of age or older and were first prescribed a statin between January 1997 and March 2011. The main outcome was new onset of diabetes, measured by a hospitalization for diabetes or a prescription for insulin or an oral antidiabetic drug. None of the patients had been diagnosed with diabetes as of their initial cardiac hospitalization.

The patients taking higher-potency statins had a significantly higher risk of developing diabetes in the first 2 years of taking the drugs (rate ratio [RR] compared to lower-potency users, 1.15; 95% CI, 1.05 to 1.26). The risk difference was greatest in the first 4 months of use (RR, 1.26; 95% CI, 1.07 to 1.47). Results were published by BMJ on May 29.

Use of higher-potency statins instead of lower-potency ones is associated with a moderate increase in diabetes risk in this secondary prevention population, the study authors concluded. These results are similar to those of some other meta-analyses and have plausible mechanisms to explain them. Some experts argue that the increased risk of diabetes is outweighed by greater protection against cardiovascular events with the higher-potency drugs, but their data come from trials that were not specifically designed to record diabetes events, the authors said.

Head-to-head comparisons of higher- and lower-potency statins have shown no difference in mortality or serious adverse events, so given this lack of benefit, clinicians should consider the risk of diabetes when choosing a statin for secondary prevention of cardiovascular disease, the authors concluded.


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Lifetime risks of hypertension quantified by large U.K. database

Blood pressure affects cardiovascular risk differently across different diseases and age ranges, according to a large, new study.

British researchers used electronic health records to gather data on 1.25 million patients who were at least 30 years of age between 1997 and 2010, all initially free of cardiovascular disease. One-fifth were treated with blood pressure medication. The median follow-up was 5.2 years. Results were published in The Lancet on May 31.

Overall, 83,098 patients developed cardiovascular disease. The lowest risk for cardiovascular disease was found in patients with a systolic blood pressure of 90 to 114 mm Hg and a diastolic blood pressure of 60 to 74 mm Hg. This was true across all age groups, and no J-shaped pattern of increased risk at the lower pressures was found. The researchers also looked at what types of cardiovascular disease were most strongly predicted by hypertension and found that high systolic pressure was most strongly associated with intracerebral hemorrhage (hazard ratio [HR], 1.44; 95% CI, 1.32 to 1.58), subarachnoid hemorrhage (HR, 1.43; 95% CI, 1.25 to 1.63), and stable angina (HR, 1.41; 95% CI, 1.25 to 1.63). On the other end of the spectrum, high systolic pressure was not significantly associated with aortic aneurysm at all; high diastolic pressure was a better predictor.

Looking at lifetime risk from age 30 on, the study found that hypertension patients (defined as those having blood pressure over 140/90 mm Hg or those taking antihypertensives) had a 63.3% risk of cardiovascular disease, compared to 46.1% in patients with normal blood pressure. The hypertensive patients developed cardiovascular disease 5 years earlier on average. Stable and unstable angina accounted for the greatest share of cardiovascular disease in younger hypertensive patients, while heart failure had an equal share to angina in patients age 80 and over.

The findings conflict with some widely held assumptions about the associations between hypertension and all cardiovascular diseases as well as the concordance between diastolic and systolic pressures and risk. The evidence of substantial lifetime effects from hypertension offer support for treating mild hypertension in younger patients, a current topic of debate. The results also support a recent shift to focus on systolic, rather than diastolic, pressure. Clinicians could generally use the study's data about specific risks to improve patient counseling and treatment decisions, the authors concluded.

An accompanying comment suggested several targets for improvement in hypertension treatment, including risk assessment, patient education and decision making, caregiver support and education, medication compliance, use of home and ambulatory monitoring, recognition of secondary hypertension, and referral to specialty care.



Test yourself


.
MKSAP Quiz: 1-year history of cough

A 38-year-old man is evaluated for a 1-year history of cough with mucoid sputum and a 6-month history of mildly progressive dyspnea. He has a 12-pack-year history of smoking. He has no history of asthma, allergies, skin disease, or liver disease.

mksap.gif

On physical examination, vital signs are normal. Pulmonary examination discloses decreased breath sounds bilaterally with no wheezing.

Laboratory studies, including a complete blood count and complete metabolic panel, are normal. Oxygen saturation is 97% breathing ambient air. The electrocardiogram is normal. CT scan of the chest shows basilar lucency without bronchiectasis. Spirometry reveals an FEV1 of 53% of predicted and an FEV1/FVC ratio of 64%. The DLCO is 67% of predicted. There is no significant improvement in airflow after bronchodilator administration.

Which of the following is the most appropriate next step in management?

A: α1-Antitrypsin level measurement
B: Initiation of an inhaled corticosteroid
C: Sweat chloride testing
D: Z and S genotyping for α1-antitrypsin alleles

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


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Infectious disease


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CDC issues health advisory on polio vaccination for international travelers

The CDC issued a health advisory last week on polio vaccination for international travelers.

