November 2015 Clinical Advisor by The Clinical Advisor

THE CLINICAL ADVISOR • NOVEMBER 2015

A PEER-REVIEWED FORUM FOR NURSE PRACTITIONERS

NEWSLINE

■ Mammography screening ■ Colorectal adenomas ■ Menopause guidelines FEATURE The IUD Rumor Mill

Clearing up misconceptions LEGAL ADVISOR

NOVEMBER 2015

| www.ClinicalAdvisor.com

TREATMENT OVERVIEW FOR

PSORIASIS

Options include topical agents, phototherapy, and systemic and biologic agents.

Thyroid cancer misdiagnosed

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PAINFUL LESIONS WITH FEVER PAGE 67

■ Dermatologic Look-Alikes VOLUME 18, NUMBER 11

DARK ENLARGING LESION PAGE 71 SAVE THE DATE April 7–9, 2016

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Editor Colby Stong, editor@ClinicalAdvisor.com Senior editor Sandhya George Associate digital content editor Hannah Dellabella Assistant editor Lauren Biscaldi 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 director Ada Figueroa Circulation manager Paul Silver National accounts manager Alison McCauley, 646.638.6098 alison.mccauley @ haymarketmedical.com Publisher Thomas P. Hennessy, 646.638.6085 tom.hennessy @ haymarketmedia.com Editorial director Kathleen Walsh Tulley Senior vice president, digital products and medical magazines Jim Burke, RPh

Unsure about a diagnosis or treatment?

Ask our

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

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)

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 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.

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

Advisor Fo

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.

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These are letters from and succe sses, obser practitioners aroun d the count vations, and below. We ry who want OUR CONSULTANTS pearl invite you to participate. s with their collea to gues. Respo share their clinical problems nding consu ltants are identified CONSULT ATIONS

TREATMEN INFECTIO T FOR URIN ARY SGLT2 RECE MALE CHILNS IN THE UNC TRACT IRCUMCIS D FOR DIAB PTOR BLOC If a male ED KERS child contin ETES Deborah L. Cross, MPH, CRNP, Laura A. Foster, CRNP, FNP, Abby A. Jacobson, PA-C, Abimbola Farinde, PhD, PharmD, With the ues istoassociate ANP-BC, program practices family medicine is a physician assistant is a professor redeve advent a circum lop urinar at Columbia ofPrimary SGLT2 recept at Delaware Valley director,cision Gerontology NP Program, Southern modal itywith Palmetto y tract infecfor type be perfor or Physicians Dermatology University of Pennsylvania School blockersGroup University 2 diabetes, med? regard ing inCare as a treatm in Wilmington, Del. is there in Orange Beach, Ala. useCharleston, S.C. ent urology is of Nursing, Philadelphia. any eviden NATHAN in patients with to protect the is well advised ce or data type 1 diabet GARDNER, es mellitu continues to to recommend a circumcupper tracts, the kidney PA-C, CPAA s?— develop ision www.ClinicalAdvisor.com PA, Castlet 44 THE CLINICAL ADVISOR • AUGUST 2015 recurren the male child s. It As it currentl several t urinary tract•on on, N.Y. conside y stands, who for infections. impede the rations that enter into glycemic control SGLT2 receptor There are ability to cleanse this decision blockers in adults with are with diet . Poor hygiene should the and quell type 2 diabete FDA-approved child have may approve and exercise, but phimosis, simpleinfection potential. s in conjunc appropriate the FDA d for use in Moreover, has stated urine AdvisorForum_CA0815.indd 44 9/29/15 tion 2:38 PM catheter patients culture ketoaci ization that with type steroid cream can be a challen they are not dosis, or those to obtain an may tempor ge. Having with severe 1 diabetes, patients with FARIN tion of the arily solve a short trial diabetic steroid the these of informa DE, PhD, PharmD renal function.—AB tendency redevelo issues, though after for infection IMBO (See bottom tion about LA once again.— cessaps, placing Dr. Farind of this page Milwaukee, COLEEN the child at e.) (203-2 for more Wis. (203-1 ) risk ROSEN, DNP, FNP-C ) , CLIN

Write us today.

Philip R. Cohen, MD,

is clinicaltions, associate professor should of dermatology, University of Texas Medical Center, The focus of Houston.

SEND TO The Clinical Advisor 114 West 26th Street, 4th floor New York, NY 10001

ICAL PEAR

Send us your letters Advisor with questio Forum, The New York, Clinical Advisor, ns and comme NY 10001. nts clinicaladvisor.c You may 114 West 26th Street,to: contact please indicate om. If you are 4th Floor, us so by includin writing in responsby e-mail at editor@ each item. e to a g the Letters are policy is edited for number in parenth published letter, to contributionsprint the author’s length and clarity. eses at the end of The will be accepte name with the letter. Clinical Advisor’s d. No anonym ous

OUR CON

VAGINAL RESULTIN DISCHARGE AND G FROM If a female TAMPON ODOR patient has USE a ask if she uses tampo history of vaginal dischar ns. If she the pelvic ge with says “yes,” exam, when condu odor, that you would do not enter the vagina cting to take in the same rotating of the specul a pap smear. Instead way the cervix um . Most retaine from side to side , start shallow until d tampons are lodged reaching in the fold

SULTAN TS

Philip R.

Cohen, MD, is clinical associate professor of dermatol ogy, of Texas MedicalUniversity Center, Houston.

62 THE CLINIC

Deborah L. Cross, MPH, ANP-BC,

is associate CRNP, director, Gerontolo program gy NP University of Pennsylva Program, nia School of Nursing, Philadelphia.

AL ADVISO

R • SEPTEM

BER 2015

AdvisorFo

E-MAIL: editor@clinicaladvisor.com

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)

Abimbola

Farinde,

PhD, PharmD,

is a professor at Columbia Southern University in Orange Beach, Ala.

• www.C

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com

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Laura A.

Foster,

practices familyCRNP, FNP, with Palmetto medicine Primary Care Physician in Charlesto s n, S.C.

Abby A.

Jacobson

is a physician , PA-C, at Delawareassistant Dermatology Valley in Wilmingt Group on, Del.

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Senior vice president, clinical communications John Pal CEO, Haymarket Media, Inc. Lee Maniscalco All correspondence to: The Clinical Advisor 114 West 26th Street, 4th Floor, New York, NY 10001 For advertising sales, call 646.638.6085. For reprints, contact Wright’s Reprints at 877.652.5295. Persons appearing in photographs in “Newsline,” “The Legal Advisor,” and “Clinical Challenge” are not the actual individuals mentioned in the articles.They appear for illustrative purposes only. The Clinical Advisor® (USPS 017-546, ISSN 1524-7317), Volume 18, Number 11, is published 12 times a year, monthly, for $75.00 per year in the United States; $85.00 in Canada; $110.00 for all other foreign, in U.S. dollars, by Haymarket Media, Inc., 114 West 26th Street, 4th Floor, New York, NY 10001. Single copy: $20 U.S.; $30 foreign. www.ClinicalAdvisor.com. To order or update your paid subscription, call 800.436.9269. Periodicals postage rate paid at New York, NY, and additional mailing offices. POSTMASTER: Send address change to DMD Data Inc. ,10255 W. Higgins Rd, Suite 280, Rosemont, IL 60018. Subscription inquiries: call 800.430.5450 to change your address or make other subscription inquiries. Requests for subscriptions from outside the United States must be accompanied by payment. All rights reserved. Reproduction in whole or in part without permission is prohibited. Copyright © 2015

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Writers’ Guidelines The Clinical Advisor welcomes submissions from its readers. Writing for us is an opportunity to share your knowledge and experience with your colleagues — and to collect a fee in the bargain! We pay an honorarium for every submission we accept. We’ll be glad to work with you to develop your ideas into compelling articles. As for length, that depends on which kind of article you submit. CLINICAL FEATURES update our readers on the latest information about conditions seen in everyday practice. Running approximately 2,500 to 5,000 words, including the references, features can be written either as regular narratives or as a series of questions and answers. Topics should be selected with the busy primary-care clinician in mind; specialists should review specialty topics from the primary-care point of view. If at all possible, articles should be accompanied by clinical photos. Charts, tables, and algorithms are also encouraged. Please include your title and affiliation. CLINICAL CHALLENGE is our popular department comprising histories of difficult cases. Each case is presented as a step-by-step, chronological account, revealing the author’s thought processes along the way. It is divided into sections in this order: the patient presentation; the patient history; the twists and turns eventually leading to a diagnosis; the treatment and outcome; and a discussion of the lessons learned or of the condition in general. The length should be about 1,500 words, and accompanying images are encouraged. Please include your title and affiliation. DERMATOLOGY CLINIC is a department that presents photos of actual cases and asks readers to identify the condition. Each case opens with one or two color photos and a 75-to-100-word description of the patient presentation, without giving away the diagnosis. This is followed by a 750-to-1,000-word summary that includes a fuller description of the ailment, an explanation of how the correct diagnosis was reached, a general review of the condition along with a differential diagnosis, and a description of the patient’s treatment and outcome. Topics must be approved by the editor prior to submission. Please include your title and affiliation. COMMENTARY is our guest editorial page. It gives you the opportunity to sound off on an issue of importance to your colleagues nationwide. A typical Commentary runs about 600 words in length. Please include your title and affiliation. To discuss your editorial ideas, contact us by phone at 646.638.6078; by e-mail to editor@ClinicalAdvisor.com; or by mail to The Clinical Advisor, 114 West 26th Street, 4th Floor, New York, NY 10001. www.ClinicalAdvisor.com • THE CLINICAL ADVISOR • NOVEMBER 2015 9

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CONTENTS NOVEMBER 2015

NEWS AND COMMENT

FEATURES

24 Newsline ■■Women with an average risk of breast cancer may begin annual mammography screening at age 45 and get screened less often, according to updated guidelines. ■■Lower doses of beta-blockers are as effective or more effective than higher doses for the survival of patients following acute myocardial infarction. ■■Vitamin D and calcium supplements do not reduce the risk of colorectal adenomas in patients who have had a precancerous colorectal adenoma removed. ■■Providers treating symptoms of menopause in women should assess the individual benefits and risks of therapeutic options, according to new guidelines. ■■Drug-resistant E. coli infections are being increasingly transmitted at community hospitals. ■■Children who have had infections, such as upper respiratory infections, or who have not received their scheduled vaccinations are at higher risk for stroke. ■■The enterovirus D68 (EV-D68) respiratory infection does not increase the risk of death or need for critical care in children. ■■And more.

