March 2013 Clinical Advisor

THE CLINICAL ADVISOR •MARCH 2013

A F O RU M F O R N U R S E P R AC T I T I O N E R S

NEWSLINE

■ Eat earlier to lose weight ■ Imaging for Alzheimer ■ Biases in prostate screening ADVISOR FORUM

■ Overuse of antibiotics ■ Refractory lip blister ■ Myasthenia gravis tip-off LEGAL ADVISOR

Unusual patient arrangement leads to a malpractice suit

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■ Dermatology Clinic

ULCER ON THE ARM OF A TRAVELER PAGE 57

■ Dermatologic Look-Alikes VOLUME 16, NUMBER 3

BILATERAL LOWER LEG PLAQUES PAGE 69 Take the Scavenger Hunt Challenge and Win an iPad! Turn to p. 28 for details

| M A R C H 2 013 | www.ClinicalAdvisor.com

CE: CERVICAL CANCER

VACCINATION The human papillomavirus (yellow) can cause normal cells on the cervix to turn abnormal.

Editor Joe Kopcha, editor@clinicaladvisor.com Managing editor Marina Galanakis Senior editor Delicia Yard Web editor Nicole Blazek Contributing editors Bruce D. Askey, MSN, CRNP; Rebecca H. Bryan, APRN, CNP; Eileen F. Campbell, MSN, CRNP; Philip R. Cohen, MD; Deborah L. Cross, MPH, CRNP, ANP-BC; Sharon Dudley-Brown, PhD, FNP-BC; Maria Kidner, DNP, FNP-C; Joan W. Kiely, MSN, CRNP; Debra August King, PhD, PA; Ann W. Latner, JD; Claire B. O’Connell, MPH, PA-C; Kathy Pereira, MSN, FNP-BC; Sherril Sego, FNP, DNP; Julee B. Waldrop, MS, PNP; Kim Zuber, PA-C Art director Andrew Bass Group art director, Haymarket Medical Jennifer Dvoretz Group production manager Kathleen Millea Circulation manager Paul Silver Audience development director John Crewe National accounts manager Alison McCauley, 646.638.6098 alison.mccauley@haymarketmedical.com Group publisher Thomas P. Hennessy, 646.638.6085 tom.hennessy@haymarketmedia.com Editorial director Jeff Forster Vice president, medical magazines and digital products Jim Burke CEO, Haymarket Media, Inc. Lee Maniscalco All correspondence to: The Clinical Advisor 114 West 26th Street, 4th Floor, New York, NY 10001 For advertising sales, call 646.638.6075.

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Copyright © 2013.

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www.ClinicalAdvisor.com • THE CLINICAL ADVISOR • MARCH 2013 3

CONTENTS MARCH 2013

NEWS AND COMMENT

■ A man develops a large arm ulcer after

traveling through Central America.

11

83

Newsline ■ For weight loss, you are when you eat ■ Imaging guidelines for Alzheimer disease ■ And more

Alternative Meds Update Fenugreek promotes lactation and affects glucose and lipid metabolism.

69

CME/CE Dermatologic Look-Alikes Can you differentiate between these plaques on the lower extremities?

74

CME/CE Posttest

78

Evidence-Based Medicine

Commentary The pathophysiologic effects of BPA 38

FEATURES 32

64

CME/CE Primary-care prevention of cervical cancer Awareness of current vaccination and screening guidelines help reduce the mortality and incidence of this disease.

ADVISOR FORUM 48

38

What is BPA and what does it do to the body?

Used in food and drink packaging, this chemical has been linked to obesity, diabetes, and reproductive disorders.

Hypopigmented arm macules 57

49

Derm Dx Read the clinical descriptions, view the images, and make your diagnosis at ClinicalAdvisor.com.

Clinical Pearls ■ Reflux disease and ear pain ■ Fish oil to avoid constipation ■ Easing pain during suturing

DEPARTMENTS 54

Consultations ■ Reducing intracranial pressure after head injury ■ Avoid overuse of antibiotics ■ And more

50

Your Comments ■ Another tip-off to myasthenia gravis ■ Reporting medical fraud can be

difficult, but worth it 55

Legal Advisor An unusual agreement causes a clinician to miss an advanced case of colon cancer.

57

CME/CE Dermatology Clinic ■ White spots on a man’s arms and chest worsen after sun exposure.

MAKING CONTACT

Follow us on Twitter @ClinicalAdvisor

Fenugreek at meals improves satiety 64

Like us on Facebook facebook.com/TheClinicalAdvisor

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Visit us on the web ClinicalAdvisor.com

Go mobile with us mobile.ClinicalAdvisor.com

EXCLUSIVE TO THE WEB AT

ClinicalAdvisor.com/web-only Web Exclusives

The Waiting Room

ClinicalAdvisor.com/WebExclusives

Official Blog of The Clinical Advisor ClinicalAdvisor.com/Blog

Depression lowers efficacy of shingles vaccine Elderly individuals with depression have diminished response to the shingles vaccine, but antidepressants may help.

Robyn Carlisle, MSN, CNM, WHNP How do you handle rude patients?

Difficult interactions with patients can damage or preclude a therapeutic relationship between provider and patient.

Cephalosporin-resistant gonorrhea emerging in the United States Neisseria gonorrhoeae is developing resistance to the only remaining class of antimicrobials available to treat gonococcal infections, the CDC reports.

Sharon M. O’Brien, MPAS, PA-C Prescribing sleep aids wisely Time demands may make it easier to give a patient a sleep aid the first time they ask, but it isn’t always the best practice.

Tedizolid equivalent to linezolid for skin infections Skin and soft tissue infections responded equally well to linezolid (Zyvox) or a short course of the investigational agent tedizolid.

Julee Waldrop, DNP, PNP, FNP Navigating healthcare services for premature infants Accessing developmental evaluations and services is one of the biggest challenges preemies and their families face.

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

CliniAd.com/15vWwrF

Cartoon Archive

The Clinical Advisor’s monthly cartoons are now available online as well.

Vesicles on a wrestler’s feet A high-school wrestler who wore leather sneakers during the day developed small, itchy blisters on his feet. What is your diagnosis?

MAKING CONTACT

Follow us on Twitter @ClinicalAdvisor

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8 THE CLINICAL ADVISOR • MARCH 2013 • www.clinicaladvisor.com

“Did you catch the guy who did it?”

Visit us on the web ClinicalAdvisor.com

Go mobile with us mobile.ClinicalAdvisor.com

© Roy Delgado

ClinicalAdvisor.com/ cartoons

Newsline

Finding victims of intimate partner violence page 16

M A R C H 2 0 13

Heart-helping drugs are under-prescribed page 26

How to help older patients with constipation page 26

© SCIENCE SOURCE / JIM VARNEY

For weight loss, you are when you eat

Those who ate their main meal earlier lost more weight.

and metabolic syndrome,” clarified lead study author Ishwarlal Jialal in a statement announcing his group’s findings, which were published online ahead of print by The Journal of Clinical Endocrinology & Metabolism. “But our research helps to dispel the myth that gluteal fat is ‘innocent.’ ” In persons with early metabolic syndrome, gluteal fat secreted high levels of chemerin and low levels of omentin-1. These proteins correlate with other factors known to increase the risk for heart disease and diabetes: For example, elevated chemerin levels correlated with high blood pressure, elevated levels of C-reactive protein and triglycerides, low levels of HDL, and insulin resistance.

Low levels of omentin-1 correlated with heightened triglyceride and blood glucose levels as well as low levels of HDL.

Women who have used emergency contraception According to the CDC, 5.8 million sexually experienced women aged 15–44 years had ever used emergency contraception in 2006–2010.

11

12 10 Percent

PATIENTS TRYING to shed excess pounds may be helped by learning that the timing of their meals is an important and independent factor in weight-loss success.

Specifically, eating the big meal of the day earlier may be associated with better weight loss.

A team in Spain led by Marta Garaulet, PhD, studied 420 individuals who followed a 20-week weight-loss regimen. The participants (49.5% female; mean age 42 years; mean BMI 31.4) were grouped into early eaters and late eaters based on whether they had their lunch—the main meal in this Mediterranean population— before or after 3:00 pm.

Those having an early lunch lost more weight and lost weight at a faster pace than did the late eaters.

Energy intake, estimated energy expenditure, dietary composition, appetite hormones, and sleep duration were similar between the two

groups. However, the late eaters had less energy-producing breakfasts and skipped breakfast more frequently than the late eaters.

“Novel therapeutic strategies should incorporate not only the caloric intake and macronutrient distribution—as is classically done—but also the timing of food,” suggested Garaulet and coauthors in International Journal of Obesity.

Clinicians should also be aware of new research indicating that pear-shaped bodies—in which more weight is carried in the buttocks, hips, and thighs—are not healthier than apple-shaped physiques, which are characterized by more abdominal fat.

“Fat in the abdomen has long been considered the most detrimental to health, and gluteal fat was thought to protect against diabetes, heart disease,

8 6

4

4 2

1

0 Source: CDC/NCHS, National Survey of Family Growth, 1995, 2002, and 2006–2010

1995

2002

2006-2010

www.ClinicalAdvisor.com • THE CLINICAL ADVISOR • MARCH 2013 11

Newsline THE FIRST criteria for the appropriate use of positron emission tomography (PET) to aid in the diagnosis of Alzheimer disease (AD) have been published jointly by the Society of Nuclear Medicine and Molecular Imaging and the Alzheimer’s Association.

The guidelines, by Keith A. Johnson and colleagues, appear online ahead of print The Journal of Nuclear Medicine.

Elevated levels of beta amyloid plaques in the brain are one of the defining pathologic features of AD. However, many otherwise normal elderly people have increased levels of these plaques, as do patients with conditions other than AD. Therefore, the clinical utility of PET imaging for beta amyloid plaques requires careful consideration.

The new guidelines state that appropriate candidates for amyloid PET imaging include patients with persistent or progressive unexplained mild cognitive impairment; patients satisfying core clinical criteria for possible AD (that is, atypical clinical course or etiologically mixed presentation); and patients with atypically young-onset dementia.

Conversely, such imaging is not appropriate for the diagnosis of patients who have core clinical criteria for probable AD with typical age of onset; for patients with a cognitive complaint that is unconfirmed on clinical examination; or for asymptomatic individuals. Amyloid PET imaging also should not be used: to determine dementia severity; when based solely on a positive family

© SCIENCE SOURCE

Imaging guidelines for Alzheimer disease

PET shows a normal brain (left) and one afflicted with AD (right).

history of dementia or presence of apolipoprotein E e4; in lieu of genotyping for suspected autosomal mutation carriers; or for nonmedical usage, such as for insurance, legal, or employment decisions. Medicare currently does not cover beta amyloid PET imaging.

THE UNITED States Preventive Services Task Force (USPSTF) now recommends that all women of childbearing age be screened to determine whether these patients are victims of intimatepartner violence (IPV), even if the women show no signs or symptoms of abuse.

Nearly 31% of women and 26% of men report experiencing some form of IPV in their lifetime, noted the statement, published online ahead of print by Annals of Internal Medicine. Writing on behalf of the USPSTF, Virginia A. Moyer, MD, MPH, also pointed

Screen even if there are no signs or symptoms of abuse.

out that these estimates likely are an under-representation due to under-reporting.

Although all women are at potential r isk for abuse, the USPSTF stated that young age, substance abuse, marital difficulties, and economic hardships elevate risk.

The task force identifies several IPV screening instruments.

Those with the highest levels of sensitivity and specificity for identifying IPV are Hurt, Insult,

16 THE CLINICAL ADVISOR • FEBRUARY 2013 • www.ClinicalAdvisor.com

Threaten, Scream (HITS ); O n g oi n g A b u s e S c r e e n / Ongoing Violence Assessment Tool (OAS/OVAT); Slapped, Threatened, and Throw (STaT); Humiliation, Afraid, Rape, Kick (HARK); Modified Childhood Trauma Questionnaire–Short Form (CTQ-SF); and Woman Abuse Screen Tool (WAST).

No evidence regarding appropriate intervals for screening was found.

Women who screen positive for IPV should be provided with, or referred to, intervention services.

© THINKSTOCK

Screen women for intimate-partner violence

Newsline PRIMARY-CARE practitioner beliefs about prostate-cancer screening account for much of the variability in the use of an informed-decision-making process by these providers (Ann Fam Med. 2013;11:67-74).

A nationwide survey completed by 246 family physicians between July 2007 and January 2008 compared physicians who ordered screening without first discussing the potential harms and benefits with the patient (24.3% of respondents) with physicians who did hold such discussions and who subsequently let the man decide whether he wanted the test (47.7% of respondents). Members of the latter group were more likely to endorse beliefs that scientific evidence does not support screening, that patients should be told about the lack of evidence, and that patients have a right to know the limitations of screening. These providers were also less likely to support the belief that a patient who wanted to be screened did

Providers who advised testing were concerned about legal risks.

not need to be educated about the test’s harms and benefits.

Among the physicians who did discuss the harms and benefits of prostate-cancer screening with patients, the providers who then recommended such testing were more likely to be concerned about the medicolegal risks associated with not screening than were physicians who let the patient decide.

The screening decision might be helped by the fi ndings of a recent computer model of 35 screening strategies that varied by start and stop ages, screening intervals, and thresholds for biopsy referral (Ann Intern Med. 2013;158:145-153). The model demonstrated that compared with standard screening, prostatespecific antigen (PSA) screening strategies that use higher thresholds for biopsy referral for older men and that screen men with low PSA levels less frequently can reduce harms while preserving lives.

Review addresses constipation in seniors A nine-step process to help older patients manage constipation includes identifying symptoms and possible secondary causes, veryifying or excluding impaction, optimizing behavior, modifying diet, and undergoing trials of various laxatives.

In their CMAJ review of treatments, Dov Gandell and colleagues further advised referral to a gastroenterologist or geriatrician as the final step in the process if none of the other steps resolved the problem.

Evidence indicated that polyethylene glycol, lactulose, or other osmotic agents can increase the secretion of water in the colon, but also can cause bloating, gas, and diarrhea. No strong evidence supports the use of such soluble fibers as psyllium. Stimulant laxatives have been shown to be effective, but long-term use may reduce effectiveness.

Exercise and increased fluid intake were not shown to relieve constipation, but have other health benefits.

26 THE CLINICAL ADVISOR • FEBRUARY 2013 • www.ClinicalAdvisor.com

Aspirin and diuretics underused ALTHOUGH THE role of aspirin in the secondary prevention of MI, and stroke, as well as death from vascular causes, has been well established, primary-care clinicians are not prescribing enough antiplatelet medications for the secondary prevention of cardiovascular events. Similarly, too few black patients with hypertension are being prescribed diuretic drugs, despite the fact that these low-cost agents are effective for this group.

Recent national surveys showed that general-medicine or primarycare physicians prescribed aspirin or other antiplatelets to patients with ischemic vascular disease only 34.8% of the time in 2007– 2008. This represented a decline from the 37.9% rate recorded for 2005–2006 (N Engl J Med. 2013;368:204-205).

“Though some patients may not be receiving antiplatelet medications because of valid contraindications, the vast majority of these patients would be candidates,” contend the researchers.

A separate research team found that most black patients in one study were still not receiving a diuretic—despite widely publicized recommendations for the use of such drugs as a first-line or add-on agent in the management of hypertension, particularly among blacks with resistant hypertension (Am J Hypertension.

