November 2017 Clinical Advisor by The Clinical Advisor

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■■Cervical cancer screening ■■Aspirin and CV events ■■VTE risk linked to height FEATURE

Preventing suicide among US veterans in primary care LEGAL ADVISOR

A patient commits murder

n Dermatology Clinic

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BREAST CANCER There is currently no consensus on how frequently mammograms should be done.

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Editor Colby Stong editor@clinicaladvisor.com Associate editor Madeline Morr 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 Editorial director Kathleen Walsh Tulley 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. 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 20, 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., 275 7th Avenue, 10th 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 © 2017

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4 THE CLINICAL ADVISOR • NOVEMBER 2017 • www.ClinicalAdvisor.com

CONTENTS NOVEMBER 2017

NEWS AND COMMENT 14

26 Preventing suicide in US veterans The suicide rate among deployed veterans is 41% higher than that in the general US population.

Newsline ■■The US Preventive Services Task

Force has released a series of draft recommendations regarding cervical cancer screening in women. ■■Discontinuation of low-dose aspirin in the absence of major surgery or bleeding results in an increased risk of cardiovascular events. ■■Venous thromboembolism is strongly associated with height in both men and women. ■■The US Preventive Services Task Force has updated its 2011 recommendations on screening for amblyopia and its risk factors in children. ■■Roux-en-Y gastric bypass is effective for weight loss, as well as remission and prevention of type 2 diabetes, hypertension, and dyslipidemia, for up to 12 years postsurgery, according to researchers.

Cervical cancer screening in women 14

CME A 19-year-old Latina college

CME Feature posttest

DEPARTMENTS 12

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

Dermatology Clinic n Fragile, bullous lesions on the trunk of a child n A yellow-orange hairless patch on a 1-year-old boy

Dermatologic Look-Alikes Lesions on the face, lip, and ear

Lesions on the face, lip, and ear 53

FEATURES 7 Mammography: a review of 1 current guidelines No consensus among current medical communities exists regarding how frequently mammography should be done or the age that it should begin. In this review, mammography screening guidelines are compared to help clinicians determine the best practices for their patients.

MAKING CONTACT

student with prediabetes This case shows how lifestyle changes can prevent the progression of prediabetes to overt T2DM.

Continues on page 6

When a patient commits murder 58

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CONTENTS 58

Legal Advisor A patient commits murder. A lawsuit alleges clinician negligence, which leaves three children without a parent.

Alternative Meds Update The medicinal use of copper dates to nearly 2000 BC. More recently, it has been used in the form of bracelets to purportedly help mitigate the pain and swelling of osteoarthritis.

DEPARTMENTS cont’d

ADVISOR FORUM 46

Clinical Pearls ■ Tips for making a personal connection with your patients

Case Files ■ Military sexual trauma: a primer for clinicians

“I’m working from home.”

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There is curr ently no consens us on how freq uen mammog tly rams should be done.

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USPSTF recommends skin cancer prevention care to begin at age 6 months The task force concluded with moderate certainty that behavioral counseling interventions have a moderate net benefit in children, adolescents, and young adults aged 6 months to 24 years with fair skin.

CDC: Nearly 40% of US adults are now obese Nearly 40% of adults in the United States are now obese, raising concerns that the ever-expanding obesity epidemic will lead to sicker Americans and higher healthcare costs. Watch the video here: ClinicalAdvisor.com/AdultObesityVideo

AAPA: Wage gap remains between female and male PAs According to the AAPA, female physician assistants are paid 89 cents for every dollar that male PAs are paid. Longer hospital stay is linked to low health literacy Low health literacy is associated with a longer hospital length of stay among general medicine patients.

The 2017 NP and PA Salary Survey Results from The Clinical Advisor’s 2017 Salary Survey show that about 55% of nurse practitioners and 54% of physician assistants earned a higher income this past year than they did in 2015-2016. View the slideshow here: ClinicalAdvisor.com/SalarySurvey2017

The Waiting Room

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

Official Blog of The Clinical Advisor ClinicalAdvisor.com/WaitingRoom Tafari Mbadiwe, MD, JD Are your colleagues continuing to perform unnecessary arthroscopies? Orthopedists may perform an arthroscopy on arthritic patients because they are wilfully blind to alternative treatments.

ClinicalAdvisor.com/cartoons

Jim Anderson, MPAS, PA-C, DFAAPA When patients need services that don’t exist Often times, PAs may run into situations where patients need services and resources in health care that do not exist.

MAKING CONTACT

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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.

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A shoulder injury after a mixed martial arts competition A 23-year-old woman presents to the emergency department with a left shoulder injury that occurred when she was competing in a mixed martial arts competition. X-rays taken in the emergency department show a left anterior shoulder dislocation. WHICH NERVE IS TYPICALLY INJURED?

• Radial • Musculocutaneous

• Median • Axillary

● See the full case at ClinicalAdvisor.com/OrthoDx_Nov17

Derm Dx An asymptomatic eruption on the legs and trunk A 76-year-old man is referred for evaluation of an asymptomatic eruption that began on his legs about 2 weeks ago and is now spreading to his trunk. The rash developed shortly after he started a new oral diabetes medication. Examination revealed multiple erythematous papules. CAN YOU DIAGNOSE THIS CONDITION?

• Acute generalized exanthematous pustulosis • Folliculitis • Pityriasis lichenoides • Pustular psoriasis ● See the full case at ClinicalAdvisor.com/DermDx_Nov17

www.ClinicalAdvisor.com • THE CLINICAL ADVISOR • NOVEMBER 2017 13

Newsline N O V E M B E R 2 017

VTE risk is linked to height in men and women page 16

Amblyopia screening advised in children page 16

Gastric bypass surgery effective long-term page 16

THE US Preventive Services Task Force (USPSTF) has released draft recommendations regarding cervical cancer screening in women. The task force concluded with high certainty that the benefits of screening every 3 years with cytology alone substantially outweigh the harms in women aged 21 to 29 years and that the benefits of screening every 3 years with cytology alone or every 5 years with high-risk human papillomavirus (hrHPV) testing alone outweigh the harms in women aged 30 to 65 years. The recommendations do not apply to women who have been diagnosed with a high-grade

precancerous cervical lesion or cervical cancer, women with in utero exposure to diethylstilbestrol, or women who have a compromised immune system. For women aged 21 to 65, the USPSTF recommends screening for cervical cancer every 3 years with cervical cytology only in women aged 21 to 29 years. The task force found evidence that screening women between ages 21 and 65 substantially reduces cervical cancer incidence and mortality. For women aged 30 to 65 years, the USPSTF recommends either screening every 3 years with cervical cytology alone or every 5 years with hrHPV testing (Grade A).

Cervical cancer screening: USPSTF recommendations

For women aged 21 to 65, the USPSTF recommends cervical cancer screening every 3 years, with cervical cytology only in those who are aged 21 to 29 years.

For women aged 65 and older, the USPSTF recommends against screening for cervical cancer in those who have had adequate prior screening and are otherwise not at high risk for developing cervical cancer (Grade D). The USPSTF recommends against screening for cervical cancer in women younger than 21 and in those who have had a hysterectomy with removal of the cervix and no history of high-grade precancerous lesion (Grade D).

Aspirin discontinuation increases risk of cardiovascular events DISCONTINUATION of low-dose aspirin in the absence of major surgery or bleeding results in an increased risk of cardiovascular events, according to a study published in Circulation. Researchers included 601,527 users of low-dose aspirin of 75 to 160 mg for primary or secondary prevention between 2005 and 2009. Patients were 40 years or older, free from previous cancer, and had a greater than 80% adherence during the first observed year of treatment. The control group consisted of 227,135 patients who collected their first low-dose aspirin dispense at least 1 year after the start of the study period. Concomitant cardiovascular disease was defined as a prior hospitalization for myocardial infarction or stroke. The first 3 months after a major bleeding or surgical procedure were excluded from the time at risk. Primary outcome was defined as a first incidence of cardiovascular disease after the start of

follow-up, defined as a hospitalization for myocardial infarction, stroke, or cardiovascular death. Approximately half of the sample were on long-term aspirin treatment without having had a prior hospitalization for cardiovascular disease. During a median of 3.0 years of follow-up, corresponding to 1,491,369 person-years at risk, 62,690 cardiovascular events occurred, with 73,636 deaths. Patients who discontinued aspirin had a higher rate of cardiovascular events than those who continued (hazard ratio, 1.37), corresponding to an additional cardiovascular event observed every year in 1 of 74 patients (37%) who discontinue aspirin. “Among long-term users of low-dose aspirin, discontinuation of aspirin in the absence of major surgery or bleeding was associated with a >30% increased risk of cardiovascular events,” the authors stated. “The risk increased shortly after discontinuation.”

14 THE CLINICAL ADVISOR • NOVEMBER 2017 • www.ClinicalAdvisor.com

Newsline VTE risk linked Amblyopia screening recommended for further treatment, which to height in men THE US Preventive Services may include the use of correcTask Force (USPSTF) has updatand women tive lenses, occlusion therapy for ed its 2011 recommendations on screening for amblyopia and its risk factors in children, as published in JAMA. Included in this update is the recommendation that all children aged 3 to 5 years undergo vision screening at least once to detect amblyopia or its risk factors. The task force found adequate evidence that vision screening tools are accurate in detecting vision abnormalities, including refractive errors, strabismus, and amblyopia and that treatment of amblyopia or its risk factors in children aged 3 to 5 years leads to improved visual acuity. Children with positive findings should be referred for a complete eye examination to confirm the presence of vision problems and

The USPSTF advises screening for children aged 3 to 5.

amblyopia, or surgical interventions for some causes of refractory strabismus. The USPSTF concluded with moderate certainty that vision screening to detect amblyopia or its risk factors in children aged 3 to 5 years has a moderate net benefit because untreated amblyopia results in permanent, uncorrectable vision loss, and the benefits of screening and treatment potentially can be experienced over a child’s lifetime. The USPSTF concludes that the benefits of vision screening to detect amblyopia or its risk factors in children younger than 3 years are uncertain, and that the balance of benefits and harms cannot be determined for this age group.

Gastric bypass surgery effective for 12 years ROUX-EN-Y GASTRIC bypass is effective for weight loss, as well as remission and prevention of type 2 diabetes, hypertension, and dyslipidemia for up to 12 years postsurgery, according to a study in the New England Journal of Medicine. The researchers included 1,156 patients (aged 18 to 72 years) with severe obesity who were categorized into 3 groups: 418 patients who sought and underwent Rouxen-Y gastric bypass (surgery group); 417 patients who sought but did not undergo surgery (nonsurgery group 1); and 321 patients who did not seek surgery (nonsurgery group 2). The investigators performed clinical examinations at baseline and at 2 years,

16 THE CLINICAL ADVISOR • NOVEMBER 2017 • www.ClinicalAdvisor.com

6 years, and 12 years to determine the presence of type 2 diabetes, hypertension, and dyslipidemia. Dr. Adams’ group found that the adjusted mean change from baseline in body weight in the surgery group was −45.0 kg at 2 years, −36.3 kg at 6 years, and −35.0 kg at 12 years. The mean change at 12 years in nonsurgery group 1 was −2.9 kg, compared with a mean change of 0 kg at 12 years in nonsurgery group 2. Regarding patients in the surgery group who had type 2 diabetes at baseline, type 2 diabetes remitted in 66 of 88 patients (75%) at 2 years, in 54 of 87 patients (62%) at 6 years, and in 43 of 84 patients (51%) at 12 years. n

VENOUS thromboembolism (VTE) is strongly associated with height in men and women, according to data published in Circulation: Cardiovascular Genetics. Researchers at Lund University in Malmo, Sweden, and colleagues based their findings on sibling pair analysis, which reduces the influence of familial confounding. A total of 1,610,870 male participants born between 1951 and 1992 without VTE were followed from enlistment until 2012, and a cohort of women without VTE (n=1,093,342) were followed from first pregnancy until 2012. The researchers used the MultiGeneration Register to identify all full-sibling pairs discordant for height. The results showed that, compared with the tallest women (>185 cm) and men (>190 cm), there was a graded decreased risk by lower height for men and women. The risk was lowest in women <155 cm (hazard ratio [HR], 0.31) and men <160 cm (HR, 0.35). A graded association in the cosibling design among men and women was observed, although a significant association in women was noted only for a difference of ≥10 cm (HR for sisters, 0.65). Among brothers, a height difference ≥10 cm was associated with an HR of 0.69. The authors note that the association between VTE and a difference of 10 cm was not weaker than in the general population sample.

FEATURE: KAREN HEROLD, DNP, WHCNP-BC, FNP-BC; BRAM GOLDSTEIN, PHD; JANUARY LOPEZ, MD

Mammography: a review of current guidelines Consensus regarding mammography screening varies, and conflicting guidelines can cause confusion for patients and providers. Seven US medical organizations have issued mammography screening guidelines.

ammography is one of the most studied screening tests in medicine; since the advent of screening mammography, the rate of breast cancer mortality has decreased by more than 30% in the United States.1 Moreover, numerous studies have corroborated that conventional mammography is the only effective population-based strategy for early detection that mitigates the risk for breast cancer–specific mortality.2,3 Surprisingly, there is no consensus among current medical communities regarding how frequently mammography should be done or the age at which it should begin. Significant debate exists about whether the benefits of mammography outweigh the potential negative effects, about what constitutes harm, and about where a benefit-harm threshold may lie, and the outcomes of research on these issues have been inconclusive. In the current review, we analyze mammography screening guidelines from US organizations to understand best practices in an effort to minimize the morbidity and mortality of breast cancer.

