September 2018 Clinical Advisor

A PEER-REVIEWED FORUM FOR NURSE PRACTITIONERS

NEWSLINE

■■Celiac disease ■■Fidaxomicin for C difficile ■■ Pediatric vaccine exemptions LEGAL ADVISOR

Is clinician testimony hearsay?

|

SEPTEMBER 2018

FASTING INSULIN VS HBA1C

Assessment of current screening methods for predicting diabetes risk There is room for improvement of current T2D screening guidelines.

DERMATOLOGIC LOOK-ALIKES

Erythematous annular lesions

FREE CE COURSE

Laparoscopic sleeve gastrectomy 2018 SALARY SURVEY

See how your salary compares with your peers!

PAGE 30

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Vice President, content, medical communications, editor Kathleen Walsh Tulley editor@clinicaladvisor.com Associate editor Madeline Morr Assistant editor Rita Aghjayan Contributing editors Mark P. Brady, PA-C; Philip R. Cohen, MD; Deborah L. Cross, MPH, CRNP, ANP; Sharon Dudley-Brown, PhD, FNP; Abimbola Farinde, PharmD; Laura A. Foster, CRNP, FNP; Abby A. Jacobson, PA; Maria Kidner, DNP, FNP; Joan W. Kiely, MSN, CRNP; Debra August King, PhD, PA; Ann W. Latner, JD; Mary Newberry, CNM, MSN; Claire Babcock O’Connell, MPH, PA; Kathy Pereira, DNP, FNP; Sherril Sego, DNP, FNP; Ann Walsh, PA-C, SCT(ASCP); Kim Zuber, PA-C Production editor Kim Daigneau Group art director, Haymarket Medical Jennifer Dvoretz Production manager Krassi Varbanov Circulation manager Paul Silver National accounts manager Alison McCauley, 973.224.6414 alison.mccauley @ haymarketmedical.com Publisher Kathleen Hiltz, 201.774.1078 kathleen.hiltz@haymarketmedia.com General manager, medical communications Jim Burke, RPh CEO, Haymarket Media, Inc. Lee Maniscalco All correspondence to: The Clinical Advisor 275 7th Avenue, 10th Floor, New York, NY 10001 For advertising sales, call 646.638.6085.

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EXPERTS If a patient has you stumped, write us and we’ll forward your query to one of our consultants and publish the response in Advisor Forum.You can also use this space to contribute a clinical pearl of your own or comment on another letter.

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.

CLINICAL PEARLS

It cannot be beat.—TERRI JORDAN, ARNP, Daytona Beach, Fla. (202-2)

NEUTROPHILS AND LYMPHOCYTES In interpreting a complete blood count with differential, anytime the neutrophils and lymphocytes are numerically close, it is a viral cause; when the neutrophils and lymphocytes are numerically distant, it is a bacterial cause.

This is very helpful in determining treatment.—DONNA CARTER, FNP-C, Scottsburg, Ind. (202-1) GENERIC “CAINE” IS EFFECTIVE FOR WOUND CARE For pain relief, most pharmacies offer a “caine” at 2-510%, and basically nothing higher, for between $5 and $30 per tube. I work in wound care and use Walmart’s

INTRA-ARTICULAR INJECTIONS FOR SEVERE OSTEOARTHRITIS Patients with severe osteoarthritis in the knees seem to do better with intra-articular injections if you have them sit up and dangle their legs off the examination table and distract the knee slightly when administering the injection.—ROSEMARY LEDBETTER, PhD, PA, Troy, Ill. (202-3)

YOUR COMMENTS SLIPPED CAPITAL FEMORAL EPIPHYSIS IN OBESE ADOLESCENTS I just read the CME/CE article by Marilou Shreve, DNP, APRN, entitled, “Assessing and treating pediatric obesity” [ June 2015]. I was concerned regarding the oversight of a critical issue in obese adolescents: the increased risk of slipped capital femoral epiphysis (SCFE). This was not addressed in the article.

The case study (p. 55) gave incomplete advice regarding the evaluation of an obese adolescent male with knee pain.

The most common etiology of the insidious onset of knee pain in children is the hip, due to referred pain from the

Equate brand—vagicaine 20% benzocaine. When using this before debriding a wound, give it three minutes to sedate the nerves, then perform the procedure. I get good results, as patients say. It relieves pain and burning for $1.88.

Advisor F

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 contact us by e-mail at editor@ 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.

orum

These are lette and successe rs from practitioners s, observat around the below. We ions, and country who OUR CONSULTANTS pearls with invite you want to shar to participa their colle e their clinic agues. Resp te. al problems onding cons ultants are identified CON SULTAT IONS

TREATM ENT FOR INFECT URINAR ION SGLT2 REC MALE CHI S IN THE UNC Y TRACT IRCUMCI LD FOR DIA EPTOR BLOCKE If a male SED child conti Deborah L. Cross, MPH, CRNP, Laura A.BET Foster,ES CRNP, FNP, Abby A. Jacobson, PA-C, RS Abimbola Farinde, PhD, PharmD, With the nues toassociate ANP-BC, is practices family medicine is a physician assistant is a professor redevprogram adven t ofPrimary circu SGLT2 recep at Delaware Valley urinaryattract director, Gerontology NP elop Program, mcisi Columbia Southern moda litywith Palmetto on be perfo for type tor infecPhysicians Dermatology University of Pennsylvania School blockersGroup University 2 diabe rmed? regarding inCare as a treatm in Wilmington, Del. in Orange Beach, Ala. useCharleston, S.C. tes, is there ent urology is of Nursing, Philadelphia. any evide NATHAN in patients with to protect the is well advise nce or data type 1 diabe GARDNE d tes mellitus?— R, PA-C, continues to to recommend a circum upper tracts, the kidne CPAAPA, ys. develo cision It p recurr•ent 44 THE ADVISOR AUGUST 2015 •on www.ClinicalAdvisor.com Castleton, severaCLINICAL l consideration urinary tract the male child who As it currently stands N.Y. , SGLT2 s that infections. for glycemic impede the receptor blocke There are control in ability to cleansenter into this decisio rs are FDA adults with n. Poor hygien should the e and quell -approved child have e may appro diet and exercise, but with type 2 diabetes phimosis, simpl infection potential. appropriate the in ved conjun FDA for use in patien Moreover, AdvisorForum_CA0815.indd urine 44 9/29/15ction 2:38 PM e cathet culture can ts with type has stated that they ketoacidosi steroid cream be a challenge. erization to obtain s, or those are not may tempo an FAR with severe 1 diabetes, patients with Having a short tion of the rarily solve renal functi diabetic steroid the trial of informINDE, PhD, Pharm these issues tenden , though after for infection D (See bottom on.—ABIMBOL ation about once again.—C cy redevelops, placin cessaA Dr. Farinde.) of this page Milwaukee g (203-2) for more , Wis. (203- OLEEN ROSEN, the child at risk 1) DNP, FNP -C, CLI Philip R. Cohen, MD,

is clinicaltions associate professor , shou ld of dermatology, University a of Texas Medical Center, The focus of Houston.

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Send us your letter Advisor Forum, The s with questions New York, and comm Clinical Advisor ents to: , 114 clinicaladvisoNY 10001. You may contacWest 26th Street , please indicatr.com. If you are writing in t us by e-mail at 4th Floor, each item. e so by including response editor@ to a the Letters are policy is edited for number in parent published letter, to heses at length and contribution print the author ’s name with clarity. The Clinicathe end of s will be accepted. l Advisor the letter.

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OUR CO

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VAGINA L RESULT DISCHARGE AND ING FRO If a female M TAMPON ODOR patient has USE a ask if she uses tamp history of vaginal disch ons. If she the pelvic arge with says “yes,” exam when cond odor, that you woul , do not enter ucting the rotating of d to take a pap smea vagina in the same the specu way r. Instead, the cervix. lum Most retain from side to side start shallow until reach ed tampons ing are lodge d in the fold

Philip R.

Cohen, MD, is clinical associa te profess of dermat or ology, of Texas MedicaUniversity l Center, Houston.

SEND TO The Clinical Advisor 275 7th Avenue, 10th floor New York, NY 10001

62 THE CLINI

Deborah L. Cross, MPH, ANP-B

CRNP, C, is associa te program director, Geronto logy NP Program University of Pennsyl vania School , of Nursing , Philadelphia.

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Laura A.

Foster,

practices familyCRNP, FNP, with Palmett medicine o Primary Care Physicia ns in Charles ton, S.C.

Abby A.

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9/29/15

2:44 PM

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Copyright © 2018

www.ClinicalAdvisor.com • THE CLINICAL ADVISOR • SEPTEMBER 2018 1

CONTENTS SEPTEMBER 2018

NEWS AND COMMENT 12 Newsline ■■Celiac disease, wheat sensitivity link examined ■■Fidaxomicin effective for long-term cure of Clostridium difficile ■■PPI and aspirin improve outcomes in Barrett esophagus ■■Lack of trust drives high exemption rates for pediatric vaccination 12 PPI and aspirin in Barrett esophagus

FEATURES 15 Fasting insulin vs HbA1c: Are we getting it right?

Only one-half of primary care providers are following current national prediabetes screening guidelines.

28 Pseudobulbar affect

28 Raising awareness of pseudobulbar affect Pseudobulbar affect is characterized by sudden, frequent, uncontrollable outbursts of crying and/or laughing.

30 Salary survey: Are you being fairly compensated?

The results of the 2018 NP/PA salary survey are in; how does your compensation compare with that of your colleagues?

34 CME/CE Case clinic: Laparoscopic sleeve gastrectomy in a 48-year-old obese male Rapid and profound changes in minimally invasive laparoscopic surgery have occurred over the past few decades.

42 Preventing asthma exacerbations

41 CME/CE Feature posttest Continues on page 8

59 Testifying in a sexual assault case

Follow us on Twitter @ClinicalAdvisor

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MORE WAYS TO FIND US!

CONTENTS SEPTEMBER 2018

DEPARTMENTS A PEER-REVIEWED FORUM FOR NURSE PRACTITIONERS

NEWSLINE

■ Celiac disease ■ Fidaxomicin for C difficile ■ Pediatric vaccine exemptions LEGAL ADVISOR

Is clinician testimony hearsay?

|

THE CLINICAL ADVISOR • JULY 2018

Web Roundup A summary of our most recent opinion, news, and multimedia content from ClinicalAdvisor.com

THE CLINICAL ADVISOR • SEPTEMBER 2018

10

SEPTEMBER 2018 | www.ClinicalAdvisor.com A PEER-REVIEWED FORUM FOR NURSE PRACTITIONERS | U www.ClinicalAdvisor.com A P E E R - R E V I E W E|DAUGUST F O RU M 2018 FOR N R S E P R AC T I T I O N E R S | J U LY 2 01 8

As we celebrate FASTING INSULIN VS HBA1C 20 years, our audience shares how their practice has changed during that time

NEWSLINE DISEASE CHAGAS

■ Lyme neuroborreliosis ■ NPs, PAs in the ED ■ Alcohol and CHD risk

PAGE 27

LEGAL ADVISOR

A clinician quits her job but sues for wrongful termination

NEWSLINE There is room for improvement of current T2D screening guidelines.

■ Hydrocodone upscheduling ■ CDC Shigella update ■ Managing preterm GER LEGAL ADVISOR

42

DERMATOLOGIC LOOK-ALIKES

Erythematous annular lesions

A HIPAA violation threatens a nurse’s career

These protozoa can multiply rapidly in Increased use ofbrain, liver, the social media has and heart. been linked to depression and anxiety.

DERMATOLOGY CLINIC

Irritative lesions in the abdomen and genital region

DERMATOLOGY CLINIC FREE CE COURSE

Laparoscopic sleeve gastrectomy

Hyperpigmented bands across all fingernails

FREE CME COURSE

Inflammatory bowel disease: a collaborative approach

2018 SALARY SURVEY

See how your salary compares with your peers!

PAGE 30

FREE CE COURSE

Precancerous GI mucosal lesions

VOLUME 21, NUMBER 7

VOLUME 21, NUMBER 9

Evidence-Based Medicine ■ Budesonide/formoterol for the prevention of serious asthma exacerbations ■ Limited formula supplementation may not adversely affect breastfeeding

Social media and health care: a closer look at Internet challenges and what clinicians can do to keep teens safe PAGE 30

SUBSCRIPTIONS & SUBMISSIONS

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Dermatology Clinic ■ Facial plaques following acne treatment ■ Hyperpigmented lesion with vanishing mole

51

Dermatologic Look-Alikes Erythematous annular lesions

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59

Legal Advisor Is clinician testimony hearsay?

CONTACT THE EDITOR • editor@ClinicalAdvisor.com • Call 646.638.6078

ADVISOR FORUM

© The New Yorker Collection 2018 from cartoonbank.com. All Rights Reserved.

57

Case Files ■ A sampling of our readers’ interesting cases, as well as a diagnostic challenge

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SOCIAL MEDIA AND ADOLESCENTS

Assessment of currentOverview of aHow growing serious are the screening methods forUS public health concern health risks associated predicting diabetes risk with social media use?

SUBMIT AN ARTICLE editor@ClinicalAdvisor.com SUBMIT A QUESTION FOR PUBLICATION • ClinicalAdvisor.com/AdvisorForum • editor@ClinicalAdvisor.com DO YOU HAVE A CLINICAL PEARL? Share your clinical pearl on a diagnosis or treatment tip with your colleagues.

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The AGA recommends PEG laxatives (like MiraLAX) as a first-line constipation treatment1

✔ 96% patient satisfaction rate* ✔ #1 GI-recommended laxative for over 10 years Start with MiraLAX for proven relief of occasional constipation. *Survey of 300 consumers, 2017.

Use as directed on product labeling or as directed by your doctor.

Reference: 1. Clinical decision support tools. American Gastroenterological Association website. http://campaigns.gastro.org/algorithms/constipation/index.html. Accessed May 12, 2017.

Bayer, the Bayer Cross, and MiraLAX are trademarks of Bayer. © 2017 Bayer May 2017 68522-PP-MLX-BASE-US-0328

1003669ha_a.indd 1

Doctor recommended, patient approved

6/2/17 10:21 AM

EXCLUSIVE TO THE WEB AT

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NEWS ClinicalAdvisor.com/News

THE WAITING ROOM

Official Blog of The Clinical Advisor ClinicalAdvisor.com/WaitingRoom

Congenital Irregularities Not Linked to Metformin Use After First Trimester When comparing infants with all nongenetic abnormalities to genetic controls, the researchers did not fi nd significant correlations for higher rates of metformin exposure during the first trimester.

Sharon M. O’Brien, MPAS, PA-C Impact of Caffeine Consumption on Sleep Quality One of the main reasons why people keep the coffee pot close at hand is because we are a chronically sleep-deprived nation. However, drinking all that coffee may be contributing to poor sleep.

CASE STUDY Clinical Advisor.com/CaseStudy

L-Glutamine Oral Therapy Reduces Sickle Cell-Related Pain Better Than Placebo

Brady Pregerson, MD Purple Fingertips in an Elderly Woman An elderly woman with a history of hypertension and metastatic bladder cancer presents to the ED with bilateral finger pain and cyanosis associated with a 15-lb weight loss. Read the full case here: ClinicalAdvisor.com/CasePurpleFingertips

Oral L-glutamine therapy significantly reduces pain crises associated with sickle cell disease compared with placebo regardless of patient hydroxyurea use.

Poor Adherence Contributes to Inadequate Uptake of Multidose Hepatitis Vaccine Schedules Adherence with and completion of the recommended multidose schedules for HepA, HepB, and HepA-HepB are low, and the vast majority of adults initiating vaccination may not be receiving the full protective benefit of these multidose vaccines.

CARTOON ARCHIVE

The Clinical Advisor’s monthly cartoons are also available online.

ClinicalAdvisor.com/cartoons

Research shows that patients diagnosed with atopic dermatitis experience feelings of dissatisfaction with regard to lifestyle, as well as impaired health and wellness.

10 THE CLINICAL ADVISOR • SEPTEMBER 2018 • www.ClinicalAdvisor.com

“We’re 21 put together.”

© Harley Schwadron 2018

Atopic Dermatitis Associated With Impaired Quality of Life, Overall Health

Advisor Dx 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 ClinicalAdvisor.com/AdvisorDx. Learn more about diagnosing and treating these conditions, and see how you compare with your fellow colleagues.

Check out some of our latest cases below!

DERM DX

Papule With Pigmented Speckles A 70-year-old woman presents for evaluation of a painless growth on her right wrist that was noted 2 months ago. She has had longstanding psoriasis now well maintained on ustekinumab. She underwent treatment with etanercept and efalizumab, the latter during a phase 2 clinical trial. She denies history of skin cancer. Exam reveals a 0.8-cm flesh-colored papule with pigmented speckles.

CAN YOU DIAGNOSE THIS CONDITION?

• Basal cell carcinoma • Granular cell tumor

• Keratoacanthoma • Merkel cell carcinoma

● See the full case at ClinicalAdvisor.com/DermDx_Sept18

In partnership with

ORTHO DX

TheJopa.org

Journal of Orthopedics for Physician Assistants

Right Hip Pain Following a Fall on Ice A 42-year-old man presents to the office with 2 months of right hip pain. He reports falling on the hip after slipping on ice, and he has been complaining of moderate pain in the hip since the fall.

The initial radiographs of the hip taken at the time of injury were negative for a fracture. Magnetic resonance imaging was conducted.

WHICH IS THE BEST TREATMENT OPTION?

• Observation and weight bearing, as tolerated • Partial weight bearing • Non-weight bearing • Urgent internal fixation ● See the full case at ClinicalAdvisor.com/OrthoDx_Sept18

www.ClinicalAdvisor.com • THE CLINICAL ADVISOR • SEPTEMBER 2018 11

Newsline INDIVIDUALS WITH clinically diagnosed celiac disease have a greater rate of functional dyspepsia, a gastrointestinal disorder highly correlated with wheat sensitivity, according to a study published in The American Journal of Gastroenterology.

A population-based group analysis was conducted to compare self-reported gluten sensitivity, physician-diagnosed celiac disease, and functional gastrointestinal disorders or symptoms.The investigators released a survey to randomly selected Australian individuals; the survey included questions regarding wheat sensitivity, gastrointestinal symptoms, demographic information, and factors contributing to health and lifestyle. Self-reported wheat sensitivity was defined as gastrointestinal symptoms upon consumption of wheat-based foods

reported by an individual with no history of celiac disease, inflammatory bowel disease, or colorectal cancer.

A total of 3542 people responded to the survey, and 3115 completed all components; 14.9% self-reported wheat sensitivity, 10.8% of whom had also been diagnosed by their physician as having gluten or wheat intolerance. A diagnosis of celiac disease was reported in 1.2% of the population. For individuals with clinically diagnosed celiac disease, the odds of additional diagnosis of functional dyspepsia and irritable bowel syndrome were significantly greater compared with those nonaffected (odds ratio [OR], 3.35 and 2.28, respectively). Self-reported wheat sensitivity was independently correlated with irritable bowel syndrome and functional

© WOJCIECH KOZIELCZYK / GETTY IMAGES

Celiac Disease, Wheat Sensitivity Link Examined

dyspepsia according to a multivariate test (OR, 3.55 and 1.48, respectively).

“Self-reported wheat sensitivity is common, with a prevalence of 14.9% in this cohort,” the authors wrote. “There is a strong association between both celiac disease and self-reported wheat sensitivity, and chronic gastrointestinal symptoms, as well as a diagnosis of [functional dyspepsia] and [irritable bowel syndrome].”

Fidaxomicin Effective for Long-Term Cure of Clostridium difficile FIDAXOMICIN was found to be more effective than metronidazole in providing a long-term cure for C difficile, according to a study published in The Lancet.

A team of investigators from the United Kingdom conducted a systematic review and network meta-analysis to compare various treatments of C difficile. Included trials involved patients aged ≥18 years who had confirmed C difficile infections, defined as active diarrhea and a positive C difficile nucleic acid amplification test, a positive C difficile cytotoxin assay result, a stool culture that showed C difficile, or pseudomembranes identified on colonoscopy.