In May, the World Health Organization (WHO) declared the international spread of polio to be a "public health emergency of international concern" and issued new vaccination requirements for travelers. As a result, the CDC issued a health advisory noting that U.S. clinicians should be aware of possible new vaccination requirements for patients planning to travel for longer than 4 weeks to countries with ongoing poliovirus transmission.

According to the WHO, 3 countries—Cameroon, Pakistan, and Syria (Syrian Arab Republic)—have been designated as "exporting wild poliovirus" and should "ensure" recent (4 to 52 weeks before travel) polio boosters among all departing residents and long-term travelers of more than 4 weeks. An additional 7 countries—Afghanistan, Equatorial Guinea, Ethiopia, Iraq, Israel, Somalia, and Nigeria—have been designated as "infected with wild poliovirus" and should "encourage" recent polio vaccination boosters among residents and long-term travelers.

The CDC noted that it routinely recommends full vaccination against polio for anyone planning to travel to a polio-affected country and a one-time booster dose of polio vaccine for adults. Anyone who stays in one of the recently named polio-affected countries for more than 4 weeks may be required to have a polio booster shot within the 4 weeks to 12 months prior to departure from that country. The CDC recommends that this booster be documented in patients' yellow International Certificate of Vaccination to avoid delays in transit or forced vaccination.

More information on the CDC's health advisory is available online.


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Two drugs may make skin structure infections easier to manage

Two new drugs may make acute bacterial skin and skin-structure infections easier to manage, including on an outpatient basis, according to 2 new studies.

In the first paper, researchers reported on 2 trials that randomized a total of 1,303 patients at sites around the world to either vancomycin with the option to cross over to oral linezolid or dalbavancin. Dalbavancin was administered at a dose of 1 g for 30 minutes on day 1, followed on day 8 by 500 mg given intravenously for 30 minutes. Vancomycin was given at a dose of 1 g (or 15 mg per kg of body weight) for 120 minutes every 12 hours for at least 3 days, with an option to switch to oral linezolid, at a dose of 600 mg every 12 hours. The research was funded by the drug's manufacturer, Durata Therapeutics. Results appeared June 5 in the New England Journal of Medicine (NEJM).

In a pooled analysis of both trials, 525 of 659 patients (79.7%) in the dalbavancin group and 521 of 653 (79.8%) in the vancomycin-linezolid group had an early clinical response, defined as cessation of spread of infection-related erythema and the absence of fever at 48 to 72 hours (weighted difference, −0.1 percentage point; 95% CI, −4.5 to 4.2). In individual analyses of the trials, the early clinical response rates were not significantly different between the drugs. The researchers concluded that dalbavancin was noninferior to vancomycin-linezolid in each trial. For patients infected with Staphylococcus aureus, including methicillin-resistant S. aureus, clinical success was seen in 90.6% of the patients treated with dalbavancin and 93.8% of those treated with vancomycin-linezolid.

Fewer patients in the dalbavancin group reported adverse events than those in the vancomycin-linezolid group, and most events were mild and thought to be unrelated to the treatment. The most common treatment-related adverse events were nausea (2.5% in the dalbavancin group and 2.9% in the vancomycin-linezolid group, P=0.062), diarrhea (0.8% and 2.5%; P=0.02), and pruritus (0.6% and 2.3%; P=0.01).

The researchers noted that results were robust in patients with major abscess, cellulitis, or wound infection and in outpatients. "Patients included in the study were ill enough to require intravenous therapy and hospital referral or admission and had a high rate of fever," the researchers wrote. "Approximately 50% of the patients in our study met the criteria for the systemic inflammatory response syndrome."

Dalbavancin was recently approved by the FDA to treat acute bacterial skin and skin-structure infections caused by susceptible bacteria, including S. aureus (including methicillin-susceptible and methicillin-resistant strains) and Streptococcus pyogenes.

A second study published in the same issue of NEJM found that a single dose of oritavancin was noninferior to twice-daily IV vancomycin for acute bacterial skin and skin-structure infections caused by gram-positive pathogens.

Funded by the Medicines Company, the double-blind trial randomized 954 adults with acute bacterial skin and skin-structure infections to either a single IV dose of 1,200 mg of oritavancin or IV vancomycin twice daily for 7 to 10 days. All 3 efficacy end points met the prespecified noninferiority margin: early clinical evaluation, 82.3% vs. 78.9% (95% CI, −1.6 to 8.4 percentage points); investigator-assessed clinical cure, 79.6% vs. 80.0% (95% CI, −5.5 to 4.7 percentage points); and proportion of patients with a reduction in lesion area of 20% or more, 86.9% versus 82.9% (95% CI, −0.5 to 8.6 percentage points). Efficacy was similar when assessed by strain of pathogen, including methicillin-resistant S. aureus. Adverse event rates were also similar, although nausea was more common among those treated with oritavancin. Oritavancin has not yet been approved by the FDA.

