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ACP InternistWeekly



In the News for the Week of 8-9-11




Highlights

Newer antidepressants not necessarily safest for older people

Selective serotonin reuptake inhibitors are associated with an increased risk of several severe adverse outcomes in older people compared with older tricyclic antidepressants, a study found. More...

Risk framing alters perception of benefit; doctors just as prone as patients, study finds

How risk information is posed influences perceptions of treatment benefit, with absolute survival rates creating the perception of weakest benefit and relative mortality reduction creating the perception of greatest benefit, researchers found in a recent study. More...


Test yourself

MKSAP Quiz: evaluating 'a sense of unsteadiness'

This week's quiz asks readers to evaluate ongoing dizziness in an elderly woman. More...


Thromboprophylaxis

Very elderly patients can benefit from well-managed vitamin K antagonist thromboprophylaxis, study suggests

Adequate management of vitamin K antagonist (VKA) therapy in trained centers allowed very old and frail patients to benefit from VKA thromboprophylaxis, an Italian study concluded. More...


Stroke

Stroke risk may increase after traumatic brain injury

Risk for stroke may increase after a traumatic brain injury, according to a new study. More...


Computers and medicine

Take ACP Internist's poll on looking up information in front of a patient

How often have you gone online in front of a patient to look up information? More...


From the College

Fred Ralston Jr., MACP, blogs at KevinMD.com

Fred Ralston Jr., MACP, ACP's immediate past president and a practicing internist in Fayetteville, Tenn., blogs about a new joint clinical practice guideline for stable COPD at KevinMD.com. 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: Darren Taichman, FACP




Highlights


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Newer antidepressants not necessarily safest for older people

Selective serotonin reuptake inhibitors (SSRIs) are associated with an increased risk of several severe adverse outcomes in older people compared with older tricyclic antidepressants (TCAs), a study found.

To investigate the association between antidepressant treatment and the risk of a number of potentially life-threatening outcomes in older people, researchers identified from 570 general practices in the U.K. a total of 60,746 patients ages 65 and older with a newly diagnosed episode of depression between 1996 and 2007. Of that group, 54,038 (89%) received at least one prescription for an antidepressant. A total of 6,484 patients (10.7% of the entire cohort) received one prescription, and 6,624 (10.9%) received 60 prescriptions or more during follow-up. The median duration of treatment was 364 days (interquartile range, 91 to 1,029).Of the nearly 1.4 million prescriptions issued, 55% were for SSRIs, 32% for TCAs, 0.2% for monoamine oxidase inhibitors (MAOIs), and 13.5% for other classes.

Antidepressant use was then analyzed against several adverse outcomes, including all-cause mortality, attempted suicide or self-harm, heart attack, stroke, falls, fractures, epilepsy or seizures, and hyponatremia. Results were published online Aug. 2 by BMJ.

SSRIs were associated with an increased risk of all-cause mortality, epilepsy or seizures, stroke, falls, fracture and hyponatremia compared with TCAs. The group of other antidepressants was associated with an increased risk of all-cause mortality, attempted suicide or self-harm, stroke, fracture, and epilepsy or seizures compared to TCAs.

Depressed patients not taking antidepressants at all had a 7% risk of dying (absolute risk of all-cause mortality) in the next year, while the comparable risks were 8.1% for those taking TCAs, 10.6% for those taking SSRIs, and 11.4 % for those taking other antidepressants. For stroke, one-year risks were 2.3%, 2.6% and 3.0% for TCAs, SSRIs, and other antidepressants, respectively, compared to 2.2% for those not on antidepressants, and one-year risks for fracture were 2.2%, 2.7% and 2.8% compared to 1.8%.

The authors attempted to reduce indication bias by restricting the study cohort to patients with a recorded diagnosis of depression so all patients had the same indication for treatment, whether treated or not. They also attempted to adjust for channeling bias by adjusting at baseline for potential confounders, such as falls, and attempted to adjust for residual confounding through a self-controlled case series analysis. The authors pointed out that TCAs were prescribed at lower doses than SSRIs and other antidepressant drugs, which could in part explain the findings.