2013;26:174-179). ■

© THINKSTOCK

Biases in prostate screening

Take the Scavenger Hunt Challenge March edition

Correctly answer the questions below— all of which can be found within this issue of The Clinical Advisor—and you’ll be entered into a random drawing to win an Apple iPad mini.

To submit your responses, simply go to CliniAd.com/1287ftI. QUESTIONS 1. What percentage of women report experiencing some form of intimate partner violence in their lifetime? (p. 16) 2. In 2007–2008, how frequently did primary-care physicians prescribe antiplatelets to patients with ischemic vascular disease? (p. 26) 3. Approximately how many cases of cervical cancer will be diagnosed in the United States in 2013? (p. 32) 4. What two strains of human papillomavirus (HPV) are the etiologic agents in approximately 70% of all cases of cervical cancer? (p. 33) 5. When did the FDA officially ban bisphenol A (BPA) in baby bottles and children’s drinking cups? (p. 43) 6. What three antivirals are used to treat recurrent herpes labialis? (p. 49) 7. What yeast causes the skin infection tinea versicolor? (p. 58) 8. Where is more than 80% of the world’s fenugreek produced? (p. 64) 9. In what year was the disorder “dermatitis atrophicans diabetica” renamed “necrobiosis lipoidica diabeticorum?” (p. 71) 10. Treatment with what substance has been shown to reduce mortality in newborns with respiratory distress syndrome? (p. 80)

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CME CE

PROGRAM OUTLINE MARCH 2013

0.5 CREDITS

Page 32 FEATURE Primary-care prevention of cervical cancer Denise M. Linton, DNS, FNP-BC Denise M. Linton, DNS, FNP-BC, has no relationships to disclose relating to the content of this article.

■ LEARNING OBJECTIVES: • Describe the risk factors for cervical cancer.

• Discuss the special clinical information to consider when providing cervical cancer vaccines.

• Name the infection most common in women using an intrauterine device.

• Explain when a Pap test must be repeated in a patient not considered high-risk.

0.5 CREDITS

Page 57 DERMATOLOGY CLINIC Discoloration worsens following sun exposure Esther Stern, NP Esther Stern, NP, has no relationships to disclose relating to the content of this article.

Arm ulcer on a Latin American immigrant Adam Rees, MD Adam Rees, MD, has no relationships to disclose relating to the content of this article.

■ LEARNING OBJECTIVES: • To identify and diagnose dermatologic conditions and review up-to-date treatment.

Page 69 DERMATOLOGIC LOOK-ALIKES Plaques on the lower extremities Kerri Robbins, MD Kerri Robbins, MD, has no relationships to disclose relating to the content of this article.

■ LEARNING OBJECTIVE: • To distinguish and properly treat dermatologic conditions with similar presentations.

Page 74 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 March 2013. 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.

Nurse Practitioner Associates for Continuing Education (NPACE) is accredited as a provider of continuing nursing education by the American Nurses Credentialing Center’s Commission on Accreditation.

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.

www.ClinicalAdvisor.com • THE CLINICAL ADVISOR • MARCH 2013 31

TABLE 1. Cervical cancer vaccines Cervarix

Gardasil

Manufacturer

GlaxoSmithKline

Merck & Co., Inc.

FDA approval

2010

2006

Vaccine type

Bivalent

Quadrivalent

Indications for use

Prevention cervical dysplasia and cancer caused

by HPV types 16 and 18

• Prevention of cervical, vaginal, vulvar, and anal dysplasia and cancer caused by HPV types 16 and 18 • Prevention genital warts caused by HPV types 6 and 11 in females and males

Age

Females age 10 to 25 years

Females and males age 9 to 26 years

Administration

0.5 mL intramuscularly

0.5 mL intramuscularly

Frequency of administration

Second dose one month after first dose; third dose six months after first dose

Second dose two months after first dose; third dose six months after first dose

Caution and contraindications

Latex allergy, pregnancy, nursing mothers

Yeast allergy, pregnancy, nursing mothers

Adverse effects

Fatigue, headache, myalgia, GI upset, arthralgia, syncope, local reaction

Heacache, fever, dizziness, syncope, seizure-like activity, local reaction

TABLE 2. Cervical cancer screening guidelines Organization

Age at first Pap test

Age at final Pap test

Frequency of screening

American College of Obstetricians and Gynecologists

21 years

65 to 70 years if more than three normal results and no abnormal results in the preceding 10 years

Every two years if younger than age 30 years; every two to three years if older than age 30 years with three consecutive normal results

American Cancer Society

21 years

65 years or older if at least three successive negative Pap tests or at least two negative Pap/HPV tests in the preceding 10 years

Every three years with either Pap test or liquid-based cytology if younger than age 30 years (every five years with Pap/HPV test preferred for women age 30-65 years)

U.S. Preventive Services Task Force

21 years

65 years

Every three years with Pap test or every five years with Pap/HPV tests

Precancerous lesions may be treated by destroying tissue with heat (i.e., electrocoagulation) or cold (i.e., cryotherapy). When there is extensive involvement of the cervical cells, laser ablation or local surgery may be performed. Invasive cervical cancers are generally treated with surgery, radiation, or both, and with chemotherapy in select cases.1 Strategies to prevent cervical cancer include vaccines, screening with the Pap test, and follow-up of abnormal Pap test results. A provider recommendation is a strong predictor of participation in a health-related behavior; primary-care clinicians are well positioned to assist women with participation in health-related behaviors that could result in a reduction in cervical cancer mortality and incidence.

Cervical cancer vaccines

More than 90% of all cases of cervical cancer are caused by HPV. Although there are more than 100 strains of HPV, types 16 and 18 are the etiologic agents in approximately 70% of all cases of cervical cancer.2 Two pharmaceutical companies received FDA approval for cervical cancer vaccines that have proven to be effective against the two oncogenic HPV strains. Primary-care clinicians need to be knowledgeable about these vaccines to provide patients, families, and caregivers with accurate information. This will allow these individuals to make informed decisions regarding vaccination. Table 1 contains relevant information about the Cervarix and Gardasil vaccines, including manufacturer; year of FDA approval; indications for use; indicated ages and gender; mode, dosage, and frequency

www.ClinicalAdvisor.com • THE CLINICAL ADVISOR • MARCH 2013 33

CME CE

CERVICAL CANCER

of administration; cautions and contraindications; and some adverse effects.2-5 Research findings

In addition to the information depicted in Table 1, primarycare clinicians need to be aware of the findings of research studies that surround the administration of the cervical cancer vaccines. This special information must than be applied to clinical practice.

Randomized clinical trials demonstrate that Gardasil: • Prevents the development of cervical intraepithelial neoplasia 2 (CIN 2) or greater that is caused by HPV type 16 or 18 among women who have never been infected • Is 97% to 100% more effective in individuals who have never had sex • Has a 44% efficacy in individuals with or without prior infection • Is effective against HPV types that are closely related to HPV types 16 and 18 and cause 20% of all cases of cervical cancer (HPV types 31, 33, 45, 52, and 58 are closely related to HPV 16, and HPV 45 is closely related to HPV 18) • Provides an average duration of protection of 42 months (there is ongoing research to determine whether the duration of protection is longer).2,3 Additional observations were made during the preand post-licensure surveillance phases of Gardasil. Mild injection-site reaction occurred during pre-licensure.

During post-licensure surveillance (between June 1, 2006 and December 31, 2008), more than 12,000 adverse events occurred. Fewer than 10% of the adverse events were serious, and most adverse reactions were similar to those of other vaccines.2 All adverse events, syncope, and venous thromboembolic events that were reported by individuals who received the vaccine are still being monitored by the CDC. Because of the possibility of syncopal episodes and subsequent falls and injury, any individual who is given Gardasil should be observed for at least 15 minutes after receiving the vaccine.2 Thromboembolic events commonly occurred in women who were on oral contraceptive pills (OCPs) or who had a family history of clotting disorder,2 so be sure to inquire about these topics when taking a patient’s history. If an individual with a personal history of OCP use or a family history of clotting disorder decides to be vaccinated, he or she should be informed of the risk for adverse events and the signs and symptoms of thromboembolic diseases. Instruct patients to report to the emergency department immediately if such signs and/or symptoms occur.

Randomized clinical trials demonstrate that Cervarix: • Is well tolerated • Has a 93% efficacy in HPV-naïve individuals • Has a decline in efficacy of 30% in individuals with or without HPV who have had sex • Has a 50% efficacy among individuals with non-vaccine HPV types.4 There is no post-licensure surveillance on Cervarix at this time.

Special information

Primary-care providers need to be aware of some special clinical information regarding both available cervical cancer vaccines.

• H PV DNA serolog y is un necessa r y pr ior to vaccination.

• It is not necessary to monitor individuals with postvaccination titers.

• Vaccines are not contraindicated in individuals who were previously infected with HPV, since these patients could be infected with other strains of HPV. • It is safe to administer Gardasil at the same time as the hepatitis B vaccine; the meningococcal vaccine; and the tetanus, diphtheria, and pertussis vaccine, but these should be administered at different sites.

• If the cervical cancer vaccine is administered to patients who are being treated with immunosuppressive therapies TABLE 3. Indications for colposcopy Persistent atypical squamous cells of undetermined significance (ASC-US), ASC-US with positive high-risk HPV Atypical squamous cells cannot exclude a high-grade squamous intraepithelial lesion (ASC-H) Atypical glandular cells (AGC) Low-grade intraepithelial lesions (LSIL) High-grade intraepithelial lesions (HSIL) Invasive cancer that is suspicious The presence of malignant cells

TABLE 4. Indications for endocervical curettage or sampling ASC-US LSIL HSIL AGC Adenocarcinoma in situ

34 THE CLINICAL ADVISOR • MARCH 2013 • www.ClinicalAdvisor.com

TABLE 5. Management of ASC-US or LSIL in women age 30 years or younger Repeat Pap test in 12 months.

If less than HSIL, repeat Pap test in 12 months.

If repeat Pap test is negative, return to routine screening.

Refer for colposcopy if ASC-US or higher.

TABLE 6. Management of HSIL or higher in women age 30 years or younger Refer for colposcopy.

If colposcopy is negative for CIN 2 or CIN 3, observe with colposcopy and repeat Pap test every six months for two years.

If HSIL persists without CIN 2 or CIN 3, perform diagnostic excisional procedure.

If HSIL or high-grade colposcopy persists for one year, perform biopsy.

If biopsy is negative, patient is observed; further management is necessary if biopsy is positive.

TABLE 7. Management of nonpregnant adults with ASC-US Repeat Pap test every six months for one year; if both tests are negative, return to routine screening; if ASC or higher, refer for colposcopy.

If colposcopy is negative and HPV status is unknown, repeat Pap test in one year.

If colposcopy is negative and HPV is positive, repeat Pap test every six months for one year or perform HPV DNA testing in one year.

If Pap test result is ASC or higher or HPV-positive, refer for colposcopy.

If HPV DNA test is negative, return to routine screening.

(e.g., corticosteroids or irradiation), there may be a reduced immune response to the vaccine.

• Pregnancy registries monitor the outcome of the fetus that is born to a woman who was inadvertently vaccinated during pregnancy.

• If an individual misses doses, it is not necessary to restart the series.

• Adverse events should be reported to Vaccine Adverse Event Reporting System (VAERS) at www.vaers.hhs.gov or 800.822.7967.2,4,5 Vaccine limitations

In addition to discussing with patients vaccine benefits, effects, and contraindications as well as results of research studies, clinicians need to address the limitations of the cervical cancer vaccines. Patients need to be informed that (1) the vaccines are not used for the treatment of such active diseases as genital, anal, vulvar, vaginal, or cervical

lesions and dysplasia; (2) the vaccines do not protect all recipients; (3) vaccine effectiveness has not been demonstrated in women who are older than age 26 years; and (4) women who are vaccinated need to continue Pap testing as recommended by their primary-care provider.1,5 The Pap test is the primary method of cervical cancer prevention because it facilitates the detection and treatment of precancerous lesions and the subsequent reduction of cervical cancer mortality and incidence. The steady decline in mortality rates from 1975 to 2003 were attributable to prevention and early detection as a result of screening with the Pap test; however, 2005-2009 rates have remained stable.1 The precise reason for this stability is unknown, but in light of the Pap test’s success in reducing mortality, it is vital that clinicians continue to refer patients for Pap testing or perform Pap tests on eligible individuals.

For many years, most Pap testing was conducted using the conventional method in which specimen was placed on a slide, fixed, and then sent to the laboratory for cytology testing. In the early 2000s, the FDA approved liquid-based cytology (LBC) testing (e.g., ThinPrep and SurePath). In LBC testing, specimens are placed in a liquid medium and sent to the laboratory for cytology testing. Although more expensive than the conventional Pap test, the LBC tests are more sensitive. As an added benefit, further testing can be performed on the sample that is already available, eliminating the need for a patient to revisit for additional sampling.

Remember that results can be falsely positive or negative.

However, since the advent of LBC, true positives (sensitivity) have increased. DNA tests to detect HPV strains associated with cervical cancer may be used alone, in conjunction with the Pap test, or when Pap test results are equivocal. The Pap test has a sensitivity of 52% to 90%; HPV testing has a sensitivity of 71% to 100%; and combined Pap and HPV DNA testing have a sensitivity of 90% to 100%.6,7 HPV DNA testing is often requested in women who are older than age 30 years.

According to the American Cancer Society, most cervical precancers develop slowly, so nearly all cancers can be prevented if a woman is screened regularly.1 However, recommendations vary with regard to when to start and stop testing and how frequently to perform Pap testing. Table 2 summarizes the guidelines of the leading organizations that make cancerscreening recommendations.1,8,9 Abnormal Pap results

Pap testing is effective as long as there is adequate followup and management of abnormal results. The follow-up of abnormal Pap test results and the identification and

www.ClinicalAdvisor.com • THE CLINICAL ADVISOR • MARCH 2013 35

CME CE

CERVICAL CANCER

treatment of precancerous cells prevent progression to cervical cancer. It usually takes approximately 10 years for precancerous cells to become cancerous. The five-year survival rate for women who are diagnosed with localized disease is 91%; the five-year relative survival rate for women with cervical cancer is only 68%.1 Clearly, clinicians must do everything possible to promote adherence with the follow-up of abnormal Pap test results.

Educating women about diagnostic tests, the meaning of abnormal test results, and the importance of follow-up and treatment can promote adherence. An abnormal Pap result may be subsequent to non-neoplastic causes or cervical-cell abnormality. Non-neoplastic causes include infections and a miscellaneous category.

The list of infections that may be present on a Pap test result includes candidiasis, trichomonas, bacterial vaginosis, herpes, and actinomyces (more common in women who have an intrauterine device in place). The sequelae of these infections range from discomfort to chronic pelvic pain and infertility, so treatment is essential.