A total of 24 studies that included 5361 patients were included in the meta-analyses (mean study sample size, 223 patients). All studies were published between 1983 and 2017. Most listed follow-up time between 21 and 30 days; one study reported outcomes at 56 days, and another reported outcomes at 90 days.The most frequent treatment was vancomycin (n=2107 participants), followed by fidaxomicin (n=881) and metronidazole (n=563). Duration of treatment ranged from 4 to 25 days.

Teicoplanin (odds ratio [OR] 0.37) and fidaxomicin (OR 0.67) were significantly more effective than vancomycin

12 THE CLINICAL ADVISOR • SEPTEMBER 2018 • www.ClinicalAdvisor.com

in achieving sustained symptomatic cure.

Vancomycin, teicoplanin, ridinidazole, fidaxomicin, and surotomycin were all more effective than metronidazole. No treatment was found to be significantly superior to vancomycin for primary symptomatic cure. Significantly fewer associated recurrences were reported with fidaxomicin compared with vancomycin and metronidazole.

“Of the currently approved treatments, fidaxomicin has the strongest evidence for being the most effective treatment in providing a long-term cure against C difficile,” the authors concluded.

Newsline

© DAVID M. MARTIN, M.D. / SCIENCE SOURCE

PPI and Aspirin Improve Outcomes in Barrett Esophagus

Combination PPI and aspirin was assessed in Barrett esophagus.

PROTON PUMP inhibitors (PPIs) administered in high doses and aspirin chemoprevention therapy additively improve health outcomes in patients with Barrett esophagus, according to research published in The Lancet.

A team of investigators in the United Kingdom conducted a randomized factorial design trial to determine the effectiveness of high-dose esomeprazole and aspirin on outcomes in patients with Barrett esophagus.

The researchers invited patients with Barrett esophagus ≥1 cm to be randomly but not blindly administered high-dose esomeprazole 40 mg twice daily or lowdose esomeprazole 20 mg once daily, with or without aspirin 300 mg once daily for ≥8 years.

Primary outcomes included effectiveness of high-dose PPI vs low-dose PPI and the effectiveness of aspirin vs no aspirin. First occurrence of all-cause mortality, esophageal adenocarcinoma, or high-grade dysplasia was the primary combined end point.

The secondary outcome measured the impact of time on patient primary combined end points, cause-specific mortality, and combined end point factored by sex.

A total 2557 patients aged ≥18 years from 84 centers in the United Kingdom and 1 center in Canada were included in the analysis over a median of 8.9 years.

Recruitment of women was limited to approximately 20% of the total enrollment in light of the lower risk of Barrett esophagus in this population. High-dose esomeprazole without aspirin was administered to 705 individuals and low-dose esomeprazole without aspirin was administered to 705; 577 received high-dose esomeprazole with aspirin, and 571 received low-dose esomeprazole with aspirin.

Participants in Canada were administered aspirin 325 mg/d, while those in the United Kingdom received 300 mg/d.

There were 313 reported primary event occurrences: 139 events in 1270 patients receiving high-dose PPI and 174 events in 1265 patients receiving low-dose PPI. No significant difference was seen with aspirin vs no aspirin (127 events in 1138 patients vs 154 events in 1142 patients).Time ratios (TR) for high- and low-dose esomeprazole and presence and absence of aspirin were 1.27 and 1.24, respectively.

In contrast, censoring patients who used other nonsteroidal anti-inflammatory drugs at initial use suggest aspirin is significantly better than no aspirin (TR, 1.29).The strongest effect was observed in patients taking high-dose esomeprazole in combination with aspirin compared with patients taking low-dose esomeprazole without aspirin (TR, 1.59).

“We have shown that high-dose PPI use protects against a composite endpoint of all-cause mortality, oesophageal adenocarcinoma, and high-grade dysplasia,” noted the investigators. “These data also raise the possibility that all patients needing long-term PPI to control reflux symptoms might benefit from the co-prescription of aspirin with acid suppression.”

14 THE CLINICAL ADVISOR • SEPTEMBER 2018 • www.ClinicalAdvisor.com

Lack of Trust Drives High Exemption Rates for Pediatric Vaccination IN AREAS where vaccine exemptions are high, exempting parent respondents to a survey were very likely to have views that vaccinepreventable diseases are not severe and that developing immunity through illness is more beneficial than vaccination, according to a study published in PLoS ONE. Investigators distributed surveys to parents with children attending elementary school in high-exemption areas of Arizona (>10%); 404 surveys were collected from 9 schools in 2 counties to understand and compare exemptor and non-exemptor views on pediatric vaccination. Of the total, 141 were exemptors (261 were non-exemptors). These participants were more inclined to worry about vaccine-related side effects and know someone with a vaccinepreventable disease but less inclined to report such diseases as serious.

In addition, the surveys suggested that exemptor parents felt it was more beneficial for a child to build immunity to disease through illness rather than to undergo vaccination.

Compared with non-exemptor parents, exemptor parents were found to be more distrustful of physicians and vaccine-related information, and they more often received health care from naturopathic providers. “[There] is a great need for development and provision of tailored educational materials and efforts that not only cite sources which the target audience trusts, but are also tested for impact prior to implementation,” noted the authors. ■

FEATURE: WESLEY B. SWITZER, MSN, RN; FELICIA STEWART, DNP, FNP-C; JAN PAAUWE-WEUST, DNP, RN

Fasting Insulin vs HbA1c: Are We Getting It Right?

The early diagnosis and management of prediabetes will have a significant impact on patient outcomes and healthcare spending.

Recommended screening techniques for diabetes include FPG, OGTT, HbA1c, and random PG levels.

N

o primary care provider can deny the impact type 2 diabetes mellitus (T2D) has on the health of its population and the economy of the United States. The American Diabetes Association (ADA) estimates the annual cost of diagnosed diabetes at an astounding $245 billion in the United States.1 The Centers for Disease Control and Prevention estimated that 30.2 million adults — 12.2% of the US adult population — were living with diabetes in 2015, 7.2 million (23.8%) of whom were undiagnosed.2 An additional 84.1 million US adults are prediabetic, with nearly 90% unaware of their condition.2 Imagine the possible impact on patient outcomes and healthcare spending if clinicians could decrease the number of undiagnosed individuals and identify those with prediabetes much earlier.

© JEAN-PAUL CHASSENET / SCIENCE SOURCE

Background

Current ADA guidelines recommend screening for diabetes and prediabetes in adults with a body mass index (BMI) >25 kg/m2 and the presence of 1 or more risk factors.3 Recommended screening techniques include fasting plasma glucose (FPG), oral glucose tolerance testing (OGTT), glycated hemoglobin (HbA1c), and random plasma glucose levels. Standardized screening of individuals at high risk of developing T2D would ideally reduce the number of those unaware of their prediabetic or diabetic state. However, in a national survey of 1240 primary care physicians, only 52.4% reported following the current national prediabetes screening guidelines.4 This represents missed opportunities to provide early intervention and potentially prevent the progression of prediabetes to T2D. www.ClinicalAdvisor.com • THE CLINICAL ADVISOR • SEPTEMBER 2018 15

FASTING INSULIN vs HbA1c

Screening for diabetes and prediabetes is recommended by the ADA for adults with a body mass index >25 kg/m2 and 1 or more risk factors.

Due to its convenience, many clinicians have come to rely exclusively on HbA1c for T2D screening. However, HbA1c offers lower sensitivity than other screening tests, and individuals have likely developed significant insulin resistance and pancreatic beta-cell dysfunction by the time it rises significantly.5 Research suggests that a state of insulin resistance occurs before the development of T2D.6 In an effort to maintain glycemic homeostasis, beta cells increase their secretion of insulin to lower blood glucose levels.7 Due to this increased workload, beta cells begin to fail.

Failure of beta cells to produce enough insulin to overcome resistance leads to impaired glucose tolerance (IGT) and eventually T2D.6 Identifying prediabetes before this marked beta-cell dysfunction occurs would greatly increase the opportunity for remission or delayed progression to T2D. This pathophysiology suggests that fasting insulin levels could identify insulin resistance long before plasma glucose and HbA1c levels rise.

Current Screening Methods

The ADA and World Health Organization (WHO) offer differing criteria for a diagnosis of prediabetes, neither of which includes fasting insulin levels as a marker of T2D risk. Research has shown varying efficacy for HbA1c, FPG, and OGTT in their ability to detect prediabetes, and differing opinions exist on the best test to screen for prediabetes. Via meta-analysis, Barry et al found the pooled sensitivity of HbA1c to be 0.49 with a specificity of 0.79 and the pooled sensitivity of FPG to be 0.25 with a specificity of 0.94.8 The researchers explained that results of both these tests are highly variable depending on population and setting. Despite OGTT being widely accepted as a more accurate tool for diagnosing T2D, it is time consuming and not widely used for initial screening.8 These limitations of current screening methods underscore the need to find a more efficacious test in terms of ease of use, accuracy, and cost.

Purpose

This literature review explores what the current published literature demonstrates about the fasting insulin level and whether or not it is efficacious in identifying prediabetes earlier than the traditional screening laboratory assessments (HbA1c, FPG, and 2-hour plasma glucose with OGTT).With nearly half the US adult population being either diabetic or prediabetic, the importance of accurate and early screening methods is obvious. This information will increase providers’ knowledge of the efficacy of T2D screening measures and assist clinicians in identifying diabetes or prediabetes risk at its earliest stages.This could potentially increase the number of individuals identified

as diabetic or prediabetic and have a profound impact on patient outcomes, disease prevention, and healthcare costs.

Search Strategy

The Cochrane Library and EBSCOhost were utilized to search for published literature from 2013 to the present containing information about utilizing a fasting insulin level as a diagnostic tool for diabetes, prediabetes, metabolic syndrome, or insulin resistance in the adult population. Additional articles containing information about the efficacy of current diabetes screening methods or prevention strategies were also reviewed.

Articles were excluded if the studies featured nonadult samples.

Additionally, non-English publications were not considered.

An initial search of the Cochrane Library for the identified time period focused on articles utilizing the term fasting insulin in the title, abstract, or keywords.The search yielded 12 Cochrane Reviews.The titles and abstracts of these results were reviewed and none were found to be pertinent to the purpose of this review.

Additional searches of the Cochrane Library substituted the search term with prediabetes, hyperinsulinism, plasma insulin, blood insulin, and predicting diabetes. None of these searches resulted in the discovery of articles that met the established inclusion criteria.

EBSCOhost was then utilized; the selected databases included Academic Search Complete, CINHAL, and Medline. Searches were limited to articles published from 2013 to 2018. A search for the subject term fasting insulin generated 39 results. Based on title and abstract review, 2 articles were retained due to their potential relevance to the adult population at risk for prediabetes or diabetes. A search for the subject terms blood insulin AND diabetes yielded 356 results with only 2 articles continuing to be included for review after title and abstract examination.A search for the subject terms hyperinsulinism AND prediabetes yielded 25 results; 1 publication met the criteria for inclusion. Additional independent and combined searches of keywords insulin lab, hyperinsulinemia, metabolic syndrome, plasma insulin, and insulin resistance were performed resulting in 5 more articles for inclusion.

A total of 10 articles were determined to meet inclusion criteria for this review of the literature. One article was a systematic review and the others were cross-sectional studies, randomized control trials, prospective studies, and retrospective studies.

Review of the Literature

Systematic Review Kelly et al performed a systematic review to evaluate the association between elevated plasma insulin levels and the traits associated with metabolic syndrome.9 The metabolic traits examined

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HbA1c offers lower sensitivity than other screening tests, and patients may develop significant insulin resistance by the time it rises significantly. included hypertension, obesity, certain cancers, polycystic ovarian syndrome (PCOS), sleep apnea, atherosclerosis, dyslipidemia, cardiovascular disease (CVD), nonalcoholic fatty liver disease, renal failure, and T2D. The researchers selected 58 articles in which insulin level was measured and evaluated them for associations between hyperinsulinism and the selected metabolic conditions.

They documented 63 instances of hyperinsulinism being found in association with the abovementioned conditions and noted only 3 instances of normal insulin levels correlating with hypertension, PCOS, and certain cancers. They concluded that the consistent links between elevated insulin level and 11 disorders associated with metabolic syndrome indicated the potential pathogenic impact of elevated insulin level on a wide range of body tissues.

Research Studies Pataky et al performed a cross-sectional longitudinal study involving 1211 adult participants to identify associations between fasting insulin level, insulin sensitivity, and lifestyle parameters with cardiometabolic risk factors.10 Among the cardiometabolic risk factors examined were blood glucose level, low-density lipoprotein (LDL), blood pressure, triglyceride level, and waist circumference. Follow-up was concluded at the 3-year mark, and multiple regression analysis was utilized to identify independent contributors to cardiometabolic risk.The researchers determined that adiponectin, tobacco use, BMI, and elevated fasting insulin level were all independently associated with the number of risk factors. Changes in fasting insulin and BMI were also found to positively correlate with the number of cardiometabolic risk factors present.The researchers concluded that fasting hyperinsulinemia was associated with cardiometabolic changes independent of hyperglycemia and insulin resistance.

Lunger et al evaluated methods for identifying insulin resistance in women with PCOS.11 Their retrospective review focused on the medical records of 147 women meeting the criteria for a diagnosis of PCOS and evaluated the impact particular variables had on insulin levels and insulin resistance indices.The efficacy of fasting insulin assessment in identifying insulin resistance was determined by calculating specificity, sensitivity, and the predictive values at various levels.Women identified as being insulin resistant via 3-hour OGTT were found to have significantly higher fasting insulin levels. Receiver operating characteristics (ROC) analysis revealed fasting insulin to be an effective measure of insulin resistance.The researchers determined that setting cut-off points for fasting insulin at <7 μU/mL and >13 μU/mL could accurately identify nearly two-thirds of the women with insulin resistance.

Welsh et al explored the relationship between early markers of insulin resistance with T2D and CVD.12 Using data previously collected in the Prospective Study of Pravastatin in the Elderly at Risk (PROSPER) trial cohort (ISRCTN Registry Number: ISRCTN40976937), they examined the connection between the homeostatic model assessment of insulin resistance (HOMA-IR), CVD, all-cause mortality, and T2D. Fasting insulin levels or HOMA-IR data were available on 4742 elderly individuals. At the 3.2-year follow-up, 283 participants had received a diagnosis of T2D. Statistical analysis of these data indicated a strong association between T2D and fasting insulin level and the HOMA-IR. Conversely, the researchers found no correlation between HOMA-IR and fasting insulin with CVD-related deaths in this population.

Ghasemi et al followed 4942 Iranian adults in an effort to determine cut-off points for measures of insulin sensitivity, insulin resistance, beta-cell function, and fasting insulin for identification of T2D risk.13 Cut-off points for predicting T2D were determined using ROC curve analysis to estimate the specificity and sensitivity of each laboratory assessment. The researchers identified the cut-off points using theYouden index and setting the sensitivity to 75% in an effort to capture high-risk individuals and avoid misclassification.They identified fasting insulin and HOMA-IR as independent predictors of T2D. The researchers elaborated on these findings by identifying optimal cut-off points (75% sensitivity) for HOMA1-IR at 1.86 for women and 1.34 Continues on page 22

POLL POSITION Hyperinsulinism is associated with all but which of the following?

■ Renal failure ■ Cigarette smoking ■ PCOS ■ Sleep apnea

15.19%

14.10%

14.10% 56.61%

For more polls, visit ClinicalAdvisor.com/Polls.

www.ClinicalAdvisor.com • THE CLINICAL ADVISOR • SEPTEMBER 2018 17

FASTING INSULIN vs HbA1c

Investigators

Study Type

Objective

Data Source

Conclusion

Kelly et al9

Systematic review

Determine relationship between elevated plasma insulin and metabolic syndrome traits.

58 articles

The consistent links between elevated insulin level and 11 disorders associated with metabolic syndrome indicated the potential pathogenic impact of elevated insulin level on a wide range of body tissues.

Pataky et al10

Cross-sectional longitudinal study

Identify associations between fasting insulin level, insulin sensitivity, and lifestyle parameters with cardiometabolic risk factors.

1211 participants

Fasting hyperinsulinemia was associated with cardiometabolic changes independent of hyperglycemia and insulin resistance.

Lunger et al11

Retrospective, crosssectional review

Assess impact of particular variables on insulin levels and insulin resistance indices in women with PCOS.

147 medical records

Cut-off points for fasting insulin (<7 μU/mL and >13 μU/mL) may accurately identify women with insulin resistance.

Welsh et al12

Long-term follow-up of randomized, double-blind, placebo-controlled trial

Examine the connection between the HOMA-IR, CVD, all-cause mortality, and T2D.

4742 participants

Identified strong association between T2D and fasting insulin level and the HOMA-IR.

Ghasemi et al13

Cross-sectional study with prospective follow-up

Determine cut-off points for measures of insulin sensitivity, insulin resistance, beta-cell function, and fasting insulin for identification of T2D risk.

4942 participants

Fasting insulin and HOMA-IR were identified as independent predictors of T2D, with optimal cut-off points identified.

Saravia et al14

Longitudinal cohort study

Evaluate the connection between fasting insulin levels and HbA1c with metabolic syndrome.

3200 male participants

Elevated insulin levels appear to identify certain cardiometabolic changes earlier than both HbA1c and measures of glucose.

Derakhshan et al15

Cross-sectional study with prospective follow-up

Investigate the relationship between beta-cell function, fasting insulin levels, and insulin resistance and progression to T2D.

3753 participants

A compensatory increase in insulin secretion occurs prior to the development of glucose abnormalities.

Yang et al16

Observational study

Assess variances in insulin resistance.

80 participants

Findings support the suggestion that the progression to T2D includes a hyperinsulinemic stage and a prediabetic stage.

Ruijgrok et al17

Population-based, prospective cohort study

Examine the links between fasting insulin, HbA1c, FPG, the HOMA-IR, and 2-hour plasma glucose with progression to T2D.

1349 participants

Fasting insulin was not found to be associated with the incidence of T2D, after adjusting for metabolic and lifestyle variables.

Pennings et al18

Population-based, retrospective cohort study

Investigate the relationship between fasting insulin levels and weight gain

3840 participants

BMI, race, smoking status, fasting glucose, weight change, and HOMA-IR were found to be significantly associated with increases in the fasting insulin level.

BMI = body mass index; CVD = cardiovascular disease; FPG = fasting plasma glucose; HbA1c = glycated hemoglobin; HOMA-IR = homeostatic model assessment of insulin resistance; PCOS = polycystic ovarian syndrome; T2D = type 2 diabetes mellitus

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for men, HOMA2-IR at 1.01 for women and 0.75 for men, and fasting insulin at 7.51 μU/mL in women and 5.48 μU/mL in men.

Saravia et al conducted a study involving 3200 male participants to evaluate the connection between fasting insulin levels and HbA1c with metabolic syndrome.14 Both HbA1c and fasting insulin levels were found to correlate strongly with metabolic syndrome and its associated traits (eg, BMI, cholesterol levels, blood pressure, waist circumference, and blood glucose).

However, plasma insulin levels showed stronger associations than HbA1c to all the associated traits of metabolic syndrome except for hyperglycemia,“… and there were significant differences between the low- and mid-range of insulin for all criteria except high blood pressure.”14 The researchers concluded that elevated insulin levels appeared to identify certain cardiometabolic changes earlier than both HbA1c and measures of glucose.

Derakhshan et al investigated the relationship between beta-cell function, fasting insulin levels, and insulin resistance and progression to T2D.15 Participants included 1532 male and 2221 female Iranian adults with no apparent glycemic impairment. They found the annual incidence rate of diabetes in this population to be 3.73/1000 person-years in the 9.2-year follow up. HOMA-IR and hyperinsulinemia were found to be associated with progression to T2D, impaired glucose tolerance, and impaired fasting glucose in both genders. However, the researchers were unable to link beta-cell dysfunction to the incidence of diabetes and surmised that this could be explained by the natural progression of diabetes.The researchers concluded that underlying pathophysiology indicates there is “…a compensatory increase in insulin secretion before the development of glucose abnormalities.”15 Yang et al assessed variances in insulin resistance in their study involving 80 adult participants.16 Individuals with glycemic dysfunction were categorized into 4 groups: normal glucose tolerance (NGT), hyperinsulinemia with NGT (HINS), impaired glucose tolerance (IGT), and newly diagnosed T2D.The researchers collected baseline data, performed OGTT, calculated simple indices of insulin resistance, and used the hyperinsulinemic-euglycemic clamp technique to measure accurate levels of insulin resistance.