An accompanying editorial said "[T]he study has clear implications for more informed prescribing and enhanced clinical monitoring," adding, "Given the potential harms, the decision to prescribe for an older person with depression should not be taken lightly."

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Risk framing alters perception of benefit; doctors just as prone as patients, study finds

How risk information is posed influences perceptions of treatment benefit, with absolute survival rates creating the perception of weakest benefit and relative mortality reduction creating the perception of greatest benefit, researchers found in a recent study.

Comprehensive information that combines absolute mortality, absolute survival, and relative mortality reduction produces the most accurate decisions. Surprisingly, the study found that framing bias was similar in doctors and patients.

To determine which risk framing format best conveys information, and to compare framing bias in doctors and in patients, researchers mailed 1,431 randomized surveys to every doctor in Geneva, Switzerland (56% response rate), and to 1,121 recently hospitalized patients (65% response rate).

Respondents were asked to interpret the results of a hypothetical clinical trial comparing an old drug to a new one. They were randomly assigned to framing formats of absolute survival (96% for the new drug vs. 94% for the old drug), absolute mortality (4% vs. 6%), relative mortality reduction (reduction by a third) or all three (fully informed condition). Results were published online July 27 by the Journal of General Internal Medicine.

The risk presentation format influenced whether doctors rated the new drug as more effective (absolute survival, 51.8%; absolute mortality, 68.3%; relative mortality reduction, 93.8%; and fully informed condition, 69.8%; P<0.001). These proportions were similar in patients (absolute survival, 51.7%; absolute mortality, 66.8%; relative mortality reduction, 89.3%; and fully informed condition, 71.2%; P<0.001). None of the differences between doctors and patients were significant (all P>0.1).

The fully informed condition was similar to the absolute risk format for both doctors (P=0.72) and patients (P=0.23), but it differed significantly from the other conditions (all P<0.01). In comparison to the fully informed condition, the odds ratio of greater perceived effectiveness was 0.45 for absolute survival (P<0.001), 0.89 for absolute mortality (P=0.29), and 4.40 for relative mortality reduction (P<0.001).

Absolute risks constitute the least biased risk format, the authors concluded. In contrast, relative risk reductions create an optimistic bias of a more than fourfold increase in the odds of a positive assessment of the new treatment. Absolute survival proportions caused a pessimistic bias, with a more than twofold decrease in the odds of a favorable assessment.

That doctors and patients had similar vulnerabilities to framing bias was unexpected, the authors wrote: "[W]e thought that doctors would be more sophisticated than patients in interpreting the scenario, less likely to be convinced by a relative mortality reduction with no absolute risk to anchor the comparison, and more apt to deduce the proportion of patients who died when the proportion who survived was given. This illustrates the difficulty that many doctors have in applying quantitative analysis skills in their practice."

The authors continued that doctors' understanding of various terms used in medical literature, such as relative risk, absolute risk, or the number needed to treat, does not translate to forming an objective, criterion-based assessment. Most doctors, they wrote, misunderstand numerical data about test accuracy, regardless of whether they are presented as sensitivity and specificity or likelihood ratios, and fail to use relevant numerical information, such as disease prevalence, when they interpret diagnostic test results.

The solution, the authors concluded, is to present risk and benefit information in absolute and relative scales and to report absolute risks in medical research reports and other original sources of medical information used by doctors.

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Test yourself


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MKSAP Quiz: evaluating 'a sense of unsteadiness'

An 89-year-old woman is evaluated for dizziness that she has had for the past year, mainly while standing and ambulating. The dizziness is described as a sense of unsteadiness. The symptoms can last for minutes to hours, and she has at least 4 to 5 episodes per day. There are no reproducible activities that cause the dizziness. She does not describe hearing loss, headache, diplopia, or other motor or sensory symptoms.

Medical history is remarkable for a 15-year history of type 2 diabetes mellitus, hypertension, hyperlipidemia, osteoporosis, and mild dementia. Current medications are hydrochlorothiazide, ramipril, simvastatin, metformin, insulin glargine, low-dose aspirin, and donepezil. She has not started any new medications recently, and she has no known drug allergies.

