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

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ACP InternistWeekly



In the News for the Week of 7-26-11




Highlights

Stopping aspirin may raise risk for non-fatal heart attacks in heart disease patients

People with heart disease who quit their low-dose aspirin regimens are at increased risk of non-fatal myocardial infarction compared with those who remain compliant, a British study concluded. More...

Two antidepressants ineffective for depression in patients with dementia

Sertraline (Zoloft) or mirtazapine (Remeron) was not better than placebo for depression in Alzheimer's disease, and both drugs were associated with higher rates of nausea and drowsiness, a British study found. More...


Test yourself

MKSAP Quiz: reevaluation after failed thyroid tests

This week's quiz asks readers to reevaluate an elderly patient after abnormal results on thyroid tests. More...


Cardiology

Intima-media thickness may improve cardiac risk prediction, study suggests

Adding a measurement of the maximum intima-media thickness of the internal carotid artery may increase the prognostic value of the Framingham risk score for cardiovascular events, according to a new study. More...


Infection control

CDC releases infection prevention guide for outpatient care

The Centers for Disease Control and Prevention has released an infection prevention guide aimed at outpatient facilities. More...


Physician editor: Darren Taichman, FACP




Highlights


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Stopping aspirin may raise risk for non-fatal heart attacks in heart disease patients

People with heart disease who quit their low-dose aspirin regimens are at increased risk of non-fatal myocardial infarction compared with those who remain compliant, a British study concluded.

To evaluate the risk of myocardial infarction and death from coronary heart disease after stopping low-dose aspirin (75 to 300 mg/d), researchers conducted a nested, case-control study of 39,513 patients ages 50 to 84 years with a first prescription for aspirin for secondary prevention of cardiovascular outcomes in 2000 through 2007.

The population was drawn from The Health Improvement Network (THIN) database, which has data on more than 3 million patients enrolled in primary care practices in the United Kingdom. Results appeared online at BMJ on July 19. Individuals were followed for a mean of 3.2 years.

During follow-up, there were 2,869 deaths from all causes, 876 non-fatal myocardial infarctions and 346 deaths from coronary heart disease. People who had recently stopped taking aspirin had a 60% increased risk of non-fatal myocardial infarction (rate ratio [RR], 1.63, 95% CI, 1.23 to 2.14) and an approximate 40% increased risk of non-fatal myocardial infarction or death from coronary heart disease (RR, 1.43; 95% CI, 1.12 to 1.84). For every 1,000 patients, there were about four more cases of non-fatal myocardial infarction per year among patients who'd recently stopped taking low-dose aspirin.

The authors noted that half of all people prescribed a low-dose aspirin regimen become non-compliant after a few years. They called for future studies to determine whether encouraging patients to continue low-dose aspirin prophylactically would decrease non-fatal myocardial infarction.

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Two antidepressants ineffective for depression in patients with dementia

Sertraline (Zoloft) or mirtazapine (Remeron) was not better than placebo for depression in Alzheimer's disease, and both drugs are associated with higher rates of nausea and drowsiness, a British study found.

Researchers conducted a parallel-group, double-blind, randomized, placebo-controlled study, the Health Technology Assessment Study of the Use of Antidepressants for Depression in Dementia (HTA-SADD), in patients using geriatric psychiatry services in nine centers. Participants were eligible if they had probable or possible Alzheimer's disease, depression (lasting more than 4 weeks), and a Cornell scale for depression in dementia (CSDD) score of 8 or more.

Patients received sertraline (150 mg/d), mirtazapine (45 mg), or placebo, all with standard care. The primary outcome was reduction in CSDD score at 13 weeks. Results appeared at The Lancet on July 19.

Severity of depression decreased in all three intervention groups compared with baseline. The greatest absolute improvement in CSDD scores at 13 weeks occurred with placebo (−5.6; SD, 4.7), compared with sertraline (−3.9; SD, 5.1) and mirtazapine (−5.0; SD, 4.9). At 39 weeks, recovery from baseline was sustained for placebo (−4.8; SD, 5.5), sertraline (−4.0; SD, 5.2) and mirtazapine (−5.0, SD, 6.1).

Overall, decreases in depression scores at 13 weeks did not differ between the 111 controls and 107 participants allocated to receive sertraline (mean difference, 1.17; 95% CI, −0.23 to 2.58; P=0.10) or mirtazapine (mean difference, 0.01; 95% CI, −1.37 to 1.38; P=0.99), or between participants in the mirtazapine and sertraline groups (mean difference, 1.16; 95% CI, −0.25 to 2.57; P=0.11).