The miscellaneous category of non-neoplastic causes of abnormal Pap results includes reactive cellular changes, parabasal cells, and hyperkeratosis. Reactive cellular changes may be secondary to inflammation without infection; a repeat Pap test should be performed in four to six months only in women who are HIV-positive. Parabasal cells, which are common in postmenopausal women, are really immature-appearing cells and do not require repeat testing. Hyperkeratosis is usually related to inflammation associated with trauma or infection and is commonly seen in women who use a diaphragm. A repeat Pap test should be obtained in six to 12 months if the patient is at risk for cervical-cell abnormality (i.e., immunocompromised or younger than age 30 years). Although treatment is generally not necessary, local application of estrogen cream may be beneficial in persistent cases of hyperkeratosis.10 Types of cervical-cell abnormalities include: (1) such squamous cell abnormalities as, atypical squamous cells (ASC), atypical squamous cells of undetermined significance (ASCUS), and atypical squamous cells cannot exclude a high-grade squamous intraepithelial lesion (ASC-H); (2) such low-grade intraepithelial lesions (LSIL) as HPV mild dysplasia or CIN 1, and high-grade intraepithelial lesion (HSIL); and (3) such moderate or severe dysplasia as CIN 2 or CIN 3, carcinoma in situ (CIS), and squamous cell carcinoma.

Management of abnormal Pap results

The management of cervical-cell abnormality depends on the type of abnormality, the age of the patient, and

the patient’s pregnancy status. Treatment of cervical-cell abnormality is usually based on the management guidelines from the American Society for Colposcopy and Cervical Pathology.11 Generally, Pap tests are repeated if the result is ASC-US or lower and if the patient is not high-risk (e.g., HIV-positive).

If the Pap test result is higher than ASC-US, diagnostic tests need to be performed.12 Diagnostic tests include colposcopy (Table 3) and endocervical curettage (ECC) or endocervical sampling (ECS) (Table 4).

During a colposcopy, the cervix is visualized with a colposcope after the application of 3% -5% acetic acid solution. A biopsy is performed if any areas of abnormality are visualized. Colposcopy is an office procedure and is not usually painful, but individuals who are very anxious may require premedication with an oral analgesic or antianxiety agent.

ECC and ECS both involve sampling endocervical tissue with a curette during pelvic examination.10 These procedures can be performed in the office. Women often experience a cramping sensation during the procedure and are premedicated with an oral analgesic.

A woman aged 30 years or younger should be managed conservatively to prevent infertility and cervical incompetence.

Infertility occurs from scarring and stenosis of the cervical os resulting from such treatments as cryotherapy and electrocoagulation. Cervical incompetence may result from treatment procedures that include laser ablation and excisional procedures.

Another reason for conservative management is that although TABLE 8. Management of nonpregnant adults with ASC-H or LSIL Refer for colposcopy If colposcopy is negative for CIN 2 or CIN 3, repeat Pap test every six months for one year or perform HPV DNA testing in one year If follow-up is negative, return to routine screening; refer for a colposcopy if follow up is ASC or higher

TABLE 9. Intial workup of nonpregnant adults with AGC Atypical endometrial cells • Sampling of the endocervical and endometrial areas • Colposcopy if sampling is negative Not atypical endometrial cells • Colposcopy with sampling of the endocervix and • HPV DNA testing and • Sampling of the endometrium (endometrial sampling is beneficial among women who are age 35 years or older and those who are at risk for neoplasia of the endometrium).

36 THE CLINICAL ADVISOR • MARCH 2013 • www.ClinicalAdvisor.com

The management of cervical cell abnormality depends on the type of abnormality, the age of the patient, and the patient’s pregnancy status.

References 1. American Cancer Society. Cancer Facts and Figures 2013. Available at www.cancer.org/Research/CancerFactsFigures/CancerFactsFigures/ ACSPC-036845.

2. Gardasil [Human Papillomavirus Quadrivalent (Types 6, 11, 16, and 18) Vaccine, Recombinant] package insert. Merck & Co., Inc.; 2011. Available at www.merck.com/product/usa/pi_circulars/g/gardasil/gardasil_pi.pdf.

3. Monthly Prescribing Reference. Gardasil. Available at www.empr.com/ gardasil/drug/1653/.

4. Monthly Prescribing Reference. Cervarix. Available at www.empr.com/ cervarix/drug/3508/.

5. Castle PE, Cox JT, Palefsky JM. Recommendations for the use of human papillomavirus vaccines. In: UpToDate, Goldberger, AL (Ed), UpToDate, Waltham, Mass.: 2013.

6. Mariani SM. Conference report—early cancer diagnosis: beating the odds. MedGenMed. 2004;6:18. Available at www.ncbi.nlm.nih.gov/pmc /articles/PMC1435596/.

7. Reust CE. Does the increased sensitivity of the new Papanicolaou (Pap) tests improve the cost-effectiveness of screening for cervical cancer? J Fam Pract. 2001;50:175.

8. ACOG Committee on Practice Bulletins—Gynecology. ACOG Practice Bulletin no. 109: Cervical cytology screening. Obstet Gynecol.

2009;114:1409-1420.

9. U.S. Preventive Services Task Force. Screening for cervical cancer.

Available at www.uspreventiveservicestaskforce.org/uspstf/uspscerv.htm.

10. Holschneider CH, Crum CP, Cervical cytology: interpretation of results.

In: UpToDate, Goldberger, AL (Ed), UpToDate, Waltham, Mass.: 2012.

11. Wright TC Jr, Massad LS, Dunton CJ, et al. 2006 consensus guidelines for the management of women with abnormal cervical cancer screening tests. Am J Obstet Gynecol. 2007;197:346-355.

12. Feltmate CM, Feldman S. Colposcopy. In: UpToDate, Goldberger, AL

Conclusion

(Ed), UpToDate, Waltham, Mass.: 2013.

It is fortunate that cervical cancer is preventable, but women are still being diagnosed with and dying from this disease.

By simply becoming educated about cervical cancer prevention strategies, primary-care clinicians can contribute to the reduction of cervical cancer incidence and mortality. Applying this knowledge to clinical practice enables providers to positively influence patients, family members, and caregivers when it comes time to decide whether to participate in cervical cancer vaccination, obtain a Pap test, and follow up abnormal Pap test results. ■ Dr. Linton is Assistant Professor, University of Louisiana at Lafayette College of Nursing and Allied Health Professions.

All electronic documents accessed February 15, 2013.

“I’m afraid we’ll need more time to fight for the check.”

www.ClinicalAdvisor.com • THE CLINICAL ADVISOR • MARCH 2013 37

© The New Yorker Collection 2013 from cartoonbank.com. All Rights Reserved.

HPV is very prevalent in this age group, infection tends to clear without treatment. This could also explain why HPV DNA testing is not generally recommended in women who are younger than age 30 years.

The management of ASC-US or LSIL and HSIL or higher in a woman age 30 years or younger are depicted in Tables 5 and 6, respectively.11 The management of nonpregnant adults with ASC-US, ASC-H, LSIL, and atypical glandular cells is summarized in Tables 7, 8, and 9, respectively.11 Individuals with the aforementioned abnormalities are usually referred for diagnostic tests, follow-up, and treatment. However, primary-care clinicians ought to be knowledgeable about the follow-up to educate patients with regard to what to expect. Providing this information will likely reduce patient anxiety and promote adherence.

In the case of a pregnant woman with LSIL, refer for colposcopy six weeks postpartum or refer for colposcopy immediately and follow up postpartum if negative for CIN 2 or CIN 3.11 This recommendation is likely based on the fact that there is a precancerous phase before cervical-cell abnormality becomes cancerous. Furthermore, this progression takes more than a decade to occur.1 HPV DNA testing may be performed with or without a Pap test among women who are age 30 years or older. If HPV DNA testing is negative, repeat the Pap test in three years. If HPV DNA testing is positive, repeat the Pap test and HPV DNA testing in one year. If the Pap test is negative but HPV DNA testing is positive, refer the patient for colposcopy.11

FEATURE: THERESA CAPRIOTTI, DO, MSN, CRNP; AND AURORA VANDEWARK

What is BPA and what does it do to the body?

Primarily used as a coating in food and drink packaging, bisphenol A has recently been linked to obesity, diabetes, and reproductive disorders.

© THINKSTOCK

B

In 2012, the FDA banned BPA in baby bottles and children’s drinking cups.

38 THE CLINICAL ADVISOR • MARCH 2013 • www.ClinicalAdvisor.com

isphenol A (BPA) is an industrial chemical that has become ubiquitous in the environment and may have widespread pathophysiologic effects. This endocrinedisrupting compound is believed to act as an estrogenic agonist and androgenic antagonist.

The chemical has been linked to such disorders as obesity, hypertension, and insulin resistance, as well as attention deficit hyperactivity disorder (ADHD) and autism. Because the full range of the potential biologic effects of BPA remains unclear, many investigations are in progress.

Although more confirmatory studies are needed regarding the biologic effects of BPA, it is estimated that greater than 93% of adults in the United States have levels of the chemical in the urine, indicating significant exposure.1 BPA is used in the manufacture of certain plastics and resins. It is found in such items as canned foods and beverages, baby bottles, dishware, toys, DVDs, hospital plastics, laboratory equipment, and dental sealants (Table 1). In most cases of exposure, BPA leaches into food and beverages from resin-coated containers and is ingested.

Until recently, BPA was believed to be harmless and has been used in the manufacture of plastics since the 1950s. Because it was known early on that BPA leached from containers into foods and beverages, scientists have been investigating the chemical for many years through animal testing. However, BPA has primarily been examined for its cancer-causing potential and has been found to be noncarcinogenic

BISPHENOL A

TABLE 1. Items known to contain BPA

How BPA exposure occurs

Cananed food

Fax paper

Canned beverages

Medical plastics and tubing

Canned liquid infant formula

Pacifier shields

CDs

Plastic baby bottles

Cell phones

Plastic laboratory equipment

Children’s toys

Plastic tableware

Coated paper used in receipts

Plastic water bottles

Dental sealants

Recycled paper products

DVDs

White dental fillings

Adapted from Roberts R. BPA exposure and health effects: educating physicians and patients.

Am Fam Physician. 2012;85:1040-1044; Groff T. Bisphenol A: invisible pollution. Curr Opin Pediatr. 2010;22:524-529; and Geens T, Aerts D, Berthot C, et al. A review of dietary and nondietary exposure to bisphenol-A. Food Chem Toxicol. 2012;50:3725-3740.

in the small doses found in food. In the early 1980s, the FDA, National Cancer Institute, and U.S. Environmental Protection Agency (EPA) found no convincing evidence of BPA carcinogenicity in the doses found in water or food.

By the late 1980s, U.S. production of BPA reached billions of pounds per year and was used in the manufacture of a growing number and variety of consumer goods.2 Once BPA had been deemed noncarcinogenic, few studies focused on its other biologic effects.

More than 90% of BPA exposure is derived from food or fluid containing BPA that has leached out from plastic- or resin-coated containers.3 The leaching of BPA into food or beverage is greatest when the container is heated or damaged. The chemical is absorbed through the GI tract and is metabolized by the liver. From the liver, BPA metabolites are transported to the kidneys and excreted in the urine. BPA can cross the placenta and may be found in amniotic fluid.4 Early studies

Between 1997 and 2005, 115 studies in the United States, Europe, and Japan were conducted on the biologic effects of BPA on animals. The proven effects of BPA on animals included fetal prostate and mammary gland maldevelopment, disruption in the chromosomal alignment in the developing eggs of females, altered immune function, metabolic abnormalities, and changes in brain and behavior (Table 2 ).1,3,5 By 2008, questions about the safety of BPA in humans had begun to capture the public’s attention.6,7 The Canadian government declared BPA toxic and banned its use in manufacturing, and environmental-health advocates in the United States called for state legislatures to restrict BPA in children’s products. Retailers and consumer groups started demanding non-BPA-containing plastics. Pediatricians

TABLE 2. Effects of BPA demonstrated in animal studies Female reproductive system

Male reproductive system

Metabolism

Brain

Other

Precocious puberty

Reduction in or loss of sexual dimorphism in brain

Obesity

Epigenetic programming of the brain structure

Disturbance of the estrous cycle

Breast lesions

Reduction in sexually dimorphic behaviors

Alterations in lipid metabolism

Epigenetic programming of behavior

Alterations in the immune system

Early fat-pad maturation in breast

Decreased sperm counts

Alterations in insulin sensitivity

Enhanced growth of mammary glands

Increased prostate weight

Epigenetic programming of the mammary glands

Prostatic lesions

Ovarian cysts

Altered prostate development

Endometrial hyperplasia

Epigenetic programming of the prostate

Breast hyperplasia Adapted from: Trasande L, Attina TM, Blustein J. Association between urinary bisphenol A concentration and obesity prevalence in children and adolescents. JAMA. 2012;308:1113-1121; Roberts R. BPA exposure and health effects: educating physicians and patients. Am Fam Physician. 2012;85:1040-1044; Rubin BS. Bisphenol A: an endocrine disruptor with widespread exposure and multiple effects. J Steroid Biochem Mol Biol. 2011;127:27-34; Ropero AB, Alonso-Magdalena P, García-García E, et al. Bisphenol-A disruption of the endocrine pancreas and blood glucose homeostasis. Int J Androl. 2008;31:194-200; Alonso-Magdalena P, Morimoto S, Ripoll C, et al. The estrogenic effect of bisphenol A disrupts pancreatic beta-cell function in vivo and induces insulin resistance. Environ Health Perspect. 2006;114:106-112; and Masuno H, Kidani T, Sekiya K, et al. Bisphenol A in combination with insulin can accelerate the conversion of 3T3-L1 fibroblasts to adipocytes. J Lipid Res. 2002;43:676-684.

40 THE CLINICAL ADVISOR • MARCH 2013 • www.ClinicalAdvisor.com

BISPHENOL A

were particularly concerned about limiting BPA exposure in pregnant women, infants, and young children.4,8

POLL POSITION

Emerging research

Should the FDA ban on BPA in baby bottles be expanded to include other containers?

BPA in food or water has the potential for widespread biologic effects in humans. Many studies link high BPA exposure with obesity and cardiovascular disease risk factors. Trasande and colleagues found a positive correlation between BPA and obesity in children and adolescents.1 In their cross-sectional analysis of urinary BPA levels in 2,838 participants aged 6 through 19 years randomly selected from the 2003-2008 National Health and Nutrition Examination Survey (NHANES), higher BMI was shown to be associated with greater urinary BPA levels.

Looking at levels of urinary BPA and the BMI and waist circumference of 2,747 adults from the 2003–2004 NHANES, Carwile and Michels found a positive correlation of higher BPA exposure with general and central obesity in the adult population.9 Wang et al. found similar results in a study of 3,390 Chinese adults older than age 40 years.10 In addition to a positive correlation of BPA with generalized obesity and abdominal obesity, the investigators also found an association between BPA and insulin resistance in the middle-aged adult population.

A study of 1,380 subjects from the 2003–2004 NHANES showed a positive correlation of increasing levels of urinary BPA with hypertension independent of such confounding risk factors as age, gender, race, smoking, BMI, diabetes mellitus, and total serum cholesterol levels.11 A positive correlation was also found between high urinary BPA levels and diabetes mellitus. Subsequent studies have reached similar conclusions.12 Lind and Lind proposed that circulating levels of BPA are related to carotid atherosclerosis in the elderly.13 Circulating levels of BPA in 1,016 subjects older than age 70 years were correlated with echogenicity of carotid artery plaque, suggesting that BPA may play a role in atherosclerosis.

