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ACP InternistWeekly



In the News for the Week of September 25, 2012




Highlights

Behavioral counseling associated with reduced alcohol consumption in people with at-risk drinking

Brief counseling interventions are associated with improved behavioral outcomes for adults who engage in risky drinking, a study found. More...

TIA and minor stroke associated with disability at 90 days

A detailed prospective study of transient ischemic attacks (TIAs) and minor stroke found 15% of patients were disabled at 90 days, even though most of them did not have a recurrent event. More...


Test yourself

MKSAP Quiz: abnormal liver chemistry tests

A 25-year-old man is evaluated after being turned down as a blood donor because of abnormal liver chemistry tests. The patient is healthy, takes no medications, does not smoke, and drinks alcohol socially. The review of systems, physical exam, vital signs and BMI are normal. What is the most appropriate diagnostic test for this patient? More...


Breast cancer

Women with luminal A breast cancer have better short-term survival but long-term survival curves don't level off

Women with luminal A breast cancer have lower mortality rates than those with other subtypes but continue to see a decrease in survival after 10 years of follow-up, according to a new study of molecular tumor subtypes. More...


Anticoagulant therapy

Restarting warfarin after GI bleeding associated with better outcomes

Patients previously on warfarin who don't resume the therapy soon after a gastrointestinal (GI) bleeding event may have a higher risk for thrombosis and death, according to a new study. More...


Kidney disease

VTE risk appears to progressively increase as eGFR decreases and albumin-creatinine ratio increases

Even mild kidney disease is associated with an increase in risk of venous thromboembolism (VTE), a new review found. More...


Resources

Reminder: Seasonal flu vaccine tool available

The U.S. Department of Health and Human Services' HealthMap Vaccine finder, a Web-based flu vaccine locator that helps physicians post their flu vaccine services, has been redesigned and is now available online. More...


From the College

Apply for the 2013 Health Policy Internship

Applications are now being accepted for the 2013 ACP Health Policy Internship program. More...


From ACP Hospitalist

The September issue is online

The September issue of ACP Hospitalist is online and includes stories about factitious disorder, disputes with colleagues, allergic reactions and more. More...


Cartoon caption contest

Vote for your favorite entry

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


Physician editor: Daisy Smith, MD, FACP



Highlights


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Behavioral counseling associated with reduced alcohol consumption in people with at-risk drinking

Brief counseling interventions are associated with improved behavioral outcomes for adults who engage in risky drinking, a study found.

annals.jpg

To evaluate the benefits and harms of behavioral counseling interventions for adolescents and adults who misuse alcohol, researchers considered 23 controlled trials of at least six months that enrolled people who misused alcohol (as identified by screening in primary care settings). People with alcohol dependence were generally excluded from the studies. No studies randomly assigned patients, practices, or clinicians to screening and comparison groups, but all randomly assigned patients to treatment after they had positive screening results.

The study was published online Sept. 25 by Annals of Internal Medicine.

The best evidence was for 10- to 15-minute multicomponent interventions. In 10 trials of 4,332 patients, intervention reduced alcohol consumption by 3.6 drinks per week from baseline (95% CI, 2.4 to 4.8 drinks/week). Among seven trials of 2,737 patients, 12% fewer adults who received intervention reported heavy drinking episodes (risk difference, 0.12; 95% CI, 0.07 to 0.16), and among nine trials with 5,973 patients, 11% more adults reported drinking under the recommended limits (risk difference, 0.11; 95% CI, 0.08 to 0.13) over 12 months compared with control participants (a finding the reviewers labeled as having moderate strength of evidence).

Long-term outcomes from two studies revealed that participants in the intervention groups maintained reductions in consumption or continued to reduce consumption, but differences between intervention and control groups were no longer statistically significant by 48 months.

Evidence was insufficient to draw conclusions about effects on accidents, injuries or alcohol-related liver problems. Trials enrolling young adults or college students showed reduced consumption and fewer heavy drinking episodes (moderate strength of evidence). Little or no evidence of harms was found, such as impaired physician-patient relationship, except for opportunity costs from time spent on the interventions, which ranged from five minutes to two hours over several in-person or telephone visits.

Researchers estimated that positive screening results would require five to 10 minutes of follow-up to assess whether patients have alcohol abuse or dependence issues and should probably be referred for specialized treatment, instead of brief behavioral counseling interventions.

"Nevertheless, support systems are probably required for effective screening and intervention. In addition, most interventions required training providers or staff," they wrote.


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TIA and minor stroke associated with disability at 90 days

A detailed prospective study of transient ischemic attacks (TIAs) and minor stroke found 15% of patients were disabled at 90 days, even though most of them did not have a recurrent event.