Breast cancer epidemiology

Worldwide, breast cancer remains the most frequent cause of cancer-related death in women.4-7 A woman’s probability of developing breast cancer changes with age,8-10 and mortality rates often reflect differences in ethnicity and geographic location. In the United States, for example, the incidence of breast cancer is highest in white and African American women, yet www.ClinicalAdvisor.com • THE CLINICAL ADVISOR • NOVEMBER 2017 17

MAMMOGRAPHY: A REVIEW OF CURRENT GUIDELINES

Risk factors for breast cancer vary and can be related to family history, genetic alterations, race, age, nulliparity, and menstrual history. the rates of breast cancer mortality are higher in African American women.9,11 The international incidence of breast cancer also varies considerably; rates are higher in Western Europe and North America and lower in Asia and sub-Saharan Africa.12,13 Fortunately, breast cancer mortality has decreased in several European countries during the past 25 years, primarily because of early detection via mammography and improved treatment.13-16 Interestingly, studies of Japanese, Chinese, and Korean persons who have immigrated to the United States indicate a progressive increase in breast cancer risk in successive generations, suggesting that behavioral factors in the previous cultures may have conferred a protective effect against the disease.17 Risk factors for the development of breast cancer also vary and can be related to family history, genetic alterations, race, age, nulliparity, menstrual history, and breast density. Additionally, hormone use, diethylstilbestrol use, alcohol consumption, physical inactivity, radiation therapy, and increased body weight are recognized and modifiable risk factors for breast cancer.18 Mammography data

In a consideration of the data on mammography screening, it is essential to understand the widely disparate views and recognize the limitations of the data on which conclusions are based. For example, the results of randomized controlled trials (RCTs) on screening mammography may be adversely affected by noncompliance and study group contamination to a greater degree than the results of other types of RCTs, especially pharmaceutical trials. Noncompliance is the failure of a subject in the intervention group to undergo mammographic screening as directed; contamination occurs when a study participant in the control group undergoes screening outside the study protocol. The effects of noncompliance and contamination effectively dilute the performance of mammography screening and effectuate an underestimation of the measure’s true benefit.19 Meta-analyses of RCTs in women 40 to 69 years of age have reported a collective mortality reduction ranging from 20% to 40%.20-22 The data in women 40 to 49 years of age are far more limited and essentially consist of subgroup analyses of larger trials and observational results. The American Cancer Society (ACS) commissioned a systematic review of the breast cancer screening literature to address questions related

to the frequency of screening mammography3; synthesis of the literature revealed that screening mammography in women 40 to 69 years of age was associated with a reduction in breast cancer deaths across a range of study designs, with inferential evidence supporting breast cancer screening for healthy women 70 years of age and older. Hellquist et al published landmark data on the effectiveness of national service screening with mammography in more than 600,000 Swedish women 40 to 49 years of age. After an average follow-up of 16 years, a 26% mortality reduction was observed in women invited to undergo screening, and a 29% decrease in women who ultimately were screened.23 Similarly, the UK Age Trial, involving more than 160,000 women 39 to 41 years of age and with 10 years of follow-up, ascertained a 24% reduction in mortality in women who were screened, but these results did not reach statistical significance.24 Alternatively, the Canadian National Breast Screening Study (CNBSS) documented that in its group of nearly 50,000 women 40 to 49 years of age, no reduction in breast cancer mortality was associated with screening mammography.25 However, the CNBSS data have been largely discredited because of flawed (ie, nonblinded) randomization, as well as inferior mammographic technique and interpretation. Problems with randomization were also evidenced by the fact that there were significantly more women with node-positive advanced cancers in the mammography (experimental) group than in the control group. Evolving technology. In addition to study design limitations, the application of outmoded screening data to current guidelines is further confounded by the constant evolution of mammographic technology. Most of the randomized studies used in developing guidelines were conducted in the 1970s and 1980s. Thereafter, digital mammography, computeraided detection, and more recently digital breast tomosynthesis have been incorporated into routine practice, vastly improving performance compared with the mammography of decades past.26 This point is fundamentally important when the value of current screening mammography is being assessed but is rarely accounted for during the development of breast cancer screening guidelines. Nonmortality benefits. When the utility of mammography is considered, substantial emphasis is placed on decreasing the mortality rates of breast cancer. Conversely, scant focus is placed on the value of the ancillary benefits of screening—namely, less extensive (ie, breast-conserving)

18 THE CLINICAL ADVISOR • NOVEMBER 2017 • www.ClinicalAdvisor.com

Similar to most medical tests, mammography is imperfect, with an estimated sensitivity and specificity of 85% and 90%, respectively. surgery, decreased use of radiation therapy, and reduced use of chemotherapy as a result of detection at an earlier stage. Limitations

Mammography has proved to mitigate a woman’s risk for dying of breast cancer.2,3 However, several potential risks and limitations attributed to screening mammography are worth considering, including financial cost, overdiagnosis, radiation exposure, and quality-of-life issues. Financial cost. Financial cost is an essential issue in mammography. The aggregate cost in 2010 for population screening ranged from $2.6 billion to $10.1 billion, depending on screening frequency, age at screening, and participation constraints.27 Ultimately, these figures should be viewed with caution when cost per quality-adjusted life-year is evaluated because they are based on fluctuating estimates of mortality reduction that are widely variable.28 Overdiagnosis. Overdiagnosis of breast cancer is a consequence of screening and has recently become a very controversial topic. In the context of breast cancer, overdiagnosis refers to the potential for screening mammography to detect a cancer that would not otherwise have been identified or considered life-threatening, especially if the patient had not undergone mammography. For evaluating breast cancer overdiagnosis, the literature is inconclusive, primarily because overdiagnosis cannot be measured directly. Clearly, it is both unethical and untenable to conduct a study of breast cancer mortality by randomizing women with a diagnosis of breast cancer to a nontreatment

POLL POSITION

Which of the following statements do you most strongly agree with? n=766

■ All women aged 40 years and older should have an annual mammogram. ■ All women aged 45–54 years should have an annual mammogram. ■ Mammography screening in women younger than age 50 years should be done on an individual basis.

28.72% 62.01% 9.27%

For more polls, visit ClinicalAdvisor.com/Polls.

arm. Instead, rates of overdiagnosis are estimated by comparing breast cancer incidence rates in screened and unscreened populations, either contemporaneously or at different endpoints, while an attempt is made to account statistically for lead time bias and differences in breast cancer risk.29 In 2012, Puliti et al conducted a literature review of numerous studies that compared breast cancer incidence rates in screened and unscreened populations; unadjusted breast cancer estimates ranged from 0% to 54%.29 However, when these figures were statistically analyzed to account for breast cancer risk and/or lead time bias, the values ranged from 1% to 10%. Bleyer and Welch concluded that on the basis of SEER (Surveillance, Epidemiology, and End Results Program) data for breast cancer incidence, 31% of all breast cancers and more than half of screening-detected breast cancers were overdiagnosed.30 Critics argue that after the exclusion of intraductal cancers, or ductal carcinoma in situ (DCIS) and after adjustments for various “assumptions” about baseline incidence, the rate of overdiagnosis was actually insignificant. Anxiety. The psychosocial effects of screening mammography can be difficult to assess. For example, the anxiety associated with a false-negative or false-positive result can adversely affect a woman’s well-being and ongoing adherence to breast cancer screening guidelines.31 Alternatively, the psychosocial effect of foregoing breast cancer screening on a woman who later is found to have breast cancer is theoretically profound, with feelings of guilt and regret compounding the emotional and psychological effects related to the new diagnosis. Therefore, one must not diminish the benefits of reassurance provided by true-negative examination results, which are eight times more frequent than false-positive results.32 Like most medical tests, mammography is imperfect, with an estimated sensitivity and specificity of 85% and 90%, respectively.33 Moreover, the accuracy of mammography decreases with increasing breast density, which can both obscure some cancers and resemble signs of breast cancer, resulting in false-negative or false-positive results.34,35 Pain and discomfort. Pain and discomfort may be attributed to breast compression during mammography screening. Inconvenience and potential morbidity may be a further concern when a subsequent biopsy is indicated. Although these issues are seemingly insignificant within the context of mortality, they are nonetheless highly relevant to patients undergoing screening mammography.

www.ClinicalAdvisor.com • THE CLINICAL ADVISOR • NOVEMBER 2017 19

MAMMOGRAPHY: A REVIEW OF CURRENT GUIDELINES

A woman’s overall lifetime risk for developing breast cancer is approximately 12.3%, and nearly 40,000 US women die of breast cancer annually. Radiation oncogenesis. The risk for radiation oncogenesis, or the induction of cancer by mammographic radiation, is a noteworthy, albeit minimal, concern. According to a cohort study of 100,000 women undergoing mammography annually from age 40 to age 55 and then biennially until age 74, there was an estimated 0.086% risk for the development of an iatrogenic cancer, with a 0.011% risk for a corresponding cancer-related death.36 This is noteworthy within the context of a woman’s overall lifetime risk for the development of breast cancer, which is approximately 12.3%, and the fact that nearly 40,000 US women die of breast cancer annually.9 Mammography for women at increased risk

The debate over screening mammograms should pertain only to women with an average risk for developing breast cancer, not those who either warrant diagnostic mammography or are classified as being at high risk (eg, have a genetic predisposition to or family history of breast cancer). Approximately 5% to 10% of breast cancers can be linked to genetic mutations; this percentage increases nearly twofold in women with a first-degree relative in whom the malignancy has been diagnosed.37 Therefore, for women who are known carriers of a breast cancer mutation or who have a confirmed family history of breast cancer via breast imaging (eg, mammography, breast magnetic resonance imaging), surveillance mammography should be prescribed in accordance with their known risk factors. Summary of screening guidelines

Three US medical organizations recommend annual screening mammography beginning at the age of 40 years, including the American College of Radiology (ACR), the National Comprehensive Cancer Network (NCCN), and the Society of Breast Imaging (SBI); these organizations do not place an upper age limit on screening mammography. In a statement at the 2016 annual NCCN conference, Therese Bevers, MD, of the University of Texas MD Anderson Cancer Center, stated, “For NCCN, several factors were considered when recommending annual screening; there are fewer cancer deaths in the annually screened population than those undergoing biennial screening; and while there are fewer deaths from breast cancer averted for women in their 40s, life-years gained are significantly greater.”38 Debra Monticciolo, MD, FACR, chair of the ACR Commission on Breast Imaging, concurs with the NCCN recommendations and states, “The ACR

has strongly reaffirmed that mammography screening saves lives; the new ACR guidelines show that if a woman wants to reduce, as much as possible, her risk of dying of breast cancer, she will choose yearly mammography starting at age 40; moving away from annual screening of women ages 40 and older puts women’s lives at risk.”39 The SBI Screening Leadership Group (Drs. Bonnie Joe, Elissa Price, and Brett Parkinson) released a recommendation for yearly mammography beginning at age 40 because this “has the greatest chance of saving lives, preserves access, and acknowledges the right of each woman to choose.”40 The American Academy of Family Practice (AAFP), the American Cancer Society (ACS), and the US Preventive Services Task Force (USPSTF) do not recommend annual screening mammography beginning at age 40. The USPSTF emphasizes the adverse consequences of screening mammography, including overdiagnosis and overtreatment, false-positive results, the potential for psychological harm, and false-negative results.41 Further, the USPSTF uses the number of women needed to screen to save one life as its metric and concludes that by this metric, there is moderate evidence that the net benefit (of annual mammography) is small for women 40 to 49 years of age, there is moderate certainty that the net benefit is moderate for biennial screening mammography in women 50 to 74 years of age, and evidence is lacking and the balance of benefits and harms cannot be determined in women 75 years of age and older.41 Screening recommendations from the AAFP are similar to those of the USPSTF; in a recent summary of recommendations, it states that “the decision to start screening mammogram prior to the age of 50 is an individual one; if women place a higher value on the potential benefit than potential harms they may choose to begin biannual screening between the ages of 40 and 49.”42 Further, the AAFP posits that among women at average risk for breast cancer, most of the benefit of screening mammography is derived from biennial screening in women ages 50 to 74 years, and women ages 60 to 69 are the most likely to avoid breast cancer death because of screening mammography.42 The ACS released new mammography screening guidelines in October 2015; according to Chief Cancer Control Officer Dr. Richard Wender, a detailed review of evidence led the committee to change the guidelines after it had completed the difficult task of balancing the benefits and harms of screening mammography beginning at age 40.43 Dr. Wender states

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MAMMOGRAPHY: A REVIEW OF CURRENT GUIDELINES

TABLE 1. Recommendations of seven US medical organizations for mammography screening Organizations

Recommendations

American College of Radiology (ACR)

Women >40 years of age should have an annual mammogram.

National Comprehensive Cancer Network (NCCN) Society of Breast Imaging (SBI) US Preventive Services Task Force (USPSTF) American Academy of Family Physicians (AAFP)

• Women 40–49 years old: The decision to start screening mammography in women younger than 50 years should be an individual one. (Women who place a higher value on the potential benefits than on the potential harms may choose to begin screening every 2 years between the ages of 40 and 49 years.) • Women 50–74 years old: Screening mammography is recommended every 2 years for women ages 50 to 74 years. • Women >75 years: Current evidence is insufficient to assess the balance of benefits and harms of screening mammography in women age 75 years and older.

American Cancer Society (ACS)

• Women 40–44 years old should have the choice to start annual breast cancer screening with mammography if they wish to do so. • Women 45–54 years old should undergo mammography annually. • Women >55 years can switch to mammography every 2 years or can continue yearly screening. • Screening should continue as long as a woman is in good health and is expected to live 10 more years or longer.43

American Congress of Obstetricians and Gynecologists (ACOG)

Women past the age of 40 years who are at average risk should undergo screening mammography every 1–2 years in consultation with their obstetrician-gynecologist. The first screening should occur no later than age 50. Beyond the age of 75, the decision to continue screening should be made by each woman together with her provider and should be informed by the woman's health status and longevity.44

that “the new ACS guidelines make it clear that all women should begin screening by the age of 45 because that is when the benefits substantially outweigh the harms.”43 The American Congress of Obstetricians and Gynecologists (ACOG) released new breast cancer screening guidelines for women who are at average risk on June 22, 2017. Christopher M. Zahn, MD, ACOG Vice President of Practice Activities, stated that the new guidelines “consider each individual patient and her values, and because of the range of current mammography recommendations, the move has been made towards encouraging obstetrician-gynecologists to help their patients make personal screening choices from a range of reasonable options.”44 The new guidelines recommend that women past the age of 40 be offered screening mammography every 1 or 2 years, with the first screening mammogram occurring no later than age 50; in women beyond the age of 75, the decision to continue screening mammography should be made by each woman together with her provider and should be informed by the woman’s health status and longevity.44 As discussed, there is little consensus among the numerous medical organizations regarding mammography screening

guidelines. The recommendations of seven US medical organizations are summarized in Table 1. Conclusion

Scientific consensus regarding the expectations and limitations of mammography varies, and conflicting screening guidelines from medical organizations cause confusion for both patients and providers. Nevertheless, appropriate decisions regarding screening mammography should reflect an individual patient’s specific risk factors in conjunction with clinician judgment. In an evaluation of the vast amount of data and numerous considerations regarding the cost and effectiveness of breast cancer screening, it becomes clear that the issues are difficult to reconcile adequately. However, two essential truths remain central to the discussion: (1) breast cancer is still the second leading cause of cancer death in women, and (2) mammography reduces breast cancer–specific mortality. n Karen Herold, DNP, WHCNP-BC, FNP-BC, Bram Goldstein, PhD, and January Lopez, MD, are affiliated with the Hoag Memorial Hospital Presbyterian in Newport Beach, California.

