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

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ACP InternistWeekly



In the News for the Week of October 2, 2012




Highlights

EHRs may improve diabetes management and achievement of treatment goals, particularly among those with worst disease control

Use of a commercially available electronic health record (EHR) was associated with improved care processes and better achievement of intermediate treatment outcomes for outpatients with diabetes, a study found. More...

Benzodiazepines may confer dementia risk for elderly patients

Patients who started taking benzodiazepines after age 65 had a greater risk of developing dementia than those who never used the drugs, a study found. More...


Test yourself

MKSAP Quiz: Transfer prevented by low food intake, new bruising, gross hematuria

A 70-year-old malnourished man with a 4-year history of Alzheimer dementia is admitted to the intensive care unit from the emergency department for treatment of community-acquired pneumonia and impending respiratory failure. He is inattentive and confused and has a weak productive cough. What is the most likely diagnosis? More...


Nephrology

Two models may offer accurate assessment of GFR in older adults

Two newly developed estimates of glomerular filtration rate (GFR) may provide more accurate assessment of kidney function in older adults, a study found. More...


Anticoagulant therapy

New-generation anticoagulants associated with bleeding after ACS in patients on antiplatelet therapy

New-generation anticoagulants are associated with increased bleeding risk when used after acute coronary syndrome (ACS) in patients taking antiplatelet agents, according to a new meta-analysis. More...


Cardiology

Guidance issued on educational, psychological interventions for ICD patients

The American Heart Association released a scientific statement on educational and psychological interventions for patients with implantable cardioverter defibrillators (ICDs). More...


Resources for geriatrics

Guidance available for managing inappropriate meds, multiple comorbidities in the elderly

The American Geriatrics Society offers several updated resources for clinicians caring for elderly patients. More...


From ACP Internist

The next issue is online and coming to your mailbox

The October issue of ACP Internist is online and coming soon to your mailbox. More...


From the College

ACP physician wins national award for internal medicine education

Philip Masters, MD, FACP, is the recipient of the 2012 Ruth-Marie E. Fincher, MD, Service Award from the Clerkship Directors in Internal Medicine (CDIM), a national organization of leaders in internal medicine education for undergraduates. More...

Council of Young Physicians call for nominations

If you want to get involved nationally with physicians post-training please consider running for a seat on the ACP Council of Young Physicians (CYP). 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 Explorers' Day holiday.


Physician editor: Philip Masters, MD, FACP



Highlights


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EHRs may improve diabetes management and achievement of treatment goals, particularly among those with worst disease control

Use of a commercially available electronic health record (EHR) was associated with improved care processes and better achievement of intermediate treatment outcomes for outpatients with diabetes, a study found.

annals.jpg

To examine the association between the EHR and disease control in diabetics, researchers looked at diabetes management and treatment outcomes sequentially across 17 medical centers from 2004 to 2009, adjusting for variables including patient characteristics, medical center, time trends and facility-level clustering.

Data were derived from a commercially available, certified EHR in place at Kaiser Permanente Northern California, an integrated delivery system that included nearly 170,000 patients with diabetes.

Results appeared in the Oct. 2 Annals of Internal Medicine.

Use of an EHR was associated with:

  • clear improvement in treatment intensification with a trend toward statistical significance after hemoglobin A1c (HbA1c) values of 9% or greater (odds ratio [OR], 1.10; 95% confidence interval [CI], 1.05 to 1.15) or low-density lipoprotein (LDL) cholesterol values of 2.6 to 3.3 mmol/L (100 to 129 mg/dL) (OR, 1.06; 95% CI, 1.00 to 1.12);
  • increases in 1-year retesting for HbA1c and LDL cholesterol levels among all patients, with the most dramatic change among patients with the worst disease control (HbA1c levels ≥9% or LDL cholesterol levels ≥3.4 mmol/L [≥130 mg/dL]); and
  • decreased 90-day retesting among patients with HbA1c levels less than 7% or LDL cholesterol levels less than 2.6 mmol/L (<100 mg/dL).

EHR use was also associated with statistically significant reductions in HbA1c and LDL cholesterol levels, with the largest reductions among patients with the worst control (0.06-mmol/L [2.19-mg/dL] reduction among patients with baseline LDL cholesterol levels ≥3.4 mmol/L [≥130 mg/dL]; P<0.001).

Researchers concluded that use of the EHR was associated with improved drug treatment intensification, monitoring and physiologic control among patients with diabetes, with greater improvements among patients with worse control and less testing in patients already meeting guideline-recommended glycemic and lipid targets.