Researchers prospectively enrolled consecutive patients with stroke rated less than 4 on the National Institutes of Health Stroke Scale or patients with TIA who were previously not disabled and had computed tomography or computed tomography angiography (CT/CTA) within 24 hours of symptoms.

Disability was assessed at 90 days using the modified Rankin Scale. Predictors of disability (modified Rankin Scale ≥2) and the relative impact of the initial event versus recurrent events were assessed. Results were published online Sept. 13 by Stroke.

Among 499 patients, 74 (15%; 95% CI, 12% to 18%) were disabled at 90 days. Baseline factors predicting disability as an outcome included being 60 years or older, having diabetes, having a premorbid modified Rankin Scale 1, having ongoing symptoms, having a CT/CTA-positive metric, or having positive diffusion-weighted imaging.

In the multivariable analysis, factors that predicted disability included ongoing symptoms (odds ratio [OR], 2.4; 95% CI, 1.3 to 4.4; P=0.004), diabetes (OR, 2.3; 95% CI, 1.2 to 4.3; P=0.009), female sex (OR, 1.8; 95% CI, 1.1 to 3; P=0.025), and CT/CTA-positive metric (OR, 2.4; 95% CI, 1.4 to 4; P=0.001).

Of the 463 patients who did not have a recurrent event, 55 were disabled (12%). Of the 36 who did have a recurrent event, 19 (53%) patients were disabled (risk ratio, 4.4; 95% CI, 3 to 6.6; P<0.0001). Researchers noted that recurrent events are a very important surrogate for disability but are numerically not the major factor in predicting disability.

"There has been a general emphasis on recurrent events after minor stroke or TIA rather than on disability, yet disability is the accepted outcome after disabling stroke," researchers wrote. "Our study is novel in that it emphasizes the need to examine disability even in minor stroke and brings together … careful clinical assessments and imaging data to emphasize this point."



Test yourself


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MKSAP Quiz: abnormal liver chemistry tests

A 25-year-old man is evaluated after being turned down as a blood donor because of abnormal liver chemistry tests. The patient is healthy, takes no medications, does not smoke, and drinks alcohol socially. His parents and siblings are alive and healthy; his maternal grandfather developed type 2 diabetes mellitus at age 75 years. The review of systems is normal.

mksap.jpg

On physical examination, vital signs and BMI are normal.

Laboratory studies:

Hemoglobin 11.9 g/dL (119 g/L)
Mean corpuscular volume 76 fL
Cholesterol (total) 155 mg/dL (4.01 mmol/L)
LDL cholesterol 85 mg/dL (2.2 mmol/L)
HDL cholesterol 33 mg/dL (0.85 mmol/L)
Bilirubin (total) 0.5 mg/dL (8.55 µmol/L)
Aspartate aminotransferase 25 U/L
Alanine aminotransferase 58 U/L
Alkaline phosphatase 110 U/L

Serologic tests for hepatitis virus infection are normal.

Which of the following is the most appropriate diagnostic test for this patient?

A) Anti-tissue transglutaminase antibody
B) α1-Antitrypsin concentration
C) Blood alcohol level
D) Liver biopsy

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


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Breast cancer


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Women with luminal A breast cancer have better short-term survival but long-term survival curves don't level off

Women with luminal A breast cancer have lower mortality rates than those with other subtypes but continue to see a decrease in survival after 10 years of follow-up, according to a new study of molecular tumor subtypes.

Researchers from Kaiser Permanente Southern California used data from the health system's cancer registry to identify women who were diagnosed with invasive breast cancer from Jan. 1, 1988 to Dec. 31, 1995, and whose tumors were classified as luminal A, luminal B, basal-like, or HER2-enriched. To determine survival, patients were followed from the date of their surgery to death, disenrollment from the health plan or the study's end in 2008. The study results were published online Sept. 18 by Cancer Epidemiology, Biomarkers & Prevention.

A total of 934 women with a mean age of 59 years were included in the study. Most of the women (86%) were of non-Hispanic white ethnicity, and 32% were diagnosed with breast cancer before age 50. Most (66%) had the luminal A tumor subtype, while 22% had basal-like tumors, 7% had HER2-enriched tumors, and 5% had luminal B tumors.

Over the 21 years of the study, 223 women (23.9%) died of breast cancer. Women with luminal A tumors survived the longest, while those with HER2-enriched and luminal B tumors had significantly shorter survival times (P<0.0001). Women with basal-like tumors had intermediate survival but tended to die sooner than women with luminal A disease. Mortality risk was higher in women with HER2-enriched tumors (hazard ratio, 2.56; 95% CI, 1.53 to 4.29) and those with luminal B tumors (hazard ratio, 1.96; 95% CI, 1.08 to 3.54) compared with luminal A tumors.