32 The IUD rumor mill: common misconceptions Disseminating accurate information can help women make informed decisions and potentially increase the overall use of intrauterine devices.

106 Commentary Basal insulin for surgical diabetic patients

MAKING CONTACT

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Revised mammography guidelines 24

44 CME/CE Psoriasis: an overview of current and emerging medications Many therapeutic options are available for psoriasis, ranging from topical agents to phototherapy and systemic and biologic agents. 54 CME/CE Feature posttest

DEPARTMENTS

Drug-resistant E. coli infections 26

20 Web Roundup A summary of our most recent opinion, news, and multimedia content from ClinicalAdvisor.com 63 Legal Advisor A clinician misdiagnoses thyroid cancer as acid reflux. Continues on page 18

Misconceptions about IUD use 32

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Visit us on the web ClinicalAdvisor.com

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CONTENTS DEPARTMENTS, cont’d 66

102 Alternative Meds Update ■■Taurine. A sulphur-containing amino acid, taurine has a number of biochemical roles in human metabolism.

CME/CE Dermatology Clinic ■ Hypertrichosis over a brown patch ■ Painful lesions with fever and malaise

71 CME/CE Dermatologic Look-Alikes Raised, dark, enlarging lesion

ADVISOR FORUM

CME/CE Dermatology posttest

Clinical Challenge ■■Painful red spot and fever in an infant. A child and her twin had tested positive for influenza B infection one week earlier.

Your Comments ■■Stopping prescription drug abuse. A reader responds to a previously published Commentary, “Narcotic abuse in the emergency department.” ■■Vaccination, parents, and children

OTC Corner ■■Omega-3 fatty acids: from fins and fish oil to flax. Omega-3 fatty acids are a healthy subgroup of polyunsaturated fatty acids (PUFAs). Most of the PUFAs that are consumed in the Western world are proinflammatory omega-6 oils, which may be a contributing factor to many chronic diseases.

Clinical Pearls ■■How to distinguish bradykinesia from psychomotor retardation ■■Metformin XR for diabetes care

Consultations ■■Many patients with coronary-related issues have normal lipid levels, so is the real benefit of statins their antiinflammatory benefits?

Painful red spot and fever in an infant 78

Fish are a source of omega-3 fatty acids 94

HOW TO CONTACT US THE CLINIC AL ADVIS OR • NOVE

TO SUBMIT A CLINICAL QUESTION FOR PUBLICATION:

MBER 2015

TO SUBSCRIBE: • www.ClinicalAdvisor.com/subscribe

A PEER -REV

■ Mammog raphy screenin ■ Colorect g al adenoma s ■ Menopa use guideline s

FEATUR E

The IUD

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

Rumor Mill

Clearing up

misconceptio

LEGAL ADV

ISOR

Thyroid canc er

misdiagnosed

✶ FREE CME COURS

ASSIS TANT

NOV EMBE

R 2015

| www.Clin icalA

dvisor.com

TREATM

ENT OVER VI

PSORIASIS

EW FOR Options inclu topical agen de ts, photothe rapy, and syste mic and biologic agen ts.

ES!

• Send it by e-mail to editor@ClinicalAdvisor.com

ER 11

• Mail it to The Clinical Advisor, 114 W. 26th St., 4th Floor, New York, NY 10001

■ Dermatolo gy Clinic

PAINFUL WITH FEVLESIONS ER PAGE

18, NUMB

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• www.ClinicalAdvisor.com/AdvisorForum

VOLUM E

TO SUBMIT AN ARTICLE: • editor@ClinicalAdvisor.com

IEWE D FORU M FOR PHYS ICIAN

NEWSLIN

■ Dermatolo gic

DARK ENL Look-Alikes LESION PAGEARGING 71 SAVE THE DATE

April 7–9,

2016

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EXCLUSIVE TO THE WEB AT

ClinicalAdvisor.com The Waiting Room

Web Exclusives

Official Blog of The Clinical Advisor

ClinicalAdvisor.com/News

ClinicalAdvisor.com/WaitingRoom Robyn Carlisle, MSN, CNM Early pregnancy loss deserves empathy and sensitivity After a couple experiences a miscarriage, their grief needs to be treated with sensitivity rather than dismissal. Jim Anderson, MPAS, PA-C, DFAAPA, ATC No excuses: clinicians should never disrespect patients Medical practitioners should always treat patients with respect, no matter how stressed or annoyed they are. Jillian Knowles, MMS, PA-C After an accident, when do you need a new car seat? Car seats must be replaced after moderate and severe car crashes, but often they do not need to be replaced after minor crashes.

Quality of cardiovascular care from NPs, PAs similar to that from physicians Nurse practitioners and physician assistants deliver similar-quality outpatient cardiovascular care compared with physicians. High number of U.S. children remain unvaccinated against measles Due to a dip in the number of vaccinated individuals, almost a quarter of children younger than age 3 years are currently susceptible to measles. Influenza vaccine can prevent pneumonia hospitalizations The influenza vaccine may be able to prevent approximately 57% of hospitalizations due to influenza pneumonia.

Multimedia ClinicalAdvisor.com/Multimedia Screening for colorectal cancer should begin at 50 Colorectal cancer is the third most common preventable cancer, but it rarely causes pain until the later stages of the disease. Teresa McKamey, RN, MSN, discusses the importance of regularly screening patients for colon cancer starting at 50 years of age. Watch it here: ClinicalAdvisor.com/ColonCancerVid

Communication between clinicians and patients can improve diagnoses A new report from the National Academies of Science, Engineering, and Medicine says that a majority of patients will receive a misdiagnosis in their lifetime. To overcome

MAKING CONTACT

this, health care teams need to communicate and work together with patients and families. Watch it here: ClinicalAdvisor.com/DiagnosisVid

AAP urges health care workers to get flu vaccine Wendy Sue Swanson, MD, MBE, discusses the new influenza vaccine recommendations from the American Academy of Pediatrics. They stress that all health care workers who work with children should be required to get the vaccine. Watch it here: ClinicalAdvisor.com/FluVaccineVid

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Go mobile with us mobile.ClinicalAdvisor.com

20 THE CLINICAL ADVISOR • NOVEMBER 2015 • www.ClinicalAdvisor.com

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Advisor Dx

EXCLUSIVE TO THE WEB

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

Ortho Dx

In partnership with

TheJopa.org

Journal of Orthopedics for Physician Assistants

Pain and swelling in the right knee A male, aged 20 years, presents with a 10-month history of progressive pain in the right knee and soft-tissue swelling. Images were obtained from anteroposterior x-ray and coronal magnetic resonance imaging. WHAT IS THE BEST TREATMENT PLAN?

• Curettage and bone grafting • Radiation and chemotherapy • Amputation above the knee with postoperative radiation • Chemotherapy, wide resection, and joint reconstruction with custom implant ● See the full case at ClinicalAdvisor.com/OrthoDx_Nov15

Derm Dx Hyperkeratotic central plaque on the arm A 58-year-old male presents for evaluation and treatment of a lesion on his arm that was first noted about 4 months ago and has continued to enlarge. Physical examination reveals a slightly elevated hyperkeratotic central plaque of 0.6 cm overlying a 1.5-cm dermal nodule. CAN YOU DIAGNOSE THE CONDITION?

• Epidermoid cyst • Pilomatricoma • Lipoma • Metastatic carcinoma ● See the full case at ClinicalAdvisor.com/DermDx_Nov15

www.ClinicalAdvisor.com • THE CLINICAL ADVISOR • NOVEMBER 2015 21

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ADS-01325-001 Rev. 001 ÂŠ 2015 Hologic, Inc. All rights reserved. Hologic, Science of Sure, Pap+HPV Together, ThinPrep and associated logos are trademarks and/or registered trademarks of Hologic, Inc. and/or its subsidiaries in the United States and/or other countries. All other trademarks, registered trademarks, and product names are the property of their respective owners. This information is intended for medical professionals in the U.S. and is not intended as a product solicitation or promotion where such activities are prohibited. Because Hologic materials are distributed through websites, eBroadcasts and tradeshows, it is not always possible to control where such materials appear. For specific information on what products are available for sale in a particular country, please contact your local Hologic representative or write to diagnostic.solutions@hologic.com.

Screening with HPV-Alone invites more risk into women’s lives than you may think. One out of 5 cases of cervical cancer were missed with HPV-Alone screening in a recent landmark, retrospective study–the largest ever conducted to evaluate the effectiveness of cervical cancer screening strategies in women ages 30-65.1* Additionally, screening with Pap+HPV Together™ (co-testing) identified more than 70% of those missed cancers.1 And it only requires one sample. So is HPV-Alone screening really worth the risk? Screen your patients with Pap+HPV Together. Because every woman deserves the best possible protection from cervical cancer. See more data at PapPlusHPV.com.

