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■ Infection prevention ■ Massage for back pain ■ Trichomoniasis spreads ADVISOR FORUM

■ Postherpetic neuralgia ■ Hepatic encephalopathy ■ When to consider dialysis

✶ FREE CE COURSES! ■ Geriatric functional screening:


■ Dermatology Clinic



■ Dermatologic Look-Alikes

VELVETY PLAQUES AND SKIN TAGS PAGE 99 Expanded job listings!

| S E P T E M B E R 2 011 |


ACL INJURIES The anterior cruciate ligament (white) minimizes stress across the knee joint.


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Persons appearing in photographs in “Newsline,” “The Legal Advisor,” and “Clinical Challenge” are not the actual individuals mentioned in the articles.They appear for illustrative purposes only. The Clinical Advisor® (USPS 017-546, ISSN 1524-7371), Volume 14, Number 9, is published 12 times a year, monthly, for $75.00 per year in the United States; $85.00 in Canada; $110.00 for all other foreign, in U.S. dollars, by Haymarket Media, Inc., 114 West 26th Street, 4th Floor, New York, NY 10001. Single copy: $20 U.S.; $30 foreign. To order or update your paid subscription, call 800.436.9269. Periodicals postage rate paid at New York, NY, and additional mailing offices. POSTMASTER: Send all address changes to: The Clinical Advisor, c/o DMDData Inc., 2340 River Road, Des Plaines, IL 60018. Call 800.430.5450 to change your address or make other subscription inquiries. Requests for subscriptions from outside the United States must be accompanied by payment. All rights reserved. Reproduction in whole or in part without permission is prohibited. Copyright © 2011.

Now you can see our cartoons online, too. Treat yourself to a smile or chuckle and view our cartoon slideshows at cartoons

“Ever notice, no two flakes are alike?” • THE CLINICAL ADVISOR • SEPTEMBER 2011 3

© Roy Delgado

Editor Joe Kopcha, Managing editor Marina Galanakis Senior editor Delicia Yard Web editor Nicole Blazek Contributing editors Bruce D. Askey, MSN, CRNP; Philip R. Cohen, MD; Peter F. Cohn, MD; JoAnn Deasy, PA-C, MPH; Melody French, PhD, PA, FNP; Virginia H. Joslin, PA-C, MPH; Norma M. Keller, MD; Debra August King, PhD, PA; Ann W. Latner, JD; Cheryl F. MacDonald, MSN, MPH, CRNP; Malka G. Messner, RPA-C, MPAS; Daniel R. Mishell Jr, MD; Claire B. O’Connell, MPH, PA-C; Patrick G. O’Connor, MD, MPH; Michael E. Ryan, DO; Sherril Sego, FNP, DNP; Lisa Stern, APRN; Karen T. Vujevich, RN-C, MSN, CRNP; Julee B. Waldrop, MS, PNP; Reuben W. Zimmerman, PA-C; Michael E. Zychowicz, RN, MS, NP-C Group art director, Haymarket Medical Jennifer Dvoretz Assistant art director Natasha Marcano-Dillon Production director Leslie Carsman Circulation manager Paul Silver Assistant circulation manager Monica Bond Audience development director John Crewe National accounts manager Alison McCauley, 646.638.6098 Group publisher Thomas P. Hennessy, 646.638.6085 Editorial director Tanya Gregory CEO, Haymarket Media Inc. Lee Maniscalco





Newsline ■ CDC issues infection-control guide for outpatient settings ■ ACOG: Start annual mammograms at age 40 years ■ Power of placebo evident in asthma treatment ■ Massage eases low back pain ■ Pistachios hailed as healthful ■ Tdap vaccine now approved for ages 65 years and up ■ Trichomonas vaginalis very common in older women ■ Secondhand smoke may cause hearing loss in adolescents

CME/CE Screening for functional deficits in older adults Presenting for nearly twice as many office visits as younger adults, this patient population merits special attention from primary-care providers.

DEPARTMENTS Improving outpatient infection prevention 13


Derm Dx Read the clinical descriptions, view the images, and then make your diagnosis at


CME/CE Dermatology Clinic ■ The hair on a 54-year-old woman’s frontal scalp and crown has been thinning for the past year.

Drug Update ■ Oral treatment to prevent blood clots in patients undergoing kneeor hip-replacement surgery

■ Red and painful bruising—described as “hard bumps” by the patient—was noted on both of her shins.

110 Commentary Comorbidities of obesity on the rise 33



Getting back in the game after ACL rupture Injuries to the knee ligaments can usually be diagnosed with a complete patient history and physical exam. New strategies against comorbidities of obesity Diabetes, heart disease, hypertension, sleep apnea, depression, and liver disease are among the most common risks associated with obesity in adults.


Follow us on Twitter @ClinicalAdvisor


Clinical Challenge A renal tumor originally diagnosed as an angiomyolipoma grew from 8 mm to 1.6 cm in nine months and was removed via partial nephrectomy.

Continues on page 6

Kidney mass detected on ultrasound 89

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Legal Advisor A clinician’s career ambitions are derailed after an unauthorized peek at the medical record of a celebrity patient is reported by a coworker.


CME/CE Dermatologic Look-Alikes Two patients present with discoloration of the eyelid—one a woman with nonpruritic velvety plaques, the other a boy with itchy dermatitis.

■ Varenicline may be associated with

small increased risk of cardiovascular and psychiatric adverse events ■ Selenium improves quality of life and ophthalmologic outcomes in patients with Graves’ orbitopathy

ADVISOR FORUM 62 Read all agreements before signing 96

103 CME/CE Posttest 104 Alternative Meds Update No link has been found between coffee consumption and the development of hypertension or heart disease. 107 Evidence-Based Medicine ■ Addition of controlled-release combination of phentermine and topiramate to lifestyle intervention may increase weight loss in overweight or obese adults


Consultations ■ Efficacy of cephalexin after raising dosage ■ Avoiding reflux when stopping PPIs ■ Management of postherpetic neuralgia ■ And more Clinical Pearls ■ An alternative to a food diary ■ Beyond “Just say no” ■ And more


Your Comments ■ Renal-protective properties of

ACE inhibitors and ARBs Elevated ALP and normocytic anemia 63

■ When to consider dialysis ■ Plenty of blame to go around

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Sibling’s status may help predict autism risk Autism recurrence rates are higher than previously estimated for younger siblings of children with an autism spectrum disorder.

Scoliosis Scoliosis is a curving of the spine that worsens with growth spurts. Scoliosis begins as a sideways curvature of the spine that typically begins in childhood and progresses to an S-shaped curve.

Clindamycin found to be the best antibiotic for pediatric SSTIs Clindamycin therapy resulted in fewer recurrences and treatment failures among children with skin and soft tissue infections vs. trimethroprim-sulfamethoxazole or beta-lactam antibiotics.

Pediatric Resource Center Promoting food safety for children with allergies Educating parents and working with them to create action plans for their child is an important part of creating a safe environment.

Women smokers at higher risk for coronary heart disease Women who smoke have a 25% greater risk for coronary heart disease (CHD) then men who smoke, data from a meta-analysis involving more than 2.4 million people indicate.

Discussing vaccine hesitancy with parents Clinicians must be prepared to have effective discussions about the benefits and risks of vaccination.

The Waiting Room Derm Dx

Official Blog of The Clinical Advisor Robyn Carlisle, MSN, CNM, WHNP

Interact with your peers by viewing the images and offering your diagnosis and comments.

Expanding nurse practitioner roles benefits patients Robyn Carlisle, MSN, CNM, WHNP, responds to a physician who told patients that NPs are “too stupid to get into medical school.”

Multiple erythematous pustules on a toddler’s hands An otherwise healthy 14-month old boy from Texas developed bilateral edematous hands. Painful erosions on the bilateral inguinal folds and intergluteal cleft A woman presented with a two-week history of erosions on her bilateral inguinal folds, perineum, and intergluteal cleft.

Practice what you preach: Promoting clinician self-health Why do so many health-care providers have trouble following their own advice?


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Page 55 FEATURE Screening for functional deficits in older adults Wanda Bonnel, PHD, GNP-BC ■ LEARNING OBJECTIVES: • Understand the incidence of chronic disease and interplay of health issues among individuals aged 65 years and older. • Learn how such tools as the Mini-Cognitive Assessment Instrument screen for dementia. • Identify screening tests used to detect early indicators of Parkinson disease. • Know what drug class can lead to incontinence in patients with no previous episodes. ■ CREDITS: 0.5

Page 85 DERMATOLOGY CLINIC Case 1: Thinning hair at the frontal scalp and crown Kerri Robbins, MD

Case 2: Painful shin lesions described as “bumps” Esther Stern, NP-C ■ LEARNING OBJECTIVES: • To increase awareness of dermatologic conditions, their diagnosis, and up-to-date treatment. ■ CREDITS: 0.25

Page 99 DERMATOLOGIC LOOK-ALIKES Discoloration of the eyelid Noah Scheinfeld, MD, JD, and Nicholas Barnes ■ LEARNING OBJECTIVE: • To improve the clinician’s ability to distinguish and properly treat dermatologic conditions with similar presentations. ■ CREDITS: 0.25

Page 103 POSTTEST This program has been reviewed and is approved for a maximum of 1 hour of AAPA Category I CME credit by the Physician Assistant Review Panel. Approval is valid for one year from the issue date of September 2011. Participants may submit the self-assessment at any time during that period. This program was planned in accordance with AAPA’s CME Standards for Enduring Material Programs and for Commercial Support of Enduring Material Programs. The Nurse Practitioner Associates for Continuing Education (NPACE) is an approved provider of continuing education by the Massachusetts Association of Registered Nurses, Inc. (MARN), an accredited approver by the American Nurses Credentialing Center’s Commission on Accreditation (ANCC). NPACE designates this educational activity for a maximum of 1 contact hour of credit. Participants should only claim credit commensurate with the extent of their participation in the activity.



New ACOG policy on mammograms page 14

S E P T E M B E R 2 0 11

Pistachios may help reduce HbAic levels page 15

Teens’ hearing hurt by secondhand smoke page 16


CDC issues infection-control guide

Infection prevention can be improved throughout the health-care system.

blood or body fluids, or after caring for patients with known or suspected infectious diarrhea; otherwise, use alcoholbased rub. • Wear a surgical mask when placing a catheter or injecting material into epidural or subdural space. • Cleanse the access diaphragms of medication vials with 70% alcohol before inserting a device into the vial. • Select disinfectants registered with the EPA or detergents/disinfectants with label claims for use in health-care settings. The CDC acknowledges that the guide is not all-encompassing but that the recommendations it contains effectively represent “the absolute minimum infection prevention expectations for safe care in outpatient (ambulatory care) settings.”

Prevalence of obesity among adults aged 20 years and older According to the CDC, black women were the most likely group to have BMI >30.



Female 42.1%


31.5% Percentage

CHARGING THAT adherence to standard infection-prevention practices in many outpatient settings is lacking, the CDC has released a guide to help educate clinicians regarding minimum expectations of safe care and to protect patients. “Repeated [infectious] outbreaks resulting from unsafe practices, along with breaches of infection control noted in ambulatory surgical centers during inspections, indicate the need for better infection prevention across our entire health-care system, including outpatient settings,” contended the CDC’s deputy director of the Division of Healthcare Quality Promotion, Michael Bell, MD. The Guide to Infection Prevention for Outpatient Settings: Minimum Expectations for Safe Care (available at pdfs/guidelines/Ambulatory-

Care-04-2011.pdf; accessed August 15, 2011) is intended for providers in such outpatient settings as primary-care offices, surgery centers, endoscopy clinics, and pain-management clinics. The guide states that all outpatient practices should have on staff at least one person with specific training in infection control. This individual should help develop a written infection-control policy and should have regular communication with providers to address specific issues or concerns. Other key recommendations include but are not limited to the following: • Even if gloves will be worn, perform hand hygiene before touching a patient, again after glove removal, and before exiting the patient-care area. • Use soap and water when hands are visibly soiled, such as by


33.0% 27.6%





Source: CDC/NCHS, National Health Interview Survey, 2010




Black Non-Hispanic • THE CLINICAL ADVISOR • SEPTEMBER 2011 13

Newsline IN A CHANGE of policy, the American College of Obstetricians and Gynecologists (ACOG) now recommends that women undergo screening mammography once a year beginning at age 40 years (Obstet Gynecol. 2011;118:372382). The organization previously advised women to have a mammogram every one to two years beginning at age 40, increasing to annually beginning at age 50. A statement issued by ACOG noted that the mammography screening recommendation was based on the incidence of breastcancer, the sojourn time for breast cancer growth (the time period between when a tumor may be detected by a mammogram while still very small and before it grows big enough to become symptomatic), and the potential

to reduce the number of deaths from the disease. Although women in their 40s have a lower overall incidence of breast cancer than do older women, those aged 40 to 49 years have the shortest average sojourn time (2.0 to 2.4 years), whereas women aged 70 to 74 years have the longest (4 to 4.1 years). “If women in their 40s have annual mammograms, there is a better chance of detecting and treating the cancer before it has time to spread than if they wait two years between mammograms,” explained Griffin. The five-year survival rate is 98% for women whose breastcancer tumors are discovered at their earliest stage. ACOG continues to recommend clinical breast exams once


ACOG: Start annual mammograms at 40

Calcium deposits (white) can be an early sign of breast cancer.

a year for women aged 40 years and older, and every one to three years for women aged 20 to 39 years. More frequent clinical breast exams, annual MRI, mammograms before age 40 years, or other breast screening may be recommended for women at high risk of developing breast cancer.

AFTER BEING treated with a placebo inhaler or sham acupuncture, asthma patients reported significantly greater improvement in symptoms than they felt after receiving no treatment—and this improvement was similar to that reported after active treatment with an albuterol inhaler. The 39 patients who completed the double-blind, crossover pilot study had been given one each of the three interventions as well as no intervention in random order during four sequential visits taking place three to seven days apart. This process was repeated

Spirometry was performed repeatedly at each visit.

until each patient had completed 12 visits. Spirometry was performed repeatedly over a period of two hours at each visit. The investigators measured maximum forced respiratory volume in 1 second (FEV1) and recorded the participants’ self-reported improvement ratings. Only albuterol improved FEV1, producing a 20% increase in that measure. By comparison, placebo inhaler, sham acupuncture, and no intervention resulted in FEV1 increases of approximately 7%. However, the active drug provided no incremental benefit


with respect to the self-reported outcomes. While acknowledging that patient self-reports should be interpreted with caution and that objective outcomes should be more heavily relied upon for optimal asthma care, the researchers noted that quality-of-life metrics, emergency-department visits, and other outcomes may be more clinically relevant to patients and their health-care providers (N Engl J Med. 2011;365:119-126; available at full/10.1056/NEJMoa1103319, accessed August 15, 2011).


Power of placebo evident in asthma treatment

RELAXATION massage and structural massage each surpassed usual care in improving pain and function in patients with chronic low back pain participating in a randomized controlled trial. A total of 401 persons aged 20 to 65 years with nonspecific chronic low back pain were assigned to receive relaxation massage, structural massage, or usual care. Relaxation massage is intended to induce a generalized sense of relaxation through circular friction, vibration, rocking and jostling, and holding; structural massage aims to resolve soft-tissue abnormalities at the root of musculoskeletal contributors to back pain. Each set of massage patients received 10 weekly treatments, with first visits lasting 75 to 90 minutes and subsequent visits lasting 50 to 60 minutes. Therapists also recommended at-home exercises. The usual-care patients received no special care for their back problems. At 10 weeks, six months, and one year, the massage groups fared much better than those receiving usual care, with the former being twice as likely to report significant improvements in pain and function compared with the usualcare patients. Approximately two-thirds of the massage patients improved substantially, compared with an estimated one-third of the usual-care group (Ann Intern Med. 2011;155:1-9).

Pistachios hailed as healthful PISTACHIO nuts have captured the attention of scientists, having been featured in four recent studies examining the dietary benefits of this food. One report involved 117 persons with type 2 diabetes assigned to one of three treatments for three months to assess the effect of mixed-nut consumption as a source of vegetable fat on serum lipids and hemoglobin (Hb)A1c. Supplementation was provided as 475 kcal per 2,000-kcal diet in the form of 75 g/day of mixed nuts (including pistachios), muffi ns, or half-portions of both. Full-nut dose (mean intake 73 g/day) reduced HbA1c by .21% absolute HbA1c units, whereas no change was seen after muffin or half-nut dose. LDL decreased significantly after full-nut dose compared with muff in; LDL reduction after half-nut dose was intermediate and not signif icantly different from the other treatments (Diabetes Care. 2011;34:1706-1711).

Those who ate in-shell pistachios consumed 41% fewer calories.

Research conducted by the U.S. Department of Agriculture and presented online by the British Journal of Nutrition also centered on the fat found in pistachios. David J. Baer, PhD, and colleagues learned that pistachio fat may not be completely absorbed by the body, indicating that this snack may actually contain fewer calories per serving than originally thought. They determined that a 30 g serving contains 160 calories—5.9% lower than previous calculations. Pistachio consumption also lowered LDL by 6% but did not significantly change total plasma cholesterol or HDL. Two other pistachio studies appearing in the journal Appetite (2011;57:414-417 and 418-420) found that (1) persons who ate in-shell pistachios consumed 41% fewer calories than those eating the shelled version, and (2) pistachio shells can provide important visual cues as a reminder of consumption that translate to reduced-calorie consumption.

Tdap vaccine now approved for ages 65 and up The FDA has approved Boostrix in persons aged 65 years and older, thereby clearing the first vaccine for preventing tetanus, diphtheria, and pertussis (Tdap) in this age group. Boostrix was originally approved for use in adolescents aged 10 through 18 years; the indication expanded to include adults aged 19 through 64 years. Although other vaccines for the prevention of tetanus and diphtheria are available to persons aged 65 years and older, none prevents all three diseases.

The incidence of pertussis has been on the rise since 2007, with large, local outbreaks occurring in 2010 in California, Michigan, and Ohio. Outbreaks of this highly contagious disease have occurred among the elderly in nursing homes and hospitals. A study of approximately 1,300 people aged 65 years and older demonstrated good antibody-level response, with the most common adverse reactions reported as headache, fatigue, and pain at the injection site. • THE CLINICAL ADVISOR • SEPTEMBER 2011 15


Massage eases low back pain

Newsline A LARGE STUDY indicates that the sexually transmitted parasite Trichomonas vaginalis (TV) is harbored by many women in their 40s, with the highest infection rate found in women aged 50 years and older. Charlotte Gaydos, MS, DrPH, and fellow researchers collected samples from 7,593 U.S. women aged 18 to 89 years undergoing routine screening for Chlamydia trachomatis (CT) and Neisseria gonorrhea (NG) in a variety of clinical settings in 21 states. The specimens were retrospectively tested for TV. As the investigators reported at the annual meeting of the International Society for STD Research, overall prevalence rates of TV, CT, and NG were 8.7%, 6.7%, and 1.7%, respectively. TV prevalence ranged from 7.5% to

8.6% in women aged 18 to 39 years, increasing to 9.8% in those aged 40 to 44 years. Highest prevalence was seen among women aged 45 to 49 years (13.4%) and those over age 50 years (13%). In contrast, CT and NG prevalence rates were less than 2% in women aged 40 and older and highest in women under age 30 years, ranging from 5.2% to 14.3% for CT and 1.3% to 3% for NG. “Trichomonas infections are quite treatable with antibiotics, and these high numbers really warrant older women getting screened by their family [clinicians] and gynecologists during routine checkups to make sure they are not infected and are not inadvertently spreading it to others,” advised Dr. Gaydos in a recent statement


Trichomonas vaginalis in older women

Trichomonas vaginalis infects the genital and urinary tract of both sexes.

describing her group’s findings. “What we are really witnessing with Trichomonas—especially in older women—is that no one ever looked, no one ever tested and diagnosed, and no one is really getting treated, so the infection persists year after year.”

Secondhand smoke may cause hearing loss AN ANALYSIS of data from 1,533 persons aged 12 to 19 year s par t icipat ing in the National Health and Nutrition Examination Survey 2005-2006 (NHANES) has uncovered an association between secondhand smoke and an increased risk of hearing loss in members of this age group, with most of them being unaware of the problem. Secondhand smoke is a known risk factor for otitis media (OM), with recurrent acute OM being more common in the nearly 60% of U.S. children exposed.

The rate of hearing loss rose with the level of serum cotinine.

Secondhand smoke also may have the potential to affect auditory development, leading to sensorineural hearing loss. The NHANES adolescents had been interviewed about their health status, family medical history, exposure to secondhand smoke, and self-recognition of hearing impairment. They also underwent physical examination, including hearing tests and blood testing for cotinine, a by-product of nicotine exposure. Compared with teens that had no secondhand-smoke exposure,


those who were exposed exhibited notably higher rates of lowand high-frequency hearing loss. The rate of hearing loss appeared to be cumulative, increasing with the level of serum cotinine. Nearly 82% of the affl icted parties did not recognize hearing difficulties. “Adolescents exposed to [secondhand smoke] may need to be closely monitored for early hearing loss with periodic audiologic testing,” cautioned the researchers (Arch Otolaryngol Head Neck Surg., 2011;137:655-662). ■

DrugUpdate New drug information from the publishers of MPR

Oral treatment to prevent blood clots Product: Xarelto Company: Janssen Pharmacologic class:

Factor Xa inhibitor Active ingredient: Rivaroxaban 10 mg; tablets. Indication: Prophylaxis of deep vein thrombosis, which may lead to pulmonary embolism in patients undergoing knee- or hipreplacement surgery. Pharmacology: Rivaroxaban is an orally bioavailable factor Xa inhibitor that selectively blocks the active site of factor Xa and does not require a cofactor (e.g., Antithrombin III) for activity. Activation of factor X to factor Xa via the intrinsic and extrinsic pathways plays a central role in the cascade of blood coagulation. Clinical trials: Three trials were conducted to evaluate the safety and efficacy of rivaroxaban. Two randomized, doubleblind, studies (RECORD 1 and 2) involving patients undergoing elective total hip replacement surgery compared rivaroxaban 10 mg once daily starting at least six to eight hours after wound closure

versus enoxaparin 40 mg once daily starting 12 hours preoperatively. In RECORD 1, 1,513 patients received rivaroxaban; 1,473 patients received enoxaparin. The total percentage of patients experiencing venous thromboembolism (VTE) was 1.1% for the rivaroxaban group compared with 3.9% for the enoxaparin group; relative risk reduction (RRR) was 71%. In RECORD 2, 834 patients received rivaroxaban; 835 patients received enoxaparin. In this study the treatment duration differed between study arms (rivaroxaban: 33.5 +/- 6.9 days; enoxaparin:

Xarelto is for patients undergoing knee- or hip-replacement surgery.