They determined that insulin sensitivity was lower in the HINS, IGT, and T2D groups but not statistically significantly different from one another.This finding indicates that insulin sensitivity is already impaired in the HINS state long before glucose tolerance becomes impaired.The researchers employed stepwise regression analysis to identify waistline measurement and fasting insulin level as independent predictors of insulin resistance. These findings support the suggestion that the progression to T2D includes a hyperinsulinemic stage and a prediabetic stage.

Ruijgrok et al analyzed baseline data from 1349 participants from the city of Hoorn, in the Netherlands.17 Their study examined the links between fasting insulin, HbA1c, FPG, the HOMA-IR, and 2-hour plasma glucose with progression toT2D.

Baseline data were collected on the aforementioned laboratory assessments as well as BMI, family history, social history, blood pressure, exercise habits, and diet. The outcomes measure was identified as the incidence of T2D utilizing the 2011 WHO diagnostic criteria.At the 6.4-year follow-up, 11.2% of the participants had been diagnosed withT2D. Logistic regression models were utilized to calculate the probability of developing T2D for each quintile of fasting insulin, HbA1c, FPG, HOMA-IR, and 2-hour plasma glucose. The researchers determined that there were strong nonlinear associations between FPG and HbA1c with T2D. As the FPG and HbA1c increased, the incidence of T2D increased more sharply. However, the correlations between insulin resistance and fasting insulin with T2D were found to be more linear. Ultimately, the researchers determined that after adjusting for metabolic and lifestyle variables, fasting insulin was not statistically significantly associated with the incidence of T2D. Pennings et al investigated the relationship between fasting insulin levels and weight gain.18 Their study included 3840 participants from NHANES who were divided into 6 groups based on fasting insulin level and level of glycemic impairment.The researchers identified 5.48 µU/mL as the cut-off point for normal fasting insulin. This study identified that participants with normal fasting insulin levels gained an average of 1.40 lb in the 10-year follow-up period while individuals with elevated fasting insulin gained an average of 11.12 lb.

Additionally, the researchers found “…BMI, race, smoking status, fasting glucose, weight change, and HOMA-IR” to be significantly associated with increases in the fasting insulin level.18 They calculated that each 1-μU/mL increase in fasting insulin resulted in 0.52 lb of added weight. Remarkably, most of the weight gain occurred before glycemic impairment was measurable, which would implicate hyperinsulinism, not hyperglycemia, as an instrumental factor in weight gain.

Discussion

The available research consistently indicates a strong association between elevated insulin levels and risk for developing metabolic dysfunction.The majority of the studies included in this review utilized varying methodologies and adequately large sample sizes from diverse populations. In an effort to minimize bias and confounding variables, inclusion and exclusion criteria were clearly stated in all included studies. Some researchers evaluated fasting insulin as a direct measure of T2D risk while others evaluated the association between fasting insulin and the traits of insulin resistance. Ultimately, the large majority of researchers concluded that elevated fasting insulin levels were associated with the early physiologic changes of metabolic syndrome and T2D. It has become widely accepted that a state of insulin resistance and hyperinsulinism precedes prediabetes and T2D. Pennings Continues on page 26

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FASTING INSULIN vs HbA1c

Targets for Future Research While the research might not yet support substantial changes to current screening guidelines, continued research is warranted to better evaluate the fasting insulin level as a diagnostic or screening tool. Several questions come to mind in terms of continued research: • Can fasting insulin levels be used as an early cost-effective risk identifier for certain metabolic disorders?

• Does early intervention decrease morbidity in those identified as having elevated fasting insulin levels?

• Are lifestyle changes enough to reverse hyperinsulinemia?

• How far ahead of a T2D diagnosis do fasting insulin levels identify metabolic dysfunction?

et al identified the association between hyperinsulinism and weight gain and suggested that weight gain is independently associated with elevated insulin level and not with hyperglycemia, as previously believed.18 The most significant weight gains occurred in the early stages of insulin resistance and at relatively low levels of insulin elevation. This suggests that significant metabolic alterations occur before the most common screening methods are able to identify glycemic impairment. These findings are consistent with those of an earlier study by Pataky et al, which indicated that hyperinsulinemia is associated with cardiometabolic changes independent of hyperglycemia and insulin resistance.10 Pennings et al conducted one of the only studies that included participants from the United States; the researchers utilized a large sample selected using the NHANES database, allowing them to select a sample with demographics representative of the national population.18 They identified the strong association between fasting insulin and common precursors and risk factors for T2D: insulin resistance and weight gain.

These findings support the suggestion that the progression to T2D includes a hyperinsulinemic stage and a prediabetic stage.16 Multiple studies with large sample sizes from varying populations identified a strong correlation between fasting elevated insulin levels and T2D or other metabolic syndrome traits.

Among them wereWelsh et al, who identified a strong association between T2D and fasting insulin level in an older adult population,12 and Saravia et al, who studied 3200 male factory workers and noted that insulin appears to identify cardiometabolic changes earlier than both HbA1c and glucose measurements.14 Derakhshan et al15 and Ghasemi et al13 both followed a large population of Iranian adults and identified hyperinsulinism as an independent risk factor for the development of T2D. Ghasemi et al identified fasting insulin level as a possible predictive tool and contributed to improved reproducibility by recognizing

suggested laboratory cut-off values for determining T2D risk.13 Current literature regarding the fasting insulin level is limited, and its role in the development of insulin resistance, metabolic syndrome, and T2D is not fully understood.While most of the studies included in this review utilized large sample sizes, the shortage of recent publications is a limitation.The researchers typically utilized convenience sampling, which introduced the opportunity for bias, and the applicability of findings was further limited by widely varying follow-up durations that ranged from 3 years to 9.2 years. Ruijgrok et al found that fasting insulin was not statistically significantly associated with the incidence of T2D in a 6.4-year follow-up,17 which contradicts other researchers’ findings. More long-term follow-up is therefore necessary to better evaluate the association between fasting insulin levels and development of T2D. While Welsh et al12 identified strong correlations between fasting insulin level and development of T2D, the advanced age of this sample — 70 to 82 years — limits more widespread generalizability. Saravia et al14 also found strong links between fasting insulin level and components of metabolic syndrome, but generalizability is limited by the all-male and largely Spanish sample. The same is true for the study by Lunger et al, in which they highlighted the potential use of fasting insulin level to identify early metabolic dysfunction in those with PCOS.11 However, the researchers utilized a relatively small sample size, and the apparent fluctuations in insulin levels among those with PCOS make generalization difficult.

The systematic review by Kelly et al merely identifies the presence of hyperinsulinism in the mentioned conditions.9 The methodology does not allow for one to identify the cause or nature of the relationship between elevated insulin level and the evaluated disorders. Similarly, Pennings et al did not directly measure the ability of the fasting insulin level to identify risk for T2D; they identified the correlation between fasting insulin and weight gain.18 Moreover, in all of the included studies, researchers only speculated on the potential cost benefits of early identification of this hyperinsulinemic state. There was no actual empirical evidence related to the cost-effectiveness of utilizing fasting insulin screenings to identify T2D risk.

Implications for Practice

While the available literature on T2D is overwhelming, it is apparent that much room exists for improvement of current screening guidelines and continued research.While the associations of FPG, HbA1c, and 2-hour plasma glucose with T2D are well studied and widely known, the role of fasting insulin level as it relates to progression of insulin resistance to diabetes is still poorly understood. Therefore, it remains unclear as to when insulin levels will start to rise and for how many years they can remain elevated before irreversible metabolic changes or beta-cell

26 THE CLINICAL ADVISOR • SEPTEMBER 2018 • www.ClinicalAdvisor.com

degradation occurs. This makes it challenging to identify the accuracy of the fasting insulin level as a predictor of T2D risk.

Hyperinsulinism has been identified in prediabetes,T2D, dyslipidemia, obesity, hypertension, PCOS, fatty liver disease, certain cancers, CVD, renal failure, and sleep apnea.9The combined burden of these conditions on the American healthcare system is astonishing. Saravia et al14 concluded that fasting insulin level appears to identify certain cardiometabolic changes earlier than both HbA1c and glucose measurements, and Pataky et al10 established that fasting hyperinsulinemia is associated with cardiometabolic changes independent of hyperglycemia and insulin resistance.

These findings underscore the potential to identify these at-risk patients much earlier than current practice allows. Individuals in earlier stages of metabolic dysfunction would theoretically require less-intense interventions to slow or reverse their diseased state.

Fasting insulin levels have been identified as simple and effective measures of insulin resistance in the absence of diabetes and could potentially identify individuals at risk of developing certain metabolic conditions. The association between fasting insulin and metabolic syndrome and T2D has been well documented in this review, and hyperinsulinism has been shown to disrupt other components of the endocrine system, as well as have harmful effects on other organ systems and tissues. Identifying this imbalance earlier could have a significant impact on the overall health of Americans. Individuals with elevated insulin levels could make preemptive lifestyle changes, thereby thwarting the development of T2D, CVD, dyslipidemia, obesity, and more. A simple laboratory test has the potential to change the way we identify at-risk individuals.

References 1. American Diabetes Association. Economic costs of diabetes in the U.S. in 2012. Diabetes Care. 2013;6(4):1033-1046.

2. American Diabetes Association. Classification and diagnosis of diabetes.

Diabetes Care. 2017;40(Suppl 1):S11-S24.

3. American Diabetes Association. Classification and diagnosis of diabetes: standards of medical care in diabetes—2018. Diabetes Care. 2018;41(Suppl 1):s13-s27.

4. Mainous AG, Tanner RJ, Scuderi CB, Porter M, Carek PJ. Prediabetes screening and treatment in diabetes prevention: the impact of physician attitudes.

J Am Board Fam Med. 2016;29(6):663-671.

5. Kanat M, DeFronzo RA, Abdul-Ghani MA. Treatment of prediabetes. World J Diabetes. 2015;6(12):1207-1222.

6. Pories WJ, Dohm GL. Diabetes: have we got it all wrong? Hyperinsulinism as the culprit: surgery provides the evidence. Diabetes Care. 2012;35(12):2438-2442.

7. Ye J. Mechanisms of insulin resistance in obesity. Front Med. 2013;7(1):14-24.

8. Barry E, Roberts S, Oke J, Vijayaraghavan S, Normansell R, Greenhalgh T. Efficacy and effectiveness of screen and treat policies in prevention of type 2 diabetes: systematic review and meta-analysis of screening tests and interventions. BMJ. 2017;356:1-16.

9. Kelly CT, Mansoor J, Dohm GL, Chapman WH, Pender JR, Pories WJ. Hyperinsulinemic syndrome: the metabolic syndrome is broader than you think. Surgery. 2014;156(2):405-411.

10. Pataky Z, Golay A, Laville M, et al. Fasting insulin at baseline influences the number of cardiometabolic risk factors and R-R interval at 3 years in a healthy population: the RISC study. Diab Metab. 2013;39(4):330-336.

11. Lunger F, Wildt L, Seeber B. Accurate screening for insulin resistance in PCOS women using fasting insulin concentrations. Gynecol Endocrinol. 2013;29(6):541-544.

12. Welsh P, Preiss D, Lloyd SM, et al. Contrasting associations of insulin resistance with diabetes, cardiovascular disease and all-cause mortality in the elderly: PROSPER long-term follow-up. Diabetologia. 2014;57(12):2513-2520.

Conclusion

13. Ghasemi A, Tohidi M, Derakhshan A, Hasheminia M, Azizi F, Hadaegh F.

Although the available literature on the prognostic value of the fasting insulin level is limited, this review highlights the potential benefit of this simple laboratory test. Healthcare providers are encouraged to adjust their practices to better focus on preventive and early detection efforts, but current screening guidelines leave much to be desired with regard to prevention of T2D and metabolic syndrome. The strength of the association between fasting insulin level and various metabolic disorders suggests that the fasting insulin level could be a valuable tool to identify those at risk of developing metabolic syndrome or T2D. While there is inadequate evidence to suggest guideline changes at this time, there is abundant evidence endorsing continued research. ■

Cut-off points of homeostasis model assessment of insulin resistance, betacell function, and fasting serum insulin to identify future type 2 diabetes: Tehran Lipid and Glucose Study. Acta Diabetol. 2015;52(5):905-915.

14. Saravia G, Civeira F, Hurtado-Roca Y, et al. Glycated hemoglobin, fasting insulin and the metabolic syndrome in males: cross-sectional analyses of the Aragon Workers’ Health Study baseline. Plos One. 2015;10(8):1-14.

15. Derakhshan A,Tohidi M, Arshi B, Khalili D, Azizi F, Hadaegh F. Relationship of hyperinsulinaemia, insulin resistance and β-cell dysfunction with incident diabetes and pre-diabetes: the Tehran Lipid and Glucose Study. Diabetic Med. 2015;32(1):24-32.

16. Yang G, Li C, Gong Y, et al. Assessment of insulin resistance in subjects with normal glucose tolerance, hyperinsulinemia with normal blood glucose tolerance, impaired glucose tolerance, and newly diagnosed type 2 diabetes (prediabetes insulin resistance research). J Diabetes Res. 2016;9270768.

Felicia Stewart, DNP, FNP-C, is affiliated with Saint Mary-of-theWoods College in St. Mary-of-the-Woods, Indiana, and Wellness For Life, LLC. Jan Paauwe-Weust, DNP, RN, is affiliated with Indiana State University in Terre Haute. Special acknowledgement to Kayur V. Patel, MD, FACEP, FACP, FACPE, FACHE, for igniting our interest in this topic and his support and engagement in future efforts in this area.

17. Ruijgrok C, Dekker JM, Beulens JW, et al. Size and shape of the associations of glucose, HbA1c, insulin, and HOMA-IR with incident type 2 diabetes: the Hoorn Study. Diabetologia. 2018;61(1):93-100.

18. Pennings N, Jaber J, Ahiawodzi P. Ten-year weight gain is associated with elevated fasting insulin levels and precedes glucose elevation. Diab Metab Res Rev. 2018;34(4):e2986.

www.ClinicalAdvisor.com • THE CLINICAL ADVISOR • SEPTEMBER 2018 27

FEATURE: TANYA SARGENT, RN, BSN

Raising Awareness of Pseudobulbar Affect Pseudobulbar affect is a significant national health issue in the United States, with approximately 2 million individuals affected.

© WESTEND61 GMBH / ALAMY STOCK PHOTO

P

Diagnostic criteria are available to help distinguish PBA from depression.

28 THE CLINICAL ADVISOR • SEPTEMBER 2018 • www.ClinicalAdvisor.com

seudobulbar affect (PBA) is a relatively common disorder of emotional expression that occurs in many neurologic disorders including amyotrophic lateral sclerosis (ALS), multiple sclerosis (MS), stroke, dementia, parkinsonian disorders, brain tumor, and traumatic brain injury.

Pseudobulbar affect is a significant national health issue in the United States, occurring in greater numbers of individuals than those affected by Parkinson disease, MS, or ALS. An estimated 2 million individuals are affected in the United States.1 According to The PBA Registry Series, the prevalence of PBA symptoms in patients with specific neurologic conditions is as follows: Alzheimer disease, 29%; ALS, 45%; MS, 46%; Parkinson disease, 26%; stroke, 38%, and traumatic brain injury, 52%.2 Despite the significant prevalence of this disorder, many providers are unaware of or frequently misdiagnose PBA. Pseudobulbar affect is characterized by sudden, frequent, uncontrollable outbursts of crying and/ or laughing that may be disproportionate or inappropriate to the social context.Although patients may experience uncontrollable crying, laughing, or both, the former appears to be a more common manifestation of PBA. Crying is often described as occurring in situations that are sad or otherwise emotionally touching but that would not have produced such a striking emotional response from the patient in the past. Examples might include a sad television show, the death of a distant relative, chuckle under normal circumstances. The degree of the emotional response by the patient is often striking, with the crying or laughter persisting for a considerable period of time and unable to be suppressed by the patient. In addition, laughing

and crying by the patient may occur in situations that are not perceived by others as being sad or funny.1 Depression vs pseudobulbar affect

The pathophysiology of PBA is incompletely understood, but symptoms are thought to result from damage to neural pathways associated with motor functioning and emotional processing.

Data suggest that PBA is underrecognized by neurologists and psychiatrists.1 As inconsolable episodes of crying are frequent with PBA, this disorder is often misdiagnosed as depression.

When misdiagnosed as depression or another personality disorder, such as bipolar disorder, inappropriate management of PBA ensues. Patients are often started on selective serotonin reuptake inhibitors (SSRIs), other antidepressants, or psychotherapy with mild to no relief of symptoms because of misdiagnosis.

To differentiate between PBA and depression, it is valuable to determine the duration of the crying episodes. Episodes of crying with depression are often longer in duration than the episodes of pathologic crying characteristic of PBA. With depression, crying episodes commonly last weeks to months in contrast to the very brief duration of PBA episodes. Both the exaggerated emotional response and the discordance between mood and emotional display are additional characteristics of PBA that are not expected with depression.1 Patients with PBA often sob uncontrollably for seemingly no reason while verbalizing that they are not sad.They often lack the neurovegetative features of depression such as sleep disturbances and changes in appetite.

Diagnostic criteria for pseudobulbar affect

Two sets of published diagnostic criteria are available to help differentiate PBA from depression.The first set of diagnostic criteria, developed by Poeck in 1969, include: emotional response is situationally inappropriate, the patient’s feelings and the affective response are not closely related, the duration and severity of the episodes cannot be controlled by the patient, and expression of the emotion does not lead to a feeling of relief.3 The second set of diagnostic criteria, developed by Cummings et al in 2006, describe a change from previous emotional responses, inconsistent with or disproportionate to mood, not dependent on a stimulus, or are excessive relative to that stimulus, cause significant distress or social/occupational impairment, are not due to another drug.4 These uncontrollable episodes of crying or laughter come with a great deal of social anxiety. Patients with PBA have no control over when these outbursts will occur or how long they will last.They are unable to voluntarily stop these episodes once they begin.This can be extremely embarrassing for these patients especially when the episodes occur in inappropriate situations and settings. Many patients with PBA experience social isolation as they avoid situations where they are in the presence of people who do not understand what may be happening to them.

Treatment

The goal of treatment of PBA is to diminish the severity and frequency of episodes.The targets of treatment are primarily norepinephrine, serotonin, or glutamate, using tricyclic antidepressants, SSRIs, and the cough suppressant dextromethorphan.1 Prior to approval by the US Food and Drug Administration of the combination of dextromethorphan hydrobromide and quinidine sulfate (Nuedexta®), all treatments had been off-label.

The treatment combines dextromethorphan hydrobromide (20 mg), the ingredient active in the central nervous system, and quinidine sulfate (10 mg), a metabolic inhibitor that enables dextromethorphan to reach therapeutic concentrations.

Although the mechanism by which the drug exerts therapeutic effects in patients with PBA is unknown, it acts on sigma-1 N-methyl-D-aspartate receptors in the brain and spinal cord.

Studies to support the effectiveness of dextromethorphan/ quinidine were performed in patients with ALS and MS. In the STAR clinical trial, the primary outcome measure — the number of laughing and crying episodes — was significantly lower in those treated with the drug combination compared with those receiving placebo.5 The number of individuals with neurologic conditions is substantial, and many of these also experience PBA, which can cause emotional distress due to social anxiety, embarrassment, and social isolation. With nearly 2 million individuals in the United States experiencing the uncontrollable crying and/or laughing of PBA, this represents a significant national health issue in need of attention from primary care providers.

Primary care providers can contribute to raising awareness of PBA and its treatment options by sharing resources with patients and their families. Resources for patients with PBA and their caregivers are available online at The National Stroke Association, the Multiple Sclerosis Association of America, and PBAInfo. ■ Tanya Sargent, RN, BSN, is a family medicine nurse practitioner in Johnstown, Pennsylvania.

References 1. Ahmed A, Simmons Z. Pseudobulbar affect: prevalence and management.

Ther Clin Risk Manag. 2013;9:483-449.

2. Brooks BR, Crumpacker D, Fellus J, Kantor D, Kaye RE. PRISM: A novel research tool to assess the prevalence of pseudobulbar affect symptoms across neurological conditions. PLoS One. 2013;8(8):e72232.

