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

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ACP InternistWeekly



In the News for the Week of June 3, 2014




Highlights

Colorectal cancer screening may be cost-effective beyond age 75 in previously unscreened patients, modeling study suggests

Colorectal cancer screening (colonoscopy, sigmoidoscopy, or fecal immunohistochemical testing) may be cost-effective for patients older than 75 who have never been previously screened, according to a new study. More...

ASCO guideline update changes tamoxifen recommendations

The American Society of Clinical Oncology (ASCO) recently released an updated guideline that increased the recommended length of tamoxifen therapy in women with hormone receptor-positive breast cancer. More...


Test yourself

MKSAP Quiz: new-onset thrombocytopenia during pregnancy

A 35-year-old woman is evaluated for new-onset thrombocytopenia. She is gravida 1 at 36 weeks' gestation. Her pregnancy has been otherwise uncomplicated. She takes only a prenatal vitamin. Following a physical exam and lab studies, what is the most appropriate management? More...


Women's health

Low-dose oral estrogen and venlafaxine demonstrate efficacy and tolerability for menopausal vasomotor symptoms

Low-dose oral estrogen and venlafaxine are effective treatments for vasomotor symptoms of hot flashes and night sweats in women during midlife, with a possible small advantage for estrogen, a study found. More...


Diabetes

New recommendations on insulin pump use

The American Association of Clinical Endocrinologists (AACE) and the American College of Endocrinology offered guidance on optimal and safe use of insulin pumps in a new consensus statement. More...


Transitions of care

Some transitional care interventions more effective than others for reducing readmissions and mortality following hospitalizations for heart failure

Home-visit programs and multidisciplinary clinics reduced all-cause readmission and mortality for up to 6 months following hospitalizations for heart failure, a meta-analysis found. More...


Education

ACP releases flashcard app to help physicians prepare for board certification

Internists can now refresh their knowledge gained during ACP's Internal Medicine Board Review and maintenance of certification exam prep courses with a new app that is freely accessible to course registrants and purchasers of course recordings. More...


From ACP Internist

The June issue of ACP Internist is online and coming to your mailbox

The June issue of ACP Internist is now online, featuring highlights of coverage from Internal Medicine 2014, including the following. 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: Daisy Smith, MD, FACP



Highlights


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Colorectal cancer screening may be cost-effective beyond age 75 in previously unscreened patients, modeling study suggests

Colorectal cancer screening (colonoscopy, sigmoidoscopy, or fecal immunohistochemical testing) may be cost-effective for patients older than 75 who have never been previously screened, according to a new study.

annals.jpg

The U.S. Preventive Services Task Force recommends against routine colorectal cancer screening in patients older than 75 who have previously been screened but does not address older patients who have never been screened. Researchers performed a microsimulation modeling study to examine when colorectal cancer screening should be considered in unscreened elderly patients, as well as which screening test might be indicated at each age.

Data from observational and experimental studies were used, and the target population was unscreened patients between 76 to 90 years of age who had no, moderate, and severe comorbid conditions. The interventions examined were one-time colonoscopy, sigmoidoscopy, or fecal immunochemical testing (FIT). Outcome measures were quality-adjusted life-years (QALYs) gained, costs, and costs per QALY gained. The study was published in the June 3 Annals of Internal Medicine.

In the base-case analysis, colorectal cancer screening was cost-effective in unscreened elderly patients with no comorbid conditions until age 86. Colonoscopy was indicated until age 83, sigmoidoscopy was indicated at age 84, and FIT was indicated at ages 85 and 86. When unscreened patients with moderate comorbid conditions were considered, screening was cost-effective until age 83, with colonoscopy indicated until age 80, sigmoidoscopy indicated until age 81, and FIT indicated at ages 82 and 83.

