Guidelines Update Vol. 3 by Physician's Weekly

A collection of popular articles on updated guidelines.

Guidelines Update

Volume 3

Read our top interviewbased articles on guidelines for managing MRSA, Alzheimerâ&#x20AC;&#x2122;s disease, diabetic neuropaty and more!

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Table of Contents 14

A Look at Diagnosing Alzheimer’s Disease – Guy M. McKhana, MD

xpert Consensus Reached on Managing E Hypertension in the Elderly – Carl J. Pepine, MD, MACC

12 Guidelines for Diabetic Neuropathy – John D. England, MD, FAAN

16 Guidelines on Assessing Adiposity – Marc-Andre Cornier, MD

20 Guidelines for PAD: A Welcome Update – Thom W. Rooke, MD, FACC

24 W elcome Guidelines for Managing MRSA in Adults & Children – Henry F. Chambers, MD

A Message From the Editor We at Physician’s Weekly are excited to present you with an eBook dedicated to feature stories we’ve covered on recent guidelines. In recent months, our we’ve published a variety of news items in this field, focusing on clinical and evidence-based research. The content in these articles relies on the expertise of our contributing physician authors. Physician’s Weekly will continue to feature guideline updates in the coming months, and we hope that you find this information useful in your practice. Please let us know your thoughts at the Contact Us page here. Sincerely,

Keith D’Oria Editorial Director, Physician’s Weekly

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A New Look at Diagnosing

Alzheimer’s Disease For the first time in nearly 3 decades, the clinical diagnostic criteria for Alzheimer’s disease and dementia have been revised, giving clinicians more advanced guidelines for moving forward with research on diagnosis and treatment.

Guy M. McKhann, MD Professor of Neurology and Neuroscience Center for Mind-Body Research Johns Hopkins University School of Medicine

ore than 27 years ago, the National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer’s and Related Disorders Association (now the Alzheimer’s

Association) released diagnostic criteria for Alzheimer’s disease (AD). At the time, AD was thought of only as a dementia. The 1984 criteria stated that the ultimate AD diagnosis was dependent on pathology. Since that time, the basic concepts of AD have changed significantly, and researchers have uncovered important clues on the diagnosis of AD and dementia.

Time for a Change The National Institute of Aging of the NIH and the Alzheimer’s Association recently called a meeting to discuss whether or not the diagnostic criteria

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required updating. Three subgroups were established to discuss the criteria, based on what would be the biggest changes in the concepts of AD (Table 1). These included that AD starts years and perhaps decades before dementia develops and symptoms are visible. The result of this collaboration was the establishment of new guidelines based on four articles collectively called the “National Institute on Aging/Alzheimer’s Association Diagnostic Guidelines for Alzheimer’s Disease.” The document was published in the April 22, 2011 online edition of Alzheimer’s & Dementia.

“The pre-symptomatic phase of AD includes people who have laboratory evidence of the disease but no symptoms,” explains Guy M. McKhann, MD, who was a member of the group that updated the diagnostic criteria. “The minimal cognitive impairment (MCI) phase includes people with memory problems who haven’t reached the stage of being demented. The final phase includes those who have dementia due to AD.” Defining AD as a spectrum that starts with early changes in the brain will help facilitate clinicians’ ability to treat presymptomatic AD in the future, according to the visit www.physiciansweekly.com

The 3 Stages of Alzheimer’s

Table 1

D ementia Due to Alzheimer’s Disease – Cognitive and behavioral symptoms that impair an individual’s ability to function in daily life. The workgroup:

Emphasized the continuing need and importance to rule out other causes of cognitive decline and of documenting progressive decline over time. Noted that the diagnosis of Alzheimer’s dementia may not always have memory impairment as its most central characteristic; a decline in other aspects of cognition (eg, word-finding, vision/spatial issues, and impaired reasoning, judgment, and problem solving) may be the presenting or most prominent symptoms at first. Proposed that, for research purposes, diagnostic certainty may be improved by incorporating certain biomarker measures; however, the usefulness and reliability of these tests in everyday medical practice still needs to be tested.

ild Cognitive Impairment (MCI) Due to M Alzheimer’s Disease – Mild changes in memory and thinking ability, enough to be noticed and measured, but not impairment that compromises everyday activities. The workgroup reports that:

This impairment increasingly can be measured in research, and is gradually being recognized in medical and specialty practice. More work is needed to distinguish those with MCI who will go onto develop Alzheimer’s dementia from those who will not. Biomarkers, as they become validated, may help increase diagnostic accuracy in research settings.

Preclinical Alzheimer’s Disease – Changes that may indicate the very earliest signs of disease. The workgroup recommended:

No diagnostic criteria for this phase of the disease. Developing approaches for data collection to see if a “preclinical” stage of the disease can be defined so that people who will develop Alzheimer’s dementia can be distinguished from those who will not. Ascertaining measurements of biomarkers and neuroimaging tests to characterize brain changes that may be predictive of Alzheimer’s disease. Developing new assessments to delineate the very earliest and subtle clinical signs of decline are also needed. Source: Adapted from: Alzheimer’s Association. Available at: www.alz.org/documents_custom/Alz_Assoc_diag_criteria_guidelines_press_release_041911.pdf.

guideline authors. It is during the asymptomatic phase that detrimental changes occur in the brain. Individuals with evidence of these changes upon testing for biomarker presence are at increased risk for cognitive and behavioral impairment, as well as 6

The field is changing ra biomarkers will become and used in progression to AD. “The use of these biomarkers in diagnosing Alzheimer’s dementia and MCI also appeared over the last 27 years,” notes Dr. McKhann. Several biomarker types have emerged since the last criteria were released (Table 2). “Some biomarkers are related to imaging, including those that show evidence of structural change in the brain and accumulation of components of the amyloid plaque—the breakdown product that helps form AD,” says Dr. McKhann. He feels that one of the biggest breakthroughs in AD research in the past decade has been the ability to image amyloid in the brain with PET scans. “The other types of biomarkers look for the presence of tau or amyloid breakdown products in spinal fluid.” There was a broad consensus among the workgroups that additional research is needed to validate the application of biomarkers in diagnosing AD. The guidelines propose using biomarkers in AD and MCI due to AD as a research agenda only, not as a current application in clinical settings. “While these biomarkers have been relatively well established when utilized properly in first-rate labs, they’re not ready for general use because of standardization issues,” adds Dr. McKhann. “The field is changing rapidly, and the hope is biomarkers will become more widely available and used in diagnoses. With these advancements, the criteria will likely need updating.”