3. Poeck K. Pathophysiology of emotional disorders associated with brain damage. In: Vinken PJ, Bruyn GW (eds). Handbook of Clinical Neurology.

Volume 3. Amsterdam: North Holland Publishing; 1969:343-367.

4. Cummings JL, Arciniegas DB, Brooks BR, et al. Defining and diagnosing involuntary emotional expression disorder. CNS Spectr. 2006;11(6):1-7.

5. Garnock-Jones KP. Dextromethorphan/quinidine. CNS Drugs. 2011;25(5):435-445.

www.ClinicalAdvisor.com • THE CLINICAL ADVISOR • SEPTEMBER 2018 29

FEATURE: SALARY SURVEY $

$ $

$

Are you being fairly compensated? $

As Clinical Advisor continues to recognize 20 years of providing valuable information to the NP and PA communities, we turn our attention to compensation. Clinical practice has evolved significantly over the years, and so too have salaries. The results of the 2018 NP/PA Salary Survey are in and available to help you when making career choices.

Ref lecting a benef it that has been increasing over the past few years, more than half of all NPs and PAs responding to the survey reported earning more in 2018 than they had during the previous year.

See how your salary compares with those of your peers as reported in the 2018 NP/PA SALARY SURVEY

NPs and PAs reported annual incomes in the 2018 survey of $111,340.87 and $120,177.91, respectively.

As described in prior years, the wage gap between men and women persists; although 92% of NP respondents and 66% of PA respondents were women, men in both professions made approximately $17,000 more than their female counterparts.

The West coast remains the region with the highest average salary for both NPs and PAs ($124,441 and

$127,408, respectively), with the northeast trailing close behind ($111,820 and $120,331, respectively). However, the majority of respondents reside and practice in the South (37%of NPs and 31% of PAs).

Family Medicine continues to be the specialty most frequently employing the services of NPs and PAs, and stand-alone clinics are the most frequently reported practice setting. However, the highest salaries were reported by both NPs and PAs working in hospitals compared with all of the other locales.

The majority of NPs (68%) expressed satisfaction with their employer; these respondents earn an average salary of $116,298. Similarly, the majority of PAs (69%) also reported being satisfied with their employer; this job role job role earned an average annual salary of $122,297. Although few PA respondents (2.13%) reportedly were very dissatisfied with their employer, they earned the highest median salary per year at $125,533.

The vast majority of NPs and PAs anticipate making as much or more than they currently make in the year to come, with more than half of all clinician respondents expecting more money in their paychecks in 2019.

30 THE CLINICAL ADVISOR â&#x20AC;˘ SEPTEMBER 2018 â&#x20AC;˘ www.ClinicalAdvisor.com

See the complete survey results online at ClinicalAdvisor.com/2018SalarySurvey

TABLE 1. Average NP salary by practice area

TABLE 2. Average PA salary by practice area

Practice area

Percent response

Average salary

Practice area

Percent response

Average salary

Family Medicine

46% (n = 331)

$104,933

Family Medicine

37.8% (n = 81)

$119,599

Pediatrics

12.9% (n = 93)

$106,506

Emergency Medicine

17.8% (n = 38)

$151,908

Psychiatry

12.2% (n = 88)

$132,298

Urgent Care

13.6% (n = 29)

$125,478

Primary Care

9.7% (n = 70)

$108,751

Orthopedic Surgery

12.6% (n = 27)

$139,445

Adult Medicine

9.6% (n = 69)

$115,774

Dermatology

10.7% (n = 23)

$166,305

Urgent Care

9.6% (n = 69)

$112,899

Cardiology

7.4% (n = 16)

$118,751

TABLE 3. Average NP salary by experience level

TABLE 4. Average PA salary by experience level

Years in practice

Percent response

Average salary

Years in practice

Percent response

Average salary

<5

25.8% (n = 375)

$107,374

<5

12.6% (n = 65)

$117,177

6-10

19.7% (n = 295)

$113,767

6-10

19.8% (n = 102)

$123,496

11-15

14.0% (n = 207)

$114,781

11-15

17.4% (n = 90)

$123,816

16-20

16.2% (n = 242)

$114,556

16-20

18.2% (n = 94)

$123,750

>20

24.3% (n = 359)

$111,656

>20

32.0% (n = 165)

$117,955

FIGURE 1. Average NP salary by geographic region

FIGURE 2. Average PA salary by geographic region

West

Midwest

Northeast

West

Midwest

Northeast

(n = 300) $124,441 average salary

(n = 343) $107,011 average salary

(n = 285) $111,820 average salary

(n = 119) $127,408 average salary

(n = 115) $119,544 average salary

(n = 121) $120,331 average salary

$

South

South

(n = 550) $108,160 average salary

(n = 161) $117,903 average salary

How the results were calculated We asked our readers to provide their current salaries, which included base pay and bonuses, in increments of $5000, ranging from $0 to more than $200,000. Medians were then determined. These findings were based on analysis of responses from 1530 NPs and 529 PAs currently in practice in the United States.

www.ClinicalAdvisor.com • THE CLINICAL ADVISOR • SEPTEMBER 2018 31

FEATURE: SALARY SURVEY

TABLE 5. Average NP salary by urban, suburban, or rural location

TABLE 6. Average PA salary by urban, suburban, or rural location

Practice location

Percent response

Average salary

Practice setting

Percent response

Average salary

Urban

39.4% (n = 583)

$112,395

Urban

37.2% (n = 196)

$119,873

Suburban

36.3% (n = 536)

$113,317

Suburban

44.9% (n = 232)

$120,994

Rural

24.3% (n = 359)

$108,996

Rural

17.0% (n = 88)

$123,703

TABLE 7. Average NP salary according to gender Female

TABLE 8. Average PA salary according to gender

Male

Female

Male

(n = 1,359)

(n = 119)

(n = 343)

(n = 173)

$110,516

$127,753

$115,049

$132,890

TABLE 9. Average NP salary according to practice setting

TABLE 10. Average PA salary according to practice setting

Practice setting

Percent response

Average salary

Practice setting

Percent response

Average salary

Clinic – Hospital

23.6% (n = 274)

$116,187

Clinic – Hospital

19.9% (n = 90)

$128,139

Clinic – Stand Alone

26.4% (n = 307)

$107,817

Clinic – Stand Alone

27.9% (n = 126)

$116,249

Office Practice

22.7% (n = 264)

$108,215

Office Practice

24.3% (n = 110)

$116,728

Hospital

15.7% (n = 182)

$125,011

Hospital

19.5% (n = 88)

$133,72

Walk-in/ Ambulatory Care

7.6% (n = 88)

$105,824

Walk-in/ Ambulatory Care

5.1% (n = 23)

$118,000

Long-term care

4.0% (n = 46)

$103,153

Education/Academic

3.1% (n = 14)

$108,572

FIGURE 3. Did you earn more money this year (NPs)?

39.9%

FIGURE 4. Did you earn more money this year (PAs)?

More

More

Less

Less

Same

35.1%

50.1% 10%

Same

53.9% 10.4%

Continues on page 33

32 THE CLINICAL ADVISOR • SEPTEMBER 2018 • www.ClinicalAdvisor.com

FIGURE 5. Do you expect to earn more money next year (NPs)?

47.1%

FIGURE 6. Do you expect to earn more money next year (PAs)?

More

More

Less

Less

39.9%

Same

48.1%

Same

54.8%

5.2%

4.8% TABLE 11. Number of patients seen per week (NPs)

TABLE 12. Number of patients seen per week (PAs)

Patients

Percent response

Patients

Percent response

<25

17.6% (n = 260)

<25

13.2% (n = 68)

26-50

25.6% (n = 382)

26-50

21.1% (n = 109)

51-75

24.7% (n = 365)

51-75

25.2% (n = 130)

76-100

19.7% (n = 291)

76-100

22.3% (n = 118)

101-125

6.9% (n = 102)

101-125

9.9% (n = 51)

125+

5.3% (n = 78)

125+

7.8% (n = 40)

TABLE 13. How satisfied are you with your employer (NPs)?

TABLE 14. How satisfied are you with your employer (PAs)?

Satisfaction

Percent response

Average salary

Satisfaction

Percent response

Average salary

Very Satisfied

26.2% (n = 387)

$120,880

Very Satisfied

26.9% (n = 139)

$120,137

Satisfied

41.4% (n = 612)

$111,716

Satisfied

42.3% (n = 218)

$124,457

Neutral

22.3% (n = 330)

$104,023

Neutral

21.2% (n = 109)

$114,611

Dissatisfied

8.2% (n = 121)

$107,852

Dissatisfied

7.6% (n = 39)

$121,731

Very Dissatisfied

1.9% (n = 28)

$102,322

Very Dissatisfied

2.0% (n = 11)

$125,533

The Clinical Advisor thanks all who participated in this year’s salary survey.

www.ClinicalAdvisor.com • THE CLINICAL ADVISOR • SEPTEMBER 2018 33

CME CE FEATURED COURSE EDUCATIONAL OBJECTIVES After participating in this activity, clinicians should be better able to: • Discuss the evolution of laparoscopic surgery and the pros/ cons of various minimally invasive surgery (MIS) procedures • Describe the new category of percutaneous laparoscopic surgery made possible by sub–3 mm diameter instruments • Recognize the benefits of smaller incisions with minimization of tissue trauma and improved cosmesis • Appreciate the importance of decreased hospital stay, improved recovery time, and minimization of tissue trauma COMPLETE THE POSTTEST: Page 41

Release Date: May 16, 2018 Expiration Date: May 16, 2019 Estimated Time to Complete: 30 minutes Maximum Credits: 0.50 AMA PRA Category 1 CreditTM 0.50 CNE Contact Hour Accredited Provider: This activity is jointly provided by Haymarket Medical Education (HME) and AKH Inc., Advancing Knowledge in Healthcare.

Commercial Supporter: This activity is supported by an educational grant from Teleflex Incorporated.

Program Description: Surgical technology is constantly evolving, leading to rapid and profound changes in minimally invasive laparoscopic surgery over the past few decades.Various approaches—each with its strengths and limitations—have been developed to help minimize tissue trauma, wound complications, and postoperative scarring. Designing surgical tools that reduce incision size must be balanced with the need to maintain access with good visualization, providing a stable conduit that allows the surgeon to move forward safely, with tools that have sufficient shaft length and strength for the intended applications.The following case illustrates the use of a system that employs instruments with a 2.9-mm shaft that are inserted percutaneously through the skin, but with standard 5-mm end effectors that are attached to the shaft through a separate standard laparoscopic port.

Intended Audience: Surgeons, gastroenterologists, physician assistants (PAs), nurses (RNs), and nurse practitioners (NPs) with a surgery specialty or interest in surgery.

Conflict of Interest Disclosure Policies: In accordance with the ACCME Standards for Commercial Support, HME requires that individuals in a position to control the content of an educational activity disclose all relevant financial relationships with any commercial interest. HME resolves all conflicts of interest to ensure independence, objectivity, balance, and scientific rigor in all its educational activities.

Faculty Chan W. Park, MD, FACS Bariatric and Minimally Invasive Surgery Tripler Army Medical Center Honolulu, HI Dr. Park receives consulting fees from W.L. Gore & Associates, Inc., Medtronic/Covidien, Physcient Inc., Teleflex Incorporated, and TransEnterix, Inc. Accredited Provider Disclosures: The staff of Haymarket Medical Education and Dorothy Caputo, MA, BSN, RN, Lead Nurse Planner, of AKH Inc., Advancing Knowledge in Healthcare, have no relevant financial relationships to disclose.

Reviewer Disclosures: Ruchit Parikh, PharmD, has ownership interest in Intercept Pharmaceuticals.

Accreditation Statement: Haymarket Medical Education is accredited by the Accreditation Council for Continuing Medical Education (ACCME) to provide continuing medical education for physicians.

Designation Statement: Haymarket Medical Education designates this enduring material for a maximum of 0.50 AMA PRA Category 1 CreditTM. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

Accreditation Statement: AKH Inc., Advancing Knowledge in Healthcare is accredited as a provider of continuing nursing education by the American Nurses Credentialing Center’s Commission on Accreditation.

Designation Statement: This activity is awarded 0.50 contact hours.

Disclosure of Unlabeled Use: This CME activity may or may not discuss investigational, unapproved, or off-label use of drugs. Participants are advised to consult prescribing information for any products discussed.The information provided in this CME activity is for continuing medical education purposes only and is not meant to substitute for the independent medical judgment of a physician relative to diagnostic and treatment options for a specific patient’s medical condition.

Disclaimer: The opinions expressed in the educational activity are those of the faculty and do not necessarily represent the views of Haymarket Medical Education, AKH Inc., Advancing Knowledge in Healthcare, or Teleflex Incorporated. Please refer to the official prescribing information for each product for discussion of approved indications, contraindications, and warnings.

Instructions: There are no fees for participating in and receiving CME credit for this activity. During the period May 16, 2018 through May 16, 2019, participants must: 1) read the learning objectives and faculty disclosures; 2) complete the pre-assessment test; 3) respond to all polling questions online; 4) study the educational activity; and 5) complete the post-test and evaluation form and submit it online.

A statement of credit will be issued only upon receipt of the above elements and a post-test score of 70% or higher. All components must be completed and submitted online at ClinicalAdvisor.com/Sept18feature.

If you have any questions relating to the CME accreditation of this activity, please contact HME at cmequestions@haymarketmedical.com.

If you have any questions relating to the CE accreditation of this activity, please contact AKH at jgoldman@akhcme.com.

If you have any questions relating to your certificate or other issues with this activity, please contact myCME. Support@haymarketmedical.com.

Jointly provided by

CME | CE FEATURED COURSE: CHAN W. PARK, MD, FACS

Case clinic: Laparoscopic sleeve gastrectomy in a 48-year-old obese male This case demonstrates how new surgical technologies can minimize tissue trauma and wound complications while reducing postoperative scarring.

S

urgical technology is constantly evolving, leading to rapid and profound changes over the past few decades.Various approaches— each with its strengths and limitations—have been developed to help minimize tissue trauma, wound complications, and postoperative scarring. Designing surgical tools that reduce incision size must be balanced with the need to maintain access with good visualization—thus providing a stable conduit that allows the surgeon to move forward safely, utilizing instruments that have sufficient shaft length and strength for the intended applications. The following case illustrates the use of a system that employs instruments with a 2.9-mm shaft that are inserted percutaneously through the skin, but with standard 5-mm end-effectors that are attached to the shaft through a separate standard laparoscopic port.

© BRUNO BOISSONNET / SCIENCE SOURCE

CASE PRESENTATION Social and medical history

Surgeons performing a laparoscopic sleeve gastrectomy.

Bruce is a 48-year-old obese biracial male. He was referred to a metabolic obesity center by his primary care physician as a potential candidate for bariatric surgery. He has a body mass index (BMI) of 42.3 kg/m2: His height is 5’10” and his body weight is 295 lb; his waist circumference is 53”.

Bruce relates that he works at a customer service desk job and struggles not only with his energy level and ability to stand or walk for lengthy periods, but also with his self-image.

Bruce had an appendectomy when he was 26 years old but no other abdominal surgeries.

www.ClinicalAdvisor.com • THE CLINICAL ADVISOR • SEPTEMBER 2018 35

CME | CE FEATURED COURSE

CASE PRESENTATION:

Physical exam at time of presentation General: 48-year-old male with morbid obesity looks to be his stated age Eyes: sclera, white; conjunctiva, pink; fundoscopy shows normalcaliber vessels, no abnormal background pigmentation, hemorrhages, or exudates; visualized macula Neuro: awake and alert; oriented to person, place, and time; normal motor tone, sensory, reflexes, and coordination HENT: normal auditory canal and eardrum; no nasal discharge, normal midline septum; normal dentition, tongue, gums, mucosa, and pharynx Neck: normal rotation and tilting; midline, mobile trachea, nonpalpable, normal-size thyroid CV: BP, right arm/auscultation – 138/94; normal auscultation and palpation of carotid arteries and precordium; normal femoral pulse Resp: normal resonant percussion and palpation of lung fields GI: no tenderness or masses on palpation Skin: no lesions Lymph nodes: not palpable Laboratory findings: All values were within normal limits.

Weight loss history When Bruce was in college, his BMI was 25.0 kg/m2. He began gaining weight after graduating and struggling emotionally with a difficult employment situation, a romantic relationship that fell apart, and the loss of his father after a fatal car accident, all within a narrow time frame. He continued gaining weight through his 30s and 40s. He tried various fad diet programs on and off through the years and always put on more weight than what he lost. Despite attempting to implement the suggestions of a dietitian and an endocrinologist for the past 10 months, he failed to lose a significant amount of weight and was unable to maintain the small weight losses he achieved. Bruce has a history of cardiovascular and metabolic disease in his family, and his hypertension, sleep apnea, and NASH are serious concerns to him and his family practitioner. He was referred to a weight loss center for consultation to explore surgical weight loss options.

Preoperative diagnosis: morbid obesity; hypertension, NASH

He states that he has a low tolerance for pain. He has been divorced for the past 5 years and he would like to start dating again—but recognizes that his obesity is a serious obstacle.

Medical records from his primary care provider describe Bruce as morbidly obese. Seven years ago, he was diagnosed with sleep apnea, hypertension, and nonalcoholic steatohepatitis (NASH).

He was prescribed an angiotensin-converting enzyme inhibitor for the hypertension and is supposed to use a continuous positive airway pressure device every night for the sleep apnea. See the Physical exam at time of presentation sidebar at left.

POLLING QUESTION

Do you agree with the primary care provider’s assessment that this patient is a likely candidate for bariatric surgery?

a. Yes

b. No

Feedback: According to the American Society for Metabolic and Bariatric Surgery (https://asmbs.org/patients/who-is-acandidate-for-bariatric-surgery), qualifications for bariatric surgery in most areas include: • BMI ≥40, or more than 100 lb overweight • BMI ≥35 and at least 1 or more obesity-related comorbidities—such as type 2 diabetes, hypertension, sleep apnea and other respiratory disorders, nonalcoholic fatty liver disease, osteoarthritis, lipid abnormalities, gastrointestinal disorders, or heart disease • Inability to achieve a healthy weight loss sustained for a period of time with prior weight loss efforts EVOLUTION OF SURGICAL TECHNIQUE POLLING QUESTION

Which of the following bariatric procedures do you think would be best for this patient?

a. Roux-en-Y gastric bypass b. Laparoscopic adjustable gastric banding c. Sleeve gastrectomy d. Duodenal switch with biliopancreatic diversion The desire to reduce surgical trauma, especially with regard to common abdominal procedures, has led to the development of a variety of minimally invasive surgery (MIS) tools and techniques. The first laparoscopic surgery was performed in 1981 and laid the foundation for MIS.1 The tenet of MIS is to safely perform surgery with equivalent outcomes compared with open surgery while minimizing the morbidity and complications associated with open surgery. To that end, approaches such as single-incision laparoscopy and needlescopic surgery have been employed with varying degrees of success.2 Common limitations

36 THE CLINICAL ADVISOR • SEPTEMBER 2018 • www.ClinicalAdvisor.com

Percutaneous surgery

The next step in the evolution of MIS has been the development of percutaneous instruments that enable surgery through fewer trocars and with less trauma.These tools permit the performance of surgical procedures without the loss of triangulation, allowing the site(s) of instrument insertion to be maintained.3,4,8 One such system is the 2.3-mm MiniLap® (Teleflex). This system allows the execution of essential surgical functions for routine laparoscopic procedures with fewer trocars, minimizing trauma and incisions and thus leaving nearly unnoticeable scars, which may prove especially valuable for pediatric patients.

A second system, the Percuvance® surgical system (also Teleflex), has been developed with instruments having a 2.9mm shaft that are also inserted percutaneously through the skin but with full, standard 5-mm end-effectors that are attached to the shaft end through a separate laparoscopic port.This system may provide a viable option in minimizing the number of larger incisions while providing a more durable end-effector compared with traditional needlescopic instruments, and it also may allow for the maintenance of safe laparoscopic principles in

© REPRINTED WITH PERMISSION OF THE PUBLISHER.

include reduced surgeon ergonomics, difficulty with instrument triangulation, and decreased quality of optics.These technologies are also associated with steep learning curves.