12.4 +/- 2.9 days). The total percentage of patients experiencing VTE was 2% for the rivaroxaban group compared with 8.4% for the enoxaparin group; RRR was 76%. The RECORD 3 trial was conducted in patients undergoing elective total-knee-replacement surgery. Patients were given either rivaroxaban 10 mg once daily (813) or enoxaparin 40 mg once daily (871). In the rivaroxaban group, the percentage of total VTE was 9.7%; the enoxaparin group had 18.8%; RRR was 48%. Adults: Take six to 10 hours after surgery once hemostasis is established. 10 mg once daily; may increase to 20 mg once daily with food if necessary. Hip: treat for 35 days. Knee: treat for 12 days. Children: Not recommended. Contraindications: Active major bleeding. Warnings/Precautions: Increased risk of spinal/epidural hematoma in anticoagulated patients receiving neuraxial anesthesia or undergoing spinal puncture; monitor for signs/ symptoms of neurological impairment. Conditions with increased risk of hemorrhage. Severe renal impairment (creatinine clearance <30 mL/min), moderate or severe hepatic impairment, hepatic disease associated with coagulopathy:

avoid. Monitor closely for blood loss with moderate renal impairment; discontinue if acute renal failure develops. Elderly. Labor & delivery. Pregnancy (Cat. C); use with caution, risk of pregnancyrelated hemorrhage. Nursing mothers: not recommended. Interactions: See Adult dose. Increased risk of bleeding with concomitant platelet aggregation inhibitors, other antithrombotic agents, fibrinolytic therapy, thienopyridines, chronic use of nonsteroidal anti-inflammatory drugs. Avoid with concomitant combined P-glycoprotein (gp) and strong CYP3A4 inhibitors (e.g., ketoconazole, itraconazole, lopinavir/ritonavir, ritonavir, indinavir/ritonavir, conivaptan). May be potentiated with concomitant renal impairment and combined P-gp and weak or moderate CYP3A4 inhibitors (e.g., erythromycin, azithromycin, diltiazem, verapamil, quinidine, ranolazine, dronedarone, amiodarone, felodipine). Adverse reactions: Bleeding, wound secretion, pain in extremity, muscle spasm, syncope, pruritus, blister. How supplied: Tabs—30, 100 (10⫻10 blister cards) For more information, call 800.526.7736 or visit ■

For more products, visit • THE CLINICAL ADVISOR • SEPTEMBER 2011 21


Getting back in the game after ACL rupture A safe return to activity is the goal of any injured athlete. Knee injuries deserve special attention, particulary those involving ligament damage.



The anterior cruciate ligament (white) provides rotational stability to the knee.


he anterior cruciate ligament (ACL) is one of the most commonly injured structures of the knee.1 An estimated 100,000 ACL ruptures are recorded each year in the United States, 60% of which require some type of surgical intervention.1 Total costs associated with ACL diagnosis and management exceeds $1 billion in North America alone.2 ACL rupture is an injury that affects more than professional athletes. It is frequent among active people in the general population as well. Physical activity is a normal part of everyday life for most individuals. Whether someone is a high-school football player, an avid runner, or a father playing catch with his son, physical activities fulfi ll competitive and social desires of people from all walks of life. Sports at any level are accompanied by numerous risk factors that can result in injury. Many injuries are minor and only require short-term rehabilitation, but others—especially ACL ruptures—can be season- or career-ending. This results in an unfortunate situation for the athlete: Such positive effects of athletic activity as social interaction and health benefits can be destroyed if an injury of considerable magnitude occurs and an athlete cannot continue to participate.2 A swift, successful return to activity is the initial priority.3 Therefore, early surgical stabilization of the ACL is recommended for athletes wishing to return to a pre-injury level of ability. Today, the gold-standard treatment for correcting an ACL rupture is surgical reconstruction


Providers should encourage athletes to make soft landings with large amounts of knee-joint flexion to lower risks and prevent ACL injuries. using autograft or allograft tendons to effectively reproduce knee stability.4 In short, an orthopedic surgeon removes the injured person’s hamstring tendons or uses donated tendons to build a new ACL. After reconstruction and rehabilitation, the athlete should regain knee stability and be able to compete at a pre-injury level. Etiology

The ACL is an important structure for forward stabilization of the knee. An ACL rupture causes impaired function and destroys the knee’s normal mechanics.5 Approximately 70% of ACL injuries arise in noncontact situations.6 Noncontact ACL injuries are six to eight times more common in women than in men.7 In the United States, the incidence is rising as a result of increasing ACL injuries among women aged 15 to 19 years.6 Anatomic, environmental, hormonal, and biomechanical factors increase an athlete’s risk for noncontact injuries.6 Anatomic risks factors primarily contribute to noncontact injuries in women. Because women have smaller intercondylar notches in the knee joint, there is an increased likelihood of ACL impingement or rupture. Typically, men have wider U-shaped intercondylar notches, reducing the likelihood of injury resulting from an anatomic or structural issue.6 Women also tend to have larger pelvises, which lead to larger Q angles. To form the Q angle, draw a line from

the anterior superior iliac spine (ASIS) of the pelvis to the center of the patella; then draw another line from the center of the patella to the tibial tuberosity. Larger Q angles are believed to result in greater amounts of stress and strain on the knees and a higher susceptibility to knee injury.6 Faulty equipment and inadequate shoe-to-surface interactions equally increase the risk of injury in both male and female athletes. Special shoes and braces are used to provide better joint alignment and knee support to eliminate environmental factors of this nature.7 Female sex hormones have recently been studied as contributors to ACL injuries. Estrogen and progesterone are thought to affect the composition and mechanics of the ACL, thus heightening a woman’s chance of injury. Finally, biomechanical factors are unique to each athlete. Degrees of muscle strength, control, and athletic ability affect each individual differently.7 Usually, ACL tears occur when large loads or forces cannot be dissipated safely through the knee. Normally, the bones and soft tissues around the knee will safely disperse the applied forces through the knee and gradually decrease the forceful momentum. If loads or forces are too strong, the body’s neuromuscular system becomes challenged, ultimately resulting in injury.8 For example, if an athlete lands with his or her lower body in a stiff position, higher ground reaction forces are transferred through the knee, placing unbearable strain on the joint and increasing chance of injury. Providers should encourage athletes to make soft landings with large amounts of knee-joint flexion to lower risks and prevent ACL injuries.9 Common athletic situations known to produce noncontact ACL injuries include events involving quick changes in direction, decelerating with cutting maneuvers, and pivoting movements or jump landings with full- or nearly full-knee extension.6 Contact injuries are responsible for approximately 30% of ACL injuries and are caused by collisions with other players or objects on the field.6 Clinical presentation

FIGURE 1. The Lachman test assesses stability of the ACL.

Patients most often describe a popping or tearing sensation immediately followed by severe pain. Common complaints include, “My knee buckled under,” or “My knee suddenly gave out.”10 Either of these scenarios should raise the question of possible ACL derangement. About 70% to 80% of patients with ACL ruptures complain of knee instability during daily activities or with specific high-level activities.11 Symptoms


Earlier recognition of an ACL rupture leads to greater patient satisfaction and provides more optimal surgical treatment and rehabilitation. occur while walking, but patients usually report an onset of symptoms after pivoting movements or abrupt changes in direction. Immediate joint dysfunction with an inability to ambulate is the most common symptom associated with ACL rupture.12 Patients describe immediate swelling of the knee after the initial mechanism of injury. Swelling is observed with ligament injury because of hemorrhaging that occurs when a ligament is torn or ruptured. Acute hemarthrosis—an extravasation of blood into a joint or synovial cavity—is a textbook sign of acute ACL injury. Pain, edema, and stiffness of the injured knee joint are consistent with hemarthosis. The sensitivity level of the patient and/or the experience level of the examiner may hinder an adequate physical examination.12 Earlier recognition of an ACL rupture leads to greater patient satisfaction11 and provides more optimal surgical treatment and rehabilitation. Primary-care workup

A complete history and physical examination will diagnose approximately 90% of all ligament injuries.13 Before examining the patient, document all past knee injuries to improve accuracy of the exam. Patients with previous ACL ruptures are more likely to incur subsequent tears.14 Because joint position can determine which anatomical structures are most likely to be injured, discerning the mechanism of injury is extremely important during the interview. A detailed summary of the accident—to include the position of the knee, direction of external forces, and description of the joint after trauma—is essential.13 Initial workup for a ruptured ACL requires a thorough physical examination. Focusing on the healthy knee aids in maneuvering the patient into a comfortable position and establishes patient-provider trust. The primary goal of the exam is to create a relaxing environment that allows easier movement of the patient. Properly examining the healthy knee first provides a necessary control for comparison during evaluation of the injured knee.15 The physical exam consists of inspection, palpation, and assessment of knee-joint function. Inspecting the knees for asymmetry will determine the presence of effusion or hemarthrosis. Three functionality tests should be performed to determine the stability of the joint and ACL. These tests evaluate joint integrity and any degree of separation by applying stress in certain directions and assessing the endpoints.

Intact ligaments produce an abrupt, firm end-feel, whereas sprained or torn ligaments have soft, indistinct endpoints.15 The best functionality test for assessing the stability of the ACL is the Lachman test (Figure 1). With the patient lying in the supine position, flex the knee 20° to 30° while the heel rests on the end of the exam table. Grasp the femur with the nondominant hand to prevent movement of the upper leg. Then, grasp the lower leg at the proximal tibia and apply a forward tug. This movement should produce a firm endpoint. If the endpoint is not firm or there is increased anterior translation of the tibia, the Lachman test is positive.15 The second functionality test to be performed is the anterior drawer test (Figure 2). With the patient lying the supine position, place the knee in 90° of flexion without rotation. Place both hands on the proximal tibia, and pull the upper part of the calf forward. An anterior drawer test is positive when the tibia moves anteriorly without an abrupt, hard endpoint.15 Finally, the pivot shift test (Figure 3) assesses anterior subluxation of the lateral tibial plateau when the lower leg is stabilized in near full extension. With increasing flexion, a palpable springlike reduction should be observed. A positive pivot shift test usually produces a thud or jerk around 10° to 20° of flexion. During a positive exam, the force created by the examiner will cause the knee joint to slip, giving a positive visual for identifying rotational knee instability.15 Continues on page 26

FIGURE 2. The anterior drawer test is used to determine the degree of tibial displacement. • THE CLINICAL ADVISOR • SEPTEMBER 2011 25


Diagnostic criteria

There are four criteria that definitively diagnose an ACL rupture. Determination is made after establishing (1) popping during injury, (2) knee instability, (3) effusion or hemarthosis, and (4) a positive Lachman test.10 The physical examination functionality tests for assessing ACL derangement are specific and moderately sensitive. Therefore, the physical examination is remarkably accurate in the hands of a trained practitioner. If the examination is negative, the likelihood that the patient has a ligament injury is exceptionally low. Patients that do not meet criteria for an ACL rupture should be managed with conservative and supportive treatment. In light of the fact that 1% to 2% of ligament pathologies are missed during physical examination, careful follow-up and re-evaluation is necessary if symptoms do not improve.12 After obtaining a positive physical exam indicating a possible ACL injury, referral to an orthopedic surgeon is essential. An MRI is not required when deciding whether to refer to a specialist. MRI adds only marginal value when determining whether a patient needs an orthopedic referral or conservative outpatient therapy.16 The main purpose of an MRI is prompt identification of any surgically treatable traumatic knee injury. The primary advantage of MRI is that it is not invasive, which makes it faster and more economical for patients and clinicians.17 A negative MRI

FIGURE 3. The pivot shift test assesses the degree of incapacitating dysfunction

WHAT DO YOU THINK? Add your comments to this article —or any article — by going to will also see what your colleagues are saying.

of the knee reliably excludes any internal abnormality requiring surgical intervention, which prevents the need for invasive diagnostic arthroscopy. If symptoms are ongoing, arthroscopy may be an orthopedic surgeon’s final diagnostic attempt.18 A thorough clinical examination, along with MRI, provides the most accurate noninvasive source of information for pathological findings of the ACL.16 Treatment and prognosis

A treatment plan should be developed after recording the patient’s initial symptoms, performing a detailed physical examination, and assessing any associated injuries that may be present. Other key factors used to determine appropriate treatment include the time interval since the initial injury, the person’s activity level, and the desired goals for returning to competition.16 Both operative and conservative interventions are considered for treating ACL injuries. Operative treatment is usually performed in athletes, while conservative treatment is likely to have a sufficient outcome for the general population. Clinicians must determine which patients can attempt a return to strenuous activities without surgical intervention. Early surgical stabilization is recommended in active patients presenting with instability.4 If surgical stabilization is deferred, inform the patient that risk of knee damage increases due to unpredictable functional ability after injury. Compared with conservative treatment, surgical reconstruction provides greater knee stability during daily as well as strenuous activities. The goal of ACL reconstructive surgery is to allow the athlete to return to competition in a timely manner without incurring further damage. After ACL reconstruction, postoperative rehabilitation is critical for a successful outcome.11 The setting and frequency of physical therapy affects the rehabilitative process. Techniques that contribute to successful postoperative outcomes include weight-bearing activities, continuous passive-motion exercises, and adjunctive modalities.19 Braces should be worn during postoperative recovery and when an athlete returns to competition.11 Functional knee braces provide mechanical and proprioceptive improvements. By improving extension, decreasing pain and graft strain,



Muscle activation is necessary for adequate protection of the ACL. Without it, mobility and stabilization of the knee joint would be impossible. and providing protection from excessive forces, these devices enhance the outcome of ACL reconstruction. Functional knee braces reduce strain on the reconstructed ligament and boost aspects of neuromuscular control.20 For patients wishing to defer surgical reconstruction of the ACL, conservative nonoperative treatments include short periods of immobilization, bracing, progressive rehabilitation programs, and regular follow-up evaluations. Prevention and education

Muscle activation is necessary for adequate protection of the ACL. Without it, mobility and stabilization of the knee joint would be impossible. The quadriceps, hamstrings, and gastrocnemius muscles are important knee stabilizers. Careful activation patterns of muscles should be determined to increase stabilization in uninjured individuals as well as in ACL-deficient subjects.21 Maintaining dynamic stability around the knee through neuromuscular control while reducing magnitude and rate of impact forces generated during landings will help in the prevention of knee injury. Proper deceleration techniques should be addressed to prevent injury to the ACL.22 Athletes should become adept at such skills as landing softly on the ball of the foot and then rolling back to the heel. To decrease stress on the ACL, athletes should be advised to engage in knee and hip flexion while landing or during lateral maneuvers. Training to increase hamstring, gluteus medius, and hip abductor strength will promote stability and lower the risk of injury.23 Using neuromuscular control to provide functional knee joint stability is an important rehabilitative measure after ACL reconstruction.23 An ACL rupture decreases proprioception, which often remains even after reconstructive surgery. Proprioception is the sensory mechanism of the body that

provides necessary information to mediate neuromuscular control and enhance functional joint stability.6 The sources of proprioception are mechanoreceptors found in muscular, articular, and cutaneous tissues. They translate mechanical events into neural signals the body understands to create balance and stability.6 Neuromuscular training is used to reduce such biomechanical risk factors as decreased proprioception and prevent knee injuries, specifically ACL injuries in athletes. The training programs focused on neuromuscular control of the lower extremities help modify landing mechanics and subsequently decrease the prevalence of noncontact ACL injuries.8 The introduction of balance, strength, and core stability training exercises induces neuromuscular changes and potential injury prevention effects in athletes.24 ■ Ms. Daitch is an associate professor in the Physician Assistant Department at Georgia Health Sciences University in Augusta, where Ms. Stembridge is a second-year student. References 1. Carey JL, Dunn WR, Dahm DL, et al. A systematic review of anterior cruciate ligament reconstruction with autograft compared with allograft. J Bone Joint Surg Am. 2009;91:2242-2250. Available at pmc/articles/PMC2730860/. 2. Silvers HJ, Mandelbaum BR. Prevention of anterior cruciate ligament injury in the female athlete. Br J Sports Med. 2007;41 Suppl 1:i52-i59. Available at 3. Maffulli N, Longo UG, Gougoulias N, et al. Long-term health outcomes of youth sports injuries. Br J Sports Med. 2010;44:21-25. 4. Pinczewski L, Roe J, Salmon L. Why autologous hamstring tendon reconstruction should now be considered the gold standard for anterior cruciate ligament reconstruction in athletes. Br J Sports Med. 2009;43:325-327. 5. Li G, Zhang S, Wang X. Biomechanical effect of anterior cruciate ligament rupture on posterior horn of lateral meniscus. Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi. 2010;24:14-16.


6. Griffin LY, Agel J, Albohm MJ, et al. Noncontact anterior cruciate liga-

Noncontact ACL injuries are six to eight times more common in women than in men.

ment injuries: risk factors and prevention strategies. J Am Acad Orthop Surg.

Acute hemarthrosis—an extravasation of blood into a joint or synovial cavity—is a textbook sign of acute ACL injury.

7. Hughes G, Watkins J. A risk-factor model for anterior cruciate ligament

The physical exam consists of inspection, palpation, and assessment of knee-joint function.

8. Irmischer BS, Harris C, Pfeiffer RP, et al. Effects of a knee ligament injury

Clinicians must determine which patients can attempt a return to strenuous activities without surgical intervention.

Res. 2004;18:703-707.

2000;8:141-150. injury. Sports Med. 2006;36:411-428. prevention exercise program on impact forces in women. J Strength Cond 9. Alentorn-Geli E, Myer GD, Silvers HJ, et al. Prevention of non-contact anterior cruciate ligament injuries in soccer players. Part 2: a review of



prevention programs aimed to modify risk factors and to reduce injury rates. Knee Surg Sports Traumatol Arthrosc. 2009;17:859-879. 10. Guillodo Y, Rannou N, Dubrana F, et al. Diagnosis of anterior cruciate ligament rupture in an emergency department. J Trauma. 2008;65:10781082. 11. Linko E, Harilainen A, Malmivaara A, Seitsalo S. Surgical versus conservative interventions for anterior cruciate ligament ruptures in adults. Cochrane Database Syst Rev. 2005;2:CD001356. Available at onlinelibrary. 12. Jackson JL, O’Malley PG, Kroenke K. Evaluation of acute knee pain in primary care. Ann Intern Med. 2003;139:575-588. 13. Dutton M. Orthopaedic Examination, Evaluation, & Intervention. 2nd edition. Pittsburgh, Pa.: McGraw-Hill Medical; 2008:932-933. 14. Swärd P, Kostogiannis I, Roos H. Risk factors for a contralateral anterior cruciate ligament injury. Knee Surg Sports Traumatol Arthrosc. 2010;18:277-291. 15. Solomon DH, Simel DL, Bates DW, et al. The rational clinical examina-

“The governor would like your help with the budget.”

tion. Does this patient have a torn meniscus or ligament of the knee? Value of the physical examination. JAMA. 2001;286:1610-1620. 16. Munshi M, Davidson M, MacDonald PB, et al. The efficacy of magnetic resonance imaging in acute knee injuries. Clin J Sport Med. 2000;10:34-39. 17. Crawford R, Walley G, Bridgman S, Maffulli N. Magnetic resonance imaging versus arthroscopy in the diagnosis of knee pathology, concentrating on meniscal lesions and ACL tears: a systematic review. Br Med Bull. 2007;84:5-23. Available at 18. Biau DJ, Tournoux C, Katsahian S, et al. Bone-patellar tendon-bone autografts versus hamstring autografts for reconstruction of anterior cruciate ligament: meta-analysis. BMJ. 2006;332:995-1001. Available at www. 19. Wright RW, Fetzer GB. Bracing after ACL reconstruction: a systematic review. Clin Orthop Relat Res. 2007;455:162-168. 20. Birmingham TB, Bryant DM, Giffin JR, et al. A randomized controlled sleeve use after anterior cruciate ligament reconstruction. Am J Sports Med. 2008;36:648-655. 21. Anderson AF, Dome DC, Gautam S, et al. Correlation of anthropometric measurements, strength, anterior cruciate ligament size, and intercondylar notch characteristics to sex differences in anterior cruciate ligament tear rates. Am J Sports Med. 2001;29:58-566. 22. Brophy RH, Silvers HJ, Mandelbaum BR. Anterior cruciate ligament injuries: etiology and prevention. Sports Med Arthrosc. 2010;18:2-11. 23. Hewett TE, Myer GD, Ford KR. Reducing knee and anterior cruciate ligament injuries among female athletes: a systematic review of neuromuscular training interventions. J Knee Surg. 2005;18:82-88. 24. Peeler J, Leiter J, MacDonald P. Accuracy and reliability of anterior cruciate ligament clinical examination in a multidisciplinary sports medicine setting. Clin J Sport Med. 2010;20:80-85. All electronic documents accessed August 15, 2011.

“I don’t feel quite as fulfilled when I’ve saved a lawyer.”


© The New Yorker Collection 2011 from All Rights Reserved.

trial comparing the effectiveness of functional knee brace and neoprene


New strategies against comorbidities of obesity Obese adults are at increased risk for such health conditions as diabetes, heart disease, hypertension, sleep apnea, depression, and liver disease.


he worldwide prevalence of obesity has nearly doubled since 1980.1 As obesity rates continue to increase dramatically, the risk for associated comorbidities is skyrocketing as well. Obese adults are at risk for many serious health conditions, including diabetes, coronary heart disease, hypertension, stroke, obstructive sleep apnea (OSA), depression, and liver disease. Lifestyle modification—including dietary adjustment, exercise, and behavioral change—has been proven to help treat obesity and its related diseases. As every clinician knows, however, behavioral changes are difficult to implement and have varying levels of success, depending on a patient’s motivation. What follows is a review of the latest treatment strategies—intended for use in collaboration with lifestyle modification—for the comorbidities of obesity.



Cross-sectional CT of an obese individual shows extensive subcutaneous fat (blue).

Diabesity is a term used to describe obese individuals who have type 2 diabetes. Such conventional diabetes treatments as sulfonylureas, thiazolidinediones (TZDs), and insulin promote weight gain, which can exacerbate further insulin resistance, worsen obesity-related comorbidities, and reduce patient compliance. Bariatric surgery (Figure 1) is currently the most successful treatment for diabesity, resulting in significant weight loss and sustained remission of diabetes in most patients.2,3 Many of the weight-loss effects of bariatric surgery have been shown to be mediated by means of postoperative • THE CLINICAL ADVISOR • SEPTEMBER 2011 33



increases in appetite-inhibitory gut hormones. Research is currently aimed at finding the pharmaceutical equivalent of bariatric surgery—a drug or combination therapy with anorexigenic gut hormones that can mimic the effects of surgery and restore a patient’s metabolism to a healthy, nondiabetic state. Glucagon like peptide (GLP)-1 receptor agonist therapy is a major breakthrough in diabetes treatment. GLP-1 is a gut incretin hormone that stimulates the release of insulin in response to elevated levels of blood glucose, inhibits the release of glucagon following meals, and slows the rate of absorption of foods from the gut into the bloodstream. In the active form, GLP-1 has a short half-life of only one or two minutes, due to rapid destruction by the dipeptidyl peptidase (DPP)-4 enzyme, making it seemingly impractical as a treatment for diabetes. However, the GLP-1 receptor agonists were designed to have a prolonged half-life attributable to reduced degradation by the DPP-4 enzyme. After many years of development, GLP-1 receptor agonists are now well established in the management of type 2 diabetes. In addition to exenatide (Byetta) and liraglutide (Victoza), several new GLP-1 receptor agonists are in development. Lixisenatide, a once-daily preparation currently in phase III clinical trials, has limited experience with only one clinical study to date. This 13-week study showed a 0.7% reduction in hemoglobin A1c with the use of lixisenatide 20 µg daily from a baseline of 7.5% in patients with type 2 diabetes.4 The National Institutes of Health registry (www. lists several ongoing clinical trials studying lixisenatide. Bydureon, an investigational, long-acting form of exenatide, has been shown to have better glycemic effect

FIGURE 1. In one form of bariatric surgery, a gastric band is placed to restrict the amount of food an individual can eat.