Gastrointestinal reactions, usually nausea, were most common with sertraline. Psychological reactions, usually drowsiness and sedation, were most common with mirtazapine. At 13 weeks, there were 15 serious adverse events in the placebo group, three severe, compared to 12 in the sertraline group, eight severe, and 14 in the mirtazapine group, 10 severe. While the number of serious events did not differ among the groups, more of these events were severe in those on antidepressants compared with placebo (P=0.003).

"Analysis of the data suggests clearly that antidepressants, given with normal care, are not clinically effective when compared with placebo for the treatment of clinically significant depression in dementia," the authors concluded. "This finding implies a need to change the present clinical practice of prescription of antidepressants as the first line treatment of depression in dementia caused by Alzheimer's disease."

They suggested that because many cases resolve with usual care and without drugs as a first-line therapy, stepped care with watchful waiting is advocated for the community treatment of depression without dementia. The first step is low-intensity psychosocial interventions, with more complex psychosocial interventions as an alternative to antidepressants as severity increases. Antidepressants might be reserved for those whose depression has not resolved within three months, "apart from those in whom drug treatment is indicated by risk or extreme severity," the authors wrote.

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Test yourself


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MKSAP Quiz: reevaluation after failed thyroid tests

A 76-year-old woman is reevaluated after results of thyroid function tests performed 2 weeks ago are abnormal. The patient otherwise feels well. She has a history of hypertension, atrial fibrillation, gastroesophageal reflux disease, and depression. Current medications are metoprolol, amiodarone, warfarin, omeprazole, and sertraline.

On physical examination, blood pressure is 125/65 mm Hg, pulse rate is 83/min, and respiration rate is 15/min. The thyroid gland is smooth and of normal size. Cardiac examination reveals an irregularly irregular rhythm. Deep tendon reflexes are normal.

Laboratory studies:

Thyroid-stimulating hormone 6.5 µU/mL (6.5 mU/L)
Thyroxine (T4), free 2.4 ng/dL (31.0 pmol/L)
Triiodothyronine (T3), free 0.8 ng/L (1.2 pmol/L)

Which of the following medications is most likely responsible for the laboratory results?

A) Amiodarone
B) Metoprolol
C) Omeprazole
D) Sertraline

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

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Cardiology


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Intima-media thickness may improve cardiac risk prediction, study suggests

Adding a measurement of the maximum intima-media thickness of the internal carotid artery may increase the prognostic value of the Framingham risk score for cardiovascular events, according to a new study.

Researchers measured the mean intima-media thickness of the common carotid artery and the maximum intima-media thickness of the internal carotid artery in members of the Framingham Offspring Study cohort to examine whether these values would affect cardiac risk prediction when added to the Framingham risk score. Participants were followed for an average of 7.2 years for outcomes of cardiovascular disease, and cardiovascular risk was reclassified according to 8-year Framingham categories (i.e., low, intermediate or high) after intima-media thickness was added. The results of the study, which was funded by the National Heart, Lung, and Blood Institute, were published in the July 21 New England Journal of Medicine.

A total of 2,965 participants with no history of cardiovascular disease were included in the study. All were part of the Framingham Offspring Study's sixth examination cycle, which took place from February 1995 through September 1998. The mean age of participants was 58 years, all were white, and 1,629 (55.3%) were women. Two hundred ninety-six first cardiovascular events occurred during the follow-up period. For these events, the standard Framingham risk score had a C-statistic of 0.748 (95% CI, 0.719 to 0.776).

When intima-media thickness measurements were added to the Framingham risk factors, the adjusted hazard ratios for cardiovascular disease were 1.13 (95% CI, 1.02 to 1.24) per 1-SD increase in mean intima-media thickness of the common carotid artery and 1.21 (95% CI, 1.13 to 1.29) for maximum intima-media thickness of the internal carotid artery. The corresponding C-statistics increased by 0.003 (95% CI, 0.000 to 0.007) and 0.009 (95% CI, 0.003 to 0.016), respectively.

When study participants' risk was reclassified according to the new risk scores, intima-media thickness of the internal carotid artery was associated with a significant increase in the net reclassification index (7.6%, P<0.001), but intima-media thickness of the common carotid artery was not (0.0%; P=0.99). When the presence of plaque, or an internal carotid artery intima-media thickness greater than 1.5 mm, was added to the model, the net reclassification index was 7.3% (P=0.01), and the C-statistic increased by 0.014 (95% CI, 0.003 to 0.025).