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Continues on page 24

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28. National Institute for Health and Clinical Excellence. Measuring

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12. Parkin DM, Bray F, Ferlay J, Pisani P. Global cancer statistics, 2002.

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13. Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D. Global cancer

29. Puliti D, Duffy S, Miccinesi G, et al; EUROSCREEN Working Group.

statistics. CA Cancer J Clin. 2011;61:69-90.

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14. Jemal A, Center MM, Desantis C, Ward EM. Global patterns of cancer

literature review. J Med Screen. 2012;19(Suppl 1):42-56.

incidence and mortality rates and trends. Cancer Epidemiol Biomarkers Prev.

30. Bleyer A, Welch G. Effect of three decades of screening mammography

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on breast-cancer incidence. NEJM. 2012;367:1998-2005.

15. Althius MD, Dozier JD, Anderson WF, Devesa SS, Brinton LA. Global

31. O’Donnell S, Goldstein B, Dimatteo MR, Fox SA, John CR, Obrzut JE.

trends in breast cancer indicence and mortality 1973-1997. Int J Epidemiol.

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50-80 years of age the role of psychological distress. Women’s Health

16. Autier P, Boniol M, LaVecchia C, et al. Disparities in breast cancer

Issues. 2010;20:343-349.

24 THE CLINICAL ADVISOR • NOVEMBER 2017 • www.ClinicalAdvisor.com

32. Breast Cancer Surveillance Consortium. Benchmarks for sensitivity and specificity for 2,061,691 screening mammography examinations from 20042008 – based on BCSC data through 2009. http://breastscreening.cancer.gov/ statistics/benchmarks/screening/2009/table7.html (Accessed July 17, 2017). 33. National Cancer Institute. Breast cancer screening (PDQ)-health professional version. https://www.cancer.gov/types/breast/hp/breastscreening-pdq (Accessed October 2, 2017). 34. Kolb TM, Lichy J, Newhouse JH. Comparison of the performance of screening mammography, physical examination, and breast US and evaluation of factors that influence them: an analysis of 27,825 patient evaluations. Radiology. 2002;225:165-175. 35. Lehman CD, White E, Peacock S, Drucker MJ, Urban N. Effect of age and breast density on screening mammograms with false-positive findings. AJR Am J Roentgenol. 1999;173:1651-1655. 36. Yaffe MJ, Mainprize JG. Risk of radiation-induced breast cancer from

“We’re there already? But I’ve only watched half my movie!”

mammographic screening. Radiology. 2011;258:98-105. 37. National Cancer Institute. BRCA1 and BRCA2: cancer risk and genetic testing. http://www.cancer.gov/cancertopics/causes-prevention/genetics/ brca-fact-sheet (Accessed July 29, 2017). 38. National Comprehensive Cancer Network (NCC). For breast cancer, when to screen or not to screen? That is the question plaguing the minds of U.S. women—and their clinicians. https://www.nccn.org/patients/ foundation/newsdetail.aspx?NewsID=672 (Accessed July 29, 2017). recommend regular mammography starting at age 40. https://www.acr. org/ About-Us/Media-Center/Press-Releases/2015-Press-Releases/ 20151020-ACR-SBI-Recommend-Mammography-at-Age-40. Published October 20, 2015 (Accessed July 29, 2017). 40. Joe B, Price E, Parkinson B; Screening Leadership Group. Screening in the 40-49 age group. https://www.sbi-online.org/Portals/0/SBI%20 16-03%20SBI%202016%20Issue%201%20DigiNews%20Final.pdf (Accessed October 2, 2017).

“Look—we’ll whistle when it’s fifteen dollars an hour.”

41. U.S. Preventive Services Task Force. Final recommendation statement. Breast cancer screening. https://www.uspreventiveservicestaskforce. org/Page/Document/RecommendationStatementFinal/breast-cancer- screening1 (Accessed July 29, 2017). 42. American Academy of Family Physicians. Summary of recommendations for clinical preventive services. http://www.aafp.org/dam/AAFP/documents/ patient_care/clinical_recommendations/cps-recommendations.pdf. Published July 2017. Accessed July 29, 2017. 43. American Cancer Society. American Cancer Society releases new breast cancer guideline. https://www.cancer.org/latest-news/american-cancersociety-releases-new-breast-cancer-guidelines.html (Accessed July 29, 2017). 44. American Congress of Obstetricians and Gynecologists (ACOG). ACOG revises breast cancer screening guidance: Ob-Gyns promote shared decision making. https://www.acog.org/About-ACOG/News-Room/ News-Releases/2017/ACOG-Revises-Breast-Cancer-Screening-Guidance-ObGyns-Promote-Shared-Decision-Making (Accessed July 29, 2017).

“I’m not sure—could I hear their ringtones?”

www.ClinicalAdvisor.com • THE CLINICAL ADVISOR • NOVEMBER 2017 25

39. American College of Radiology (ACR). ACR and SBI continue to

FEATURE: JOY A. DUGAN, MPH, PA-C; TRACIE A. COTTON, RN, MSN, NP-C; TRACEY L. FOSTER, MSA/HAS;

KARA HAUPT, MS; GAYLE COLE, RN, MSN, CNM

Preventing suicide in US veterans Greater awareness and enhancing communication between patients and primary care providers can help lower the risk of suicide among US veterans.

ccording to the Department of Labor,1 veterans are men and women who have served on active duty in the United States Armed Forces and include members of the Reserve and National Guard who are called to federal active duty. Since September 11, 2001, more than one and a half million veterans have served in military operations (Table 1).2These deployments resulted in a spike in the incidence of mental health disorders, including depression and post-traumatic stress disorder (PTSD).3 Nearly half a million veterans have sought care for the treatment of PTSD, which a major risk factor for suicide, from the U.S. Department of Veterans Affairs (VA).4 According to the Centers for Disease Control and Prevention (CDC),5 suicide is the tenth leading cause of death among Americans, accounting for 41,000 deaths in 2013. More than half of all suicides are related to firearms.5 Men are four times more likely than women to complete a suicide attempt, 5 primarily because women are more likely to use less lethal means, such as drug overdose. Also, a racial disparity exists within completed veteran suicides; whites are more likely than AfricanAmericans, Hispanics, or Asians to complete a suicide attempt.6,7 According to the VA, 22 veterans and one active duty soldier committed suicide every day in 2012, or one every 65 minutes. Although 22 deaths per day has become a figure commonly cited to increase awareness of veteran suicide, the statistic has been debated. One study analyzing 26 THE CLINICAL ADVISOR • NOVEMBER 2017 • www.ClinicalAdvisor.com

the National Violent Death Reporting System (NVDRS) found a misclassification bias.8 The authors determined that although the system is valid for the surveillance of veteran suicide, younger persons (<25 years old) who committed suicide were misclassified on death certificates as veterans when they were in fact current military personnel.8 Furthermore, only approximately 20 states were included in this 2012 VA estimation of 22 veteran deaths per day. A 2015 article in the Washington Post argued that 22 deaths per day was likely an overestimate. Other data indicate that the numbers of suicide-related deaths may be closer to 18 to 22 per day.9 Regardless of the exact number of deaths, providers should carefully screen veterans for suicide risk. The suicide rate among deployed veterans is 41% higher than that in the general U.S. population.6 Suicidal ideation is four times more common in veterans with PTSD than in veterans without the disorder,10 a finding that must be kept in mind when veterans are assessed for suicide risk. Approximately 45% of veterans who committed suicide had contact with a primary care provider within 1 month of the act.11 Additionally, among the patients who had completed a suicide attempt, twice as many had been seen by primary care providers as by mental health providers.12 In one key study, only 24% of patients who completed suicide had been screened for suicidal intent, despite being seen by a primary care provider within 28 days of their death.13 Many veterans seek primary care outside the VA system,14 yet primary care providers are often unprepared to navigate the healthcare needs of military personnel and veterans. This is especially true of members of the Reserve and National Guard, who typically receive care outside the VA system. In this article, using the American Academy of Nursing initiative “Have you ever served in the military?” as a basis for patient evaluation,15 we offer tools to help guide conversations with military and veteran patients. Risk factors for veteran suicide are discussed to educate nurse practitioners and physician assistants about the unique healthcare needs of veterans and soldiers serving since September 11, 2001.

death in veteran suicides are firearms and alcohol. Veterans are 58% more likely than nonveterans to use a firearm to commit suicide.17 Other risk factors for veteran suicide are summarized in Table 2. These risk factors should guide the provider while he or she is taking the history and performing the physical examination. In addition to assessing patients for the risk factors listed in Table 2, the provider should consider asking for a detailed history, as outlined in Table 3. Sexual trauma, specifically military sexual trauma, is a risk factor for suicide.18 The term military sexual trauma (MST) is used by the VA to refer to any sexual assault or harassment Continues on page 30

TABLE 1. Post–9/11 military operations with dates2 Operation Enduring Freedom: military operations in Afghanistan from October 7, 2001, through December 28, 2014 Operation Freedom’s Sentinel: military operations in Afghanistan from January 1, 2015, to the present Operation Iraqi Freedom: military operations in Iraq from March 19, 2003, through August 31, 2010 Operation New Dawn: military operations in Iraq from September 1, 2010, through December 15, 2011

TABLE 2. Risk factors for veteran suicide Male gender7 Firearm access History of sexual trauma18,19 Age 18-29 years Substance abuse disorder Service in a unit with a history of suicide or suicide attempts30,31 Concurrent psychiatric illness Suicide attempt before joining military32 Homelessness

Risk factors

Gender differences in the rates of veteran suicides have been explored, and the rate of suicide in female veterans is markedly increased compared with the rate in their nonveteran peers.16 The female veteran suicide rate was found to be more than 300% higher than projected for the year 2000. This is a consequence, in part, of the greater number of female soldiers involved in combat, and of the significant number of female soldiers experiencing sexual abuse. The top overall causes of

Unemployment after separation from service Nonroutine discharge from military service33 Lower enlisted rank7 Recent demotion in rank7 Deployment within last 12 months34 Separation from service within past 3 years6

www.ClinicalAdvisor.com • THE CLINICAL ADVISOR • NOVEMBER 2017 27

PREVENTING SUICIDE IN US VETERANS

TABLE 3. Detailed history to assess a veteran's risk for suicide Review of symptoms 1. Strong emotions: feeling depressed, sudden emotional reactions, easily made angry or irritable, hopelessness, paranoia 2. Feelings of numbness, feeling "flat," or difficulty experiencing emotions, including happiness, joy 3. Trouble falling or staying asleep 4. Disturbing and/or recurring nightmares; memories, thoughts, or flashbacks of traumatic events 5. Difficulty with attention, concentration, and memory 6. Use of alcohol or drugs to cope with emotions 7. Difficulties in relationships: feeling disconnected from others, feelings of isolation, difficulty trusting others, difficulty with authority 8. Sexual difficulties: dyspareunia, sexual avoidance, erectile dysfunction 9. Chronic pain, headaches 10. Weight changes, appetite changes, or eating problems 11. Other related psychosomatic symptoms 12. Thoughts of hurting oneself or others 13. Feelings of shame, embarrassment 14. Anhedonia 15. Feelings of excessive guilt, trauma-related guilt, responsibility for what happened; feeling as if acts are unforgivable Social history 1. Military history: branch, rank, assignment to hostile or combative location(s), military occupation, having experienced enemy fire or witnessed casualties 2. Current employment 3. Relationship status 4. Access to firearms 5. Religion 6. Income 7. Exposure to noise, chemicals, gases, demolition of munitions, pesticides, depleted uranium, burn pits, or other hazardous substances 8. Whether anybody in the patient's unit ever committed suicide 9. Whether the patient would like to discuss other things about current or prior military service Past medical history 1. History of depression, anxiety, or other mental health issue before enlistment 2. Whether care is being sought at the VA 3. Whether the patient has a service-connected disability or condition 4. Whether the patient has been a victim of sexual assault or harassment while serving in the military 5. History of traumatic brain injury or concussion 6. History of leishmaniasis, malaria, rabies, typhoid fever, tuberculosis, or viral hepatitis during deployment 7. Prior thoughts of suicide or attempted suicide Family history 1. Depression, bipolar disorder, post-traumatic stress disorder (PTSD), or psychiatric illness 2. Suicide or suicide attempt

that occurs while a person is serving in the military.19 Table 4 further defines MST and sexual harassment. The VA reports that about 1 in 4 women and 1 in 100 men answer yes when screened by a VA provider for MST. MST is associated with an increased risk for mental disorder diagnoses, including PTSD, anxiety, and depression.18 Although rates of MST are higher among women, because of the potential stigma attached to reporting MST, it is estimated that many men underreport it. Veterans 18 to 29 years of age are at the highest risk for completing suicide.16 According to the National Institute of Mental Health,20 the young adult brain is still developing in people in their twenties. Specifically, the volume of gray matter, the outer layer of the cortex of the brain, is still fluctuating. Changes in this area of the brain reflect the maturation of the emotional centers of the brain. Although the intellectual centers of the brain are fully formed in young adults, fluctuations in the volume of gray matter can be associated with unstable emotions and impulsive behavior.20 Data indicate that a mental health or behavioral disorder has been diagnosed in more than 41% of veterans currently living in the United States.21 Common issues within the veteran population include mood disorders such as depression and manic-depressive disorders, as well as disorders associated with binge drinking and substance abuse, both of which increase the risk for suicide.21 As noted by Olenick and colleagues, “Military culture includes, but is not limited to, values, customs, traditions, philosophical principles, ethos, standards of behavior, standards of discipline, teamwork, loyalty, selfless duty, rank, identity, hierarchy, ceremony and etiquette, cohesion, order and procedure, codes of conduct, implicit patterns of communication, and obedience to command.”21 This type of life is very different from civilian life and needs to be treated as such to avoid complications resulting from separation from military service and issues related to complex multiple deployments. Veterans have identified these issues specifically as problem areas during adjustment to civilian life.21 Physical and environmental stressors that influence the mental health status of veterans and active duty personnel must also be considered: chronic pain, amputations, homelessness, hazardous exposures, and the difficulties of civilian reintegration. A key to suicide prevention is helping veterans reintegrate into civilian life by “providing veterans with training that builds on their military knowledge and skill, employment post-separation from service, homelessness prevention, and mental health programs that promote civilian transition.”21 Primary care clinicians must be aware of the risks and stressors