Nevertheless, there is continued interest in the development of less-invasive technology for surgery that would result in gentler tissue handling, decreased need for retraction and dissection, and reduced operative trauma. Evolution of minilaparoscopy has led to several innovations that aim to decrease postoperative pain and minimize scarring.3,4 With needlescopic surgery, patient positioning and surgeon ergonomics are identical to those for standard laparoscopy.

Needlescopic instruments are used in a similar configuration as standard laparoscopy, which obviates the need to relearn how to perform a procedure, eliminating the steep learning curve associated with other proposed technologies.2 Potential advantages include decreased abdominal wall trauma and risk of future herniation, decreased risk of wound infection with a smaller skin incision, and a virtually invisible scar, improving postoperative cosmesis.5 Sympathetic nervous system activation is less compared with traditional laparoscopy and likely contributes to decreased narcotic requirements in the postoperative period for MIS.6 The use of needlescopic instruments has been limited in application by the small size of the instrument head (<3 mm), lack of strength of the instruments in tissue handling, and limited instrument heads available for use.7 Furthermore, in addition to the risk posed by the sharpness of the instrument tip itself, the small size of the instrument head/jaw can cause injury when used to grasp intestinal tissue, as it “pinches” rather than grasps a wider surface area.

FIGURE 1: Illustration of relative skin incision sizes prior to closure, using a 2.9-mm shaft, a 5-mm port, and a 10-mm port2

the setting of decreased caliber access.This approach minimizes abdominal wall trauma while maintaining the functionality of traditional laparoscopic instruments.2,9 Comparative incision size vs 5-mm and 10-mm ports is shown in Figure 1.

The 2.9-mm shaft Percuvance instrument has performance characteristics similar to a traditional laparoscopic instrument.

The 2.9-mm shaft is extracorporealized through a separate laparoscopic trocar and is technically simple, as is the actual exchange of different end-effectors.The process of changing the instrument tips takes place outside of the abdominal cavity. Experience shows that there is no disengagement of instrument tips and no laxity or looseness of the tips. If the instrument is removed from the abdominal wall, there is no loss of pneumoperitoneum, allowing the surgeon to resite the instruments multiple times.2 The Percuvance surgical system is indicated for the penetration of soft tissue to access certain areas of the abdomen.

The system is used to grasp, manipulate, cut, cauterize, and deliver Hem-o-lok® ligating clips during laparoscopic surgery.

Operative time, complication profiles, and length of hospital stay are similar to those of standard laparoscopic procedures.2 POLLING QUESTION:

In your opinion, which (if any) of the following benefits would you expect with use of percutaneous instruments for common abdominal procedures, such as cholecystectomy, compared with using standard laparoscopic instruments?

(Select all that apply.)

a. Less pain b. Smaller scars c. Quicker recovery

d. Improved self-esteem e. None of the above f. Other

www.ClinicalAdvisor.com • THE CLINICAL ADVISOR • SEPTEMBER 2018 37

CME | CE FEATURED COURSE

OBESITY SURGERY: CURRENT OPTIONS

Many endoscopic surgical interventions for obesity have been studied, including small-bowel and gastric bypass procedures, banded gastroplasty, gastric banding, biliopancreatic bypass, intragastric balloon, transoral gastroplasty, and sleeve gastrectomy (SG), among others.10,11 Several surgical approaches have emerged as favorable treatment options for patients with morbid obesity that provide long-standing quality-of-life (QoL) improvement.12 Roux-en-Y gastric bypass (RYGB) requires rerouting of the intestines, while SG does not require intestinal anastomoses and is a faster procedure with less time under anesthesia, potentially less dumping as a side effect, and less risk of specific micronutrient deficiencies.Although RYGB results in more stable weight loss, it is associated with higher readmission rates due to adverse events.12 There are technical difficulties involved in performing RYGB in severely obese patients, and such patients may have limited success from RYGB, attributed to pouch dilation and loss of restriction at the gastro-jejunal anastomosis over time.Two of the major complications after RYGB include anastomotic leak (2%-4%) and gastro-jejunal stricture (0.5%-4.9%).13-15 Patients may lose a larger amount of weight and sustain the weight loss for longer with RYGB compared with SG. However, SG has recently become more common as a viable alternative to RYGB in the resolution of obesity-related comorbidities since RYGB results in greater grade 1 complications, extended length of hospital stays, and more emergency department visits.16,17 Furthermore, multiple comorbidities have been shown to be relieved after SG, including hypertension, diabetes mellitus, obstructive sleep apnea, and hyperlipidemia.14 Another benefit of SG compared with malabsorptive procedures such as RYGB is that endoscopic procedures not possible after surgical reconstruction of the small bowel are possible after SG. This becomes especially important in evaluating patients with suspected gastritis or biliary pathology, which become difficult to evaluate endoscopically after RYGB.14 Therefore, SG is trending to be the surgery of choice at most bariatric surgery centers.

Although weight loss may be greater following RYGB compared with SG at 2 years,17 the difference does not appear to be clinically significant, and both groups show continued weight loss during long-term follow-up. A recent study of patients randomized to either SG (n=121) or RYGB (n=119) found that excess weight loss at 5 years was 49% and 57% in each group, respectively—an 8.2% difference, with prespecified equivalence margins of −9% to +9% excess weight loss. There were also comparable improvements in type 2 diabetes mellitus (T2DM), hypertension, dyslipidemia, and QoL scores in both groups.18 In another randomized trial (N=217), the 2 surgery types also had similar positive impacts on several comorbid conditions,

including T2DM, dyslipidemia, hypertension, and obstructive sleep apnea.19 Similar rates of early- and late-stage complications were reported with both procedures in both trials, although both noted better resolution of gastroesophageal reflux disease with RYGB.18,19 Thus, on balance, these studies confirm the utility of SG in the management of morbid obesity.16,20 Minimally invasive technique for obesity surgery

The utilization of minimally invasive laparoscopic bariatric surgery provides multiple advantages over the older, open surgical methods. Laparoscopic surgery provides earlier ambulation after surgery, less postoperative abdominal pain, lower postoperative risks of pneumonia and deep venous thrombosis, decreased length of hospital stay, improved cosmetic appearance, lower risk of postoperative wound complications (including infection and hernia development), and an earlier return to societal activities, including job activities.11 Bariatric surgery is an evolving field, which will continue to expand given current epidemiologic trends. Developments in instrumentation and surgical techniques, including single-access and natural orifice approaches, may offer further benefit.20,21 Surgical process for sleeve gastrectomy: Incision size and ports

Many variations exist regarding surgical technique for SG.The basic tenets include pyloric preservation with gastrectomy beginning 2 cm to 6 cm proximal to the pylorus, mobilization of the entire greater curvature with exposure and identification of the left crus and base of the right crus, avoidance of stricture at the gastric incisura, and proper apposition of the anterior and posterior aspects of the stomach to create a sleeve-like stomach with a uniform internal diameter throughout, while avoiding spiraling or corkscrewing of the sleeve and avoiding a large, retained fundic pouch.

CASE PRESENTATION, continued Management decision

The surgical options are discussed with Bruce, who understands that laparoscopic SG (LSG) has shown equivalence or superiority to currently accepted procedures of RYGB and laparoscopic adjustable gastric banding (LAGB) with short- and medium-term follow-up periods. Bruce would like to lose weight and improve his QoL. He is counseled about having realistic expectations from bariatric surgery, with typical weight loss with SG of about 60% to 72% of excess weight within 1 year. Bruce understands that even though he is unlikely to achieve a normal BMI, the procedure will likely have a significant impact on his hypertension and sleep apnea.

Although there is limited experience to date, the Percuvance system can be used with morbidly obese patients without

38 THE CLINICAL ADVISOR • SEPTEMBER 2018 • www.ClinicalAdvisor.com

any modification in the operative technique. Outcomes are similar to what has been observed with minimally invasive laparoscopic surgery.There is a relative paucity of data regarding any potential limitations with the Percuvance system: the shafts are somewhat more flexible than standard laparoscopic instruments, which can lead to “bowing” or “flexing” of the instrument shaft, but this does not limit the actual functionality of the instrument. Another observation is that, because the instruments are not placed through a trocar, there may be a degree of “friction” during movement in and out of the abdominal wall—but again, this does not result in any meaningful limitation in functionality.

A potential concern with the Percuvance system is that the instrument tip needs to be put on and taken off the shaft, so the surgeon or assistant must remember not to simply pull the instrument out when near the end of a procedure. It is also important that the instrument is placed far enough away from a standard trocar (and even farther in patients with a thick abdominal wall) to be able to bring the tip of the Percuvance through the port; the port also needs to be aligned with the Percuvance to deliver the tip through the port.There is a small learning curve for this exchange, and the surgeon has to be able to work with “backwards” views of the laparoscope if working with only 1 standard trocar, since the Percuvance will be coming straight at the camera.

Use of the Percuvance system for bariatric surgery

In a report on 15 consecutive abdominal surgery patients at Cleveland Clinic, the Percuvance system was reported to be equal to that of standard 5-mm laparoscopic instrumentation.

Initial experience with the percutaneous system demonstrated effective exchange of 5-mm port sites for needlescopic instruments, with similar handling to traditional laparoscopic instruments. The standard operative technique during use of Percuvance instruments did not need to be modified, and operative times were similar to those when using traditional

laparoscopic instruments, as was expected length of stay. This interchangeable system may allow performance similar to standard laparoscopic port instrument orientation and principles in the setting of decreased-caliber access.Three of the 15 patients underwent bariatric surgery for morbid obesity (Table 1).2 CASE PRESENTATION, continued Details of Bruce’s surgical management

Bruce is particularly anxious to have a procedure that will minimize scarring—not from the perspective of vanity, although many men can be just as concerned about postoperative scars as women, but because he is concerned about protecting his privacy regarding having the procedure as he explores new romantic relationships or socializes at beach or pool parties where he might not be wearing a shirt. He knows that some people are judgmental about weight loss surgery, regarding it as an easy way out compared with losing weight through diet and exercise alone.

Given these considerations, Bruce undergoes SG employing 2.9-mm shaft instruments. Despite his obesity, the tools were able to penetrate the thick abdominal wall and the surgeon was able to retract/expose tissues as needed with adequate triangulation. See Sidebar: Surgical procedure: Laparoscopic sleeve gastrectomy (LSG) on page 16.

There were no late complications at 2 months following LSG and, at 6 months, Bruce had lost a total of 53 pounds, or 47% of his excess weight (113 lb), putting him on target to achieve his goal of 183 lb and a BMI of 26. Bruce will continue to receive support in his weight loss efforts as well as general medical follow-up. His primary care provider should be alert to the potential for the formation of gallstones. Rapid weight loss after bariatric surgery is one of many known risk factors for gallstone development, with about 15% of patients who undergo bariatric surgery requiring cholecystectomy.Although some surgeons have advocated prophylactic cholecystectomy or pharmacologic treatment (ursodiol) in the postoperative

TABLE 1. Patient demographics and operative data for bariatric surgery cases2 Patient

Age (years)

BM (kg/m2)

ASA Score*

OR Time (min)

Total Access Site Number

Percuvance Access Site Number

3

62

41

2

154

5

1

5

68

38

3

130

5

1

7

57

47

3

169

4

2

*ASA, American Society of Anesthesiologists

www.ClinicalAdvisor.com • THE CLINICAL ADVISOR • SEPTEMBER 2018 39

CME | CE FEATURED COURSE

period, the appropriate management of gallstones and gallbladder disease in patients undergoing bariatric surgery remains patient- and surgeon-specific.22-25 In a prospective study of 1398 patients undergoing laparoscopic RYGB, LAGB, or LSG, the frequency of cholecystectomy was significantly higher after RYGB (10.6%) compared with either LAGB (2.9%; P<.001) or SG (3.5%; P=.004).25 The frequency was highest within the first 6 months (3.7%), declining over time to less than 1% per year after 3 years.

Ursodiol administration did not affect cholecystectomy rates (P=.97), and significant inter-surgeon variability was noted.

In fact, the strongest predictor of postoperative cholecystectomy was excess weight loss of more than 25% within the first 3 months (P<.001). In addition, white patients had 1.45 times higher cholecystectomy rates than did black patients.

SURGICAL PROCEDURE:

Laparoscopic sleeve gastrectomy (LSG) Instrument access: 5-mm incision/port for laparoscope; 15-mm incision/port for stapling and specimen removal (both incisions placed in periumbilical skinfolds to maximize cosmesis); two 2.9-mm percutaneous instruments in bilateral subcostal margins and used for retraction/graspers; and one 2.9-mm subxiphoid incision for percutaneous liver retractor Estimated blood loss: 20 mL Closure: 15-mm fascial opening closed with 0-Vicryl suture; skin closed with 4-0 Monocryl and skin glue; 5-mm skin incision closed with 4-0 Monocryl and skin glue; 2.9-mm skin incisions closed with skin glue.

Intraoperative anesthesia: transverse abdominis plane (TAP) block and local anesthetics Postoperative pain and analgesic requirement: a nonsteroidal anti-inflammatory drug (NSAID)* is continued for 3 to 5 days postoperatively Operative time: 50 minutes

In Bruce’s case, these data suggest that he is not likely to require cholecystectomy—but should he develop gallstones, he may be a candidate for treatment with a standard laparoscopy or with a percutaneous surgical system such as Percuvance.

SUMMARY

Percutaneous laparoscopy is a new category of laparoscopic surgery that makes MIS even less invasive through yet smaller incisions, resulting in less trauma and minimizing scars. The Percuvance system appears to have several advantages over older approaches for gastrointestinal/abdominal procedures such as cholecystectomy and LSG because it combines streamlined access with highly functional, under 3-mm diameter instrumentation. Importantly, as this case illustrates, it is able to perform a wide range of laparoscopic procedures with the strength and functionality of traditional laparoscopic instruments while also minimizing trauma, because it requires smaller incisions.

In addition to the broad benefits in terms of safety and efficacy, the use of this approach addressed 2 additional goals that were especially important to the patient. One was to minimize pain and the other was to improve cosmesis, with minimal scarring that allows him to keep his bariatric surgical history private if he does not wish to share that information with others. ■ References 1. Krpata DM, Ponsky TA. Needlescopic surgery: what’s in the toolbox?

Surg Endosc. 2013;27:1040-1044.

2. Chang J, Boules M, Rodriguez J, Kroh M. Minilaparoscopy with inter­change­ able, full 5-mm end effectors: first human use of a new minimally invasive operating platform. J Laparoendosc Adv Surg Tech. 2016;26(1):1-5.

3. Saad S, Strassel V, Sauerland S. Randomized clinical trial of single-port, minilaparoscopic and conventional laparoscopic cholecystectomy. Br J Surg.

2013;100:339-349.

4. Ghezzi F, Cromi A, Siesto G, et al. Minilaparoscopic versus conventional laparoscopic hysterectomy: results of a randomized trial. J Minim Invasive Gynecol. 2011;18(4):455-456.

5. Tagaya N, Abe A, Kubota K. Needlescopic surgery for liver, gallbladder and spleen diseases. J Hepatobiliary Pancreat Sci. 2011;18(4):516-524.

Safety: no intraoperative or postoperative complications within 30 days after surgery

6. Schmidt J, Sparenbert C, Fraunhofer S, Zirngibl H. Sympathetic nervous

Discharge time: postoperative day 1, with adequate pain control and resumption of oral intake

Endosc. 2002;16(3):476-480.

Follow-up: 2 weeks; minimal scarring or wound-related complications

8. Cockbain AJ. Randomized clinical trial of single-port, minilaparoscopic and

*Bariatric center followed policy to minimize narcotic use in general and avoid discharging patients with narcotic pain medications.

system activity during laparoscopic and needlescopic cholecystectomy. Surg 7. Tagaya N, Kubota K. Reevaluation of needlescopic surgery. Surg Endosc.

2012;26:137-143. conventional laparoscopic cholecystectomy. Br J Surg. 2013;100:339-349.

9. David G, Boni L, Rausei S, et al. Use of 3mm percutaneous instruments with 5mm end effectors during different laparoscopic procedures. Int J Surg.

2013;11(S1):S61-S63.

40 THE CLINICAL ADVISOR • SEPTEMBER 2018 • www.ClinicalAdvisor.com

10. Batchelder AJ, Williams R, Sutton C, Khanna A. The evolution of minimally invasive bariatric surgery. J Surg Res. 2013;183:559-566.

11. Rashti F, Gupta E, Ebrahimi S, et al. Development of minimally invasive techniques for management of medically-complicated obesity. World J Gastroenterol. 2014;20(37):13424-13445.

12. Ignat M,Vix M, Imad I, et al. Randomized trial of Roux-en-Y gastric bypass versus sleeve gastrectomy in achieving excess weight loss. Br J Surg. 2016;104(3):248-256.

13. Murphy R, Evennett NJ, Clarke MG, et al. Sleeve gastrectomy versus Roux-en-Y gastric bypass for type 2 diabetes and morbid obesity: doubleblind randomised clinical trial protocol. BMJ Open. 2016;6:e011416.

14. Ramaswamy A. Laparoscopic sleeve gastrectomy. Society of American Gastrointestinal and Endoscopic Surgeons website. https://www.sages.org/ wiki/laparoscopic-sleeve-gastrectomy/. Accessed April 30, 2018.

15. Ettleson MD, Lager CJ, Kraftson AT, et al. Roux-en-Y gastric bypass versus sleeve gastrectomy: risks and benefits. Minerva Chir. 2017;72(6):505-519.

16. Skinner A, Tatsuno B, Mitsugi Y, et al. Sleeve gastrectomy versus Roux-en-Y gastric bypass: a retrospective review of weight-loss and resolution of co-morbidities. Presented at: SAGES 2012 Scientific Session and Postgraduate Courses: March 7-10, 2012; San Diego, CA. Abstract P451. https://www.sages.org/meetings/annual-meeting/abstracts-archive/sleevegastrectomy-versus-roux-en-y-gastric-bypass-a-retrospective-reviewof-weight-loss-and-resolution-of-co-morbidities/. Accessed April 30, 2018.

17. Lager CJ, Esfandiari NH, Subauste AR, et al. Roux-En-Y gastric bypass vs. sleeve gastrectomy: balancing the risks of surgery with the benefits of weight loss. Obes Surg. 2017;27(1):154-161.

18. Salminen P, Helmiö M, Ovaska J, et al. Effect of laparoscopic sleeve gastrectomy vs laparoscopic Roux-en-Y gastric bypass on weight loss at 5 years among patients with morbid obesity. The SLEEVEPASS randomized clinical trial. JAMA. 2018;319(3):241-254.

19. Peterli R, Wölnerhanssen BK, Peters T, et al. Effect of laparoscopic sleeve gastrectomy vs laparoscopic Roux-en-Y gastric bypass on weight loss in patients with morbid obesity. The SM-BOSS randomized clinical trial. JAMA. 2018;319(3):255-265.

20. Arterburn D, Gupta A. Comparing the outcomes of sleeve gastrectomy and Roux-en-Y gastric bypass for severe obesity. JAMA. 2018;319(3):235-237.

21. Li L, Tian J, Tian H, et al. The efficacy and safety of different kinds of laparoscopic cholecystectomy: a network meta analysis of 43 randomized controlled trials. PLoS One. 2014;9(2):e90313.

22. Quesada BM, Kohan G, Roff HE, et al. Management of gallstones and gallbladder disease in patients undergoing gastric bypass. World J Gastroenterol.

2010;16(17):2075-2079.

23. Sioka E, Zacharoulis D, Zachari E, et al. Complicated gallstones after laparoscopic sleeve gastrectomy. J Obes. 2014;468203. Published online 2014 Jul 3. doi: 10.1155/2014/468203.

24. Li VK, Pulido N, Fajnwaks P, et al. Predictors of gallstone formation after bariatric surgery: a multivariate analysis of risk factors comparing gastric bypass, gastric banding, and sleeve gastrectomy. Surg Endosc. 2009;23(7):1640-1644.

25. Tsirline VB, Keilani ZM, El Djouzi S, et al. How frequently and when do patients undergo cholecystectomy after bariatric surgery? Surg Obes Relat Dis. 2014;10(2):313-321.