The authors noted that their study involved only white participants and that the follow-up period, 7.2 years, was shorter than the 10-year period for which the Framingham risk score was developed, among other limitations. However, they concluded that intima-media thickness of both arteries predicted cardiovascular outcomes but that only measures of the internal carotid artery yielded significant improvement in cardiovascular risk classification.

"We believe the intima-media thickness of the internal carotid artery should be measured in addition to the thickness of the common carotid artery for purposes of cardiovascular risk assessment," they wrote, cautioning that they measured this variable "offline" with an algorithm and their results might therefore be different from those obtained on ultrasonography. They called for further studies to determine how the presence of plaque affects cardiovascular risk stratification.

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Infection control


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CDC releases infection prevention guide for outpatient care

The Centers for Disease Control and Prevention has released an infection prevention guide aimed at outpatient facilities.

Although more medical care is now taking place in outpatient facilities, infection control procedures are not always followed strictly in these settings, the agency said in a recent press release. The guide, titled "Guide to Infection Prevention for Outpatient Settings: Minimum Expectations for Safe Care," is modeled on existing CDC guidelines that are currently applied mainly in hospital settings. Its recommendations for outpatient facilities and practices include the following:

  • develop and maintain infection prevention and occupational health programs,
  • ensure that at least one individual with training in infection control is employed by or regularly available to the facility and is responsible for overseeing the facility's infection prevention program,
  • develop appropriate written infection-prevention policies and procedures based upon evidence-based guidelines, regulations, or standards,
  • provide job- or task-specific infection prevention education and training to all health care personnel,
  • ensure availability of sufficient and appropriate supplies for adherence to standard precautions,
  • perform regular audits and competency evaluations of staff's adherence to infection prevention practices,
  • use the CDC's infection prevention checklist for outpatient settings to assess infection control practices, and
  • adhere to local, state, and federal requirements on health care-associated infection surveillance, reportable diseases, and outbreak reporting.

The complete guide, along with the accompanying infection prevention checklist, a free CME course, and education materials for clinicians and patients, is available online.

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MKSAP Answer and Critique



The correct answer is A. Amiodarone. This item is available to MKSAP 15 subscribers as item 76 in the Endocrinology and Metabolism section.

Amiodarone has been associated with several abnormalities in thyroid function, including amiodarone-induced thyrotoxicosis (hyperthyroidism [type 1] and thyroiditis [type 2]), hypothyroidism, and inhibition of thyroxine (T4) to triiodothyronine (T3) conversion. Because of the drug's high iodine content and fat solubility, its effects on the thyroid gland have been reported to persist from months to up to 1 year. The results of this patient's thyroid function studies are consistent with decreased T4 to T3 conversion with a concomitant increase in the serum thyroid-stimulating hormone level, which can occur with use of amiodarone. The decision to discontinue amiodarone can be complex. Amiodarone is usually not discontinued unless it fails to control the underlying arrhythmia. In patients with hypothyroidism who must continue amiodarone, thyroid replacement therapy is indicated. In patients with previously normal thyroid gland function who discontinue amiodarone, hypothyroidism often resolves.

Amiodarone-induced thyrotoxicosis can be a management challenge. Theoretically, antithyroidal drugs are preferred in type 1 (hyperthyroidism) and prednisone therapy in type 2 (thyroiditis). In practice, however, a combination of both may be needed in patients with either type.

Whereas propranolol is known to affect T4 to T3 conversion, other β-blockers, such as metoprolol, are not. Discontinuing metoprolol in this patient is unlikely to restore normal thyroid function.

Omeprazole and other proton-pump inhibitors can affect hormone absorption in patients on thyroid hormone replacement therapy. Given that this patient is not receiving levothyroxine, the use of omeprazole does not explain her findings.

Sertraline appears to enhance thyroid hormone metabolism but does not cause the abnormal results on thyroid function tests seen in this patient.

Key Point

  • Amiodarone has been associated with thyrotoxicosis, hypothyroidism, and inhibition of thyroxine (T4) to triiodothyronine (T3) conversion.

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Test yourself

A 76-year-old woman is evaluated for a 3-month history of left knee pain of moderate intensity that worsens with ambulation. She reports minimal pain at rest and no nocturnal pain. There are no clicking or locking symptoms. She has tried naproxen and ibuprofen but developed dyspepsia; acetaminophen provides mild to moderate relief. The patient has hypertension, hypercholesterolemia, and chronic stable angina. Medications are lisinopril, metoprolol, simvastatin, low-dose aspirin, and nitroglycerin as needed. Following a physical exam, lab results and radiograph, what is the next best step in management?

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