POLL POSITION When asked whether a government tax on junk food would reduce obesity, 70% of your peers responded that it would not, according to the results of our online poll.

No 70%

Other Yes 4% 26%

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than conventional exenatide.5 In October 2010, the FDA declined to approve Bydureon, requesting further testing to measure cardiovascular risk in patients taking the drug; the manufacturer plans to resubmit to the FDA in the second half of 2011.6 Bydureon was approved in the European Union in June 2011.7 All of the GLP-1 receptor agonists currently require parenteral administration, which can interfere with patient compliance. Oral versions of GLP-1 are being developed and are currently in phase I clinical trials. Hypertension

Cardiovascular disease (CVD) remains the leading cause of death throughout the world.8 The World Health Organization predicts deaths from CVD and stroke to exceed 20 million within the next decade. Risk factors include hypertension (HTN), diabetes, obesity, and tobacco use. The leading risk factor for mortality, HTN is responsible for nearly 13% of deaths worldwide.9 Percutaneous renal denervation is a new and evolving HTN treatment. The procedure involves insertion of a percutaneous catheter into the common femoral artery and threaded to the renal arteries; six radiofrequency ablation treatments are then delivered distally and proximally from the bifurcation to the ostium. Each ablation involves delivery of eight watts of energy lasting two minutes.10 Patients with resistant essential HTN who have undergone this procedure have shown a reduction in systolic BP of 27 mm Hg at 12 months.10 Decreased arterial pressure after renal denervation is a result of reduced peripheral sympathetic nervous system activity.10 Based on animal research, it is assumed that denervation of the efferent nerves will result in reduced renin release, reduced sodium retention, and increased renal blood flow,



TABLE 1. Measuring the ankle-brachial pressure index (ABPI) 0.91-1.3



Mild peripheral artery disease (PAD)


Moderate PAD


Severe PAD

ABPI=ankle systolic pressure divided by brachial systolic pressure Adapted from Bhasin N, Scott DJ. Ankle Brachial Pressure Index: identifying cardiovascular risk and improving diagnostic accuracy. J R Soc Med Med.. 2007;100:4-5. Available at jrsm.rsmjournals .com/cgi/content/full/100/1/4, accessed August 15, 2011.

producing a normalization of arterial pressure.10 Data also support the idea that afferent sensory nerve denervation will attenuate the kidneys’ effect on centrally mediated sympathetic nervous system activity. Over time, the cause of a person's HTN may change due to altering variables. Therefore, denervation of efferent and afferent renal nerves is expected to produce a long-term treatment effect. New HTN guidelines are expected within the year from the Kidney Disease: Improving Global Outcomes (KDIGO) foundation and The Eighth Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure ( JNC 8). Coronary artery disease and peripheral artery disease

Atherosclerosis (Figure 2) presenting as coronary artery disease (CAD) and/or peripheral artery disease (PAD) is a significant and costly result of obesity. Medical treatments for this systemic disease remain relatively unchanged. However, there is renewed focus on prevention and early detection as evidenced by the new heart-disease guidelines for women from the American Heart Association.11 Risk factors for PAD include HTN, diabetes, hyperlipidemia, and tobacco use. Because PAD can be asymptomatic, a comprehensive vascular exam is essential. Persons who are at highest risk are aged 70 years or older, smokers (current or past), and/or diabetic. The ankle-brachial pressure index (Table 1) should be measured in the office. This calculates the ratio of the ankle to brachial systolic pressure and is determined using a sphygmomanometer and a handheld Doppler


device. If PAD is detected early, treatment goals can center on risk reduction and limiting further disease progression. Improving morbidity and mortality outcomes and walking distance are the two primary objectives of PAD treatment. A supervised exercise treatment (walking program) is essential. This treatment can be costly and is often not reimbursed, but has been proven to provide significant improvements in functional outcomes. Maximal walking ability can be increased by 150%—greater than any pharmacologic approach. Pharmacotherapy options are effective in patients suffering from mild to moderate PAD and intermittent claudication (Figure 2). Antithrombotic therapy (aspirin or clopidogrel [Plavix]) is a simple and low-cost intervention that provides a 23% risk reduction. Two medications are FDA-approved for the treatment of intermittent claudication: Cilostazol (Pletal) has been shown to increase pain-free walking distance by 50%, but may not be used in individuals with heart failure or those with an ejection fraction <40%; the second medication is pentoxifylline (Pentopak, Pentoxil, Trental).12 In addition to antithrombotic therapy, PAD treatment is also aimed at comprehensive risk reduction through smoking cessation and tight lipid and glycemic control. Revascularization by either endovascular or surgical treatment is the fi nal treatment option. Several emerging adjuvant treatments are under investigation, including the use of growth factor, gene therapy, and stem-cell transplantation to promote local tissue growth.13-15 Cell-based cardiac repair offers new hope for the treatment of PAD, CAD, and heart failure. Mixed dyslipidemia

Elevated triglycerides (TG) and low HDL are the hallmark lipid values seen in metabolic syndrome. In these patients, there is often small, dense LDL; a non-HDL (total cholesterol minus HDL) level is a more accurate reflection of the total number of atherogenic particles. The non-HDL goal is defined as 30 points higher than the identified LDL goal. An additional test to understand the total atherogenic burden is an apolipoprotein B (ApoB). The desired ApoB level for a high-risk patient is <80 mg/dL. Lifestyle modification remains the first and best treatment strategy, as the main causes of mixed dyslipidemia are overweight, poor diet, and low level of physical activity. Interventions targeting all

“The problem is that junk food is cheap, even with a tax. If healthier food were more affordable than processed food, there would be less of an obesity epidemic.” — Michelle Croach, CRNP-PMH, Edgewater, Md. (via





FIGURE 2. Stenosis of the femoral artery (red) is usually caused by the deposition of plaques of atheroma and can lead to claudication.

FIGURE 3. Continuous positive airway pressure (CPAP) is the first-line treatment for obstructive sleep apnea for most people.

three factors will result in lower TG levels and a slow but progressive increase in HDL. For persons who present with a significant family history of early CAD or stroke, a lipoprotein (Lp)(a) level will affirm the level of risk; if elevated, family members should be counseled to get screened. In individuals with elevated Lp(a), the goal is to decrease LDL (at least <100 mg/dL and more desirably <70 mg/dL). There is some disagreement as to whether Lp(a) is a risk marker only or a treatment target as well. Individuals with an elevated Lp(a) are at higher risk of embolic events (i.e., stroke or MI), and aspirin therapy is usually indicated in these cases. Niacin therapy will reduce Lp(a) levels, but it is not clearly understood whether treating Lp(a) values will affect outcomes. Niacin may be therapeutic because of its beneficial effects on TG, LDL, and HDL levels. Advanced lipid testing is an evolving science. Researchers are now looking at medications found to increase HDL levels. One such drug class is the cholesterylester transfer protein (CETP) inhibitors. The assumption is that increasing HDL may reduce cardiovascular events. A few years ago, testing of torcetrapib was discontinued due to BP elevations observed in the treatment arm. Dalcetrapib and anacetrapib are two new CETP inhibitors currently in development that have not been found to increase BP readings. However, the question of whether raising HDL levels is beneficial remains unanswered.16 Many dietary supplements can have a beneficial effect on health. Natural alternatives can be safe when monitored and managed by a primary-care provider (PCP). Lovaza (omega-3-acid ethyl esters) is a prescription medication containing 900 mg per capsule of eicosapentaenoic acid and

docosahexaenoic acid, the active ingredients that affect lipids. When considering an OTC option, look for an alternative with the same active-ingredient strength. Red yeast rice (RYR) is another popular supplement used to treat dyslipidemia, especially among the small percentage of patients who cannot tolerate a statin medication due to myalgias. The active ingredient in RYR is monacolin K, an equivalent of lovastatin (Altocor, Altoprev, Mevacor). A full dose of RYR 600 mg b.i.d. is equal to lovastatin <10 mg. RYR contains other monacolins that may further inhibit 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase. The monacolins are thought to be less likely to deplete such mevalonate metabolites as ubiquinone or coenzyme Q10 and guanosine triphosphate binding protein, which are believed to mediate statin-induced muscle injury. When paired with lifestyle changes, RYR has been shown to lower LDL levels up to 27%.17 Patients must be cautious when taking RYR, as hepatotoxicity is a concern; liver function tests (LFTs) should be monitored regularly. Myopathy and rhabdomyolysis, similar to that seen with statins, have been reported in persons using RYR. Several OTC preparations of niacin (vitamin B3) work to reduce LDL and TG levels and increase HDL levels. Immediate, extended-release (Niaspan), and sustained-release preparations are available. The OTC niacin preparations will cause a flushing response similar to that seen with Niaspan. This flushing can be thought of as an expected therapeutic response. Regular LFT monitoring is recommended with the use of these medications. A number of OTC therapies claim to improve lipid levels, but plant stanols and sterols have been shown to lower


LDL levels up to 15% with recommended dosing.18 Several types of preparations are available, including pills, yogurts, and spreads. Obstructive sleep apnea


OSA is a common disorder that affects 25% to 35% of obese individuals.19 It is characterized by recurring episodes of limited airflow during sleep as a result of upper airway collapse. This alteration in airflow often results in oxygen desaturation, causing poor sleep, excessive daytime somnolence, and a host of metabolic, inflammatory, neuropsychiatric, respiratory, and cardiovascular disorders. OSA is often under-recognized and under-diagnosed. At the time of diagnosis, the average OSA patient has been symptomatic for approximately seven years and has visited his or her PCP approximately 17 times.20 Inconvenient testing is one explanation for the high number of undiagnosed cases of OSA. The polysomnography single-night test traditionally has been considered the only diagnostic test for OSA. However, this test can be difficult for some patients to undergo due to limited accessibility to a sleep lab, cost, and the patient’s inability to fall asleep in the lab setting. Multi-night home sleep testing (HST) was created as a more convenient, inexpensive, and efficient means of detecting OSA. Until 2008, however, HST was considered unproven, and most third-party payers would not cover treatment with continuous positive airway pressure (CPAP) (Figure 3) when OSA was diagnosed by means of a HST device. In March 2008, the Centers for Medicare and Medicaid Services issued a National Coverage Determination policy stating that the evidence supported use of HST to

CLINICAL SLIDESHOW To help identify peripheral artery disease in your patients, view the slideshow at

establish the diagnosis of OSA in some patients and would cover CPAP treatment based on that diagnosis. With home testing now being an option, scores of patients who may have otherwise gone undiagnosed will be able to seek treatment for OSA. Depression

Depression and weight gain often go hand in hand. Antidepressants commonly cause weight gain during acute and long-term use. Individuals who struggle with obesity are often characterized by negative body image, depressed mood, and unrealistic weight-loss goals. Cognitive behavioral therapy (CBT) remains a mainstay for depression treatment and works to challenge and change these unhealthy beliefs. However, many patients with clinical depression seek other nonpharmacologic interventions for reasons of cost, accessibility, and convenience. There has been increased interest in exercise, yoga, and meditation in the treatment of mild to moderate depression. An extensive literature review reveals that exercise produces meaningful reductions in depression symptoms comparable to those achieved through CBT.21,22 High-energy aerobic exercise (i.e., weekly expenditure of >17.5 kcal/kg) or resistance training has been shown to reduce depression symptoms more efficiently than low-energy exercise (i.e., weekly expenditure of <7 kcal/kg).23 Yoga is also recommended as a therapeutic option for depression treatment. Mindful meditation, which often incorporates hatha yoga, has been shown to reduce stress, depression, and fatigue. Mindful meditation can also be combined with CBT to treat depression.24 Nonalcoholic steatohepatitis

FIGURE 4. Biopsy shows fatty infiltration, ballooning degeneration of hepatocytes, and pericellular fibrosis in a patient with NASH.

The most common liver disease in the Western world, nonalcoholic steatohepatitis (NASH) (Figure 4) is closely associated with components of the metabolic syndrome, such as obesity, hypertriglyceridemia, and insulin resistance. The combination of advancing age, increased weight, and type • THE CLINICAL ADVISOR • SEPTEMBER 2011 45


Pioglitazone was associated with highly significant reductions in steatosis and inflammation as well as improvements in insulin resistance. 2 diabetes leads to an increased risk of developing NASH and advanced fibrosis.25 The primary goal of treatment is to slow the progression of fibrosis and prevent cirrhosis, which occurs in 15% of NASH patients.26 The accepted standard of NASH treatment is gradual weight loss of 10% of body weight plus aerobic exercise. Many studies have shown the impact that dietary changes have on obesity and improving insulin sensitivity, two major risk factors for NASH. In addition to lifestyle and diet modifications, pharmacologic treatment modalities are now available for select patients. TZDs improve insulin resistance and promote the redistribution of fat from the liver and muscle to adipose tissue. Multiple randomized controlled trials have examined the effectiveness of these agents in NASH. The recently published PIVENS (Pioglitazone or Vitamin E for NASH Study)—the largest randomized, placebo-controlled clinical trial of therapies ever conducted for NASH—found that pioglitazone (Actos) use was associated with highly significant reductions in steatosis and inflammation as well as improvements in insulin resistance.27 TZDs are associated with weight gain, however, which may weaken their long-term usefulness. Currently, there are no American Gastroenterological Association recommendations for pharmacologic treatment of NASH. However, many clinicians use TZDs (specifically pioglitazone) as second-line treatment, with the possible exception of some patients with diabetes and NASH.25 Vitamin E is a fat-soluble vitamin with powerful antioxidant properties. PIVENS has shown that 800 IU/day of a specific form of vitamin E (α-tocopherol) is associated with significant improvement in NASH compared with placebo.27 Liver enzymes tend to worsen after vitamin E discontinuation, indicating a need for long-term use.25 It is important to note that the benefits of vitamin E have not been supported in patients with diabetes or cirrhosis, nor has the FDA approved vitamin E for the treatment of NASH. Nevertheless, many clinicians recommend its use and start patients with active NASH and without diabetes on vitamin E (α-tocopherol) 800 IU/day.25


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Obesity and its many comorbidities continue to increase. Although research will lead to novel management approaches, the mainstay of obesity treatment and prevention is lifestyle change. The multicenter Diabetes Prevention Program study as well as the more recent Look Ahead trial exemplify the impact that lifestyle modifications have on weight and metabolic risk factors. It is imperative that PCPs encourage, motivate, and educate their patients as to the importance of lifestyle change to help combat the obesity epidemic. ■ Ms. Cleary is a nurse practitioner with the Lipid Disorders and Metabolic Syndrome Clinic at the Northwestern Medical Faculty Foundation's Center for Lifestyle Medicine in Chicago where Ms. Webb is a family nurse practitioner and diabetes educator. References 1. Finucane MM, Stevens GA, Cowan MJ, et al. National, regional, and global trends in body-mass index since 1980: systematic analysis of health examination surveys and epidemiological studies with 960 country-years and 9.1 million participants. Lancet. 2011;377:557-567. 2. Sjöström L, Narbro K, Sjöström CD, et al. Effects of bariatric surgery on mortality in Swedish obese subjects. N Engl J Med. 2007;357:741-752. Available at 3. Buchwald H, Estok R, Fahrbach K, et al. Weight and type 2 diabetes after bariatric surgery: systematic review and meta-analysis. Am J Med. 2009;122:248-256. 4. Ratner RE, Rosenstock J, Boka G; DRI6012 Study Investigators. Dosedependent effects of the once-daily GLP-1 receptor agonist lixisenatide in patients with Type 2 diabetes inadequately controlled with metformin: a randomized, double-blind, placebo-controlled trial. Diabet Med. 2010;27:10241032. Available at 5. Buse JB, Drucker DJ, Taylor KL, et al. DURATION-1: exenatide once weekly produces sustained glycemic control and weight loss over 52 weeks. Diabetes Care. 2010;33:1255-1261. Available at 6. FDAnews Drug Daily Bulletin. Amylin eyes Bydureon resubmission in second half of year. Available at ?issueId=14435&articleId=133951.

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7. PRNewswire. Bydureon receives marketing authorization in Europe.

17. Becker DJ, Gordon RY, Halbert SC, et al. Red yeast rice for dyslipi-

Available at

demia in statin-intolerant patients: a randomized trial. Ann Intern Med.



8. World Health Organization. The top 10 causes of death. Available at

18. Jones PJH, Kubow S. Lipids, sterols, and their metabolites. In: Shils

ME, Shike M, Ross AC, et al, eds. Modern Nutrition in Health and Disease.

9. World Health Orginization. Global health risks: mortality and burden

Philadelphia, Pa.: Lippincott Williams & Wilkins:92-122.

of disease attributable to selected major risks. Available at

19. Ahmed MH, Byrne CD. Obstructive sleep apnea syndrome and fatty


liver: association or causal link? World J Gastroenterol. 2010;16:4243-4252.

10. Katholi RE, Rocha-Singh KJ, Goswami NJ, Sobotka PA. Renal nerves

Avaialble at

in the maintenance of hypertension: a potential therapeutic target. Curr

20. Rahaghi F, Basner RC. Delayed diagnosis of obstructive sleep apnea:

Hypertens Rep. 2010;12:196-204.

don’t ask, don’t tell. Sleep Breath. 1999;3:119-124.

11. Mosca L, Benjamin EJ, Berra K, et al. Effectiveness-based guidelines for

21. Mead GE, Morley W, Campbell P, et al. Exercise for depression.

the prevention of cardiovascular disease in women—2011 update: a guide-

Cochrane Database Syst Rev. 2009;3:CD004366.

line from the American Heart Association. Circulation. 2011;123:1243-1262.

22. Daley A. Exercise and depression: a review of reviews. J Clin Psychol

Available at

Med Settings. 2008;15:140-147.

12. Olin JW, Sealove BA. Peripheral artery disease: current insight

23. Legrand F, Heuze JP. Antidepressant effects associated with different

into the disease and its diagnosis and management. Mayo Clin Proc.

exercise conditions in participants with depression: a pilot study. J Sport

2010;85:678-692. Available at

Exerc Psychol. 2007;29:348-364.


24. Michalak J, Heidenreich T, Meibert P, Schulte D. Mindfulness predicts

13. Korf-Klingebiel M, Kempf T, Schlüter KD, et al. Conditional trans-

relapse/recurrence in major depressive disorder after mindfulness-based

genic expression of fibroblast growth factor 9 in the adult mouse heart

cognitive therapy. J Nerv Ment Dis. 2008;196:630-633.

reduces heart failure mortality after myocardial infarction. Circulation.

25. Satapathy SK, Sanyal AJ. Novel treatment modalities for nonalcoholic


steatohepatitis. Trends Endocrinol Metab. 2010;21:668-675.

14. Krishna KA, Krishna KS, Berrocal R, et al. Myocardial infarction and

26. Ekstedt M, Franzén LE, Mathiesen UL, et al. Long-term follow-

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up of patients with NAFLD and elevated liver enzymes. Hepatology.


15. Henning RJ. Stem cells in cardiac repair. Future Cardiol. 2011;7:99-117.

27. Sanyal AJ, Chalasani N, Kowdley KV, et al. Pioglitazone, vitamin E, or

16. Kappelle PJ, van Tol A, Wolffenbuttel BH, Dullaart RP. Cholesteryl

placebo for nonalcoholic steatohepatitis. N Engl J Med. 2010;362:1675-

ester transfer protein inhibition in cardiovascular risk management:

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online ahead of print).

“O.K., but don’t call me again until you have something more specific than ‘Life isn't fair.’” 48 THE CLINICAL ADVISOR • SEPTEMBER 2011 •


■ LEARNING OBJECTIVES : • Understand the incidence of chronic disease and interplay of health issues among individuals aged 65 years and older. • Learn how such tools as the Mini-Cognitive Assessment Instrument screen for dementia. • Identify screening tests used to detect early indicators of Parkinson disease. • Know what drug class can lead to incontinence in patients with no previous episodes. ■ COMPLETE THE POSTTEST: Page 103 ■ ADDITIONAL CME/CE: Pages 85, 99


Screening for functional deficits in older adults Assessment of functional impairments in an aging population is one of the most daunting challenges facing primary-care clinicians.


Presbycusis— age-related high-frequency hearing loss—is common among older patients.


n aging population brings new opportunities and challenges for primary-care providers (PCPs). Increasing numbers of older adults are presenting for office visits, almost twice as often as younger adults. This creates need and emphasizes the important role of the PCP in older-adult office visits.1 The growing number of older adults relates in part to aging baby boomers and more elders living to advanced years; this includes the oldest old and sometimes the frail elder. Since older adults are a unique population, honing elder assessment skills for efficient screening and effective care is vital. Focusing on function should be central to all evaluations of older adults and is considered a minimum competency in the care of these individuals.2,3 Since older adults often present with long histories and multiple chronic medical problems, a functional approach to assessment provides an effective and efficient method of determining individual needs.2 Functional screenings remind providers to keep the big picture in mind when assessing and diagnosing. • THE CLINICAL ADVISOR • SEPTEMBER 2011 55



Completing at least simple screens of common problem areas helps avoid missing important factors that may sabotage treatment plans. This article provides an overview of the interplay of multiple factors associated with the aging process, key screening points in functional assessment as a basis for screening older adults to determine their health-care needs, and further resources to enhance care for elders. Functional assessment screening has particular relevance for those older adults with advanced age and multiple comorbidities. Purposes of functional screening

Think of functional status as a snapshot of how patients are currently negotiating everyday life. Changes in patient function may be the first indicator of a decline in physical or mental health.2 Considering how common a complex presentation is in the older adult, starting with a functional screen serves multiple purposes. It can be an efficient starting point when dealing with an array of nonspecific symptoms, exploring possible etiologies, and separating normal aging changes from symptoms. Identifying the big picture of function allows PCPs to work backward in identifying causative factors for the functional deficits, eventually leading to the capture of conventional diagnoses. Starting with functional screening provides the opportunity to gain further confirmatory data specific to patient concerns. Standardized approaches to completing and recording functional status provide the added benefit of easy comparisons over time.

complicated by the coexistence of physical changes associated with aging and symptoms from chronic disease.1 Nonspecific response to illness or masked symptoms. Unfortunately, frail elders do not always present with obvious symptoms that can be easily linked to a specific diagnosis. Such atypical responses as acute confusion or falls can indicate further systemic problems. Syndromes. Elders often present with syndromes or functional deficits that differ from traditional medical diagnoses. Syndromes—defined as a common collection of symptoms (e.g., incontinence or dementia)—are frequently identified in elders.4 There are benefits to the advice, “Think syndromes,” as typical diagnoses do not always match presenting symptoms. Acute problems on top of chronic illness. Acute problems on top of chronic illness also need to be considered. For example, acute physical illnesses can exist concomitantly with dementia. Recognizing and treating such acute problems as urinary tract infections (UTIs) is critical because of the potential physical and functional consequences of these conditions. Medication regimens. Medications can benefit or confound treatment of elders. Extensive lists of medications— sometimes from multiple providers and pharmacies—present a plethora of challenges. OTC medications are frequently incorporated into this mix. Polypharmacy often leads to otherwise preventable problems for elders.