CME CE

POSTTEST Expiration date: May 16, 2019

A statement of credit will be issued only upon receipt of a completed pre-assessment test, polling questions, activity evaluation form, and posttest with a score of 70% or higher. All components must be completed and submitted online at ClinicalAdvisor.com/ Sept18feature.

CREDITS: 0.50 Case clinic: Laparoscopic sleeve gastrectomy

1. Which of the following statements regarding minimally invasive surgery (MIS) compared to conventional open surgery is correct? a. MIS techniques have proven superior in virtually every application in which they have been assessed. b. Despite some technical limitations with certain MIS devices, surgeons find the techniques easy to master. c. Limitations with some MIS platforms include reduced surgeon ergonomics, difficulty with instrument triangulation, and decreased quality of optics. d. Despite less tissue trauma with MIS, activation of the sympathetic nervous system contributes to comparable postoperative narcotic requirements.

2. Which of the following is a key limitation of needlescopic surgery compared with standard laparoscopy? a. Patient positioning has a negative impact on surgeon ergonomics. b. It involves a steep learning curve due to different instrument configuration. c. There is an increased risk for wound infection, despite smaller skin incisions. d. Its utility is hindered by the small size of the instrument head and lack of strength of the surgical instruments.

3. Compared with Roux-en-Y gastric bypass (RYGB) surgery, sleeve gastrectomy (SG) results in: a. Fewer late-stage complications. b. Comparable resolution of comorbidities (ie, diabetes, hypertension, and obstructive sleep apnea). c. Better resolution of gastroesophageal reflux disease. d. Decreased quality of life (QoL) scores.

4. Obesity surgery with the Percuvance system: a. Allows for performance similar to standard laparoscopic systems. b. Cannot be used in individuals with a body mass index of >35 kg/m2. c. Requires significant modification of operative technique. d. Results in higher complication rates.

TO TAKE THE POSTTEST please go to: ClinicalAdvisor.com/Sept18feature

www.ClinicalAdvisor.com • THE CLINICAL ADVISOR • SEPTEMBER 2018 41

Evidence-Based Medicine

© TERRY VINE / GETTY IMAGES

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, Massachusetts, and assistant clinical professor in family medicine at the University of Massachusetts Medical School in Worcester. DynaMed (www.ebscohost.com/dynamed/) is a database that provides evidencebased information on more than 3000 clinical topics and is updated daily through systematic surveillance covering more than 500 journals.The most important evidence identified is summarized here.

As-needed budesonide/formoterol may be an alternative to daily maintenance corticosteroids.

BUDESONIDE/ FORMOTEROL FOR THE PREVENTION OF SERIOUS ASTHMA EXACERBATIONS Level 2 [mid-level] evidence Regularly administered low-dose inhaled corticosteroids are recommended as maintenance therapy for mild persistent asthma. However, patient adherence to maintenance therapy is low and using only an as-needed combined corticosteroid/beta-agonist inhaler may be attractive to many patients.

In the SYGMA 2 noninferiority trial, 4215 patients with mild persistent asthma were randomly assigned to either

as-needed combination budesonide 200 mcg/formoterol 6 mcg inhaler or maintenance budesonide 200 mcg inhaler twice daily for 1 year.1 The asneeded budesonide/formoterol regimen also included twice-daily placebo doses, and the maintenance budesonide regimen also included an as-needed terbutaline 0.5-mg inhaler. Exacerbations were considered severe if they required systemic corticosteroids for ≥3 days, an emergency department visit leading to systemic corticosteroids, or hospitalization. Overall symptom severity was assessed with the Asthma Control Questionnaire-5 score (total score range 0-6), with symptom improvement defined as a ≥0.5-point decrease from baseline. Treatment completion was accomplished by 91% of patients, and 99% were included in the analyses.

Noninferiority for as-needed budes­ onide/formoterol was met: the annualized rate of severe asthma exacerbations was 0.11 with as-needed budesonide/ formoterol vs 0.12 with maintenance budesonide, rate ratio 0.97.The 2 groups had similar risks of experiencing at least 1 severe exacerbation during the year (8.5% vs 8.8%), proportion of patientdays without using as-needed inhalers (69% vs 76%), and adherence to maintenance doses (64% vs 63%). Daily inhaled corticosteroid use was numerically less with as-needed budesonide/ formoterol (median 66 vs 268 mcg), but a statistical comparison was not reported. However, as-needed budesonide/

42 THE CLINICAL ADVISOR • SEPTEMBER 2018 • www.ClinicalAdvisor.com

formoterol was associated with a slightly lower likelihood of symptom improvement (40.3% vs 44.3%, P <.05). Rates of adverse events were similar between the 2 groups (42.5% vs 44% of patients), the most common of which was viral upper respiratory tract infection (7.4% vs 8%); however, statistical comparisons were not reported.

The results from the SYGMA 2 trial demonstrated that, in adolescents and adults with mild persistent asthma, an as-needed budesonide/formoterol inhaler may be an alternative to daily maintenance corticosteroids. In secondary analyses, the as-needed regimen also may have reduced inhaled corticosteroid exposure, but it was slightly inferior regarding symptom improvement.Whether or not these differences are clinically relevant may depend on the individual patient. Also, the longterm effects of these differences, particularly with regard to a potential role of corticosteroids in preventing airway remodeling, remain to be seen. On the other hand, an as-needed regimen may be more attractive than a maintenance regimen for many patients.

Continues on page 44

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).

Evidence-Based Medicine

References 1. Bateman ED, Reddel HK, O’Byrne PM, et al.

As-needed budesonide/formoterol versus maintenance budesonide in mild asthma. N Engl J Med. 2018;378:1877-1887.

2. O’Byrne PM, FitzGerald JM, Bateman ED, et al. Inhaled combined budesonide/fomoterol as needed in mild asthma. N Engl J Med. 2018;378:1865-1876.

LIMITED FORMULA SUPPLEMENTATION MAY NOT ADVERSELY AFFECT BREASTFEEDING Level 2 [mid-level] evidence Exclusive breastfeeding — except for vitamins, minerals, and medications — for the first 6 months of life is recommended by several health organizations.

However, before abundant maternal milk production is established, some exclusively breastfed newborns may have an increased risk of hyperbilirubinemia and dehydration. Supplementation during early life is discouraged due to concerns that it may alter intestinal microbiota and have a negative impact on continued breastfeeding.

In a recent trial, 164 healthy singleton infants born at ≥37 weeks’ gestation (age range, 24 to 72 hours) who were exclusively breastfed and had pronounced weight loss (≥75th percentile for age) were randomly assigned to limited formula supplementation vs continuation with exclusive breastfeeding. Supplementation consisted of giving the newborn 10 mL of formula via a feeding syringe after each breastfeeding; supplementation was discontinued after abundant maternal milk production was established. Breastfeeding status was

Infants were given 10 mL of formula via a feeding syringe after each breastfeeding.

assessed via telephone interview conducted by an outcome assessor blinded to treatment allocation.

Newborns in the supplementation group received formula on an average of 5.4 times per day for a median of 2 days, and 37% of newborns in the control group had been given some formula by 1 week of age.There were no significant differences in the rates of breastfeeding at 1 month (86.5% with supplementation vs 89.7% with exclusive breastfeeding, risk ratio for cessation 1.21; 95% CI, 0.55-3.16) or rates of breastfeeding without formula use in the previous 24 hours (54.6% vs 65.8%). None of the newborns in the supplementation group were readmitted to the hospital, while 5 newborns (4.8%) in the control group were (P = .06). The reasons for readmission in the control group were hyperbilirubinemia in 3, umbilical infection in 1, and unknown in 1.

The findings of this trial suggest that early limited formula supplementation of breastfeeding does not significantly reduce rates of continued breastfeeding at 1 month. The confidence in this

44 THE CLINICAL ADVISOR • SEPTEMBER 2018 • www.ClinicalAdvisor.com

finding is tempered by the wide 95% confidence interval in risk of breastfeeding cessation, which includes the possibilities of both beneficial and adverse clinically significant differences. It should be noted that supplementation was given via a feeding syringe rather than a bottle, and this may have helped to avoid nipple confusion, which may interfere with breastfeeding in some infants.

A possible benefit of early supplementation in these neonates was suggested by the reduced rate of hospital readmissions, but this difference did not reach statistical significance. Preliminary analyses of intestinal microbiota conducted on 15 convenience stool samples taken during the trial were promising in that they suggest that the limited use of formula may not reduce the abundance of Lactobacillus or increase the abundance of Clostridia. These findings, however, require further investigation. Finally, the generalizability of the findings is limited by the low representation of women younger than 25 years of age (<15%), a population at increased risk of early discontinuation from breastfeeding.

In summary, this trial suggests that temporary and limited syringe-administered formula supplementation until an abundant maternal milk supply is established may be considered for selected neonates and their mothers. ■ Reference Flaherman VJ, Narayan NR, Hartigan-O’Connor D, Cabana MD, McCulloch CE, Paul IM. The effect of early limited formula on breastfeeding, readmission, and intestinal microbiota: a randomized clinical trial. J Pediatr. 2018;196:84-90..

For more Evidence-Based Medicine articles, visit ClinicalAdvisor.com/EBM.

© ARCHITETTA / GETTY IMAGES

The companion SYGMA 1 trial reported consistent results and also reported that as-needed budesonide/ formoterol was superior to as-needed terbutaline monotherapy.2

Dermatology Clinic CASE #1

Facial plaques following acne treatment LEAH DOUGLAS, BS; JOAN FERNANDEZ, BS; CHRISTOPHER RIZK, MD

A 29-year-old woman with a history of acne presents to the clinic with 3 discrete, atrophic, blue-tinged plaques on her face. The plaques were located on her forehead and cheeks bilaterally. The patient states the lesions had been present for several months and had slowly worsened until they stabilized at their current appearance. The patient reported that the lesions occurred after she went to a physician for “acne treatment.” The patient has no other medical conditions or relevant social history.

What is your diagnosis? Turn to page 46

CASE #2

Hyperpigmented lesion with vanishing mole JESSICA SHEU, BA; JOAN FERNANDEZ, BS; CHRISTOPHER RIZK, MD

A 20-year-old woman presents to the clinic with a circular hypopigmented lesion on her right cheek. The patient stated that she used to have a mole in the same location. Over time she noticed a white area around the mole that enlarged to the current size of the lesion. After a few months she noticed the mole in the center of the lesion had disappeared. On further questioning, she denies any personal or family history of skin cancer.

What is your diagnosis? Turn to page 48 www.ClinicalAdvisor.com • THE CLINICAL ADVISOR • SEPTEMBER 2018 45

Dermatology Clinic CASE #1

Corticosteroid-induced atrophy

Corticosteroids have been a mainstay of dermatologic therapy since 1952, when Sulzberger and Witten demonstrated the efficacy of topical hydrocortisone in the treatment of eczematous dermatitis.1 Since that time, the indications for corticosteroid use have greatly expanded to include pathologies such as atopic, papulosquamous, inflammatory, autoimmune, blistering, vascular, and granulomatous dermatoses.2 Corticosteroids are used as first-line therapy for many dermatologic diseases including atopic dermatitis, psoriasis, contact dermatitis, lichen planus, seborrheic dermatitis, and bullous pemphigoid.

Topical and intralesional corticosteroids are widely useful in the clinical setting due to their anti-inflammatory, immunosuppressive, vasoconstrictive, antiproliferative, and antipruritic properties. The basic structure of hydrocortisone has been modified numerous times, producing a class of drugs with a wide spectrum of potencies, absorptive potentials, and therapeutic effects. Many chemical modifications to hydrocortisone have been motivated by efforts to reduce the cutaneous and systemic sequelae of corticosteroid use.2 The profound atrophogenic effects of topical and intralesional corticosteroids are a long-recognized and well-documented phenomenon.

Atrophic striae associated with corticosteroid use was first reported in 1963 by Epstein et al in 5 male patients treated for inguinal intertrigo with a topical antifungal containing 0.1% triamcinolone acetonide.3 Clinically, topical and intralesional corticosteroid atrophy results in thin, translucent, shiny, and wrinkly skin that may have other steroid-associated features including telangiectasias, striae, and stellate pseudoscars.4,5 Corticosteroid-induced skin atrophy increases susceptibility to even minor trauma, resulting in delayed wound healing and easy bruisability.4 The 2016 Burden of Skin Disease report by the American Academy of Dermatology described the prevalence of various skin disorders within the US population, including contact dermatitis (4%), atopic dermatitis/eczemas (1.5%), seborrheic dermatitis (1%), and psoriasis (0.5%).6 Topical corticosteroids are first-line therapy for each of these conditions, and even low-potency steroids can induce atrophy; therefore, a remarkable proportion of the population is at risk.

Multiple factors exist that can increase a patient’s likelihood of developing topical steroid-induced skin atrophy, specifically those that enhance the percutaneous absorption of topical

corticosteroids. Anatomic sites with thin epidermis — such as the intertriginous areas, inguinal region, genitalia, eyelids, backs of hands, and periorbital areas — as well as moisture and occlusion of the areas of application all increase the rate of steroid absorption, thereby increasing the risk of atrophy.5 Patients who are at the extremes of age are also at increased risk for atrophy secondary to the increased skin fragility present in the elderly and the increased body surface area-to-weight ratio present in children.4 Additionally, increased exposure time and concentration of the corticosteroid applied are both associated with more severe atrophy.7 This atrophy can be seen as quickly as 1 week following the initiation of high-potency topical steroids under occlusion and as quickly as 2 weeks with topical lower-potency steroids.8 These lower-potency steroids are preferred for use in children and the elderly, for long-term use, and for use in areas of the body with thinner skin (eg, face). As a general rule, use of high-potency steroids should not exceed 3 weeks.9

A distinguishing feature of steroid atrophy is a lack of the epidermal scaling seen in inflammatory diseases.

The pathophysiology of steroid-induced skin atrophy begins at the cellular level, with the steroid molecule binding to a glucocorticoid receptor in the cytoplasm.This steroid-receptor complex is subsequently transported to the nucleus, where it binds to regulatory elements in the promoter regions of glucocorticoid-responsive genes, thereby modulating the transcriptional activity of many downstream genes.Atrophy results from a reduction in both epidermal and dermal thickness.

Levels of hyaluronic acid and hyaluronic acid receptor CD44 are depleted in atrophic skin, impairing dermal water retention.10 Corticosteroids exert antagonistic effects on collagen and elastin; dermal fibroblasts become shrunken, and type I and type III collagen synthesis is diminished.10 These alterations in tissue architecture increase susceptibility to tearing, giving rise to striae.11 It is hypothesized that the vasoconstrictive effect of corticosteroids causes rebound hyperdilation with prolonged use, resulting in the formation of telangiectasias.12 The diagnosis of steroid atrophy is made clinically based on the physical examination and a reported history of intralesional, potent, and/or prolonged topical steroid use. Skin thinning can be assessed and the diagnosis can be confirmed by biopsy, if necessary.

Many dermatologic lesions involve epidermal atrophy, dermal atrophy, and lipoatrophy and thus can mimic the

46 THE CLINICAL ADVISOR • SEPTEMBER 2018 • www.ClinicalAdvisor.com

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Dermatology Clinic dermo-epidermal atrophy induced by topical corticosteroids.

The differential diagnosis of steroid atrophy includes morphea, lichen sclerosis, scarring from various dermatosis, trauma-induced fat necrosis, and radiation-induced changes.8 A distinguishing feature of steroid atrophy is a lack of the epidermal scaling seen in inflammatory diseases.8 Additionally, histologic examination can be used to distinguish steroid atrophy from other diagnoses and will reveal marked epidermal thinning with decreased corneocytes, flattening of rete ridges, loss of mucopolysaccharides resulting in compaction and reorientation of collagen and elastin fibers, fibroblast shrinking, and overall dermal thinning.10,13 Treatment of corticosteroid-induced atrophy requires discontinuation of the offending agent. Sun protection should be recommended to avoid further atrophy from ultraviolet rays.8 Additionally, substantial evidence has shown that concurrent application of retinoic acid with topical corticosteroids reduces atrophy, and that the application of retinoids after the development of steroid atrophy can help reverse the atrophy and the other superficial changes associated with steroid use.8,14 Pulsed-dye laser may also help reverse the atrophy by promoting collagen deposition and dermal elastin production.15 Dermal fillers can also be used for severe steroid atrophy in cosmetically sensitive areas. However, it is important to counsel patients that the effects of skin atrophy are usually only partially reversible, and that it can take months to years to see significant improvements in skin composition and appearance.

The patient in this case was treated with intralesional triamcinolone in an attempt to address large acne nodules on her face. Unfortunately, too high a concentration was used leading to the atrophic lesions visualized in the image. Since the lesions were located in cosmetically sensitive areas (her face), the patient was treated with 3 rounds of dermal filler over 6 months.After the filler treatments, the patient made a full recovery.

Leah Douglas, BS, is a medical student; Joan Fernandez, BS, is a medical student; and Christopher Rizk, MD, is a dermatology resident at the Baylor College of Medicine in Houston.

References 1. Sulzberger MB, Witten VH. The effect of topically applied compound F in selected dermatoses. J Invest Dermatol. 1952;19(2):101-102.

2. Lahiri K, ed. A Treatise on Topical Corticosteroids in Dermatology: Use, Misuse and Abuse. New York, NY: Springer; 2017.

3. Epstein NN, Epstein WL, Epstein JH. Atrophic striae in patients with inguinal intertrigo: pathogenesis. Arch Dermatol. 1963;87(4):450-457.

4. Hengge UR, Ruzicka T, Schwartz RA, Cork MJ. Adverse effects of topical glucocorticosteroids. J Am Acad Dermatol. 2006;54(1):1-18.

5. Fisher DA. Adverse effects of topical corticosteroid use. West J Med. 1995;162(2):123-126.

6. Lim HW, Collins SAB, Resneck JS, et al. The burden of skin disease in the United States. J Am Acad Dermatol. 2017;76(5):958-972.e2.

7. Frosch PJ, Behrenbeck EM, Frosch K, Macher E. The Duhring chamber assay for corticosteroid atrophy. Br J Dermatol. 1981;104(1):57-66.

8. Craft N, Fox LP, Goldsmith LA, et al. VisualDx: Essential Adult Dermatology.

1st ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2010.

9. Ference JD, Last AR. Choosing topical corticosteroids. Am Fam Physician.

2009;79(2):135-140.

10. Burns T, Breathnach S, Cox N, Griffiths C. Rook’s Textbook of Dermatology, 8th Edition. Hoboken, NJ; Wiley-Blackwell; 2010.

11. Kharb S, Gundgurthi A, Dutta MK, Garg MK. Striae atrophicans: a mimic to Cushing’s cutaneous striae. Indian J Endocrinol Metab. 2012;16(Suppl 1):S123.

12. Rapaport MJ, Rapaport V. The red skin syndromes: corticosteroid addiction and withdrawal. Expert Rev Dermatol. 2006;1(4):547-561.

13. Lehmann P, Zheng P, Lavker RM, Kligman AM. Corticosteroid atrophy in human skin. A study by light, scanning, and transmission electron microscopy.

J Invest Dermatol. 1983;81(2):169-176.

14. McMichael AJ, Griffiths CE, Talwar HS, et al. Concurrent application of tretinoin (retinoic acid) partially protects against corticosteroid-induced epidermal atrophy. Br J Dermatol. 1996;135(1):60-64.

15. Mansouri P, Ranjbar M, Abolhasani E, Chalangari R, Martits-Chalangari K, Hejazi S. Pulsed dye laser in treatment of steroid-induced atrophy. J Cosmet Dermatol. 2015;14(4):E15-E20.

CASE #2

Halo nevus

A halo nevus is a rare benign dermatologic entity characterized by a typical whitish rim encircling the existing melanocytic nevus resembling a halo.1 In 1916, Sutton clinically described 3 such lesions as “leukoderma acquisitum centrifugum.”2 Therefore, Sutton is widely credited for describing halo nevus.3 In Borroni and Vignati’s article highlighting the history of halo nevus, Kaposi actually gave Hebra credit for being the first to accurately describe a halo nevus in the literature.4 Happle also suggested that the alternative term, “Grunewald nevus,” was more appropriate than the term “Sutton nevus.”2 It is now well accepted that the inflammatory response seen in a halo nevus is mostly lymphocytic in nature, often with a small number of melanophages.5 Clinically, patients may start to notice an area of erythema or redness around a nevus.This area of erythema then starts to depigment, leaving a halo of white skin around the nevus.

