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ACP InternistWeekly



In the News for the Week of February 5, 2013




Highlights

Some but not all antidepressants associated with QT prolongation

Citalopram and some other antidepressants were associated with prolongation of the QT interval, a new study found. More...

Groups release appropriate use criteria for amyloid PET

The Society of Nuclear Medicine and Molecular Imaging and the Alzheimer's Association recently released appropriate use criteria for amyloid positron emission tomography (PET) in clinical practice. More...


Test yourself

MKSAP Quiz: deep venous thrombosis following surgery

A 28-year-old man is evaluated 24 hours after a new diagnosis of a left calf deep venous thrombosis. One week ago, he underwent orthopedic surgery. Two weeks ago, he returned from vacationing in Italy on an 8-hour flight. Current medications are enoxaparin, 80 mg subcutaneously twice daily, and warfarin, 5 mg/d. What is the most appropriate management of this patient's venous thromboembolism? More...


Prostate cancer

Prostate cancer treatment options result in similar 15-year outcomes

Functional outcomes among men undergoing prostatectomy or radiotherapy for prostate cancer differed at two and five years of follow-up, but significant differences were no longer present by 15 years, a study found. More...

Research model supports strategies that increase PSA screening interval and age-specific thresholds for biopsy

Using higher thresholds for biopsy referral for older men and screening men with initially low prostate-specific antigen (PSA) levels less frequently seem to reduce harms of screening while preserving lives, a study found. More...


Heart failure

Geriatric conditions may be associated with increased risk for heart failure hospitalization

Certain geriatric conditions in older persons with heart failure may be modifiable risk factors for hospital admission, according to a new study. More...


Internal Medicine 2013

ACP Annual Business Meeting to be held

All members are encouraged to attend ACP's Annual Business Meeting to be held during Internal Medicine 2013. Current College Officers will retire from office and incoming Officers, new Regents and Governors-elect will be introduced. More...


Transitions of care

ACP supports the "Care About Your Care" initiative

ACP has joined with many other organizations to help improve care transitions and reduce avoidable readmissions. More...


CME update

ACP & Pri-Med expand education partnership

ACP and Pri-Med are expanding their partnership to develop a new national continuing medical education (CME) curriculum. 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


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Some but not all antidepressants associated with QT prolongation

Citalopram and some other antidepressants were associated with prolongation of the QT interval, a new study found.

The cross-sectional study used electronic health record data on 38,397 adult patients treated between 1990 and 2011 in one Massachusetts health system. All of the patients had a prescription for an antidepressant or methadone (which was included to demonstrate assay sensitivity because of its known effect on QT interval) and had an electrocardiogram (EKG) recorded between 14 and 90 days of the prescription. Studied antidepressants included citalopram, escitalopram, fluoxetine, paroxetine, sertraline, amitriptyline, bupropion, duloxetine, mirtazapine, nortriptyline and venlafaxine.

Results were published by BMJ on Jan. 29.

Researchers found a dose-response association with QT prolongation for citalopram (adjusted beta, 0.10; P<0.01), escitalopram (adjusted beta, 0.58; P<0.001) and amitriptyline (adjusted beta, 0.11; P<0.001), but not for the other antidepressants. Bupropion was associated with QT shortening (adjusted beta, 0.02; P<0.05). More than 400 study subjects had an EKG before and after a dose increase; 59 patients whose citalopram dose was increased from 10 mg to 20 mg had a significant increase in QT (mean increase, 7.8 ms; adjusted P<0.05), as did 107 patients whose dose went from 20 mg to 40 mg (mean increase, 10.3 ms; adjusted P<0.01). Thirteen patients whose bupropion dose increased from 100 mg to 200 mg had a significant decrease in QT (mean decrease, 19.2 ms; adjusted P<0.05).

The study confirmed an association between citalopram and QT prolongation that had been previously identified by other research and FDA warnings, the study authors concluded. Modest prolongation was also found with amitriptyline and escitalopram, but not the other drugs, suggesting that there might some variation in risk within the treatment class. The authors cautioned, however, that the effect sizes were small and that their study population was older and sicker than the average outpatient cohort, since physicians are more likely to order EKGs for such patients.