Making a Diagnosis The most recent guidelines pay more attention to the differential diagnosis of AD, according to McKhann. “When deciphering AD from vascular disease of the brain or other neurodegenerative diseases, clinicians

apidly, and the hope is e more widely available n diagnoses. —Guy M. McKhann, MD should keep in mind that AD is an age-dependent process. The proportion of 65-year-olds who have AD is probably less than 10%, but it’s probably 35% to 40% among 90-year-olds.” A proportion of those who have AD also have other neurological problems that can make diagnoses challenging. As such, Dr. McKhann stresses that providers become aware of these criteria and refer patients on to AD specialists in order to ascertain a firmer grip on the diagnosis. “The new criteria capitalize on the latest scientific knowledge and technological advances,” Dr. McKhann says, “allowing for improved diagnosis and earlier detection and treatment of AD. If you wait until full-blown dementia develops, it’s too late.”

Two Types of Alzheimer’s Biomarkers Table 2

The incorporation of biomarkers of underlying Alzhiemer’s disease state and formalization of different stages of the disease are important advances in diagnosing Alzheimer’s. The new criteria indicate that biomarkers be divided into two major categories:

Biomarkers of beta-amyloid accumulation. These are:

Abnormal retention of beta-amyloid identifying tracer compounds on PET imaging. Low levels of beta-amyloid 1-42 in cerebrospinal fluid (CSF).

B iomarkers of neuronal degeneration or injury. These are:

Elevated levels of the protein tau (both total and phosphorylated tau) in CSF. Decreased fluorodeoxyglucose 18F (FDG) uptake on PET imaging in a specific pattern involving the brain’s temporo-parietal cortex. Atrophy on structural MRI in a specific topographic pattern involving the brain’s medial, basal and lateral temporal lobes, and medial and lateral parietal cortices. Source: Adapted from: Alzheimer’s Association. Available at: www.alz.org/documents_ custom/Alz_Assoc_diag_criteria_guidelines_press_release_041911.pdf.

Guy M. McKhann, MD, has indicated to Physician’s Weekly that he serves on a data safety monitoring board for Merck; has worked as a consultant for the Dana Foundation and Merck; and has received grants or research aid from the Dana Foundation, NIH, and NINDS. For more information on this article, including references, visit www.physiciansweekly.com.

Additional Resources: Alzheimer’s Association. New Criteria and Guidelines for Alzheimer’s Disease Diagnosis. Available at: www.alzheimersanddementia.org/content/ncg. McKhann GM, Knopman DS, Chertkow H, et al. The diagnosis of dementia due to Alzheimer’s disease: recommendations from the National Institute on Aging and the Alzheimer’s Association workgroup. Alzheimer’s & Dementia. 2011. Available at: www.alzheimersanddementia.org/webfiles/images/journals/jalz/2_JALZ1252_proof.pdf. Albert MS, DeKosky ST, Dickson D, et al. The diagnosis of mild cognitive impairment due to Alzheimer’s disease: recommendations from the National Institute on Aging and Alzheimer’s Association workgroup.Alzheimer’s & Dementia. 2011. Available at: www.alzheimersanddementia.org/webfiles/images/journals/jalz/3_JALZ1255_proof.pdf. Sperling RA, Aisen PS, Beckett LA, et al. Toward defining the preclinical stages of Alzheimer’s disease: recommendations from the National Institute on Aging and the Alzheimer’s Association workgroup. Alzheimer’s & Dementia. 2011. Available at: www.alzheimersanddementia.org/webfiles/images/journals/jalz/4_JALZ1250_proof.pdf.

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Consensus Reached on

Managing

Hypertension in the Elderly

An expert consensus statement offers recommendations for the appropriate management of hypertension in patients aged 65 and older, emphasizing effective strategies to reduce blood pressure in this difficult-to-treat population.

Carl J. Pepine, MD, MACC Professor of Medicine, Division of Cardiovascular Medicine University of Florida College of Medicine

ypertension affects the overwhelming majority of Americans over the age of 65, but many of these individuals are unaware of their elevated blood pressure. Evidence suggests that even elderly people with diagnosed hypertension do not have their condition adequately controlled. In the May

2011 Journal of the American College of Cardiology, the American College of Cardiology and the American Heart Association (ACC/AHA) released the first expert consensus document on hypertension in the elderly. “Many hypertension trials in the past have excluded elderly patients, so this consensus relies heavily on subgroups of recent trials and expert opinion rather than data from clinical trials done only in the elderly,” explains Carl J. Pepine, MD, MACC, who co-chaired the writing committee that created the document. “Our hope is to provide physicians with systematic recommendations to lower blood pressure (BP) in older adults and to remind them of some specific issues relevant to the elderly.”

Clinical Relevance & Goals Dr. Pepine says that there is limited clinical evidence available on specific target BP goals and therapeutic options for elderly patients with hypertension. â&#x20AC;&#x153;Fortunately, recent data from large clinical trials of multiple elderly cohorts, including the Hypertension in the Very Elderly Trial (HYVET), have suggested that treatment of hypertension is beneficial among this older population,â&#x20AC;? he says. While the target BP in the elderly population has not yet been validated, evidence supports the current recommendation of achieving BP less than 140/90 mm Hg for patients up to age 80. Between the ages of 80 and 85, a BP of less than 145/90 mm Hg is acceptable.