According to Shankar and coauthors, BPA may have a role in the development of peripheral arterial disease as well as cardiovascular disease risk factors, including weight gain, insulin resistance, and endothelial dysfunction.14 Perinatal exposure to endocrine-disrupting compounds (including BPA) appear to be associated with the occurrence of autism as well as ADHD in children.15

BPA is such a widely used chemical, there are substantial commercial interests dedicated to keeping the substance in products, on the market, and unregulated.16 There simply are not enough hard data to persuade national legislators to work against corporate interests.17 In an effort to address this problem, two NIH organizations—the National Institute of Environmental Health Sciences (NIEHS) and the National Toxicology Program—have developed an integrated and multipronged consortium-based approach to optimize BPA research.17 This effort aims to provide more credible information and resolve controversies over the potential human health effects of BPA exposure.18 Due to ongoing questions and concerns, many manufacturers of infant and baby items have voluntarily chosen to start using BPA-free plastics in their products, and 10 states have passed legislation limiting BPA use in products intended for use by infants and children.5 In July 2012, the FDA officially banned BPA in baby bottles and children’s drinking cups, but the prohibition does not apply more broadly to the use of BPA in other containers, such as cans and water bottles. The agency has stated that the decision is not a reversal of its position on BPA, but a move to boost consumer confidence.19 The FDA previously turned down a petition from the Natural Resources Defense Council that called for a complete ban of BPA in all food and beverage containers.20

What is being done?

What to tell your patients about BPA

In general, regulatory authorities have concluded that current studies are insufficient and preclude a complete understanding of the effects of BPA in humans. Since

• Reduce use of canned foods and beverages unless the label specifically states that the container is BPA-free.

3%

n=764

Yes No 97%

For more polls, visit CliniAd.com/10TDwDb

Continues on page 47

www.ClinicalAdvisor.com • THE CLINICAL ADVISOR • MARCH 2013 43

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• Read the latest news about breakthrough treatments, disease outbreaks, drug approvals and recalls, and clinical research.

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BISPHENOL A

• When possible, opt for glass, porcelain, or stainless steel containers, particularly for hot food or liquids.

• Avoid using plastic containers for hot food or liquid.

• Do not pour hot liquids into a plastic baby bottle unless it is BPA-free.

• Discard worn or scratched baby bottles and cups.

• Before mixing water with powdered infant formula, boil in a BPA-free container and allow to cool to lukewarm.

• Do not heat canned ready-to-feed liquid formula on the stove or in boiling water.

• Do not heat baby bottles of any kind in the microwave.

• Only use containers marked “dishwasher-safe” in the dishwasher and “microwave-safe” in the microwave.

Direct patients to the following resources for more information on BPA and what is being done to improve consumer safety: the EPA’s BPA Action Plan Summary (epa.gov/ oppt/existingchemicals/pubs/actionplans/bpa.html, accessed February 15, 2013), the U.S. Department of Health and Human Services BPA Information for Parents (www.hhs.gov/safety/ bpa/, accessed February 15, 2013), and the NIEHS Questions and Answers about BPA (www.niehs.nih.gov/health/topics/ agents/sya-bpa/, accessed February 15, 2013).

4. Groff T. Bisphenol A: invisible pollution. Curr Opin Pediatr. 2010;22: 524-529.

5. Roberts R. BPA exposure and health effects: educating physicians and patients. Am Fam Physician. 2012;85:1040-1044.

6. Lang IA, Galloway TS, Scarlett A, et al. Association of urinary bisphenol A concentration with medical disorders and laboratory abnormalities in adults. JAMA . 2008;300:1303-1310.

7. Walsh B. The chemical within. BPA is everywhere. Is it dangerous? We don’t really know. Time. 2011;178:22.

8. Vom Saal FS, Nagel SC, Coe BL, et al. The estrogenic endocrine disrupting chemical bisphenol A (BPA) and obesity. Mol Cell Endocrinol.

2012;354:74-84.

9. Carwile JL, Michels KB. Urinary bisphenol A and obesity: NHANES 2003-2006. Environ Res. 2011;111:825-830.

10. Wang T, Li M, Chen B, et al. Urinary bisphenol A (BPA) concentration associates with obesity and insulin resistance. J Clin Endocrinol Metab.

2012;97:E223-E227.

11. Shankar A, Teppala S. Urinary bisphenol A and hypertension in a multiethnic sample of US adults. J Environ Public Health. 2012;2012:481641.

Available at www.ncbi.nlm.nih.gov/pmc/articles/PMC3272835/.

12. Shankar A, Teppala S. Relationship between urinary bisphenol A levels and diabetes mellitus. J Clin Endocrinol Metab. 2011;96:3822-3826.

13. Lind PM, Lind L. Circulating levels of bisphenol A and phthalates

Conclusion

are related to carotid atherosclerosis in the elderly. Atherosclerosis.

Past research concentrated on the carcinogenicity of low doses of BPA, with no convincing evidence of its cancer-causing potential. New research on low doses of BPA suggests an association with a variety of adverse health effects. Current studies link BPA to multiple pathophysiologic disorders, including obesity, hypertension, insulin resistance, and neurobehavioral problems in children. These new findings challenge the long-standing scientific presumption of BPA’s safety. More investigation is needed to determine the potential adverse health effects of BPA in humans and to understand the multiple pathways through which it acts. ■

2011;218:207-213.

14. Shankar A, Teppala S, Sabanayagam C. Bisphenol A and peripheral arterial disease: Results from the NHANES. Environ Health Perspect.

2012;120:1297-1300.

15. de Cock M, Maas YG, van de Bor M. Does perinatal exposure to endocrine disruptors induce autism spectrum and attention deficit hyperactivity disorders? Acta Paediatr. 2012;101:811-818.

16. Betancourt AM, Eltoum IA, Desmond RA, et al. In utero exposure to bisphenol A shifts the window of susceptibility for mammary carcinogenesis in the rat. Environ Health Perspect. 2010;118:1614-1619.

17. Borrell B. Toxicology: The big test for bisphenol A. Nature.

2010;464:1122-1124.

Dr. Capriotti is Clinical Associate Professor, Villanova University College of Nursing, Villanova, Pa., where Ms. Vandewark is a junior-level honors student.

18. Birnbaum LS, Bucher JR, Collman GW, et al. Consortium-based science: the NIEHS’s multipronged, collaborative approach to assessing the health effects of bisphenol A. Environ Health Perspect. 2012;120:1640-1644.

19. Tavernese S.”FDA makes it official: BPA can’t be used in baby bottles

References

and cups.” New York Times. July 17, 2012. Available at www.nytimes.

1. Trasande L, Attina TM, Blustein J. Association between urinary bisphe-

com/2012/07/18/science/fda-bans-bpa-from-baby-bottles-and-sippy-cups.

nol A concentration and obesity prevalence in children and adolescents.

html.

JAMA . 2012;308:1113-1121.

20. U.S. Department of Health and Human Services. FDA Letter to Natural

2. Vogel SA. The politics of plastics: the making and unmaking of bisphenol

Resources Defense Council - Petition Denial. March 30, 2012. Available at

a “safety.” Am J Public Health. 2009;99:S559-S566.

www.regulations.gov/#!documentDetail;D=FDA-2008-P-0577-0007.

3. Geens T, Aerts D, Berthot C, et al. A review of dietary and non-dietary exposure to bisphenol-A. Food Chem Toxicol. 2012;50:3725-3740.

All electronic documents accessed February 15, 2013.

www.ClinicalAdvisor.com • THE CLINICAL ADVISOR • MARCH 2013 47

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 MARCH 2013

Consultations Reducing intracranial pressure after head injury . . . . . . . . . . . . . . .48 Overuse of antibiotics must be avoided . . . . . . . . . . . . . . . . . . . .48 Refractory lip blister . . . . . . . . . . . . .49 Cephalosporins in patients allergic to penicillin . . . . . . . . . . . . .49

Clinical Pearls Reflux disease and ear pain . . . . . . . .49 Fish oil provides calcium and avoids constipation . . . . . . . . . . . . . .50 Easing pain during suturing . . . . . . . .50

Your Comments Another tip-off to myasthenia gravis . .50

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@ clinicaladvisor.com.

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.

Reporting medical fraud can be difficult, but worth it . . . . . . . . . . . .50

CONSULTATIONS REDUCING INTRACRANIAL PRESSURE AFTER HEAD INJURY Is there a correlation between the use of 3% hypertonic saline and reduction of intracranial pressure (ICP) in traumatic brain injury (TBI) patients?—TRACY STANKAN, MSN, CRNP, Windber, Pa. Several TBI resuscitation protocols were found to include IV infusion of hypertonic saline. The concentration of hypertonic saline ranged from 1.8% to 7.5%, with 3% being common. The resultant decrease in ICP as well as fluid-volume restoration is widely recognized.

Maintenance of a plasma osmolality of 310 mOsm/kg to 320 mOsm/kg is adequate for the desired cerebral vasoconstrictive effect in TBI.—Sherril Sego, FNP-C, DNP (173-1)

OVERUSE OF ANTIBIOTICS MUST BE AVOIDED As happens each cold-and-flu season, anyone who develops the slightest cough or sore throat is convinced that it is pneumonia or strep throat. With the media attention given to West Nile virus and whooping cough, my patients are even more convinced that they must have an antibiotic, even when the symptoms are clearly viral or allergic in nature. How can I avoid unnecessary antibiotic use while

OUR CONSULTANTS

Rebecca H. Bryan, APRN, CNP,

Eileen Campbell, MSN, CRNP,

Philip R. Cohen, MD,

is a 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.

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

48 THE CLINICAL ADVISOR • MARCH 2013 • www.ClinicalAdvisor.com

Deborah L. Cross, MPH, CRNP, ANP-BC, is associate program

director, Gerontology NP Program, University of Pennsylvania School of Nursing, Philadelphia.

Maria Kidner, DNP, FNP-C,

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

still satisfying my patients?—ANGELA M. YOUNG, PA-C, Charlotte, N.C. Antibiotic overuse is a serious problem and puts both the individual and the general population at risk. Unnecessary use of antibiotics, especially with broad-spectrum antimicrobials, contributes to microbial resistance, the development of superbugs, and treatment against side effects. All clinicians share in the responsibility to avoid unnecessary antibiotic use and should be familiar with guidelines and recommendations for proper use. The CDC has a vast array of materials to help clinicians make better decisions and to advance patient understanding of proper antibiotic use. The Get Smart campaign (www.cdc.gov/ getsmart/, accessed February 15, 2013) promotes patient education through fact sheets, brochures, videos, posters, and online interactive programs. Physician assistants also have an obligation to advance the cause of proper antibiotic use and challenge other clinicians not to overuse antibiotics or succumb to unwarranted pressure to do so.— Claire Babcock O’Connell, MPH, PA-C (173-2)

REFRACTORY LIP BLISTER A woman came to see me with a fever blister on the vermilion border of the lip. Six months earlier, she had treated a herpes infection with acyclovir (Zovirax), but it had no effect on the fever blister. What treatment do you recommend?— CHINWE V. NDUKA, MPS, PA-C, New York City It may be appropriate to first determine or confirm the diagnosis of the lip blister. Herpes simplex virus (HSV) infection can be established by performing a viral culture with virus subtyping from the blister base and fluid. Alternatively, a Tzanck smear preparation from the blister base can be evaluated for the presence of multinucleated epithelial giant cells. Recurrent herpes labialis can be treated with acyclovir (200 mg every four hours, five times daily, for five days), valacyclovir (Valtrex)

(500 mg b.i.d. for three to five days or 2 g every 12 hours for one day [two doses total]), or famciclovir (Famvir) (125 mg b.i.d. for five days). Failure of the blister to respond to antiviral therapy may indicate an alternative diagnosis for the lesion or an acyclovir-resistant strain of HSV.—Philip R. Cohen, MD (173-3)

CEPHALOSPORINS IN PATIENTS ALLERGIC TO PENICILLIN Penicillin allergy is common in primary care. I am often reluctant to use a cephalosporin in these individuals, especially when better alternatives exist. Are there guidelines or recommendations for the use of cephalosporins in patients allergic to penicillin?—JOHN RICE, PA-C, Dunbar, W. Va. A recent literature review of the use of cephalosporins in penicillinallergic patients looked at all studies publishing evidence of crossreactivity from 1950 through 2011. The odds ratio (OR) of cross-reactivity with first-generation cephalosporins is significant (OR 4.8; confidence interval [CI] 3.7-6.2), but is not significant with later-generation cephalosporins (OR 1.1; CI 0.6-2.1). This correlates with a 1% risk of cross-reactivity with first-generation cephalosporin use and substantially less with other cephalosporins. The authors concluded that the risk with later-generation cephalosporins is negligible, but fell short of recommending their use if another alternative is available. (J Emerg Med. 2012;42:612-620).—Claire Babcock O’Connell, MPH, PA-C (173-4)

CLINICAL PEARLS REFLUX DISEASE AND EAR PAIN Always consider gastroesophageal reflux disease (GERD) as a causative factor in a patient with chronic or recurrent

Debra August King, PHD, PA,

Mary Newberry, CNM, MSN

Claire O’Connell, MPH, PA-C,

Sherril Sego, FNP-C, DNP,

Julee B.Waldrop, DNP,

is senior physician assistant at New York-Presbyterian Hospital, New York City.

provides well-woman gynecologic care as a midwife with Prima Medical Group, Greenbrae, Calif.

teaches in the PA Program at the New Jersey Medical School and Rutgers University, Piscataway, N.J.

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

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

www.ClinicalAdvisor.com • THE CLINICAL ADVISOR • MARCH 2013 49

Advisor Forum ear pain, especially if the pain is bilateral.—KRISTEN JOHNSON, NP, Savannah, Ga. (173-5)

© 2013, Roy Delgado

FISH OIL PROVIDES CALCIUM AND AVOIDS CONSTIPATION Many postmenopausal women require calcium and vitamin D supplements. However, the calcium can cause constipation, which may hinder compliance. Try 1,000 mg of omega-3 fish oil instead. To decrease the fishy smell, freeze the capsules before ingesting.—BEV REEVES-DUDLEY, CRNA, Liberty, Mo. (173-6)

EASING PAIN DURING SUTURING After irrigating a wound, use a drop of mepivacaine (Carbocaine) to reduce minor pain during suturing. This is especially helpful with small children.—ANGELINA LEDONNE, APRN-BC, Chicago (173-7)

“Thanks for seeing me on your vacation, Doctor.”

REPORTING MEDICAL FRAUD CAN BE DIFFICULT, BUT WORTH IT When you report illegal and unethical activities, be ready for the fallout (“Fraudulent practices set off alarms,” January 2013). Do not think for a minute that anyone is going to jump to your defense, because that could take years, and you have to cope in the meantime. I was brave enough to testify against a physician at several hearings, and that’s when my identity was revealed. If I had to do it over again, I would have reported him but remained anonymous. My duty is to protect patients. Any health-care professional who does not report this type of activity is an accomplice and deserves the same fate as the perpetrator.—CYNTHIA MALOWITZ, MSN, ANP-BC, FNP-C, Corpus Christi, Tex. (173-9) ■ 50 THE CLINICAL ADVISOR • MARCH 2013 • www.ClinicalAdvisor.com

© 2013, Roy Delgado

ANOTHER TIP-OFF TO MYASTHENIA GRAVIS One of the clinical clues to an almost certain case of myasthenia gravis (“A collaborative approach to myasthenia gravis,” December 2012) is the variability (apart from the fatigability) of the ocular presentation within the same individual. The patient will typically report that the ptosis is asymmetric and varies between the two eyes at different times.—PUNITHA VICTOR, MD, Vellore, India (173-8)

© 2013, Smeltzer

YOUR COMMENTS

Derm Dx

EXCLUSIVE TO THE WEB

INTERACT WITH YOUR PEERS by viewing the images and offering your diagnosis and comments. To post your answer, obtain more clues, or view similar cases, visit CliniAd.com/10KIbCF. Learn more about diagnosing and treating these conditions, and see how you compare with your fellow colleagues.