In women with HER2-enriched and luminal B tumors, survival dropped steeply during the first three to four years of follow-up but then leveled off in subsequent years, while women with basal-like tumors had a sharper decline in the first two to two-and-a-half years and a more gradual decrease to approximately 13 years. Women with the luminal A subtype saw a steady decrease in survival persisting after 10 years of follow-up.

The authors acknowledged that some tumor subtypes may have been misclassified, that they did not have data on treatment for recurrent disease, and that their cohort was treated before certain targeted therapies were available, among other limitations. However, they concluded that in this cohort of women, molecular subtypes strongly predicted risk for death from breast cancer, with a higher overall mortality rate for HER2-enriched and luminal B tumors and a persistent long-term risk for the luminal A subtype.

"Despite its markedly higher survival probabilities in earlier years of follow-up, luminal A subtype was the only subtype that continued a steady drop in survival over the 20-year period with little leveling off in later years," the authors wrote. They called for future studies to examine how the relationship between subtypes and survival varies by race and ethnicity and to determine factors to influence survival in women with luminal A disease.



Anticoagulant therapy


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Restarting warfarin after GI bleeding associated with better outcomes

Patients previously on warfarin who don't resume the therapy soon after a gastrointestinal (GI) bleeding event may have a higher risk for thrombosis and death, according to a new study.

Researchers from Kaiser Permanente Colorado performed a retrospective cohort study to examine time to resumption of anticoagulation and incidence of thrombosis, recurrent GI bleeding and death in the 90 days after a GI bleeding event. Clinical and administrative data were used to identify patients who developed GI bleeding while taking warfarin, stopped the therapy, and then did or did not restart it within 90 days. Outcomes were compared between the "resumed therapy" and "did not resume therapy" groups. The study results were published early online Sept. 17 by Archives of Internal Medicine.

A total of 442 patients with an index event of warfarin-associated GI bleeding were included in the study. Approximately half of the patients were men, and the mean age was 74.2 years. Overall, 46.2% of patients had taken aspirin in the 90 days before their first GI bleeding event.

Two hundred sixty patients (58.8%) resumed warfarin therapy within 90 days of the index event, and 182 (41.2%) did not. Resuming warfarin therapy was associated with a lower adjusted risk for thrombosis and death (hazard ratios, 0.05 [95% CI, 0.01 to 0.58] and 0.31 [95% CI, 0.15 to 0.62], respectively) and did not appear to significantly increase the risk for recurrent GI bleeding (hazard ratio, 1.32 [95% CI, 0.50 to 3.57]).

The authors noted that they could not assess all of the factors involved in physicians' clinical decisions about therapy, that there is potential for confounding, and that they did not have data on aspirin use after the index bleeding event. However, they concluded that thrombosis and death after GI bleeding are more likely in patients who do not resume warfarin therapy within 90 days, and that the benefits of the therapy will outweigh the risk in many cases. They called for further research to determine the optimal interval of warfarin interruption after GI bleeding and to better define which patients can tolerate a longer interruption in therapy.

An accompanying editorial outlined three key findings from the study: Patients and physicians are usually willing to restart warfarin after GI bleeding; anticoagulation was usually restarted within a week of the bleeding event; and recurrent bleeding events, none of which were fatal, occurred at an acceptably low rate.

Based on the available data, the editorialists wrote, "We believe that most patients with warfarin-associated GI bleeding and indications for continued long-term antithrombotic therapy should resume anticoagulation within the first week following the hemorrhage, approximately 4 days afterward." However, they advised against also continuing antiplatelet therapy in these patients without a "compelling indication" to do so and said that the study's findings should not be applied to patients taking new anticoagulant agents, such as dabigatran and rivaroxaban.



Kidney disease


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VTE risk appears to progressively increase as eGFR decreases and albumin-creatinine ratio increases

Even mild kidney disease is associated with an increase in risk of venous thromboembolism (VTE), a new review found.

The pooled analysis of individual data included five prospective cohort studies of almost 100,000 people in Europe and the United States. A total of 1,178 VTEs occurred during the follow-up of about six years. Using Cox regression models, the researchers calculated that patients with decreased estimated glomerular filtration rate (eGFR) had a higher risk of VTE than patients with an eGFR of 100 mL/min/1.73m2. The hazard ratio (HR) was 1.29 (95% CI, 1.04 to 1.59) for an eGFR of 75 mL/min/1.73m2, 1.31 (95% CI, 1.00 to 1.71) for an eGFR of 60 mL/min/1.73m2, 1.82 (95% CI, 1.27 to 2.60) for an eGFR of 45 mL/min/1.73m2 and 1.95 (95% CI, 1.26 to 3.01) for an eGFR of 30 mL/min/1.73m2.

