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

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ACP InternistWeekly



In the News for the Week of May 21, 2013




Highlights

Three questions improve physicians' predictions of musculoskeletal pain treatment outcomes

Three questions can predict whether an older patient with musculoskeletal pain will still have pain six months later, a study found. More...

Age, comorbidity should inform decisions on how to treat low- or intermediate- risk prostate cancer

Older men with prostate cancer and multiple major comorbid conditions are at high risk for other-cause mortality within 10 years of diagnosis and should consider this when deciding between conservative management and aggressive treatment for low- or intermediate-risk disease, a study concluded. More...


Test yourself

MKSAP Quiz: 5-day history of leg pain and swelling

A 52-year-old man is evaluated in the emergency department for a 5-day history of right leg pain and swelling. He has never had a previous episode of venous thromboembolism. More...


Statins

Model may predict which coronary artery disease patients benefit from high-dose statins

Incremental treatment effects of high-dose statin therapy over usual-dose statin therapy in coronary artery disease patients can be estimated by a prediction model made up of 13 easy-to-measure clinical predictors that are readily available in clinical practice, a study concluded. More...

Intensive-dose statins don't confer greater diabetes risk for post-MI elderly than moderate doses

Older patients with myocardial infarction (MI) who take intensive-dose statins have the same risk of developing diabetes as those who take moderate-dose statins, a new study found. More...


Women's health

Midlife surgical menopause not associated with increased cardiovascular risk when compared to natural menopause

Hysterectomy with or without oophorectomy in midlife was not associated with increased risk for cardiovascular disease (CVD) in a new study. More...


From the College

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

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...

Editorial note: ACP InternistWeekly will not be published next week due to the Memorial Day holiday.


Physician editor: Daisy Smith, MD, FACP



Highlights


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Three questions improve physicians' predictions of musculoskeletal pain treatment outcomes

Three questions can predict whether an older patient with musculoskeletal pain will still have pain six months later, a study found.

The prospective observational cohort study included 403 consecutive patients, age 50 or older, presenting to a general practice in the United Kingdom with noninflammatory musculoskeletal pain. The treating physicians asked the patients five questions about their pain and then recorded their own prognostic judgments. Patients were interviewed about their pain symptoms six months later, and researchers compared accuracy of the physicians' prognostication alone with a combination of their prognostication and some of the interview questions.

Results were published on May 13 by JAMA: Internal Medicine.

Three questions asked at the initial visit improved identification of patients who still had pain after six months:

  • When was the last time you were free of pain for a month or more? (Less than three months or at least three months)
  • In the last month, how much has this pain interfered with your daily activities, where 0 is no interference and 10 is unable to carry on? (0-4 or 5-10)
  • Have you had pain anywhere else in the last month? (Yes or no)

Overall, 48.1% of the study participants still had pain at six months, and the combination of the indicators and physician judgment predicted 69% of them (C-statistic, 0.72 for combination vs. 0.62 for physician judgment). The questions improved prognostication by correcting physicians' tendency to predict overly optimistic outcomes, the researchers found.

The identification of these predictive, easy-to-obtain pieces of information could help with the "bewildering proliferation of tools developed for each of the many different syndromes and sites of musculoskeletal pain" and eventually lead to development of a risk score like those used to predict cardiovascular disease, the study authors said. Identification of patients who are likely to have long-term pain could allow physicians to target interventions at those who need them most, the study authors said.

An accompanying editorial noted that individualization of pain treatment is important and that overly optimistic prognostications can delay important discussions of factors that could influence long-term patient management, including depression and avoidance of activities.


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Age, comorbidity should inform decisions on how to treat low- or intermediate- risk prostate cancer

Older men with prostate cancer and multiple major comorbid conditions are at high risk for other-cause mortality within 10 years of diagnosis and should consider this when deciding between conservative management and aggressive treatment for low- or intermediate-risk disease, a study concluded.

annals.jpg

Specifically, risk for other-cause mortality increased with the number of major comorbid conditions, particularly in older men, the study noted. Prostate cancer mortality varied according to disease risk but not by number of comorbid conditions.

Researchers conducted a nationally representative, population-based, prospective cohort study among 3,183 men with nonmetastatic prostate cancer. Data were drawn from the Prostate Cancer Outcomes Study, a population-based cohort of men diagnosed with prostate cancer reported to the National Cancer Institute Surveillance, Epidemiology and End Results program.