Pushing older patients to lower treatment goals (eg, less than 130/80 mm Hg) is not suggested because this may lead to adverse effects from medications needed to reach these goals or from simply having low BP. Data supporting lower specific BP goals, based on coexisting conditions for the prevention and management of coronary artery disease, are lacking in elderly cohorts.

Diagnostic Difficulties Due to age and comorbidities among the elderly with hypertension, the management of hypertension for these individuals is often complex. Despite visit www.physiciansweekly.com

Clinicians should treat older patients as they would treat younger individuals, and make efforts to improve BP control regardless of age. —Carl J. Pepine, MD, MACC

the presence of comorbid illnesses, there is strong evidence that better control of BP will reduce risks of secondary cardiovascular events. “One condition often unrecognized in the elderly population is orthostatic hypotension, which occurs when BP drops as individuals go from a seated to standing position,” says Dr. Pepine. “Our recommendation is that, at least once, BP should be recorded in several positions.” Some elderly patients have orthostatic hypertension in which BP rises to abnormal levels when they go from seated to standing positions.

Treatment Options According to the ACC/AHA guidelines, physicians should consider lifestyle modification (Table) and drug therapy when treating hypertension in elderly patients. Lifestyle modification has been shown to be as effective in this population as in younger patients. There is also strong clinical evidence that elderly patients with hypertension benefit greatly from pharmacologic BP reduction. HYVET documented

Table

reduced adverse outcomes with antihypertensive drugs in patients with hypertension aged 80 and older. ACE inhibitors, β-blockers, angiotensin receptor blockers, diuretics, and calcium channel blockers can be considered for lowering BP and reducing cardiovascular outcomes among the elderly (Figure). “When considering drug options for elderly patients, the duration and severity of the hypertension and comorbid conditions should play a role in treatment decisions,” says Dr. Pepine. “Medications that treat hypertension and reduce risks for heart disease and stroke should be considered.” Initial anti-hypertensive drugs should be administered at the lowest dose and gradually increased depending on BP response. The average elderly patient takes more than six prescription drugs daily, which may ultimately interfere with adherence. Dr. Pepine adds that efforts to reduce dosing and pill burdens should be encouraged whenever possible, and combination drugs should be considered.

Recommended Lifestyle Modifications Recommendation

Approximate Systolic BP Reduction Range

Maintain normal body weight (BMI, 18.5-24.9 kg/m2)

5-20 mm Hg/ 10-kg weight loss

Adopt DASH eating plan

Consume a diet rich in fruits, vegetables, and low-fat dairy products with a reduced content of saturated and total fat

8-14 mm Hg

Dietary sodium reduction

Reduce dietary sodium intake to no more than 100 mEq/L (2.4 g sodium or 6.0 g sodium chloride)

2-8 mm Hg

Physical activity

Engage in regular aerobic physical activity (eg, brisk walking) at least 30 min/day most days of the week

4-9 mm Hg

Moderation of alcohol consumption

Limit consumption to no more than 2 drinks/day in most men; no more than 1 drink/day in women and lighter-weight people

2-4 mm Hg

Modification Weight reduction

* For overall cardiac risk reduction, stop smoking. The effects of implementing these modifications are dose and time dependent and could be higher in some individuals. Abbreviations: BP, blood pressure; DASH, Dietary Approaches to Stop Hypertension. Source: Adapted from: Aronow WS, et al. J Am Coll Cardiol. 2011;57:2037-2114.

A Patient Population Worthy of Treatment As society continues to age, more and more elderly patients are expected to have hypertension. “Clinicians should treat older patients as they would treat younger individuals, and make efforts to improve BP

Figure

control regardless of age,” Dr. Pepine says. “Treating older individuals—especially octogenarians—will help to decrease mortality and improve quality of life for these people as they reach their ‘golden years.’ In cases in which there is uncertainty about the optimal course of action, referrals to specialists should also be considered.”

Algorithm for Treating Hypertension in the Elderly Principles of Hypertension Treatment • Target SBP is ≤140 mm Hg in patients aged 55-79 • Target SBP is ≤140 mm Hg in patients aged 80+ • Achieved values <140 mm Hg for those aged ≤79 are appropriate; but for those aged 80+, 140-145 mm Hg, if tolerated, can be acceptable. Lifestyle Modifications Not at Target Blood Pressure Initial Drug Choices Without Compelling Indications

With Compelling Indications Compelling Indication

Initial Therapy Options*

Stage 1 Hypertension

Stage 2 Hypertension

SBP 140-159 mm Hg or DBP 90-99 mm Hg

SBP ≥160 mm Hg or DBP ≥100 mm Hg

• Heart failure

THIAZ, BB, ACEI, ARB, CA, ALDO ANT

• Post-myocardial infarction

BB, ACEI, ALDO ANT, ARB

• CAD or high CVD risk

THIAZ, BB, ACEI, CA

ACEI, ARB, CA, diuretic, or combination

Majority will require at least 2 medications to reach goal if at least 20 mm Hg above target. Initial combinations should be considered. The combination of amlopidine with an RAS blocker may be preferred to a diuretic combination, though either is acceptable.

• Angina pectoris

BB, CA

• Aortapathy/ aortic aneurysm

BB, ARB, ACEI, THIAZ, CA

• Diabetes

ACEI, ARB, CA, THIAZ, BB

Not at Target Blood Pressure Optimize dosages or add additional drugs until goal blood pressure is achieved. Refer to a clinical hypertension specialist if unable to achieve control.

• Chronic kidney disease • Recurrent stroke prevention • Early dementia

ACEI, ARB, THIAZ, ACEI, ARB, CA Blood pressure control * Combination therapy.

Abbreviations: ACEI, ACE inhibitor; ALDO ANT, aldosterone antagonist; ARB, angiotensin receptor blocker; BB, β-blocker; CA, calcium antagonist; CAD, coronary artery disease; CVD, cardiovascular disease; DBP, diastolic blood pressure; RAS, renin-angiotensin system; SBP, systolic blood pressure; and THIAZ, thiazide diuretic. Source: Adapted from: Aronow WS, et al. J Am Coll Cardiol. 2011;57:2037-2114.