An editorial related to both studies commented that while both drugs have been available since the 1990s, they could transform the treatment of acute bacterial skin and skin-structure infection.

"Neither antibiotic is more efficacious than vancomycin, but either agent is certainly easier to administer," the editorial stated. "These agents make it possible to treat patients with complicated skin and skin-structure infections, who might otherwise require hospitalization, on an outpatient basis without compromising efficacy and without the need for laboratory monitoring or an indwelling intravenous catheter. This approach could profoundly affect how these infections are managed, by reducing or in some cases eliminating costs and risks of hospitalization."



Anticoagulation


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Rivaroxaban has similar safety, efficacy versus warfarin in older and younger nonvalvular afib patients

Rivaroxaban appears to have similar safety and efficacy compared with warfarin in both older and younger patients with nonvalvular atrial fibrillation, although stroke and major bleeding rates were higher in the former group, a new study found.

Researchers from the ROCKET AF trial, which was funded by Johnson & Johnson Pharmaceutical Research & Development and Bayer Healthcare, performed a prespecified secondary analysis to compare outcomes of rivaroxaban and warfarin treatment in older versus younger patients. Patients were included in ROCKET AF if they had nonvalvular atrial fibrillation and previous stroke, transient ischemic attack, or systemic embolism or at least 2 risk factors for stroke. Patients were randomly assigned to receive adjusted-dose warfarin with a target international normalized ratio of 2.0 to 3.0 or rivaroxaban, 20 mg/d (15 mg/d in those with a creatinine clearance <50 mL/min). The primary study end point was stroke and systemic embolism according to intention to treat. The study results were published online June 3 by Circulation.

ROCKET AF included 14,264 patients, 6,229 of whom (44%) were 75 years of age or older. The median age was 79 years in elderly patients and 66 years in younger patients. The study involved a total of 10,866 patient-years of exposure, over which rates of primary events (2.57% vs. 2.05% per 100 patient-years; P=0.0068) and major bleeding (4.63% vs. 2.74% per 100 patient-years; P<0.0001) were higher in older patients than in younger patients. However, for rivaroxaban versus warfarin, rates of stroke and systemic embolism as well as major bleeding were consistent among older and younger patients. Stroke and systemic embolism occurred among 2.29% of elderly patients taking rivaroxaban and 2.85% of those taking warfarin per 100 patient-years (hazard ratio, 0.80; 95% CI, 0.63 to 1.02), while rates among younger patients were 2.00% versus 2.10% per 100 patient-years (hazard ratio, 0.95; 95% CI, 0.76 to 1.19). Major bleeding rates among elderly patients were 4.86% per 100 patient-years in those taking rivaroxaban and 4.40% per 100 patient-years in those taking warfarin (hazard ratio, 1.11; 95% CI, 0.92 to 1.34), compared with 2.69% versus 2.79% per 100 patient-years in younger patients (hazard ratio, 0.96; 95% CI, 0.78 to 1.19). Rates of hemorrhagic stroke were also similar in both younger and older patients.

The authors noted that ROCKET AF might not have lasted long enough to capture the true rates of potential adverse events and that included patients were all at fairly high risk for stroke, among other limitations. However, they wrote, "The main clinical implication of this study is that in elderly patients with nonvalvular [atrial fibrillation] at high risk of stroke, factor Xa inhibition with rivaroxaban is as effective as adjusted-dose anticoagulation with warfarin."

An accompanying editorial pointed out that "new oral anticoagulants may offer increased convenience for elderly patients, because of their more predictable pharmacologic profiles, a rapid onset of action, a broader therapeutic window, and no specific requirement for routine coagulation monitoring," in addition to fewer food and drug reactions than warfarin. The authors suggested that existing bleeding risk scores could be improved in the elderly and noted that warfarin is still the preferred therapy in some patients, such as those with mechanical valves or left ventricular thrombi and those in whom the ability to monitor international normalized ratio is helpful. Warfarin is also less expensive, the authors stressed.

"Regardless of the medication chosen, however, older patients must always be treated cautiously due to an increased risk of stroke and bleeding, and additional challenges related to drug interactions," the editorialists wrote. "As additional data is gathered in this large and higher risk population, our ability to guide optimal use in terms of risk/benefit as well as choose the optimal medication/dosage and mitigate drug interaction, will expand and lead to better care of our older patients. However, while there is no doubt about the benefits of oral anticoagulation in the elderly, focus must be placed on reducing their risk."