The importance of functional screening

The elderly population is a heterogeneous group. In addition to having diverse cultural backgrounds, older adults differ greatly from one another in terms of functional abilities. Problems faced by this patient population are often multifactorial. Health issues or syndromes may emerge from a number of concurrent problems in the frail older adult patient. The following points summarize some complexities of assessing the older adult. Physical aging. Multiple physiologic changes accompany the aging process, affecting each body system to some degree. These changes affect different individuals at different rates and are influenced by current and previous lifestyles.4 The ability to distinguish normal aging changes from disease states is a key competency.3 Comorbidities and chronic disease. An estimated 80% of individuals aged 65 years and older have at least one chronic disease, and as many as 50% have two or more. Assessment is

Primary-care office visits and functional screening

Functional screening components can be completed separately or integrated into a more traditional systems review. Complementary to the more typical disease-focused history and physical, the functional screen promotes mindfulness of potential common problems in individuals of advanced age. Completing at least simple screens of frequently seen problem areas helps the clinician identify important factors that can affect treatment plans. Approaches to the primary-care screening can be organized into three areas: (1) initiating the visit; (2) key functional screening areas; and (3) visit closure. Initiating the visit

Ask the patient to bring in his or her medical passport/ health summary and medications. Since longevity means more information to share, coaching patients to bring even a simple passport with approximate dates of acute illnesses


or surgeries and ongoing chronic problems can make the visit more efficient. Additionally, asking patients to keep and share symptom journals can improve time management and quality of care. Bags of clearly labeled medication containers allows the PCP to compare the patient’s understanding with the written expectations. For complex patient presentations, the PCP may find it useful to develop a worksheet that summarizes functional issues along with traditional diagnoses and ongoing treatments. Organizing major points may help synthesize and identify health-related patterns. Concerns can emerge that are not otherwise evident and can help name the patient problem or identify areas requiring further workup.

Key functional screening areas

A systematic functional screen helps sort out the often complex presentations as well as differentiate normal aging changes from physical diagnoses. Key components to address in this systematic screen include: sensory status, cognitive and behavioral disorders, mobility and function, eating and nutrition, incontinence/elimination issues, and social support/environmental resources. Table 1 lists commonly recommend screenings from the literature. Successful responses to the task or question indicate a negative screen. Positive findings call for more detailed workup. Sensory status. A majority of older adults have visual and hearing impairments that can often be improved with

TABLE 1. 1. Recommended functional screening areas

Sensory status

Cognitive and behavioral disorders

Mobility and function

Sample approaches

Follow-up resources for positive screening responses*

• Ask the patient to read large print or a Snellen chart with corrective lenses in place.

• National Institutes of Health. Low vision vision.. Available at

• Ask the patient to respond to a whispered-voice test (or use audiometry).

• National Institute on Deafness and Other Communication Disorders. Hearing loss and older adults. adults. Available at

• Depression: Ask if feeling sad, blue, or hopeless has bothered the patient in the past month. Follow-up to a positive response is done using a standardized screen, such as the Geriatric Depression Scale.

• National Institute of Mental Health. Older Adults: Depression and Suicide Facts. Facts. Available at /publications/older-adults-depression-and-suicide-facts-factsheet/index.shtml.

• Dementia: Ask the patients to repeat three unrelated words provided by the examiner and then to recall the words after three minutes. Forgetting the words indicates the need for follow-up with a standardized tool, such as the Mini-Cognitive Assessment Instrument or the Mini-Mental State Examination.

• Alzheimer’s Association. Diagnostic procedures. procedures. Available at _procedures.asp.

• Administer the Timed Up and Go Test.

• Iowa Geriatric Education Center. Geriatric assessment tools. Available at

• Ask if the patient has had any falls in the past year.

Eating and nutrition

• Follow up using standard screens as indicated.

• The American Geriatrics Society. Prevention of Falls in Older Persons.. Available at Persons

• Ask if the patient has lost weight in the past three months without trying.

• MedlinePlus. Nutrition for seniors. seniors. Available at medlineplus/nutritionforseniors.html.

• Ask the patient to describe a normal meal. • Complete an oral-cavity examination. Incontinence/elimination issues

Social support/ environmental resources

• Ask if the patient has lost his or her urine and gotten wet in the past year.

• National Association for Continence. NAFC library. Available at

• Ask follow-up questions as indicated.

• National Institute on Aging. Concerned about constipation? Available at constipation.htm.

• Ask the patient who would provide help in case of illness or an emergency.

• Administration on Aging. Elders and families. families. Available at

• Ask if the patient has trouble with stairs, lighting, bathroom, or other home hazards.

• American Association of Retired Persons. Caregiving resource center. Available at

*All electronic documents accessed August 15, 2011. • THE CLINICAL ADVISOR • SEPTEMBER 2011 57



“The three Ds”—depression, dementia, and delirium—can be common in the oldest-old population and a challenge to differentiate. corrective devices.2 Given the vital roles of vision and hearing in communication and social activity, the importance of screening for opportunities to improve these senses cannot be overstated. Presbyopia (age-related diminished vision) and presbycusis (age-related gradual high-frequency hearing loss) are common physical changes. Elders can be screened quickly for these problems. For example, check visual acuity by asking the patient to read large print or complete a Snellen chart screen with corrective lenses in place. Either audiometry or the whispered-voice test (in which the examiner, out of the patient’s view, asks the patient to repeat a whispered phrase) serves as a simple screen of functional hearing.2 Check for hearing deficits related to cerumen impaction. Any vision or hearing deficits indicate the need for patient follow-up to determine opportunities for corrective devices that can promote safe and meaningful interaction. Cognitive and behavioral disorders. Sometimes referred to as “the three Ds,” depression, dementia, and delirium can be common in the oldest-old population and a challenge to differentiate. Any of these deficits impact overall function. Depression has been called the common cold of late life. Late-onset disorders may relate to late-life stressors. Multiple TABLE 2. 2. Mini-Cognitive Assessment Instrument (Mini-Cog) Step 1: Ask the patient to repeat three unrelated words Step 2: Ask the patient to draw a simple clock set to 11:10 Step 3: Ask the patient to recall the three words from Step 1. Number of words recalled from Step 1

Result of clockdrawing test

Interpretation of screen for dementia

























Adapted from Borson S, Scanlan J, Brush M, et al. The Mini-Cog: a cognitive “vital signs” measure for dementia screening in multi-lingual elderly. Int J Geriatr Psychiatry. Psychiatry. 2000;15:1021-1027.

physical and emotional losses in aging are painful and can compound the potential for depression. Screening for depression is important since symptoms can be more nonspecific in elders. A basic screening question asks, “Have you been bothered by feeling sad or hopeless in the past month?” Follow-up to a positive response should include a standardized test, such as the Geriatric Depression Scale.5 Weight loss can indicate a need for further depression screening. Elderly white men have the highest rate of completed suicide, making screening for and follow-up treatment of depression in older adults imperative.6 Include questions about alcohol intake or substance abuse; these are common sources of relief from emotional pain.7 Dementia typically has a slow, insidious progression of symptoms. An estimated 50% of persons aged 85 years and older will be affected by or develop Alzheimer disease (AD).8 A simple screen includes asking an older patient to repeat three unrelated words provided by the examiner and then to recall these words three minutes later. Forgetting the words indicates the need for follow-up with the either the Mini-Cognitive Assessment Instrument (Mini-Cog) (Table 2) or the Mini-Mental State Examination to gain more detailed information.7 Delirium—an acute but treatable syndrome—must be differentiated from dementia, which has a slow and chronic progression. A history of rapid functional change or change in patient behavior (e.g., increased lethargy, confusion, or agitation) is often the first sign of an acute problem. Such infections as UTI or pneumonia are common causes of delirium. Fluid and electrolyte imbalances, constipation/ impaction, and adverse drug reactions are other common differentials. Approaches to evaluating rapid functional change should focus on identifying acute causative factors. Mobility and function. Overall mobility and function are critical factors affecting elders’ capacity for self-care and ability to stay safely and independently in their homes. Such standardized scales addressing activities of daily living (ADLs) and instrumental activities of daily living (IADLs) as the Katz ADL and the Lawton IADL are recommended for those having difficulties.2 ADLs are self-care activities that a person performs daily, whereas IADLs relate to more detailed activities of daily home management. While function includes interaction of such factors as cognition and motivation, simple upper- and lower-body screens provide useful indicators to assess need for further screening.


Asking patients to remove shoes and socks provides an opportunity to identify functional deficits and is a useful screen for foot problems. To identify basic functional range of motion in the upper body, ask the patient to move his or her arms in three positions: (1) arms stretched up toward the ceiling; (2) hands lowered to touch the back of the neck; and (3) hands brought together to touch the lower back. Picking up such small objects as a paper clip or penny provides a further screen of manual dexterity. For assessment of the lower body, the individual’s gait provides an initial indicator of function. Early indicators of such diagnoses as Parkinson disease may be detected. Specifically, the Timed Up and Go (TUG) Test is recommended. The TUG screens strength, coordination, and walking ability. In this test, the patient is asked to rise from an armless chair, walk three meters, return, and sit down while the provider observes.4 Inability to complete in 14 seconds is considered a positive finding. Falls or the fear of falling are often major factors in older adults’ loss of independence. Falls can be symptomatic of specific disorders or attributed to a combination of factors. After hearing a positive response to the question, “Have you had any falls in the past year?” the clinician should obtain from the patient a detailed fall history, including frequency and circumstances. Reports of repeated falls indicate the need to determine contributing intrinsic or extrinsic factors.2 Asking patients to remove shoes and socks provides an additional opportunity to identify functional deficits and is a useful screen for foot problems. Such problems as improper footwear or foot disorders can lead to functional deficits. Eating and nutrition. Dental problems, which PCPs often miss, are common and can lead to infections and systemic disorders. Some medications can lead to decreased saliva and altered taste. Meal management and self-care eating abilities may be overlooked. Nutritional screening and follow-up assessments can address the following possible issues: • weight changes • adverse effects of medication on appetite • eating-related self-care deficits • oral health deficits (e.g., dental problems or dry mouth) • chewing or swallowing disorders • eating problems of those with such specific diagnoses as Alzheimer disease. Questions more detailed than, “Are you eating?” are required to determine diet patterns. For example, asking, “What is a normal breakfast or dinner for you?” elicits a more

detailed response. Changes in weight patterns are another important indicator. Although the discussion relevant to frail elders is often limited to weight loss and problems of underweight, obesity remains a major concern with many health-care implications and should not be overlooked. Incontinence/elimination issues. Elimination concerns can be embarrassing and uncomfortable for elders. Urinary incontinence in particular can lead to social isolation or even physical injury caused by falls from hurrying to the bathroom and slipping. Incontinence relates to function in that it is a factor in activity choices and can even affect living arrangements. The question, “Have you lost your urine and gotten wet in the past year?” can be followed up with more detailed questions regarding frequency and severity.4 Determining such iatrogenic factors as lack of ability to manage clothing or access toilet facilities is particularly relevant in a functional screen.2 A new medication may lead to incontinence in individuals with no previous episodes. Diuretics can lead to urgency and frequency; narcotics and sedative-hypnotics can lead to sedation and decreased mobility; and drugs with anticholinergic effects can lead to retention and overflow incontinence. The embarrassment, health risks, and decreased quality of life for patients make urinary incontinence an important issue to address.2 Constipation and impaction from such common causes as limited fluid intake, decreased activity, and medication side effects are also important elimination concerns to discuss, as they can lead to discomfort and decreased appetite as well as acute symptoms.4 Clarify what constipation means to the patient, and determine an appropriate follow-up plan. Social support/environmental resources. Support from people and environmental resources becomes increasingly important with the illnesses and frailties common in advanced age. There is often a loss of these resources for the oldest old, as friends and family precede in death. Particularly for those declining in function, it is important to determine whether the individual has consistent support and a safe environment. A basic screening question asks, “Who would help you if you got sick or had an emergency?” Consideration of the patient’s usual living arrangements or environmental setting is part of a functional screen. While the benefits of environmental observation may be limited in primary care, ask, “Do you have trouble with stairs, lighting, bathroom, or other home hazards?” Often such simple environmental adaptations as revised room arrangements • THE CLINICAL ADVISOR • SEPTEMBER 2011 59



or grab bars can make a difference in functional abilities. If screening suggests problems, further evaluation can include referral to an appropriate specialist. Visit closure

Because of the unique qualities of older adults, this patient population requires individualized treatment plans. The best plans find a balance among the older adult’s functional abilities, needs, and resources. The optimal care plan also may vary by environmental setting.2 There are some simple tips to consider as the visit concludes. Prioritize and treat what is easily treatable. Some conditions commonly occur (e.g, UTIs). After determining care priorities, consider best treatments in light of other comorbidities and functional deficits. Gain best evidence from research, expert clinician practice, and patient preference. Focus in particular on steps that promote functional ability and quality of life. Consider physical aging changes when prescribing medications. Whenever possible, avoid prescribing highrisk drugs to elders. Provide older patients with clear written guides for taking medications, and alert them to potential side effects. Keep the treatment plan simple. The treatment plan should fit the patient’s abilities. Written follow-up care guides and patient reminders should contain simple bulleted information in large-font print. Refer those who need to be referred. A team approach that includes physical, occupational, and speech therapists can enhance a function-oriented plan. The problem-oriented plan should be available to all providers.9 Guide families to needed support resources. Provide contact information for such groups as the local Area Agencies on Aging ( and the American Association of Retired Persons ( Such specialty organizations as the Alzheimer’s Association ( or the Parkinson’s Disease Foundation ( provide educational resources and support groups that many patients and family members find beneficial. Target the most complex cases. Once the patients that require the most involvement have been identified, determine what type of further monitoring (if any) is needed. Consider the benefits of a case manager, and include family caregivers in developing strategies for the coordination of support services. Health promotion and disease prevention is important for people of all ages. Basic principles of improved nutrition and adequate exercise—related to functional level—apply.

Health promotion diagnostic screening guides differ for those of advanced age with limited predicted longevity. Age-appropriate screening, counseling, and preventiveservices guidelines can be accessed through the Agency for Healthcare Research and Quality ( Summary

Screening for functional deficits provides the PCP with a good starting point in caring for older adults with long health histories and comorbidities. Functional screening allows for further systematic assessment and helps clarify patient strengths. Consider functional screens the first step in establishing a realistic and patient-focused care plan. By promoting optimal functional abilities, PCPs can help elders maintain independence with a focus on safety and quality of life. ■ Dr. Bonnel is an associate professor at the University of Kansas School of Nursing, Kansas City. The author has no relationships to disclose regarding the content of this article. References 1. Administration on Aging. Profile of older Americans: 2010. Available at 2. Kane RL. Ouslander JG, Abrass IB, Resnick, B. Essentials of Clinical Geriatrics, 6th ed. New York, N.Y.: McGraw-Hill Professional; 2009. 3. Leipzig RM, Granville L, Simpson D, et al. Keeping granny safe on July 1: a consensus on minimum geriatrics competencies for graduating medical students. Acad Med. 2009;84:604-10. 4. Ham RJ, Sloane PD, Warshaw GA. Primary Care Geriatrics: A Case-Based Approach. St. Louis, Mo.: Mosby; 2006. 5. Yesavage JA, Brink TL, Rose TL, et al. Development and validation of a geriatric depression screening scale: a preliminary report. J Psychiatr Res. 1982-1983;17:37-49. 6. National Institute of Mental Health. Older adults: Depression and suicide facts. Available at 7. Reuben DB. Geriatrics at Your Fingertips, 13th ed. Belle Meade,N.J.: American Geriatrics Society; 2011:60-65. 8. Alzheimer’s Association. Diagnostic procedures. Available at www.alz .org/professionals_and_researchers_diagnostic_procedures.asp. 9. Elsawy B, Higgins KE. The geriatric assessment. Am Fam Physician. 2011;83:48-56. 10. Agency for Healthcare Research and Quality. Electronic preventive services selector helps clinicians deliver prevention at the point of care. Available at All electronic documents accessed August 15, 2011.


Advisor Forum These are letters from practitioners around the country who want to share their clinical problems and successes, observations, and pearls with their colleagues. Responding consultants are identified below. We invite you to participate.

Inside the Forum SEPTEMBER 2011

Consultations Confirming suspicions of hepatic encephalopathy . . . . . . . . . .69 Diagnosing scalp conditions . . . . . . . .69 Can a gluten-free diet tame inflammation? . . . . . . . . . . . . .69 Comparing methods of calculating ejection fraction. . . . . . . . . . . . . . . .70 Discoid lupus erthyematosus laboratory follow-up . . . . . . . . . . . .70 And more . . . . . . . . . . . . . . . . . . 70-72

Clinical Pearls An alternative to a food diary . . . . . . .72 Beyond “Just say no” . . . . . . . . . . . . .75 Put your lips together and blow . . . . .75 And more . . . . . . . . . . . . . . . . . . . . .75

Your Comments Renal-protective properties of ACE inhibitors and ARBs . . . . . . . .75 When to consider dialysis . . . . . . . . . .76 Plenty of blame to go around . . . . . . .76

Send us your letters with questions and comments to: Advisor Forum, The Clinical Advisor, 114 West 26th Street, 4th Floor, New York, NY 10001. You may also fax (646) 638-6117, or contact us by e-mail at letters@ If you are writing in response to a published letter, please indicate so by including the number in parentheses at the end of each item. Letters are edited for length and clarity. The Clinical Advisor’s policy is to print the author’s name with the letter. No anonymous contributions will be accepted.

CONSULTATIONS EFFICACY OF CEPHALEXIN AFTER RAISING DOSAGE Is there any evidence that changing a patient’s cephalexin dose from 500 q.i.d. to 1,000 b.i.d. has decreased efficacy in terms of infection (i.e., cellulitis) control?—JEN FLANNERY, PA-C, Seattle The recommended dose of cephalexin for uncomplicated skin and soft-tissue infection is 250 mg every six hours or 500 mg every 12 hours. Efficacy is not affected by changing dosage schedule. In severe infection the dosage can be doubled.—Claire Babcock O’Connell, MPH, PA-C (155-1)

AVOIDING REFLUX WHEN STOPPING PPIS Some of my geriatric patients are frail and others robust. Most have been on acid blockers for years. Can they be weaned off these medications without causing a reflux flare?—PAULA J. SUMNER, MSN, CS, FNP-BC, Pittsboro, N.C. Proton pump inhibitors (PPIs) and histamine (H2) blockers were only ever tested—and indicated—for short-term use. Unfortunately, both cause a common adverse effect of rebound hypersecretion of acid, leading to increased acid reflux symptoms as patients try to discontinue use. A study recently performed in the Netherlands put patients who


Bruce D. Askey, MSN, CRNP, is

Rebecca H. Bryan, APRN, CNP, is a

Eileen Campbell, MSN, CRNP,

Philip R. Cohen, MD, is clinical

Peter F. Cohn, MD, is chief of

a clinician in the Department of Hepatology/ Gastroenterology at the Guthrie Clinic in Sayre, Pa.

lecturer in the Family Health NP Program, University of Pennsylvania School of Nursing, Philadelphia.

is associate program director, Family Health NP Program, University of Pennsylvania School of Nursing, Philadelphia

associate professor of dermatology, University of Texas Medical Center, Houston.

cardiology and professor of medicine at State University of New York at Stony Brook.


Deborah L. Cross, MPH, CRNP, ANPBC, is associate

program director, gerontology NP program, University of Pennsylvania School of Nursing, Philadelphia

JoAnn Deasy, PA-C, MPH,

Virginia H. Joslin, PA-C, MPH, is

a primary-care clinician, teaches in the PA program at Pace UniversityLenox Hill Hospital, New York City.

assistant professor and PA Program division director at Emory University School of Medicine in Atlanta.

were symptom-free on PPIs for six weeks. At the end of the study, every participant had symptoms of gastroesophageal reflux disease (Gastroenterology. 2009;137:80-87). Fortunately, there is hope. Patients can confidently wean themselves off of PPIs and H2 blockers by decreasing frequency of dosing while treating symptomatically with such antacids as Mylanta or Tums. Another recent study demonstrated relief with chewing mint gum, which increases peristalsis and moves the acid through the gut (J Dent Res. 2005;84:1062-1065, available at, accessed August 15, 2011). Discontinue PPIs whenever possible, as they can lead to decreased absorption of such important nutrients as vitamin B12 and are associated with increased risk of fracture. However, there are patients that require long-term PPI therapy, such as those with large hiatal hernias.—Rebecca H. Bryan, APRN, CNP (155-2)

MANAGEMENT OF POSTHERPETIC NEURALGIA A woman aged 55 years has herpes zoster that affects the trigeminal nerve on the right side of her face. The post-herpetic pain is continuous and unbearable. Multiple drugs, including gabapentin (Neurontin) and topiramate (Topamax), have been unsuccessful. She cannot tolerate any anticonvulsants. She is currently taking morphine under the care of a pain specialist. This is the only thing that relieves her pain. She does not want to live the rest of her life on heavy-duty pain medications, but cannot function otherwise. What nonpharmacologic or referral options are available?—BODIL MORRIS, ARNP, Altamonte Springs, Fla.

available at, accessed August 15, 2011). Systemic agents used to treat PHN include opioid analgesics (e.g., morphine, oxycodone), tricyclic antidepressants (e.g., amitriptyline [Elavil, Endep, Vanatrip], desipramine [Norpramin]), and anticonvulsants (e.g., gabapentin [Fanatrex, Gabarone, Neurontin], pregabalin [Lyrica], lamotrigine [Lamictal]). Topical agents most frequently used include lidocaine 5% patch or gel and capsaicin cream (ranging from 0.025% to 0.075%) (J Am Osteopath Assoc. 2009;109:S7-S12, available at cgi/content/full/109/6_suppl_2/S7, accessed August 15, 2011); recently, an 8% capsaicin patch has been developed and has been shown to be effective (J Pain Palliat Care Pharmacother. 2011;25:3241). Less common topical therapies include acetylsalicylic acid (in either acetone, alcohol, chloroform, or ether) and geranium oil. Such nonpharmacologic treatments as acupuncture, behavioral therapies (relaxation techniques), and transcutaneous electrical nerve stimulation have also been used (Int J Clin Pract. 2009;63:1386-1391, available at, accessed August 15, 2011).—Philip R. Cohen, MD (155-3)

ELEVATED ALP AND NORMOCYTIC ANEMIA What is the significance of an isolated alkaline phosphatase (ALP) of 161 IU/L in the absence of gallbladder, pancreas, or liver disease? Is there any correlation with a normocytic anemia?—V. ROBERSON, NP-C, Aiken, S.C.