Results were published in the May 21 Annals of Internal Medicine.

Fourteen-year cumulative other-cause mortality rates were 24%, 33%, 46% and 57% for men with zero, one, two and three or more comorbid conditions, respectively. For men diagnosed at age 65 years, subhazard ratios for other-cause mortality among those with one, two or three or more comorbid conditions versus none were 1.2 (95% CI, 1.0 to 1.4), 1.7 (95% CI, 1.4 to 2.0), and 2.4 (95% CI, 2.0 to 2.8), respectively.

Among men with three or more comorbid conditions, 10-year mortality rates for other causes were 26%, 40% and 71% for those age 60 or younger, those age 61 to 74, and those age 75 or older at diagnosis, respectively. Prostate cancer-specific mortality was 3% in patients with low-risk disease, 7% for those with intermediate-risk disease and 18% for those with high-risk disease. It varied by 10% to 11% among all numbers of comorbid conditions.

Aggressive therapy may benefit men with little or no comorbid disease, but it is not as valuable in men with more comorbidities, a competing-risks model suggested. Men with zero or one comorbid condition who were managed conservatively had increases of 2.4 (95% CI, 1.6 to 3.5) and 2.2 (95% CI, 1.5 to 3.3), respectively, in the subhazard of prostate cancer mortality compared with those treated aggressively. Men with two comorbid conditions (hazard ratio [HR], 1.6; 95% CI, 1.0 to 2.7) or three or more comorbid conditions (HR, 1.5; 95% CI, 0.9 to 2.5) who were managed conservatively did not have a statistically significant increase in prostate cancer mortality.

Researchers also conducted an analysis that included men who chose androgen deprivation therapy as primary treatment in the aggressive management group in order to explore the decision of any therapy versus none. The results were virtually identical, except for those from the competing-risks model analyzing the subhazard of prostate cancer mortality associated with no treatment. Although men with no comorbid conditions still had an increased risk (HR, 2.0; 95% CI, 1.3 to 3.0), men with one (HR, 1.1; 95% CI, 0.7 to 1.9), two (HR, 1.2; 95% CI, 0.7 to 2.2), or three or more (HR, 1.1; 95% CI, 0.6 to 2.0) comorbid conditions were not at increased risk.

The authors wrote, "These data provide a basis on which to counsel men about their risk for prostate cancer-specific and other-cause mortality and are based on simple variables commonly available to the clinician at the time of treatment decision: age, number of major comorbid conditions at diagnosis, and tumor risk. Older men with multiple major comorbid conditions should be informed of their higher probability of death from other causes before deriving a survival benefit from surgery or radiation therapy for low- and intermediate-risk disease."



Test yourself


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MKSAP Quiz: 5-day history of leg pain and swelling

A 52-year-old man is evaluated in the emergency department for a 5-day history of right leg pain and swelling. He has never had a previous episode of venous thromboembolism. Following a physical exam and ultrasonography, what is the most appropriate management of this patient's transition to warfarin therapy?

mksap.gif

On physical examination, temperature is 36.5 °C (97.7 °F), blood pressure is 120/75 mm Hg, pulse rate is 85/min, and respiration rate is 22/min. BMI is 30. The right lower extremity is swollen. Cardiopulmonary examination discloses clear lungs and tachycardia.

A right popliteal vein deep venous thrombosis is confirmed by venous duplex compression ultrasonography. The patient is given low-molecular-weight heparin (LMWH).

Which of the following is the most appropriate management of this patient's transition to warfarin therapy?

A: At least 3 days of LMWH plus warfarin with a target INR of 1.5 or higher for 24 hours
B: At least 3 days of LMWH plus warfarin with a target INR of 2 or higher for 24 hours
C: At least 5 days of LMWH plus warfarin with a target INR of 2 or higher for 24 hours
D: At least 5 days of LMWH plus warfarin with a target INR of 1.5 or higher for 24 hours

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


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Statins


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Model may predict which coronary artery disease patients benefit from high-dose statins

Incremental treatment effects of high-dose statin therapy over usual-dose statin therapy in coronary artery disease patients can be estimated by a prediction model made up of 13 easy-to-measure clinical predictors that are readily available in clinical practice, a study concluded.