The cost-effective upper age limit for screening in unscreened patients with severe comorbid conditions was 80 years, with colonoscopy indicated up to age 77, sigmoidoscopy indicated up to age 78, and FIT indicated at ages 79 and 80. All of these calculations assumed a willingness-to-pay threshold of $100,000 per QALY gained. Reducing the threshold to $50,000 per QALY gained decreased the upper ages at which screening was cost-effective to 84, 80, and 77 years in patients with no, moderate, and severe comorbid conditions, respectively.

The authors noted that their model considered only patients at average risk for colorectal cancer and that they did not analyze patients by sex and race. However, they concluded that based on their study, colorectal cancer screening should be considered "well beyond age 75 years" in elderly U.S. patients who had not previously been screened.

Future research, the authors said, should attempt to determine the optimal number of FIT screenings in relatively young elderly patients who do not want to have screening colonoscopy or sigmoidoscopy. In addition, they said, more studies are necessary on the effect of the benefits, burdens, and harms of screening on patients' decision making and on the appropriate age to stop screening in adequately screened patients based on comorbid conditions.


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ASCO guideline update changes tamoxifen recommendations

The American Society of Clinical Oncology (ASCO) recently released an updated guideline that increased the recommended length of tamoxifen therapy in women with hormone receptor-positive breast cancer.

Previously, ASCO had recommended that premenopausal women with hormone receptor-positive breast cancer be treated with 5 years of tamoxifen therapy and that postmenopausal women with hormone receptor-positive breast cancer receive at least 5 years of sequential adjuvant therapy with an aromatase inhibitor or tamoxifen followed by an aromatase inhibitor.

To update these guidelines, a committee performed a systematic review of randomized, clinical trials published from January 2009 to June 2013 and of 3 historical trials whose data were already available in the literature. All of the included trials compared 5 years of tamoxifen therapy with 10 years of therapy or with indefinite therapy. Survival, disease recurrence, and adverse events were the outcomes of interest. The updated recommendations were published online May 27 by the Journal of Clinical Oncology.

Five studies were included in the analysis. In the 2 largest, which were also the most recent and had the longest reported follow-up, 10 years of tamoxifen use conferred a breast-cancer survival advantage. Three of the 5 trials showed an improvement in overall mortality, while 2 of the historical studies found higher mortality in the extended tamoxifen arm. Ten years of tamoxifen use was also associated with lower risk for disease recurrence in 2 of the trials overall and in the estrogen-receptor positive subset of another trial, compared with 5 years of use. Among the 3 studies that reported on contralateral breast cancer, 1 found a statistically significant lower risk with extended tamoxifen therapy and 2 showed no statistically significant difference between groups.

On the basis of these data, the ASCO update committee recommended that pre- or perimenopausal women diagnosed with hormone receptor-positive breast cancer should receive 5 years of adjuvant tamoxifen treatment but that after 5 years, additional therapy should be based on menopausal status. Pre- or perimenopausal women or those whose menopausal status is unknown or undetermined should be offered 10 total years of tamoxifen treatment. Postmenopausal women who have received 5 years of adjuvant tamoxifen therapy should be offered the choice of continuing tamoxifen or changing to an aromatase inhibitor, for a total of 10 years of adjuvant endocrine therapy. Both of the updated recommendations are based on high-quality evidence and are considered strong.

The committee noted that the studies analyzed for the guideline update had differing median follow-up lengths and were performed in different decades. In addition, some of the patients in the included studies did not have hormone receptor-positive disease or their hormone receptor status was not known, and few new data were available on adverse events with longer duration of adjuvant tamoxifen, among other limitations.

The committee recommended that future studies examine patients who have taken aromatase inhibitors for more than 5 years, as well as optimal treatment duration for patients who took tamoxifen for less than 5 years. More information on predictors of recurrence risk and on likely benefits of treatment according to tumor stage, biomarkers, and time since diagnosis is also needed, the committee said.