"Our findings, which are consistent across many steps in the care pathway and are proportional to clinical risk levels, suggest actual improvements in the clinical care of patients with diabetes," the researchers wrote. "These early effects on linked care processes and patient outcomes also suggest the potential for future downstream improvements in major clinical event rates and health. The lack of any measurable unintended harm in the outcomes for this study is also important because implementation of an EHR could worsen as well as improve care."


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Benzodiazepines may confer dementia risk for elderly patients

Patients who started taking benzodiazepines after age 65 had a greater risk of developing dementia than those who never used the drugs, a study found.

Researchers examined 3,777 community-dwelling French people age 65 years and older in a prospective cohort study on brain aging. They observed the subjects for three to five years to identify factors that led to benzodiazepine initiation, and then followed them for 15 years. Eligible subjects (n=1,063, mean age 78.2 years) were dementia-free and didn't start taking benzodiazepines until at least the third year of follow-up. The main outcome was incident dementia confirmed by a neurologist.

Results were published online by BMJ Sept. 27.

Nearly 9% (n=95) of patients started taking benzodiazepines during the study. These new users were more likely to be single or widowed, have less education, have more significant depressive symptoms, use antihypertensives, use platelet inhibitors or oral anticoagulants, and consume wine less regularly.

About 24% (n=253) of all patients developed dementia, including 30 benzodiazepine users and 223 non-users. Starting benzodiazepines was associated with a significant increase in the risk of developing dementia (hazard ratio [HR], 1.60; 95% confidence interval [CI], 1.08 to 2.38), a result that was basically unchanged when adjusted for depressive symptoms (HR, 1.62; 95% CI, 1.08 to 2.43).

In absolute numbers, the chance of dementia occurring was 4.8 per 100 person-years in the group that took benzodiazepines versus 3.2 per 100 person-years in the non-using group.

Benzodiazepines are useful for treating acute anxiety and persistent insomnia, but evidence is mounting that their use may have adverse outcomes in the elderly, including falls, fall-related fractures and now dementia, the authors wrote.

The effect on dementia in this study remained after adjustment for potential confounders, including cognitive decline before starting benzodiazepines and clinically significant symptoms of depression, they noted. They noted, too, that their study included "a run-in time of at least three years to allow adjustment for factors associated with starting benzodiazepines, thus reducing the possibility of reverse causation."

"Physicians should carefully assess the expected benefits of the use of benzodiazepines" and limit prescriptions to a few weeks when possible, they said. "In particular, uncontrolled chronic use of benzodiazepines in elderly people should be cautioned against," they wrote.



Test yourself


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MKSAP Quiz: Transfer prevented by low food intake, new bruising, gross hematuria

A 70-year-old malnourished man with a 4-year history of Alzheimer dementia is admitted to the intensive care unit from the emergency department for treatment of community-acquired pneumonia and impending respiratory failure. He is inattentive and confused and has a weak productive cough. His only medications are donepezil and memantine.

mksap.jpg

Temperature was 38.3 °C (101.0 °F), blood pressure was 100/62 mm Hg, pulse rate was 110/min, and respiration rate was 26/min; BMI was 18 kg/m2. Arterial oxygen saturation on ambient air was 92%. Pulmonary examination revealed crackles in the right lower lobe. A chest radiograph confirmed an extensive right lower lobe pneumonia.

The patient was treated with ceftriaxone and azithromycin, oxygen, and low-dose unfractionated heparin, 5000 U, three times daily. During the subsequent 48 hours, he had several episodes of hypotension and oxygen desaturation that responded to intubation, mechanical ventilation, and intravenous fluids. By day 4, his serum creatinine level increased to 4.0 mg/dL (305.2 µmol/L) before returning to his hospital-admission value of 1.2 mg/dL (91.6 µmol/L) by day 7. On day 8 he was successfully extubated and transferred to the medicine ward. His wife agreed to his transfer to a nursing home.

At day 10 of hospitalization he is ready for transfer, but he is eating little and develops new bruising on his extremities and gross hematuria.

Day 10 laboratory studies:

Platelet count 152,000/µL (152 × 109/L)
INR 7.7
Activated partial thromboplastin time 46 s
Thrombin time 16 s (control, 15 s)
Fibrinogen 450 mg/dL (4.5 g/L)
D-dimer assay Mildly elevated
Mixing study Corrects to near normal

Which of the following is the most likely diagnosis?