Vital signs are normal; there is no evidence of orthostasis. BMI is 27. A cardiopulmonary examination is normal. The patient has a positive Romberg sign and is unsteady on tandem gait. Rapid alternating movements are slowed. The patient has a corrected visual acuity of 20/50 in the right eye and 20/70 in the left eye. Vibratory sense and light touch are diminished in a stocking pattern in the lower extremities, and ankle jerk reflexes are 1+. The patient's Mini-Mental State Examination score is 26/30 (normal ≥24/30), unchanged from one year ago. She has no motor abnormalities and no cranial nerve abnormalities. A Dix-Hallpike maneuver does not elicit vertigo or nystagmus.

A complete blood count, metabolic profile, and thyroid function studies are normal.

Which of the following management options is the best choice for this patient?

A) Brain MRI
B) Meclizine
C) Physical therapy
D) Replace aspirin with aspirin/extended-release dipyridamole

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

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Thromboprophylaxis


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Very elderly patients can benefit from well-managed vitamin K antagonist thromboprophylaxis, study suggests

Adequate management of vitamin K antagonist (VKA) therapy in trained centers allowed very old and frail patients to benefit from VKA thromboprophylaxis, an Italian study concluded.

To evaluate the quality of anticoagulation and the incidence of bleeding, Italian researchers performed a prospective observational study that enrolled from 27 centers 4,093 patients 80 years of age or older who were naive to VKA for thromboprophylaxis of atrial fibrillation (AF) or after venous thromboembolism (VTE).

Major end points of the study were:

  • first major bleeding, defined as fatal, intracranial (documented by imaging), ocular causing blindness, articular, or retroperitoneal bleeding;
  • when surgery or another invasive procedure was needed to stop bleeding;
  • when transfusion of more than 2 units of blood was required; or
  • when hemoglobin was reduced by more than 2 g/dL.

Follow-up was stopped after the first major bleed occurred, after the cessation of oral anticoagulation, or when a patient was no longer monitored by the participating center. Results were published online Aug. 1 by Circulation.

The follow-up was 9,603 patient-years; median age at the beginning of follow-up was 84 years (range, 80 to 102 years). During follow-up, 385 patients died (total mortality rate, 4.0 per 100 patient years). Of these, 26 (6.8%) died of hemorrhagic complications, 112 (29.1%) of cardiovascular disease, 34 (8.8%) of sudden death, 12 (3.1%) of stroke, 56 (14.5%) of cancer, and 145 (37.7%) of another disease unrelated to VKA treatment.

There were 179 major bleedings (rate, 1.87 per 100 patient-years), of which 53 (rate, 0.55 per 100 patient-years) were intracranial and 26 were fatal (rate, 0.27 per 100 patient-years). The rate of bleeding was higher in men than in women (relative risk [RR], 1.4; 95% CI, 1.12 to 1.72; P=0.002) and among patients 85 years of age or older compared with younger patients (RR, 1.3; 95% CI, 1.0 to 1.65; P=0.048).

The first three months of treatment were associated with a high risk of bleeding (RR, 2.4), as were renal failure, history of previous bleeding events, history of falling (a fivefold higher risk), and active cancer. Patients with prior gastroenterological bleedings were especially prone to recurrence (hazard ratio, 6.2).

The distribution of bleeding events in relation to indication for VKA treatment was higher among patients on VKA for VTE compared with patients on VKA for AF (RR, 1.4; 95% CI, 1.1 to 1.8; P=0.03).

The authors wrote, "In this large study on very old patients on VKA treatment, the rate of bleeding complications was low, suggesting that age in itself should not be considered a contraindication to treatment. Adequate management of VKA therapy through careful monitoring of patients in specifically trained centers allows very old and frail patients to benefit from VKA thromboprophylaxis."

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Stroke


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Stroke risk may increase after traumatic brain injury

Risk for stroke may increase after a traumatic brain injury (TBI), according to a new study.

Researchers in Taiwan used a national database to compare stroke risk in patients who had sustained a TBI and those who had not. The population-based study included 23,199 patients with a diagnosis of TBI who had received ambulatory or inpatient care and 69,597 control patients without TBI matched for sex, age, and year of index health care use. Patients were followed for five years, and both short-term and long-term effects were assessed. The study results were published online July 28 by Stroke.