Test yourself


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MKSAP Quiz: new-onset thrombocytopenia during pregnancy

A 35-year-old woman is evaluated for new-onset thrombocytopenia. She is gravida 1 at 36 weeks' gestation. Her pregnancy has been otherwise uncomplicated. She takes only a prenatal vitamin.

mksap.gif

On physical examination, temperature is normal, blood pressure is 110/65 mm Hg, pulse rate is 110/min, and respiration rate is 22/min. There are no ecchymoses or petechiae. Abdominal examination discloses no right upper quadrant pain. She has a gravid uterus. Neurologic examination is normal, and there is no peripheral edema.

Laboratory studies:

Hematocrit 33%
Hemoglobin 11.0 g/dL (110 g/L)
Leukocyte count 9500/µL (9.5 × 109/L)
Mean corpuscular volume 85 fL
Platelet count 95,000/µL (95 × 109/L)
Fibrinogen 350 mg/dL (3.5 g/dL)
Alanine aminotransferase Normal
Aspartate aminotransferase Normal
Urinalysis Normal

No schistocytes or platelet clumping is seen on the peripheral blood smear.

Which of the following is the most appropriate management?

A: Corticosteroids
B: Emergent delivery of fetus
C: Intravenous immune globulin
D: Plasma exchange
E: Repeat complete blood count in 1 to 2 weeks

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


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Women's health


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Low-dose oral estrogen and venlafaxine demonstrate efficacy and tolerability for menopausal vasomotor symptoms

Low-dose oral estrogen and venlafaxine are effective treatments for vasomotor symptoms of hot flashes and night sweats in women during midlife, with a possible small advantage for estrogen, a study found.

To determine the efficacy and tolerability of oral estrogen and venlafaxine in alleviating menopause symptoms, researchers recruited 339 perimenopausal and postmenopausal women with at least 2 bothersome symptoms per day (mean, 8.1 per day) between December 2011 and October 2012. Participants were randomized to double-blind treatment with low-dose oral 17β-estradiol (0.5 mg/d) (n=97), low-dose venlafaxine hydrochloride extended-release (75 mg/d) (n=96), or placebo (n=146) for 8 weeks.

The primary outcome was the mean daily frequency of symptoms after 8 weeks of treatment. Secondary outcomes were symptoms' severity, bother, and interference with daily life. Intention-to-treat analyses compared the change in symptom frequency. Results appeared at JAMA Internal Medicine on May 26.

Compared with baseline, at week 8, the mean symptom frequency in the estrogen group decreased 52.9% to 3.9 symptoms per day (95% CI, 2.9 to 4.9 symptoms per day). In the venlafaxine group, symptoms decreased 47.6% to 4.4 symptoms per day (95% CI, 3.5 to 5.3 symptoms per day). In the placebo group, symptoms decreased 28.6% to 5.5 per day (95% CI, 4.7 to 6.3 symptoms per day). Estrogen reduced the frequency of symptoms by 2.3 more incidents per day than placebo (P<0.001), and venlafaxine reduced the frequency of symptoms by 1.8 more per day than placebo (P=0.005). Low-dose estrogen reduced the frequency of symptoms by 0.6 more per day than venlafaxine (P=0.09).

The results were consistent for symptom severity, bother, and interference. Treatment satisfaction was highest (70.3%) for estrogen (P<0.001 vs. placebo), lowest (38.4%) for placebo, and intermediate (51.1%) for venlafaxine (P=0.06 vs. placebo). Both interventions were well tolerated, and 11 participants (3.2%) stopped treatment because of adverse events (4 with estrogen, 5 with venlafaxine, and 2 with placebo.)

No statistically significant interactions of treatment effects were observed with age, race/ethnicity, body mass index, smoking, menopausal status, symptom duration, or baseline symptom level frequency for venlafaxine or estrogen versus placebo (P>0.05 for all).

"The results of this trial provide clinically relevant data about the magnitude of the effect of low-dose oral ET [estrogen therapy] and an SNRI [serotonin-norepinephrine reuptake inhibitor] in improving VMS [vasomotor symptom] frequency, severity, bother, and interference in the same population of symptomatic women, enabling standardization of baseline symptom profiles of treated participants for the first time to date," the authors wrote. "Our findings extend the results of previous placebo-controlled trials of these individual treatments alone by demonstrating that SNRIs have a meaningful therapeutic effect on VMS, which is in the range of that with low-dose ET."