Carl J. Pepine, MD, MACC, has indicated to Physician’s Weekly that he has or has had no financial interests to report. For more information on this article, including references, visit www.physiciansweekly.com. visit www.physiciansweekly.com

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John D. England, MD, FAAN The Grace Benson Professor and Head of Neurology Louisiana State University Health Sciences Center School of Medicine Fellow American Academy of Neurology

New Guidelines for

Diabetic

Neuropathy The American Academy of Neurology has released new guidelines on the management of painful diabetic neuropathy that provide evidence-based information on use of a range of treatment strategies.

he prevalence of neuropathy among those with diabetes has been estimated to be as high as 50%. Painful diabetic neuropathy (PDN), which tends to affect the feet and legs, has been estimated to affect roughly 16% to 20% of the more than 25 million people in the United States who are living with diabetes. The condition often goes unreported and even more are untreated, with an estimated 40% of patients not receiving care for PDN. A Need for Guidance“Painful diabetic neuropathy is a big problem for all healthcare providers who treat patients with diabetes,” says John D. England, MD,

FAAN. “There are increasingly more drugs being developed and brought to market that can be used for treating diabetic neuropathy. For a busy practitioner, it’s often difficult to keep up with all of the new evidence and to decide what a rational, tiered approach should be to treatment.” Part of the issue is the volume of literature on the topic. In 2007, when members of the American Academy of Neurology (AAN) felt there was a need to update guidelines for the treatment of PDN, the process started with more than 2,200 papers. Of them, 463 were deemed relevant and 79 were highly pertinent to the guidelines. Since then, many more studies have emerged. visit www.physiciansweekly.com

In the May 17, 2011 issue of Neurology, the AAN published its first evidence-based guidelines on use of a range of pharmacologic and non-pharmacologic treatments for diabetic neuropathy. “There is no ‘cookbook’ approach to treatment for PDN,” explains Dr. England, who co-chaired the AAN panel that developed the guidelines. “We can, however, use the scientific evidence in the literature and make sure that it conforms to our clinical judgment and patient preferences. What one patient may respond to may be very different from that of another. The evidence provides some guidance on how we should treat this complication of diabetes.” Dr. England adds that it is important to explain to patients that it is not common for patients to achieve complete pain relief even though medications are available to help relieve some of their pain.

Key Recommendations Physicians need to be particularly careful with pain measurements because pain is a subjective complaint, says Dr. England. “Pain is measured with standardized scales, but what level of pain relief is actually experienced by patients is a subjective response. That is why well-studied research populations are needed. We want to exclude any potential

Table 1

confounding factors. Over the past couple decades, the AAN has developed a robust system for classifying evidence from the therapeutic trials that study this patient population.” Using this system, Dr. England and colleagues rated the level of evidence for several therapeutic modalities that can be used to treat patients with PDN. “It should be noted that many of these patients have severe enough pain that they require multiple modalities to help them,” noted Dr. England. He adds that most of the agents listed in Table 1 reduce pain by 30% to 50%, on average. Therefore, mixing and matching agents and other therapies is often required to help patients feel as comfortable as possible. “In addition, several agents are still being used to treat this population when there is either insufficient evidence to support or even evidence against their use,” says Dr. England. “Physicians should refer to the AAN guidelines to learn which drugs have the best scientific evidence supporting their use to treat PDN.”

A Need for Change Dr. England says special attention should be paid to the medications indicated for PDN that have

Summarizing Treatment Recommendations Recommended Drug and Dose

Not Recommended

Level A

Pregabalin, 300–600 mg/day

Level B

Gabapentin, 900–3600 mg/day

Oxcarbazepine

Sodium valproate, 500–1200 mg/day

Lamotrigine

Venlafaxine, 75–225 mg/day

Lacosamide

Duloxetine, 60–120 mg/day

Clonidine

Amitriptyline, 25–100 mg/day

Pentoxifylline

Dextromethorphan, 400 mg/day

Mexiletine

Morphine sulphate, titrated to 120 mg/day

Magnetic field treatment

Tramadol, 210 mg/day

Low-intensity laser therapy

Oxycodone, mean 37 mg/day, max 120 mg/day

Reiki therapy

Capsaicin, 0.075% qid Isosorbide dinitrate spray Electrical stimulation, percutaneous nerve stimulation x 3–4 weeks Source: Adapted from: Bril V, et al. Neurology, 2011;76:1758-1765. Available at www.neurology.org/content/early/2011/04/08/WNL.0b013e3182166ebe.

Physicians should refer to the AAN guidelines to learn which drugs have the best scientific evidence supporting their use to treat PDN. — John D. England, MD, FAAN level B recommendations. “Unfortunately, the paucity of data makes it challenging for physicians to truly know which therapeutic interventions are better and the ideal candidates for each option,” he says. “We need comparative effectiveness trials to determine which drugs in the treatment of PDN are superior.” Among other changes Dr. England would like to see made in research is the selection of a single pain rating scale (Table 2). “Using such a scale in all trials would enable investigators to compare trials against each other with greater accuracy. Also, aside from a few recent studies, most analyses only measure pain relief. They should also measure quality of life and function. Patients could have some pain relief but still experience deteriorated quality of life and function, depending on adverse events from medications. We have come a long way in improving the management of diabetic neuropathy, but we still have a long way to go. The only way that we’re going to get better is to fund more research.”