Postherpetic neuralgia (PHN) occurs in approximately 10%-15% of herpes zoster patients and is defined as pain lasting at least three months after resolution of the rash ( J Fam Pract 2009;58:384d-384f,

ALP is present in many human tissues, including bone, intestine, kidney, liver, placenta, and WBCs. An elevated ALP may be seen in disorders of any of these and is also commonly seen in neoplastic disorders. Women in the third trimester of pregnancy can have elevated levels of ALP. Levels vary with age and increase during adolescent growth spurts and in people between the ages of 40 and 65

Susan Kashaf, MD, MPH, is assistant

Sherril Sego, FNP-C, DNP, is a

Daniel G.Tobin, MD, is assistant

Julee B.Waldrop, DNP, is associate

primary-care nurse practitioner at the Department of Veterans Affairs Medical Center in Kansas City, Mo.

professor of medicine, Yale University School of Medicine, New Haven, Conn.

professor at the University of Central Florida (UCF), Orlando, and practices pediatrics at the UCF Health Center.

professor of medicine, Yale University School of Medicine, New Haven, Conn.

Maria Kidner, DNP, FNP-BC, is

a nurse practitioner with Cheyenne Cardiology Associates in Cheyenne, Wyo.

Debra August King, PhD, PA, is senior

physician assistant, New YorkPresbyterian Hospital, New York City.

Claire Babcock O’Connell, MPH, PA-C, is an

associate professor, University of Medicine and Dentistry of New Jersey, PA program, Piscataway.

Reuben W. Zimmerman, PA-C, is a full-time

practitioner with Esopus Medical, PC, an independent family practice in Rifton, N.Y. • THE CLINICAL ADVISOR • SEPTEMBER 2011 63

Advisor Forum

CONFIRMING SUSPICIONS OF HEPATIC ENCEPHALOPATHY A patient is suspected of having hepatic encephalopathy (HE) attributable to liver failure from alcoholism. He has asterixis but no mental confusion or mental status changes. Does this patient really have encephalopathy if asterixis is the only manifestation?—MiRIAM ANDERSON, NP-C, Fargo, N.D. HE is a common complication of cirrhosis, characterized by a number of neuropsychiatric manifestations ( J Hepatol. 2011;54:10301040). Neuropsychologic impairment, which is common among outpatients with cirrhosis, is frequently asymptomatic and is often not perceived by the clinician. Minimal hepatic encephalopathy (MHE) has recently been described in an effort to capture the subtle and early phases of the spectrum of encephalopathy (Curr Gastroenterol Rep. 2011;13:26-33). MHE has been associated with a poorer quality of life and driving impairment and vehicle accidents. The West Haven scale establishes four stages of HE based on alterations in the state of consciousness, intellectual function, behavior, and neuromuscular signs. Depending on how your patient is assessed, he may have minimal encephalopathy or grade 1 HE under the West Haven criteria. With grade 1 HE, the patient may exhibit any of the following: trivial lack of awareness, euphoria or anxiety, shortened attention span, and impairment of ability to add or subtract. The associated asterixis may consist of a few flapping motions.—Sharon Dudley-Brown, PhD, FNP-BC, co-director, gastroenterology & hepatology, nurse practitioner fellowship program, Johns Hopkins University Schools of Medicine & Nursing, Baltimore (155-5)

DIAGNOSING SCALP CONDITIONS How can clinicians tell the difference between seborrheic dermatitis and scalp psoriasis?—VICTOR CZERKASIJ, FNP-C, APRN-BC, Cleveland, Tenn. When there are other clinical stigmata of psoriasis (e.g., diseaseassociated cutaneous plaques or nail changes), the same diagnosis for


years, especially women. Normocytic anemia is the most frequently encountered type of anemia, with anemia of chronic disease being the most common normocytic anemia. The evaluation of the patient with normocytic anemia and elevated ALP requires a thorough history and accurate physical exam to reveal the underlying causes of these abnormalities, which may or may not be related.—Eileen F. Campbell, MSN, CRNP (155-4)

Enhanced micrograph of a blood smear shows evidence of anemia.

the accompanying scalp lesions would likely be favored. However, differentiating severe seborrheic dermatitis from psoriasis localized only to the scalp can be clinically challenging and perhaps not always possible. Some consider these entities as endpoints of a disease spectrum and include sebopsoriasis as a diagnosis whose clinical features fall between the two conditions.—Philip R. Cohen, MD (155-6)

CAN A GLUTEN-FREE DIET TAME INFLAMMATION? Is there a connection between celiac disease (CD) and inflammation? If so, would it be wise to treat both at the same time or try a gluten-free diet (GFD) first and see if that controls the inflammation as well?—LESLIE READ, Santa Cruz, Calif. There is an association between CD and inflammation. CD is characterized by an autoimmune response in genetically susceptible individuals, resulting in small-intestine mucosal injury. However, not everyone presents with classical intestinal symptoms; in fact, 50% present with such atypical symptoms as anemia, osteoporosis, infertility, and neurologic and dermatologic problems. CD is associated with many other autoimmune diseases, such as type 1 diabetes, Sjögren’s syndrome, psoriasis, thyroiditis, inflammatory arthritis, and alopecia. In addition, CD is thought to be associated with an increased risk of malignancies, especially lymphomas or cancer of the immune system (Nat Rev Gastroenterol Hepatol. 2010;7:204213, available at nrgastro.2010.23.html, accessed August 15, 2011). Without knowing where the inflammation is located, I can’t be more specific in my answer. However, a GFD is reasonable. For • THE CLINICAL ADVISOR • SEPTEMBER 2011 69

Advisor Forum example, in dermatitis herpetiformis—a dermatologic manifestation of CD—treatment aimed solely at the skin is not effective, whereas a GFD improves the skin and the gut. To test the theory, however, the patient must follow a very strict GFD, which can be quite challenging and costly. Symptomatic relief must be achieved as early as two weeks after beginning a strict GFD.—Sharon Dudley-Brown, PhD, FNP-BC, co-director, gastroenterology & hepatology, nurse practitioner fellowship program, Johns Hopkins University Schools of Medicine & Nursing, Baltimore (155-7)

COMPARING METHODS OF CALCULATING EJECTION FRACTION How does the ejection fraction (EF) calculated during the sestamibi imaging of a cardiac stress test correlate with an EF measured with a two-dimensional cardiogram?—PATRICIA GABLE, FNP-BC, Cadillac, Mich. The EF is calculated by the computer assessment of gated images obtained during a sestamibi imaging test. The short axis gated images obtain data from the apex to the base; the horizontal gated images obtain data from the posterior to anterior; and the vertical gated images obtain data septal to lateral. The equipment determines how many slices (more slices mean better data). The ECG is then correlated to the gated images before the volume at end diastole and systole is finally calculated. This all sounds impressive, but the EF from nuclear stress testing is often erroneous if the heart size is

small (as in many women) or large with cardiomyopathies, or there are arrhythmias during the scanning process. The EF obtained by echocardiography is directly dependent on the images obtained by the sonographer and the experience of the reader. It is quite reliable with good images and a talented reader. The best EF is by either multigated acquisition (MUGA) scan or ventriculography during left-heart catheterization.—Maria Kidner, DNP, FNP-C (155-8)

DISCOID LUPUS ERYTHEMATOSUS LABORATORY FOLLOW-UP How often should blood tests be repeated to rule out systemic lupus erythematosus (SLE) in a patient positive for discoid lupus erythematosus (DLE)?—SHERRY GURALNICK COHEN, CRNP-F, Owings Mills, Md. The progression of localized DLE to DLE as part of SLE has been observed. Callen noted six of 62 patients with DLE who either had (two patients) or developed (four patients) SLE or mixed connective tissue disease (Arch Dermatol. 1982;118:412-416). This is similar to Millard and Rowell, who noted SLE to develop in 6.5% of their patients with DLE (Arch Dermatol. 1979;115:1055-1058). Specific guidelines for repeating blood tests to rule out SLE in a patient with DLE have not been established; however, it has been suggested that “the tests may need to be repeated every year or so” (, accessed June 15, 2011).—Philip R. Cohen, MD (155-9)

© The New Yorker Collection 2011 from All Rights Reserved.

TONSILLOPHARYNGITIS VS. PERITONSILLAR ABSCESS What is the best way to differentiate tonsillopharyngitis from a peritonsillar abscess?—AMY ROZELLE, NP, St. Petersburg, Fla.

“Human Resources.”

Tonsillopharyngitis can be caused by viral infections or by bacterial infections, the most common of which is group A beta-hemolytic streptococci (GABHS). The typical presenting symptoms of GABHS tonsillopharyngitis are sudden onset of sore throat, pain on swallowing, fever, and the absence of cough or rhinorrhea. Physical exam findings include tonsillopharyngeal erythema, with or without tonsillar exudate, and swollen, tender anterior cervical nodes. A peritonsillar abscess is a suppurative complication of bacterial tonsillitis, usually caused by GABHS, and involves extension of the infection through the tonsillar fibrous capsule into the peritonsillar space. Presenting symptoms of peritonsillar abscess include fever, malaise, sore throat, odynophagia, dysphagia, trismus, and voice change (often referred to as “hot potato voice”). Physical exam


Advisor Forum SURGICAL CLEARANCE GUIDELINES Many dentists, optometrists, and other specialty providers are sending adult patients to our primary-care clinic for surgical or procedural clearance. Are there standards of practice for such patients?—DEBRA C. ALLEN, MSN, ANP/GNP, Reidsville, N.C.


There are no clinical guidelines for surgical clearance by the primarycare provider. Many specialists request that the patient be evaluated prior to a procedure—especially those over age 50 years and/or those with chronic medical problems—to determine the risk of complication during and immediately after the procedure. The evaluation should include an assessment of the status of the medical problems and any special instructions related to the dosing of medications leading up to or on the day of the procedure.—Eileen F. Campbell, MSN, CRNP (155-12) Peritonsillar abscess (shown) is usually a complication of tonsillitis.

may reveal asymmetric edema of the palate, contralateral deflection of a swollen uvula, fluctuant peritonsillar fullness, drooling, and cervical adenopathy. This infection requires immediate attention. Needle aspiration of the peritonsillar space is recommended and is most accurately done by an experienced otolaryngologist.—Eileen F. Campbell, MSN, CRNP (155-10)

WHEN TO GIVE THE ZOSTER VACCINE An elderly patient presented with an acute reaction of shingles. How soon after treatment is it advisable to administer the zoster vaccine (Zostavax)? A month? A year? I have gotten conflicting answers from both sides of the spectrum.— ANNA LISA GUZMAN, PA-C, MPAS, Edinburg, Tex. Zostavax is recommended as a single subcutaneous dose for persons aged 60 years and older. The vaccine is contraindicated in persons with a history of allergy to gelatin, neomycin, or other component of the vaccine; immunodeficiency (malignancy affecting bone marrow or lymph system, HIV, or AIDS); receiving immunosuppressive therapy, including high-dose corticosteroids; and pregnancy. The CDC recommends that qualifying individuals be vaccinated regardless of extent of documentation of prior varicella or zoster. The CDC remains somewhat vague on the timing of vaccine after an outbreak of shingles. The published wording is, “The general guideline for any vaccine is to wait until the acute stage of the illness is over and symptoms abate” (available at shingles/hcp-vaccination.htm, accessed August 15, 2011).—Claire Babcock O’Connell, MPH, PA-C (155-11)

WHICH RADIOLOGIC TEST TO USE FOR ABDOMINAL PAIN How do I know which radiologic tests to choose when evaluating abdominal pain?—DOROTHY MALONE RISING, ANP, CDE, Johnson, Vt. Contrast is required whenever there is a differential of cancer. If a patient presents with acute abdominal pain consistent with appendicitis, diverticulitis, or the like, contrast is not necessary; inflammation will be evident on a plain CT. Another consideration for use of contrast includes the renal function of the patient, which is particularly important to assess prior to contrast administration for older patients. If you are concerned about any abnormality in the lower half of the abdomen, abdomen/pelvis CT is necessary, because anatomical regions overlap. If the concern is cholecystitis, perforated gastric ulcer, or anything else in the epigastric region, a full abdominal CT is recommended.—Rebecca H. Bryan, APRN, CNP (155-13)

CLINICAL PEARLS Congratulations to the winners of’s inaugural Clinical Pearls contest. The five readers below will each receive a $100 American Express Gift Cheque. The remaining five winners will appear in the October 2011 issue. Thanks to all who entered.

AN ALTERNATIVE TO A FOOD DIARY I am always looking for creative ways to encourage my patients to eat healthier and lose weight. I used to have them write down what they ate and bring it to their next


Advisor Forum

BEYOND “JUST SAY NO” Ask a teenager to create his or her own anti-drug, tobacco, or alcohol advertisement. It will give you insight into the triggers to his or her use of these substances.—BEVERLY ROSSITER, CRNP, Indiana, Pa. (155-13)

PUT YOUR LIPS TOGETHER AND BLOW To help patients with chronic obstructive pulmonary disease utilize pursed-lip breathing, I tell them to “smell the roses” (a long inspiration) and “blow out the candles” (a long exhalation).—ELENA RUOCCO, RN, MSN, FNP-BC, Houston (155-15)

A VISUAL AID FOR THE METRIC SYSTEM Metric conversions can be a challenge. For a practical illustration of an abstract concept, use a packet of artificial sweetener. Each packet contains exactly 1 g of sweetener. I distribute a packet to my students and have them pour it out on the table. They are then instructed to divide the “medication” into various quantities (e.g., 500 mg, 250 mg, 0.125 g, etc). This increases their understanding of these amounts when dealing with medication administration.—TRACEY GILLAN, RN, MSN, APRN-BC, East Setauket, N.Y. (155-16)

II receptor blocker (ARB) (Item 151-8). In fact, as the patient loses function, an ACE/ARB is more important to maintain kidney function. You incorrectly cite the Kidney Disease Outcomes Quality Initiative’s Clinical Practice Guidelines on Hypertension and Antihypertensive Agents in Chronic Kidney Disease (available at professionals/KDOQI/guidelines_bp/, accessed August 15, 2011), which recommends discontinuing the ACE/ARB if the SCr increases <30% over baseline (not from normal). This applies to those few patients with renal artery stenosis (RAS) who will have an abnormal percentage increase in SCr after taking an ACE/ARB.—KIM ZUBER, PA-C, Alexandria, Va. Ms. Zuber’s statement that this drug class is renal-protective is absolutely true. Multiple studies confirm that the use of these medications slows the progression of nephropathies (of any etiology) to end stage renal disease. However, use of these drugs is not without several very significant concerns. The initial drop in glomerular filtration rate (GFR) (along with a rise in SCr) is well documented. Patients with more progressed renal impairment must be carefully monitored to assure that this drop is tolerated. Comorbid factors of age, atherosclerosis, RAS, and volume depletion also can lead to unanticipated serious drops in renal function. Other issues involved in chronic renal insufficiency include rising potassium levels, which can also be aggravated by ACE inhibitors. Concomitant medications must also be monitored. While a single hard-and-fast rule may not apply across the board, the assumption that ACE inhibitors and ARBs

© The New Yorker Collection 2011 from All Rights Reserved.

appointment, but this was not always successful. I now ask them to bring in their grocery receipt. This allows me to make suggestions on how to shop differently. We talk about affordable replacements for unhealthy food choices, and I praise them for the wise choices they did make.—TRISH GAGNON, PA-C, Augusta, Maine (155-14)

LOWER-POTASSIUM POTATOES Before cooking, soak potatoes in water overnight to reduce their potassium content. This is especially useful for dialysis patients, who must watch their intake of this mineral.—ELIA KECK, NP, San Antonio, Tex. (155-17)

YOUR COMMENTS RENAL-PROTECTIVE PROPERTIES OF ACE INHIBITORS AND ARBS There is no serum creatinine (SCr) level that would keep a practitioner from using an ACE inhibitor or angiotensin

“Why do you think you crossed the road?” • THE CLINICAL ADVISOR • SEPTEMBER 2011 75

Advisor Forum should automatically be used in every patient with renal insufficiency is not correct.—Sherril Sego, FNP-C, DNP (155-18)

WHEN TO CONSIDER DIALYSIS In a discussion of whether ACE inhibitors and angiotensin II receptor blockers (ARBs) are recommended for patients with renal disease (Item 153-02), you incorrectly identify verapamil and diltiazem as dihydropyridine (DHP) calcium channel blockers (CCBs); they are non-DHP CCBs. You likely meant to list nifedipine, amlodipine, and felodipine. More troubling is the recommendation to start dialysis in patients with stage 4 chronic kidney disease (CKD). This would be malpractice. Dialysis is to be considered for stage 5 CKD. ACE/ARB therapy should be continued as long as tolerated by hyperkalemia throughout stage 4 CKD and sometimes into stage 5 CKD, as long as uremic symptoms are not significant.—DANIEL LEVY, MD, PhD, Chicago

“It’s a working vacation.”

Thank you for the correction regarding verapamil and diltiazem. I apologize for the error. As for the second comment, patients in stage 4 kidney disease will likely need dialysis or transplant very soon. Perhaps it is more accurate to say dialysis or transplant is considered (rather than recommended) in such cases. The decision to place a patient on dialysis depends on many factors, not just the glomerular filtration rate (GFR), which is what determines the stage of kidney disease. Many patients do go on dialysis when the GFR falls to stage 4 levels.—Claire Babcock O’Connell, MPH, PA-C (155-19)

“Sorry, boys, but we’re cutting back on bean counters till we have beans.” © The New Yorker Collection 2011 from All Rights Reserved.

PLENTY OF BLAME TO GO AROUND The clinician’s actions in this case were a clear invasion of privacy (“Revealing a tattoo costs a clinician,” July 2011). The patient consented to exposure of his person, but taking pictures for a nonclinical purpose exceeds that consent. However, the staffer who took exception to the clinician’s acts also violated the patient’s expectation of privacy. What patient confidence was the staffer protecting when she called the newspaper? Any facts revealed during the course of treatment that were communicated to anyone—without an express or at least implied need to know—was a violation. The fact the staffer called anonymously is telling. A true patient advocate would have reported the behavior to a supervisor and made an occurrence report. Instead the staffer indulged in payback for long-held resentments about a colleague’s sense of entitlement and privilege. The whistleblower in this story shares culpability with the picture-happy clinician.—KEITH FORD, RN, JD, Fort Mohave, Ariz. (155-20) ■

“It’s a brand-new religion based on balancing the budget.”


Derm Dx Test your clinical acumen with our monthly quizzes

Skin-colored papules over the nose lingered for years A black man, aged 48 years, presented with several papules on his nose as well as larger plaques on his forehead, which had been present and slowly growing for many years. What is your diagnosis?

• • • •

Granuloma annulare Cutaneous sarcoidosis Tinea corporis Syphilis

Violaceous annular plaques on the trunk A 31-year-old Latino man with diabetes presents to the dermatology clinic with pruritic plaques on the base of the neck and bilateral lateral trunk. What is your diagnosis?

• • • •

Granuloma annulare Sarcoidosis Pityriasis rosea Tinea corporis

To post your answer, obtain more clues, or view similar cases, visit Learn more about diagnosing and treating these conditions, and see how you compare with your peers.

Check out these other Derm Dx cases: Multiple erythematous pustules on a toddler’s hands

Painful erosions on the bilateral inguinal folds and intergluteal cleft • THE CLINICAL ADVISOR • SEPTEMBER 2010 79


Expand your practice In addition to the award-winning news and features found every month in our print edition, is an invaluable resource that now offers: • Free on-line CME/CE • Job advice and salary information • Medical slideshows • Derm Dx

• PLUS the opportunity to sign up for weekly newsletters and submit clinical questions and pearls to our popular Advisor Forum

To see all this and much more, visit

Writers’ Guidelines The Clinical Advisor welcomes submissions from its readers. Writing for us is an opportunity to share your knowledge and experience with your colleagues — and to collect a fee in the bargain! We pay an honorarium for every submission we accept. We’ll be glad to work with you to develop your ideas into compelling articles. As for length, that depends on which kind of article you submit. CLINICAL FEATURES update our readers with the latest information about conditions seen in everyday practice. Running no more than 2,500 words, features can be written either as regular narratives or as a series of questions and answers. Topics should be selected with the busy primary-care clinician in mind; specialists should review specialty topics from the primary-care point of view. If at all possible, articles should be accompanied by clinical photos, for which we pay extra. Charts, tables, and algorithms are also encouraged. References are optional; if you opt not to use any, please provide a recommended reading list of books, articles, and Web sites. In addition, include your curriculum vitae, which should list all current titles and affi liations. CLINICAL CHALLENGE is our popular department comprising histories of difficult cases. Each case is presented as a step-by-step, chronological account, revealing the author’s thought processes along the way. It is divided into sections in this order: the patient presentation; the patient history; the twists and turns eventually leading to a diagnosis; the treatment and outcome; and a discussion of the lessons learned or of the condition in general. We pay extra for any photographs or images that we use. The length should be about 1,500 words. Please include your title, affi liations, and curriculum vitae. DERMATOLOGY CLINIC is a department that presents photos of actual cases and asks readers to identify the condition. Each case opens with one or two color photos and a brief description of the patient and/or his or her presentation, without giving away the diagnosis. This is followed by a 750- to 1,000-word summary that includes a fuller description of the ailment, how the correct diagnosis was achieved, a general review of the condition along with a differential diagnosis, and a description of the patient’s treatment and outcome. Topics must be approved by the editor prior to submission. COMMENTARY is our guest editorial page. It gives you the opportunity to sound off on an issue of importance to your colleagues nationwide. Support your views with as many facts, statistics, studies, and personal anecdotes as possible. A typical Commentary runs about 600 words in length. To discuss your editorial ideas, contact us by phone at 646.638.6077; by e-mail to; or by mail to: The Clinical Advisor, 114 West 26th Street, 4th Floor, New York, NY 10001.