The study can't answer the question of whether patients on antidepressants should routinely receive EKGs, the authors said, but it may suggest that bupropion treatment would be a reasonable alternative to increasing a patient's dose of citalopram. They called for randomized trials to confirm these apparent associations.


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Groups release appropriate use criteria for amyloid PET

The Society of Nuclear Medicine and Molecular Imaging and the Alzheimer's Association recently released appropriate use criteria for amyloid positron emission tomography (PET) in clinical practice.

The two groups convened a task force to look at specific clinical scenarios in which amyloid PET could be considered appropriate. Elevated levels of amyloid plaques on PET can be an indicator of Alzheimer's disease but can also be present in normal elderly people and in patients with other clinical syndromes, the authors wrote. Their goal was to carefully examine the role of amyloid PET and its potential place in clinical practice, providing clinicians with information to help them give optimal care while also considering cost-effectiveness. The task force evaluated peer-reviewed published studies and developed recommendations based on consensus expert opinion.

The task force concluded that amyloid imaging is appropriate in patients with persistent or progressive mild cognitive impairment, patients who satisfy core criteria for Alzheimer's disease but have unclear clinical presentation, and patients with progressive dementia and atypically early age of onset (usually ≤65 years), if all of the following criteria are also met:

  • The patient has a cognitive complaint with objectively confirmed impairment.
  • Alzheimer's disease is a possible diagnosis, but diagnosis remains uncertain after comprehensive evaluation by a dementia expert.
  • Knowledge of the presence or absence of amyloid plaque pathology is expected to increase diagnostic certainty and change management.

The task force concluded that amyloid imaging is inappropriate:

  • in patients with core clinical criteria for probable Alzheimer's disease and typical age of onset,
  • to determine dementia severity,
  • based only on a family history of dementia or presence of apolipoprotein E ε4,
  • in patients with a cognitive complaint that is unconfirmed on clinical exam,
  • in place of genotyping for suspected autosomal mutation carriers,
  • in asymptomatic individuals and
  • for nonmedical use.

The task force also discussed the limitations of amyloid PET in clinical evaluation, its anticipated impact on patient care, and areas for further research. The full document is available free of charge online.



Test yourself


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MKSAP Quiz: deep venous thrombosis following surgery

A 28-year-old man is evaluated 24 hours after a new diagnosis of a left calf deep venous thrombosis. One week ago, he underwent orthopedic surgery. Two weeks ago, he returned from vacationing in Italy on an 8-hour flight. Current medications are enoxaparin, 80 mg subcutaneously twice daily, and warfarin, 5 mg/d.

mksap.gif

On physical examination, temperature is normal, blood pressure is 145/85 mm Hg, pulse rate is 72/min, and respiration rate is 18/min. BMI is 25. His lungs are clear. His left calf is erythematous and edematous.

Duplex ultrasound obtained yesterday confirms a left posterior tibial vein thrombosis. Laboratory results from his emergency department visit reveal factor V Leiden heterozygosity.

The patient asks why he developed this blood clot and how long he will have to take warfarin.

Which of the following is the most appropriate management of this patient's venous thromboembolism?

A: Low-intensity warfarin (INR, 1.5-2) for at least 3 months
B: Standard-intensity warfarin (INR, 2-3) for at least 12 months
C: Standard-intensity warfarin (INR, 2-3) for at least 3 months
D: Standard-intensity warfarin (INR, 2-3) for life

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


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Prostate cancer


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Prostate cancer treatment options result in similar 15-year outcomes

Functional outcomes among men undergoing prostatectomy or radiotherapy for prostate cancer differed at two and five years of follow-up, but significant differences were no longer present by 15 years, a study found.