* A positive HPV screening result may lead to further evaluation with cytology and/or colposcopy. Reference: 1. Blatt AJ, Kennedy R, Luff RD, Austin RM, Rabin DS. Comparison of cervical cancer screening results among 256,648 women in multiple clinical practices. Cancer Cytopathol. 2015 April (Study included ThinPrep®, SurePath, Hybrid Capture 2 assay).

Newsline N O V E M B E R 2 015

New treatment guidelines for menopause page 26

High stress jobs are linked to stroke risk page 28

Higher stroke risk for children with infections page 30

WOMEN WITH an average risk of breast cancer may begin annual mammography screening at age 45 and get screened less often, according to new guidelines issued by the American Cancer Society (ACS) and published online ahead of print October 20 in JAMA. In an update to its 2003 breast cancer screening guidelines, the ACS commissioned an interdisciplinary guideline development group made up of clinicians, biostatisticians, epidemiologists, economists, and patient representatives to perform a systematic evidence review of current breast cancer screening literature and a metaanalysis of observational studies and randomized controlled trials.

“The 2015 updated recommendations from the ACS are intended to balance the goal of reducing the burden of breast cancer against the understanding that breast cancer screening is a preventative health intervention applied to the entire eligible population of women, most of whom will not develop breast cancer in their lifetime,” wrote lead investigator Kevin C. Oeffinger, MD, Director of the Adult Long-Term Follow-Up Program at Memorial Sloan Kettering Cancer Center in New York City, and colleagues. The new recommendations are as follows: 1) Women with an average risk of breast cancer should undergo regular mammography screening

Updated guidelines for mammogram screening

Women with an average risk of breast cancer should undergo regular mammography screening beginning at age 45.

beginning at age 45 and continuing yearly until age 54. Women aged 40 to 44 should have the opportunity to begin annual screening, and women age 55 and older should transition to biannual screening; 2) women should continue to undergo mammography screening based on these recommendations so long as their overall health is good and they have a life expectancy of 10 years or longer; and 3) the ACS no longer recommends clinical breast examinations among average-risk women at any age.

Low doses of beta-blockers effective for survival after heart attack LOWER DOSES are as effective or more effective than higher doses of beta-blockers for the survival of patients following acute myocardial infarction, according to a study published online September 21 in the Journal of the American College of Cardiology. Jeffrey J. Goldberger, MD, MBA, and fellow investigators found that patients who received a quarter of a high dose of betablockers that has been used in previous clinical trials demonstrated decreases in mortality that were as high as 20% to 25%, when compared with patients who received the full dose. The researchers analyzed data in a multicenter registry on 6,682 patients who had had an acute myocardial infarction; median follow-up for these patients was 2.1 years and 90% were receiving beta-blockers. Patients in the study who took betablockers, regardless of dose, survived longer, compared with

patients who did not receive beta-blockers. The researchers found that within 2 years, death occurred in 14.7% of patients who received the full dose of beta-blockers, 12.9% of those receiving half of that dose, 9.5% of those receiving a quarter of the dose, and 11.5% of those receiving an eighth of the dose. In addition, beta-blockers have side effects, including fatigue, sexual dysfunction, and depression, which would make prescribing lower doses to patients following a heart attack a more attractive option. More research is necessary to determine what doses are most effective for different populations, Dr. Goldberger said. “There is probably not one right dose for every single patient,” he said. “It doesn’t make sense that the same dose will work for an 80-year-old frail man who had a small heart attack as a burly 40-year-old man with a huge heart attack.”

24 THE CLINICAL ADVISOR • NOVEMBER 2015 • www.ClinicalAdvisor.com

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Newsline THE RATE of infections caused by extended-spectrum beta-lactamase-producing (ESBL)-Escherichia coli (E. coli) that is highly resistant to antibiotics has more than doubled in community hospitals, according to a study published online October 13 in Infection Control & Hospital Epidemiology. Joshua Thaden, MD, PhD, and colleagues studied 26 community hospitals in the southeastern United States, finding that the incidence of ESBL-E. coli infections increased from 5.28 to 10.5 per 100,000 patients from 2009 to 2014. During that period, the number of community hospitals that reported ESBL-E. coli infections increased from 17 (65%) to 20 (77%). The researchers found that approximately three-quarters of the infections

ESBL-E. coli infections more than double in community hospitals.

were picked up after exposure at a hospital or encounters with the health care system, as opposed to community-associated infections. However, the group did note an increase in community-associated infections of ESBL-E. coli. In comparison, the researchers found that the incidence of infections caused by ESBL-producing Klebsiella pneumonia remained constant. Dr. Thaden noted that a lack of active screening for ESBLproducing bacteria in most hospitals results in inadequate infection prevention measures, such as contact isolation and patient cohorting, adding that “silently” colonized patients increase the risk of transmission to vulnerable patients via health care workers or environmental contamination.

New treatment guidelines for menopause PROVIDERS treating symptoms of menopause in women should assess the individual benefits and risks of therapeutic options, according to guidelines issued by the Endocrine Society and published online October 7 in the Journal of Clinical Endocrinology and Metabolism. Authored by a task force chaired by Cynthia A. Stuenkel, MD, their recommendations for providers include the following: • Women with a uterus who decide to undergo menopausal hormone therapy with estrogen and progestogen should be informed of the risks and benefits of that therapy, including the increased risk for breast cancer once treatment is discontinued. • All women, including those receiving hormone therapy for menopause, should

be advised to follow guidelines for breast cancer screening. • Transdermal estrogen therapy by patch, gel, or spray is the recommended treatment; however, it does have an increased risk of venous thromboembolism. • In women taking estrogen to relieve hot flashes, progestogen prevents uterine cancer; however, it is not necessary for women who have undergone a hysterectomy. • Selective serotonin reuptake inhibitors, serotonin-norepinephrine reuptake inhibitors, gabapentin, or pregabalin are recommended for the management of moderate-to-severe hot flashes in women who prefer not to take or are contraindicated for hormone therapy.

Vitamin D for colorectal adenomas? VITAMIN D and calcium supplements do not reduce the risk for the development of colorectal adenomas in patients who have had a precancerous colorectal adenoma removed, according to a study published October 15 online ahead of print in the New England Journal of Medicine. Lead author John A. Baron, MD, and fellow investigators studied 2,259 patients aged 45 years to 75 years and who had had polyps removed from their colon. The patients, who had no remaining polyps at enrollment, were randomly assigned to receive 1,000 IU of vitamin D3 daily, 1,200 mg of calcium daily, both of these, or none of these. Almost half of the patients (43%) had one or more adenomas at follow-up screening colonoscopy in the 3 to 5 years following the initial screening. There was no significant difference in the frequency of new polyps in patients who took vitamin D supplements, calcium supplements, or both, when compared with those who took neither. Previous research has suggested that vitamin D and calcium supplementation have beneficial effects against colorectal cancer, according to one of the study’s authors Dennis J. Ahnen, MD. “It could be that vitamin D and/or calcium work later in the process of carcinogenesis to prevent dangerous cancers, but not their precancerous predecessors,” he said.

Drug-resistant E. coli infection rates increase at community hospitals

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Newsline Enterovirus D68 does not increase mortality in children

The investigators compared the severity of illness between children with EV-D68 and those with other rhinovirus and enterovirus infections who were admitted to the McMaster Children’s Hospital in Hamilton, Ontario. The study included 297 children, 93 of

High stress jobs are linked to increased stroke risk HIGH STRESS JOBS are associated with a higher risk of stroke, according to a meta-analysis published October 14 online ahead of print in Neurology. Researchers reviewed six studies with a total of nearly 140,000 participants who were followed for 3 to 17 years. Jobs were classified into 4 groups based on worker control over daily tasks and how hard they worked, as well as on the psychological demands of the job: passive jobs, low stress jobs, high stress jobs, and active jobs. Across all six studies, total participants with high stress jobs ranged from 11% to 27%. Participants with high stress jobs had a 22% higher risk of stroke, compared with those with low stress jobs; women with high stress jobs had a 33% higher stroke risk. All participants with high stress jobs were 58% more likely to have an ischemic stroke. Participants with either passive or active jobs had no increased risk of stroke. In an editorial, Jennifer J. Majersik, MD, MS, recommended interventions aimed at increasing job control and flexibility in job structure, such as telecommuting.

EV-D68 respiratory infection does not increase risk of death in children.

whom tested positive for EV-D68. Children with EV-D68 were more likely to have respiratory distress, be admitted to the hospital, and receive magnesium sulfate or IV salbutamol, compared with those with other rhinovirus or enterovirus infections. However, rates of admission to the pediatric critical care unit and death among children with EV-D68 were similar to those of children without EV-D68. Children with EV-D68 were more likely to have a family history of allergies or asthma. This suggests that patients with pre-existing atopic conditions may be more susceptible to EV-D68 than rhinoviruses and other enteroviruses.