A) Disseminated intravascular coagulation
B) Heparin toxicity
C) Presence of a lupus inhibitor
D) Vitamin K deficiency

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


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Nephrology


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Two models may offer accurate assessment of GFR in older adults

Two newly developed estimates of glomerular filtration rate (GFR) may provide more accurate assessment of kidney function in older adults, a study found.

annals.jpg

To derive the Berlin Initiative Study (BIS) equation, researchers designed a cross-sectional, random community-based population of participants age 70 years or older (mean age, 78.5 years) from a large insurance company. Data were split for analysis into two sets for equation development and internal validation.

Two estimates of GFR were developed and validated, one based on creatinine only (BIS1) and one based on both creatinine and cystatin C measurements (BIS2). Results appear in the Oct. 2 Annals of Internal Medicine.

The new BIS2 equation yielded the smallest bias, followed by BIS1 and Cockcroft-Gault equations. All other equations considerably overestimated GFR.

The BIS equations confirmed a high prevalence of persons older than 70 years with a GFR less than 60 mL/min per 1.73 m2 (BIS1, 50.4%; BIS2, 47.4%; measured GFR, 47.9%). The total misclassification rate for this criterion was smallest for the BIS2 equation (11.6%), followed by the cystatin C equation 2 (15.1%), a GFR estimation equation proposed by the Chronic Kidney Disease Epidemiology Collaboration. Among the creatinine-based equations, BIS1 had the smallest misclassification rate (17.2%), followed by the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation (20.4%).

Researchers noted that the BIS2 equation should be used to estimate GFR in persons age 70 years or older with normal or mild to moderately reduced kidney function. If cystatin C is not available, the BIS1 equation is an acceptable alternative.

"Compared with current creatinine-based or creatinine- and cystatin C-based equations, the new BIS1 and BIS2 equations showed better precision and excellent agreement with [measured]GFR, especially in a population with an [estimated]GFR greater than 30 mL/min per 1.73 m2 (CKD [chronic kidney disease] stages 1 to 3)," researchers wrote. "This is important because a validated equation to estimate GFR in older adults, especially in cases of normal or only moderately reduced kidney function, has been lacking."

Also, researchers noted that older adults may be a unique population in which traditional assumptions about GFR are not necessarily true and the existing, commonly used methods for estimating GFR may not be accurate. In elderly participants, the Modification of Diet in Renal Disease (MDRD) study equation yielded higher estimated GFRs across CKD stages than did the CKD-EPI and especially the Cockcroft-Gault equation. This contrasts with the situation in younger adults in whom implementation of the CKD-EPI equation has reduced CKD prevalence but agrees with current results seen in older adults.

"The most striking result was that incorporation of cystatin C in the equation decreased the effect of age and sex," researchers wrote. "This confirms the independence of cystatin C from age- and sex-associated conditions and may thus make it the preferred laboratory variable to be included in a GFR-estimating equation in an elderly population where reduction in muscle mass is common."



Anticoagulant therapy


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New-generation anticoagulants associated with bleeding after ACS in patients on antiplatelet therapy

New-generation anticoagulants are associated with increased bleeding risk when used after acute coronary syndrome (ACS) in patients taking antiplatelet agents, according to a new meta-analysis.

Researchers analyzed data from randomized, placebo-controlled trials that examined anti-Xa or direct thrombin inhibitors in post-ACS patients who were receiving antiplatelet therapy. Stent thrombosis, overall mortality rate and a composite end point including major ischemic events were evaluated as efficacy measures. Thrombolysis in myocardial infarction (MI) bleeding events were the safety end point. The researchers calculated the net clinical benefit of therapy by summing composite ischemic events and major bleeding events.

Results were published online Sept. 24 by Archives of Internal Medicine.

Seven trials published between Jan. 1, 2000 and Dec. 31, 2011 were included in the meta-analysis. The trials involved 31,286 patients who had been admitted to the hospital for unstable angina pectoris, ST-segment elevation MI, or non-ST-segment elevation MI. Patients with severe cardiac, renal or liver insufficiency and those with high bleeding risk were excluded. Follow-up ranged from three months to five years.

Overall, new-generation oral anticoagulants were associated with a significant increase in major bleeding in patients receiving antiplatelet therapy after ACS (odds ratio, 3.03; P<0.001). Risk for stent thrombosis or composite ischemic events was significantly but moderately reduced with the new agents, while no significant effect was seen on overall mortality. The new anticoagulants did not appear to provide an advantage over placebo in net clinical benefit (odds ratio, 0.98; P=0.57).