Test your clinical acumen with our monthly quiz

CME Dermatology Clinic CE

■ LEARNING OBJECTIVES: To increase awareness of dermatologic conditions, their diagnosis, and up-to-date treatment. ■ COMPLETE THE POSTTEST: Page 103

■ ADDITIONAL CME/CE: Pages 55, 99


Thinning hair at the frontal scalp and crown KERRI ROBBINS, MD

A woman aged 54 years presented with a complaint of hair loss. She stated that for the past year, she felt as though her hair was becoming very thin, especially on the frontal scalp and the crown of her head. There was no pain or pruritus associated with the hair loss. She had not tried any previous treatments. The patient’s father started losing his hair in his late 20s, but there was no other family history of hair disorders. No fatigue, cold intolerance, weight gain, or dandruff were reported. A review of systems was positive for menstrual irregularities. What is your diagnosis? Turn to page 86


Painful shin lesions described as “bumps” ESTHER STERN, NP-C

A woman aged 58 years presented to the dermatology clinic with a complaint of painful bruising on both of her legs over the past several weeks. She described the feeling of the lesions as similar to “hard bumps.” The patient reported no recent trauma and had not started any new medications prior to the onset of symptoms. The woman did report a preceding cough and said she had felt “run down” recently. A review of systems was otherwise negative. On examination, several erythematous and tender nodules were noted on the patient’s anterior shins. An examination of the nearby joints was unremarkable. What is your diagnosis? Turn to page 87 • THE CLINICAL ADVISOR • SEPTEMBER 2011 85



Dermatology Clinic

Androgenetic alopecia

Androgenetic alopecia is a disorder that is characterized by patterned and progressive hair loss caused by genetic factors, which in turn affect the hormones (androgens). Although the disorder has been known to start as early as age 11 years, it mainly affects adults in their 20s. Approximately 80% of white men have a form of androgenetic alopecia by age 70 years.1 A smaller percentage of women express the trait. The inheritance is believed to be polygenic, meaning it can be inherited from one or both parents. Men with androgenetic alopecia are believed to have much stronger familial ties to the disease than women.2 Testosterone, the key hormone needed for puberty in men, is responsible for such secondary sex characteristics as growth of muscle mass, voice changes, sex drive, growth of the phallus and scrotum, and development of pubic and axillary hair. Dihydrotestosterone (DHT) is another hormone important during puberty. DHT is responsible for hair growth in the ears, nostrils, beard region, and limbs. It is also responsible for hair recession in the temporal region of the scalp, as well as for acne and growth of the prostate. Testosterone is converted to DHT by 5␣-reductase, an enzyme that has two isoenzymes, known as type I and type II.3,4 Type I 5␣-reductase is primarily found in the liver and sebaceous glands. Type II 5␣-reductase, which is responsible for androgenetic alopecia, predominates in the liver, prostate gland, and hair follicles of the scalp, beard, and chest.3 When the body produces an increased amount of 5␣-reductase, it leads to an increase in DHT. An increase in DHT causes the production of miniaturized hair follicles and a reduction in the amount of hair fibers. The hairs are also associated with a shorter anagen phase (growing phase), which results in hairs that are in the telogen phase (resting phase) for a longer period of time.5 While the hairs are arrested in the telogen phase, they are much more susceptible to falling out during everyday grooming (i.e., washing and brushing the hair). Women have a very similar pathogenesis for androgenetic alopecia. Because of alterations in androgen metabolism at the follicle, however, women are susceptible to the disorder during perimenopausal and menopause periods as well as during puberty.6 Systemic hormonal changes are also believed to contribute to the hair loss. Women who

develop balding shortly after puberty are more likely to have a family history that is positive for pattern baldness in both male and female family members. Overall, androgenetic alopecia is less severe in women than in men. Diagnosis of androgenetic alopecia in men is fairly easy. Patients will often present expressing a concern about thinning hair. The classical pattern of hair loss follows a symmetrical and progressive recession of the frontotemporal hairline, along with thinning of the vertex of the scalp. Hamilton developed a classification system based on the pattern and severity of hair loss. Norwood later reclassified the patterns into the major classification system now used to diagnose male pattern baldness. The amount and pattern of hair loss may vary between individuals. Miniaturization of terminal anagen hairs to smaller vellus hairs is the hallmark of androgenetic alopecia.7 The small, fine, hypopigmented vellus hairs will be present in large amounts prior to permanent shedding. Initially, the scalp skin will be normal; as the disorder advances, however, the scalp will become smooth and shiny. Women with androgenetic alopecia will have diffuse thinning of hair on the crown and frontal scalp, with sparing of the frontal hairline. Ludwig developed the classification system for hair loss in women.2 A sufficient biopsy is needed to properly diagnose androgenetic alopecia. A punch biopsy >4 mm in diameter with transverse sectioning is needed for quantitative evaluation. A horizontal section at the level of the lower infundibulum will allow for appreciation of the increased amounts of miniaturized hair follicles. For women, there should also be a hormonal evaluation, especially if there are menstrual irregularities.8 Although the diagnosis of androgenetic alopecia is fairly straightforward, a few hair diseases are commonly mistaken for the disorder. Any nonscarring alopecia, such as alopecia areata and telogen effluvium, may be mistaken for androgenetic alopecia.4 Others include iron deficiency, hyperthyroidism, systemic lupus, trichotillomania, and seborrheic dermatitis.2,9 Obtain a good history and diagram the patient’s family tree to determine whether the parents or grandparents had androgenetic alopecia. Early-onset or severe alopecia in women should suggest the possibility of pathologic hyperandrogenism, and appropriate laboratory tests should be performed. Patients with androgenetic alopecia may suffer from low self-esteem, anxiety, and depression, especially if the onset of the disorder occurs during the teenage years. For this reason, it is important to diagnose androgenetic alopecia at an early stage and initiate treatment in the hopes of halting the progression of the disease. At this time,


only topical minoxidil (Rogaine) (2% and 5%) and oral fi nasteride (Propecia, Proscar) are approved by the FDA to treat androgenetic alopecia.4 Minoxidil is approved for use in men and women, and those using the product should expect to halt hair loss and produce longer, larger-caliber hairs. Unwanted facial hair (if the medication comes in contact with facial skin) and contact dermatitis are major side effects of minoxidil. Oral finasteride is approved for use in men older than age 18 years and works by inhibiting Type II 5␣-reductase. Those using this medication should expect a halt of their hair loss and an increased amount of hair counts. Major side effects, which are seen in less than 2% of individuals, include such changes in sexual function as decreased libido, ejaculatory dysfunction, and erectile dysfunction. Gynecomastia and decreased levels of prostate-specific antigen may also be seen. In women of childbearing age, finasteride and spironolactone (Aldactone) can lead to feminization of a male fetus and should only be used in postmenopausal women. For advanced progression of androgenetic alopecia, such hair prostheses or surgical procedures as scalp flaps, hair transplant, and scalp reduction may be considered.2 The prognosis for androgenetic alopecia is fair. Progression is usually very gradual and can last for decades. It is very important to stop the progression of hair loss early, because most hair loss is permanent. Current treatments are successful, and surgical procedures can be performed to transplant hair in sites of alopecia. The patient in this case was diagnosed with androgenetic alopecia and was treated with topical 5% minoxidil. On follow-up, she stated that her hair loss had halted and that she felt as though her hair was thicker. She has had no significant progression of her disease. Dr. Robbins is a resident in the department of dermatology at Baylor College of Medicine in Houston. The author has no relationships to disclose relating to the content of this article. References 1. Olsen EA, Messenger AG, Shapiro J, et al. Evaluation and treatment of male and female pattern hair loss. J Am Acad Dermatol. 2005;52:301-311. 2. Fitzpatrick TB, Johnson RA, Wolff K, Suurmond R, eds. Color Atlas and Synopsis of Clinical Dermatology, 5th ed. New York, N.Y.: McGraw-Hill; 2005:959-962. 3. Paller AS, Mancini AJ. Hurwitz Clinical Pediatric Dermatology, 3rd ed. Philadelphia, Pa.: Elsevier Saunders; 2006.160-161. 4. JL Bolognia, JL Jorizzo, RP Rapini, eds. Dermatology, 2nd ed., St. Louis, Mo.: Elsevier-Mosby; 2008:987-988.

5. Simpson N, Barth J. Hair patterns: hirsuties and baldness. In: Dawber RPR, ed. Disease of the Hair and Scalp, 3rd ed. Malden, Mass.: Blackwell Science, Inc.; 1997:67-122. 6. Knochenhauer E, Azziz R. Ovarian hormones and adrenal androgens during a woman’s life span. J Am Acad Dermatol. 2001;45:S105-S115. 7. TP Habif. Skin Disease: Diagnosis and Treatment, 2nd ed., Philadelphia, Pa.: Elsevier Mosby; 2005:516-519. 8. DE Elder, R Elenitsas, BL Johnson, GF Murphy, X Xu, eds. Lever’s Histopathology of the Skin. 10th ed., Philadelphia, Pa.: Lippincott Williams & Wilkins; 2009:479-481. 9. RP Rapini. Practical Dermatopathology. Philadelphia, Pa.: Elsevier Mosby; 2005:99-145.


Erythema nodosum

A deep, 4-mm punch biopsy confirmed the suspected diagnosis of erythema nodosum (EN). This inflammatory skin condition is caused by a septal panniculitis, an inflammation of the subcutaneous fat. EN typically presents acutely with clusters of poorly defined erythematous tender nodules on the anterior or lateral aspects of the lower legs. Less frequently, EN may occur on the upper legs, extensor arms, neck, or face. Lesions are usually symmetrical, measuring 1 to 10 cm in diameter. Early in the disease, the skin overlying the nodules is red and shiny, and the lesions are tense and hard. Within days to weeks, the nodules flatten, fluctuate, and progress to bluish-purple bruiselike lesions.1 Most lesions eventually resolve within several weeks without any ulceration, scarring, or atrophy. Young women are most frequently affected, although EN occurs in both sexes and all ages. Patients often report symptoms of flulike illness, malaise, or fever. Arthralgia is common at the onset or preceding the eruption. Although any joint may be involved, the ankles, knees, or wrists are affected most frequently. Typical joint symptoms include erythema, edema, and tenderness. EN is thought to be a reactive process or delayed hypersensitivity reaction to a variety of stimuli. It is most commonly associated with streptococcal infection.2 Sarcoidosis is a very common cause in adults, and when it occurs concurrently with hilar adenopathy, the disease is termed Löfgren’s syndrome.3 TB is a significant etiology in countries where this disease is • THE CLINICAL ADVISOR • SEPTEMBER 2011 87


Dermatology Clinic

still endemic. Infection with Yersinia, Salmonella, Campylobacter, or Shigella may precipitate EN. Coccidioidomycosis is the most common cause of EN in the American Southwest. Drugs that may induce EN include bromides, iodides, sulfonamides, gold salts, penicillin, oral contraceptive pills (OCPs), and hormonal replacement therapies. In addition, ulcerative colitis, Crohn’s disease, and hematologic malignancy—most commonly lymphoma—may cause an eruption. Finally, pregnancy is an important etiology in many patients.1 Repeated episodes of EN may occur with subsequent pregnancies or with the use of OCPs in sensitive individuals. Although diagnosis is most often clinical, skin biopsy is helpful in more atypical cases to rule out a nodular vasculitis, insect bites, or other pathology. Deep-skin incisional biopsy is preferred, although a deep punch may be satisfactory. Histopathology reveals a septal panniculitis with no vasculitis. The septa of subcutaneous fat are thickened and infi ltrated by inflammatory cells that extend to the periseptal areas of the fat lobules. The composition of the infl ammatory infi ltrate differs with stage of the lesion. Initially, edema, hemorrhage, and neutrophils are responsible for the inflammation. As lesions evolve, periseptal fibrosis, lymphocytes, multinucleated giant cells, and granulation tissue appear. Miescher’s radial granulomas are a histopathologic hallmark feature of EN. These are small well-defined nodular aggregates of histiocytes arranged radially around a central stellate cleft. The differential diagnosis of EN should include other forms of panniculitis. EN migrans—seen mostly in older women—is usually painless and has a more prolonged course. Erythema induratum typically only affects the posterior calves, and lesions may resolve with ulceration or scarring. Subacute localized infections should also be considered. In addition to skin biopsy, clinical workup usually includes a throat culture or antistreptolysin titer to rule out current or recent infection with group A beta-hemolytic streptococcus. Erythrocyte sedimentation rate is usually high. If clinically indicated, stool examination can exclude infection with common GI illness-causing organisms. A person complaining of cough or pulmonary systems should have a chest x-ray done to exclude sarcoidosis or TB and to

document the presence or absence of hilar adenopathy. An intradermal TB skin test should be performed if indicated by history. A comprehensive travel and exposure history is if often necessary to discover other etiologies. Management of EN involves identifying and treating the underlying etiology, rest and elevation of the affected extremity in the acute stage, and use of such medications as aspirin, colchicine, or other non-steroidal anti-inflammatory agents. In most patients, EN is self-limiting and resolves within six to eight weeks. Bedrest and use of support hose may hasten recovery. Potassium iodide has been shown to provide quick relief of lesional tenderness, arthralgia, and fever in some patients.4 Intralesional injection of corticosteroids may help control persistent lesions. Systemic corticosteroids are rarely indicated. Some medications (e.g., aspirin and ibuprofen) that are used to treat EN have been implicated as rare causes of the condition. These agents should be stopped if EN symptoms are exacerbated while the patient is taking them. In rare instances, EN may become chronic or persistent. Recurrences are more likely if the underlying infection is still present or if the patient resumes regular physical activity too quickly. The patient in this case was educated regarding the diagnosis and self-limiting nature of the disease. A chest x-ray revealed no pathology, and her screening bloodwork was within normal limits. She was advised to follow up with her primary-care provider for regular health maintenance. In addition, it was recommended that she rest often, use support hose, and take OTC ibuprofen as needed. ■ Ms. Stern is a family nurse practitioner at Advanced Dermatology & Skin Surgery, P.C., in Lakewood, N.J. The author has no relationships to disclose relating to the content of this article. References 1. Requena L, Requena C. Erythema nodosum. Dermatol Online J. 2002;8:4. Available at /enodosum/requena.html. 2. Labbé L, Perel Y, Maleville J, Taïeb A. Erythema nodosum in children: a study of 27 patients. Pediatr Dermatol. 1996;13:447-450. 3. Pettersson T. Sarcoid and erythema nodosum arthropathies. Baillieres Best Pract Res Clin Rheumatol. 2000;14:461-476.


4. Horio T, Imamura S, Danno K, Ofuji S. Potassium iodide in the treat-

Test your diagnostic skills. Our FREE archive of Dermatology Clinic and Dermatologic Look-Alikes is now available online at


ment of erythema nodosum and nodular vasculitis. Arch Dermatol.

All electronic documents accessed August 15, 2011.


Clinical Challenge Kidney mass detected on ultrasound doubles in size over nine months

Ms. M, aged 64 years, was referred to our clinic with an enlarging right renal tumor. The tumor was incidentally detected on ultrasound, which her primary-care provider (PCP) ordered in response to her nonpalpable ovaries.



Imaging was ordered when the patient’s clinician could not palpate her ovaries.


Ms. M had a history of hypothyroidism, osteopenia, insomnia, and anxiety disorder. Her medications included levothyroxine (Levoxyl, Synthroid) 50 μg, fluoxetine (Prozac) 20 mg, raloxifene (Evista) 60 mg, temazepam (Restoril) 15 mg, docusate 100 mg, acetaminophen/ hydrocodone (Vicodin) 7.5 mg/500 mg, calcium carbonate 1,200 mg, fish oil 1,000 mg, vitamin D 2,000 IU, and a multivitamin. She had a family history of cancer (leukemia) and Alzheimer disease. Ms. M had undergone two surgeries to repair a detached retina and had a negative breast biopsy. The patient did not complain of abdominal or flank pain and reported no chest pain, shortness of breath, hematuria, or melena.


FIGURES 1 & 2. Originally diagnosed as an 8-mm angiomyolipoma, the tumor (arrow) measured 1.6 cm on CT nine months later.

During a normal pelvic exam, Ms. M’s PCP could not feel her ovaries and ordered an abdominal ultrasound, which revealed a tumor on the right kidney. The tumor was initially diagnosed as an angiomyolipoma. Four months later, a second ultrasound confirmed an 8-mm echogenic nodule. A triphasic renal CT with IV contrast ordered nine months later to confirm the angiomyolipoma revealed a fat-poor, hypovascular tumor that enhanced from 34 to 70 Hounsfield units. The mass was located in the lateral cortex of the right kidney, and in comparison with previous ultrasound studies, appeared to have more than doubled in size to 1.6 cm (Figures 1 and 2). The radiologist felt that this tumor was unlikely an angiomyolipoma • THE CLINICAL ADVISOR • SEPTEMBER 2011 89

Clinical Challenge and would not rule out renal cell carcinoma until proven otherwise. A 3- ⫻ 5-mm cyst in the mid-pole of the right kidney and a 1.6 cm hepatic cyst in the right lateral lobe of the liver were also noted on CT. Prior to Ms. B’s fi rst referral appointment, the case was presented to a multidisciplinary small kidney tumor conference for review by urologists, pathologists, and radiologists. The physicians unanimously dismissed the possibility of an angiomyolipoma after review of the CT scans. The decided diagnosis was renal cell carcinoma.

3. TREATMENT AND OUTCOME The multidisciplinary panel thought the tumor’s proximity to the liver made it a bad candidate for percutaneous cryoablation therapy. A hand-assisted laparoscopic right partial nephrectomy was recommended instead. The partial nephrectomy was performed two months later without complications and with a warm ischemia time of 18 minutes. A pathologist confirmed negative intraoperative margins and removed the 2.5 ⫻ 2 ⫻ 2 cm specimen for pathologic study. On examination, the overall specimen had a tan, smooth stroma and contained a well-demarcated yellow nodule measuring 1.6 cm. Under microscopy, frozen sections revealed nonmitotic cytology with large nuclei. The pathology report showed a rare metanephric adenoma with negative surgical margins. Ms. M suffered superficial wound separation after surgery, which was treated with trimethoprim/sulfamethoxazole (Septra) b.i.d. for one week and daily irrigation with hydrogen peroxide. No other postoperative complications or complaints were reported. Her 10-week follow-up exam

FIGURE 3. After partial nephrectomy, kidney function was normal.

showed well-healed wounds, no evidence of hernia, and a serum creatinine level of 0.55 mg/dL, which compared well with a preoperative creatinine of 0.6 mg/dL. Ms. M’s follow-up CT scans showed normal bilateral kidney function without ureteral leakage (Figure 3). No further follow-up was recommended following the resection of a benign lesion with minimal risk of recurrence.

4. DISCUSSION A metanephric adenoma of the kidney is a rare benign neoplasm that is at least twice as likely to present in women than in men. Although patients presenting with metanephric adenomas typically range in age from 5 to 83 years,1 a classic metanephric adenoma was recently reported in a girl aged 2 years.2 Most tumors are asymptomatic and are incidentally detected on ultrasound or CT. Some patients present with palpable masses, hematuria, polycythemia, arterial hypertension, fever, and/or flank pain. Sonographic and CT imaging of metanephric adenomas show round, well-circumscribed solid masses that do not project extrarenally and rarely distort the renal contour; however, isolated cases of lobulated or distorting lesions have been reported in the literature.1,3,4 Metanephric adenomas are characteristically hypoechoic and hyperdense and enhance on contrast studies.4-6 On MRI, metanephric adenomas have presented as hypointense or isointense lesions with hyperintense centers suggestive of fat or liquid.4,5 The mean size of tumors presented in the literature is 5.5 cm, with no preference for the right or left kidney.1 Metanephric adenomas require differential diagnosis from nephrogenic rests, Wilms’ tumors, renal cell carcinomas, and metastatic cancers.3 They are often mistakenly diagnosed as renal cell carcinomas or epithelial Wilms’ tumors based on radiology and share similar cytologic features with papillary renal cell carcinomas.5 Nephrogenic rests and Wilms’ tumors contain blastemas; metanephric adenomas do not. Furthermore, metanephric adenomas can be distinguished by their lack of mitotic atypias or other cellular abnormalities. Histologically, metanephric adenomas can be distinguished from papillary renal cell carcinomas by their lack of macrophagic cells, low cytoplasmic volume, less distinguishable nucleoli, and uniform chromatin.7,8 Differentiation from metastatic cancers—particularly of the thyroid gland or lung—is less straightforward and may require immunohistochemical analysis.3 With regard to Wilms’ tumors, age proves a useful distinguishing factor, as 90% of Wilms’ tumors present in children younger than • THE CLINICAL ADVISOR • SEPTEMBER 2011 93

Clinical Challenge age 6 years,8 and metanephric adenomas have a mean age presentation of 41 years.1 Surgical excision of these tumors reveals unencapsulated, well-circumscribed lesions with tan, yellow, gray, or pink fleshy cut surfaces.1,4 Microscopically, metanephric adenomas are comprised of round, uniform epithelial cells with acinar, tubular, and glomerular structures, and a low cytoplasm-to-nuclei ratio.9 Typical cells consist of large round or oval nuclei and lack mitotic figures, suggestive of a benign tumor. Metanephric adenomas have the highest incidence (12%) of associated polycythemia among renal tumors, and patients often present with high hematocrit and hemoglobin levels.1 This was not the case with Ms. B, who presented with hematocrit and hemoglobin levels below the normal range. Until recently, metanephric adenomas were assumed to be entirely benign with no reports of metastases; however, two cases have been reported in the literature: Metastases to the para-aortic, hilar, and aortical bifurcation lymph nodes were seen in a girl aged 7 years,9 and a woman aged 21 years presented with a metanephric adenoma and malignant spindle cell carcinoma, newly termed “metanephric adenosarcoma.”10 Although reports of metanephric adenomas with atypical cytology suggest that this tumor pathology may be less straightforward than originally thought, conservative nephrectomy and longterm follow-up are still accepted as the most reasonable standard of care. Further investigation of distinguishing radiologic and genetic features of metanephric adenomas will help to diminish overtreatment of benign tumors and promote nephron-sparing surgery as a viable and ideal option, especially in young children. ■

4. Navarro O, Conolly B, Taylor G, Bägli DJ. Metanephric adenoma of the kidney: a case report. Pediatr Radiol. 1999;29:100-103. 5. Schmelz HU, Stoscheck M, Schwerer M, et al. Metanephric adenoma of the kidney: Case report and review of the literature. Int Urol Nephrol. 2005;37:213-217. 6. Ebine T, Ohara R, Momma T, et al. Metanephric adenoma treated with laparoscopic nephrectomy. Int J Urol. 2004;11:232-234. 7. Jiménez-Heffernan JA, Tejerina E, González-Peramato P, et al. Cytologic features of metanephric adenoma of the kidney. Cytojournal. 2009;6:7. Available at 8. Renshaw AA, Freyer DR, Hammers YA. Metastatic metanephric adenoma in a child. Am J Surg Pathol. 2000;24:570-574. 9. Burger M, Junker K, Denzinger S. Metanephric adenoma of the kidney: a clinicopathological and molecular study of two cases. J Clin Pathol. 2007;60:832-833. Available at PMC1995803/. 10. Picken MM, Curry JL, Lindgren V, et al. Metanephric adenosarcoma in a young adult: morphologic, immunophenotypic, ultrastructural, and fluorescence in situ hybridization analyses. Am J Surg Pathol. 2001;25:1451-1457. All electronic documents accessed August 15, 2011.