Recommendations for Future Research

Table 2

• A formalized process for rating pain scales for use in all clinical trials should be developed. • Clinical trials should be expanded to include effects on quality of life and physical function when evaluating efficacy of new interventions for painful diabetic neuropathy (PDN); the measures should be standardized. • Future clinical trials should include head-tohead comparisons of different medications and combinations of medications. • Because PDN is a chronic disease, trials of longer duration should be done. • Standard metrics for side effects to qualify effect sizes of interventions need to be developed. • Cost-effectiveness studies of different treatments should be done. • The mechanism of action of electrical stimulation is unknown; a better understanding of its role, mode of application, and other aspects of its use should be studied. Source: Adapted from: Medical Care Criteria Committee. Hepatitis C. New York State Department of Health AIDS Institute. Available at: www.hivguidelines.org/clinical-guidelines.

John D. England, MD, FAAN, has indicated to Physician’s Weekly that he serves on the speakers’ bureau for and has received funding for travel or speaker honoraria from Talecris Biotherapeutics and Teva Pharmaceutical Industries. He also receives research support from the NIH/NINDS, AstraZeneca, and Pfizer, and holds stock/stock options in Pfizer and Talecris Biotherapeutics. For more information on this article, including references, visit www.physiciansweekly.com.

Additional Resources: Bril V, England J, Franklin GM, et al. Evidence-based guideline: treatment of painful diabetic neuropathy : Report of the American Academy of Neurology, the American Association of Neuromuscular and Electrodiagnostic Medicine, and the American Academy of Physical Medicine and Rehabilitation. Neurology. 2011 Apr 11 [Epud ahead of print]. Available at: www.neurology.org/content/early/2011/04/08/WNL.0b013e3182166ebe. Boulton AJ, Vinik AI, Arezzo JC, et al. Diabetic neuropathies: a statement by the American Diabetes Association. Diabetes Care. 2005;28:956-962. Gordois A, Scuffham P, Shearer A, et al. The health care costs of diabetic peripheral neuropathy in the US. Diabetes Care. 2003;26:1790-1795.

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New Guidelines on

Assessing

Adiposity

A scientific statement from the American Heart Association discusses challenges and issues associated with assessing adiposity. Recommendations are provided for identifying at-risk overweight and obese patients.

Marc-Andre Cornier, MD Associate Professor of Medicine, Division of Endocrinology, Metabolism and Diabetes University of Colorado School of Medicine, Anschutz Medical Campus Staff Endocrinologist, Department of Medicine Denver Health Medical Center

he rate of obesity in the United States has reached the epidemic level despite efforts by healthcare providers and patients to improve health-related behaviors and increased efforts to better understand its pathophysiology. “Assessment for excess adiposity

is of critical importance,” says Marc-Andre Cornier, MD. To address the issue of assessing adi-posity, the American Heart Association (AHA) released a scientific statement to help clinicians. The statement, which was published in the November 1, 2011 issue of Circulation, provides practical guidance for clinical researchers who seek to identify precise measurements for their patients. It also provides recommendations for clinicians who care for patients whose excess weight is a clinical problem. “Before clinicians can recommend treatment options or talk to patients about obesity prevention, they need to know whether a patient is obese,” says

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In addition to BMI and waist circumference measurements, utilizing blood tests for various metabolic and cardiovascular disorders is recommended. Dr. Cornier, who was the lead author of the AHA scientific statement. He adds that there are also new Medicare guidelines for covering obesity treatment that require clinicians to identify whether or not patients are obese. Medicare will cover provider visits for weight loss counseling in patients who screen “positive” for obesity.

Reviewing the Methodologies Healthcare providers and systems are not regularly assessing for excess adiposity with even the simplest, least costly methods, says Dr. Cornier. “Most methods for assessing excess adiposity are not ready for routine clinical use,” he says. “Measuring BMI and waist circumference is currently best to assess adiposity. These are strategies all clinicians should be practicing on a regular basis for patients. Other newer, complex, and more expensive tools are cur-

Potential Utility of Methods for Assessing Body Composition

Table 1

Clinical Use

Method Anthropometry

Skinfold thickness

Ultrasound

Near-infrared interactance

Hydrostatic weighing

Air displacement plethysmography

DEXA

CT/MRI

–

Bioelectric impedance

Notes: ++, accepted method; +, uncommonly used method; and –, not recommended for clinical use. Abbreviation: DEXA, dual-energy X-ray absorptiometry. Source: Adapted from: Cornier M, et al. Circulation. 2011;124:1996-2019.

— Marc-Andre Cornier, MD

rently available, but physicians need to do a better job utilizing the simpler tools we currently have at our disposal.” Most of the evidence in the literature on assessing adiposity has been focused on measuring BMI and waist circumference. Waist circumference is a marker of visceral fat, which is associated with fat deposited in the liver, muscle, heart, and other areas thought to be associated with metabolically active fat that causes metabolic disease. “Measuring for body fat composition is of growing importance,” explains Dr. Cornier (Table 1). “More and more studies show that the percent of one’s body that is made up from fat is of far more importance than their weight.” Fat distribution measurements are also important because they can show clinicians where fat is deposited. This in turn enhances risk assessments (Table 2). While imaging tests like CT and MRI are ideal for assessing fat distribution, both are expensive and therefore not recommended for clinical use in the AHA scientific statement. “Dualenergy X-ray absorptiometry, or DEXA, scanning is commonly used for measuring bone density and could be also used to measure body composition and distribution,” says Dr. Cornier. “Unfortunately, such a strategy is expensive and may not provide more information than a waist circumference or BMI measurement.” Skinfold thickness is a another simple test that can be used to assess adiposity, but it only looks at one part of the body and focuses only on subcutaneous fat, which has little or no asso ciation with metabolic or cardiovascular disease. Hydrostatic weighing is another potential testing option, but Dr. Cornier notes that it is difficult

to utilize this tool because it requires patients to be put into a pool. Despite a relatively low associated cost, ultrasound for assessing adiposity has not been studied closely enough, and more research is warranted. “In addition to BMI and waist circumference measurements, utilizing blood tests for various metabolic and cardiovascular disorders is recommended,” Dr. Cornier says. “This combination can provide much information at little cost.”