Vesicles and inflammation on a teenage wrestler’s feet A high-school wrestler presented with recent onset of itchy blisters on the feet. Hydrocortisone cream, an OTC antifungal, and topical herpes medication were ineffective. Moist socks were noted during the exam.

WHAT IS YOUR DIAGNOSIS?

• • • •

Dyshidrotic eczema Candidiasis Erythrasma Tinea pedis

● See the full case at CliniAd.com/15vWwrF

Bluish-grey skin discoloration on the forearms and shins A Hispanic man with systemic lupus erythematosus developed bluish-grey discoloration on his forearms and shins. He was taking prednisone, hydroxychloroquine, mycophenolate mofetil, and alendronate.

WHAT IS YOUR DIAGNOSIS?

• • • •

Prednisone hyperpigmentation Hydroxychloroquine hyperpigmentation Mycophenolate mofetil hyperpigmentation Alendronate hyperpigmentation

● See the full case at CliniAd.com/ViGi10

Have you missed any recent Derm Dx cases? Go to CliniAd.com/10KIbCF for a complete archive of past quizzes as well as additional images of last month’s other cases.

Dirty skin that can’t be washed

54 THE CLINICAL ADVISOR • MARCH 2013 • www.ClinicalAdvisor.com

Wrinkly skin and blackheads

LEGAL ADVISOR CASE

Severe colon cancer goes undetected

BY ANN W. LATNER, JD

Dr. D was a primary-care clinician with her own practice. One thing that Dr. D had learned over the course of more than three decades in practice was that patients differed greatly in what they wanted from a health-care provider. One of Dr. D’s more unusual patients was Mr.T, age 67 years.

At their first appointment, Mr.T told her that he was not looking for a primary-care provider and that he only wanted her to check his BP. “I know my BP is borderline high, and I want to have it monitored by you. I will come see you twice a year. I will pay out of pocket. But I am not looking for anything more than having my BP checked.”

At first, Dr. D tried to reason with the patient.

“If you don’t have a primary-care provider, you should,” she explained. “And don’t you want to have a complete physical?”

“No,” insisted Mr.T.“I don’t want a physical or anything else. Just take my BP, please.”

Dr. D was somewhat puzzled, but she started a patient file for Mr.T. In the file, she noted his BP readings every six months. Mr.T stayed under Dr. D’s treatment for more than five years.

© THINKSTOCK

A clinician finds herself culpable after agreeing to an unorthodox arrangement with a patient.

“I don’t think that doctor ever once suggested that my husband get a colonoscopy or anything.

Maybe if she had, he would still be alive.”

One day, Mr.T failed to show up for his regular appointment, and Dr. D had her office manager give him a call.

“He is in the hospital,” reported the office manager, after speaking with Mr. T’s wife. “He had had some very bad stomach pain and no bowel movement for several days. So he went to the emergency department.”

“I’ll see how he’s feeling,” replied Dr. D. Mr. T was not doing well. An abdominal pelvic ultrasound and a pelvic CT scan showed free intraperitoneal air, indicating a perforated bowel. Mr. T was taken for emergency surgery. During the surgery, it was discovered that he had colon cancer. The pathology report revealed invasive adenocarcinoma that had metastasized to the lymph nodes. Mr. T was told that he had stage 3 colon cancer.

Continues on page 56

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.

www.ClinicalAdvisor.com • THE CLINICAL ADVISOR • MARCH 2013 55

LEGAL ADVISOR Within the next few months, the cancer spread to Mr. T’s lungs, and his condition deteriorated. He died fewer than six months after his diagnosis.

After Mr. T’s death, his widow contacted an attorney to explore her options.

“My husband was going to Dr. D’s office every six months for five years before he was diagnosed with cancer,” she told the attorney. “I don’t think that doctor ever once suggested that my husband get a colonoscopy or anything. Maybe if she had, he would still be alive.”

“If it is true that he was seeing this clinician for five years and she never suggested any screenings, then perhaps we do have a case,” replied the attorney. “I will get copies of his medical records from Dr. D.”

If services are declined, write it in the patient’s record so that there is evidence of vital care being offered and refused.

Once the attorney obtained the medical records, he hired an expert physician to review them and then give his opinion.

“These are some of the strangest medical records I have ever seen,” the expert remarked. “It’s hard to believe, but it appears that the clinician did nothing other than check Mr. T’s BP for five years.”

“What should the doctor have been doing?” asked the attorney.

“A general physical, blood work, and certainly some sort of colorectal cancer screening—either a digital rectal exam, a fecal occult blood test, or a sigmoidoscopy or colonoscopy.

For a patient of that age, these things should be standard.”

The attorney called Mr. T’s widow and told her that he would take the case. He filed a malpractice lawsuit against Dr. D. Dr. D’s heart sank when she received the papers notifying her about the lawsuit. She immediately realized that the medical records looked odd with just BP readings. Plus, she had never made notes anywhere—including in the patient’s file—about the special arrangement that she and Mr. T had in which he had declined any other services.

Dr. D met with the defense attorney provided by her malpractice insurance provider.The attorney recommened that they begin the discovery and deposition process but consider a settlement if it looked like the case would go to trial.

Dr. D’s attorney warned her that during the depositions she would be questioned by the plaintiff ’s attorney and that

it was very important that she be honest and consistent since anything she said in the deposition could be used in the trial. As expected, the plaintiff ’s counsel questioned Dr. D regarding whether the standard of care had been met by not providing or suggesting any colorectal cancer screenings. Dr. D was forced to admit that the standard of care for a primary-care physician does require such screenings, but she immediately informed Mrs. T’s attorney that she wasn’t Mr.T’s primary-care physician, and that he’d only hired her to do BP screenings.

The attorney looked skeptical, and asked whether Dr. D had written that in the patient file or anywhere in the notes from the past five years. Dr. D had no choice but to respond that she had not.

On the advice of her own lawyer, Dr. D settled the case for a sum of $1.5 million.

Legal background

Depositions provide both parties in a lawsuit with the opportunity to question witnesses in preparation for trial. They are conducted as part of the discovery process in civil cases.

During depositions, witness testimony is transcribed. The transcript then can be used at trial to contradict what the witness says at that time. No judge is present at depositions; the attorneys handle the entire process.

Protecting yourself

At one point or another, most clinicians will likely be confronted with a patient who does not want to follow advice or declines full examinations. While you cannot force an individual to undergo a blood test, Pap smear, or colorectalcancer screening, the standard of practice requires the clinician to offer these services and inform patients about the benefits and risks. If a patient opts to decline services, be sure to record it in his or her record so that there is evidence of vital care being offered and refused.

Dr. D had an unusual relationship with her patient, who simply wanted hypertension screenings and nothing else.

The patient made it clear what he did, and did not want right from the beginning, which was his right. However, Dr. D’s error was in not detailing this arrangement anywhere in the patient record or in her notes. Once Mr.T passed away, there was no one left to confirm the arrangement, and Dr. D appeared to be negligent. A note in the patient’s chart could have changed the outcome of this case. ■ Ms. Latner, a former criminal defense attorney, is a freelance medical writer in Port Washington, N.Y.

56 THE CLINICAL ADVISOR • MARCH 2012 • www.ClinicalAdvisor.com

CME CE

Dermatology Clinic ■ LEARNING OBJECTIVES: To identify and diagnose dermatologic conditions and review up-to-date treatment.

■ COMPLETE THE POSTTEST: Page 74

■ ADDITIONAL CME/CE: Pages 32, 69

Turn to page 31 for additional information on this month’s CME/CE courses.

CASE #1

Discoloration worsens following sun exposure ESTHER STERN, NP

A man, aged 34 years, was concerned about numerous white spots on his arms and chest. He first noticed the discoloration in midsummer.

As his skin became more tanned, the color difference progressively worsened. No similar lesions were noted elsewhere. The patient reported a history of frequent sun exposure. He has no significant medical history and does not take any medications. Physical examination revealed numerous scaly hypopigmented macules on the bilateral upper and lower arms and mild involvement of the chest.

What is your diagnosis? Turn to page 58

CASE #2

Arm ulcer on a Latin American immigrant ADAM REES, MD

An ulcer on the arm of a 34-year-old man was expanding. The ulcer started a few weeks earlier as a small papule. The man had entered the United States illegally from Cuba, traveling through the jungles of Costa Rica and Guatemala to get to Mexico and eventually across the border. He was otherwise healthy and took no medications. No fever was reported. A punch biopsy demonstrated an ulceration with pseudoepitheliomatous hyperplasia and multiple macrophages filled with small parasites.

What is your diagnosis? Turn to page 59 www.ClinicalAdvisor.com • THE CLINICAL ADVISOR • MARCH 2013 57

CME CE

CASE #1

Dermatology Clinic

Tinea versicolor

Tinea versicolor, also known as pityriasis versicolor, is a very common skin infection that is caused by the yeast Malassezia furfur. The condition presents with hypopigmented pink or hyperpigmented scaly nummular macules. The individual macules may coalesce into larger scaly plaques. These plaques are most frequently located on the chest, upper abdomen, shoulders, back, and upper arms. Other oily areas of the skin also commonly affected include the pubis, neck, and intertriginous areas. Rarely, and usually in immunocompromised patients, tinea versicolor may present on the scalp, genitalia, palms, and soles.1 Although most patients with tinea versicolor are asymptomatic, some complain of mild to moderate itching. The most frequent associated complaints are generally of a

When tinea versicolor presents in the classic locations, the diagnosis is relatively simple and requires no further testing. cosmetic nature, particularly during the summer months when patients are concerned about their appearance while wearing swimsuits.

The pigment changes associated with tinea versicolor result from the yeast’s production of dicarboxylic acid, which inhibits the enzyme tyrosinase necessary for melanin production. Even after successful treatment and eradication of the yeast, the pigment changes may persist for several months until the affected areas regain pigmentation or until the postinfl ammatory hyperpigmentation slowly resolves.

When tinea versicolor presents in the classic locations, the diagnosis is relatively simple and requires no further testing. In atypical cases, a skin scraping or even a biopsy may be necessary to confirm the diagnosis. On microscopic examination, fungal hyphae and various-sized spores will be observed in the stratum corneum. This combination is frequently referred to as the “spaghetti and meatballs” presentation.

Tinea versicolor tends to be a chronic and recurrent condition, frequently reappearing in warm-weather months.

Patients who have seborrheic dermatitis or hyperhidrosis are more frequently affected, as are those living in a tropical environment.

The differential diagnoses include pityriasis rosea, seborrheic dermatitis, lupus, syphilis, and pityriasis rubra pilaris.

In the hypopigmented variant, mycosis fungoides and vitiligo should be ruled out.

Several topical treatment therapies for tinea versicolor exist. Selenium sulfide applied daily to the affected areas and then rinsed after 10 minutes is an inexpensive option.

Selenium sulfide is also effective in a single overnight application. In addition, imidazoles, triazoles, ciclopirox (Penlac), zinc pyrithione, salicylic acid, and benzoyl peroxide can be used topically. The challenge is in finding the appropriate vehicle for application over a large area.

Many patients find the foam vehicle easiest to use. Oral itraconazole (Onmel, Sporanox) and fluconazole (Diflucan) have also proven effective.2 Although the treatment of tinea versicolor is relatively simple, reducing the high frequency of recurrences can be challenging. Patients should be informed that recurrences are common and that prophylactic treatment is often necessary. Shampooing the affected areas weekly or monthly with shampoos containing selenium sulfide (e.g., Selsun Blue), ketoconazole, or zinc pyrithione (e.g. Head and Shoulders) is simple and effective. Monthly treatment with oral itraconazole or flucanozlae can also be considered in resistant cases.3 The man in this case was treated with topical ketoconazole (Extina, Nizoral, Xolegel) b.i.d. for two weeks. Three weeks later, he reported complete clearance of the lesions.

Ms. Stern is a family nurse practitioner at Advanced Dermatology & Skin Surgery, P.C., in Lakewood, N.J. References 1. James WD, Berger TB, Elston DM. Andrews’ Diseases of the Skin: Clinical Dermatology. 11th ed. Philadelphia, Pa.: Saunders-Elsevier; 2011:313.

2. Muhammad N, Kamal M, Islam T, et al. A study to evaluate the efficacy and safety of oral fluconazole in the treatment of tinea versicolor.

Mymensingh Med J. 2009;18:31-35.

3. Faergemann J, Gupta AK, Al Mofadi A, et al. Efficacy of itraconazole in the prophylactic treatment of pityriasis (tinea) versicolor. Arch Dermatol.

2002;138:69-73. Available at archderm.jamanetwork.com/article. aspx?articleid=478654.

All electronic documents accessed February 15, 2013.

58 THE CLINICAL ADVISOR • MARCH 2013 • www.ClinicalAdvisor.com

CASE #2

Leishmaniasis

Leishmaniasis is caused by more than 15 species of Leishmania, which are flagellated protozoa parasites. The parasites are transmitted by the bite of the Phlebotomus and Lutzomyia species of sand fly. Once inoculated into the skin, the parasites are taken up by macrophages and clinical disease ensues.1,2 Leishmaniasis occurs worldwide but primarily affects people in South America, Central America, the Mediterranean basin, Asia, and Africa. The three clinical subtypes are cutaneous (affecting only the skin), mucocutaneous (affecting both skin and mucous membranes), and visceral (affecting the liver, spleen, and lymph nodes). Leishmaniasis is subdivided by geographic region, with the New World type occurring in the Americas and the Old World type occurring in Asia, Africa, and the Mediterranean basin. More than 400,000 cases of leishmaniasis are reported yearly, with the vast majority found in Saudi Arabia, Afghanistan, Syria, Brazil, and Peru.1,2 Old World cutaneous leishmaniasis is primarily caused

by L. major and L. tropica. In the New World, cutaneous disease is caused by L. mexicana, and mucocutaneous disease is caused by L. braziliensis. L. donovani (Kenya, India, Bangladesh, Sudan), L. infantum (in a geographic belt from Portugal to China), and L. chagasi (in Mexico and South and Central America) cause visceral leishmaniasis.

In cutaneous leishmaniasis, a small papule initially develops at the site of inoculation and subsequently may become ulcerated or warty. The lesions may be solitary, or they may spread by means of the lymphatic system to produce satellite lesions. Frequently, the cutaneous lesions heal spontaneously with scarring; however, some lesions may become chronic or even disseminated.1.2 Mucocutaneous leishmaniasis starts as cutaneous disease; within months to years, the patient develops mucosal disease.

The lips, nose, and oropharynx are characteristically affected. Lesions appear clinically as edema, infi ltrated plaques, ulceration, or even frank destruction of cartilage.1,2 In visceral leishmaniasis, also referred to as kala-azar, patients develop symptoms of fever, cough, lymphadenopathy, hepatosplenomegaly, and wasting in one to 36 months after inoculation. The GI, renal, and pulmonary systems may be affected, leading to death. A curious syndrome known as post-kala-azar dermal leishmaniasis may occur after successful

treatment of visceral leishmaniasis. In this syndrome, patients develop dermal nodules, verrucous papules, and hypopigmented macules. The skin eruption may occur many years after the original treatment period.