Ms. Ivanowicz is a research scholar with McKay Urology in Charlotte, N.C., where Mr. Switek and Dr. Teigland are clinicians specializing in urologic oncology. References 1. Davis CJ Jr, Barton JH, Sesterhenn IA, Mostofi FK. Metanephric adenoma. Clinicopathological study of fifty patients. Am J Surg Pathol. 1995;19:1101-1114. © Roy Delgado

2. Netto JMB, Esteves TC, Mattos RCMS, et al. Metanephric adenoma: a rare differential diagnosis of renal tumor in children. J Ped Urol. 2007;3: 340-341. 3. Kuroda N, Toi M, Hiroi M, Enzan H. Review of metanephric adenoma of the kidney with focus on clinical and pathobiological aspects. Histol Histopathol. 2003;18:253-257. Available at Vol_18/18_1/Kuroda-18-253-257-2003.pdf.

“A hacker named Goldilocks has entered our home page”




Sometimes, one look is all it takes An eager, young clinician learns the hard way that discretion is the first rule of law in medicine.


When she was offered a position as a nurse practitioner at a well-known and highly regarded clinic, Ms. J was delighted. After graduating, Ms. J had worked in a small practice and garnered a good deal of hands-on experience. But after five years, she was ready for something more challenging. The interviews were rigorous, but Ms. J expected that from such a prestigious institution. Her friendly, calm demeanor stood her in good stead throughout the process, and after a series of interviews, Ms. J was offered the job. On her first morning, she was given a copy of the clinic’s rules, regulations, and policies. Ms. J was instructed to read, sign, and return the policy manual by the end of her first week. That evening, Ms. J casually flipped through the manual and signed the form at the end. She dropped it off the next morning and didn’t give it a second thought until almost two years later. For the first 22 months of her employment, Ms. J felt that she had grown considerably as a clinician. Her work was interesting and challenging and her supervisors were supportive and gave her ample opportunity to develop her skill.

Ms. J peeked at the patient’s records and quickly closed the file without looking at the diagnosis or other medical information.


Ms. J’s curiosity, however, was a distinct drawback. It was not unusual for famous people— actors, actresses, athletes, and musicians—to seek treatment at the clinic. The media camped out in the clinic’s parking lot and often tried to elicit information from the clinic staff. One day, Ms. J was putting some patient files away when she noticed a familiar name on a patient folder at the nurses’ station. The fairly common name was also that of a well-known actress. Curious as to whether it was, in fact, the actress, Ms. J peeked at the records to verify the age of the patient. Her suspicions confirmed, she quickly closed the file without looking at the diagnosis or other medical information. But, unbeknownst to her, another employee had witnessed the act and reported it. At the end of the day, Ms. J was called into the office and asked directly whether she had Cases presented are based on actual occurrences. Names of participants and details have been changed. Cases are informational only; no specific legal advice is intended. Persons pictured are not the actual individuals mentioned in the article.

LEGAL ADVISOR looked at the patient’s records. Ms. J admitted that she had, simply to verify if the patient was who she thought it was. “I didn’t look at anything personal, and I didn’t tell anyone that she was here,” she added. Nevertheless, and much to her surprise, Ms. J was fired. While discussing her unexpected unemployment, a friend suggested that Ms. J speak to an attorney about suing the clinic to get her job back. “It’s not like you publicized the actress’s medical condition or ran to the press,” said her friend. “You really didn’t do anything other than verify that it was the actress who was being treated. No one was harmed and no one even had to know about it.”

opinion on potential outcomes while giving the attorney an opportunity to get an overview of the case and decide whether it’s worth taking. In cases in which an attorney is paid on a contingency basis (most personal injury cases are contracted in this way), he or she does not get paid unless the outcome is favorable to the client. It is therefore essential for the attorney to choose cases that have a high rate of success. Even when a case is not contracted on contingency and the attorney is paid by the hour, the chance of success must still be carefully weighed. For a litigator, there is no point in taking on a case when there is little to no chance of winning. Protecting yourself

“I didn’t divulge anything,” agreed Ms. J. “There was no HIPAA violation, so why should they have fired me?” Ms. J found an attorney who specialized in employment law and went in for a consultation. The attorney asked Ms. J to bring a copy of the clinic’s policy manual. The attorney listened to Ms. J’s story and carefully looked through the employment manual. Then he asked Ms. J the crucial question: whether she had signed anything when she was given the manual. Ms. J recalled signing a one-page statement acknowledging that she had read and agreed to the terms in the handbook. “I’m sorry,” he said, “but I advise you to focus your energy on looking for a new job.” “But why?” asked Ms. J. The lawyer explained that there was no case. When Ms. J was hired two years earlier, she signed a statement indicating that she would comply with a clearly spelled-out privacy policy, including a proviso against looking at patient fi les unless the patient in question was directly under her care. The handbook specifically stated that any breach of the clinic’s privacy policy would be grounds for immediate dismissal.

Patient privacy is a serious matter, and health-care facilities are tightening their policies to ensure that patients are protected. Ms. J believed that a quick peek at the patient’s file would do no harm, especially if she didn’t look at the diagnostic information. But she ignored the clinic’s clear-cut policy. Beyond that, her oath as a patient-care provider should have precluded her from behaving in such a manner. New hires are often overwhelmed with administrative paperwork, but one bit of advice should hold—never sign anything that you haven’t read. By signing and returning the form, Ms. J agreed to the policies contained therein. Had she read the handbook, Ms. J probably would have resisted the temptation to look at a patient’s record and would have not lost a lucrative and upwardly mobile job. ■

© The New Yorker Collection 2011 from All Rights Reserved.

The employee handbook explicitly stated that any breach of the clinic’s privacy policy would be grounds for dismissal.

Legal background

Most attorneys offer gratis consultations to people who are considering a lawsuit. A free consult gives both parties a chance to decide whether they can work together successfully. It also provides the potential client with a professional

“You don’t KNEAD me anymore.”


Dermatologic Look-Alikes


■ LEARNING OBJECTIVE: To improve the clinician’s ability to distinguish and properly treat dermatologic conditions with similar presentations. ■ COMPLETE THE POSTTEST: Page 103

■ ADDITIONAL CME/CE: Pages 55, 85

Discoloration of the eyelid NOAH SCHEINFELD, MD, JD, AND NICHOLAS BARNES



Velvety plaques and skin tags were noted near the right eye of a black woman aged 65 years. The area did not itch, burn, or hurt, and the patient did not know how long the skin had been like this. She was taking hydrochlorothiazide for hypertension and metformin for type 2 diabetes. When it was explained that removal of the tags was a cosmetic procedure, the patient declined this procedure. She was sent back to primary care for a full exam.

A boy aged 8 years with a family history of atopy presented with eyelid dermatitis. The boy’s mother was concerned and reported that the child rubbing his itchy eyelids at night had caused the rash. No treatment had been tried at the time of the visit. The patient was given a prescription for pimecrolimus (Elidel) cream 1%, instructed to use ice packs on his eyelids at night, and referred to an allergist for further treatment. • THE CLINICAL ADVISOR • SEPTEMBER 2011 99



Dermatologic Look-Alikes

Acanthosis nigricans

Acanthosis nigricans (AN) results from epidermal keratinocyte stimulation and dermal fibroblast proliferation secondary to increases in insulin, insulin-like growth factor, and other aspects that occur against a background of insulin resistance, obesity, cancer, diabetes, and other diseases. The disorder occurs commonly in the general population, and most cases are linked to obesity and insulin resistance. In one large population study, AN was present in 7% of school-age children.1 The percentage increased to 66% of children who weighed more than 200% of their ideal body weight. Despite similar obesity rates, an unequal distribution of the disease was found based on ethnicity. The prevalence was highest in blacks (13%) and Hispanics (5%) and lower in whites (0.5%). AN affects both genders equally. AN manifests with mildly to moderately rugose, velvety, dark-brown plaques. The plaques occur most commonly at flexural areas, specifically the axillae, neck, inframammary, and inguinal creases. Other areas can be involved, but this is uncommon. Papillomatosis (multiple fingerlike growths) commonly occurs on cutaneous and mucosal surfaces. Skin tags can be found in and around areas of AN. The onset of AN is slow and subtle, often taking years to develop. While most cases are attributable to insulin resistance (prediabetes) or diabetes, AN can also herald the development of an underlying cancer. AN associated with malignancy usually presents in a more striking and sudden fashion. While AN in malignancy can affect the standard flexural areas, malignancy-associated AN manifests in such unusual sites as the mucous membranes, the palms and soles, and even the eyelid. Eyelid involvement in AN is rare and can be associated with malignancy. Some believe that eyelid AN such a reliable predictor of malignancy that its appearance requires a thorough systemic evaluation,2 but that may be an overstatement. Because of changes in epidemiology and the overall decrease of stomach cancer, AN is no longer a reliable paraneoplastic indicator. In 1900, stomach cancer—which is linked to AN— was the most common type of cancer in the United States and is now rare. Representing approximately 55% of cases of AN, gastric adenocarcinoma is the most common malignancy now associated with the disorder. Other malignancies

associated with AN include malignant lymphoma, squamous cell carcinoma of the cervix, bronchial carcinoma, and bronchogenic squamous cell carcinoma.2-6 Most cases of AN are not related to malignancy. AN in the general population indicates a state of hyperinsulinemia. Any suspicion of AN should elicit an inquiry about a family history of diabetes. A recent study reported a prevalence of 17% of AN in African individuals with type 2 diabetes.7 Investigators also have found that children with AN are almost four times more likely to have hyperinsulinemia than are children without the disorder.8 The differential diagnosis for AN includes the reticulated papillomatosis of Gougerot-Carteaud syndrome, tinea versicolor, erythrasma and related infections, Dowling-Degos disease and its variants, and intertrigo. The distinctive physical exam findings and medical history usually allow a diagnosis of AN to be made clinically. The first sign noticed by patients is hyperpigmentation, with the affected skin having a darker or “dirty” appearance. Thickening of the epidermis and deepening of the skin folds (rugation) follows.9 When making a diagnosis of AN, ask about family history of diabetes, obesity, and insulin resistance. It is also helpful to ask about personal history of weight changes, as obesity-related AN may follow weight gain, and AN of malignancy can correlate with weight loss. Hormonal agents, birth control pills, growth hormones, human chorionic gonadotropin, antiretrovirals, and nicotinic acid have been reported to cause AN.8,10 Cases of AN have also been linked to increased androgen production, and some are idiopathic. Palifermin (Kepivance)—a modified version of recombinant keratinocyte growth factor (KGF) designed to decrease the incidence of mucositis associated with stem-cell transplantation—caused striking but transient AN, perhaps due to KGF and fibroblast growth factor.11 If the presentation is atypical and there is uncertainty about the diagnosis of AN, a biopsy may be indicated. Histology reveals hypertrophy and hyperplasia of the epidermis and papillary dermis accompanied by hyperkeratosis and acanthosis. Typically, there is an increase in extracellular matrix, resulting in papillary extension into the dermis.8 There is no infl ammatory infi ltrate of any significance into the dermis.10 Sometimes, AN may be associated with horn pseudocyst formation resembling the changes seen in a seborrheic keratosis.12 Although histologic examination occasionally demonstrates increased melanin in the basal epithelium, hyperkeratosis and papillomatosis account primarily for the darkened appearance of the skin lesion.4,10 Examination under an electron microscopic shows an


increase in tonofi laments.13 Other studies have shown an unusually high expression of keratin 18 and 19 proteins.14 Most medical treatments for AN are ineffective. Treatment is targeted at the underlying cause for the disorder. For malignancy-associated AN, treatment of the primary cancer will resolve the disorder. AN can then be used as a marker for disease recurrence.4 Since AN is most often caused by insulin resistance, glucose control should be the primary focus of treatment. Achievement of euglycemia in diabetic patients is accompanied by marked regression of AN.15 Weight loss can abate AN in many cases.16 In addition, oral metformin has been shown to significantly improve obesityassociated AN.17-19 If the patient desires further treatment, topical application of 0.1% tretinoin (Vesanoid) cream can be tried to lighten the lesion; 8 combining tretinoin with 12% ammonium lactate cream has also been successful.16-20 Another study proved the effectiveness of topical calcipotriol.21 If topical therapy fails, oral isotretinoin or acitretin may be tried.16, 22 Extremely thick lesions can have a bad odor, and treatment with antibacterial soaps may help in these cases.23 One year after the initial examination, the patient’s glucose and hemoglobin A1c were normal, according to her internist. The eye plaques and skin tags were unchanged.


Allergic shiner

A discussion of the allergic shiner must address the intersection of two disease categories—eyelid dermatitis and atopy. Eyelid dermatitis is a very common condition, the leading causes of which are allergic contact dermatitis, irritant contact dermatitis, atopic dermatitis, seborrheic dermatitis, nonspecific xerotic dermatitis, and psoriasis. Most people with eyelid dermatitis do not have a family history of atopic dermatitis. Atopy is a combination of three conditions: allergic rhinitis, atopic dermatitis, and asthma. Signs of allergic rhinitis include red, itchy, and watery eyes; itchy mouth, throat, ears, and face; swollen eyelids; fatigue; and the allergic shiner. Signs of atopic dermatitis include the allergic shiner; Dennie-Morgan lines around the eyes; lichenification; red to brownish-gray

patches; itching; small bumps that leak fluid and crust over when scratched; and thickened and sensitive, cracked, scaly, or raw skin from scratching.24 Approximately 50% of the individuals who develop atopic dermatitis display symptoms before the age of 1 year, and nearly 80% display symptoms within the first five years of life. The basis of atopy is as much genetic as it is immunologic. In many cases, the skin suffers a lack of effective ceramides. That is, atopic dermatitis is often caused by a defect in fi laggrin rather than a defect in the Th2 arm of the immune system. Many of the rashes of atopic dermatitis involve rubbing, and an allergic shiner is no exception. Other areas that are frequently involved include the antecubital and popliteal fossae and the lateral ankle. The discomfort engendered by atopy has a substantial impact on patients’ quality of life. The medical history can reveal information regarding an atopic family history and the atopic progression in the child. Avoiding medications that contain corticosteroids optimizes treatment for atopic dermatitis. Heavy and prolonged use of topical corticosteroids is suboptimal. Long-term use of even topical steroids can be linked with such side effects as skin atrophy, telangiectasia, striae, steroid-induced dermatoses, rosacea, and acne exacerbation. Rarely, systemic effects include osteonecrosis, hypothalamic-pituitary-adrenal axis suppression, growth retardation, and ocular problems.25 Alternatives to topical corticosteroids include the calcineurin inhibitors pimecrolimus cream or tacrolimus (Prograf ) ointment. Calcineurin inhibitors should ideally be used for short periods (two to four weeks), but clinical reality often necessitates longer use. Calcineurin inhibitors also effectively and safely treat atopic dermatitis, with the most commonly observed local adverse events being skin irritation and a burning sensation.25 Recent reports note that some moisturizers can help with eyelid dermatitis and allergic shiners. These devices provide antioxidant, antiprotease, and anti-inflammatory activity and assist in restoring the natural balance of lipids, one of the primary causes of the epidermal abnormalities seen with atopic dermatitis. Ceramide-hyaluronic acid emollient foam was found to be superior to pimecrolimus cream 1% in the treatment of eyelid dermatitis.25 OTC lotions and creams for treating atopic skin include EpiCeram, MimyX, Atopiclair, CeraVe, and Cetaphil. Treatment for the rhinitis aspect of atopy requires a strategy that uses environmental control, immunotherapy, and pharmacologic therapy. Immunotherapy can be seen as potentially prophylactic, capable of altering the course of • THE CLINICAL ADVISOR • SEPTEMBER 2011 101


Dermatologic Look-Alikes

allergic rhinitis. An allergic shiner associated with allergic rhinitis will improve as the rhinitis abates. Individuals with atopic dermatitis are at much greater risk of developing cataracts than are controls.26 The idea that steroid use causes cataracts in these patients has mostly been disapproved; the atopic genetic makeup is what leads to cataracts. Finally, there may be an association between longer eyelashes and atopic dermatitis.27 In this case, an allergist prescribed cetirizine (Zyrtec) syrup 5 mL nightly. In one month, the rash was much improved. ■

11. Lee M, Grassi M. Acanthosis nigricans in a patient treated with palifermin. Cutis. 2010;86:136-137. 12. Brown J, Winkelmann RK. Acanthosis nigricans: a study of 90 cases. Medicine. 1968;47:33-51. 13. Uyeda K, Sotomatsu S, Oshima Y. Malignant acanthosis nigricans: report of cases and electron microscopic observation. Acta Derm (Kyoto) 1974;69:7-13. 14. Bonnekoh B, Wevers A, Spangenberger H, et al. Keratin pattern of acanthosis nigricans in syndromelike association with polythelia, polycystic kidneys, and syndactyly. Arch Dermatol. 1993;129:1177-1182. 15. Fareau GG, Maldonado M, Oral E, Balasubramanyam A. Regression of acanthosis nigricans correlates with disappearance of anti-insulin receptor

Dr. Scheinfeld is assistant clinical professor of dermatology at Columbia University in New York City, where he has a private practice. Mr. Barnes is a fourth-year student at Dartmouth Medical School in Hanover, N.H. The authors have no relationships to disclose relating to the content of this article.

autoantibodies and achievement of euglycemia in type B insulin resistance syndrome. Metabolism. 2007;56:670-675. 16. Kapoor, S. Diagnosis and treatment of Acanthosis Nigricans. Skinmed. 2010;8:161-164. 17. Wasniewska M, Arrigo T, Crisafulli G, et al. Recovery of acanthosis nigricans under prolonged metformin treatment in an adolescent with normal


weight. J Endocrinol Invest. 2009;32:939-940.

1. Stuart CA, Pate CJ, Peters EJ. Prevalence of acanthosis nigricans in an

18. Srinivasan S, Ambler GR, Baur LA, et al. Randomized, controlled trial

unselected population. Am J Med. 1989;87:269-272.

of metformin for obesity and insulin resistance in children and adolescents:

2. Curth HO, Hilberg AW, Machacek GF. The site and histology of the cancer

improvement in body composition and fasting insulin. J Clin Endocrinol Metab.

associated with malignant acanthosis nigricans. Cancer. 1962;15:364-382.

2006;91:2074-2080. Available at

3. Andreev VC. Malignant acanthosis nigricans. Semin Dermatol 1984;3:265-272.

19. Bellot-Rojas P, Posadas-Sanchez R, Caracas-Portilla N, et al.

4. Groos EB, Mannis MJ, Brumley TB, Huntley AC. Eyelid involvement in

Comparison of metformin versus rosiglitazone in patients with Acanthosis

acanthosis nigricans. Am J Ophthalmol. 1993;115:42-45.

nigricans: a pilot study. J Drugs Dermatol. 2006;5:884-889.

5. Janier M, Blanchet-Bardon C, Bonvalet D, et al. Malignant acanthosis

20. Blobstein SH. Topical therapy with tretinoin and ammonium lactate for

nigricans associated with non-Hodgkin’s lymphoma. Report of 2 cases.

acanthosis nigricans associated with obesity. Cutis. 2003;71:33-34.

Dermatologica. 1988;176:133-137.

21. Lee HW, Chang SE, Lee MW, et al. Hyperkeratosis of the nipple associ-

6. Fox H, Gunn AD. Acanthosis nigricans and bronchial carcinoma. Br J Dis

ated with acanthosis nigricans: treatment with topical calcipotriol. J Am

Chest. 1965;59:47-50.

Acad Dermatol. 2005;52:529-530.

7. Ogbera AO, Akinlade A, Ajose O, Awobusuyi J. Prevalence of acantho-

22. Walling HW, Messingham M, Myers LM, et al. Improvement of

sis nigricans and its correlates in a cross-section of Nigerians with type 2

acanthosis nigricans on isotretinoin and metformin. J Drugs Dermatol.

diabetes mellitus. Trop Doct. 2009;39:235-236.


8. Mukhtar Q, Cleverley G, Voorhees RE, McGrath JW. Prevalence of

23. García Hidalgo L. Dermatological complications of obesity. Am J Clin

acanthosis nigricans and its association with hyperinsulinemia in New

Dermatol. 2002;3:497-506.

Mexico adolescents. J Adolesc Health. 2001;28:372-376.

24. Berger WE. Allergic rhinitis in children: diagnosis and management

9. Schwartz RA. Acanthosis nigricans. J Am Acad Derm. 1994;31:1-19.

strategies. Paediatr Drugs. 2004;6:233-250.

10. Ellis DL, Kafka SP, Chow JC, et al. Melanoma, growth factors, acantho-

25. Frankel A, Sohn A, Patel RV, Lebwohl M. Bilateral comparison study

sis nigricans, the sign of Leser-Trélat, and multiple acrochordons. A possi-

of pimecrolimus cream 1% and a ceramide-hyaluronic acid emollient

ble role for alpha-transforming growth factor in cutaneous paraneoplastic

foam in the treatment of patients with atopic dermatitis. J Drugs Dermatol.

syndromes. N Engl J Med. 1987;317:1582-1587.

2011;10:666-672. 26. Haeck IM, Rouwen TJ, Timmer-de Mik L, et al. Topical corticosteroids in atopic dermatitis and the risk of glaucoma and cataracts. J Am Acad


Dermatol. 2011;64:275-281.

Test your diagnostic skills. Our FREE archive of Dermatology Clinic and Dermatologic Look-Alikes is now available online at

27. Levy Y, Segal N, Ben-Amitai D, Danon YL. Eyelash length in children and adolescents with allergic diseases. Pediatr Dermatol. 2004;21:534-537. All electronic documents accessed August 15, 2011.



POSTTEST Expiration date: September 2012

The Nurse Practitioner Associates for Continuing Education (NPACE) is an approved provider of continuing education by the Massachusetts Association of Registered Nurses, Inc. (MARN), an accredited approver by the American Nurses Credentialing Center’s Commission on Accreditation (ANCC). The Nurse Practitioner Associates for Continuing Education designates this educational activity for a maximum of 1.0 contact hours of credit. Participants should only claim credit commensurate with the extent of their participation in the activity. Posttests must be completed and submitted online. NPs may register at no charge at must receive a score of 70% or better on each test taken to obtain credit.





Dermatology Clinic

Dermatologic Look-Alikes

page 55

page 85

page 99

Screening for functional deficits in older adults.