Diabetes


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New recommendations on insulin pump use

The American Association of Clinical Endocrinologists (AACE) and the American College of Endocrinology offered guidance on optimal and safe use of insulin pumps in a new consensus statement.

The document, published in the May Endocrine Practice, updates a consensus statement issued by AACE in 2010. The new statement adds information about improvements in pump technology, including the first pump with a system to suspend insulin therapy if a low-glucose reading is noted and a disposable insulin delivery system for type 2 diabetes. The statement also reviews data on the use of pumps in specific patient populations, such as children, pregnant women, and type 2 diabetics (including continuous subcutaneous use of concentrated regular U-500 insulin). The statement's section on patient safety issues has also been updated.

The statement offers recommendations on selection of patients for insulin pump use. The ideal candidate for a pump has either type 1 diabetes or intensively managed, insulin-dependent type 2 diabetes; performs 4 or more insulin injections and blood glucose measurements daily; and is motivated, willing, and able to use the technology safely and effectively, including maintaining frequent contact with a health care team.

The statement also discusses use of pumps in hospitals and recommends that if a hospitalized patient is not able to manage his or her own pump, the specialist(s) responsible for ambulatory pump management should be contacted. Hospital patients and physicians should also be encouraged not to discontinue pump infusions and should contact specialists as needed. The April ACP Hospitalist also discusses inpatient management of insulin pumps.

The consensus statement also offers a number of recommendations on education and training of patients who use pumps. Initial and ongoing training should be provided by a multidisciplinary team under the direction of an experienced endocrinologist or diabetologist. The statement also provides data on comparisons of different pumps, safety issues, and cost-effectiveness.



Transitions of care


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Some transitional care interventions more effective than others for reducing readmissions and mortality following hospitalizations for heart failure

Home-visit programs and multidisciplinary clinics reduced all-cause readmission and mortality for up to 6 months following hospitalizations for heart failure, a meta-analysis found.

annals.jpg

Researchers conducted a meta-analysis of 47 trials published between January 1990 and October 2013 that reported a readmission or mortality rate within 6 months of a hospitalization. Studies included adults recruited during or within 1 week of an index hospitalization for heart failure. They compared a transitional care intervention with another eligible intervention or with usual care. Interventions included education of patient or caregiver before or after discharge, planned or scheduled outpatient clinic visits (primary care or multidisciplinary heart failure [MDS-HF] clinic), home visits, telemonitoring, structured telephone support, transition coach or case management, or interventions to increase clinician continuity.

Results were published online by Annals of Internal Medicine on May 27.

Both home visits and multidisciplinary clinic interventions reduced all-cause readmissions over 3 to 6 months (high strength of evidence; number needed to treat [NNT], 7 to 9). Structured telephone support and telemonitoring interventions were not effective in reducing readmissions (moderate strength of evidence for both). Similarly, nurse-led clinic interventions were not effective (low strength of evidence), and there was not enough evidence to determine whether primarily educational interventions were effective for this outcome.

Home visits (moderate strength of evidence; NNT, 7) and telephone interventions (high strength of evidence; NNT, 14) reduced the risk for heart failure-specific readmissions. Telemonitoring did not (moderate strength of evidence). There was only 1 trial, with unknown consistency, for multidisciplinary clinic interventions, nurse-led interventions, or primarily educational interventions, which was not enough evidence to determine whether they reduced readmissions for heart failure.

Mortality rates stratified by intervention category and outcome timing showed that some of the interventions reduced mortality compared with usual care (moderate strength of evidence): home-visiting programs (NNT, 33), multidisciplinary clinic interventions (NNT, 18), and telephone support (NNT, 27). Telemonitoring, nurse-led clinics, and primarily educational interventions did not reduce mortality (low strength of evidence). There was not enough evidence to determine whether primary care interventions and cognitive training programs affected mortality.