Confirming the presence of the parasites by skin biopsy, scraping, or fine-needle aspiration makes the diagnosis of leishmaniasis. On histology, the skin lesions demonstrate ulceration overlying pseudoepitheliomatous hyperplasia. Look for a mixed inflammatory infiltrate consisting of plasma cells, neutrophils, lymphocytes, and macrophages. The parasites are found within the macrophages and appear as 2-µm to 4-µm oval structures that lack a capsule. The abscence of a capsule helps to distinguish leishmaniasis from Histoplasma capsulatum, which may otherwise appear similar histologically. The organisms localize around the periphery of the macrophages and are better visualized using a special Giemsa stain.

Leishmania may be cultured on specialized media, but cultures are only positive in 40% of cases.1,2 Polymerase chain reaction (PCR) is considered the most sensitive test.3 Other tests include indirect immunofluorescence, enzymelinked immunosorbent assay, immunoprecipitation, and isoenzyme electrophoresis.

The differential diagnosis includes such infections as syphilis, noma (also called gangrenous stomatitis, this necrotizing is infection caused by various bacteria in an immunocompromised host), paracoccidioidomycosis, and various other deep fungal or atypical mycobacterial infections. Clinically, the cutaneous lesions may occur as basal or squamous cell carcinomas. Ulcerative lesions affecting the mucous membranes of the central face may mimic angiocentric natural-killer/Tcell lymphoma or Wegener’s granulomatosis. The ulcers of leishmaniasis may even mimic pyoderma gangrenosum. The presence of pseudoepitheliomatous hyperplasia on histology may mimic squamous cell carcinoma, and the presence of parasitized macrophages may mimic such infections as histoplasmosis and penicilliosis.

The treatment of leishmaniasis varies based on the subtype of infection and the severity of the clinical presentation. Old World cutaneous disease is frequently self-limited and does not necessarily require treatment.4 New World disease caused

by L. brasiliensis may progress to destructive mucocutaneous disease and therefore requires treatment. Standard systemic therapy consists of a pentavalent antimonial medication, such as sodium stibogluconate or meglumine antimoniate.

Significant side effects of these medications include cardiotoxicity leading to QT prolongation, pancreatitis, hepatitis, thrombocytopenia, and renal failure. Other systemic therapies include amphotericin B (Amphocin, Fungizone),

www.ClinicalAdvisor.com • THE CLINICAL ADVISOR • MARCH 2013 59

Dermatology Clinic

itraconazole (Onmel, Sporanox), ketoconazole (Nizoral), and others.5–7 Leishmaniasis may be prevented through the use of insect repellants and through public-health measures to reduce animal reservoirs of disease.

In this case, the initial biopsy indicated squamous cell carcinoma. Since there was clinical suspicion for an infectious rather than a malignant etiology of the skin lesions, a second biopsy was performed. In the second biopsy the pathologist noted unencapsulated organisms within tissue macrophages.

This histologic finding, along with the clinical picture of an expanding ulcer and the history of weeks spent in Central America, made leishmaniasis highly likely. Experts at the CDC provided support in obtaining a tissue culture and performing a PCR on the specimen. The CDC also provided guidance regarding treatment. At the time of this writing, the patient had been admitted to the hospital for treatment with IV sodium stibogluconate for 20 days.

More information regarding the diagnosis and treatment of leishmaniasis can be found at the CDC website (www .cdc.gov/parasites/leishmaniasis/health_professionals/ index.html, accessed February 15, 2013). This website is an invaluable resource for any health-care professional managing leishmaniasis in the United States. ■

© 2013, Roy Delgado

CME CE

“Don’t touch it. That’s my wife talking to me.”

© 2013, Smeltzer

Dr. Rees is a first-year dermatology resident at Baylor College of Medicine in Houston.

References 1. Lupi O. Protozoa and worms. In: Bolognia JL, Jorizzo JL, Rapini RP, eds.

Dermatology. 2nd ed. St. Louis, Mo.: Mosby/Elsevier; 2008:1263-1268.

2. Grekin RC, Samalaska CP, Vin-Christian K. Parasitic infestations, stings,

“Relax. I’m planning to ask the doctor to super-size my cholesterol medicine.”

and bites. In: James WD, Berger TG, Elston DM, eds. Andrews’ Diseases of the Skin: Clinical Dermatology. 11th ed. Philadelphia, Pa.: Saunders Elsevier; 2006:415-419.

3. Lemrani M, Hamdi S, Laamrani A, Hassar M. PCR detection of Leishmania in skin biopsies. J Infect Dev Ctries. 2009;3:115-122. Available at www.jidc.org/index.php/journal/article/view/19755741.

4. Lee SA, Hasbun R. Therapy of cutaneous leishmaniasis. Int J Infect Dis. 2003;7:86-93.

5. Sundar S, Chakravarty J, Agarwal D, et al. Single-dose liposomal amphotericin B for visceral leishmaniasis in India. N Engl J Med. 2010;362:504-512.

Available at www.nejm.org/doi/full/10.1056/NEJMoa0903627.

Dis. 2003;16:397-401.

7. Murray HW. Leishmaniasis in the United States: treatment in 2012. Am J Trop Med Hyg. 2012;86:434-440.

All electronic documents accessed February 15, 2013.

60 THE CLINICAL ADVISOR • MARCH 2013 • www.ClinicalAdvisor.com

“Are you going to believe me or 12 strangers on a jury?”

© 2013, Roy Delgado

6. Berman J. Current treatment approaches to leishmaniasis. Curr Opin Infect

ALTERNATIVE MEDS UPDATE What you should know about the herbs and supplements patients use

By Sherril Sego, FNP-C, DNP. Ms. Sego is a staff clinician at the VA Hospital 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.

Fenugreek

© SCIENCE SOURCE / NIGEL CATTLIN

Like many herbal supplements, fenugreek’s use extends far back into history. Seeds of this Near Eastern plant were found in King Tutankhamun’s tomb and have been radiocarbon dated to 4000 BC.1 Fenugreek, or Trigonella foenum-graecum, is popular around the world for its flavor in foods and its use as a supplement. Related to the pea family, fenugreek often is used as a dried herb or spice and is also eaten as a fresh vegetable.1 This annual plant is found around the Mediterranean and the Middle East, with more than 80% of the world’s crop produced in India.2

Background The seeds of the fenugreek plant, which are used for medicinal purposes, are found in clusters of long, slender, sickle-shaped pods.3 Chemically, the seeds contain saponins and alkaloids, along with other antioxidants and a high percentage of soluble dietary fiber.3 Fenugreek contains a wealth of other nutrients, such as proteins, amino acids, and significant amounts of calcium, phosphorus, and iron.4

Science One of the oldest medicinal uses for fenugreek is as a galactogogue. Galactogogues are herbal substances that promote the production of milk in humans.The proposed mechanism of action in these herbal compounds is through dopaminergic receptors in the brain, triggering increased prolactin release.5 A common concern for newborn infants is the weight loss that is often problematic in the first few days of life. In one

small study, 66 immediate-postpartum mother-infant pairs were randomized to daily fenugreek tea, placebo, or no treatment. By the end of the third day infant weight loss was significantly less in the active-treatment group than in the other two groups, which also correlated with the greater breast milk volume noted in the mothers given fenugreek.6 Many holistic lactation specialists recommend fenugreek, especially when the volume of milk produced by the mother is low. In anecdotal data from more than 1,200 women, one lactation consultant documented that milk production will increase 24 to 72 hours after taking fenugreek and continue at that level, even following cessation of the supplement.7 The second major action of fenugreek involves of glucose and lipid metabolism. A number of studies suggest that preprandial ingestion of fenugreek seed supplement flattens the postprandial glucose elevation and lipid spike.8 The hypothesized reason for this response is the density of soluble dietary fiber in the seeds. In a basic-research trial scientists administered fenugreek seed supplement twice daily for

64 THE CLINICAL ADVISOR • MARCH 2013 • www.ClinicalAdvisor.com

ALTERNATIVE MEDS UPDATE 28 days to lab rats.8 At the study’s end, all atherogenic lipids (triglycerides and LDL cholesterol) were significantly decreased, and the favorable HDL cholesterol levels were increased.

In a clinical trial, 25 individuals newly diagnosed with type 2 diabetes were randomized to either a daily dose of fenugreek seed supplement or standard diet and exercise for two months.9 At the end of the study, glycemic tests showed no difference from baseline levels. However, area under curve of glucose as well as insulin showed a marked reduction, with a statistical sensitivity of p<0.001.As with the rat model, serum triglycerides were also decreased, and HDL cholesterol levels increased.9 Obesity is the most talked about marker of metabolic syndrome and insulin resistance. Fenugreek not only slows gastric glucose absorption but improves cellular uptake of glucose as well.10 Because of its high fiber content, fenugreek consumption with meals increased satiety, causing participants to eat less.11 Canadian researchers randomized 24 adult obese subjects to either fenugreek-containing supplement daily or placebo.11 Study examiners monitored the participants’ weight and abdominal and hip circumference at baseline and at the end of the six-week trial.The subjects did not change their daily habits or diet.

Compared with the placebo group, patients taking fenugreek lost 5 lb and more than 4 inches of abdominal and hip circumference, compared with 0 lb and 0.5 inches lost by the placebo group.11

to combat these conditions is a daily challenge for health-care providers. Fenugreek has been shown to be effective in aiding weight loss and appears to perpetuate a healthy glucose and lipid status. ■ References 1. National Center for Complementary and Alternative Medicine. Fenugreek. Avaialble at www.nccam.nih.gov /health/fenugreek.

2. Parthasarathy VA, Kandinnan K, Srinivasan V, eds.

Organic Spices. New Delhi, India: New India Publishing Agency; 2008:694.

Fenugreek is thought to aid in weight loss by regulating glucose levels.

3. Fetrow C, Avila J, eds. Professional’s Handbook of Complementary & Alternative Medicines. Springhouse Publishing; Springhouse, Pa.; 1999.

Many studies suggest that preprandial ingestion of fenugreek seed supplement flattens the postprandial glucose elevation and lipid spike.

4. National Nutrient Database. Fenugreek. Available at ndb.nal.usda.gov/ndb/foods/show/239.

5. Gabay MP. Galactogogues: medications that induce lactation. J Hum Lact. 2002;18:274-279. Avialable at jhl .sagepub.com/content/18/3/274.long.

6. Turkyilmaz C, Onal E, Hirfanoglu IM, et al. The effect of galactogogue herbal tea on breast milk production and short-term catch-up of birth weight in the first week of life.

J Altern Complement Med. 2011;17:139-142.

7. Breastfeeding Online. Fenugreek: one remedy for low milk production. Available at www.breastfeedingonline .com/fenuhugg-print.html.

8. Hannan JM, Roykeya B, Farugue O, et al. Effect of soluble dietary fibre fraction of Trigonella foenum graecum on glycemic, insulinemic, lipidemic and platelet aggregation status of Type 2 diabetic model rats. J Ethnopharmacol.

2003;88:73-77.

Cost, how supplied, safety

9. Gupta A, Gupta R, Lal B. Effect of Trigonella foenumgraecum (fenugreek) seeds on glycaemic control and

Fenugreek is inexpensive and available in healthfood stores. The most popular formulation is as a powder-filled capsule, but whole-grain seeds are also available. As with any other plant, allergic reactions are possible, so persons with atopic histories should use caution. Fenugreek is also contraindicated in pregnant women because of its potential for inducing labor.3

insulin resistance in type 2 diabetes mellitus: a double blind placebo controlled study. J Assoc Physicians India.

2001;49:1057-1061.

10. Mathern JR, Raatz SK, Thomas W, Slavin JL. Effect of fenugreek fiber on satiety, blood glucose and insulin response and energy intake in obese subjects. Phytother Res. 2009;23:1543-1548.

11. Woodgate D, Conquer J. Effects of a stimulant-free adults: a six-week exploratory study. Curr Ther Research.

2003;64:248-262.

In a society in which obesity and type 2 diabetes are epidemic, finding safe and effective aids 68 THE CLINICAL ADVISOR • MARCH 2013 • www.ClinicalAdvisor.com

All electronic documents accessed February 15, 2013.

© THINKSTOCK

dietary supplement on body weight and fat loss in obese

Summary

CME CE

Dermatologic Look-Alikes ■ LEARNING OBJECTIVE: To distinguish and properly treat dermatologic conditions with similar presentations.

■ COMPLETE THE POSTTEST: Page 74

■ ADDITIONAL CME/CE: Pages 32, 57

Turn to page 31 for additional information on this month’s CME/CE courses.

Plaques on the lower extremities KERRI ROBBINS, MD

CASE #1

CASE #2

A woman, aged 55 years, presented with bilateral lowerextremity erythema, edema, and pain for two months.

She had been treated with two distinct courses of oral antibiotics for presumed cellulitis without improvement.

Further discussion revealed a one-year history of occasional edema in the lower extremities. Medical history was significant for diabetes, hypertension, and heart failure. Vital signs were within normal limits. Erythematous indurated plaques were noted on bilateral lower extremities. Pitting edema and overlying warmth were also appreciated.

A woman, aged 40 years, complained of a rash on her bilateral lower extremities. The lesions were first thought to be insect bites, but the areas expanded and changed colors centrally over the course of six months. There was no pain, pruritus, dysesthesia, edema, or warmth, and no prior treatment had been initiated. History was significant for type 1 diabetes mellitus. On physical exam, atrophic yellow-brown plaques with prominent telangiectasias and a well-defined erythematous indurated border were appreciated on bilateral shins.

www.ClinicalAdvisor.com • THE CLINICAL ADVISOR • MARCH 2013 69

CME CE

CASE #1

Dermatologic Look-Alikes

Lipodermatosclerosis

Lipodermatosclerosis (LDS) is also known as sclerosing panniculitis, hypodermitis sclerodermiformis, or chronic panniculitis with lipomembranous changes. LDS is a disorder of the subcutaneous fat and often occurs in the setting of chronic venous insuff iciency (CVI). LDS has a relatively short documented history that is directly intertwined with CVI. In the early 1900s, Homans first hypothesized that static venous blood in any part of the body leads to a decreased amount of oxygen in the region and causes the skin in the immediate area to atrophy and ulcerate. In 1953, Piulacks speculated that arteriovenous fistulas in the skin cause hypoxia in the region, leading to detrimental changes in the skin. This was particularly true for the lower extremities. Finally, in 1955, Huriez first described LDS as an indurated lesion he called hypodermitis sclerodermiformis.1 LDS is a disorder that predominantly affects women older than age 40 years. It is believed that LDS is caused by CVI and fibrinolytic abnormalities.2 Patients may also suffer from such comorbidities as diabetes, hypertension, heart failure, kidney failure, peripheral vascular disease, and/or obesity. They may also have a prior history of venous thrombosis. The damage

The acute phase is often characterized by erythema, warmth, and pain in the medial portion of the lower extremity. associated with LDS is triggered by venous hypertension, which leads to increased capillary permeability. Capillary permeability in turn causes the leakage of fibrinogen, which polymerizes to form fibrin cuffs around the vessels. The end result is a significant decrease in oxygen exchange, which ultimately leads to tissue anoxia. It is also believed that deficiencies in proteins C and S, as well as stimulation of collagen in the area, may contribute to the disorder.3 In the acute phase, individuals will often present with erythema, warmth, and pain in the medial portion of the lower extremity, particularly above the malleolus. During

the chronic phase, there is marked sclerosis of the subcutis and dermis, which may be accompanied by overlying hemosiderosis. The sclerosis causes the skin to become extremely stiff with clear boundaries from the adjacent normal skin.