30 THE CLINICAL ADVISOR • NOVEMBER 2017 • www.ClinicalAdvisor.com

common to civilian re-entry, and they must be prepared to help patients who are veterans undergo this key transition with both compassion and appropriate referrals. Preventive factors

Studies show that communal and familial support is protective against veteran suicide.22,23 According to one hypothesis, an increased awareness of veteran suicide among a population decreases the risk for veteran suicide (the “yellow ribbon” effect).22 This effect is attributed to the change in the “public’s view of military service and of veterans, and, probably, the way it led to changes in veterans’ perceptions of the way America valued their history of service.”22 Other protective factors include self-reported feelings of control over one’s life, hardiness, and resilience.23 For Operation Iraqi Freedom and Enduring Freedom veterans, increased social support and an increased sense of worth within the community are protective factors against suicide completion.23 Clinical significance

There is a common misconception among primary care providers that veterans use the VA for their care. The current estimate is that only 40% of eligible new veterans use VA care.24 As of 2000, 45% of suicide victims had contact with a primary care clinician within 1 month of their suicide. Only a small portion of these patients had contact with a mental health practitioner. For most of them, primary care clinicians were the first and only line of defense against veteran suicide.11 Nonetheless, there is little available literature to help primary care clinicians describe the characteristics of veterans who have committed suicide after seeing a primary care provider.11 The American Association of Nurses in 2013 began a campaign entitled “Have you ever served in the military?”15 This simple question can initiate what may be a difficult conversation for both clinician and patient. A review of symptoms and questions to ask during the social, medical, and family history that can help identify symptoms and risk factors for veteran suicide are outlined in Table 3. Clinical resources

Suicide Prevention Mobile App. This mobile phone app, hosted by the Substance Abuse and Mental Health Services Administration,25 is a training tool to reduce veteran suicide. It is free for primary care providers. A five-step approach is used for suicide risk assessment, conversation starters, training and resources, behavioral and treatment locator services, and case studies.

TABLE 4. Department of Veterans Affairs’ definition of military sexual trauma and sexual harassment19 • Military sexual trauma (MST) is defined by the Department of Veterans Affairs (VA) as “psychological trauma, which in the judgment of a VA mental health professional, resulted from a physical assault of a sexual nature, battery of a sexual nature, or sexual harassment which occurred while the Veteran was serving on active duty, active duty for training, or inactive duty training.” (Title 38 U.S. Code § 1720D, Counseling and treatment for sexual trauma) • Sexual harassment is defined as “repeated, unsolicited verbal or physical contact of a sexual nature which is threatening in character.” [Editor’s note: For more information about MST, see Advisor Forum, p. 46.]

The Durkeim Project. This research project was launched in 2013 by Patterns and Predictions and The Veterans Education and Research Association of Northern New England, with support from Facebook. It monitors suicidal behaviors in veterans and active duty military personnel on social media (Twitter, Facebook, LinkedIn) based on trigger words and phrases.26 This is a voluntary, opt-in project that monitors a database of enrollees to help prevent suicide among veterans who are in crisis. This goal of this initiative is to provide clinicians with real-time assessments and the opportunity to intervene. Veterans Crisis Line. Many suicide crisis lines are available throughout the country. The VA hosts the Veterans Crisis Line. Veterans can call 1-800-273-8255 or text to 838255 for free, confidential assistance. Vet Center Program. Community-based counseling centers provide mental health and readjustment counseling to both veterans and active duty service members and their families (www.vetcenter.va.gov). Veterans Choice Program. The Veterans Choice Program (VCP) was instituted by the VA to increase care, coverage, and access for veterans and to decrease wait times for veterans needing care.27 Veterans must qualify for the program, but once approved, they can receive care within their community rather than wait for an appointment through traditional VA channels. To qualify for the VCP, a veteran must live a minimum of 40 miles away from the closest traditional VA center or have to wait 30 days or longer for an appointment. Providers who are interested in participating in the program can obtain more information on the VA website. The VCP can also improve veteran access to mental health services because patients requiring care can be seen by community mental health providers rather than be placed on a waiting list for an appointment with a VA mental health provider.

www.ClinicalAdvisor.com • THE CLINICAL ADVISOR • NOVEMBER 2017 31

PREVENTING SUICIDE IN US VETERANS

Provider education resources. Two useful websites for obtaining further clinical education include those of the Uniformed Services University and the VA.28,29 The USU website has four 2-hour modules for civilian providers that give an overview of military culture, rank, treatment options, and resources. These modules can serve as a primer for providers who require an overview of military service and culture. On the VA website, a Community Provider Toolkit offers online training for providers and patient education handouts. The VA website also includes information about military culture and veteran-specific health care.

6. Kemp J, Bossarte R. Suicide data report, 2012. Department of Veterans Affairs, Mental Health Services, Suicide Prevention Program. http://www. nytimes.com/interactive/2013/02/02/us/suicide-statistics-from-thedepartment-of-defense.html. Published 2013. Accessed October 8, 2017. 7. Schoenbaum M, Kessler RC, Gilman SE, et al. Predictors of suicide and accident death in the Army Study to Assess Risk and Resilience in Servicemembers (Army STARRS): results from the Army Study to Assess Risk and Resilience in Servicemembers (Army STARRS). JAMA Psychiatry. 2014;71(5):493-503. doi:10.1001/jamapsychiatry.2013.4417 8. Huguet N, Kaplan MS, McFarland BH. The effects of misclassification biases on veteran suicide rate estimates. Am J Public Health. 2014;104:151-155. 9. Lee MYH. The missing context behind the widely cited statistic that

Conclusion

there are 22 veteran suicides a day. Washington Post. February 4, 2015.

Veteran suicide remains a serious public health epidemic that can have lasting harmful effects on individuals, families, and communities. With this article, we hope to increase primary care provider awareness of veteran suicide risk by enhancing communication between patients and providers. Resources such as the Substance Abuse and Mental Health Services Administration free mobile app and the American Nursing Association “Have you ever served in the military?” program are excellent platforms for beginning discussions with all patients. After asking questions about military service, providers will likely be surprised by the number of current and former military personnel under their care.

https://www.washingtonpost.com/news/fact-checker/wp/2015/02/04/themissing-context-behind-a-widely-cited-statistic-that-there-are-22-veteransuicides-a-day/?utm_term=.ce09c5d6f927. Accessed October 8, 2017. 10. Jakupcak M, Cook J, Imel Z, Fontana A, Rosenheck R, McFall M. Posttraumatic stress disorder as a risk factor for suicidal ideation in Iraq and Afghanistan war Veterans. J Trauma Stress. 2009;22:303-306. doi: 10.1002/jts.20423 11. Dobscha S, Denneson L, Kovacs A, et al. Correlates of suicide among veterans treated in primary care: case-control study of a nationally representative sample. J Gen Intern Med. 2014;29(Suppl 4):S853-S860. doi: 10.1007/s11606-014-3028-1 12. McDowell AK, Lineberry TW, Bostwick JM. Practical suicide-risk management for the busy primary care physician. Mayo Clin Proc. 2011;86:792-

Joy A. Dugan, MPH, PA-C, is an adjunct assistant professor, Touro University California Joint MSPAS/MPH Program, in Vallejo, Calif., and Gayle Cole, RN, MSN, CNM, is an associate professor, South College, in Knoxville, Tenn.

800. doi: 10.4065/mcp.2011.0076 13. Hepner KA, Rowe M, Rost K, et al. The effect of adherence to practice guidelines on depression outcomes. Ann Intern Med. 2007;147:320-329. doi:10.7326/0003-4819-147-5-200709040-00007 14. Bagalman E. The number of veterans that use VA health care services:

References

a fact sheet. Congressional Research Service. https://www.fas.org/sgp/crs/

1. Bureau of Labor Statistics, U.S. Department of Labor. Employment

misc/R43579.pdf. Published June 3, 2014. Accessed October 8, 2017.

situation of veterans—2011. https:www.bls.gov/news.release/archives/

15. Have you ever served in the military? American Academy of Nursing.

vet_03202012.pdf. Published March 20, 2012. Accessed October 8, 2017.

http://www.haveyoueverserved.com. Accessed October 8, 2017.

2. Torreon BS. U.S. periods of war and dates of recent conflicts.

16. Hoffmire CA, Kemp JE, Bossarte RM. Changes in suicide mortality

Congressional Research Service. https://www.fas.org/sgp/crs/natsec/

for veterans and nonveterans by gender and history of VHA service use

RS21405.pdf. Published September 29, 2016. Accessed October 8, 2017.

2000-2010. Psychiatr Serv. 2015;66:959-965. http://media.thedenverchannel.

3. Department of Veterans Affairs. Gulf War era veterans report: pre-9/11.

com/document/2015/06/09/Veterans_Suicide_Study_2015_19545583_

https://www.va.gov/vetdata/docs/specialreports/gw_pre911_report.pdf.

ver1.0.pdf. Accessed October 8, 2017.

Published February 2011. Accessed October 8, 2017.

17. Kaplan MS, Huguet N, McFarland BH, Newsom JT. Suicide among male

4. Health care use by Gulf War & OEF/OIF/OND veterans. October 1,

veterans: a prospective population-based study. J Epidemiol Community

2001 – September 30, 2013. U.S. Department of Veterans Affairs. http://

Health. 2007;61:619-624. doi: 10.1136/jech.2006.054366

www.publichealth.va.gov/epidemiology/reports/health-care-use-gulfwar-

18. Kimerling R, Makin-Byrd K, Louzon S, Ignacio RV, McCarthy JF. Military

oefoifond/index.asp. Accessed October 8, 2017.

sexual trauma and suicide mortality. Am J Prev Med. 2015;100:1409-1412.

5. Suicide and self-inflicted injury. Centers for Disease Control and

doi: 10.1016/j.amepre.2015.10.019

Prevention. http://www.cdc.gov/nchs/fastats/suicide.htm. Updated

19. VA services for military sexual trauma. U.S. Department of Veterans Affairs.

March 17, 2017. Accessed October 8, 2017.

http://www.mentalhealth.va.gov/msthome.asp. Accessed October 8, 2017.

32 THE CLINICAL ADVISOR • NOVEMBER 2017 • www.ClinicalAdvisor.com

20. National Institute of Mental Health. The teen brain: still under construction. https://infocenter.nimh.nih.gov/pubstatic/NIH%2011-4929/ NIH%2011-4929.pdf. Published 2011. Accessed October 8, 2017. 21. Olenick M, Flowers M, Diaz V. US veterans and their unique issues: enhancing health care professional awareness. Adv Med Educ Pract. 2015;6:635-639. 22. Katz I. Lessons learned from mental health enhancement and suicide prevention activities in the Veterans Health Administration. Am J Public Health. 2012;102(Suppl 1):S14-S16. 23. Pietrzak R, Goldstein M, Malley J, Rivers A, Johnson D, Southwick S. Risk and protective factors associated with suicidal ideation in veterans of Operation Enduring Freedom and Iraqi Freedom. J Affect Disord. 2010;123:102-107. 24. Hinojosa R, Hinojosa M, Nelson K, Nelson D. Veteran family reintegration, primary care needs, and the benefit of the patient-centered medical home model. J Am Board Fam Med. 2010;23(6):770-774. 25. Get connected with SAMHSA’s free mobile apps. Substance Abuse and Mental Health Services Administration. http://www.store.samhsa.gov/ apps. Accessed October 8, 2017. 26. “The Durkeim Project” will analyze opt-in data from veterans’ social media and mobile content – seeking real-time predictive analytics for suicide risk. Durkeim Project. http://www.durkheimproject.org/news/durkheim-projectwill-analyze-opt-in-data/. Published July 2, 2013. Accessed October 8, 2017. 27. Veterans Choice Program. U.S. Department of Veteran Affairs. https:// 28. Military culture course modules. Uniformed Services University, Center for Deployment Psychology. http://deploymentpsych.org/militaryculture-course-modules. Accessed October 8, 2017. 29. Military culture resources. U.S. Department of Veterans Affairs. Community Provider Toolkit. https://www.mentalhealth.va.gov/communityproviders/military_resources.asp. Accessed October 8, 2017.

“I paint what I smell.”

30. Ursano RJ, Kessler RC, Naifeh JA, et al. Risk of suicide attempt among soldiers in Army units with a history of suicide attempts. JAMA Psychiatry. 2017;74:924-931. doi: 10.1001/jamapsychiatry.2017.1925 31. Bryan CJ, Cerel J, Bryan AO. Exposure to suicide is associated with increased risk for suicidal thoughts and behaviors among National Guard military personnel. Compr Psychiatry. 2017;77:12-19. doi.10.1016/j.comppsych.2017.05.006 32. Bryan CJ, Bryan AO, Ray-Sannerud BN, Etienne N, Morrow CD. Suicide attempts before joining the military increase risk for suicide attempts and severity of suicidal ideation among military personnel and veterans. Compr Psychiatry. 2014;55:534-541. doi: 10.1016/j.comppsych.2013.10.006 33. Brignone E, Fargo JD, Blais RK, Carter ME, Samore MH, Gundlapalli AV. Non-routine discharge from military service: mental illness, substance use disorders, and suicidality. Am J Prev Med. 2017;52:557-565. doi: 10.1016/j. amepre.2016.11.015 34. Kim HM, Levine DS, Pfeiffer PN, et al. Postdeployment suicide risk increases over a 6-month period: predictors of increased risk among Midwestern Army National Guard soldiers. Suicide Life Threat Behav. 2017;47:421-435. doi: 10.1111/sltb.12303

“Use your inside scream.”

www.ClinicalAdvisor.com • THE CLINICAL ADVISOR • NOVEMBER 2017 33

www.va.gov/opa/choiceact/index.asp. Accessed October 8, 2017.