Smoking is associated with high risk of type 2 diabetes A HIGH RISK for type 2 diabetes exists among both current smokers and those regularly exposed to second-hand smoke, according to a study published September 18 online ahead of print in The Lancet Diabetes & Endocrinology. Researchers conducted a metaanalysis of 88 previous studies that investigated the association between smoking and type 2 diabetes risk. The study authors examined the health data of nearly 6 million participants and found that current smoking increased type 2 diabetes risk by 37%. Former smoking increased the risk by 14%, and passive smoking increased the risk by 22%. Those who quit smoking had an 11% increased risk more

than 10 years after quitting. The investigators also noted that the degree of smoking affected the results. Increased type 2 diabetes risk was 21%, 34%, and 57% for light, moderate, and heavy smokers, respectively. It is estimated that nearly 27.8 million cases of diabetes worldwide can be attributed directly to active smoking. “Cigarette smoke should be considered as a key modifiable risk for diabetes,” said study co-author Frank Hu, MD, professor of nutrition and epidemiology at the Harvard School of Public Health. “Public health efforts to reduce smoking will have a substantial impact on the global burden of type 2 diabetes.”

THE ENTEROVIRUS D68 (EVD68) respiratory infection does not increase the risk of death or need for critical care in children, according to a study published October 13 online ahead of print in the Canadian Medical Association Journal. In 2014, EV-D68 affected a significant number of children in the United States and Canada. An increase in the number of hospitalizations and admissions to intensive care units led some to believe that the EV-D68 strain was more virulent than other strains of the enterovirus. Researchers tested this hypothesis in a study of children admitted to the hospital with rhinovirus or enterovirus infections.

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Best Practices in Effective Healthcare Collaboration The Clinical Advisor Summit is a 3-day conference offering focused sessions in high-demand practice and clinical areas to enhance the professional development of clinicians.

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Newsline Mammography More Medicaid plans are now without CAD covering post-delivery IUDs EXPANDING Medicaid coverage will offer more women the choice to get an intrauterine device (IUD) or contraceptive implant immediately after giving birth, according to a study published September 28 online ahead of print in Contraception. Between 40% and 60% of lowincome women who want to get an IUD or implant never attend a follow-up appointment after having their child due to constraints such as transportation and childcare. By offering reimbursement for an IUD or implant at the same time as delivery, Medicaid will give these women the opportunity to get the birth control they want. This can help reduce unintended pregnancies too close to the birth of the first child, which can carry risks for both the mother and fetus.

More low-income women may now be able to get an IUD.

Researchers interviewed 40 Medicaid agencies via telephone. Agencies that did provide postdelivery contraception reimbursement often cited health benefits and cost-savings as key reasons for their decision. Among agencies that did not provide this service, concerns about potential health risks and financial uncertainty were often referenced. In 3 years, the number of states that offer Medicaid reimbursement for an IUD or contraceptive implant has increased from zero to 19. Medicaid agencies in an additional 8 states are considering offering this reimbursement. The study authors hope that Medicaid agencies in more states, as well as private insurance companies, will begin to cover postpartum contraception.

Higher stroke risk in children with infections CHILDREN WHO HAVE had infections, such as upper respiratory infections, or who have not received their scheduled vaccinations have a higher risk for stroke, according to research published September 30 online ahead of print in Neurology. Heather J. Fullerton, MD, and colleagues analyzed data on 355 children aged 29 days to 18 years who had had an arterial ischemic stroke and 354 children who had not had a stroke. The children were enrolled in an international case-control study (The Vascular Effects of Infection in Pediatric Stroke). Of the children who had had a stroke, 18% had infections during the week before their strokes, compared with 3% of

children in the control group. The researchers determined a 6.3-fold increased risk of arterial ischemic stroke in children who had had an infection. The group also found that the children who had strokes were less likely to have received all or most of their recommended vaccinations. In an accompanying editorial, José Biller, MD, and Geoffrey L. Heyer, MD, wrote, “While further study is needed to clarify how infection increases stroke risk, one can speculate that the physiologic changes related to infection (systemic inflammation, dehydration, and activation of the coagulation system) could tip the balance in a child who is already at risk for stroke.” n

DIGITAL SCREENING mammography is as accurate without computer-aided detection (CAD) as it is with the technology, according to a study published September 28 online ahead of print in JAMA Internal Medicine. Constance D. Lehman, MD, PhD, and colleagues studied more than 625,000 mammograms with (n=495,818) or without (n=129,807) CAD that were performed on 323,973 women. Within one year of screening, 3,159 cases of breast cancer were identified. CAD was not associated with improvement in screening performance. Mammography with CAD had a sensitivity of 85.3%, whereas it was 87.3% without CAD; specificity was 91.6% with CAD and 91.4% without CAD. The researchers observed no difference in the overall rate of detection of breast cancer (4.1 per 1,000 women screened with and without CAD) or in the rate for the detection of invasive breast cancers (2.9 vs. 3.0 per 1,000 women screened with or without CAD, respectively). Mammography with CAD became widely used following a decision from the Centers for Medicare and Medicaid Services (CMS) to provide increased reimbursements for the technology in 2002. However, data on the value of CAD are limited, the authors said. “Computer-aided detection does not improve the diagnostic accuracy of mammography,” they concluded in their study.

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FEATURE: LIBBY LEVINE, MS, AGNP-BC

The IUD rumor mill: Common misconceptions Disseminating accurate information can help women make informed decisions and potentially increase the overall use of intrauterine devices.

Long-acting reversible contraception has an efficacy rate greater than 99%.

ong-acting reversible contraception (LARC), which includes both subcutaneous implants and intrauterine devices (IUDs), is the most effective form of contraception. Nurse practitioners and physician assistants who are knowledgeable about IUDs and can anticipate the concerns of patients and other providers are well-positioned to increase IUD use. This may help decrease the number of unplanned pregnancies in the United States. Around the world, rates of IUD usage are high; for instance, rates in Uzbekistan are 50%, in Vietnam 31%, in China 41%, in Egypt 36%, and in Finland 23%.1 However, in the United States, only 5.2% of women of reproductive age use IUDs.1 This is despite the fact that methods of LARC are the most effective form of birth control aside from abstinence and have an efficacy rate of more than 99%.2 Like vasectomy and female sterilization, methods of LARC are rated Tier 1, the most effective form of contraception, by the World Health Organization and the U.S. Centers for Disease Control and Prevention.3 This article explores potential reasons for the low rates of IUD usage in the United States, despite high rates of usage elsewhere in the world and the high rates of efficacy associated with this method of contraception. Because 98% of women on LARC are using IUDs (as opposed to subcutaneous contraceptive implants),4 this article focuses mainly on IUD usage and perceptions. It will address common patient and provider misconceptions regarding the use of IUDs. Different types of IUDs will be described,

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including what is currently available in the United States and patient satisfaction, contraindications, side effects, and complications with each type, with the intent of clarifying how many of these common concerns are misguided. Types of IUDs

Of the 3 IUDs currently available in the United States, two are hormonal. These two contain differing amounts of the hormone levonorgestrel (LNG). LNG decreases sperm motility by thickening cervical mucus and also makes changes to the endometrium to prevent implantation. The first hormonal IUD, the LNG-releasing intrauterine system (Mirena; Bayer HealthCare Pharmaceuticals, Wayne, NJ), contains 52 mg of LNG and releases 15 mcg/d to 20 mcg/d. It can stay in place for up to 5 years. The second hormonal IUD, the LNG intrauterine system 13.5 (Skyla; Bayer HealthCare Pharmaceuticals), contains 13.5 mg of LNG, is slightly smaller, and releases approximately 6 mcg/d.5 It can be left in for no more than 3 years. Nonhormonal and made of copper, the third IUD (Paragard; Teva Women’s Health, North Wales, PA) can stay in place for up to 10 years. The copper ions in this IUD prevent sperm motility and the activation of enzymes needed for sperm survival. These spermicidal mechanisms prevent fertilization (Table 1).6 Patient satisfaction

Once a woman decides to use an IUD, studies have shown that she has a very high likelihood of being pleased with her choice. In addition to being a Tier 1 form of birth control, the IUD has been shown to have the highest rates of satisfaction and continued use. The Contraceptive CHOICE Project, which surveyed more than 9,000 women who use contraception, found that approximately 86% of women

who chose a LNG IUD and 81% of women who chose the copper IUD were satisfied with their chosen method.7 This was compared with only half of those who chose non-LARC methods.8 The continuation rates for the LNG and copper IUD at 12 months (88% and 85%, respectively) and 24 months (79% and 77%, respectively) are also much higher, compared with those of non-LARC methods at 12 and 24 months (57% and 41%, respectively; Table 2).7-9 Continuation rates for nulliparous women are approximately the same as continuation rates for multiparous women, according to the Contraceptive CHOICE Project.7 LNG IUD users also have very similar continuation rates at 12 months, regardless of age, with the notable exception that copper IUD users who are aged less than 20 years have a slightly higher discontinuation rate (28%), compared with women older than age 20 years (15%).10 Common reasons for discontinuation within the first 6 months, according to a 2012 study of 5,928 participants by Grunloh et al,11 were pain, cramping, and irregular, frequent, or heavy bleeding. Recommendations

The American College of Obstetricians and Gynecologists (ACOG) and the U.S. Medical Eligibility Criteria (MEC) for Contraceptive Use state that all 3 IUDs are safe for use in nulliparous women and adolescents. IUDs are also safe in women with a history of pelvic inflammatory disease (PID) or ectopic pregnancy, who are immediately postpartum, or immediately following abortion/miscarriage (except in the presence of puerperal sepsis).9 The ACOG also states that IUDs are safe in women with a history of IUD expulsion. The ACOG, along with 3 recent studies, has recommended LARC as first-line contraception for all women7,9,11; the ACOG endorses LARC methods as the “best form of reversible contraception.”9