To compare long-term urinary, bowel and sexual function after radical prostatectomy or external-beam radiation therapy, researchers enrolled men from the Prostate Cancer Outcomes Study (PCOS) in whom prostate cancer had been diagnosed in 1994 or 1995. The cohort comprised 1,655 men with localized prostate cancer between the ages of 55 and 74 years who had undergone either surgery (1,164 men) or radiotherapy (491 men). Functional status was assessed at baseline and at two, five and 15 years after diagnosis.

Results appeared online Jan. 31 at the New England Journal of Medicine.

Patients were more likely to have urinary incontinence after prostatectomy than radiotherapy at two years (odds ratio [OR], 6.22; 95% CI, 1.92 to 20.29) and five years (OR, 5.10; 95% CI, 2.29 to 11.36). However, no significant between-group difference was seen at 15 years. Patients were more likely to have erectile dysfunction after prostatectomy than radiotherapy at two years (OR, 3.46; 95% CI, 1.93 to 6.17) and five years (OR, 1.96; 95% CI, 1.05 to 3.63), but no significant difference was seen at 15 years. Patients were less likely to have bowel urgency after prostatectomy than radiotherapy at two years (OR, 0.39; 95% CI, 0.22 to 0.68) and five years (OR, 0.47; 95% CI, 0.26 to 0.84), but there was no significant difference at 15 years.

Researchers noted that men undergoing either prostate cancer treatment had declines in all functional outcomes throughout early, intermediate and long-term follow-up. For example, at 15 years, erectile dysfunction was nearly universal, affecting 87% in the prostatectomy group and 93.9% of those in the radiotherapy group. But only 43.5% of men in the prostatectomy group and 37.7% of those in the radiotherapy group reported being bothered by this, which the authors attributed to declining sexual interest with age or acceptance of sexual dysfunction over time.

They wrote, "Considering the often long duration of survival after treatment for prostate cancer, these data may be used to counsel men considering treatment for localized disease."


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Research model supports strategies that increase PSA screening interval and age-specific thresholds for biopsy

Using higher thresholds for biopsy referral for older men and screening men with initially low prostate-specific antigen (PSA) levels less frequently seem to reduce harms of screening while preserving lives, a study found.

annals.jpg

To evaluate comparative effectiveness of alternative PSA screening strategies, researchers created a model of prostate cancer incidence and mortality, quantifying harms and lives saved for 35 PSA screening strategies. The model was based on national and trial data on PSA growth, screening and biopsy patterns, incidence, treatment distributions, treatment efficacy and mortality.

Results and a summary for patients appeared in the Feb. 5 Annals of Internal Medicine.

Researchers assessed the screening strategies because of current controversy over age to start (40 or 50 years) and stop (69 or 74 years) screening; screening intervals (annual or biennial); and thresholds for biopsy referral (PSA level of 4.0 µg/L; PSA level of 2.5 µg/L; PSA level of 4.0 µg/L or PSA velocity of 0.35 µg/L per year; or PSA level >95th percentile for age [2.5, 3.5, 4.5, and 6.5 µg/L for ages 40 to 49, 50 to 59, 60 to 69, and 70 to 74 years, respectively]).

Without screening, the risk for prostate cancer death is 2.86%. The strategies studied included the following:

  • A strategy that screens men age 50 to 74 years annually with a PSA threshold for biopsy referral of 4 µg/L reduces the risk for prostate cancer death to 2.15%, with risk for overdiagnosis of 3.3%.
  • A strategy that uses higher PSA thresholds for biopsy referral in older men achieves a similar risk for prostate cancer death (2.23%) but reduces the risk for overdiagnosis to 2.3%.
  • A strategy that screens biennially with longer screening intervals for men with low PSA levels achieves similar risks for prostate cancer death (2.27%) and overdiagnosis (2.4%), but reduces total tests by 59% and false-positive results by 50%.

Researchers noted that aggressive screening strategies, particularly those that lower the PSA threshold for biopsy, do reduce prostate cancer mortality relative to the reference strategy while possibly raising the harms of unnecessary biopsies, diagnoses and treatments.

Also, they wrote, there are substantial improvements in the harm-benefit tradeoff of PSA screening with less frequent testing and more conservative criteria for biopsy referral in older men.