The mean age of patients in both groups was 41.6 years, and more than half (53.6%) were men. At three months, 2.91% of patients in the TBI group and 0.30% in the non-TBI group had had strokes. At one year and five years, these percentages were 4.17% versus 0.96% and 8.20% versus 3.89%, respectively. After adjustment for comorbid conditions and sociodemographic characteristics, patients with TBI had a 10.21 (95% CI, 8.71 to 11.96) times greater risk for stroke at three months, a 4.61 (95% CI, 4.16 to 5.11) times greater risk at one year and a 2.32 (95% CI, 2.17 to 2.47) times greater risk at five years. Patients with TBI also had a greater risk for all subtypes of stroke, especially intracerebral hemorrhage, over the five-year follow-up period.

The authors acknowledged that the database used for the study included only patients who sought treatment for TBI and stroke, that some patients could have been lost to follow-up, and that data on clinical severity, imaging and such variables as smoking and body mass index were not available. However, they concluded that their study shows an elevated risk for stroke after TBI. "A coordinated and systematic approach should be adopted to prevent patients with TBI from subsequent stroke and to optimize outcomes," they wrote. "Future studies are needed to elucidate the mechanisms by which TBI is associated with stroke."

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Computers and medicine


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Take ACP Internist's poll on looking up information in front of a patient

Researching medical knowledge online involves knowing three different types of resources: summary sites, society sites and primary literature. Knowing when to use each ensures the physician makes the correct diagnosis, and preserves the patient's confidence. How often have you gone online in front of a patient to look up information?

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From the College


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Fred Ralston Jr., MACP, blogs at KevinMD.com

Fred Ralston Jr., MACP, ACP's immediate past president and a practicing internist in Fayetteville, Tenn., is the College's new monthly contributor to KevinMD.com, one of the Web's most influential medical blogs. Dr. Ralston's first post looks at the new joint clinical practice guideline for stable COPD developed by ACP and three other physician organizations.

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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-20110809-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 C) Physical therapy. This item is available to MKSAP 15 subscribers as item 34 in the General Internal Medicine section.

Disequilibrium in the elderly is often described as a vague sense of unsteadiness, most often occurring while standing or walking. It is different than orthostatic hypotension in that symptoms are not always temporally related to moving from a seated to a standing position and are not associated with a drop in blood pressure. Disequilibrium in the elderly is often multifactorial, with contributors including peripheral neuropathy, visual loss, a decline in bilateral vestibular function, deconditioning, autonomic neuropathy, and medication side effects. Treatment of disequilibrium involves reducing polypharmacy, installing safety features in patients' homes, providing assistive devices such as walkers and canes, correcting eyesight and hearing if possible, and instituting physical therapy to improve muscle strength. Referral to physical therapy would be an appropriate first step for this patient.

Neuroimaging should usually be reserved for patients with signs suggesting potentially serious underlying conditions, such as cerebellar or focal neurologic symptoms or vertical nystagmus. There is no evidence that this patient has a new neurologic lesion. Therefore, obtaining an MRI is not indicated.

Meclizine can be of use in patients with prolonged or sustained vertigo such as in acute viral labyrinthitis. However, for intermittent episodes of unsteadiness, it is not likely to be of benefit and will add to her polypharmacy.

The combination of aspirin and dipyridamole is an effective strategy for the secondary prevention of ischemic stroke. However, there is no evidence that such treatment improves disequilibrium in the elderly.

Key Point

  • Dizziness in geriatric patients is often multifactorial and caused by deficits in multiple sensory systems and medication side effects.

Click here to return to the rest of ACP InternistWeekly.

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Test yourself

A 66-year-old man comes for a preoperative evaluation before total joint arthroplasty of the left knee. He has a 25-year history of rheumatoid arthritis. He has had progressive pain in his left knee with activity, which limits his ability to hike. The patient has similar pain in the right knee, but it is less severe. He reports no recent morning stiffness. He is able to climb two or three flights of stairs without chest pain or shortness of breath. He has no other medical problems and reports no additional symptoms. Medications are methotrexate and folic acid. Following a physical exam and lab tests, what is the next best step in management?

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