TABLE 1.Types of intrauterine devices. Hormonal

Nonhormonal

NAME

Levonorgestrel-releasing intrauterine system

Levonorgestrel intrauterine system 13.5

Intrauterine copper contraceptive

BRAND NAME (manufacturer)

Mirena (Bayer HealthCare Pharmaceuticals, Wayne, NJ)

Skyla (Bayer HealthCare Pharmaceuticals)

Paragard (Teva Women’s Health, North Wales, PA)

MECHANISM OF ACTION

• Decreases sperm motility by thickening cervical mucus • Makes changes to the endometrium to prevent implantation

• Spermicidal copper ions prevent sperm motility and the activation of enzymes needed for sperm survival • Prevents fertilization

DURATION

Up to 5 years

Up to 10 years

Up to 3 years

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IUD MISCONCEPTIONS

In spite of high efficacy rates, many clinicians are hesitant to provide IUDs due to misconceptions regarding patient populations and side effects. Several factors potentially contribute to the reluctance of patients and providers to follow expert recommendations and embrace the use of IUDs. The next section will discuss research from studies that examined patient and provider perspectives on IUDs. Provider and patient perspectives

In spite of high efficacy rates, many clinicians are hesitant to provide IUDs due to misconceptions regarding patient populations and side effects. A 2013 global study by Black et al12 found that 1,862 obstetrician–gynecologists (OBGYNs), nurse practitioners (NPs), and physician assistants (PAs) reported not offering IUDs to nulliparous patients for the following reasons: (1) difficulty in insertion; (2) concern about PID; (3) insertion pain; and (4) infertility. In a study by Harper and associates13 of 812 physicians, NPs, and PAs, more than half of respondents would not consider nulliparous women (54%), women who are postabortion (61%), or women who have had a sexually transmitted infection (STI) in the past 2 years (61%) to be candidates for IUDs; 31% would not offer IUDs to women with a history of ectopic pregnancy, and 48% would not offer IUDs to women who have had PID in the last 5 years. A third study by Luchowski et al,14 which surveyed 1,552 OBGYNs, found that 46% did not agree that IUDs could be inserted immediately postpartum, 20.4% disagreed that IUDs TABLE 2. Satisfaction, continuation, and discontinuation rates among IUD and non-LARC users.7-11 IUDs LNG, %

Copper, %

NonLARC, %

At 12 months

At 24 months

Adults

Adolescents

Rate Satisfaction rate at 12 months

Continuation rate

Discontinuation rate at 12 months

IUD, intrauterine device; LNG, levonorgestrel; LARC, long-acting reversible contraception

Concerns that both providers and patients share about IUDs.4, 12-15 • Difficult and painful insertions in nulliparous and adolescent women • Increased risk of —ectopic — pregnancy —PID/infertility — IUD, intrauterine device; PID, pelvic inflammatory disease

could be inserted after an abortion or miscarriage, 33.2% would not consider nulliparous women to be appropriate candidates for an IUD, and 57% would not consider adolescents to be appropriate candidates for IUDs. In addition, 15.6% believed IUDs increase a patient’s chance of developing PID. Many providers are hesitant to provide IUDs, and many women are reluctant to use them. A 2010 study of 1,665 women by Hladky et al15 illustrated that their major concerns included increased pelvic pain (33%-43%), infertility (20%33%), and ectopic pregnancy (24%-31%). Another study concluded that adolescents and young adults identify pain with insertion and removal as the most feared side effect of IUDs.4 Studies demonstrate that patients and providers share similar concerns.4,12-15 Both groups are concerned that IUD insertions in nulliparous and adolescent women are more difficult and painful. They are also concerned that IUDs increase a patient’s risk of ectopic pregnancy and infertility through an increased risk for PID. Some providers believe that nulliparous and adolescent women, women who are postpartum and postabortion/ miscarriage, and women with a history of ectopic pregnancy, PID, or STIs are not candidates for IUD use. The next section reviews the ACOG recommendations and data on contraindications for use and side effects that add to the evidence that these concerns are largely unfounded. Difficulty and pain with insertion

As discussed above, patients and providers are concerned about difficulty and pain with IUD insertion, especially in the adolescent and nulliparous population. Some nulliparous and adolescent women may have more pain upon insertion; however, providers should be able to perform the insertion without technical difficulty in most women in these populations.8 Difficulty with insertion is rare. In cases in which

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IUD MISCONCEPTIONS

Providers should make every effort to inform patients about the insertion procedure of the IUD during a preinsertion visit. the provider has difficulty, misoprostol may facilitate the insertion.10,16 It is also possible that doses of ibuprofen greater than 600 mg may relieve some pain, although studies have yet to confirm this definitively.16 In adolescents, concerns about pain during insertion have been associated with increased fear before the procedure. Easing an adolescent’s expectation of pain before insertion may help reduce her anxiety and lead to a less painful experience.15 Adolescents often express anxiety about their first pelvic examination. Ensuring that the adolescent has had a gentle and painless pelvic examination prior to the visit during which the IUD is inserted is another way providers can ease anxiety about the insertion procedure.17 The patient will be more familiar with the pelvic examination before the IUD insertion, and the entire procedure will produce less anxiety. In summary, providers should make every effort to inform patients about the insertion procedure during a preinsertion visit. Patients who are concerned about insertion pain should be told to take 600 mg to 800 mg of ibuprofen before the procedure and reassured that fear of pain is often worse than the actual pain.16,18 Patients should also be informed that the insertion will not be any more complicated if they are younger or nulliparous, and efforts should be made to ease their anxiety. If providers are able to convey these messages, patients’ fears associated with IUD insertions will likely be reduced. Contraindications, infections, and infertility

In an effort to clarify common provider and patient misconceptions about contraindications, a summary of actual contraindications follows. IUDs are contraindicated in women with severe uterine distortion, who are or might be pregnant, who are experiencing unexplained abnormal bleeding, who have tuberculosis, and who are immunocompromised.6,19 Although no adverse effects related to Wilson’s disease or copper allergies have been reported, women with these conditions should not use the copper IUD.6 Women who have cervical cancer or untreated endometrial cancer also should not have an IUD inserted. However, in women with cervical cancer, the IUD usually does not need to be removed if it is already in place. Women with breast cancer should not use a LNG IUD.20 In addition to these contraindications, there is one from which many misconceptions stem—infection. IUD insertions are contraindicated in women with an active pelvic infection. However, women who develop PID while an IUD is

in place usually do not have to have the IUD removed, as long as the PID is treated.20 The risk of PID is slightly higher in women who have an IUD inserted in the presence of an STI than in women who have an IUD inserted without an STI.8 However, an IUD can be inserted in the presence of a vaginal STI, as long as it is treated.8 The ACOG states that evidence does not support routine antibiotic prophylaxis or screening for STIs in most patient populations. However, because adolescents aged 15 years to 19 years are at high risk for STIs, they should be screened before insertion.9 Due to potential bacterial contamination from the insertion procedure, women with IUDs are 6 times more likely to contract PID in the fi rst 20 days after an insertion.6 However, after that initial time period, women with IUDs are not at increased risk of PID.9 The LNG IUDs may even reduce PID rates. No studies have found an increased risk of infertility due to PID in nulliparous or adolescent IUD users compared with multiparous or older IUD users.9 It is important to note that, although certain patient populations are at increased risk for STIs and PID, the use of an IUD does not increase the risk of PID or infertility.9 Contrary to many providers’ and patients’ perceptions, IUDs are safe for use in women with a history of ectopic pregnancy6; they do not increase the risk of ectopic pregnancy. IUD users are 50% less likely to have an ectopic pregnancy compared with women who do not use contraception.20 Clarifying this fact and discussing concerns about infection and infertility with accurate and current information allows patients to make better-informed decisions about their contraception methods.

POLL POSITION

IUDs are safe for: n=1,614

■ nulliparous women and adolescents ■ women with a history of ectopic pregnancy ■ women with a history of pelvic inflammatory disease ■ all of the above

34.26% 62.64% 2.35% 0.74%

For more polls, visit ClinicalAdvisor.com/Polls.

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IUD MISCONCEPTIONS

Recommendations on IUDs from the American College of Obstetricians and Gynecologists.7,9,11 • IUDs are safe for —Nulliparous — women —Adolescents — —Women — who are ■■ immediately postpartum ■■ immediately postabortion/miscarriage —Women — with a history of ■■ PID ■■ ectopic pregnancy ■■ IUD expulsion • IUDs should be offered as first-line contraception for all women • IUDs are the best form of reversible contraception IUD, intrauterine device; PID, pelvic inflammatory disease