Using age-specific PSA thresholds for biopsy referral reduces false-positive results by a relative 25% and overdiagnoses by 30% while preserving 87% of the lives saved under the reference strategy. Alternatively, using longer screening intervals for men with low PSA levels reduces false-positive results by a relative 50% and overdiagnoses by 27% while preserving 83% of the lives saved under the reference strategy, the study found.

These adaptive, personalized strategies represent prototypes for a smarter approach to screening, researchers concluded.

Researchers wrote, "As shown in the PLCO [Prostate, Lung, Colorectal and Ovarian Cancer Screening] trial and supported by our model results across a broad range of alternative strategies, there are diminishing returns to intensive screening. If we recognize that realistic screening strategies must achieve an acceptable balance of benefits and harms as opposed to unconditionally maximizing benefits, we can improve on the effectiveness of existing PSA-based screening for prostate cancer."



Heart failure


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Geriatric conditions may be associated with increased risk for heart failure hospitalization

Certain geriatric conditions in older persons with heart failure may be modifiable risk factors for hospital admission, according to a new study.

Researchers used data from the population-based Cardiovascular Heart Study to determine whether and how geriatric conditions are related to long-term risk for all-cause hospitalization in patients with heart failure. Community-dwelling older patients who had a new diagnosis of heart failure were included, and data from annual exams and medical records were examined.

The authors defined geriatric conditions as those that occur in older patients, typically have multiple causes, and are not necessarily related to a specific disease. They looked at slow gait, muscle weakness (i.e., weak grip), cognitive impairment and depressive syndromes and used Anderson-Gill regression modeling to examine whether any of these were related to hospital admission after a heart failure diagnosis. The study results were published online Feb. 4 and will appear in the Feb. 12 Journal of the American College of Cardiology.

A total of 758 patients (mean age at diagnosis, 79.7 years) had a new diagnosis of heart failure, with a mean hospital admission rate of 7.9 per 10 person-years (95% CI, 7.4 to 8.4 per 10 person-years). Diabetes mellitus, New York Heart Association functional class III or IV, chronic kidney disease, slow gait, depressed ejection fraction, depression and muscle weakness were independently associated with hospitalization (hazard ratios, 1.36, 1.32, 1.32, 1.28, 1.25, 1.23 and 1.19, respectively).

The authors noted that data for the study were first collected in 1989 and that heart failure management and possibly risk factors for hospitalization have changed substantially since then. They also acknowledged that patients were censored at the time of death, that the full effect of comorbid conditions was not known, and that the mean patient age was higher than that in most heart failure registries. However, they concluded that three potentially modifiable geriatric conditions—slow gait, depression and muscle weakness—are associated with risk for hospitalization in patients with heart failure and that such risk factors should be assessed routinely at diagnosis.

The author of an accompanying editorial agreed that it is important to examine hospitalization risk factors in older patients but pointed out that the evidence to support risk factor modification is currently weak. Exercise training has only been studied in younger patients, resistance training to improve weak grip has been evaluated only in small cohort studies of exercise endurance, and no consensus has been reached on the effect of treatment for depression, he noted.

The editorialist suggested that based on the current results, it "seems reasonable" for physicians to evaluate muscle strength, gait speed and psychological status in clinically stable patients with newly diagnosed heart failure. "At this time, however, response to slow gait or weak grip is limited to risk stratification, with possible increased follow-up intensity," he wrote. "Hopefully, future clinical trial results will provide clearer direction."



Internal Medicine 2013


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ACP Annual Business Meeting to be held

All members are encouraged to attend ACP's Annual Business Meeting to be held during Internal Medicine 2013. Current College Officers will retire from office and incoming Officers, new Regents and Governors-elect will be introduced.