To develop and validate a model for prediction of the incremental treatment effect of high-dose statins for individual patients in terms of reduction of 5-year absolute risk for myocardial infarction, stroke, coronary death or cardiac resuscitation, researchers created a Cox proportional hazards model comprising 13 easy-to-measure clinical predictors. The criteria were age, sex, smoking, diabetes, total cholesterol, high-density lipoprotein cholesterol, systolic blood pressure, history of myocardial infarction, coronary artery bypass grafting, congestive heart failure or abdominal aortic aneurysm, glomerular filtration rate, and statin dose.

The model was developed using data from 10,001 patients in the Treating to New Targets (TNT) trial. External validation was based on data from 8,888 patients in the Incremental Decrease in End Points Through Aggressive Lipid Lowering (IDEAL) trial. Results were published online before print on May 14 by Circulation.

IDEAL confirmed adequate goodness-of-fit and calibration but moderate discrimination (C-statistic, 0.63; 95% CI, 0.62 to 0.65), the study authors wrote. When trial results were combined, the model identified a group of 11.7% whose predicted five-year number needed to treat (NNT) was 25 or lower and a group of 41.9% whose predicted NNT was 50 or higher.

Estimation of the incremental treatment effect of high-dose versus usual-dose statin therapy in coronary artery disease patients may allow selection of high-risk patients who benefit most from more aggressive therapy, the authors noted.

"We recognize that the model's discrimination could be further improved by including additional information on biomarkers, such as C-reactive protein (hs-CRP), or imaging, such as carotid intima-media thickness or coronary [computed tomography]-angiography," the authors wrote. "Yet, because such information is not readily available for most patients, this would come at the expense of more limited applicability in clinical practice."


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Intensive-dose statins don't confer greater diabetes risk for post-MI elderly than moderate doses

Older patients with myocardial infarction (MI) who take intensive-dose statins have the same risk of developing diabetes as those who take moderate-dose statins, a new study found.

In a retrospective study, Canadian researchers examined the records of 17,080 patients older than 65 years with acute coronary syndrome (ACS) who survived MI after hospital discharge between April 1, 2004, and March 31, 2010. They compared clinical outcomes of patients who took intensive-dose statins to those who took moderate-dose statins. The former dosage included atorvastatin ≥40 mg, rosuvastatin ≥20 mg, or simvastatin ≥60 mg. Moderate dosage included atorvastatin <40 mg, rosuvastatin <20 mg, or simvastatin <60 mg. The primary outcome was new development of diabetes after discharge; other outcomes were all-cause mortality and repeat hospitalization for ACS. Results were published online May 14 by Circulation: Cardiovascular Quality and Outcomes.

At five years, patients who took moderate-dose statins were just as likely as those who took intensive-dose statins to develop diabetes (13.0% of patients in the former group and 13.6% in the latter; P=0.19). The combined five-year mortality/ACS rate was lower in the intensive-dose group than in the moderate-dose group (44.8% vs. 46.5%; P=0.044). This combined outcome was driven mainly by a lower rate of ACS associated with intensive-dose statins (P=0.039); there was no significant difference in mortality rates (34.8% in both groups).

The findings should help allay concerns that prescribing higher doses of statins might lead to higher rates of new-onset diabetes in elderly patients with ACS, since recent studies have found a link between statins and incident diabetes, the authors noted. The intensive dose of statins is recommended by guidelines for ACS patients, and in this study significantly reduced the risk of recurrent ACS at five years with a number needed to treat of 77, they noted.



Women's health


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Midlife surgical menopause not associated with increased cardiovascular risk when compared to natural menopause

Hysterectomy with or without oophorectomy in midlife was not associated with increased risk for cardiovascular disease (CVD) in a new study.

Researchers used data from the Study of Women's Health across the Nation (SWAN), a multisite, community-based prospective study, to compare changes in CVD risk factors up to and after natural menopause and up to and after hysterectomy with and without oophorectomy. At baseline, women included in the study had an intact uterus and at least one ovary, were 42 to 52 years of age, were not pregnant, were not using reproductive hormones, and had had at least one menstrual cycle in the preceding three months. Data for the current analysis were collected between 1996 and 2008.