Side effects and complications

Providing counseling about the side effects of IUDs correlates with satisfaction and continuation rates.19 In her 2013 review, Hillard17 shows that adolescents, early adolescents in particular, tend to disregard warnings unless they are overstated. She suggests counseling adolescents to expect side effects rather than warning them that they may experience side effects. It is important that adolescents are informed that bleeding will decrease with LNG IUDs and that cramping from the copper IUD will most likely decrease over time and can be subdued with nonsteroidal anti-inflammatory drugs.18 Providers should explain the side effects of each type of IUD, paying close attention to common concerns among all patient groups and with a particular focus on clarifying those concerns. Providers should note that the LNG IUDs have been shown to reduce bleeding and pain from dysmenorrhea17; however, the copper IUD will likely increase bleeding and cramping, especially in the first few months after insertion. Patients with a history of menorrhagia or dysmenorrhea may be better served by one of the LNG IUDs.6 If patients are informed of side effects ahead of time, they will be less likely to react strongly to them if they occur. Providers are less concerned about IUD expulsion and uterine perforation.12-14 However, IUD expulsions and uterine perforations can develop into severe complications and are consequences for which providers should be vigilant. Of the two complications, expulsion is more common, occurring in approximately 5% of IUD users.19 Providers should be aware that IUD expulsion rates may be slightly higher in adolescent

women, women with severe dysmenorrhea, most women with a history of expulsions, women who have had an immediate insertion after an abortion or miscarriage in the first trimester (when compared with an abortion or miscarriage in the second trimester), and women who have an immediate postpartum insertion (when compared with delayed insertion). Immediate insertion of an IUD after vaginal delivery also has a higher rate of expulsion than after cesarean deliveries; however, the ACOG states that the benefits of immediate postpartum insertion may outweigh the risks because delayed insertion requires another office visit that patients may not attend.6,9,22 It is also important to note that a previous expulsion is not a contraindication for the use or insertion of an IUD.9 The risk of uterine perforation is rare. Recent studies estimate that as few as 0.4 to 1 perforation occurs in every 1,000 insertions. When they do occur, the perforations are rarely dangerous.16,17,22,23 Perforation in an asymptomatic patient is not an emergency.19 A recent study showed that breastfeeding at the time of insertion created a sixfold increase in the risk of perforation.24 Other risk factors include clinician inexperience in IUD insertion, myometrial defects, an immobile uterus, or a retroverted uterus.25 A previous perforation is not a contraindication for IUD use or insertion. Conclusions

Surveys and studies have shown that many common provider misconceptions are unfounded. Common misconceptions include the belief that nulliparous women, adolescent women, women who are postpartum or postabortion/miscarriage, women who have a recent history of PID or STIs, and women who have a history of ectopic pregnancy are not appropriate candidates for IUDs. In the United States, providers are often hesitant to offer IUDs to nulliparous and adolescent women because they have concerns about difficult insertions, pelvic pain, infertility, and PID. The data above illustrate that most of these concerns are unsubstantiated. In addition to a gap in provider knowledge regarding IUDs, there is also an educational gap among patients. In one survey, only 50% of adolescents had heard of LARC.26 Patients frequently fear infertility and an increased risk of ectopic pregnancy, as well as increased pelvic pain and pain upon insertion. However, many of these concerns are unsupported, or can be ameliorated, if providers explain the potential side effects in advance. Providers also note that patients are more satisfied with LARC methods than any non-LARC method. To potentially increase the use of this efficacious and welltolerated form of contraception, it is important to clarify the

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facts for both patients and providers alike and to address the most common concerns. In spite of the ACOG and MEC recommendations and numerous studies, many continue to hold on to misinformation. Among NPs, PAs, and doctors, it should be reinforced that: (1) IUD insertions in nulliparous and adolescent women are not more difficult than in any other group; (2) IUDs do not increase a patient’s risk of PID or infertility; (3) women who are nulliparous, adolescent, postpartum, or postabortion/miscarriage can safely use IUDs; and (4) a history of ectopic pregnancy, PID, or STIs does not preclude IUD use. Disseminating accurate information that addresses the specific concerns many providers and patients have about IUDs will empower women to make informed decisions and may increase use of IUDs to a rate that is closer to the rest of the world. n

11. Grunloh D, Casner T, Secura GM, et al. Characteristics associated with discontinuation of long-acting reversible contraception within the first 6 months of use. Obstet Gynecol. 2013;122(6):1214-1221. 12. Black KI, Lotke P, Lira J, et al. Global survey of healthcare practitioners’ beliefs and practices around intrauterine contraceptive method use in nulliparous women. Contraception. 2013;88(5):650-656. 13. Harper CC, Blum M, De Bocanegra HT, et al. Challenges in translating evidence to practice: the provision of intrauterine contraception. Obstet Gynecol. 2008;111(6):1359-1369. 14. Luchowski AT, Anderson BL, Power ML, et al. Obstetrician–gynecologists and contraception: Long-acting reversible contraception practices and education. Contraception. 2014; 89(6):578-583. 15. Hladky KJ, Allsworth JE, Madden T, et al. Women’s knowledge about intrauterine contraception. Obstet Gynecol. 2011;117(1):48-54. 16. Smith E, Daley AM. A clinical guideline for intrauterine device use in adolescents. J Am Acad Nurse Pract. 2012;24:453-462.

Ms. Levine received her masters in nursing from Columbia University in February 2015. She can be reached at libbyslevine@gmail.com

17. Hillard PJ. Practical tips for intrauterine devices use in adolescents. J Adolesc Health. 2013;52(4 suppl):S40-S46. 18. Brakman A, Gold M. Teen topic: Consider IUC method for teen

References

contraception. AHC Media Web site. Available at ahcmedia.com/

1. World Contraceptive Patterns 2013. United Nations Web site. Available

articles/21171-teen-topic-consider-iuc-method-for-teen-contraception

at un.org/en/development/desa/population/publications/family/contracep-

19. Yoost J. Understanding benefits and addressing misperceptions and

tive-wallchart-2013.shtml

barriers to intrauterine device access among populations in the United

2. American College of Obstetricians and Gynecologists. ACOG Practice

States. Patient Prefer Adherence. 2014;8:947-957.

bulletin no. 133: Benefits and risks of sterilization. Obstet Gynecol.

20. Dean G, Goldberg AB. Intrauterine contraception: Devices,

2013;121(2 Pt):392-404.

candidates, and selection. UpToDate website. Updated

3. Contraception for adolescents: what’s new? U.S. Department of Health

September 1, 2015. Available at uptodate.com/contents/

& Human Services Web site. Available at hhs.gov/ash/oah/oah-initiatives/

intrauterine-contraception-devices-candidates-and-selection

ta/experience_expertise_curtis.pdf

21. Medical eligibility criteria for contraceptive use. World Health

4. Kavanaugh ML, Frohwirth L, Jerman J, et al. Long-acting reversible con-

Organization Web site. Available at who.int/reproductivehealth/

traception for adolescents and young adults: Patient and provider perspec-

publications/family_planning/MEC-5/en

tives. J Pediatr Adolesc Gynecol. 2013;26(2):86-95.

22. Hardeman J, Weiss BD. Intrauterine devices: An update. Am Fam

5. Sklya [package insert]. Wayne, NJ: Bayer HealthCare Pharmaceuticals

Physician. 2014;89(6):445-450.

Inc; 2013.

23. Kaislasuo J, Suhonen S, Gissler M, et al. Uterine perforation caused

6. Speroff L, Darney PD. A Clinical Guide for Contraception. 5th ed.

by intrauterine devices: Clinical course and treatment. Hum Reprod.

Philadelphia, PA: Lippincott Williams & Wilkins; 2010.

2013;28(6):1546-1551.

7. Peipert JF, Zhao Q, Allsworth JE, et al. Continuation and satisfaction of

24. Heinemann K, Westhoff CL, Grimes DA, Möhner S. Intrauterine devic-

reversible contraception. Obstet Gynecol. 2011;117(5):1105-1113.

es and the risk of uterine perforations: Final results from the EURAS-IUD

8. O’Neil-Callahan M, Peipert JF, Zhao Q, et al. Twenty-four-month contin-

study. Obstet Gynecol. 2014;123(suppl 1):3S.

uation of reversible contraception. Obstet Gynecol. 2013;122(5):1083-1091.

25. Dean G, Goldberg AB. Intrauterine contraception:

9. Committee on Adolescent Health Care Long-Acting Reversible

Management of side effects and complications. UpToDate web-

Contraception Working Group, The American College of Obstetricians

site. Updated July 14, 2015. Available at uptodate.com/contents/

and Gynecologists. Committee opinion No. 539: adolescents and long-

intrauterine-contraception-management-of-side-effects-and-complications

acting reversible contraception: Implants and intrauterine devices. Obstet

26. Teal SB, Romer SE. Awareness of long-acting reversible

Gynecol. 2012;120:983-988.

contraception among teens and young adults. J Adolesc Health. 2013;52

10. American College of Obstetricians and Gynecologists. ACOG Practice

(4 suppl):S35-S39.

Bulletin No. 121: Long-acting reversible contraception: Implants and intrauterine devices. Obstet Gynecol. 2011;118(1):184-196.

All electronic documents accessed on October 5, 2015.