CME FEATURED COURSE

n EDUCATIONAL OBJECTIVES At the conclusion of this activity, participants should be better able to: • Describe the health risks associated with overweight and obesity, including prediabetes • Identify patients who meet the criteria for a diagnosis of prediabetes • Advise patients on the advantages and limitations of various dietary interventions for metabolic health and weight control • Use shared decision-making to help overweight/obese patients adopt and maintain healthy behaviors to prevent the development and/or progression of diabetes n COMPLETE THE POSTTEST: Page 45

Release Date: April 5, 2017 Expiration Date: November 30, 2018 Estimated Time to Complete: 1 hour 15 minutes Accredited Provider: This activity is provided by Haymarket Medical Education. Commercial Supporter: This activity is supported by an educational grant from Atkins. Program Description: The prevalence of prediabetes and diabetes among US adolescents aged 12-19 years more than doubled during the first decade of this century, from 9% to 23%. This serious, progressive disease is a particular concern among Hispanic/ Latino individuals and other minority groups, who have an even higher prevalence than the white population. For many people, the diagnosis of type 2 diabetes mellitus (T2DM) is delayed until symptoms and, often, irreversible complications occur. Thus, prevention—or at least delay—in the development of this disease is an urgent public health concern. Effective treatment often must address a host of clinical, cultural, and psychological issues that go beyond diet and exercise. This interactive Case Clinic illustrates how lifestyle changes centered on a low-carbohydrate weight-loss diet can prevent the progression of prediabetes to overt T2DM.

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 1.25 AMA PRA Category 1 Credits TM. Physicians should claim only the credit commensurate with the extent of their participation in the activity. Accreditation Statement: The following activity has been approved by the ACCME, whose approval is recognized by the Commission on Dietetic Registration and, as such, RDs/DTRs will be able to receive 1.25 CPEU. 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.

Intended Audience: Primary care providers including family physicians, internists, OB/GYNs, endocrinologists, cardiologists, nurse practitioners (NPs), physician assistants (PAs), nurses, and dieticians

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

Conflict of Interest 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 to ensure independence, objectivity, balance, and scientific rigor in all its educational activities.

Instructions: There are no fees for participating in and receiving CME/CE credit for this activity. During the period April 5, 2017 through November 30, 2018, participants must: 1) read the learning objectives and faculty disclosures; 2) complete the pre-assessment test; 3) study the educational activity; 4) respond to the polling questions; and 5) complete the post-test and submit it online.

Faculty Holly R. Wyatt, MD University of Colorado Anschutz Health and Wellness Center Associate Professor, CU School of Medicine Division of Endocrinology, Metabolism and Diabetes Aurora, CO

A statement of credit will be issued only upon receipt of the above elements and a posttest score of 70% or higher. All components must be completed and submitted online at ClinicalAdvisor.com/Nov17feature.

Dr. Wyatt receives royalty fees from UpToDate. She also does contracted research for DuPont, GI Dynamic, National Cattlemans Association and Novo Nordisk. Accredited Provider Disclosure: Haymarket Medical Education staff involved in the planning and content review of this activity have no relevant financial relationships to disclose.

If you have any questions relating to the CME certification of this activity, please contact HME at cmequestions@haymarketmedical.com. If you have any questions relating to your certificate or other issues with this activity, please contact myCME.Support@haymarketmedical.com. Provided by

CME

FEATURED COURSE: HOLLY R. WYATT, MD

A 19-year-old Latina college student with prediabetes This case illustrates how lifestyle changes centered on a low-carbohydrate diet can prevent the progression of prediabetes to overt T2DM. ■ PATIENT CASE

Susannah S., a Latina 19-year-old student and emergency room admitting clerk, presents to her primary care clinician for a well-woman checkup and physical required by her new job. Susannah is 5’5” and weighs 166 lbs. Her waist circumference is 38”. She has gained 8 lbs over the last 3 to 4 years. Susannah reports that her eating habits are “okay” and like those of her friends and family. She doesn’t exercise much: She drives to school and work, has a sedentary job, spends time watching movies and on social media, and makes jewelry in her spare time when she isn’t studying. She goes to bed late, but has to be up early for school. Susannah is not particularly worried about her weight and says that she is generally healthy. She eats fast food often, loves pizza and French fries, and often grabs a taco or fried chicken for lunch at school; at work, she drinks lots of caffeinated, high-sugar energy drinks. Susannah expects that her checkup will be quick and will go well. POLLING QUESTION

What would be your likely first steps with this patient? (Select as many as apply.)

For most patients with prediabetes, a low-carbohydrate diet is recommended.

a. Calculate her body mass index (BMI) b. Do a laboratory workup, including lipid panel and glucose measurement c. Put her on a strict calorie-controlled diet d. Recommend a regular exercise regimen and dietary changes

www.ClinicalAdvisor.com • THE CLINICAL ADVISOR • NOVEMBER 2017 35

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FIGURE 1. Increasing prevalence of T2DM with increasing carbohydrate intake, 1960-1996 Prevalence of diabetes (persons/1000) 0 5 10 15 20 25 30 35 60 62 64

Carbohydrate intake

Prevalence of T2DM

68 70

Year (1960 - 1996)

72 74 76 78 80 82 84 86 88 90 92 94 96 300 325 350 375 400 425 450 475 500 525

Carbohydrate intake (g/d) Source: Gross LS, Li L, Ford ES, Liu S. Increased consumption of refined carbohydrates and the epidemic of type 2 diabetes in the United States: an ecologic assessment. Am J Clin Nutr. 2004;79:774–779.

The “diabesity” epidemic

Type 2 diabetes mellitus (T2DM) is a growing problem worldwide, with more than 19 million people affected in the US alone.1 Hispanic/Latino individuals and other minority groups have an even higher prevalence than the white population.2 T2DM is a serious, progressive disease, with microvascular and macrovascular consequences, and while it may be treated it cannot yet be cured. For many people with T2DM, the diagnosis is delayed until there are complications and symptoms.3 A current goal is the prevention, or at least the delay, of the development of this disease. It has long been recognized that excess weight is associated with the development of T2DM4 and that obesity is one of the main etiological factors. The current epidemic of the disease is believed to be largely attributable to the increased incidence of obesity.5 Epidemiological studies have shown that the risk of developing T2DM increases exponentially with a body mass index (BMI) >28 kg/m 2.6

The pathophysiology connecting the two can be largely attributed to insulin resistance and insulin deficiency.7 It also has been shown that the epidemic rise of T2DM in the US is accompanied by a concomitant increase in consumption of refined carbohydrates (Figure 1), which also correlates with the increase in obesity.8 The underlying principle of carbohydrate restriction and data on the effects of a low-carbohydrate diet in T2DM suggest that carbohydrate restriction may play an important nonpharmacologic role in reversing the current epidemic of “diabesity.” In the US, close to 40% of adult men and 30% of adult women fall into the overweight category, with a BMI of 25 to less than 30.9 Obesity is defined as a BMI equal to or greater than 30. Everyone who becomes obese was first overweight, and the change can go unnoticed. Most people gain weight very gradually over time, with the average gain being about 0.8 lb per year. But these slow and modest increases in weight do increase the risk of serious comorbidities.10-15 This makes it particularly important for

36 THE CLINICAL ADVISOR • NOVEMBER 2017 • www.ClinicalAdvisor.com

20 18 16 14 12 10 8 6 4 2 0

16.1 13.1

Percentage (%)

FIGURE 2. Prevalence of prediabetes in children/adolescents in the United States, 2005-2006

3.4

Impaired Impaired Glucose Fasting Tolerance Glucose (IGT) (IFG)

20 18 16 14 12 10 8 6 4 2 0

IGT and/or IFG

16.9

17.2

10.3

Non- Mexican- Non Hispanic American Hispanic Whites Blacks

Source: Li C, Ford ES, Zhao G, Mokdad AH. Prevalence of prediabetes and its association with clustering of cardiometabolic risk factors and hyperinsulinemia among U.S. adolescents: National Health and Nutrition Examination Survey 2005-2006. Diabetes Care. 2009;32:342-347.

clinicians to help patients to consider the current and future implications of being overweight. Can patients be both fat and fit? One challenge in communicating with patients about the risks of overweight and obesity is that they may have received conflicting information about a paradoxical relationship between weight and mortality. The evidence is strong for the association of obesity and premature mortality, all-cause mortality, and development of multiple comorbidities, including hypertension, dyslipidemia, and T2DM. Nevertheless, there are exceptions to the paradigm of “more fat equals more metabolic disease,” raising the question of whether it is possible to be both obese and metabolically healthy.16 In reality, despite being metabolically healthy, these individuals have an increased mortality risk over time.17 There also is evidence that healthy obese adults tend to become unhealthy in the long-term.18 Further evidence that “healthy obesity” is more myth than reality comes from recent observations that white fat tissue samples from obese individuals classified as either metabolically healthy or unhealthy actually show nearly identical, abnormal changes in gene expression in response to insulin stimulation.19

86 million individuals, have prediabetes—and only 11% of individuals were aware of this condition.20,21 In adolescents aged 12 to 19 years, the prevalence of prediabetes and diabetes increased from 9% to 23% from 1999 to 2008.22 The prevalence of impaired fasting glucose (IFG) and impaired glucose tolerance (IGT) among adolescents aged 12 to 19 years in the US in 2005 and 2006, using American Diabetes Association (ADA) criteria, are shown in Figure 2.23 Given the potential consequences, it is essential that clinicians recognize prediabetes and identify interventions to modify those risk factors to prevent disease progression (see Box). Prediabetes itself has long-term consequences that include hypertension, cancer, and Alzheimer’s disease (AD). The risk for developing cancer, specifically of the stomach/colorectum, liver, pancreas, breast, and endometrium (all P <.05) is increased by 15% with prediabetes.24 Insulin resistance, a causal factor in both prediabetes and T2DM, increases the risk of developing AD in association with reductions in the cerebral glucose metabolic rate.25

S Screen A Assess and advise

Recognition and diagnosis of prediabetes

Prediabetes is a condition whereby an individual’s glycemic parameters are higher than normal, but not yet high enough for a diagnosis of diabetes. People with prediabetes are at very high risk of developing T2DM. Recent data show that 37% of US adults aged 20 years or older, or approximately

F Follow up E Evaluate progress

A useful acronym for working with patients suspected of having prediabetes is SAFE: Screen, Assess and advise, Follow up, Evaluate progress. There is an association between social and environmental factors and the development of both obesity and T2DM. A better understanding is needed of the variables that lead to obesity, prediabetes, and T2DM so that they may be modified and to help identify individuals who are at risk.

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It is only through the diagnosis of prediabetes and subsequent interventions that clinicians may prevent or at least delay diabetes and its associated complications. Importance of screening for prediabetes

It is only through the diagnosis of prediabetes and subsequent interventions very early in its development that clinicians can prevent or at least delay the development of diabetes and its associated complications, thus decreasing the burden on the individual and on society. Without intervention, about 25% of people with nondiabetic hyperglycemia or prediabetes progress to full diabetes within 3 to 4 years.26 People with prediabetes, and those with a BMI above the normal range, are at high risk for developing diabetes and cardiovascular disease (CVD).27,28 Because there are no specific symptoms of prediabetes, people are generally not aware that they have this condition.20 Primary care clinicians need to be alert to the signs pointing toward prediabetes and be prepared to offer suggestions for lifestyle changes that can reverse this condition, by returning blood glucose levels to the normal range before deterioration of beta cells occurs. Clinicians need to be proactive in an effort to improve outcomes for their patients. Part of the screening process involves determining who might have risk factors for prediabetes and T2DM. One step is to ask patients to take the ADA Type 2 Diabetes Risk Test, available online at www. diabetes.org/risktest; a printable PDF (in both English and Spanish) is also available for download. This self-assessment tool allows patients to quickly identify whether they are at risk for prediabetes and encourages them to follow up with their physician for further assessment.29

The ADA recommends screening all adults with risk factors, including those who are overweight (BMI ≥25 kg/ m 2) or obese (BMI ≥30 kg/m 2), although the at-risk BMI may be lower in some ethnic groups (eg, ≥23 kg/m 2 in Asian Americans).28 They also recommend that all adults over the age of 45 be tested routinely, even in the absence of other risk factors. If the results of testing are normal, the screening should be repeated at ≥3-year intervals, or more frequently depending on initial test results and individual patient risk factors. Testing should be repeated at least yearly in patients with prediabetes.26,30 Although increased waist circumference has been identified as a risk factor for cardiometabolic disease, the ADA does not include it in its screening recommendations. Diagnostic criteria for prediabetes

The 2017 ADA Standards of Care recommend that all overweight and obese patients be screened for prediabetes and diabetes using IFG, IGT as measured by an oral glucose tolerance test (OGTT), and/or an elevated hemoglobin A1c (HbA1c).28 Prediabetes is defined as an HbA1c of 5.7% to 6.4% and/or a fasting blood glucose of 100 to 125 mg/dL and/or an OGTT 2-hour blood glucose of 140 mg/dL to 199 mg/dL (Figure 3).26 While these plasma glucose levels do not meet the criteria for diabetes, they are too high to be considered normal. They should not be viewed as clinical entities by themselves, however, but rather as risk factors for diabetes and CVD.

FIGURE 3. Cutpoints for diagnosis of prediabetes and diabetes Fasting Plasma Glucose Diabetes Mellitus

2-hour Plasma Glucose on OGTT

Hemoglobin A1C

Diabetes Mellitus

126 mg/dL

Prediabetes

200 mg/dL

Prediabetes 100 mg/dL

Normal

6.5%

Prediabetes 140 mg/dL

Normal

5.7%

Normal

Source: American Diabetes Association. Diagnosis and classification of diabetes mellitus. Diabetes Care. 2014;37(suppl 1):S81-S90.

Any abnormality calls for repeat testing and confirmation on a separate day. The diagnosis of diabetes can also be made based on unequivocal symptoms and a random glucose >200 mg/dL.