The meeting will be held on Saturday, April 13, 2013 at the Moscone Center in San Francisco from 12:45 p.m. to 1:45 p.m., with David L. Bronson, MD, FACP, ACP President, presiding. Dennis R. Schaberg, MD, MACP, will present the Annual Report of the Treasurer. A key feature of the meeting is the presentation of ACP's priorities for 2013-14 by Executive Vice President and Chief Executive Officer Steven E. Weinberger, MD, FACP. Members will have the opportunity to ask questions following Dr. Weinberger's presentation.



Transitions of care


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ACP supports the "Care About Your Care" initiative

ACP has joined with many other organizations to help improve care transitions and reduce avoidable readmissions. Launched in 2011, "Care About Your Care" is an initiative of the Robert Wood Johnson Foundation that focuses attention on what people can do to provide and receive better health care. The website offers both patient and physician resources. More information is available online.



CME update


.
ACP & Pri-Med expand education partnership

ACP and Pri-Med are expanding their partnership to develop a new national continuing medical education (CME) curriculum.

The new curriculum will support educational content for over 90% of the live Pri-Med meetings. As part of the expanded partnership, Pri-Med will re-launch its annual conference series and feature a new medical education curriculum from ACP that focuses on coordinated, team-based care and aligns with clinical care gaps and subspecialty needs. ACP will also continue to provide the educational curriculum for a series of regional meetings.



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-20130205-cartoon.jpg

"No, your news isn't hard for me to swallow, Doc. It just takes a while."

This issue's winning cartoon caption was submitted by Harry J. Cerezo, a medical student member. Thanks to all who voted! The winning entry captured 59% of the votes.

The runners-up were:

"At least your diagnosis is not a zebra."

"I'd like to proceed with X-rays. Of course, the cervical spine series will take a bit longer than usual."


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MKSAP Answer and Critique



The correct answer is C: Standard-intensity warfarin (INR, 2-3) for at least 3 months. This item is available to MKSAP 16 subscribers as item 12 in the Hematology/Oncology section.

MKSAP 16 released Part A on July 31. More information is available online.

Standard-intensity warfarin (INR, 2 to 3) for at least 3 months is the most appropriate management of this patient with a triggered episode of venous thromboembolism (VTE). Although distal (calf vein) deep venous thrombosis (DVT) is associated with a low risk for pulmonary embolism, these thrombi confer a substantial risk for progression into the proximal deep venous system in the absence of anticoagulation. In one randomized study, 29% of patients treated with a 5-day course of unfractionated heparin alone developed recurrent VTE compared with none in the group receiving warfarin for 3 months.

This patient has several identifiable risk factors for VTE: recent major orthopedic surgery, recent travel, and factor V Leiden heterozygosity. Major inpatient surgery is associated with a 70-fold increased risk for VTE; ambulatory surgery is associated with a 10-fold increased risk. The risk associated with surgery is greatest in the first few weeks after surgery and declines thereafter, reaching baseline as long as 12 months later. Therefore, this patient's recent orthopedic surgery played a major role in the pathogenesis of his calf vein DVT. In comparison, travel is associated with a modest twofold increased risk for VTE, and factor V Leiden is associated with a fivefold increased risk of VTE. Although factor V Leiden is associated with a significant risk for initial VTE, it is not associated with a significant risk for recurrent VTE (1.5-fold). Consequently, the presence of factor V Leiden in this patient does not mandate prolonged therapy.

Low-intensity warfarin (INR, 1.5-2) for 3 months would not be the optimal choice for this patient's triggered episode of calf vein DVT. Low-intensity warfarin therapy was found to be inferior to standard-intensity warfarin therapy (INR, 2-3) for treatment of patients with idiopathic VTE. Low-intensity therapy was initiated after at least 3 months of standard-intensity therapy (INR, 2-3). Low-intensity warfarin therapy has never been tested for the initial 3 months of VTE treatment.

Lifelong warfarin (INR, 2-3) is not the best management approach for this patient with a triggered episode of VTE. The bleeding risks of long-term warfarin (at least 1% to 2% per year) outweigh the risk of recurrence (0.7% per year).

Key Point

  • Standard-intensity warfarin for at least 3 months is the most appropriate management for patients with risk factors for venous thromboembolism.

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