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CME CE FEATURED COURSE

n LEARNING OBJECTIVES After completing the activity, the participant should be better able to: • Assess the side effects, interactions, and contraindications of the various psoriasis treatments • Demonstrate methods to decrease complications from psoriasis and from the therapies that are available • Identify risk factors, such as smoking or alcohol consumption, that may exacerbate psoriasis and increase the chance of cardiovascular disease n COMPLETE THE POSTTEST: Page 54 n ADDITIONAL CME/CE CREDIT: Page 66, 71, 76

This activity is provided by Haymarket Medical Education (HME) for physician credit. This activity is co-provided by Medical Education Resources (MER) for nursing contact hours. Release Date: November 13, 2015 Expiration Date: November 12, 2016 Estimated time to complete the educational activity: 30 minutes Statement of Need: Many health care professionals other than dermatologists may not be aware of the range of therapies, particularly systemic, available for patients with moderate to severe psoriasis, outside of topical therapies, phototherapy, or the older biologics, which can be ineffective or come with significant end-organ toxicities. It is important that clinicians be aware of the common adverse effects of newer treatments. Target Audience: This activity has been designed to meet the educational needs of primary care health care professionals who will treat patients with psoriasis. Faculty Eman Bahrani, BA Baylor College of Medicine, Houston Maura Holcomb, MD Baylor College of Medicine, Houston Accreditation Statements Physician Credit: HME is accredited by the Accredita tion Council for Continuing Medical Education (ACCME) to provide continuing medical education for physicians. Credit Designation: HME designates this enduring material for a maximum of 0.5 AMA PRA Category 1 CreditTM. Physicians should claim only the credit commensurate with the extent of their participation in the activity. Nursing Credit: MER is accredited as a provider of continuing nursing education by the American Nurses Credentialing Center’s Commission on Accreditation. Credit Designation: This CE activity provides 0.5 contact hour of continuing nursing education. MER is a provider of continuing nursing education by the California Board of Registered Nursing, Provider #CEP 12299, for 0.5 contact hour. This activity qualifies for 0.25 pharmacotherapy credit. American Academy of Physician Assistants (AAPA) The AAPA accepts certificates of participation for educational activities certified for AMA PRA Category 1 Credit™ from organizations accredited by ACCME or a recognized state medical society. Physician assistants may receive a maximum of 0.5 hour of Category I credit for completing this program. Disclosure Policy 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 in an effort to ensure independence, objectivity, balance, and scientific rigor in all its educational programs. Furthermore, HME seeks to verify that all scientific research referred to,

CME-Feature-Psoriasis_CA1115.indd 44

reported, or used in a CME/CE activity conforms to the generally accepted standards of experimental design, data collection, and analysis. HME is committed to providing its learners with high-quality CME/CE activities that promote improvements in health care and not those of a commercial interest. The faculty reported the following financial relationships with commercial interests whose products or services may be related to the content of this CME activity: Faculty Disclosures

Name of faculty

Reported Financial Relationship

Eman Bahrani, BA

No relevant financial relationships

Maura Holcomb, MD

No relevant financial relationships

Staff/Planners’ Disclosures The planners, managers, and reviewers for this program reported the following financial relationships with commercial interests whose products or services may be related to the content of this CME activity: HME planners, managers, and reviewers have no relevant financial relationships to disclose. MER planners, managers, and reviewers have no relevant financial relationships to disclose. Disclosure of Unlabeled Use: This educational activity may contain discussion of published and/or investigational uses of agents that are not indicated by the FDA. HME and MER do not recommend the use of any agent outside of the labeled indications. Please refer to the official prescribing information for each product for discussion of approved indications, contraindications, and warnings. Method of Participation: There are no fees for participating in and receiving CME/CE credit for this activity. During the period of November 13, 2015, through November 12, 2016, participants must: 1) read the learning objectives and faculty disclosures; 2) study the educational activity; 3) complete the posttest and submit it online (clinicians may register at www.myCME.com); and 4) complete the evaluation form online. A statement of credit will be issued only upon receipt of a completed activity evaluation form and a completed posttest with a score of 70% or better. Disclaimer: The content and views presented in this educational activity are those of the authors and do not necessarily reflect those of HME or MER. Any procedures, medications, or other courses of diagnosis or treatment discussed or suggested in this activity should not be used by clinicians without evaluation of their patient’s conditions and possible contraindications on dangers in use, review of any applicable manufacturer’s product information, and comparison with recommendations of other authorities. The information presented in this activity is not meant to serve as a guideline for patient management.

10/27/15 1:55 PM

CME CE FEATURED COURSE: EMAN BAHRANI, BA, AND MAURA HOLCOMB, MD

Psoriasis: an overview of current and emerging medications Many therapeutic options are available for patients with psoriasis, ranging from topical agents to phototherapy and systemic and biologic agents.

Psoriasis is a complex immune-mediated disease that can manifest in the skin and joints.

soriasis is a complex immune-mediated disease that affects approximately 120 million people globally and requires chronic management.1 The condition manifests itself in the skin, joints, or both, and exhibits associated comorbidities that increase risk for early death, including metabolic syndrome, cardiovascular disease, psoriatic arthritis, depression, anxiety, nonalcoholic fatty liver disease, Crohn’s disease, and lymphoma.2 Physicians should encourage lifestyle changes to reduce modifiable cardiovascular risk factors, such as smoking, which has been shown to independently increase risk of onset and exacerbation of psoriasis. Excessive alcohol intake has been reported in up to one-third of patients with psoriasis, likely due to psychologic distress. Excess alcohol ingestion is also a risk factor for cardiovascular disease.3 As emerging research illustrates its increasing complexity, psoriasis is now considered a systemic inflammatory disorder.2 Clinically, there are 5 types of psoriasis: plaque psoriasis, guttate or eruptive psoriasis, inverse psoriasis, pustular psoriasis, and erythrodermic psoriasis. Plaque psoriasis is the most common form, with monomorphic, well-demarcated erythematous plaques under a silvery scale, typically on the scalp and extensor surfaces. Guttate psoriasis exhibits teardrop shaped lesions with scale. Inverse psoriasis is found in the intertriginous or flexural areas. Pustular psoriasis can present as either palmoplantar pustulosis or as the serious generalized pustular psoriasis. Any form can evolve into erythrodermic psoriasis, a rare

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The prevalence of psoriasis within certain populations ranges from less than 1% to more than 10%, depending on ethnic and geographic factors. and serious complication of the disease with significant risk of mortality. Psoriasis can affect the skin, nails, scalp, and joints to different degrees in each patient.2,4 The prevalence of psoriasis within certain populations ranges from less than 1% to more than 10%, depending on ethnic and geographic factors, with a 2% prevalence rate in Europe and North America.5 Family studies have shown a genetic predisposition for the disease, with the literature illustrating certain susceptibility alleles in immune-related genes.6,7 Dysregulation between the innate and adaptive immune systems, tumor necrosis factor (TNF)-α, and the interleukin (IL)-23–T helper cell 17 (Th17) axis, among other immune reactions in the cells of the skin, have all been shown to be involved in the pathogenesis of psoriasis.2,8 Management varies according to severity and effect on quality of life and should be tailored to each individual patient. There are many therapeutic options available, ranging from topical agents, to phototherapy and systemic and biologic agents.1,2 This article discusses established therapies for psoriasis and their indications for use, as well as emerging treatments that hold promise for the future. Meet the patient

A 55-year-old postmenopausal woman with a past medical history of hypertension, dyslipidemia, non–insulin-dependent diabetes, and a 30-year history of psoriasis presents to a dermatology clinic with worsening symptoms and spread of her disease that were causing her physical and mental distress. She had been using various topical medications with only partial control. She had tried photochemotherapy in the form of psoralen plus ultraviolet (UV)-A (PUVA) treatments several years ago, but could not maintain weekly treatments because the 40-mile drive to the clinic was too inconvenient. In the last 2 years, she had 1 basal cell carcinoma and 1 squamous cell carcinoma excised. Her medications include metformin and simvastatin. She smoked 1 pack per day (ppd) of cigarettes in her 20s and 30s, but cut down to one-half ppd after being informed that smoking may aggravate her psoriasis. She drinks approximately 3 glasses of wine per night and says they help her sleep. Her physical examination reveals an obese woman with fair skin and psoriasis involving 25% of her body surface area (BSA), when it had previously involved less than 10% of her BSA. Erythematous, tender patches and plaques with silvery

scales are visible on the trunk, lower back, and upper and lower extremities. Thick plaques with silvery white scale are found throughout the scalp. Her palms and the plantar aspects of her feet also exhibit mild erythematous patches. There is no onychodystrophy, and no signs or symptoms of psoriatic arthritis are evident. Mild disease

For mild disease, which affects 70% to 80% of patients with psoriasis, first-line management remains topical treatments. Glucocorticoids and vitamin D derivatives, or their combination, are typically sufficient for mild psoriasis. Topical calcineurin inhibitors (tacrolimus or pimecrolimus) are reserved for difficult anatomic sites, such as the face and intertriginous areas, which are more prone to the adverse effects of the other topical agents.2 For the scalp, combinations of corticosteroids and vitamin D3 analogues are most effective, though very potent corticosteroids alone are more effective than vitamin D3 derivatives.9 Moderate-to-severe disease

There is no single definition in the literature of what constitutes moderate-to-severe psoriasis. The Psoriasis Area and Severity Index (PASI), percentage of BSA affected, and the Dermatological Life Quality Index provide physicians with some metrics to differentiate mild disease from moderate-or-severe psoriasis. However, these guidelines and their numeric cutoffs are cumbersome to calculate and use in daily practice and may not take into account the full clinical and subjective picture of disease burden. For example, although predominant psoriatic nail involvement may not constitute a significant percentage of BSA, it can negatively affect quality of life and be difficult to treat topically.2,10 The Consensus Guidelines of the National Psoriasis Foundation Medical Board thus define moderateto-severe psoriasis as disease that “cannot or would not be expected to achieve adequate control using topical agents, with adequacy defined by the patient’s own perception of the disease and its burdens.”10 Patients with moderate-to-severe psoriasis are often treated with a combination of phototherapy and topical or systemic therapy. Table 1 summarizes some key points regarding systemic therapies discussed in this article. Narrow-band UV-B (311 nm and 313 nm) is the more widely used phototherapy, whereas photochemotherapy,