38 THE CLINICAL ADVISOR • NOVEMBER 2017 • www.ClinicalAdvisor.com

Weight loss is potentially important for overweight persons with prediabetes, as it may delay or prevent progression to type 2 diabetes mellitus. Unfortunately, the 3 tests that can be used to determine prediabetes are not always well correlated.31,32 Of the 3, the OGTT 2-hour test is felt to be the most reliable for diagnosing T2DM. Nevertheless, there are some advantages to the HbA1c test because patients do not need to fast or to drink a sweet liquid and wait 2 hours, and there is less day-to-day variability. However, the HbA1c test is less sensitive and more expensive, and it is an indirect measure of the average of blood glucose levels over time. Whatever method is employed, blood tests need to be performed twice to confirm the presence of prediabetes; in addition, care must be taken to assure that samples are stored in appropriate conditions before testing. Currently, point-of-service testing for HbA1c is not completely reliable, although it is predicted that these tests will improve over time, making the HbA1c test more convenient. ■ PATIENT CASE—Initial laboratory findings

Based on her height (5’5”) and weight (166 lb), Susannah’s BMI is 27.6, clearly putting her at increased risk for cardiometabolic disorders. Initial screening yielded the following results: • HbA1c: 5.9% • Blood pressure: 129/85 mm Hg • Lipid profile ——Triglycerides (TG): 230 mg/dL ——Low-density lipoprotein (LDL): 125 mg/dL ——Very low-density lipoprotein (VLDL): 45 mg/dL ——High-density lipoprotein (HDL): 42 mg/dL POLLING QUESTION

What would be your recommendations for this patient at this point? (Select as many as apply.) a. b. c. d.

Return for additional testing to confirm a diagnosis Counsel her on lifestyle changes, including a low-carbohydrate diet and increase in physical activity Advise her to initiate a strict calorie- and fat-reduction diet Initiate metformin therapy

intentional weight loss sustained over time may be associated with reduced mortality.36,37 Similarly, several large randomized controlled trials (RCTs) have shown that weight loss is also a potentially important management strategy for overweight persons with prediabetes, as it may delay or prevent the progression to clinically defined type 2 diabetes.38 The ADA recommends that clinicians advise individuals at high risk for developing diabetes about the benefits of modest weight loss and participating in regular physical activity.28 A systematic review of studies found that weight loss of as little as 3% over 1- and 2-year periods that was sustained for up to 10 years showed improvements in cardiometabolic risk factors, including blood glucose, blood pressure, and triglycerides.39 The Diabetes Prevention Program Outcomes Study (DPPOS) assessed long-term diabetes risk reduction in a multiethnic cohort that closely resembled the US population with prediabetes. In an analysis of participants who could achieve normal glucose regulation vs those with persistent prediabetes, they found that early intervention in people with prediabetes reduced the risk of developing T2DM by 25% to 72%.40 Lifestyle counseling A variety of factors, including poor diet, insufficient exercise, and smoking influence the risk for the development of cardiometabolic disease (Table 1). However, it should TABLE 1. Modifiable risk factors of diabetes/ prediabetes for cardiovascular disease Nonmodifiable

Modifiable

Age

Physical inactivity

Race/ethnicity

Overweight/obesity

Gender

Hypertension

Family history

Smoking Abnormal lipid metabolism

Treatment recommendations

Weight loss and weight control are key goals for persons with prediabetes and those with diabetes. Weight loss improves insulin sensitivity and glycemic control, lipid profiles, blood pressure, mental health, and quality of life.28,33-35 Moderate

High plasma glucose levels Source: American Diabetes Association. Standards of medical care in diabetes – 2017. Diabetes Care. 2017;40(suppl 1):S1-S135.

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FEATURED COURSE

Prominent diabetes prevention studies have shown lifestyle changes to be beneficial in preventing or delaying diabetes, with effects sustained for up to 20 years. be stressed that diet is a predominant risk factor for poor health in general, surpassing tobacco smoking and high blood pressure.41,42 Patients should also be advised about the importance of good sleep habits (see Box: A good night’s sleep). Lifestyle changes allow patients to alter modifiable risk factors for prediabetes and diabetes. Patients who are asymptomatic but whose metabolic measurements indicate prediabetes may not understand that there is a progression

A good night’s sleep Sleep disorders are an important factor in a wide range of health conditions, including obesity and T2DM.1 Poor sleep quality and duration (both short and long) have been associated with higher A1C levels in individuals with T2DM.2 The relationship appears to be bidirectional: that is, diabetes may cause sleep disorders, while sleep disorders may also complicate the control of diabetes. As a consequence, the ADA Standards of Care recommend the assessment of sleep pattern and duration as part of the comprehensive medical evaluation.3 There is also a strong link between sleep and obesity. The relationship between short sleep duration and weight gain has been illustrated in numerous cross-sectional and longitudinal studies of both adults and children.4-7 There is also a well-established association of obesity and obstructive sleep apnea.8 Although the pathophysiologic mechanisms have not been fully defined, disturbances in sleep quality and architecture seem to alter energy balance parameters and induce weight gain.9 By the same token, weight loss may improve sleep—and improved sleep may promote weight loss. 1. Institute of Medicine. Sleep Disorder s and Sleep Deprivation: An Unmet Public Health Problem. Washington, DC: The National Academies Press; 2006. https://www. iom.edu/~/media/Files/Report%20Files/2006/Sleep-Disorders-and-Sleep-Deprivation-AnUnmet-Public-Health-Problem/Sleepforweb.pdf. Accessed March 8, 2017. 2. Cappuccio FP, D’Elia L, Strazzullo P, Miller MA. Quantity and quality of sleep and incidence of type 2 diabetes: A systematic review and meta-analysis. Diabetes Care. 2010;33:414-420. 3. American Diabetes Association. Standards of medical care in diabetes – 2017. Diabetes Care. 2017;40(S1):S1-S135. 4. Chen X, Beydoun MA, Wang Y. Is sleep duration associated with childhood obesity? A systematic review and meta-analysis. Obesity (Silver Spring). 2008;16: 265-274. 5. Keith SW, Redden DT, Katzmarzyk PT, et al. Putative contributors to the secular increase in obesity: exploring the roads less traveled. Int J Obes (Lond). 2006;30: 1585-1594. 6. Liu J, Zhang A, Li L. Sleep duration and overweight/obesity in children: review and implications for pediatric nursing. J Spec Pediatr Nurs. 2012;17:193-204. 7. Hasler G, Buysse DJ, Klaghofer R, et al. The association between short sleep duration and obesity in young adults: a 13-year prospective study. Sleep. 2004;27: 661-666. 8. Jensen MD, Ryan DH, Apovian CM, et al. 2013 AHA/ACC/TOS guideline for the management of overweight and obesity in adults: a report of the American College of Cardiology/ American Heart Association Task Force on Practice Guidelines and The Obesity Society. J Am Coll Cardiol. 2014;63(25 Pt B):2985-3023. 9. St-Onge M-P, Schecter A. Sleep disturbances, body fat distribution, food intake and/or energy expenditure: pathophysiological aspects. Horm Mol Biol Clin Investig. 2014;17(1):29-37.

from one to the other over time. It may help to point out that everyone who is obese was first overweight; no one goes from normal weight to obese without being overweight. A review of lifestyle interventions in people with impaired glucose tolerance found that changes in diet designed for weight loss combined with physical activity reduced progression to T2DM. These interventions were cost effective as well as clinically effective.43 The most prominent diabetes prevention studies have both shown that lifestyle changes are beneficial in terms of preventing or delaying onset of diabetes, with effects sustained for as long as 20 years.38,44,45 Moderate weight loss and improved lifestyle choices produce a sustained improvement in insulin sensitivity and could help prevent T2DM.43 Lifestyle intervention in the DPPOS resulted in reduced body weight and HbA1c levels that persisted through 10-year follow-up.44,45 When patients are told that they have prediabetes and/or are at risk for developing diabetes, they may be uncertain and may not understand the importance of dealing with their condition sooner rather than later. Making lifestyle changes is not easy to either achieve or maintain. Surprisingly, there is little research on the specific effect on a patient’s behavior of being told that they have prediabetes.45,46 Finding out about prediabetes could be a welcome warning sign that allows for modifications in lifestyle (improved diet, increased physical activity, smoking cessation) to prevent ever moving to full diabetes. Seizing the opportunity to act—and, thus, to prevent the need for medication and/or surgery—can be empowering for patients. ■ PATIENT CASE—Next steps

Susannah has no symptoms and considers herself well. It is, therefore, difficult for her clinician to convince her that lifestyle changes are necessary to prevent future serious health problems. She is reluctant to change her diet and to start any kind of an exercise program and starts asking about weight-loss medication and bariatric surgery. After some discussion, she says that she might try modifying her eating patterns if she is not “put on a diet” and if she can still eat some of the foods she loves. Finding a fun activity to help her begin to exercise will also be a challenge. POLLING QUESTION

What nutritional program would you recommend for this patient? a.

A low-fat, low-calorie (≤2000 kcal/d) diet without regard to the percentage of calories from protein or carbohydrates

40 THE CLINICAL ADVISOR • NOVEMBER 2017 • www.ClinicalAdvisor.com

Studies have compared low-calorie/low-fat diets with low-carbohydrate diets and found greater weight loss with low-carbohydrate diets at 6 months and 1 year. b.

c. d.

A low-carbohydrate (≤20% of total energy/<20-60 g/d), high-saturated/low-unsaturated fat (<10% saturated fat) diet A very low-carbohydrate ketogenic (<20 g/d) diet A high-carbohydrate (≥53% of total energy), low-fat (<10% saturated fat) diet that emphasizes low-glycemic index foods

Low-fat vs low-carbohydrate diets Clinicians are faced with the problem of not only advising patients to change their eating patterns, but also of working with each patient to determine which dietary approach is likely to work best for them. While weight gain traditionally is attributed solely to number of calories consumed, it is now understood that the quality of the food consumed also impacts overall health.47 Low-carbohydrate diets are inherently higher in cholesterol, saturated fats, and animal products than low-fat diets, and most commercial low-carbohydrate diet programs do not place any limit on daily fat or protein consumption. Studies generally assess the effects of such on weight loss, glucose metabolism, blood pressure, and lipid levels. It is important to recognize, however, that the definition of such diets is highly variable, making it difficult to compare different approaches.48 Some diet programs restrict carbohydrates to a percentage of calories consumed, and others restrict absolute grams of carbohydrates. This makes meta-analyses particularly difficult. In general, most low-carbohydrate diets allow 20 to 60 g/d of carbohydrates (<20% of total daily calorie intake), while very-low-carbohydrate/ketogenic diets typically restrict carbohydrates to less than 20 g/d. Other less-restrictive diets allow up to 130 g/d of carbohydrates. Many of the low-carbohydrate programs work in phases, with the initial phase the most restrictive, to change metabolism quickly and promote early weight loss. Carbohydrates that are metabolized slowly are added back in phases until a weight maintenance phase is attained. Many studies have compared low-calorie/low-fat diets with low-carbohydrate diets and found greater weight loss with the low-carbohydrate diets, particularly at 6 months and 1 year.48-53 One of the few studies that combined a change in eating habits with behavioral counseling and exercise (mostly walking) that also had an extended (2-year) time horizon found no significant difference in weight loss

with low-fat vs low-carbohydrate diets.49 Both groups lost 11% of body weight at 1 year; some weight regain occurred, but both groups maintained a loss of 7% of body weight at 2 years. However, only the low-carbohydrate diet resulted in sustained improvement in HDL-cholesterol levels. One systematic review and meta-analysis covering 23 reports and 1141 patients examined the effects of lowcarbohydrate diets by comparing data following the diet to baseline values for the same patients. They did not look at the low-carbohydrate diets in comparison to other types of diets.54 This review found that, compared with baseline, the low-carbohydrate diets were associated with clinically important improvements in cardiovascular risk factors. There were significant decreases in body weight, BMI, abdominal circumference, systolic and diastolic blood pressure, plasma triglycerides, fasting plasma glucose, plasma insulin and plasma C-reactive protein, and glycated hemoglobin, with a significant increase in HDL cholesterol. Practical considerations in patient counseling

For a patient with prediabetes and a BMI that places him or her in the overweight category, an initial target weight loss of 1 to 2 pounds per week is ideal, with a long-range goal of at least 7% loss of body weight. Patients who undertake a low-carbohydrate diet should be educated about the importance of the quality of carbohydrates consumed. A diet with fewer processed meats, fewer refined carbohydrates, a greater fiber-to-carbohydrate ratio, more whole grains, and more low-glycemic index fruits and vegetables is healthier and more likely to improve a patient’s health.47 Increasing physical activity can be done in stages. The exercise program should include at least 150 minutes per week of moderate-intensity aerobic activity (50%-70% of maximum heart rate) spread over 3 or more days each week. No more than 2 days should pass without exercise. Resistance training at least 2 times per week is important unless contraindicated for particular patients. In helping patients design their activity plan, take into consideration their age and previous level of physical activity. The increase in activity has benefits beyond weight control. These include increased insulin sensitivity; improved lipid levels, particularly raised HDL cholesterol; lowered blood pressure; improved blood glucose control; reduced risk of CVD; and improved mood. Ongoing intervention produces the most success for the majority of patients.

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FEATURED COURSE

Counseling tips The ADA has developed a wide array of tools to help with counseling patients, including patient education handouts on lifestyle modification topics ranging from carbohydrate counting to getting started with physical activity. Many of these materials are available for download in several languages, including Spanish, at the ADA’s Diabetes Prosm website. Counseling should focus on developing specific objectives and letting the patient take the lead whenever possible, with regular reassessment of their progress and any obstacles they may encounter. It is easiest to achieve counseling goals and objectives by following the FIRM mnemonic: keep them Few in number, Individualized, Realistic, and Measureable in terms of frequency and duration. Source: Saunders JT, Pastors JG. Practical tips on lifestyle management of type 2 diabetes for the busy clinician. Curr Diab Rep. 2008;8:353-360.