The authors noted that some of the included trials had high rates of drug discontinuation or had short follow-up periods. In addition, the trials evaluated different drugs in different dosages and used different definitions of composite outcomes. However, the authors concluded that anti-Xa and direct thrombin inhibitors are linked to increased major bleeding risk in ACS patients receiving antiplatelet therapy, to the point that the net clinical benefit of the drugs is neutral.

"Because the use of new-generation P2Y12 ADP-receptor antagonists may result in greater reductions of ischemic events, with substantially lower risk for bleeding complications, the role of oral anticoagulant agents after an ACS is debatable," they wrote.

An invited commentary pointed out that while the relative risk for major bleeding seemed dramatic, the absolute risk increase was 0.9%, 1.3% for novel oral anticoagulants compared with 0.4% for control therapy. However, the absolute risk decreases for the composite ischemic outcome and for MI were −1.3% (6.5% vs. 7.8%) and −0.8% (3.7% vs. 4.5%), respectively, and the absolute risk differences for net clinical benefit and for overall death were each −0.5%.

"The benefit is largely canceled by the harm; therefore, the routine use of [novel anticoagulants] among patients with ACS is unwarranted," the commentary author wrote. He called for additional research to examine the use of newer anticoagulants in specific populations of patients with ACS.



Cardiology


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Guidance issued on educational, psychological interventions for ICD patients

The American Heart Association released a scientific statement last week on educational and psychological interventions for patients with implantable cardioverter defibrillators (ICDs).

An expert panel analyzed existing scientific evidence to examine psychological and quality-of-life outcomes after ICD receipt. The group also looked at data supporting interventions to improve ICD patients' educational and psychological needs, provided clinical recommendations for improving outcomes, and identified areas for future research.

The statement, which was published online Sept. 24 by Circulation, was endorsed by the Heart Rhythm Society and the American Association of Critical-Care Nurses.

The clinical practice recommendations covered four categories: preimplantation; postimplantation, early recovery and adjustment; ICD events; and end of life. They included the following:

  • Emphasize the protective value of the ICD against sudden cardiac arrest but no effect on the underlying cardiac condition separate from biventricular pacing or other functions of the device, if present.
  • Review the expected impact of the ICD on usual activities, including driving, travel, sexual and physical activity, and length of time for restrictions, if any.
  • Provide instructions on wound care, medications, and pain and symptom management, and address concerns before hospital discharge.
  • Provide a clear and succinct shock plan for what the patient and family are expected to do in the event of a shock.
  • Promote problem solving, access to information, and ways to seek social support as problem-focused coping strategies. Consider structured support groups that focus on providing information and positive coping skills.
  • Discuss the meaning of shocks with patients when they occur.
  • Hold face-to-face discussions when possible with the patient and his or her family regarding the specifics of any advisory or recall.
  • At end of life, review patient and family understanding of their disease, goals of care, and desired outcomes, as well as the relationship of the ICD to those stated goals. Discuss the potential to deactivate the shocking component of the ICD.

The panel experts recommended "that psychological and [quality-of-life] assessments be integrated into the designs of all mortality and morbidity focused clinical trials of new devices and ICD populations and that family members be included to the degree possible."

The full text of the statement is available free of charge online.



Resources for geriatrics


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Guidance available for managing inappropriate meds, multiple comorbidities in the elderly

The American Geriatrics Society offers several updated resources for clinicians caring for elderly patients.

The AGS Updated Beers Criteria for Potentially Inappropriate Medication Use in Older Adults are available online, including a free smartphone app, a pocket card, and teaching slides.

Also available are "Guiding Principles for the Care of Older Adults with Multimorbidity," which aim to help clinicians manage elderly patients with three or more chronic diseases. Clinical tools and implementation practices are included.

More information is available online.



From ACP Internist


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The next issue is online and coming to your mailbox

The October issue of ACP Internist is online and coming soon to your mailbox. Topics include:

acpi-20121002-internist.jpg

Patients and prayer amid medical practice. It's more important than ever to recognize and understand cultures and spiritual beliefs, including and beyond the end of life.

PPI's benefits can outweigh their possible risks. The key to proper use of proton-pump inhibitors is monitoring patients closely to determine if they are benefitting from long-term therapy, or could potentially discontinue or reduce their dose.

White coat hypertension presents an elusive challenge. Although white coat hypertension is chalked up to general anxiety, it may be the medical setting, and specifically the physician, that acts as the trigger.

More stories, including a MKSAP Quiz on hematology and oncology and an account of how one physician diagnosed his own mysterious symptoms, are online.



From the College


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ACP physician wins national award for internal medicine education

Philip Masters, MD, FACP, is the recipient of the 2012 Ruth-Marie E. Fincher, MD, Service Award from the Clerkship Directors in Internal Medicine (CDIM), a national organization of leaders in internal medicine education for undergraduates.