A Look Into the Future Dr. Cornier believes that near infrared interactance and air displacement plethysmography could be clinically relevant methods for assessing adiposity in the near future. “These are strategies that would not be too costly,” he says. “However, bioelectric impedance may be the most practical and inexpensive method. It has the potential to improve the measurement of body composition and may be a cheaper and simpler approach. Although more research is needed, it’s feasible that bioelectric impedance may be ready for greater use in the next 5 to 10 years.” In the meantime, Dr. Cornier recommends that an emphasis be placed on obesity as a serious societal

Potential Utility of Methods for Assessing Body Fat Distribution

Table 2

Method

Clinical Use

Waist circumference

+++

Hip circumference

Thigh circumference

Neck circumference

Ratios Waist-to-hip

Waist-to-height

Waist-to-thigh

Imaging CT

–

MRI

–

Notes: +++, widely accepted method; ++, accepted method; +, uncommonly used method; and –, not recommended for clinical use. Source: Adapted from: Cornier M, et al. Circulation. 2011;124:1996-2019.

problem, both medically and financially, that needs to be controlled and prevented. “It’s important that physicians learn how best to assess for excess adiposity and know the associated risk factors. For now, most patients should be assessed for adiposity using BMI and waist circumference measurements.”

Marc-Andre Cornier, MD, has indicated to Physician’s Weekly that he has or has had no financial interests to report. For more information on this article, including references, visit www.physiciansweekly.com.

Additional Resources: Cornier M, Després J, Davis N, et al. Assessing adiposity: a scientific statement from the American Heart Association. Circulation. 2011;124:1996-2019. Strazzullo P, D’Elia L, Cairella G, et al. Excess body weight and incidence of stroke: meta-analysis of prospective studies with 2 million participants. Stroke. 2010;41:e418-e426. Gruson E, Montaye M, Kee F, et al. Anthropometric assessment of abdominal obesity and coronary heart disease risk in men: the PRIME study. Heart. 2010;96:136-140. Jacobs E, Newton C, Wang Y, et al. Waist circumference and all-cause mortality in a large US cohort. Arch Intern Med. 2010;170:1293-1301. Blüher M. The distinction of metabolically “healthy” from “unhealthy” obese individuals. Curr Opin Lipidol. 2010;21:38-43. Ibrahim M. Subcutaneous and visceral adipose tissue: structural and functional differences. Obes Rev. 2010;11:11-18.

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Guidelines for PAD A Welcome Update Updated guidelines for the diagnosis and management of peripheral arterial disease (PAD) include expanded criteria for an earlier PAD diagnosis, increased efforts for smoking cessation, and improved use of clot-preventing medications and other interventions.

Thom W. Rooke, MD, FACC Krehbiel Professor of Vascular Medicine Mayo Clinic School of Medicine

eripheral arterial disease (PAD) is a common and dangerous condition that affects millions of Americans, especially those with a history of diabetes or smoking. Despite efforts to increase awareness in the medical community, the disease remains largely underdiagnosed. For many patients, PAD is asymptomatic and may not lead to recognizable symptoms. In turn, a diagnosis may be delayed. If left untreated, PAD has been shown in published research to be predictive of heart attack, stroke, leg amputations, and death.

In 2005, the American College of Cardiology Foundation (ACCF) and the American Heart Association (AHA), along with collaborating societies, released guidelines for the management of PAD. In 2011, the ACCF/AHA updated these guidelines to reflect new data in the diagnosis and treatment of the condition. “The 2011 guideline includes new information for diagnosing PAD, smoking cessation, the use of antiplatelet therapy, and interventions for treating severely ischemic limbs and abdominal aortic aneurysms (AAAs),” says Thom W. Rooke, MD, FACC, who chaired the committee that developed the 2011 guidelines. “The update can assist primary care clinicians, cardiologists, pulmonologists, interventional radiologists, vascular surgeons, and vascular medicine specialists in improving patient care.”

Diagnosing PAD The 2011 ACCF/AHA guideline includes a recommendation to lower the age at which ankle-brachial visit www.physiciansweekly.com

Table 1

Smoking Cessation Level of Evidence

Recommendation Patients who are smokers or former smokers should be asked about status of tobacco use at every visit.

Patients should be assisted with counseling and developing a plan for quitting that may include pharmacotherapy and/or referral to a smoking cessation program.

Individuals with lower extremity PAD who smoke cigarettes or use other forms of tobacco should be advised by each of their clinicians to stop smoking and offered behavioral and pharmacologic treatment.

In the absence of contraindication or other compelling clinical indication, one or more of the following pharmacologic therapies should be offered: varenicline, bupropion, or nicotine replacement therapy.

Abbreviations: PAD, peripheral artery disease.

index (ABI) diagnostic testing should be performed in the practice setting. “Previously, the recommendation was for patients aged 70 or older to receive an ABI,” says Dr. Rooke. “That threshold has been lowered to age 65 or older based on mounting evidence demonstrating that people in this age range have a 20% chance of having either symptomatic or asymptomatic PAD.” Furthermore, ABI diagnostic testing is now recommended for patients aged 50 and older if they have a history of diabetes or smoking because they are considered at especially high risk for PAD.

Quitting Smoking Recommendations for physicians to help people with PAD quit smoking are strengthened in the 2011 ACCF/AHA guideline update (Table 1). Doctors are now recommended to consistently ask current and former smokers about tobacco use at each visit. In addition, physicians should be proactive about offering support through counseling, pharmacologic therapies, and formal smoking cessation programs. “In addition to other health benefits, getting patients to quit smoking can have a significant impact on outcomes in PAD,” says Dr. Rooke. “Smoking cessation can lower risks of disease-related comorbidities, including heart attack, stroke, and lower limb amputation.”