Strategies for shared decision-making The communication between a clinician and a patient can make or break the outcome, particularly when lifestyle changes are involved. At the outset, it is important for the clinician to determine what the patient already knows and understands (or misunderstands) about his or her health status. It can be hard to communicate with a patient who doesn’t want to know that there may be something that needs to change, particularly if the patient has not come to the office with a specific problem. Part of the clinician’s task for such patients is to assess whether the patient desires, or will be able to comprehend, additional information. Figuring out what is of importance to the patient and what might capture their attention is crucial.55 Following the initial visit, subsequent visits, with followup blood tests as indicated, will allow for a more precise diagnosis and may also allow the patient to process information shared in the first visit. Shared decision-making and consideration of the patient’s personal preferences as well as cultural considerations are the key to working with overweight patients and to helping them to begin lifestyle changes (see Box, Counseling tips). Once a patient understands that losing excess weight will provide both immediate and long-term benefits, it is more likely that he or she will maintain a program of altered eating patterns and increased physical activity. Patients who successfully lose weight report they feel better overall. They enjoy greater vitality, a more positive mental outlook, a better social life, and are physically able to do things they could not do before.

Diabetes self-management education (DSME) and diabetes self-management support (DSMS) encourage behavior change that leads to the maintenance of healthy diabetesrelated behaviors.28 DSME and DSMS are ongoing processes that address psychosocial concerns. Nevertheless, regular follow-up that reinforces your ongoing concern and support is crucial to success. At each interaction, it is important to address modifiable risk factors and evaluate the success of the current plan. If it isn’t working for the patient, the plan may need to be revised to something that has a better likelihood of success. A patient with prediabetes should be screened annually and given tools to help implement diet and activity plans, as well as referrals to other members of the interdisciplinary healthcare team where appropriate. ■ PATIENT CASE—Outcome

At the conclusion of the initial visit, Susannah’s clinician provides her with patient education information about prediabetes from authoritative sources, including the National Diabetes Education Initiative, the American Diabetes Association, and the National Institute of Diabetes and Digestive and Kidney Diseases. She is scheduled to return the next week to meet with members of the diabetes education team to work together to develop an individualized program of lifestyle change, which includes implementation of a low-carbohydrate diet that incorporates the Latino cuisine she prefers. She continues to receive regular support and counseling over the next 6 months, at which time she returns for a comprehensive follow-up visit. She has lost 18 lbs, bringing her close to her target weight of ~145 lbs (BMI <25 kg/ m 2). Her HbA1c is now 5.2%, and her blood pressure and lipids are also in the normal range. Susannah is clearly proud that she has mastered cooking healthy versions of the foods she grew up with—as a bonus, both her parents have lost weight along with her, as she now does a good deal of the family cooking. In addition to adhering to a low-carbohydrate diet, she now exercises regularly by walking while listening to downloadable audio novels on her smartphone, instead of sitting at home and streaming movies. She acknowledges that she has not had much time to pursue her hobby of jewelry-making, but she is planning to start selling pieces through an online website after she graduates and is not so busy studying and working part-time. Conclusions

In summary, clinicians must develop a strategic management plan to proactively identify, assess, follow up, and evaluate

42 THE CLINICAL ADVISOR • NOVEMBER 2017 • www.ClinicalAdvisor.com

patients with prediabetes. Modest weight loss of 5% to 10% of body weight can prevent or delay its development and improve associated cardiometabolic risk factors. A teambased approach to assisting individuals with prediabetes to achieve their target goals and objectives is the most effective method for working with individual patients. In spite of a diagnosis of prediabetes, patients should understand that the development of overt diabetes is far from inevitable. Lifestyle changes are always the first step, and patients should be offered robust support in undertaking these interventions prior to considering pharmacotherapy and/or bariatric surgery. For most patients with prediabetes, a low-carbohydrate diet with a focus on carbohydrate quality is recommended in conjunction with an increase in physical activity. These simple measures—when undertaken with adequate support and encouragement from the primary care team—can help prevent the development of overt diabetes, along with its attendant morbidity and mortality. n

study among men and women. Obes Res Clin Pract. 2010;4(3): e171-e181. 11. Eliassen AH, Colditz GA, Rosner B, Willett WC, Hankinson SE. Adult weight change and risk of postmenopausal breast cancer. JAMA. 2006;296(2):193-201. 12. Thygesen LC, Grønbaek M, Johansen C, et al. Prospective weight change and colon cancer risk in male US health professionals. Int J Cancer. 2008;123(5):1160-1165. 13. Willett WC, Manson JE, Stampfer MJ, et al. Weight, weight change, and coronary heart disease in women. Risk within the ‘normal’ weight range. JAMA. 1995;273(6):461-465. 14. Colditz GA, Willett WC, Rotnitzky A, Manson JE. Weight gain as a risk factor for clinical diabetes mellitus in women. Ann Intern Med. 1995;122(7):481-486. 15. Rexrode KM, Hennekens CH, Willett WC, et al. A prospective study of body mass index, weight change, and risk of stroke in women. JAMA. 1997;277(19):1539-1545. 16. Muñoz-Garach A, Cornejo-Pareja I, Tinahones FJ. Does metabolically healthy obesity exist? Nutrients. 2016;8(6). 17. Kramer CK, Zinman B, Retnakaran R. Are metabolically healthy

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44 THE CLINICAL ADVISOR • NOVEMBER 2017 • www.ClinicalAdvisor.com

CME

POSTTEST Expiration date: November 30, 2018

A statement of credit will be issued only upon receipt of a completed preassessment 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/Nov17feature. CREDITS: 1.25 | A 19-year-old Latina college student with prediabetes

1. Which of the following statements regarding the “diabesity” epidemic in the United States is true? a. The increased prevalence of diabetes, but not of obesity, is linked to a concomitant increase in consumption of refined carbohydrates in recent decades. b. The increased prevalence of both obesity and diabetes is associated with a concomitant increase in consumption of refined carbohydrates in recent decades. c. Gradual weight gain with aging (~0.8 lb/year) does not increase the risk of serious comorbidities. d. Individuals who are obese but metabolically healthy have no increase in mortality risk compared with nonobese individuals. 2. Risk factors for cardiometabolic disease may be increased due to which of the following? a. Poor sleep habits b. Low-carbohydrate diet c. High-fat diet d. Sudden increase in physical activity 3. The American Diabetes Association (ADA) recommends diabetes screening in all adults with which of the following risk factors? a. Both men and women ≥35 years of age b. Women ≥35 years of age; men ≥45 years of age c. Body mass index (BMI) ≥25 kg/m2 (≥23 kg/m2 in Asian Americans) d. Waist circumference ≥35 inches for women; ≥40 inches for men 4. According to the ADA, prediabetes is defined as: a. Presence of ≥3 risk factors for diabetes b. Fasting blood glucose (FBG) 140-199 mg/dL

c. Oral glucose tolerance test (OGTT) 2-hour blood glucose 100-125 mg/dL d. HbA1c 5.7%-6.4% 5. What degree of weight loss is needed to see a reduction in cardiometabolic risk factors in individuals with prediabetes? a. 3% to ≤5% sustained for >1 year b. 10% to 15% sustained for >1 year c. 10% to 15% sustained for >5 years d. There is no strong evidence that weight loss improves outcomes in this population. 6. BL is an overweight (BMI 27 mg/kg2) 23-year-old patient who has recently learned he is at risk of diabetes and is now classified as having prediabetes. He understands that he needs to lose weight and be conscientious about what he is eating. You both decide that a low-carbohydrate weight-loss diet would be optimal. Along with eating fewer carbohydrates, what other dietary intake patterns should BL adhere to? a. Unlimited amounts of fruits and vegetables b. Unlimited amounts of whole grains and nuts c. Only low-fat or no-fat foods d. More dietary fiber for a higher fiber-to-carbohydrate ratio 7. Which of the following statements regarding physical activity in patients who are hoping to lose weight is best supported by clinical trial data? a. Patients should exercise vigorously ≥5 days a week. b. Patients should undertake resistance training ≥2 times per week. c. Exercise has little, if any, benefit in weight loss. d. Exercise has little effect on blood glucose control.

TO TAKE THE POSTTEST please go to: ClinicalAdvisor.com/Nov17feature

www.ClinicalAdvisor.com • THE CLINICAL ADVISOR • NOVEMBER 2017 45

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

CASE FILES

TIPS FOR MAKING A PERSONAL CONNECTION WITH YOUR PATIENTS I have been a physician assistant for more than 22 years, with the last 9 years focused in pain management. I work with some of our poorer patients on the south side of San Antonio. Even though I have only so much time for each patient and am very busy, I make certain that I sit down, face the patients eye-to-eye, and listen to them. There is a great difference between hearing a patient and listening to what he or she is saying. The eye contact helps me make a personal connection with my patients. I make each one feel that he or she is the only patient whom I am seeing that particular day. Also, I never stand over a patient. And, finally, I try to instill some humor when I see patients. It might be the only time that they will smile that day.—HOWARD KAGAN, PA-C, San Antonio (229-1)

MILITARY SEXUAL TRAUMA: A PRIMER FOR CLINICIANS Contributed by Sherril Sego, FNP-C, DNP (See photo at bottom of this page for more information about Dr. Sego.)

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.

The issue of posttraumatic stress disorder (PTSD) in military veterans is commonly acknowledged. The mindset of “just get over it” has long been understood to be both unrealistic and scientifically unfounded. Even the realization that trauma leading to PTSD does not have to be directly related to combat is well-established. What is not widely discussed is the definite gender gap in PTSD due to sexual trauma in female veterans. Military sexual trauma (MST) includes any sexual activity in which a service member is involved against his or her will. These acts range from sexual harassment to rape. Every year, an estimated 1 in 4 females and 1 in 100 males in the military experience some event that meets the accepted definition of sexual trauma: “Psychological trauma that resulted from a physical assault of a sexual nature, battery of a sexual nature, or sexual harassment which occurred while the veteran was serving on active duty, active duty for training, or inactive duty training.” As with civilian sexual assault, the reporting rate of sexual assault in the military is thought to be as low as 25% of actual

OUR CONSULTANTS

Philip R. Cohen, MD,

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

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.

46 THE CLINICAL ADVISOR • NOVEMBER 2017 • www.ClinicalAdvisor.com

Laura A. Foster, CRNP, FNP,

Abby A. Jacobson, MS, PA-C,

practices family medicine with Palmetto Primary Care Physicians in Charleston, S.C.

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

incidents. Some facts related to this low number are fear of retribution or retaliation, continued contact with the perpetrator due to duty assignment, and lack of follow-through from the chain of command. Male MST reporting rates are believed to be even lower due to the stigma attached. The evolution of the recognition and treatment of MST by both the Department of Defense (DoD) and the US Department of Veterans Affairs (VA) has been long and agonizing. The number of women actively serving in the military is now about 14%, or well over 200,000. In the 15 years of the global war on terror, nearly 300,000 women have been deployed to a designated combat zone. Of all reported cases of MST, more than 25% occurred in this type of environment. It is due to this, as well as the previously mentioned conditions, that MST differs from civilian sexual assault. Despite the increasing number of women in the military, it is still predominantly a “man’s world.” Add to that basic demographic a high-adrenalin environment and the increased assimilation of women into all areas of service, and some would call it the perfect storm for sexual assault. In light of these facts, the VA screens all veterans for MST at their initial visit. Even in this setting, patients are often hesitant to report the assault. Repeated screening after there has been time to establish a more trusting patient/provider relationship often reveals an unreported incident. MST itself is not an actual diagnosis, but PTSD that is subsequent to MST meets DSM-5 criteria. Differentiating MST as an event from PTSD due to MST must follow the established criteria for PTSD due to any incident. The following questions help guide a more accurate diagnosis and potential treatment: “In your life, have you ever had any experience that was so frightening, horrible, or upsetting that, in the past month, you:

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.

1. Have had nightmares about it or thought about it when you did not want to? 2. Tried hard not to think about it or went out of your way to avoid situations that reminded you of it? 3. Were constantly on guard, watchful, or easily startled? 4. Felt numb or detached from others, activities, or your surroundings?”

As with any form of PTSD, treatment is often guided by the symptoms and their severity. Psychotherapeutic counseling coupled with pharmacologic management of symptoms of depression, anxiety, insomnia, nightmares, panic attacks, and others is recommended. For patients expressing relationship difficulties, couples education and therapy should be offered. Regardless of the statistics and social implications, public education should be very clear: Sexual assault is NEVER okay, “asked for,” or “no big deal.” The DoD is making large strides in educating troops and commanding officers about the zero tolerance policy of sexual assault, but change has been slow in this huge, complex organization. Primary care providers should be alert to the signs and symptoms that might indicate prior sexual assault in male or female patients. Veteran or not, this is an issue that needs widespread understanding and attention from healthcare professionals. (229-2) n References 1. VA. Military sexual trauma. https://www.vets.gov/health-care/ health-conditions/military-sexual-trauma/ 2. Barth SK, Kimerling RE, Pavao J, McCutcheon SJ, Batten SV, Dursa E, et al. Military sexual trauma among recent veterans: Correlates of sexual assault and sexual harassment. Am J Prev Med. 2016;1:77–86. 3. Mengeling MA, Booth BM, Torner JC, Sadler AG. Reporting sexual assault in the military: Who reports and why most servicewomen don’t. Am J Prev Med. 2014;1:17–25.