Dr. Masters is a senior medical associate for content development at ACP and a physician-editor for ACP InternistWeekly.

The Ruth-Marie E. Fincher, MD, Service Award is presented annually to a CDIM member who has made sustained and extraordinary contributions to the mission of CDIM through leadership and service to the association. Dr. Masters has served CDIM as a member, chair of multiple committees and programs, and president. He will receive the award later this month during the 2012 CDIM National Meeting, held as part of Academic Internal Medicine Week 2012.


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Council of Young Physicians call for nominations

If you want to get involved nationally with physicians post-training please consider running for a seat on the ACP Council of Young Physicians (CYP). The CYP is responsible for advising ACP about programming to enhance the professional development for young physicians, fostering their involvement in College activities, and increasing the value of ACP membership for physicians post-training.

For details, go online to The Young Physician's Corner.



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-20121002-cartoon.jpg

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

This issue's winning cartoon caption was submitted by Teresa Loden, a Medical Student Member at the A.T. Still University-Kirksville College of Osteopathic Medicine. Thanks to all who voted! The winning entry captured 50.5% of the votes.

The runners-up were:

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

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


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MKSAP Answer and Critique



The correct answer is D) Vitamin K deficiency. This item is available to MKSAP 15 subscribers as item 37 in the Hematology and Oncology section.

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

Clotting factors II, VII, IX, and X, as well as protein C and protein S, require vitamin K–dependent gamma carboxylation for full activity. Dietary vitamin K is obtained primarily from the intake of dark green vegetables and is modified by gut flora to the active form. Interruption of bile flow prevents absorption of vitamin K. Antibiotic-related elimination of enteric bacteria limits intestinal sources of vitamin K, whereas warfarin directly antagonizes vitamin K activity. The prothrombin time (PT) is the first clotting time to become prolonged, but the activated partial thromboplastin time (aPTT) will also lengthen with further factor deficiencies. Therefore, a progressively prolonged PT (with the PT proportionately more prolonged than the aPTT) and a normal thrombin time in a malnourished patient receiving antibiotics should raise the suspicion for vitamin K deficiency. In adults with normal hepatic function, oral or subcutaneous vitamin K usually corrects the clotting times within 24 hours; intravenous vitamin K confers an increased risk for anaphylaxis. Fresh frozen plasma is used when urgent correction is required.

In this patient, the normal thrombin time and platelet count and elevated fibrinogen level are not suggestive of a diagnosis of disseminated intravascular coagulation (DIC) or liver disease. DIC would be a consideration in patients with a constellation of findings, including elevated levels of fibrin degradation products and/or fibrinogen D-dimer, sometimes accompanied by a prolonged PT, a decreased fibrinogen level, and thrombocytopenia.

Antibodies directed against clotting factors are rare but can result in potentially lethal, acquired bleeding disorders. Most such antibodies are considered idiopathic, but they may develop because of drugs or as part of an underlying illness, such as malignancy or autoimmune disorders (for example, systemic lupus erythematosus or rheumatoid arthritis). Diagnosis is made by identification of a protracted clotting time that does not correct with a mixing study. Quantifying the inhibitor by obtaining an inhibitor titer helps determine treatment options. Causes of such acquired bleeding disorders include the use of fibrin sealants during procedures, the presence of antiphospholipid antibodies, and the use of antibiotics. Because the PT/INR mixing study corrects to normal, a lupus inhibitor is excluded in this patient. In addition, low-dose heparin has no effect on INR and should not result in the clinical bleeding present in this patient. Finally, positive D-dimer results are to be expected in any hospitalized, ill patient with ongoing inflammation, and in the absence of any other findings, have no diagnostic significance.

Key Point

  • A progressively prolonged prothrombin time (PT) and activated partial thromboplastin time (aPTT) (with the PT proportionately more prolonged than the aPTT) with a normal thrombin time in a malnourished patient who has received antibiotics is suggestive of vitamin K deficiency.

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Test yourself

A 72-year-old woman is evaluated during a routine examination. She has very severe COPD with multiple exacerbations. She has dyspnea at all times with decreased exercise capacity. She does not have cough or any change in baseline sputum production. She is adherent to her medication regimen, and she completed pulmonary rehabilitation 1 year ago. She quit smoking 1 year ago. Her medications are a budesonide/formoterol inhaler, tiotropium, and an albuterol inhaler as needed. Following a physical and pulmonary exam, what is the most appropriate next step in management?

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