Other Important Recommendations In addition to changes in diagnosing PAD and increasing smoking cessation efforts, the 2011 22

Source: Adapted from: Rooke TW, et al. J Am Coll Cardiol. 2011;58:2020-2045.

guideline update broadens the indications for using antiplatelet therapies and antithrombotic drugs (Table 2). “The use of therapies that prevent clotting is important when treating patients with PAD,” Dr. Rooke says. Several new Class IIa and IIb recommendations were made in the update, while other recommendations from the 2005 guidelines were modified to reflect new evidence that has emerged in recent years. Leg artery angioplasty is indicated as a first-line treatment for certain individuals with severe PAD who may require amputation. Balloon angioplasty, however, is not an ideal treatment for all patients with PAD. The guidelines now recommend angioplasty as the initial procedure to improve distal blood flow for patients with limb-threatening lower extremity ischemia and an estimated life expectancy of 2 years or less. Bypass surgery is recommended for these patients if they have an estimated life expectancy of more than 2 years. New recommendations were also added for managing AAAs. Open or endovascular repair of infrarenal AAAs and common iliac aneurysms is now indicated in patients who are good surgical candidates. Open aneurysm repair can be used in good surgical candidates who cannot comply with the periodic longterm surveillance that is required after endovascular repair. However, it is unknown whether or not patients with infrarenal aortic aneurysms who are at high surgical or anesthetic risk will benefit from endovascular repair.

Looking Forward When PAD is undetected and poorly managed, it is among the most costly cardiovascular diseases. “We still have a long way to go in order to improve the management of PAD,” says Dr. Rooke. “The 2011 ACCF/AHA guideline update can serve as a roadmap to the most appropriate practices and

interventions based on evidence-based science, but opportunities remain to further our knowledge and efforts for prevention and earlier, life-saving interventions. Until more data emerge, promoting use of these guidelines in hospitals and healthcare systems may reduce the burden of PAD and improve clinical outcomes associated with the disease.”

Thom W. Rooke, MD, FACC, has indicated to Physician’s Weekly that he has or has had no financial interests to report. For more information on this article, including references, visit www.physiciansweekly.com.

Table 2

Antiplatelet & Antithrombotic Drugs

Recommendation

Level of Evidence

Class I Antiplatelet therapy is indicated to reduce the risk of MI, stroke, and vascular death in individuals with symptomatic atherosclerotic lower extremity PAD, including those with intermittent claudication or critical limb ischemia, prior lower extremity revascularization (endovascular or surgical), or prior amputation for lower extremity ischemia.

Aspirin, typically in daily doses of 75 to 325 mg, is recommended as safe and effective antiplatelet therapy to reduce the risk of MI, stroke, or vascular death in individuals with symptomatic atherosclerotic lower extremity PAD, including those with intermittent claudication or critical limb ischemia, prior lower extremity revascularization (endovascular or surgical), or prior amputation for lower extremity ischemia).

Clopidogrel (75 mg per day) is recommended as a safe and effective alternative antiplatelet therapy to aspirin to reduce the risk of MI, ischemic stroke, or vascular death in individuals with symptomatic atherosclerotic lower extremity PAD, including those with intermittent claudication or critical limb ischemia, prior lower extremity revascularization (endovascular or surgical), or prior amputation for lower extremity ischemia.

Class IIa Antiplatelet therapy can be useful to reduce the risk of MI, stroke, or vascular death in asymptomatic individuals with an ABI less than or equal to 0.90.

Class IIb The usefulness of antiplatelet therapy to reduce the risk of MI, stroke, or vascular death in asymptomatic individuals with borderline abnormal ABI, defined as 0.91 to 0.99, is not well established.

The combination of aspirin and clopidogrel may be considered to reduce the risk of cardiovascular events in patients with symptomatic atherosclerotic lower extremity PAD, including those with intermittent claudication or critical limb ischemia, prior lower extremity revascularization (endovascular or surgical), or prior amputation for lower extremity ischemia, and those who are not at increased risk of bleeding and who are at high perceived cardiovascular risk.

Class III: No benefit In the absence of any other proven indication for warfarin, its addition to antiplatelet therapy to reduce the risk of adverse cardiovascular ischemic events in individuals with atherosclerotic lower extremity PAD is of no benefit and is potentially harmful due to increased risk of major bleeding. Abbreviations: ABI, ankle-brachial index; MI, myocardial infarction; PAD, peripheral artery disease.

Source: Adapted from: Rooke TW, et al. J Am Coll Cardiol. 2011;58:2020-2045.

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Welcome Guidelines for Managing MRSA in Adults & Children Clinicians are often challenged with managing MRSA infections, but the Infectious Diseases Society of America has released new guidelines that provide a framework to help determine how to evaluate and treat individuals with uncomplicated and invasive infections caused by MRSA.

Henry F. Chambers, MD Professor of Medicine Chief, Division of Infectious Diseases San Francisco General Hospital Director, Infectious Diseases Fellowship Training Program University of California, San Francisco

RSA has been well documented as a significant cause of both healthcare–associated and community–associated infections. It is the predominant cause of skin infections among patients presenting to the emergency room and can also cause more serious, invasive infections, which account for about 18,000 deaths each year in the United States. “MRSA has an enormous clinical and economic impact,” explains Henry F. Chambers, MD. “Many clinicians often have difficulties when

managing these infections. When these patients are not properly managed, the results can be severe. Poor management can also promote antibiotic resistance, which is fast becoming a growing concern among clinicians.”

A Framework for Clinicians In the February 1, 2011 issue of Clinical Infectious Diseases, an expert panel of the Infectious Diseases Society of America (IDSA) released its first evidence-based, consensus guidelines on the treatment of MRSA infections. The primary objective of the guidelines was to provide recommendations on the management of some of the most common clinical syndromes encountered by adult and pediatric clinicians who care for patients with these infections. The IDSA expert panel addressed issues relating to the use of vancomycin therapy in the treatment of

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MRSA infections, including dosing and monitoring, current limitations of susceptibility testing, and the use of alternate therapies for those patients with vancomycin treatment failure and infection due to strains with reduced susceptibility to the drug. “The guidelines provide a framework to help clinicians determine the most appropriate means to evaluate and treat patients with uncomplicated and invasive infections caused by MRSA,” explains Dr. Chambers, who co-chaired the panel that developed the guidelines. “They discuss the management of a variety of clinical syndromes associated with MRSA disease, including skin and soft tissue infections (SSTIs), bacteremia and endocarditis, pneumonia, bone and joint infections, and central nervous system infections. These recommendations are provided in addition to those on the appropriate use of vancomycin.” The guidelines have been endorsed by the Pediatric Infectious Diseases Society, the American College of Emergency Physicians, and the American Academy of Pediatrics.