At annual follow-up visits for 11 years, researchers measured sociodemographic characteristics, menopausal status, surgeries, BMI, medication use, lifestyle factors, lipid levels, blood pressure, insulin resistance, and hemostatic and inflammatory variables. Annual changes in CVD risk factors before and after the final menstrual period or surgery were compared. The study results were published online May 15 by the Journal of the American College of Cardiology.

A total of 3,302 premenopausal women were included in SWAN. By 2008, 1,769 had reached natural menopause, 77 had had a hysterectomy with ovarian conservation, and 106 had had a hysterectomy with bilateral oophorectomy. Multivariable analysis found that changes in cholesterol, apolipoprotein B, insulin resistance (as estimated by the Homeostasis Model of Assessment–Insulin Resistance), systolic blood pressure, plasminogen activatory inhibitor-1, and factor VIIc were similar for women with natural and surgical menopause over time.

Changes in other cardiovascular risk factors, including triglycerides, tissue plasminogen activator and apolipoprotein A, did differ with hysterectomy plus ovarian conservation compared with natural menopause. These risk factor changes conferred a protective cardiovascular effect for women post hysterectomy with ovarian conservation. Women who underwent hysterectomy with bilateral oophorectomy had larger increases in C-reactive protein beforehand compared with women before natural menopause, but this difference resolved after surgical and natural menopause occurred.

The authors noted that they could not evaluate the effect of age at surgery or the effect of surgery on clinical events and that the study sample was not representative of the general population, among other limitations. However, they concluded that based on their results, women in their 40s and 50s who had surgical menopause were not at greater cardiovascular risk than women who had natural menopause. "These results should provide reassurance to women and their clinicians that hysterectomy with or without ovarian conservation in mid-life is not likely to substantially accelerate women's CVD risk," they wrote.



From the College


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Governance Committee seeks Regent candidates for 2014

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 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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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-20130521-cartoon.jpg

"I had something else in mind when I asked for an outline of the patient's condition."

This issue's winning cartoon caption was submitted by Jennifer L. Norris, MD, ACP Member. Thanks to all who voted! The winning entry captured 61.9% of the votes.

The runners-up were:

"Yeah, I guess it would bother most people, but an office with a window is an office with a window."

"I guess we're too late. He's already flat-lining."


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MKSAP Answer and Critique



The correct answer is C: At least 5 days of LMWH plus warfarin with a target INR of 2 or higher for 24 hours. This item is available to MKSAP 16 subscribers as item 29 in the Hematology and Oncology section. More information is available online.

The best management of this patient's transition from parenteral LMWH to warfarin therapy requires at least 5 days of overlap with LMWH and warfarin therapy and an INR of 2 or more for 24 hours. Randomized clinical trials have demonstrated that 5 to 7 days of unfractionated heparin is as effective as 10 to 14 days when transitioning to warfarin therapy. Shorter durations of parenteral anticoagulation in the transition to vitamin K antagonists have not been tested and, theoretically, could confer a higher risk for recurrent thromboembolism. Warfarin acts as an anticoagulant by impairing hepatic synthesis of vitamin K-dependent coagulation factors rather than by directly inhibiting the function of already synthesized factors. Therefore, once an appropriate warfarin dose is initiated, the onset of therapeutic anticoagulation is dictated by the half-life of the coagulation factors. If a patient is receiving an adequate warfarin dose, it takes at least 5 days for vitamin K-dependent factor activity levels to decrease sufficiently for therapeutic anticoagulation (INR of 2-3) to occur. Consequently, parenteral anticoagulant therapy (LMWH) should be continued along with warfarin for at least 5 days and until a therapeutic INR of 2 or more for 24 hours is achieved to avoid an increased risk for recurrent thromboembolism.

Key Point

  • In patients with acute venous thromboembolism, parenteral anticoagulation should be administered concomitantly with warfarin for at least 5 days and until an INR of 2 or more has been achieved for 24 hours.

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Test yourself

A 66-year-old man is evaluated for vague abdominal pain of several months' duration and a 10-kg (22-lb) weight loss. He drinks alcohol socially but does not smoke. The patient is otherwise well, has good performance status, and takes no medications. Following a physical exam, lab studies, and a CT scan, what is the most appropriate initial management of this patient?

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