"Our findings provide guidance to quality improvement efforts aimed at reducing readmission and mortality rates for persons with HF [heart failure]," the authors noted. "Home-visiting programs and MDS-HF clinic interventions currently have the best evidence for reducing all-cause readmissions and mortality up to 6 months after an index hospitalization for persons with HF."



Education


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ACP releases flashcard app to help physicians prepare for board certification

Internists can now refresh their knowledge gained during ACP's Internal Medicine Board Review (IMBR) and MOC exam prep courses with a new app that is freely accessible to course registrants and purchasers of course recordings.

Available for iPhone, iPad, and Android, the ACP Flashcards App features more than 200 flashcards across 16 categories, as well as the ability to mark flashcards correct or incorrect and create custom sets of cards to facilitate focused study. Users can also access a mobile Web version by logging in with their ACP usernames and passwords. Purchasers of ACP's IMBR or MOC exam prep recordings from Playback Now can enter their Playback Now usernames and passwords for access.



From ACP Internist


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The June issue of ACP Internist is online and coming to your mailbox

The June issue of ACP Internist is now online, featuring highlights of coverage from Internal Medicine 2014, including the following.

acpi-20140603-internist.jpg

Disclosing medical errors the right way. After a medical error, patients want an explicit statement that an error occurred, what happened, and the implications for their health. They want an outright apology, not a statement of regret. Work from global organizations is refining the right way to disclose errors.

Get rid of GERD without unneeded costs, tests. Gastroesophageal reflux disease can be diagnosed in the office, without the need for expensive tests such as endoscopy. Learn how to make the right diagnosis without being confounded by symptoms that might steer a patient toward the wrong specialist.

For effective smoking cessation, turn ambivalence into action. Smokers sometimes want to want to quit. Their ambivalence is the effect of nicotine, which rewires the brain. Instead of being wary of the patient's mixed feelings, use them as a sign to try nicotine replacement therapy systems that make the cravings more manageable.

These stories, more coverage from Internal Medicine 2014, and the latest Test Yourself with the MKSAP Quiz are online.



Cartoon caption contest


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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-20140603-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 E: Repeat complete blood count in 1 to 2 weeks. This item is available to MKSAP 16 subscribers as item 56 in the Hematology & Oncology section. More information is available online.

Repeating the complete blood count in 1 to 2 weeks is appropriate. This patient has new-onset asymptomatic thrombocytopenia developing in the last trimester of pregnancy that is characterized by a platelet count higher than 50,000/µL (50 × 109/L), which suggests gestational thrombocytopenia. Gestational thrombocytopenia is the most common cause of pregnancy-associated thrombocytopenia. The cause of gestational thrombocytopenia is unknown, although it is not believed to have an immune basis. Gestational thrombocytopenia occurs in approximately 5% of pregnancies. Conversely, thrombocytopenia developing in the first two trimesters of pregnancy that is characterized by platelet counts lower than 50,000/µL (50 × 109/L) suggests immune (also termed "idiopathic") thrombocytopenic purpura.

Several studies have confirmed that maternal and fetal outcomes are excellent in patients with platelet counts higher than 50,000/µL (50 × 109/L), and no resulting maternal or fetal complications, such as fetal thrombocytopenia, should occur. Consequently, no therapeutic interventions, including intravenous immune globulin, plasma exchange, or corticosteroids, are required in this patient, and the fetus does not need to be emergently delivered.

Key Point

  • Gestational (mild) thrombocytopenia is the most common cause of pregnancy-associated thrombocytopenia and has a benign course.

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Test yourself

A 69-year-old woman is evaluated for a lump under her arm found on self-examination. She is otherwise healthy and has no other symptoms. Medical and family histories are unremarkable, and she takes no medications. A needle aspirate of the right axillary mass reveals adenocarcinoma. Bilateral mammography and breast MRI are normal. CT scan of the chest, abdomen, and pelvis demonstrates the enlarged axillary lymph node and no other abnormalities. What is the most appropriate initial treatment?

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