Case #1: Androgenetic alopecia

Case #1: Acanthosis nigricans (AN)

1. What is a characteristic of androgenetic alopecia in women? a. Sparing of the front hairline b. Increased susceptibility before puberty c. Stronger familial ties than in men d. Spironolactone (Aldactone) used in premenopausal period

1. Most cases of AN are linked with a. Ulcerative colitis b. Rheumatoid arthritis c. Gout d. Insulin resistance

1. What is the estimated percentage of individuals aged 65 years and older who have at least one chronic disease? a. 20% b. 40% c. 60% d. 80% 2. What activity is included on the MiniCognitive Assessment Instrument? a. Repeating three unrelated sentences. b. Listing medications taken on a daily basis. c. Drawing a simple clock setting d. Describing what the patient is eating. 3. What test is used to detect early indicators of Parkinson disease? a. Timed Up and Go Test b. Alternate Step Test c. Stair Ascent and Descent d. Heel-to-Toe Walking 4. What drug class may lead to incontinence in individuals with no previous episodes? a. Diuretics b. Sedative-hypnotics c. Anticholinergics d. All of the above TO TAKE THE POSTTEST please go to CMEFeatureSept2011

2. What is a side effect associated with finasteride (Propecia, Proscar) in men? a. Nasal congestion b. Gynecomastia c. Contact dermatitis d. Facial flushing Case #2: Erythema nodosum (EN) 3. EN is most commonly associated with what infection? a. Shigella b. Streptococcus c. Salmonella d. Campylobacter 4. Patients should be informed that which medication used to treat EN has been implicated as a rare cause of EN? a. Ibuprofen b. Colchicine c. Potassium iodide d. Codeine

TO TAKE THE POSTTEST please go to DermClinicSept2011

2. What is the most common malignancy associated with AN? a. Malignant lymphoma b. Bronchial carcinoma c. Gastric adenocarcinoma d. Squamous cell carcinoma of the cervix Case #2: Allergic shiner 3. Long-term use of which topical medication can lead to skin atrophy, telangiectasia, and striae? a. Clotrimazole b. Corticosteroids c. Benzoyl peroxide d. Neomycin 4. Individuals with atopic dermatitis are at much greater risk of developing a. Cataracts b. Glaucoma c. Conjunctivitis d. Arcus senilis

TO TAKE THE POSTTEST please go to CMEDermLookAlikeSept2011 • THE CLINICAL ADVISOR • SEPTEMBER 2011 103


POSTTEST Expiration date: September 2012

This program has been reviewed and is approved for a maximum of 1 hour of AAPA Category I CME credit by the Physician Assistant Review Panel. Approval is valid for one year from the issue date of August 2011. Participants may submit the self-assessment at any time during that period. This program was planned in accordance with AAPA’s CME Standards for Enduring Material Programs and for Commercial Support of Enduring Material Programs. Posttests must be completed and submitted online. PAs may register at no charge at To obtain 1.0 hour of AAPA Category I CME credit, you must receive a score of 70% or better on each test taken. CREDITS: 0.5




Dermatology Clinic

Dermatologic Look-Alikes

page 55

page 85

page 99

Screening for functional deficits in older adults.

Case #1: Androgenetic alopecia

Case #1: Acanthosis nigricans (AN)

1. What is a characteristic of androgenetic alopecia in women? a. Sparing of the front hairline b. Increased susceptibility before puberty c. Stronger familial ties than in men d. Spironolactone (Aldactone) used in premenopausal period

1. Most cases of AN are linked with a. Ulcerative colitis b. Rheumatoid arthritis c. Gout d. Insulin resistance

1. What is the estimated percentage of individuals aged 65 years and older who have at least one chronic disease? a. 20% b. 40% c. 60% d. 80% 2. What activity is included on the MiniCognitive Assessment Instrument? a. Repeating three unrelated sentences. b. Listing medications taken on a daily basis. c. Drawing a simple clock setting d. Describing what the patient is eating. 3. What test is used to detect early indicators of Parkinson disease? a. Timed Up and Go Test b. Alternate Step Test c. Stair Ascent and Descent d. Heel-to-Toe Walking 4. What drug class may lead to incontinence in individuals with no previous episodes? a. Diuretics b. Sedative-hypnotics c. Anticholinergics d. All of the above TO TAKE THE POSTTEST please go to CMEFeatureSept2011

2. What is a side effect associated with finasteride (Propecia, Proscar) in men? a. Nasal congestion b. Gynecomastia c. Contact dermatitis d. Facial flushing Case #2: Erythema nodosum (EN) 3. EN is most commonly associated with what infection? a. Shigella b. Streptococcus c. Salmonella d. Campylobacter 4. Patients should be informed that which medication used to treat EN has been implicated as a rare cause of EN? a. Ibuprofen b. Colchicine c. Potassium iodide d. Codeine

TO TAKE THE POSTTEST please go to DermClinicSept2011

2. What is the most common malignancy associated with AN? a. Malignant lymphoma b. Bronchial carcinoma c. Gastric adenocarcinoma d. Squamous cell carcinoma of the cervix Case #2: Allergic shiner 3. Long-term use of which topical medication can lead to skin atrophy, telangiectasia, and striae? a. Clotrimazole b. Corticosteroids c. Benzoyl peroxide d. Neomycin 4. Individuals with atopic dermatitis are at much greater risk of developing a. Cataracts b. Glaucoma c. Conjunctivitis d. Arcus senilis

TO TAKE THE POSTTEST please go to CMEDermLookAlikeSept2011 • THE CLINICAL ADVISOR • SEPTEMBER 2011 103

ALTERNATIVE MEDS UPDATE What you should know about the herbs and supplements patients use By Sherril Sego, FNP-C, DNP. Dr. Sego is a staff clinician at the VA Medical Center in Kansas City, Mo., where she practices adult medicine and women’s health. She also teaches at the nursing schools of the University of Missouri and the University of Kansas.



The world’s most popular morning beverage has been alternately praised and condemned. In addition to its beckoning aroma, coffee has many potent chemical entities and is far from a benign drink. Coffea arabica is believed to have been first grown in the ninth century in what is now Yemen.1 North and South Americans began growing coffee plants in the early 1700s.1 South America now produces more than 50% of the world’s coffee.

Science Because of the stimulant effect caffeine has on the central nervous system, concerns regarding hypertension and cardiac issues have been intensely studied. More than 1,000 men were followed for up to 33 years with periodic assessments of BP and daily coffee intake.2 This trial failed to show a strong link between coffee intake and the development of hypertension. A cohort of the Nurses’ Health Study followed more than 150,000 women who had no prior diagnosis of hypertension. After 12 years of monitoring, no linear association was found between coffee consumption and hypertension development.3 Another trial followed 44,000 men and 84,000 women for up to 20 years. Participants were monitored for the development of coronary heart disease as evidenced by either a fatal or nonfatal MI occurrence. Again, after all the data was examined, no evidence was found to link coffee consumption with an increased risk of heart disease.4

Coffee consumption has also been looked at in relation to the development of Alzheimer disease and Parkinson disease. The Cardiovascular Risk Factors, Aging and Dementia trial examined multiple factors. Among the more than 1,400 participants followed for up to 21 years, Alzheimer risk was 64% lower for those who had consistently consumed three to five cups of coffee per day since midlife compared with those drinking no or only little coffee.5 Although the effect of caffeine on cognitive function is assumed to be protective, it is not clearly understood. The proposed mechanism of action focuses on caffeine’s ability to interact with the dopaminergic and cholinergic systems in the brain, exerting a preservative effect on these functions where dementia diseases degrade them.5 In a 30-year longitudinal study of more than 8,000 men, the primary outcome measure was the incidence of the development of Parkinson disease relative to the estimated average daily coffee intake. Findings were highly suggestive of a protective mechanism of coffee intake against the


ALTERNATIVE MEDS UPDATE development of Parkinson disease. The standard age-adjusted incidence of Parkinson was 10.4/10,000 person-years for the men with no coffee intake, but only 1.9/10,000 person-years for men who drank at least 28 ounces of coffee per day.6 It was proposed that caffeine may prevent the inhibition of dopaminergic transmission by adenosine, which then reduces the clinical symptoms of Parkinsonism.6 Other studies of coffee and caffeine’s impact on neurodegenerative diseases show what appears to be an actual reduction in beta-amyloid production.7 Amyloids—chemical byproducts of multiple metabolic mechanisms—develop into thickened layers that block and inhibit normal function of cells and nerves, much like atherogenic plaque. Finally, coffee consumption has been shown to reduce the incidence of certain cancers. A recent meta-analysis found an estimated 24% lower risk of colon cancer per cup consumed.8 This protective effect, however, did not correlate with breast-cancer risk.

Safety, interactions Pregnant women who consumed <200 mg of caffeine per day had a 1.4 times higher rate of miscarriage than did non-coffee drinkers. When intake was >200 mg/day, the risk increased to 2.2 times greater.9 Coffee itself has few interactions but will accentuate the effects of any stimulant drug. Migraine medications as well as amphetaminetype drugs for behavior disorders show an additive effect when taken with coffee.

harvest, increased demand, and other international economic issues.

Summary Contrary to popular belief, coffee will not stunt your growth or contribute to your early demise. Although there are obvious situations in which coffee should be avoided, (e.g., pregnancy), moderate consumption is perfectly safe. ■ References 1. Purdue University Center for New Crops & Plant

Coffee consumption has been linked to lower incidence of dementia.

Products. Coffea Arabica L. Available at www.hort.purdue. edu/newcrop/duke_energy/coffea_arabica.html. 2. Klag MJ, Wang NY, Meoni LA, et al. Coffee intake and

Coffee itself has few interactions but will accentuate the effects of any type of stimulant drug.

risk of hypertension: the Johns Hopkins precursors study. Arch Intern Med. 2002;162:657-662. Available at archinte. 3. Winkelmayer WC, Stampfer MJ, Willett WC, Curhan GC. Habitual caffeine intake and the risk of hypertension in women. JAMA. 2005;294:2330-2335. 4. Lopez-Garcia E, van Dam RM, Willett WC, et al. Coffee consumption and coronary heart disease in men and women: a prospective cohort study. Circulation. 2006;113:2045-2053. Available at 5. Eskelinen MH, Ngandu T, Tuomilehto J, et al. Midlife coffee and tea drinking and the risk of late-life dementia: a population-based CAIDE study. J Alzheimers Dis. 2009;16:85-91. 6. Ross GW, Abbott RD, Petrovitch H, et al. Association of coffee and caffeine intake with the risk of Parkinson disease. JAMA. 2000 May 24-31;283(20):2674-9. Available at 7. de Mendonça A, Cunha RA. Therapeutic opportunities for caffeine in Alzheimer’s disease and other neuro-

Dose, how supplied, and cost

degenerative disorders. J Alzheimers Dis. 2010; 20 Suppl

Regular coffee contains 1% -2% caffeine as an active ingredient. A 6-oz. cup of coffee has anywhere from 60 to 120 mg of caffeine, depending on the brewing method. Coffee is found in multiple forms, from instant powders and crystals to whole roasted beans that may be ground to each consumer’s preference. The cost is very reasonable; however, it has increased by 44% since mid-2010, primarily due to a poor 106 THE CLINICAL ADVISOR • SEPTEMBER 2011 •

y67770t367q41176/fulltext.html 8. Arab L. Epidemiologic evidence on coffee and cancer. Nutr Cancer. 2010;62:271-283. Available at www 9. Weng X, Odouli R, Li DK. Maternal caffeine consumption during pregnancy and the risk of miscarriage: a prospective cohort study. Am J Obstet Gynecol. 2008;198:279. All electronic documents accessed August 15, 2011.


1:S1-S2. Available at

Evidence-Based Medicine This department uses the best available scientific findings to offer practice guidance on a wide range of conditions seen in primary care.The author, Alan Ehrlich, MD, is a deputy editor for DynaMed, Ipswich, Mass., and assistant clinical professor in Family Medicine, University of Massachusetts Medical School in Worcester. DynaMed ( is a database that provides evidence-based information on more than 3,200 clinical topics and is updated daily through systematic surveillance covering more than 500 journals.The most important evidence identified is summarized here.

ADDITION OF CONTROLLEDRELEASE COMBINATION OF PHENTERMINE AND TOPIRAMATE TO LIFESTYLE INTERVENTION MAY INCREASE WEIGHT LOSS IN OVERWEIGHT OR OBESE ADULTS Level 2: Mid-level evidence Phentermine was used for the medical management of weight loss in combination with fenf luramine or dexfenf luramine until side effects related to cardiac valvular disease and pulmonary hypertension were linked to the fenfluramine/dexfenfluramine component. Since then, phentermine has been used for weight loss either as monotherapy or in combination with other medications. The CONQUER trial evaluated the addition of a controlled-release combination of phentermine and topiramate to a lifestyle-and-diet intervention for weight loss and metabolic risk reduction in 2,487 patients who were overweight to morbidly obese (BMI 27-45). Patients were randomized to one of two doses of the study drug (high dose: phentermine 15 mg plus topiramate 92 mg; low dose: phentermine 7.5 mg plus topiramate 46 mg) vs. placebo once daily for 56 weeks. All patients had at least two weight-related comorbidities (hypertension, dyslipidemia, diabetes or prediabetes, or abdominal obesity). Outcome data were available for 69% of the patients at one year. Mean weight loss was 10.2 kg for the high-dose combination, 8.1 kg for the low-dose combination and 1.4 kg for placebo (p <0.0001). Significantly more patients in each combination group had weight loss of at least 5% compared with placebo (70% for high dose, 62% for low-dose, 21% for placebo, p <0.0001), with an NNT of three for each dose. The drug combination was associated with greater rates of dry mouth, paresthesia,

constipation, dizziness, and dysgeusia (Lancet. 2011;377:1341-1352). The weight loss seen with the low-dose phentermine combination was comparable to that found in a recent trial of controlled-release phentermine as monotherapy (Diabetes Obes Metab. 2010;12:876-882).

Mean weight loss was 10.2 kg for the high-dose combination, 8.1 kg for the low-dose combination, and 1.4 kg for placebo.

VARENICLINE MAY BE ASSOCIATED WITH SMALL INCREASED RISK OF CARDIOVASCULAR AND PSYCHIATRIC ADVERSE EVENTS Level 2: Mid-level evidence The FDA recently announced a labeling change for the smoking-cessation aid varenicline (Chantix) concerning cardiovascular risks. The concern arose largely from a trial in which 714 patients with stable cardiovascular disease were randomized to varenicline vs. placebo for 12 weeks. Cardiovascular events were reported in 7% of the varenicline group vs. 5.6% of controls, but this difference was not statistically significant (Circulation. 2010;121:221-229, available at, accessed August 15, 2011). The FDA has asked the manufacturer to provide a meta-analysis of its safety data for varenicline. In the meantime, independent investigators reported a systematic review of 14 randomized trials (including the trial cited above) evaluating the cardiovascular risks of varenicline. The other 13 trials (7,502 patients) all had much lower incidence of cardiovascular events (pooled The quality of the evidence supporting each item is rated from Level 1 (highest) to Level 3 (lowest). Absolute risk reductions are presented as the number needed to treat (NNT) for one patient to benefit. Absolute risk increases are presented as the number needed to harm (NNH). â&#x20AC;˘ THE CLINICAL ADVISOR â&#x20AC;˘ SEPTEMBER 2011 107

Evidence-Based Medicine


rates 0.593% vs. 0.237%), although the definition of cardiovascular outcomes varied across studies. In meta-analysis of these 13 trials, varenicline was associated with significantly increased risk (odds ratio 2.54, 95% CI 1.26-5.12), but the NNH was very high, ranging from 103 to 1,627 (CMAJ. 2011; published online ahead of print, available at www.cmaj .ca/content/early/2011/07/04/cmaj.110218.long, accessed August 15, 2011). The risk for psychiatric adverse events may be more concerning than these cardiovascular events. The FDA previously required a Boxed Warning to indicate increased risk of serious neuropsychiatric symptoms including changes in behavior, hostility, agitation, depressed mood, suicidal thoughts and behavior, and attempted suicide. Evidence for the risk of neuropsychiatric events has largely come from case reports, and there have been hundreds of cases reported to the FDA, including 272 cases of completed suicide (Institute for Save Medication Practices, available at quarterwatch/2010Q3.pdf, accessed August 15, 2011). However, quantifying this risk is uncertain, and the specific association with varenicline is unclear. A cohort study in 2009 with 80,660 patients found similar rates of self-harm among users of varenicline, bupropion and nicotine-replacement products (Level 2: Mid-level evidence) (BMJ. 2009;339:b3805, available at, accessed August 15, 2011). The risks of these potential adverse events must be weighed against the mortality benefit associated with smoking cessation and the demonstrated efficacy of varenicline as a

Swelling of the tissue in the orbit causes the eyes to bulge in patients with Graves’ orbitopathy.

cessation aid ( JAMA. 2008;299:2037-2047, available at jama, accessed August 15, 2011). In the trial cited by the FDA for cardiovascular risk, the varenicline group had significantly higher rates of confirmed continuous abstinence than did the placebo group from nine weeks to one year (19.2% vs. 7.2%, p <0.0001, NNT 9). Also, in a Cochrane review, varenicline was associated with higher rates of continuous abstinence compared with placebo (NNT 6-9 at 24 weeks in analysis of 10 trials with 4,443 patients). The most common adverse events were nausea, headache, and insomnia (Cochrane Database Syst Rev. 2011;2:CD006103).

SELENIUM IMPROVES QUALITY OF LIFE AND OPHTHALMOLOGIC OUTCOMES IN PATIENTS WITH GRAVES’ ORBITOPATHY Level 1: Likely reliable evidence Graves’ disease is the most common cause of hyperthyroidism and frequently causes changes to the eye and surrounding structures, including retraction of the eyelid, bulging of the eye, and restricted eye movements. Even mild symptoms can affect quality of life. A recent randomized trial evaluated the efficacy of two drugs, selenium and pentoxifylline, to either improve or limit the progression of symptoms in patients with mild Graves’ orbitopathy (N Engl J Med. 2011;364:1920-1931, available at www.nejm .org/doi/full/10.1056/NEJMoa1012985, accessed August 15, 2011). A total of 159 patients were randomized to selenium 100 mcg orally twice daily vs. pentoxifylline 600 mg orally twice daily vs. placebo for six months. Quality of life was measured on a 100-point scale that included measures of visual function and appearance. A change of at least six points was considered clinically important. At six months follow-up, the selenium group had increased rates of clinically important improvement (74% vs. 24% for placebo, p <0.001, NNT 2) and decreased rates of clinically important worsening (17% vs. 44%, p <0.001, NNT 3). Selenium was also associated with higher rates of improvement in overall ophthalmologic assessment (61% vs. 36%, p <0.01, NNT 4). This difference was primarily due to significant improvements in eyelid aperture and soft-tissue signs in the selenium group. There were no significant differences in proptosis or eye-muscle motility. The improvements seen in the selenium group persisted at 12-month follow-up. There were no significant differences between pentoxifylline and placebo in quality-of-life scores or ophthalmologic outcomes, but pentoxifylline was associated with increased risk of skin and GI adverse events. ■ • THE CLINICAL ADVISOR • SEPTEMBER 2011 117

COMMENTARY Rachael Buitrago, CPNP, is an ANCC-board-certified pediatric nurse practitioner in a private office in South Florida, and has taught as adjunct nursing faculty at local universities.

Adolescents need HPV shots early It’s very frustrating to work in health care today. As a nurse practitioner working in pediatrics, I’ve always spent some portion of an office visit talking to patients and parents about preventive health measures, but somewhere over the past several decades, health-promotion and disease-prevention efforts have been lost. Today’s providers now see the need to focus on preventive medicine with acute care, but the question is: Are we really doing enough to promote health? Practitioners need to take a look at adolescents and young adults and devise a plan that will teach parents the benefits of healthy lifestyles for themselves and their children. Statistics show

Remember, this is a sexually transmitted infection that is spread through skin-to-skin contact.

that most first sexual encounters occur in the seventh grade, when the average student is 12 to 13 years of age. According to the CDC, risky sexual behavior is the leading cause of morbidity and mortality among U.S. adolescents. Each year, there are approximately 19 million new sexually transmitted disease (STD) infections, almost half of which afflict individuals aged 15 to 24 years. And let’s not forget about teen pregnancy. These risks have been noticeably rising as the incidence of human papillomavirus (HPV) increases. HPV is the most common sexually transmitted infection in the nation, with an estimated 6 million new cases each year. More than 100 types of HPV affect humans; 40 involve the genital areas. HPV types 16 and 18 are responsible for cervical cancer in females, but the virus is also responsible for penile and anal cancers in males and oropharynx cancers in both genders. Research shows that HPV is transmitted not only through bodily fluids but through skin-to-skin contact as well. Gardasil is a quadrivalent vaccine intended for the prevention of HPV types 16 and 18 as well as types 6 and 11, which are responsible for genital warts in both genders. The vaccine is administered as a series of three injections over the course of six months. It is recommended for females and males aged 9 to 26 years. Although the vaccine’s purpose is to prevent HPV that may lead to cervical cancer,

commercials for the product don’t state that HPV also causes genital warts or that it’s the most common STD in the adolescent age group. This underrepresentation of the harmful effects of HPV may put the public at risk. Common reasons that parents give when declining the vaccine for their children are, “My teen is not sexually active,” or “Maybe we’ll wait until he/she is a bit older.” This thinking negates the vaccine’s preventive purpose. Parents who are educated as to how HPV is spread and the benefits of the vaccine often change their minds about approving it for their son or daughter. Remember, this is an STD that is spread through skin-to-skin contact. Also, an adolescent who is not sexually active today may be a mere six months down the road—the amount of time it takes to administer the HPV vaccine. The idea is to vaccinate the individual prior to his or her participation in any sexual behaviors. Vaccination most definitely does not serve as the “go-ahead” for teens to engage in sexual activity; it merely protects against one STD that can be fatal later in life. Many other STDs can still be contracted through unprotected sex following HPV vaccination. As health-care professionals, it is our duty to educate parents on the full benefits of the HPV vaccine. We must also encourage adolescents to make informed decisions when considering entering into sexual relationships. ■ • THE CLINICAL ADVISOR • SEPTEMBER 2011 119


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NP WANTED Crozer-Keystone Health Network (CKHN) is the largest primary care and specialty physician network in Delaware County, Suburban Philadelphia, and a member of the Crozer-Keystone Health System (CKHS), the largest employer in Delaware County with over 7000 employees, encompassing five hospitals and several outpatient pavilions. Delaware County Memorial Hospital and Crozer-Chester Medical Center, the largest of the five hospitals, are Certified Stroke Centers. Crozer-Keystone Health Network (CKHN) has several opportunities: • The Department of Endocrinology is seeking a full-time Nurse Practitioner for their busy multiphysician, multi-location practice. Position responsibilities include, but are not limited to, providing patient care services in the inpatient and ambulatory settings through assessments and exams, ordering diagnostic procedures and developing treatment plans. • The Department of Neurology is seeking a full-time Nurse Practitioner for their Delaware County Memorial Hospital location in general neurology, providing patient care services in the inpatient and ambulatory settings. A Physician Assistant or Nurse Practitioner is also being sought for their Taylor Hospital campus working primarily in the outpatient setting of the Sleep Medicine division.

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In all opportunities, the PA/NP will work under the direction of an assigned physician and will follow established medical protocols. This incumbent will demonstrate a high level of autonomy and will participate in case management and continuing care collaborating with attending physicians, specialists, and other members of the health care team to deliver effective, efficient, safe and high quality care. • Board certification and State licensure required • Two years experience in the respective role preferred • Experience with electronic medical record strongly desired CKHN offers competitive salary and provides a generous benefits package including medical/dental/ vision insurance, paid holidays, paid time off, tuition reimbursement, and more. To learn more about CKHS, please visit Please submit CV and salary requirements to Pam DeVito, Administrative Director via email: • THE CLINICAL ADVISOR • SEPTEMBER 2011 121


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September 2011 Clinical Advisor  
September 2011 Clinical Advisor  

The Clinical Advisor is a monthly journal for nurse practitioners and physician assistants in primary care. Its mission is to keep practitio...