48 THE CLINICAL ADVISOR • SEPTEMBER 2018 • www.ClinicalAdvisor.com

Occasionally, over time the original nevus (in the center of the white halo) may start to lighten and even disappear (thus possibly leaving a depigmented circle).

Halo nevi are reported to occur in approximately 1% of the population and are most commonly located on the trunk; however, they may appear in multiple locations.6 Both genders are equally affected, and most halo nevi appear during an individual’s teenage or young adult years.6 There is no predilection for race.6 The natural history of halo nevi is not well understood, but there have been reported cases of patients with a history of congenital halo nevi or vitiligo, which suggests a possible link.

The exact pathophysiology leading to the development of a halo nevus has not been clearly delineated.

The relation between halo nevi and vitiligo remains unclear, but the two diseases do share a common pathologic end point — the destruction of normal melanocytes.Additionally, both of these pathologies are associated with antimelanocyte tumor responses.7 One case by Kawaguchi et al described a patient with multiple halo nevi after a short period of sunbathing, which suggested a possible relationship between sun exposure and halo nevi development.8 The onset of multiple halo nevi has also been noted to occur after treatment with various immunotherapies including interferon-alfa, infliximab, imatinib, and tocilizumab.8 Halo nevi are more commonly linked with benign melanocytic nevi, but rarely they can occur within nevi with various degrees of atypia, in nonmelanocytic tumors, in inflammatory lesions, and in melanoma. A band-like lymphohistiocytic infiltrate in the dermis is the characteristic histopathologic feature.9 Halo nevi usually persist for a decade or longer, and education about the prolonged history may be necessary to reassure patients about the benign nature of the lesion and to avoid unnecessary excisions.10 Traditionally, halo nevi have been clinically described as dysplastic lesions; however, the presence of dysplasia has not been found on histologic examination.10 In 1974, after performing a series of ultrasound studies, Hashimoto suggested that autophagocytosis of melanosomes in halo nevi was responsible for the depigmentation that is observed clinically.11 At the time of his experiments, Hashimoto was unsure whether the lymphocytic infiltration seen in halo nevi played a primary or secondary role in the early stages of the nevus’ development.11 In 1999,

Musette et al hypothesized that halo nevi were caused by an autoimmune-like response.12 While there have been many proposed etiologies, the exact pathophysiology leading to the development of a halo nevus has still not been clearly delineated. However, it has been widely accepted that cellmediated immunity plays a primary role in pathogenesis.13 Granulomatous inflammation has been found on histologic examination of halo nevi, but this finding was only reported in those lesions that occurred with cysts, folliculitis, or trauma, and it was also noted that the presence of this inflammation was not a primary response to a halo nevus but rather secondary to an underlying event.14 Additionally, some have suggested that one possible explanation for the granulomatous inflammation seen in some halo nevi is the coexistence of a systemic granulomatous disease, such as an infectious process caused by atypical mycobacteria or sarcoidosis.15 In halo nevi going through regression, granulomatous inflammation may occur due to an exaggerated cell-mediated immune response; T lymphocytes may produce lymphokines excessively, which could then act as an attractant for large numbers of macrophages with an activated phenotype.15 As is evident from the description above, there are multiple potential causes underlying the presence of granulomatous inflammation seen in some cases of halo nevi, and practitioners must look out for other pathology that could contribute to this finding.

When considering a diagnosis of halo nevus, one must also include melanoma in the differential. Despite the fact that halo nevi are very rarely associated with melanoma, the central lesions should be evaluated and biopsied if any diagnostic uncertainty exists.16 Halo nevi can also at times be similar in presentation to vitiligo, and it is important to differentiate the two in these cases. An example where the differentiation between the 2 diagnoses has been at times challenging is in patients with Turner syndrome. These patients have been reported to have an increased prevalence of halo nevi rather than the sometimes misdiagnosed vitiligo.17 Lastly, dysplastic nevus should also be included in the differential diagnosis when evaluating a patient with a suspected halo nevus.10 The treatment for halo nevi has proven to be somewhat controversial. Because of the fact that halo nevi are suspected to arise from nevus cells that are atypical or going through malignant transformation, some may choose to treat these aggressively. However, this suspicion has yet to be proven and therefore leaves room for physician discretion in the treatment plan.7 The current recommendations for the management of halo nevi are broad, ranging from observation without intervention to excisional biopsy.7 Treatment plans may also be guided by cosmetic concerns that the patient might have.

For example, many patients in Asian countries are concerned

www.ClinicalAdvisor.com • THE CLINICAL ADVISOR • SEPTEMBER 2018 49

Dermatology Clinic about the cosmetic effects of the hypopigmentation surrounding the lesion, especially when located on the face.7 For the patient described in this case, the lesion had not been changing for several months. Therefore, the physician decided to monitor the lesion rather than perform a biopsy.

The patient was given the option to excise the lesion if it was displeasing to her cosmetically, but she instead elected to continue with yearly observation. ■

7. Mulekar SV, Issa AA, Eisa AA. Treatment of halo nevus with a 308-nm excimer laser: a pilot study. J Cosmet Laser Ther. 2007;9:245-248.

8. Kawaguchi A, Yamamoto T, Okubo Y, Mitsuhashi Y, Tsuboi R. Multiple halo nevi subsequent to a short period of sunbathing. J Dermatol.

2015;42:543-544.

9. Mooney MA, Barr RJ, Buxton MG. Halo nevus or halo phenomenon?

A study of 142 cases. J Cutan Pathol. 1995;22:342-348.

10. Aouthmany M, Weinstein M, Zirwas MJ, Brodell RT. The natural history of halo nevi: a retrospective case series. J Am Acad Dermatol. 2012;67:582-586.

Jessica Sheu, BA, is a medical student; Joan Fernandez, BS, is a medical student; and Christopher Rizk, MD, is a dermatology resident at the Baylor College of Medicine in Houston.

11. Hashimoto K. Ultrastructural studies of halo nevus. Cancer. 1974;34: 1653-1666.

12. Musette P, Bachelez H, Flaguel B, et al. Immune-mediated destruction of melanocytes in halo nevi is associated with the local expansion of a limited number of T cell clones. J Immunol. 1999;162(3):1789-1794.

1. Kamińska-Winciorek G, Szymszal J. Dermoscopy of halo nevus in own

13. Roenigk HH, Deodhar SD, Krebs JA, Barna B. Microcytotoxicity and

observation. Postepy Dermatol Alergol. 2014;31:152-158.

serum blocking factors in malignant melanoma and halo nevus. Arch Dermatol.

2. Happle R. [Grünewald nevus]. Hautarzt. 1994;45(12):882-883.

1975;111:720-725.

3. Findlay GH. The histology of Sutton’s naevus. Br J Dermatol. 1957;69:

14. Cohen PR, Rapini RP. Nevus with cyst. A report of 93 cases. Am J

389-394.

Dermatopathol. 1993;15:229-234.

4. Borroni G, Vignati G. Should Sutton nevus really be called Grünewald-

15. Denianke KS, Gottlieb GJ. Granulomatous inflammation in nevi undergo-

Sutton nevus? Am J Dermatopathol. 1993;15:506-508.

ing regression (halo phenomenon): a report of 6 cases. Am J Dermatopathol.

5. Elder D, Elenitsas R, Murphy G. Atlas and Synopsis of Lever’s Histopathology

2008;30:233-235.

of the Skin. Philadelphia, PA: Wolters Kluwer/Lippincott Williams & Wilkins

16. Frank SB, Cohen HJ. The halo nevus. Arch Dermatol. 1964;89:367–373.

Health, 2012.

17. Brazzelli V, Larizza D, Martinetti M, et al. Halo nevus, rather than vitiligo, is a

6. Kopf AW, Morrill SD, Silberberg I. Broad spectrum of leukoderma

typical dermatologic finding of Turner’s syndrome: clinical, genetic, and immu-

acquisitum centrifugum. Arch Dermatol. 1965;92:14-33.

nogenetic study in 72 patients. J Am Acad Dermatol. 2004;51:354-358.

© The New Yorker Collection 2018 from cartoonbank.com. All Rights Reserved.

References

“No, no, no! Thirty days hath September!”

50 THE CLINICAL ADVISOR • SEPTEMBER 2018 • www.ClinicalAdvisor.com

Dermatologic Look-Alikes Erythematous annular lesions TALIA NOORILY, BA; JOAN FERNANDEZ, BS; CHRISTOPHER RIZK, MD

CASE #1

CASE #2

A 24-year-old woman presents to the clinic with a 4-month history of an erythematous annular lesion on the dorsal arm.The lesion is neither painful nor pruritic, and the patient reports no associated symptoms. Measuring approximately 2 cm in greatest diameter, the lesion is composed of 3-mm papules. The patient reports that the lesion has slowly expanded over time. She has not tried any topical medications. She is healthy and has no chronic medical conditions.

A 47-year-old non-Hispanic white woman presents to the clinic with a history of a chest lesion for several years.The lesion consists of grouped 1-mm erythematous papules with surrounding annular erythema with a diameter of 1 cm. The lesion is painless and nonpruritic. Although she does not know exactly when the lesion first appeared, she recalls first noticing it several years ago. She reports that it may have grown slightly since that time. She has not tried any topical medications.

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Dermatologic Look-Alikes CASE #1

Granuloma Annulare

Granuloma annulare is a relatively common, self-limited, and benign skin disorder that presents in both children and adults.The condition was first described as a “ringed eruption of the fingers” by Thomas Colcott Fox in 1895.1 Today, there exist multiple classifications of granuloma annulare, including localized and generalized forms, as well as subcutaneous, patch and perforating granuloma annulare. The various types differ in clinical presentation and appearance, but they share a similar histopathology.

Granuloma annulare most frequently presents in female patients, with a female-to-male ratio of 2:1.2 It is also more common in children and young adults; two-thirds of those affected are younger than 30 years of age.2 The overall incidence and prevalence of granuloma annulare has not been studied on a large scale; however, one review article estimates that granuloma annulare was diagnosed in 0.1% to 0.4% of new patients presenting to dermatologists.3 The pathogenesis of the condition is not entirely understood. Proposed triggers include trauma, vaccinations, insect bites, and various viral infections including hepatitis B and C, Epstein-Barr virus, and HIV.4 Although research has been conducted to assess a potential association between granuloma annulare and diabetes mellitus, the association is controversial due to lack of large-scale epidemiologic studies.2

Two-thirds of those affected with granuloma annulare are younger than 30 years of age.

Granuloma annulare may present with a variety of clinical characteristics. The localized form usually presents as an annular or arciform asymptomatic plaque without scale.The plaque may be erythematous, violaceous, or skin colored and often has an area of central clearing. Some lesions may present with discrete 1- to 2-mm papules at the outer edge of the lesion; other lesions develop a firm, continuous border, which upon careful inspection is composed of individual small, 1- to 3-mm papules that coalesce into a larger annular plaque, usually <6 cm.2 Localized granuloma annulare most

often presents in the wrists, ankles, and on the dorsal aspect of the hands and feet. More than half of patients will have more than one lesion. In generalized granuloma annulare, papules and plaques present in widespread areas of the trunk and extremities.The lesions are most commonly distributed symmetrically. Generalized granuloma annulare usually presents at a later age than the localized subtype.

Subcutaneous granuloma annulare presents as deep dermal or subcutaneous asymptomatic nodules with no overlying skin changes. Lesions are most commonly located on the anterior tibial surfaces, buttocks, hands, and scalp of children.5 Perforating granuloma annulare consists of small papules with central umbilication, crust, or ulceration.These lesions occur most frequently on the dorsal aspects of the fingers and hands. Patch granuloma annulare presents as symmetric erythematous patches on the extremities and trunk.2 With so many different variants of granuloma annulare, the diagnosis often must be made microscopically. Histologic examination of granuloma annulare demonstrates a dermal lymphohistiocytic infiltrate with degenerated collagen and mucin deposition.The cells most commonly organize in an interstitial or palisading granulomatous pattern.The interstitial histologic pattern demonstrates histiocytes scattered between collagen fibers, with basophilic mucin deposits among the collagen bundles.The palisading granulomatous pattern demonstrates a central core of degenerating collagen, elastic fibers, and mucin, with histiocytes and lymphocytes at the circumference. In subcutaneous granuloma annulare, the palisaded granulomatous pattern can be seen in the deep dermis and subcutaneous fat.2 Due to the variety of clinical presentations, the differential diagnosis for granuloma annulare is broad. Localized granuloma annulare simulates other annulare entities including tinea corporis, annular elastolytic giant cell granuloma (AEGCG), and sarcoidosis. Granuloma annulare can be differentiated from tinea corporis clinically by lack of scale in the former.

Definitive diagnosis of tinea corporis can be confirmed by performing a potassium hydroxide preparation or fungal culture. AEGCG appears clinically as a pink annular plaque with central atrophy and hypopigmentation; these lesions most commonly occur in sun-exposed areas. Histologically, both AEGCG and granuloma annulare may contain palisading granulomas. However, the two are set apart by loss of dermal elastic fibers and absent mucin in AEGCG. Cutaneous sarcoidosis may present as red-brown annular plaques and papules, with a predilection for the face. Sarcoidosis is often associated with systemic symptoms. Histologically, sarcoidosis may be distinguished from granuloma annulare by the presence of noncaseating sarcoidal granulomas in the former.6

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Continues on page 54

Dermatologic Look-Alikes Generalized papular granuloma annulare may appear similar to flat warts, insect bites, eruptive xanthomas, or secondary syphilis. Clinical correlation and biopsy should be used to distinguish the different entities.2 Subcutaneous granuloma annulare must be distinguished from rheumatoid nodules, the nodules of rheumatic fever, and deep granulomatous infections. Rheumatoid nodules simulate subcutaneous granuloma annulare both clinically and in histopathology; subcutaneous granuloma annulare lesions are also known as pseudorheumatoid nodules. Classic rheumatoid nodules occur in individuals with severe, seropositive arthritis.7 Therefore, nodules appearing in young children are more likely to be subcutaneous granuloma annulare, while lesions occurring in older individuals with rheumatoid arthritis are more likely rheumatoid nodules.

Due to the variety of clinical presentations, the differential diagnosis for granuloma annulare is broad.

Oftentimes, the diagnosis of granuloma annulare can be made clinically. No serologic test exists for this condition.

One must carefully rule out the other conditions in the differential diagnosis including the annular, papular, and nodular lesions previously described. Biopsy can confirm the presence of granuloma annulare.

In localized and asymptomatic disease, reassurance and clinical observation are recommended, as granuloma annulare is a self-limited condition. Half of cases of localized granuloma annulare will completely resolve in 2 years without intervention.2 For individuals with localized disease that persists, firstline therapy consists of topical or intralesional corticosteroids.

Response to this treatment is variable; however, some studies have found intralesional therapy to be greatly effective.8 Topical steroid should be applied once or twice daily for 2 to 4 weeks. Intralesional steroid, usually triamcinolone, should be injected at the border of the lesions every 6 to 8 weeks.9 Topical tacrolimus may also be effective. For more extensive disease, phototherapy or systemic medications including hydroxychloroquine, isotretinoin, and dapsone may be used. Granuloma annulare often recurs in the same area as the original lesions, and the majority of recurrences resolve spontaneously.2 For the patient in our case, biopsy of the lesion confirmed the diagnosis of localized granuloma annulare. She was reassured as to the benign nature of the condition and elected not to pursue treatment. She followed up in the clinic every 3 months and the lesion resolved after approximately 15 months.

CASE #2

Primary cutaneous B-cell lymphoma

Primary cutaneous B-cell lymphoma is a non-Hodgkin lymphoma, the primary site of which is the skin. These lymphomas have no evidence of extracutaneous involvement at the time of the initial staging evaluation. Historically, cutaneous B-cell lymphomas were always considered to be secondary to dissemination from a lymph node or other extracutaneous source. It was not until the 1980s that cutaneous B-cell lymphomas were first recognized as a separate entity.10 Cutaneous B-cell lymphomas make up approximately 25% of primary cutaneous lymphomas, with T-cell lymphomas comprising the other 75%.11 There are 3 main classes of primary cutaneous B-cell lymphoma: primary cutaneous follicle center lymphoma (PCFCL), primary cutaneous marginal zone B-cell lymphoma (PCMZL), and primary cutaneous diffuse large B-cell lymphoma, leg type.12 Primary cutaneous lymphoma affects one person per 100,000 to 200,000 people in Western countries annually.The incidence of primary cutaneous B-cell lymphoma differs by region. An epidemiologic study in the United States demonstrated that only 4.5% of primary cutaneous lymphomas were classified as B cell in origin; however, in some European countries, cutaneous B-cell lymphomas comprise 22.5% of primary cutaneous lymphomas.13 Primary cutaneous B-cell lymphoma affects adults (median age, 51 years), with a maleto-female ratio of 1.5:1. Unlike mycosis fungoides (T-cell lymphoma), which has a high prevalence in black patients, primary cutaneous B-cell lymphoma almost exclusively affects non-Hispanic white patients.14 The pathogenesis of primary cutaneous B-cell lymphoma is unknown, and there are no known risk factors for the disease. It has been hypothesized that chronic exposure to antigens stimulates cutaneous B-cell lymphoma development. Some studies and case reports suggest an association between primary cutaneous B-cell lymphoma and Borrelia burgdorferi or certain viruses; these studies have been unsubstantiated to date.15 The presentation and histology of cutaneous B-cell lymphoma differ by subtype. PCFCL is defined as a neoplastic proliferation of germinal center cells in the skin. It presents as singular or clustered pink-to-purple papules, plaques, or nodules. A peripheral ring of erythema often surrounds these lesions. PCFCL lesions favor the head, neck, and trunk.

54 THE CLINICAL ADVISOR • SEPTEMBER 2018 • www.ClinicalAdvisor.com

Granuloma Annulare2-4

Cutaneous B-cell Lymphoma15

Dermatologic Presentation

• Erythematous, violaceous, or skin-colored annular or arciform plaques • Subcutaneous nodules without overlying skin changes • Papules with or without ulceration; erythematous patches

• PCFCL: solitary or grouped erythematous/violaceous papules, plaques, or tumors • PCMZL: pink to red-brown papules, plaques, or nodules • DLBCLLT: solitary or clustered erythematous nodules

Associations

• Diabetes mellitus (controversial)

• Borrelia burgdorferi, viruses (controversial)

Etiology

• Unknown

• Unknown

Characteristic Location

• Localized granuloma annulare : wrists, ankles, dorsal hands, dorsal feet • Generalized granuloma annulare: symmetrically on trunk and extremities • Subcutaneous granuloma annulare: anterior tibial surfaces, buttocks, hands, and scalp • Perforating granuloma annulare: dorsal fingers and hands • Patch granuloma annulare: extremities and trunk

• PCFCL: head, neck, trunk • PCMZL: upper extremities, trunk, head • DLBCLLT: distal leg

Histology

• Dermal lymphohistiocytic infiltrate with degenerated collagen and mucin deposition

• PCFCL: dermal and subcutaneous proliferation of centrocytes and centroblasts in follicular/diffuse growth pattern • PCMZL: dermal and subcutaneous proliferation of marginal-zone B cells in nodular or patchy pattern • DLBCLLT: dermal sheet-like infiltrate of large B cells with prominent nucleoli and mitotic figures

Diagnosis

• Clinical picture; biopsy

• Biopsy; thorough staging

Treatment

• Reassurance and observation • Topical and intralesional corticosteroids • Phototherapy

• Indolent lesions: close clinical observation, localized radiotherapy, surgical excision • DLBCLLT: systemic chemotherapy and/or rituximab

PCFCL is a slow-growing, indolent neoplasm. Skin lesions may be present for decades, with a period of gradual growth and a latent phase, before diagnosis. Systemic “B” symptoms are extremely rare in PCFCL.16 These tumors rarely metastasize and prognosis is favorable.15 On histologic examination, PCFCL demonstrates a follicular and/or diffuse growth pattern of centrocytes and centroblasts in the dermis and subcutaneous tissue.The tumor is positive for CD20, CD79a, and Bcl-6 on immunohistochemical staining. Unlike other follicular lymphomas, PCFCL is rarely associated with the Bcl-2 t(14;18) translocation.14 PCMZL presents as red-violet papules, plaques, or nodules most commonly located on the trunk, upper extremity, or head. PCMZL is a neoplasm of marginal-zone B-cells. It carries an excellent prognosis, with a 5-year survival rate of nearly 100%. Cutaneous relapse after resolution may occur. On histologic examination, a nodular, patchy, or diffuse infiltrate

of marginal-zone B-cells (small cells with irregular nuclei and pale cytoplasm) joined by various other immune cells can be visualized in the dermis and subcutaneous tissue. On immunohistochemical staining, the neoplasm is positive for CD20, CD43, and Bcl-2, but negative for CD5, CD10, and Bcl-6.14 Primary cutaneous DLBCLLT most commonly presents in elderly female patients as single or grouped red-to-brown nodules on a lower extremity.The nodules may be admixed with smaller papules, and ulceration of the lesions may occur.