Key Recommendations The IDSA guidelines offer primarily expert opinion on the management of MRSA because that is often the only currently available information. “The guide-

Using Antimicrobial Therapy After Incision & Drainage

Table 1

The following items identify when the use of antimicrobial therapy after incision and drainage that results from community-associated MRSA is recommended: • Severe or extensive disease (eg, involving multiple sites of infection) or rapid progression in presence of associated cellulitis. • Signs and symptoms of systemic illness. • Associated comorbidities or immunosuppression (diabetes mellitus, HIV infection/AIDS, neoplasm). • Extremes of age. • Abscess in area difficult to drain completely (eg, face, hand, and genitalia). • Associated septic phlebitis. • Lack of response to incision and drainage alone. Source: Liu C, et al. Clin Infect Dis. 2011;52:285-322.

MRSA has an enor economic impact. Man difficulties when mana lines are designed to be a living document, meaning they will evolve as new information and antibiotics become available,” says Dr. Chambers. He adds that some of the key recommendations include guidance on when to use antimicrobial therapy after incision and drainage resulting from community-associated MRSA (Table 1). “Incision and drainage alone is likely adequate for most simple abscesses or boils, and antibiotic therapy is not needed. Antibiotic therapy is, however, recommended for other specific situations in the guidelines.” The management of all MRSA infections should include identification, elimination, and/or debridement of the primary source and other sites of infection when possible. This includes cases in which there is drainage of abscesses; removal of central venous catheters, prosthetic devices or other implants; and debridement of osteomyelitis. The guidelines also indicate that education on personal hygiene and appropriate wound care is recommended for all patients with SSTIs. Patients should be instructed to keep drained wounds covered with clean, dry bandages and maintain good personal hygiene, particularly after touching infected skin. Patients should also be educated to avoid reusing or sharing personal items that have contacted infected skin. “The guidelines also list key performance measures in managing MRSA infections that all clinicians should follow,” Dr. Chambers says (Table 2). “Within these performance measures is guidance on the appropriate dosing of vancomycin as well as efforts that should be taken to promote good clinical practices.”

Looking Ahead Each section of the IDSA guidelines begins with a specific clinical question and is followed by recom-

rmous clinical and ny clinicians often have aging these infections. — Henry F. Chambers, MD mendations as well as summaries of the most relevant evidence that support the recommendations. “The intent was to create a roadmap for clinicians to follow and the rationale for why these recommendations were made,” says Dr. Chambers. “However, while the guidelines provide good practice recommendations to guide clinicians, we still have knowledge gaps to address. For example, we’re hoping to learn more about the optimal management and duration of therapy for osteomyelitis and SSTIs, among other MRSA infections, and which, among several alternatives, are the most effective regimens. There is much more to be learned so that we can optimize the management of MRSA infections. The current guidelines will hopefully serve as a bridge to covering knowledge gaps in the future.”

5 Key Performance Measures in Managing MRSA

Table 2

The management of all MRSA infections should include identification, elimination and/ or debridement of the primary source and other sites of infection when possible (eg, drainage of abscesses, removal of central venous catheters, and debridement of osteomyelitis).

In patients with MRSA bacteremia, follow-up blood cultures 2-4 days after initial positive cul tures and as needed thereafter are recommended to document clearance of bacteremia.

To optimize serum trough concentrations in adult patients, vancomycin should be dosed according to actual body weight (15-20 mg/kg/dose every 8-12 hours), not to exceed 2 g per dose. • Trough monitoring is recommended to achieve target concentrations of 15-20 μg/mL in patients with serious MRSA infections and to ensure target concentrations in those who are morbidly obese, have renal dysfunction, or have fluctuating volumes of distribution. • The efficacy and safety of targeting higher trough concentrations in children requires additional study but should be considered in those with severe sepsis or persistent bacteremia.

4. 5.

When an alternative to vancomycin is being con sidered for use, in vitro susceptibility should be confirmed and documented in the medical record. For MSSA infections, a β-lactam antibiotic is the drug of choice in the absence of allergy. Source: Liu C, et al. Clin Infect Dis. 2011;52:285-322.

Henry F. Chambers, MD, has indicated to Physician’s Weekly that he has received grant support from Pfizer and has consulted for Pfizer, Astellas, and Ortho-McNeil. For more information on this article, including references, visit www.physiciansweekly.com.

Additional Resources: Liu C, Bayer A, Cosgrove SE, et al. Clinical practice guidelines by the Infectious Diseases Society of America for the treatment of methicillin-resistant Staphylococcus Aureus infections in adults and children. Clin Infect Dis. 2011;52:285-322. Available at:http://cid.oxfordjournals.org/content/early/2011/01/04/cid.ciq146.full Calfee DP, Salgado CD, Classen D, et al. Strategies to prevent transmission of methicillin-resistantStaphylococcus aureus in acute care hospitals. Infect Control Hosp Epidemiol. 2008;29(Suppl 1):S62-S80. Klevens RM, Morrison MA, Nadle J, et al. Invasive methicillin-resistant Staphylococcus aureusinfections in the United States. JAMA. 2007;298:1763-1771. Rybak MJ, Lomaestro BM, Rotschafer JC, et al. Vancomycin therapeutic guidelines: a summary of consensus recommendations from the Infectious Diseases Society of America, the American Society of Health-System Pharmacists, and the Society of Infectious Diseases Pharmacists. Clin Infect Dis.2009;49:325-327.

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