LDS may also be found in the lower aspect of an abdominal pannus. The classical appearance of LDS is thought to resemble an inverted champagne or wine bottle.

Avoid performing biopsies on lesions of LDS. The lack of clotting factors in the area and poor circulation may lead to poor wound healing. If a sample must be taken, a thin elliptical incision should be made on the margin of the lesion that extends into the deep fat.

Histologically, LDS is a lobular panniculitis with focal macrophage infi ltration and fibrosis around shrunken lobules. Within the lobules, fat pseudocysts are lined with a lipomembrane. A lipomembrane is a thin eosinophilic or pale amphoteric layer that has fine, feathery projections into the cavity. Lipomembranous changes are often seen in LDS but are not specific for the disease. There may also be focal areas of fat necrosis, dermal fibrosis, loss of epidermal appendages, and fibrous tissue replacement of the subcutaneous fat. The lipomembrane is positive for periodic acid–Schiff, as well as CD68 and lysozyme, suggesting a contribution of these enzymes from macrophages. Chronic lesions are only weakly positive or negative for CD68 and lysozyme.

Early lesions of LDS are often mistaken for cellulitis, erythema induratum, or erythema nodosum. Signs of venous insufficiency lack of fever or leukocytosis, poor response to antibiotic therapy, and/or a bilateral presentation should help the clinician differentiate LDS from cellulitis. Venous function studies should be considered if available. Other disorders that are often included in the differential diagnoses include necrobiosis lipoidica, morphea, erythema nodosum, erysipelas, diabetic dermopathy, liposarcoma, and traumatic panniculitis.

The mainstays of LDS treatment include leg elevation and compression therapy. Some advocate the use of intralesional corticosteroids in conjunction with compression therapy.

Patients should also be advised to optimize the treatment of any medical conditions that may be contributing to their venous insufficiency. Some success has been reported with use of the anabolic steroid stanozolol (Winstrol) (2mg to 5mg b.i.d.).4 Stanozolol must be given early in the disease course and is thought to enhance fibrinolysis, leading to reduced pain, degree of involvement, and cutaneous induration. Patients should be cautioned of the side effects, which include sodium retention, lipid abnormalities, hepatotoxicity, and virilization in women. Oxandrolone (Oxandrin),

70 THE CLINICAL ADVISOR • MARCH 2013 • www.ClinicalAdvisor.com

an alternative anabolic steroid, is thought to have fewer androgenic effects and pose less risk for hepatotoxicity. Successful treatment with ultrasound, phlebectomy, pentoxifylline (Pentoxil, Trental), hydroxychloroquine (Plaquenil), and fasciotomy has also been reported.4-6 Even with rigorous treatment, LDS tends to run a chronic progressive course.

The woman in this case was treated with leg elevation and compression therapy, resulting in stabilized disease.

CASE #2

Necrobiosis lipoidica

Necrobiosis lipoidica (NL) is classified as a noninfectious palisaded granulomatous dermatitis. In 1929, Oppenheim named the disorder dermatitis atrophicans diabetica. In 1932, Urbach renamed the disease necrobiosis lipoidica diabeticorum (NLD). Up to this point, the disorder was thought to always be associated with diabetes mellitus. In 1935, Goldsmith encountered the first afflicted nondiabetic patient and renamed the disorder necrobiosis lipoidica.

While this is the preferred name, NLD remains an ingrained abbreviation in dermatologic literature.

In 1966, Muller and Winkelmann conducted a study to analyze the co-occurrence of NL and diabetes mellitus.7 The results revealed that approximately 65% of patients with NL had type 1 diabetes mellitus. A more recent study revealed that only 11% of patients had a diagnosis of diabetes mellitus at the time of presentation, and an additional 11% were later diagnosed with impaired fasting glucose or frank diabetes mellitus.8 Interestingly, only 0.03% of patients with diabetes mellitus will develop NL, and there is no proven correlation between a patientâ&#x20AC;&#x2122;s level of glycemic control and the probability of developing the disorder. However, individuals who have both NL and diabetes mellitus have a higher rate of such diabetes-related complications as peripheral neuropathy, limited joint mobility, and retinopathy.9 NL affects women approximately three times more often than it does men, and the disease usually appears between age 20 and 40 years. Unfortunately, the pathogenesis remains largely unknown. Immunoreactants have been found within the vessel walls of lesional and nonlesional skin, leading

investigators to believe that NL may be an immunologically mediated vascular disease.10 Others postulate that the microangiopathic vessel changes seen in diabetic patients may result in collagen degeneration and subsequent dermal inflammation. Some believe that anti-collagen antibodies may be the basis of the collagen degeneration; however, no significant increase in antibody level has been appreciated. Elevated platelet adhesion, increased thromboxane A2 production, and increased blood viscosity are additional theories that have not been validated.

Early lesions of NL begin as firm, elevated, red-brown papules. Over time, these lesions expand to develop oval or irregularly round plaques with a well-defined erythematous or violaceous border and a central atrophic yellow portion that may contain numerous telangiectasias and ectatic veins. The lesions are usually symmetric, and 85% of cases occur on the shins. Lesions found elsewhere (e.g., the upper extremities, face, and scalp) are usually annular or serpiginous and tend to be less atrophic. While lesions are typically asymptomatic, some patients complain of pain, pruritus, or dysesthesias.

One third of NL cases will ulcerate.

A punch biopsy of NL will often appear rectangular rather than tapered. Histologically, the epidermis tends to be atrophic with loss of the normal rete ridge pattern. A superficial, deep, and interstitial inflammatory process can be appreciated in the reticular dermis, and this inflammation often extends into the subcutaneous fat. The inflammation is composed of lymphocytes, histiocytes, multinucleate giant cells, and plasma cells. Layered palisaded granulomas with

Individuals who have both necrobiosis lipoidica and diabetes mellitus have a higher rate of diabetes-related complications. pale pink degenerated collagen alternating with histiocytes will appear at low magnification. This pattern is said to look like a layer cake.

Although NL has a distinctive clinical appearance, there are a number of atypical presentations, and early forms can be difficult to recognize.11 The differential diagnosis of NL includes granuloma annulare, necrobiotic xanthogranuloma, sarcoidosis, diabetic dermopathy, stasis dermatitis, and lipodermatosclerosis. An equivalent degree of epidermal atrophy, the presence of telangiectasias, or the yellow-brown discoloration is not normally appreciated in granuloma annulare

www.ClinicalAdvisor.com â&#x20AC;˘ THE CLINICAL ADVISOR â&#x20AC;˘ MARCH 2013 71

Dermatologic Look-Alikes

or sarcoidosis. Granuloma annulare is also most commonly seen on the distal extremities, including the hands and feet, which may help to differentiate it from NL. The lesions of diabetic dermopathy, stasis dermatitis, and lipodermatosclerosis are also commonly located on the shins, but these dermatoses are usually hyperpigmented rather than yellow. The presence of varicose veins, edema, induration, ulcerations, and eczematous eruptions may also help the clinician to distinguish these disorders from NL. Yellow plaques also characterize necrobiotic xanthogranuloma, but they are most often periocular and associated with a paraproteinemia.

There is no effective treatment for NL. Unfortunately, tight glucose regulation has no effect on the course of the disease. If the patient desires treatment, superpotent topical steroids under occlusion are considered first-line. Some clinicians advocate the use of topical calcineurin inhibitors.12 Intralesional injections of triamcinolone into the advancing border may be used to halt disease progression. Clinicians must ake care not to inject the central atrophic area, as ulceration may ensue. Systemic corticosteroids may be considered but will elevate the serum glucose.13 Other reported therapies include niacinamide, topical tretinoin, cyclosporine (Gengraf, Neoral, Sandimmune), granulocyte-macrophage colonystimulating factor, bovine collagen, topical psoralen UVA, UVA1 phototherapy, mycophenolate mofetil (CellCept), etanercept (Enbrel), thalidomide (Thalomid), stanozolol (Winstrol), inositol niacinate, nicofuranose, ticlopidine (Ticlid), pentoxifylline (Pentoxil, Trental), and perilesional heparin. If surgical intervention is necessary because of severe ulceration, excision down to deep fascia or periosteum is peformed to prevent recurrence, followed by split-thickness skin grafting.

NL is usually a chronic disease. In one study, spontaneous remission after an average of eight to 12 years was reported in 17% of patients.7 Areas that ulcerate are prone to infection. Rarely, squamous cell carcinoma has arisen in lesions of NL. The patient in this case was not bothered by her lesions and did not desire any therapeutic intervention. ■

2. Greenberg AS, Hasan A, Montalvo BM, et al. Acute lipodermatosclerosis is associated with venous insufficiency. J Am Acad Dermatol.

1996;35:566-568.

3. Falanga V, Bontempo FA, Eaglstein WH. Protein C and protein S plasma levels in patients with lipodermatosclerosis and venous ulceration. Arch Dermatol. 1990;126:1195-1197.

4. Kirsner RS, Pardes JB, Eaglstein WH, Falanga V. The clinical spectrum of lipodermatosclerosis. J Am Acad Dermatol. 1993;28:623-627.

5. Choonhakarn C, Chaowattanapanit S. Lipodermatosclerosis: improvement noted with hydroxychloroquine and pentoxifylline. J Am Acad Dermatol. 2012;66:1013-1014.

6. Damian DL, Yiasemides E, Gupta S, Armour K. Ultrasound therapy for lipodermatosclerosis. Arch Dermatol. 2009;145:330-332. Available at archderm.jamanetwork.com/article.aspx?articleid=711923.

7. Muller SA, Winkelmann RK. Necrobiosis lipoidica diabeticorum. A clinical and pathological investigation of 171 cases. Arch Dermatol. 1966;93:272-282.

8. O’Toole EA, Kennedy U, Nolan JJ, et al. Necrobiosis lipoidica: only a minority of patients have diabetes mellitus. Br J Dermatol. 1999;140:283-286.

9. Boulton AJ, Cutfield RG, Abouganem D, et al. Necrobiosis lipoidica diabeticorum: a clinicopathologic study. J Am Acad Dermatol. 1988;18:530-537.

10. Quimby SR, Muller SA, Schroeter AL. The cutaneous immunopathology of necrobiosis lipoidica diabeticorum. Arch Dermatol. 1988;124:1364-1371.

11. Mistry N, Chih-Ho Hong H, Crawford RI. Pretibial angioplasia: a novel entity encompassing the clinical features of necrobiosis lipoidica and the histopathology of venous insufficiency. J Cutan Med Surg. 2011;15:15-20.

12. Binamer Y, Sowerby L, El-Helou T. Treatment of ulcerative necrobiosis lipoidica with topical calcineurin inhibitor: case report and literature review. J Cutan Med Surg. 2012;16:458-461.

13. Petzelbauer P, Wolff K, Tappeiner G. Necrobiosis lipoidica: treatment with systemic corticosteroids. Br J Dermatol. 1992;126:542-545.

All electronic documents accessed February 15, 2013.

Dr. Robbins is a resident in the Department of Dermatology at Baylor College of Medicine in Houston.

References 1. Huriez, Lagache, Desmons, Pelce. [Leg ulcers and trophic disorders of venous origin; data from the study of one thousand hospitalized patients with ulcers]. Rev Prat. 1955;5:2703-2721.

72 THE CLINICAL ADVISOR • MARCH 2013 • www.ClinicalAdvisor.com

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CME CE

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POSTTEST Expiration date: March 2014

Nurse Practitioner Associates for Continuing Education (NPACE) is accredited as a provider of continuing nursing education by the American Nurses Credentialing Center’s Commission on Accreditation.

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 www.myCME.com.You must receive a score of 70% or better on each test taken to obtain credit.

CREDITS: 0.5

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Feature

Dermatology Clinic

Dermatologic Look-Alikes

page 32

page 57

page 69

Primary-care prevention of cervical cancer

Case #1: Tinea versicolor

Case #1: Lipodermatosclerosis 1. What is a comorbidity associated with lipodermatosclerosis (LDS)? a. Kidney failure b. Peripheral vascular disease c. Diabetes d. All of the above

1. What is a risk factor for cervical cancer? a. Nulliparity b. Obesity c. Multiple sexual partners d. Extended use of a diaphragm 2. What special clinical information needs to be considered when providing the available cervical cancer vaccines? a. It is necessary to monitor individuals with postvaccination titers. b. It is safe to administer Gardasil at the same time as the hepatitis B vaccine. c. Vaccines are contraindicated in individuals previously infected with human papillomavirus (HPV). d. HPV DNA serology is necessary prior to vaccination.

3. Which infection is more common in women with an intrauterine device? a. Candidiasis b. Trichomonas c. Herpes d. Actinomyces 4. A Pap test is repeated with which result if the patient is not considered high-risk? a. Atypical squamous cells of undetermined significance b. Low-grade intraepithelial lesion c. Cervical intraepithelial neoplasia 1 d. High-grade intraepithelial lesion TO TAKE THE POSTTEST please go to CliniAd.com/XZ0CV0

1. The plaques of tinea versicolor are most frequently found on the a. Scalp b. Upper abdomen c. Genitalia d. Palms and soles 2. Patients with which dermatologic illness are more frequently affected by tinea versicolor? a. Pityriasis rosea b. Seborrheic dermatitis c. Lichen planus d. Psoriasis Leishmaniasis 3. What is considered the most sensitive test for Leishmania? a. Polymerase chain reaction b. Indirect immunoflourescence c. Enzyme-linked immunosorbent assay d. Isoenzyme electrophoresis 4. What cardiac side effect is associated with the standard treatment for leishmaniasis? a. ST depression b. Peaked T wave c. Abnormal QRS shape d. QT prolongation

2. What is a mainstay of LDS treatment? a. Nonsteroidal anti-inflammatory drugs b. Systemic antibiotics c. Leg elevation d. Physical therapy Case #2: Necrobiosis lipoidica 3. The lesions of necrobiosis lipoidica (NL) are usually symmetric, with 85% being found on the a. Shins b. Upper extremities c. Scalp d. Face 4. What feature helps distinguish NL from granuloma annulare and sarcoidosis? a. Hyperpigmented rather than yellow lesions b. Presence of telangiectasias c. Presence of induration d. Pain in the lower extremity

TO TAKE THE POSTTEST please go to CliniAd.com/XewbKr

74 THE CLINICAL ADVISOR • MARCH 2013 • www.ClinicalAdvisor.com

CME

POSTTEST Expiration date: March 2014

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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 www.myCME.com. 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

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Feature

Dermatology Clinic

Dermatologic Look-Alikes

page 32

page 57

page 69

Primary-care prevention of cervical cancer

Case #1: Tinea versicolor

Case #1: Lipodermatosclerosis

1. What is a risk factor for cervical cancer? a. Nulliparity b. Obesity c. Multiple sexual partners d. Extended use of a diaphragm 2. What special clinical information needs to be considered when providing the available cervical cancer vaccines? a. It is necessary to monitor individuals with postvaccination titers. b. It is safe to administer Gardasil at the same time as the hepatitis B vaccine. c. Vaccines are contraindicated in individuals previously infected with human papillomavirus (HPV). d. HPV DNA serology is necessary prior to vaccination.