A worse albumin-creatinine ratio (ACR) than 5.0 mg/g was also associated with higher risk of VTE: for 30 mg/g, the HR was 1.34 (95% CI, 1.04 to 1.72); for 300 mg/g, the HR was 1.60 (95% CI, 1.08 to 2.36); and for 1,000 mg/g, the HR was 1.92 (95% CI, 1.19 to 3.09). The associations of the two measurements with VTE were independent of each other and traditional cardiovascular risk factors, the researchers said. They concluded that mild changes in both eGFR and ACR are independently associated with more VTE, and that the risk increases progressively as eGFR declines and ACR increases. The study was published online by Circulation on Sept. 13.

The results clarify previous inconsistent findings on this question, the authors said, and support the existence of a direct association between chronic kidney disease and VTE. That association may result from endothelial injury or changes in procoagulant proteins, they suggested. Because these levels of chronic kidney disease are prevalent in the general population and are more modifiable with medication than most VTE risk factors, some VTEs might be prevented by attention to this relationship. Future studies should assess the impact of drugs that improve albuminuria on VTE, the authors said.



Resources


.
Reminder: Seasonal flu vaccine tool available

The U.S. Department of Health and Human Services' HealthMap Vaccine finder, a Web-based flu vaccine locator that helps physicians post their flu vaccine services, has been redesigned and is now available online.

The portal allows physician practices to enter information on their vaccine services into the online database, which can be accessed by the public. The website will play a significant role in helping patients access clinicians committed to improving the public health of their communities. More information is available online.



From the College


.
Apply for the 2013 Health Policy Internship

Applications are now being accepted for the 2013 ACP Health Policy Internship program.

The internship, which takes place in spring 2013, provides one Associate Member and one Medical Student Member with the opportunity to gain legislative knowledge and advocacy skills while working with the College's Washington office to prepare for ACP's annual Leadership Day. Applications are due by Oct. 22. Additional information can be found online.



From ACP Hospitalist


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The September issue is online

The September issue of ACP Hospitalist is online and includes stories about the following.

Diagnosing and treating factitious disorder. Incidence estimates suggest that more than 1% of medical admissions could be factitious, and that's not counting the patients no one catches. Learn how to spot and manage fibbing patients.

Disputes with colleagues. Occasional disagreements in the workplace are inevitable. If you know how to negotiate effectively, though, you can turn conflict into positive change for all concerned.

Allergic reactions in the hospital are sometimes hard to detect because their presentation is often delayed, but key steps in diagnosis and management can go a long way.



Cartoon caption contest


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Vote for your favorite entry

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

acpi-20120925-cartoon.jpg

"This isn't exactly what I pictured when your office said you were 'going green.'"

"I find this a much more relaxing way to see 18 patients per day."

"Yes, your symptoms are par for the course."

Go online to pick the winner, who receives a $50 gift certificate good toward any ACP program, product or service. Voting ends on Monday, Oct. 1, with the winner announced in the Oct. 2 issue.


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MKSAP Answer and Critique



The correct answer is A) Anti-tissue transglutaminase antibody. This item is available to MKSAP 15 subscribers as item 45 in the Gastroenterology section.

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

Celiac disease is a small-bowel disorder characterized by mucosal inflammation, villous atrophy, and crypt hyperplasia, which occur on exposure to gluten. The disease is rather common, affecting nearly 1% (1/133 persons) of the population. Although many affected patients have diarrhea and steatorrhea, as well as bloating, abdominal pain, and malabsorption of vitamins and minerals, other patients are asymptomatic at diagnosis. Such patients may be found to have anemia or osteoporosis as part of routine health maintenance testing. Still others present with neurologic symptoms, dermatitis herpetiformis, or elevated concentrations of liver enzymes. The elevated alanine aminotransferase in this patient should normalize with a gluten-free diet if he has celiac disease. The patient's elevated alkaline phosphatase concentration is likely the result of increased bone turnover as a result of vitamin D and calcium malabsorption. Celiac disease is one of the most common causes of osteoporosis in men. Measurement of serum anti-tissue transglutaminase antibodies has a sensitivity and specificity of approximately 90% for celiac disease.

α1-Antitrypsin deficiency affects approximately 1 in 1600 persons, and although measurement of α1-antitrypsin is an appropriate test in the work-up of abnormal liver function tests, it is not the next best test because of the low prevalence of the disease compared to celiac disease, and it cannot explain the patient's anemia. The patient admits to social use of alcohol, and this is to be strictly avoided in the setting of liver disease. Unless the patient was actively drinking alcohol around the time of the testing, measuring the blood alcohol would not be helpful. Furthermore, in alcoholic liver disease, the aspartate aminotransferase concentration is usually greater than the alanine aminotransferase. Liver biopsy would be an extreme measure to take as a result of a mildly abnormal set of liver chemistry tests and is not indicated as an initial step.

Key Point

  • Measurement of serum anti-tissue transglutaminase antibodies has a sensitivity and specificity of approximately 90% for celiac disease.

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