Maintenance of certification


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ACP provides update about ABIM's MOC program

In response to numerous concerns and complaints expressed by ACP members about the Maintenance of Certification (MOC) requirements from the American Board of Internal Medicine (ABIM), ACP leaders have made the MOC issue their number-one priority and outlined recent steps taken by the College to address members' concerns.

In a letter to members, ACP leaders cited an editorial published in Annals of Internal Medicine, co-authored by ACP's current Chair of the Board of Regents, the President, and the Chair of the Board of Governors; a meeting held in March with leaders from the internal medicine subspecialty societies; and a series of ongoing meetings and discussions between elected leaders and the CEOs of ACP and ABIM.

ACP is committed to addressing the issue and achieving the best outcomes for members and their patients. The letter in its entirety is available online.



From Annals of Internal Medicine


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Annals calls for Personae photographs in celebration of ACP's centennial

In recognition of the American College of Physicians' 100th anniversary, Annals of Internal Medicine is seeking photographs of internal medicine physicians to feature on each issue of the journal during 2015, ACP's centennial year.

Annals of Internal Medicine will choose photos that capture personality and celebrate the diversity of individuals who devote their professional lives to the practice of internal medicine. Readers and others are encouraged to submit photographs of internal medicine physicians for consideration.

Written permission to publish the photograph from the subject (or subjects) of the photograph or the subject's guardian or next of kin must accompany submissions. The subject must understand that, if selected for publication, the photograph will not only appear on the cover of the journal but also in digital versions of the journal and associated publications.

More information about the submission process is available online.



CMS update


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Reminder: CMS Open Payment registration began June 1

On June 1, physicians and teaching hospital representatives could begin registering to participate in the Physician Payments Sunshine Act/Open Payment Program.

This program will publicly report specified transfer of value and ownership information between industry and physicians/teaching hospitals made between Aug. 1 and Dec. 31, 2013. Although registration is a voluntary process, it is required if the physician or teaching hospital wants to review and dispute any of the data reported about them by industry prior to public release. Further registration information is available online.



From the College


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Governance Committee seeks Regent candidates for 2015

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 2015.

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 2 individuals other than the nominator) by Aug. 1, 2014.

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 non-medical), and
  • identification of 2 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 College.

Please send your confidential nominations, no later than Aug. 1, 2014, 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, 2014, will be advanced to the Governance Committee for review.

If you have any questions, please contact Florence Moore toll free at (800) 523-1546, ext. 2814, or direct at (215) 351-2814.



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.

acpi-20140610-cartoon.jpg

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


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MKSAP Answer and Critique



The correct answer is A: α1-Antitrypsin level measurement. This item is available to MKSAP 16 subscribers as item 93 in the Pulmonology and Critical Care section. More information is available online.

The most appropriate next step in management is measurement of the α1-antitrypsin (AAT) level. This patient's symptoms and spirometry findings are consistent with COPD. In this young patient with COPD, AAT deficiency is a likely cause. AAT is an antiproteolytic enzyme that neutralizes neutrophil elastase. AAT deficiency results in excessive amounts of neutrophil elastase in the lung, which destroys elastin and causes early-onset obstructive pulmonary disease, typically panacinar emphysema with basilar predominance. Some patients with AAT deficiency may develop liver and skin disorders. AAT deficiency should be evaluated in selected patients with COPD because of the availability of specific therapy. AAT deficiency should be considered in patients with persistent airflow obstruction (particularly those diagnosed with COPD at age 45 years or younger), nonsmokers with emphysema, patients with predominantly basilar lung disease, and patients with chronic liver disease.

Inhaled corticosteroids may be indicated in patients with severe COPD in addition to a long-acting bronchodilator, but they should not be used as monotherapy in any stage of COPD.

Sweat chloride testing is the diagnostic test for cystic fibrosis. Bronchiectasis and purulent sputum are hallmarks of this disease. However, this patient has no evidence of bronchiectasis on CT scan. Patients with this degree of airflow obstruction and no purulent sputum would not have cystic fibrosis.

Genotyping for the most common AAT alleles is usually performed in patients who have documented deficiency of AAT, but it is premature to perform genotyping before documenting AAT deficiency.

Key Point

  • α1-Antitrypsin deficiency should be evaluated in selected patients with COPD because of the availability of specific therapy.

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Test yourself

A 66-year-old man comes for a preoperative evaluation before total joint arthroplasty of the left knee. He has a 25-year history of rheumatoid arthritis. He has had progressive pain in his left knee with activity, which limits his ability to hike. The patient has similar pain in the right knee, but it is less severe. He reports no recent morning stiffness. He is able to climb two or three flights of stairs without chest pain or shortness of breath. He has no other medical problems and reports no additional symptoms. Medications are methotrexate and folic acid. Following a physical exam and lab tests, what is the next best step in management?

Find the answer

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