Although this subtype is designated “leg type,” these tumors present elsewhere on the body in approximately 20% of patients.15 The prognosis for DLBCLLT is poor, with a 5-year disease-specific survival rate of only 40% to 50%. Histologic examination demonstrates diffuse proliferation of large centroblasts and immunoblasts that are twice the size of normal lymphocytes. Many cells contain prominent nucleoli and mitotic figures. The infiltrate occupies the dermis in sheets.

www.ClinicalAdvisor.com • THE CLINICAL ADVISOR • SEPTEMBER 2018 55

Dermatologic Look-Alikes The neoplastic cells stain positive for CD20, CD79a, Bcl-2, FOX-P1, and MUM1, with variable expression of Bcl-6 and negative expression of CD10.14,17 All of the primary cutaneous B-cell lymphomas must be distinguished from each other and from other cutaneous lymphomas. Examination of histopathologic morphology and performance of immunohistochemical staining allows differentiation between the various subtypes of primary cutaneous lymphomas. It is especially critical to differentiate PCFCL from DLBCLLT, as both present with large B-cell infiltrates, but the latter has a more aggressive course with poor prognosis. This can be accomplished via immunophenotyping. Cutaneous T-cell lymphomas such as mycosis fungoides are distinguished by their positive expression of T-cell markers, including CD3.15 Primary cutaneous B-cell lymphomas must also be differentiated from other inflammatory processes, such as infection or arthropod bites, which may have a similar clinical appearance and histopathology. The cutaneous follicular hyperplasia of an inflammatory process, however, will have clearly defined follicles, mantle zones, and the presence of tingible body macrophages.18

intravenous rituximab.17 After completion of therapy, patients should be monitored closely and assessed for relapse.

As for the patient in our case, an excisional biopsy demonstrated PCFCL. She elected to receive radiotherapy to her lesion, and she is currently undergoing treatment. ■ Talia Noorily, BS, is a medical student; Joan Fernandez, BS, is a medical student; and Christopher Rizk, MD, is a dermatology resident at the Baylor College of Medicine in Houston.

References 1. Fox TC. Ringed eruption of the fingers. Br J Dermatol. 1895;7:91.

2. Rosenbach MA, et al. Non-infectious granulomas. In: Bolognia J, Schaffer JV, Cerroni L (eds). Dermatology. 4th ed. Philadelphia: Elsevier Saunders; 2018:1644-1663.

3. Muhlbauer JE. Granuloma annulare. J Am Acad Dermatol. 1980;3:217-230.

4. Prendiville JS. Granuloma annulare. In: Wolff, K, Goldsmith, LA, Katz, SI, et al (eds). Fitzpatrick’s Dermatology in General Medicine. 7th ed. New York, NY: McGraw-Hill Companies, Inc.; 2008:369.

5. Requena L, Fernández-Figueras MT. Subcutaneous granuloma annulare.

Semin Cutan Med Surg. 2007;26:96-99.

6. Espana A. Figurate erythemas. In: Bolognia J, Schaffer JV, Cerroni L (eds).

“Watchful waiting” with close clinical follow-up may be the best option for select indolent lesions.

Dermatology. 4th ed. Philadelphia: Elsevier Saunders;2018:320-331.

7. García-Patos V. Rheumatoid nodule. Semin Cutan Med Surg. 2007;26:100-107.

8. Dabski K, Winkelmann RK. Generalized granuloma annulare: clinical and laboratory findings in 100 patients. J Am Acad Dermatol. 1989;20:39-47.

9. Brodell RT. Granuloma annulare. In: Post T (ed). UpToDate. Waltham, Mass.: UpToDate; 2014. www.uptodate.com. Accessed April 12, 2018.

10. Cerroni L. Skin Lymphoma – The Illustrated Guide. Oxford: Wiley-Blackwell, 2014.

Diagnosis is based on histopathology of the skin biopsy, evaluating for cell morphology, pattern of growth, and immunohistochemical properties. The biopsy must include the reticular dermis and fat, and excisional biopsies are often preferred.14 Complete staging must be performed to rule out secondary cutaneous involvement from an extracutaneous source, most commonly a lymph node. Staging includes complete blood count, peripheral blood flow cytometry, and computed tomographic and positron emission tomographic imaging. Measurement of lactate dehydrogenase can also be used to rule out nodal lymphoma, as the level should fall within normal limits in primary cutaneous lymphomas.15 Patients with PCFCL and PCMZL who have few lesions have several treatment options: direct radiotherapy of the lesion, surgical excision, or surgical excision followed by radiotherapy. For select indolent lesions, “watchful waiting” with close clinical follow-up may be the best option. Intralesional rituximab is another potential therapy for indolent, localized lesions.15 Patients with disseminated B-cell lymphomas or DLBCLLT usually require systemic chemotherapy plus

11. Willemze R, Jaffe ES, Burg G, et al. WHO-EORTC classification for cutaneous lymphomas. Blood. 2005;105:3768-3785.

12. Swerdlow SH, Campo E, Pileri SA, et al.The 2016 revision of the World Health Organization classification of lymphoid neoplasms. Blood. 2016;127:2375-2390.

13. Zackheim HS,Vonderheid EC, Ramsay DL, et al. Relative frequency of various forms of primary cutaneous lymphomas. J Am Acad Dermatol. 2000;793-796.

14. Suarez AL, Pulitzer M, Horwitz S, Moskowitz A, Querfeld C, Myskowski PL. Primary cutaneous B-cell lymphomas: part I. Clinical features, diagnosis, and classification. J Am Acad Dermatol. 2013;69:329.e1-13.

15. Cerroni L. B-Cell Lymphomas of the Skin. In: Bolognia J, Schaffer JV, Cerroni L (eds). Dermatology. 4th ed. Philadelphia: Elsevier Saunders; 2018:2113-2126.

16. Bergman R, Kurtin PJ, Gibson LE, Hull PR, Kimlinger TK, Schroeter AL. Clinicopathologic, immunophenotypic, and molecular characterization of primary cutaneous follicular B-cell lymphoma. Arch Dermatol. 2001;137:432-439.

17. Grange F, Beylot-Barry M, Courville P, et al. Primary cutaneous diffuse large B-cell lymphoma, leg type: clinicopathologic features and prognostic analysis in 60 cases. Arch Dermatol. 2007;143:1144-1150.

18. Jacobsen E, Freedman AS, Willemze R. Primary cutaneous follicle center lymphoma. In: Post T (ed). UpToDate. Waltham, Mass.: UpToDate; 2014. www. uptodate.com. Accessed April 17, 2018.

56 THE CLINICAL ADVISOR • SEPTEMBER 2018 • www.ClinicalAdvisor.com

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.

CASE FILES PREVERTEBRAL SWELLING FROM PUNCTURE Contributed by Philip Hehn, PA-C A 23-month-old female sustained a trip-andfall with a pencil in her mouth. There were no initial signs of bleeding, the pencil was intact, and child was acting appropriately.

The parents brought the child into the emergency department 6 hours later as she woke up crying in pain. It was noted that her cry sounds different and is best described as inspiratory stridor as seen in croup.

Axial computed tomographic images of the neck reveal prevertebral swelling from a puncture likely resulting in abscess/hematoma. There was no involvement of the internal carotid artery.

SUBPERIOSTEAL ORBITAL HEMATOMA Contributed by Stephen J. Laquis MD, FACS, and Jonel Gomez MSN, ARNP A 26-year-old woman was referred for evaluation of a left orbital mass. At first the patient was unable to recall an injury to the left orbit. Further inquiry revealed that 3 nights prior she had been celebrating her first night out since having a baby and had enjoyed enough cocktails to cause her to fall while exiting a car. She awoke in the morning with what was described by the patient as a subconjunctival hemorrhage, ecchymosis around her left eye, and protrusion of the eye. This worsened over

the course of 3 days, prompting her to go to the emergency department, from which she was then referred for oculoplastic evaluation to determine the etiology of the proptosis and diplopia in upgaze.

Computed tomographic imaging demonstrated a left superior concave orbital soft tissue mass of homogeneous consistency extending from the level of the mid orbit to apex. Magnetic resonance imaging was also performed with similar findings.

A differential diagnosis of hemorrhage, abscess, or lymphoma was considered. After 4 weeks of observation, the proptosis and diplopia resolved.

The imaging findings of a concave orbital mass with homogeneous enhancement and associated proptosis is indicative of a subperiosteal fluid collection.The 2 most common etiologies for a mass with this classic configuration are abscess and hematoma. An abscess would be associated with adjacent sinusitis and signs and symptoms of orbital cellulitis. A hematoma would have presented as this case did with a history of trauma.

MYCOBACTERIUM TUBERCULOSIS INFECTION Contributed by Tasneam Shagroni, MD A 50-year-old man with a history of HIV presents with 2 weeks of fevers, chills, night sweats, dry cough, and malaise. He was off of his highly active antiretroviral therapy (HAART) for 2 years.The patient was incarcerated 1 month prior to his presentation.

His CD4 lymphocyte count was 257 cells/μL and his HIV viral load was 177,000 copies/mL. Chest radiography revealed severe diffuse interstitial

Send us your letters with questions and comments to: Advisor Forum, The Clinical Advisor, 275 7th Avenue, 10th Floor, New York, NY 10001.You may contact us by e-mail at editor@ 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.

www.ClinicalAdvisor.com • THE CLINICAL ADVISOR • SEPTEMBER 2018 57

Advisor Forum Our Consultants Philip R. Cohen, MD,

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

nodular and micronodular opacities in a miliary pattern throughout the lungs. Sputum cultures and bronchoalveolar lavage grew Mycobacterium tuberculosis. He was treated for miliary pulmonary tuberculosis with rifampin, isoniazid, pyrazinamide, and ethambutol and was re-initiated on HAART therapy with clinical improvement in symptoms.

Deborah L. Cross, MPH, CRNP, ANP-BC,

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

Abimbola Farinde, PhD, PharmD,

is a professor at Columbia Southern University in Orange Beach, Ala. Laura A. Foster, CRNP, FNP,

practices family medicine with Palmetto Primary Care Physicians in Charleston, S.C. Abby A. Jacobson, MS, PA-C,

is an assistant professor at Thomas Jefferson University and a dermatology PA at Family Dermatology of Reading, Pa. Debra August King, PhD, PA,

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

Mary Newberry, CNM, MSN,

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

Claire O’Connell, MPH, PA-C,

is an associate professor at the Rutgers University Physician Assistant Program, Piscataway, N.J. Katherine Pereira, DNP, FNP,

is assistant professor, Duke University School of Nursing, Durham, N.C. Sherril Sego, FNP-C, DNP,

is an independent consultant in Kansas City, Mo.

HYPERPIGMENTATION OF THE UPPER BACK Contributed by Kathleen Haycraft, DNP, FNP/ PNP-BC, DCNP An 80-year-old man was referred by his cardiologist for assessment of an asymptomatic rash on his upper back.The rash had been present for 3 months.

When questioned, the patient reported that he had used a rectangular, mid-sized heating pad on the upper back. He stated it worked better than pain pills.The diagnosis was determined to be erythema ab igne.The patient was advised to discontinue use of the heating pad.

SUBCUTANEOUS GROIN ABSCESS Contributed by Linda Liu, DNP, ANP-BC GNPBC, ACHPN-BC A mass located above the left groin of an 85-yearold woman was found to be a subcutaneous abscess. The mass was originally present 4 years ago as a small, soft, freely mobile mass consistent with lipoma. She reported that 5 days earlier, she had tenderness and slight redness to the area.

Over the next 5 days, the mass grew in size, with a significant amount of erythema and swelling extending over the pubic area. On day 5, a small amount of bleeding was noted. Ultrasound revealed a mass located in the left inguinal region in the subcutaneous soft tissue directly subjacent to the skin with lobulated margins and horizontal

58 THE CLINICAL ADVISOR • SEPTEMBER 2018 • www.ClinicalAdvisor.com

orientation measuring 2.6 × 1.8 × 2.3 cm in size, representing a subcutaneous abscess.The abscess was treated by incision and drainage with resolution; no antibiotic was needed.

KENNEDY TERMINAL ULCER Contributed by Charles Buscemi, PhD, ARNP, FNP-BC, CWCN First described more than 30 years ago, Kennedy terminal ulcers (KTUs) are associated with the dying process.Although the exact etiology is not known, they are thought to occur as a result of shunting of the blood away from the skin as it dies (skin failure).This process is similar to other types of organ failures that occur during the dying process. KTUs appear as a sudden discoloration of the skin usually on the sacral area in a butterfly or pear shape and are usually purple or black.

Properly diagnosing KTUs affords the clinician an opportunity to help family members with providing terminal care. A 91-year-old Hispanic woman was referred for wound care services with a stage III sacral pressure ulcer.Two weeks into care, she developed a KTU, following which she was referred to hospice.The patient died 6 days later.

A DIAGNOSTIC DILEMMA Contributed by Anne Clavon, PhD, MS,ARNP, CCRC A middle-aged black woman has been experiencing swelling of her arms and legs for the past 5 years. The swelling appears every 3 to 5 months. She has been evaluated by several physicians, including a rheumatologist, but no one can provide a definitive diagnosis. Lupus cell test is always negative, as are scleroderma and rheumatoid tests.When the swelling appears, she complains of stabbing pain in that extremity. Any suggestions as to potential referral or additional diagnostic testing? ■

LEGAL ADVISOR CASE

© PHIL BOORMAN / GETTY IMAGES

Is Clinician Testimony Hearsay?

An NP is called to testify in a sexual abuse case.

BY ANN W. LATNER, JD

As a healthcare practitioner, having to testify in court is not reserved for just medical malpractice cases.This month we look at a situation in which the testimony of a nurse practitioner contributed to the conviction of a child sexual predator.

Ms N was a nurse practitioner working in the safe child center of the outpatient pediatric wing of a regional hospital. She had recently been certified as a Sexual Assault Nurse Practitioner and had begun seeing young patients who had been victims of assault.Although stressful and difficult, Ms N felt the work was worthwhile if she could help young survivors of abuse.

One day an 11-year old girl, KC, was brought to the medical center by her mother and a police officer.The girl lived with her mother in a poor area of dilapidated bungalow houses and trailer homes. Earlier that day, the girl’s mother had left her alone while she went to the store.While the mother was gone, a neighbor saw the girl, looking frightened, emerge from an abandoned trailer followed by Mr M, an adult male who lived nearby.

Concerned, the neighbor called the girl’s mother and the police.After the girl told her mother that

A Sexual Assault Nurse Examiner undergoes specialized training in the care of patients who experience sexual trauma.

Mr M had touched her, the police officer suggested that they take KC to the safe child center at the hospital to be examined.

When they arrived to the hospital, the police officer who was with KC and her mother took Ms N aside and told her that the child was developmentally disabled and seemed more like a 7-year-old than an 11-year-old. Ms N thanked him for the information and then went into the examination room to speak with KC. In the exam room, Ms N introduced herself to the child and her mother and explained that she was a nurse who was going to make sure that KC was okay. She weighed and measured the child while asking her simple questions such as her name, where she went to school, and the name of her regular pediatrician.When the girl seemed comfortable with her, Ms N asked KC if something had happened earlier that day.“Yes,” said the child, 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 • SEPTEMBER 2018 59

LEGAL ADVISOR nodding.The girl then told Ms N that “the neighbor who lives in the red house” had taken her into an abandoned trailer.

“Do you know the name of that neighbor?” asked Ms N. “Yeah,” said the girl. She then identified the man by name.

“Okay,” said Ms N. “What happened in the trailer?”

KC told Ms N that Mr M had pulled down her pants and touched her with his hands and mouth “down there,” gesturing with her hands toward her vulvar region. After a few minutes she was able to squirm away and run out of the house.

Ms N wrote everything the girl said in her notes, as well as the results of the examination, which indicated that no actual penetration had taken place.

There are several exceptions to the hearsay rule that allow out-of-court statements to be used as evidence Afterward, Ms N spoke with the police officer, who told her that the child had identified a neighbor by name. After putting the name into the police database, it was discovered that the neighbor, Mr M, was a sex offender who had failed to register once he had moved into KC’s neighborhood. Based on the information that KC had told her mother and the police officer, and the information she had told Ms N, the police began preparing an arrest warrant for Mr M. Mr M was subsequently arrested. He was a convicted sexual offender who was out of jail and was supposed to have registered as a sex offender when he moved to a new community.

Because this was a repeat offense, the prosecutor was not offering an incentive for Mr M to take a plea deal; thus, he decided that he would take his chances at trial.

At the trial, Ms N was called as a witness for the prosecution. She testified about her certification as a sexual assault specialist and explained to the jury that the purpose of her examination of KC was to diagnose any physical, psychological, or emotional injuries the victim may have suffered and to prescribe an appropriate course of treatment. She then described her conversation with KC, including the fact that the child had identified the perpetrator by name. Although the defense attorney objected loudly to this, shouting “Objection!

Hearsay!”, the judge allowed Ms N to testify.

After the trial, the jury found Mr M guilty and sentenced him to 40 years in jail. Almost immediately, Mr M filed an appeal, saying that the lower court had abused its discretion by allowing Ms N to testify as to what KC had told her.The defense attorney argued that this was inadmissible hearsay.

The appellate court disagreed, allowed Ms N’s testimony to stand, and affirmed the defendant’s verdict and sentence.

Legal Background

Hearsay evidence is defined as “an out of court statement … offered to prove the truth of the matter asserted,”1 and it is generally not admissible in court. Ms N’s statement that KC told her during the examination that Mr M was the person who touched her is, in fact, hearsay. However, in the United States, there are several exceptions to the hearsay rule that allow out-ofcourt statements to be used as evidence in court. One of these is if the statement is made for “medical diagnosis or treatment.”

Hearsay evidence is usually inadmissible because it is considered untrustworthy. However, courts have held that “an individual seeking medical care is unlikely to lie about her medical history or symptoms because she knows that a false statement may cause misdiagnosis or mistreatment.”2 The appellate court held that KC’s statements to Ms N fall squarely within the scope of the exception to the hearsay rule. “KC spoke to the nurse practitioner as part of a sexual assault examination,” wrote the court in its decision.“As the nurse practitioner testified, one of the purposes of such an examination is to diagnose any physical, psychological, or emotional injuries the victim may have suffered and to prescribe an appropriate course of treatment.

To diagnose and treat KC’s injuries, the nurse practitioner first had to find out what happened to her, and so she asked KC, ‘did something happen?’ KC’s statements describing the abuse she suffered were made in response to that question.”

The court ruled that the statements satisfied the hearsay exception because “they were made for purposes of medical diagnosis or treatment, and were ‘reasonably pertinent’ to that subject.”

The court upheld the defendant’s sentence.

Protecting Yourself

Depending on your type of practice, you may find yourself in court someday — hopefully not as a defendant — but even testifying as a witness can be stressful. And memory is imperfect.

Therefore, the best way to protect yourself here is the same as the best way to protect yourself in many legal situations: take copious, detailed notes.While memory can dim, good notes can be dependently relied upon indefinitely. ■ Ms Latner, a former criminal defense attorney, is a freelance medical writer in Port Washington, NY. References 1. New York State Unified Court System. Guide to New York Evidence, Article 8. Hearsay.

2. US v Kootswatewa, 3:15-cr-08034-DLR-1 (Cal 2017).

www.ClinicalAdvisor.com • THE CLINICAL ADVISOR • SEPTEMBER 2018 60

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