3. Which infection is more common in women with an intrauterine device? a. Candidiasis b. Trichomonas c. Herpes d. Actinomyces 4. A Pap test is repeated with which result if the patient is not considered high-risk? a. Atypical squamous cells of undetermined significance b. Low-grade intraepithelial lesion c. Cervical intraepithelial neoplasia 1 d. High-grade intraepithelial lesion TO TAKE THE POSTTEST please go to CliniAd.com/XZ0CV0

1. The plaques of tinea versicolor are most frequently found on the a. Scalp b. Upper abdomen c. Genitalia d. Palms and soles 2. Patients with which dermatologic illness are more frequently affected by tinea versicolor? a. Pityriasis rosea b. Seborrheic dermatitis c. Lichen planus d. Psoriasis Leishmaniasis 3. What is considered the most sensitive test for Leishmania? a. Polymerase chain reaction b. Indirect immunoflourescence c. Enzyme-linked immunosorbent assay d. Isoenzyme electrophoresis 4. What cardiac side effect is associated with the standard treatment for leishmaniasis? a. ST depression b. Peaked T wave c. Abnormal QRS shape d. QT prolongation

1. What is a comorbidity associated with lipodermatosclerosis (LDS)? a. Kidney failure b. Peripheral vascular disease c. Diabetes d. All of the above 2. What is a mainstay of LDS treatment? a. Nonsteroidal anti-inflammatory drugs b. Systemic antibiotics c. Leg elevation d. Physical therapy Case #2: Necrobiosis lipoidica 3. The lesions of necrobiosis lipoidica (NL) are usually symmetric, with 85% being found on the a. Shins b. Upper extremities c. Scalp d. Face 4. What feature helps distinguish NL from granuloma annulare and sarcoidosis? a. Hyperpigmented rather than yellow lesions b. Presence of telangiectasias c. Presence of induration d. Pain in the lower extremity

TO TAKE THE POSTTEST please go to CliniAd.com/XewbKr

74 THE CLINICAL ADVISOR • MARCH 2013 • www.ClinicalAdvisor.com

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 (www.ebscohost.com/dynamed/) is a database that provides evidence-based information on more than 3,000 clinical topics and is updated daily through systematic surveillance covering more than 500 journals.The most important evidence identified is summarized here.

NURSING PROTOCOLS FOR FEVER, HYPERGLYCEMIA, AND SWALLOWING MANAGEMENT IN PATIENTS WITH ACUTE STROKE MAY REDUCE DEPENDENCE Level 2: Mid-level evidence Fever, hyperglycemia, and swallowing dysfunction after an acute stroke have been associated with poor outcomes. Guidelines call for monitoring and management of these symptoms over the first several days (Stroke. 2007;38:1655-1711).

A cluster-randomized trial evaluated the use of explicit management protocols at 19 acute stroke centers in Australia. Centers were randomized to one of two treatment approaches (Lancet. 2011; 378:1699-1706).The intervention centers implemented a multidisciplinary program using nursing protocols to manage fever, hyperglycemia, and swallowing dysfunction in patients with acute stroke during the first 72 hours following admission. The program included educational meetings to discuss the protocols and team-building exercises to reduce barriers to their implementation. Control centers provided care based on an abridged version of existing guidelines. A total of 1,126 patients were enrolled.

In an analysis of 89.6% of randomized patients at 90 days’ follow-up, the intervention was associated with a significant decrease in death or dependence (42% vs. 58%, p=0.002, NNT 7). Dependence was defined as a modified Rankin score >2. (A score of 0 indicates no symptoms and a score of 1 indicates ability to carry out all usual activities despite some symptoms; higher scores indicate greater disability.)

Mortality was not significantly different between the groups (4% vs. 5%).The intervention group had better physical-function scores (p=0.002), but there was no significant difference in mental-function scores. There was also no significant difference in

independence for activities of daily living (ADLs) as indicated by a Barthel Index score ≥60 (0–100 scale with higher score indicating better functioning).The intervention was associated with a trend toward greater complete independence (Barthel Index score >95, p=0.07).

Daily inhaled corticosteroid treatment has been associated with reduced growth in young children.

78 THE CLINICAL ADVISOR • MARCH 2013 • www.ClinicalAdvisor.com

BUDESONIDE GIVEN ONLY DURING ACUTE RESPIRATORY ILLNESS MAY PREVENT ASTHMA AS EFFECTIVELY AS DAILY BUDESONIDE IN YOUNG CHILDREN WITH HISTORY OF WHEEZING Level 2: Mid-level evidence Inhaled corticosteroids (ICS) have been shown to reduce wheezing and asthma exacerbations in preschool-aged children (Pediatrics. 2009;123: e519-e525), and daily low-dose ICS treatment is recommended for children younger than age 5 years with persistent asthma ( J Allergy Clin Immunol. 2007;120:S94-S138). However, daily ICS treatment has been associated with reduced growth in young children (N Engl J Med. 2006;354:1985-1997).The MIST trial evaluated the efficacy of intermittent ICS treatment for prevention of exacerbation in 278 children aged 12–53 months (N Engl J Med. 2011;365:19902001). Children with recurrent wheezing were randomized to inhaled budesonide 1 mg twice daily for seven days only during respiratory-tract illness (intermittent) vs. daily inhaled budesonide 0.5 mg. Inclusion criteria included at least one 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).

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Location Location Location 3. The Conference Hotel, The Venetian and The Palazzo, offers first-class accommodations.

Keynote Address by Dr. Donna Shalala and Dr. Barbara Safriet 4. Dr. Shalala will share her insight into the Institute of Medicine (IOM) Report. Dr. Safriet will discuss regulation and legislation.

Bon Appétit 5. Few cities in the world can boast about the wide array of dining options available, from all-you-can-eat buffets to some of the finest restaurants in the world. Las Vegas has options for every culinary taste.

Continuing Education 6. Up to 42 contact hours of continuing education (CE) will be offered at the 28th National Conference. This program is pending approval for CE and pharmacology credit by the AANP Accreditation Program.

Networking 7. Visit with friends and make new acquaintances at the conference.

Join us as we shape the future and celebrate the past.

Explore the Exhibit Hall 8. In addition to 270 exhibits with up-to-date information on available products and services, be sure to visit the AANP Boutique to get your “new” AANP branded apparel and specialty items. The Market Place is where you can get personal interest items such as jewelry and other products.

Industry Supported/Sponsored Events 9. Registered attendees may receive complimentary access, on a first-come first-serve basis, to a limited number of educational presentations with food service by attending the CE symposia and non-CE product theaters.

On-Line Conversation 10. AANP shares the latest NP news through social media and we want to hear from you. Get involved today at LinkedIn, Facebook, Twitter, YouTube, ENP Network and Generation NP. National conference is the perfect venue to integrate social media into your professional life.

Experience Vegas Attractions 11. The city houses numerous performance venues, spas, clubs and even kid-friendly attractions. Take a gondola ride at The Venetian, check out the view atop Paris’ Eiffel Tower or enjoy the fantastic fountain show at the Bellagio. Be sure to swing by the Freemont Street Experience in downtown Vegas, a five-block pedestrian walkway that hosts free concerts and performances throughout the week.

Additional Workshops Offered June 18, 2013

There are so many reasons to attend – register today at http://www.aanp.org/conferences and receive housing information on your conference registration receipt.

Evidence-Based Medicine

HYDROMORPHONE FOR POSTOPERATIVE PAIN DOES NOT APPEAR TO INCREASE DELIRIUM IN ELDERLY PATIENTS HAVING HIP FRACTURE SURGERY Level 2: Mid-level evidence Postoperative delirium is common in elderly patients following surgery for hip-fracture repair. Some clinicians may be reluctant to fully treat the postoperative pain due to concerns that opioid treatment could increase delirium risk. In particular, meperidine (Demerol) has been found to be associated with increased risk of delirium in elderly postoperative patients in a systematic review (Anesth Analg. 2006;102:1255-1266). A study investigated the effects of the opioid hydromorphone on cognitive impairment in a cohort of 236 consecutive patients (mean age 82 years) having hip fracture surgery ( J Am Geriatr Soc. 2011;59:2256-2262). Patients were assessed at baseline for preexisting dementia and were followed for postoperative pain, hydromorphone use, and incidence of delirium. Patients with preoperative delirium were excluded.

At baseline, 28% of patients had dementia determined by preoperative exam or history. Hydromorphone was given intravenously postoperatively to maintain a pain score <3 on a 0–10 oral rating scale. The drug was given to 93% of patients without dementia and to 83% of patients with dementia. There was no significant association between hydromorphone use and delirium in either patients without dementia (p=0.33) or patients with dementia (p=0.4). Mean pain scores and opioid use were significantly lower in patients with dementia compared to those without dementia. The strongest predictor of postoperative delirium was pre-existing dementia: delirium occurred in 51.5% of patients with dementia and in 15.3% of patients without dementia (odds ratio 5.86, p<0.001).

Intensive-care-unit admission was also strongly associated with delirium (odd ratio 2.71, p=0.006).

© PHOTO RESEARCHERS, INC. / DU CANE MEDICAL

asthma exacerbation requiring systemic glucocorticoids, emergency care, or hospitalization in the previous year. Children were excluded for six or more courses of oral glucocorticoids or two or more hospitalizations for wheezing within one year.

A total of 213 children (76.6%) completed one year of followup. There were no significant differences in the rates of exacerbation requiring oral glucocorticoids (0.95 vs. 0.97 per patient-year) or urgent-care visits for asthma (2.37 vs. 2.4 per patient-year).

Intermittent budesonide treatment was associated with a significant reduction in cumulative budesonide dose (mean 46 mg vs.

150 mg, p <0.05).There were no significant differences in time to first or second asthma exacerbation, or in change in height or weight from baseline at one-year follow-up.

Demerol linked to delirium in patients with hip fracture (shown).

MINIMALLY INVASIVE SURFACTANT TREATMENT REDUCES NEED FOR VENTILATION IN SPONTANEOUSLY BREATHING PRETERM INFANTS REQUIRING INCREASED OXYGEN Level 1: Likely reliable evidence Treatment with surfactant has been shown to reduce mortality in newborns with respiratory distress syndrome. In these patients, surfactant is usually given via endotracheal intubation during mechanical ventilation. Infants born prematurely are at increased risk of respiratory distress.A randomized trial evaluated a new, minimally invasive approach for giving surfactant to preterm infants with increased oxygen requirements (Lancet.

2011;378:1627-1634).

A total of 220 spontaneously breathing preterm infants (gestational age 26–28 weeks; birth weight <1.5 kg) were randomized to surfactant plus standard treatment vs. standard treatment alone.All infants were stabilized with continuous positive airway pressure (CPAP) and had rescue intubation and mechanical ventilation if necessary. In the surfactant group, infants who were spontaneously breathing and stable on CPAP but also required >30% supplemental oxygen had surfactant administered via a thin catheter inserted into the trachea by laryngoscopy.

Addition of surfactant reduced the need for mechanical ventilation on day 2 or 3 of life (28% vs. 46%, p=0.008, NNT 6) and during the entire hospital stay (33% vs. 73%, p<0.0001, NNT 3). The median duration of ventilation was 0 days for the surfactant group and 2 days for the usual-treatment group (p<0.05). Need for supplemental oxygen at 28 days was significantly lower in the surfactant group (30% vs. 45%, p=0.032, NNT 7).There were no significant differences in mortality or serious adverse events. ■

80 THE CLINICAL ADVISOR • MARCH 2013 • www.ClinicalAdvisor.com

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CLASSIFIEDS

For advertising information, contact: Russell Johns Associates, LLC 1001 S Myrtle Ave, #7, Clearwater, FL 33756 Phone: 877.394.1388 or 727.443.7667 • Fax: 727.445.9380 • E-mail: ca@russelljohns.com

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Rehabilitation Services Physician Assistant

Established Family Practice Clinic in Santa Teresa, NM seeking NP/PA for full-time position.

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Call Minerva De Veau at: (575) 589-1144.

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82 THE CLINICAL ADVISOR • MARCH 2013 • www.ClinicalAdvisor.com

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COMMENTARY Judi Greif, RN, MS, APN-C, is a family nurse practitioner currently residing in East Brunswick, N.J.

www.BogusDrugs.com Recently, I went to a medical conference attended by key opinion leaders and experts in disease management. One of the physicians present commented that his patients were resorting to purchasing generic versions of a particular drug online or from abroad because they could not afford to use the name-brand agent. However, there happened to be a representative from the pharmaceutical company that manufactures that drug in attendance, and he had to inform the doctors that there was no generic equivalent of this medication available anywhere in the world! In other words, not only were patients misinformed and taking a drug that was at best unapproved and ineffective

I had not really thought about the implications for desperate patients who fall victim to these scams.

and, at worst, dangerous, but even specialists in this field were also misinformed and potentially recommending illegal, harmful, counterfeit medications to their patients. If doctors themselves are unaware that a given drug does not have a generic equivalent, how are we to expect patients to know?

Disturbed by this episode, I decided to investigate the scope of the problem. Up until that meeting, I had deleted the myriad of “spam” e-mails I receive on an almost daily basis promising “Drugs from a Canadian Pharmacy” without really thinking—annoyed, but not really troubled, by these bogus advertisements.

I had not really stopped to think about the implications for patients who, desperate for affordable and necessary medicines, fall victim to these unscrupulous scams.

As it turns out, thousands of illegal Internetbased pharmacies exist. In October 2012, the U.S. Food and Drug Administration took legal action against more than 4,100 Internet-based pharmacies that illegally peddle unapproved drugs to American consumers (available at www.fda.gov/ NewsEvents/Newsroom/PressAnnouncements/ ucm322492.htm, accessed February 15, 2013).

These actions included leveling civil and criminal charges, seizing illegal products, and removing offending websites. The FDA initiative was part of Operation Pangea, an annual global cooperative effort spearheaded by Interpol. Operation

Pangea involved authorities from 100 countries last year, when the program led to the shutdown of more than 18,000 illicit pharmacy websites and the seizure of approximately $10.5 million worth of counterfeit pharmaceutical products worldwide (available at www.interpol.int/ Crime-areas/Pharmaceutical-crime/Operations/ Operation-Pangea, accessed February 15, 2013).

In addition, the Institute of Medicine has just issued a new consensus report, Countering the Problem of Falsified and Substandard Drugs.

Because many patients do not have prescription drug plans and medications are expensive, it is easy to see why people may turn to these alternatives in desperation. As we struggle to cope with the crisis of health-care coverage for all in this country, we as clinicians must carefully question our patients about the source of their prescription drugs to make sure they are obtaining these products from legitimate sources. We should also ask patients whether the cost of a particular drug is an issue, and choose a medication that is more cost-effective whenever possible, realizing that some patients may be too embarrassed to admit that they cannot afford to fi ll their prescriptions.

Last but not least, we must educate patients, caregivers, and colleagues regarding the existence of unscrupulous establishments that are ready to make money at the expense of people’s health and even their lives. ■

www.ClinicalAdvisor.com • THE CLINICAL ADVISOR • MARCH 2013 83