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Conventional systemic therapies for psoriasis include acitretin, methotrexate, and cyclosporine, which have been used for more than 10 years. such as PUVA (320-400 nm), is used less frequently. Although phototherapy is effective, it is time consuming, as it is performed 2 to 5 times per week in a clinical environment. Therefore, phototherapy is mainly used for acute disease control rather than chronic management.2,11 PUVA increases the risk of skin cancers, especially after 200 treatments, which also limits its chronic use.11 Absolute contraindications to phototherapy include genetic defects that increase light sensitivity or risk of skin cancer, lupus erythematosus, and pregnancy or lactation (for pregnancy, the contraindication applies to oral PUVA only). Phototherapy was developed based on the observation that exposure to sunlight helped reduce the symptoms of many skin diseases. Phototherapy has been shown to inhibit keratinocyte proliferation, induce apoptosis in cells of the immune system, and inhibit Th1 and Th17 proliferation, as well as stimulation of the Th2 system.2,12 Conventional systemic therapies. Conventional systemic therapies used for psoriasis treatment include acitretin, methotrexate, and cyclosporine, which have been used for more than 10 years.2,13 Acitretin is an oral retinoid and is teratogenic, limiting its use in women of childbearing age. Dosing starts at 10 mg/d to 25 mg/d and is increased according to the patientâ&#x20AC;&#x2122;s ability to tolerate its side effects. However, in the case of generalized pustular psoriasis, it should be started at a high dose and titrated down if a lower dose is effective. Its adverse effects include increases in xerosis and triglyceride level and abnormal liver function tests. Acitretin is also classified as Pregnancy Category X and inappropriate for use in women of childbearing age or men who wish to conceive; in rare cases, the drug has been associated with decreased night vision, skeletal hyperostosis, or pseudotumor cerebri.13,14 Acitretin is more effective when used in combination with topical vitamin D3 derivatives such as calcipotriene, or phototherapy or biologics. Among the drawbacks of acitretin are that it has a slow onset of action and may only thin psoriatic plaques, rather than effectively eliminating them, when used alone. It is not as effective a monotherapy as methotrexate or cyclosporine at tolerable doses,2,14 but acitretin is helpful in treating specific subtypes of psoriasis, such as generalized, palmoplantar, pustular, and hyperkeratotic psoriasis.14 One advantage of acitretin is that it has less potential for end-organ toxicity than methotrexate or cyclosporine.10

Methotrexate inhibits DNA replication by disrupting cellular folic acid metabolism and is the oldest systemic therapy for moderate-to-severe psoriasis. Although it is cytostatic, it also leads to reduced T-cell gene expression, increases endogenous levels of adenosine, and decreases antibody responses, which are direct anti-inflammatory effects. Methotrexate is available in 2.5-mg tablets, prescribed as 7.5 mg to 25 mg taken once weekly. Subcutaneous methotrexate, also dosed once weekly, exhibits improved bioavailability, efficacy, and tolerability in patient studies of rheumatoid arthritis.13 Cumulative use of methotrexate increases risk of liver toxicity, but folate supplementation can reduce that risk,15 as well as the risks of bone marrow suppression and gastrointestinal side effects.10 A multicenter, randomized controlled trial found that 40% of subjects achieved a 75% reduction in PASI scores (PASI 75) at 24 weeks.13,16 The most common side effects of methotrexate include nausea, diarrhea, fatigue, and headaches. Additionally, liver function tests should be performed every 4 to 12 weeks, as hepatotoxicity may manifest early as elevated transaminases. Guidelines from the American Academy of Dermatology have reduced the need for liver biopsies in patients without risk factors for hepatic fibrosis to every 3.5 g to 4.0 g of total cumulative dose.17 Some European countries have standardized the measurement of classic and newly validated serum biomarkers, such as amino terminal propeptide of type III procollagen. A complete blood count is necessary to screen for myelosuppression and kidney function must be monitored prior to and during use because methotrexate is renally excreted. Methotrexate is an abortifacient and classified as Pregnancy Category X; it is also contraindicated during lactation. The drug should be discontinued in both men and women at least 3 months prior to attempting to conceive. Methotrexate can be combined with other systemic medications or phototherapy for additive or synergistic responses. Combinations allow for lower doses of the individual drugs and improved overall efficacy.13 Cyclosporine is an oral calcineurin inhibitor that lowers the production of IL-2 and other proinflammatory cytokines that activate T cells. It is used in many immune-mediated disease states, including moderate-to-severe psoriasis. It is typically dosed at 2.5 mg/kg/d to 5.5 mg/kg/d.13 Cyclosporine is fast acting and is therefore considered a first-line treatment for types of pustular psoriasis and erythrodermic psoriasis as a

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TABLE 1. Summary of major systemic medications for moderate-to-severe psoriasis. Systemic drug

Mechanism of action

FDA approval for moderate-severe psoriasis Side effects and risks

CYCLOSPORINE2,10,13,18,34

Oral calcineurin inhibitor

1997, severe psoriasis

Nephrotoxicity, headache, hypertension, elevated triglyceride level, hirsutism, gum hyperplasia, electrolyte changes, increased risk of squamous and basal cell carcinoma

METHOTREXATE10,13,15,16,17,34 Inhibits DNA replication by disrupting folate metabolism

1970s, severe psoriasis

Hepatotoxicity, nausea, diarrhea, fatigue, headaches, myelosuppression

ACITRETIN2,10,13,14,34

Oral retinoid that regulates epithelial cell growth

1997, psoriasis

Xerosis, elevated triglyceride level, elevated liver enzymes, decreased night vision, headache, pseudotumor cerebri, skeletal hyperostosis

ETANERCEPT2,10,34

TNF-α inhibitor

2004, psoriasis; 2002, PsA

Flu-like symptoms, URIs, injection site reactions, increased risk of infections, autoimmune disorders, lymphoma

ADALIMUMAB2,10,19,20,34

TNF-α inhibitor

2005, PsA; 2008, psoriasis

Flu-like symptoms, URIs, injection site reactions, increased risk of infections, autoimmune disorders, lymphoma

INFLIXIMAB2,10,19,20,21,34

TNF-α inhibitor

2005, PsA; 2006, psoriasis

Flu-like symptoms, URIs, injection-site reactions, increased risk of infections, autoimmune disorders, lymphoma

ALEFACEPT10,22,23,34

Interferes with T-cell surface proteins, triggering apoptosis

2003, plaque psoriasis

Risk of CD4 T lymphocyte depletion

USTEKINUMAB10,24,25,26,34

Blocks IL-12 and IL-23, disrupting development of Th17 lymphocytes

2009, psoriasis; 2013, PsA

No significant risks due to immunosuppression, but long-term data lacking

SECUKINUMAB2,27,34

Inhibits IL-17A, cytokine produced by Th17, and other immune cells

2015, plaque psoriasis

Rates and severity of infection no higher than that of etanercept; increased risk of URIs

APREMILAST2,13,28,29,34

Oral small molecule PDE4 inhibitor

2014, plaque psoriasis, psoriatic arthritis

5%-10% weight loss, diarrhea, nausea, headache

TOFACITINIB13,30,31

Oral small molecule JAK1/ JAK3 inhibitor

Under FDA review

Cytopenias, anemias, increased liver test results, increased cholesterol level, increased creatinine level, increased rates of herpes zoster outbreaks and infection, such as URI

CBC, complete blood count; FDA, U.S. Food and Drug Administration; IL, interleukin; JAK, janus kinase; PASI, Psoriasis Area Severity Index; PASI 75, percentage of subjects achieving a 75% reduction in PASI scores; PDE, phosphodiesterase; PsA, psoriatic arthritis; SCC/BCC, squamous cell carcinoma/basal cell carcinoma; TB, tuberculosis; Th17, T helper cell 17; TNF, tumor necrosis factor; UPT, urine pregnancy test; URI, upper respiratory infection

rescue drug. A dose of approximately 5 mg/kg/d has shown a reliable average PASI 75 rate of 70%.13,18 Once a course of cyclosporine is complete, management is switched to a therapy with fewer long-term adverse effects. Long-term use and high doses of cyclosporine are associated with renal damage, hypertension, hypertriglyceridemia, electrolyte abnormalities, and increased risk of squamous and basal cell carcinomas. Therefore, it is used intermittently for no longer than 12 weeks at a time and is effective for management of flares. Baseline laboratory and blood pressure tests are necessary prior to its use. While

on the medication, weekly blood pressure measurements and monthly comprehensive metabolic panels with lipids, magnesium, and potassium are necessary. Cyclosporine has many relative contraindications and is metabolized through the cytochrome P450 liver system; thus, it is important to be aware of a patient’s medical history, diagnoses, and current medications and potential interactions prior to its use.2,10,13 Because cyclosporine can only be used temporarily, it is often combined with or titrated down while also using overlapping therapy, such as methotrexate, acitretin, or biologic agents.13

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Monitoring before and during use

FDA pregnancy category

Comments

Kidney function tests, blood pressure measurements

Category C; can only be given when benefits outweigh the risks to the fetus

Fast-acting; used first-line for pustular and erythrodermic psoriasis as a rescue drug; used intermittently for no longer than 12 weeks for flares due to side effects

Liver function tests, CBC, kidney function liver biopsy for every 3.5–4.0g total cumulative dose, or more often for those with risk factors of hepatic fibrosis

Abortifacient, category X; men should wait 3 months and women 4 months after stopping methotrexate before trying to conceive

Common first-line systemic drug for continuous management of chronic plaque psoriasis; can be combined with other systemic medications or phototherapy for additive or synergistic effects

Women must have 2 negative UPT results prior to use and use 2 effective forms of birth control while on this medication

Category X; should not be taken for 3 years before pregnancy

More effective when used in combination with topical vitamin D3 derivatives or phototherapy or biologics; helpful in generalized, palmoplantar, pustular, and hyperkeratotic subtypes of psoriasis

Screen for latent TB, occasional blood tests recommended