Claire O’Connell, MPH, PA-C,

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.

www.ClinicalAdvisor.com • THE CLINICAL ADVISOR • NOVEMBER 2017 47

Dermatology Clinic CASE #1

Fragile, bullous lesions on the trunk of a child SIRUS JESUDASEN, BS, CHRISTOPHER RIZK, MD

An 8-year-old African-American boy presents with a 3-day history of fever, pain, and a rash on his trunk. On examination, the patient has several fragile, bullous lesions on his trunk, many of which have eroded, exposing erythematous, annular lesions. The patient is febrile and shaking in the office, and he appears to be in pain. He has no other relevant social or family history and does not take any medications. His mother is very concerned about her son. What is your diagnosis? Turn to page 50

CASE #2

A yellow-orange hairless patch on a 1-year-old boy MICHELLE LEE, BA, DAVID RIZK, BA, CONNIE WANG, MD

A 1-year-old boy presents with a single, L-shaped, yelloworange hairless patch over the left preauricular skin. The patient’s mother notes that her son has never grown hair in that location. The mother is concerned because the area used to be smooth, but it now seems to be changing. The patient has a history of prematurity and low birthweight, but he is otherwise healthy. The patient has no relevant social or family history. What is your diagnosis? Turn to page 51 48 THE CLINICAL ADVISOR • NOVEMBER 2017 • www.ClinicalAdvisor.com

Dermatology Clinic CASE #1

Bullous impetigo

Bullous impetigo is a highly contagious infection of the epidermis caused by the bacterium Staphylococcus aureus that is most commonly seen in neonates. It typically presents with fragile, flaccid bullae that easily rupture, leaving annular erosions with an erythematous base and central healing.1 Limited infections typically resolve in 2 to 3 weeks without scarring.2 Although bullous impetigo can present in any individual, it most commonly occurs during the neonatal period, and to a lesser degree in children (especially those under age 5).1 Some cases of bullous impetigo have also been reported during pregnancy, and should be included in the differential diagnosis for blistering conditions in pregnant women.3,4 Several risk factors can increase the risk or severity of infection. Factors such as poor hygiene, high humidity, warm temperatures, atopic diathesis, and Staphylococcus aureus colonization can all predispose individuals to impetigo infections.5 In adults, pharmacologic immunosuppression, AIDS, and lymphoma chemotherapy have been shown as risk factors for bullous impetigo.6,7 Bullous impetigo is most often found in intertriginous areas of the body, such as diaper areas, as well as axilla and neck folds; it can often be found on the buttocks of infants. Initial presentation of the disease typically involves small vesicles that develop into flaccid blisters.8 Their contents are initially clear but, over time, become more purulent.9 The roof of the blister eventually ruptures, revealing an erythematous base that may appear shiny or wet.8 Rupture may also result in a peripheral collarette and lead to confluence of lesions.8 The bacterial skin infection of impetigo can be subcategorized into two types: nonbullous impetigo (or impetigo contagiosa), which comprises approximately 70% of cases, and bullous impetigo, which comprises approximately 30% of cases.9 Although nonbullous impetigo may be caused by Streptococcus or S aureus infection, bullous impetigo is almost solely caused by S aureus, which produces exfoliative toxin A and B.8 Exfoliative toxin A, a serine protease produced by the bacteria, binds and destroys desmosomes in the granular layer of the epidermis through cleavage of the desmosomal cadherin desmoglein-1.8,9 The thin epidermal barrier of the stratum corneum is left intact, resulting in bullae formation in the superficial epidermis.9

Diagnosis of bullous impetigo is predominantly clinical. Skin swabs are not helpful due to their inability to differentiate between normal colonization of the skin and the pathogenic cause of infection.1 However, drainage and inoculation of pustule fluid for Gram stain and culture can aid in the diagnosis.1,5 The appearance of epidermal infections similar to bullous impetigo contains a broad differential diagnosis. It is important to rule out bullous erythema multiforme and Stevens-Johnson syndrome, as early identification of both hypersensitivity reactions can have a significant impact on prognosis.10,11 Autoimmune bullous dermatoses should also be ruled out, although some of these conditions, such as bullous pemphigoid, usually occur in older adult populations. Often, bullous insect bite reactions and potential viral infection by herpes simplex virus are highest on the differential diagnosis when considering bullous impetigo.11 In these cases, obtaining a thorough medical history, along with close examination of the blisters, can aid in differentiating these disorders. When fluid-filled vesicles are present, culture of fluid from vesicles can be used to differentiate the disorders. Bullous impetigo is often self-resolving when the infection is limited, but numerous options are available for treatment. Oral antibiotics, such as penicillin derivatives or clindamycin, may be utilized in cases of severe or systemic infection.1,8 For mild or moderate cases, topical antibiotic therapy is safe and optimal.6 Mupirocin 2% is a common topical treatment option that is highly effective against S aureus as well as most Streptococcus species.1,8 Retapamulin 1% ointment has also been shown to be clinically effective; however, it may cause localized pruritus.8,12 It should be noted that some children appear to have recurrent flares of bullous impetigo. This may be caused by colonization of S aureus. In these cases, the acute bought of impetigo should be treated, as discussed above, and the child should undergo decolonization treatment over time. Decolonization can occur via extended treatment of the nares and intertriginous regions with mupirocin spray and ointment, respectively. Our patient in this case was diagnosed with a severe case of bullous impetigo. Due to systemic symptoms and widespread lesions, the patient was treated with a course of oral clindamycin, which led to the resolution of his symptoms. Sirus Jesudasen, BS, is a medical student at the Baylor College of Medicine, and Christopher Rizk, MD, is a dermatology resident at the Baylor College of Medicine in Houston. References 1. Hartman-Adams H, Banvard C, Juckett G. Impetigo: diagnosis and treatment. Am Fam Physician. 2014;90:229-235.

50 THE CLINICAL ADVISOR â&#x20AC;˘ NOVEMBER 2017 â&#x20AC;˘ www.ClinicalAdvisor.com

2. Koning S, van der Sande R, Verhagen AP, et al. Interventions for impetigo. Cochrane Database Syst Rev. 2012;1:CD003261. 3. Piechowicz L, Garbacz K, Budzyńska A, Dąbrowska-Szponar M. Outbreak of bullous impetigo caused by Staphylococcus aureus strains of phage type 3C/71 in a maternity ward linked to nasal carriage of a healthcare worker. Eur J Dermatol. 2012;22:252-255. 4. Cohen PR. Bullous impetigo and pregnancy: case report and review of blistering conditions in pregnancy. Dermatol Online J. 2016;22: pii: 13030/qt7533z2m0. 5. Duggal SD, Bharara T, Jena PP, et al. Staphylococcal bullous impetigo in a neonate. World J Clin Cases. 2016;4:191-194. 6. George A, Rubin G. A systematic review and meta-analysis of treatments for impetigo. Br J Gen Pract. 2003;53:480-487. 7. Bukowski M, Wladyka B, Dubin G. Exfoliative toxins of Staphylococcus

and hairless. After puberty, secondary to hormonal influence, the plaques tend to become scaly, bumpy, and papular. These changes are due to epidermal growth and an increase in the number of sebaceous glands during puberty. The verrucous changes that occur during puberty can be alarming, and are a common cause for dermatology visits. In 20% of nevus sebaceous cases, a neoplastic growth develops within the nevus. Most commonly, benign adnexal neoplasms arise within nevus sebaceous lesions, such as trichoblastomas and syringocystadenoma papilliferum. However, malignant neoplasms such as basal cell carcinoma can also arise within the nevi. Thus, atypical changes within a nevus sebaceous lesion must be biopsied to rule out malignant transformation.1-4

aureus. Toxins (Basel). 2010;2:1148-1165. 8. Pereira LB. Impetigo—review. An Bras Dermatol. 2014;89:293-299. 9. Bangert S, Levy M, Hebert AA. Bacterial resistance and impetigo treatment trends: a review. Pediatr Dermatol. 2012;29:243-248. 10. Brown J, Shriner DL, Schwartz RA, Janniger CK. Impetigo: an update. Int J Dermatol. 2003;42:251-255.

The differential diagnosis includes juvenile xanthogranuloma, epidermal nevus, and syringocystadenoma papilliferum.

11. Ki V, Coleman R. Bacterial skin and soft tissue infections in adults: a review of their epidemiology, pathogenesis, diagnosis, treatment and site of care. Can J Infect Dis Med Microbiol. 2008;19:173-184. 12. Koning S, van der Wouden JC, Chosidow O, et al. Efficacy and safety of retapamulin ointment as treatment of impetigo: randomized double-blind multicentre placebo-controlled trial. Br J Dermatol. 2008;158:1077-1082.

CASE #2

Nevus sebaceous

Nevus sebaceous was first described in 1895 by Josef Jadassohn. As a result, this condition is also referred to as nevus sebaceous of Jadassohn or organoid nevus. Nevus sebaceous is a benign hamartoma of the skin involving immature hair follicles, epidermal cells, sebaceous glands, and apocrine glands.1-4 There is equal incidence in males and females, and two-thirds of cases are present at birth.5 Other cases develop during infancy or early childhood. Very few familial cases have been described, as most cases seem to occur sporadically.6-9 Nevus sebaceous appears most frequently on the head, with 50% of cases on the scalp. The condition appears as oval or linear verrucous plaques that range in size. In early childhood, the plaque appears slightly raised or smooth, yellow, waxy,

Histology of nevus sebaceous is characterized by immature hair follicles. Before puberty, there are few immature sebaceous glands. After puberty, hyperplasia of sebaceous glands and apocrine glands, as well as epidermal hyperplasia, are apparent. The sebaceous glands can be located more superficially within the dermis than they usually are. Nevus sebaceous of Jadassohn syndrome is a rare combination of linear nevus sebaceous, epilepsy, and intellectual disability. In nevus sebaceous syndrome, the plaque tends to be linear and large (≥10 cm), and spans multiple dermatomes.10 Other areas involved in this congenital syndrome include ocular, skeletal, vascular, and urogenital systems. Neurologic assessments and imaging should also be performed to identify or rule out rare abnormalities, especially if the plaque is large and located in the centrofacial area. The differential diagnosis of nevus sebaceous includes juvenile xanthogranuloma, epidermal nevus, and the syringocystadenoma papilliferum. Juvenile xanthogranuloma is a rare, benign disorder of dermal dendrocytes that presents in early childhood as red to yellow plaques with papules. They are located commonly on the head, neck, and upper trunk. Histology shows mononuclear cells and multinucleated giant cells, some of which may have features of Touton giant cells.2-5 Epidermal nevi are benign hamartoma of the skin that present on the torso or limbs, but rarely on the scalp or face. These brown or skin-colored papules appear along the lines of Blaschko. Histology demonstrates flattened papillary

www.ClinicalAdvisor.com • THE CLINICAL ADVISOR • NOVEMBER 2017 51

projections of the epidermis and orthokeratotic hyperkeratosis.1-3 Syringocystadenoma papilliferum is a rare, benign tumor of the apocrine sweat glands. Commonly located on the scalp, syringocystadenoma papilliferum exists as an isolated papule or is associated with nevus sebaceous. Histology is characterized by papillomatous epidermal invaginations of basilar cuboidal cells surrounded by 2 layers of columnar cells. Apocrine secretory cells are present as the inner layer.1-5 Diagnosis of nevus sebaceous is usually based on clinical examination findings of a raised, yellow-orange, hairless verrucous plaque on the face or scalp. When the diagnosis of nevus sebaceous is suspected, the lesion should be observed closely but does not have to be surgically removed. Historically, surgery used to be the initial treatment. New studies showing the lower rates of malignant degeneration have caused a shift to less aggressive management. However, some parents of children with nevus sebaceous prefer to have the lesions excised for cosmetic reasons. If the parents and clinician decide to observe the lesion, they should expect the lesion to darken and thicken during puberty. However, the family and clinician should be suspect of any new growths within the lesion that may herald the formation of a benign (trichoblastoma or syringocystadenoma papilliferum) or malignant (basal cell carcinoma) neoplasm within the nevus sebaceous lesion. In the event of the a new growth within the nevus sebaceous lesion, the lesion should be biopsied to rule out malignancy.10 The patient in this vignette was diagnosed with nevus sebaceous. The natural progression of the lesion was explained to the mother, who then opted to observe the lesion closely rather than elect surgical removal. n

Michelle Lee, BA, is a medical student at the Baylor College of Medicine in Houston, David Rizk, BA, is a medical student at the University of South Alabama in Mobile, and Connie Wang, MD, is a dermatology resident at the Baylor College of Medicine in Houston.

“When it comes to blowing leaves around uselessly and creating an insane amount of noise, this model can’t be beat.”

“Number three is Mr. Hugo, our seventh grade teacher—the one whose exam contained questions not covered in the assigned reading.”

References 1. Jaqueti G, Requena L, Sánchez Yus E. Trichoblastoma is the most common neoplasm developed in nevus sebaceus of Jadassohn: a clinicopathologic study of a series of 155 cases. Am J Dermatopathol. 2000;22:108-118. 2. Cifuentes L, Ziai M. Images in clinical medicine. Nevus sebaceous. N Engl J Med. 2012;366:1923-1923. 3. Schachner LA, Hansen RC. Pediatric Dermatology. Maryland Heights, MO: Mosby Elsevier; 2011. 4. Ujiie H, Kato N, Natsuga K, Tomita Y. Keratoacanthoma developing on nevus sebaceous in a child. J Am Acad Dermatol. 2007;56(2 suppl):S57-S58. 5. Habif TP, Campbell JL Jr, Chapman MS, Dinulos JG, Zug KA. Benign skin tumors. In: Habif TP, Campbell JL Jr, Chapman MS, Dinulos JG, Zug KA, eds. Skin Disease: Diagnosis and Treatment. 3rd ed. Philadelphia, PA: Saunders Elsevier; 2011:424-463. 6. Hughes SM, Wilkerson AE, Winfield HL, Hiatt KM. Familial nevus sebaceus in dizygotic male twins. J Am Acad Dermatol. 2006;54(2 suppl):S47-S48. 7. Happle R, König A. Familial naevus sebaceus may be explained by paradominant transmission. Br J Dermatol. 1999;141:377. 8. Levinsohn JL, Tian LC, Boyden LM, et al. Whole-exome sequencing reveals somatic mutations in HRAS and KRAS, which cause nevus sebaceus. J Invest Dermatol. 2013;133:827-830. 9. Kim D, Benjamin LT, Sahoo MK, Kim J, Pinsky BA. Human papilloma virus is not prevalent in nevus sebaceus. Pediatr Dermatol. 2014;31:326-330. 10. James WD, Berger TG, Elston DM, Neuhaus IM. Andrew’s Diseases of the Skin: Clinical Dermatology. 11th ed. Philadelphia, PA: Elsevier; 2011.

52 THE CLINICAL ADVISOR • NOVEMBER 2017 • www.ClinicalAdvisor.com

Dermatology Clinic

Dermatologic Look-Alikes Lesions on the face, lip, and ear JOAN FERNANDEZ, BS, CHRISTOPHER RIZK, MD

CASE #1

CASE #2

A 65-year-old man presents with two lesions on his face. The patient states that the lesions have grown slowly on his cheek and lower lip over the past year. They are not painful and do not itch. He came in because they cause him trouble when shaving. On examination, the patient has a 1.0 × 0.8-cm pearly papule with overlying telangiectasias and a rolled border on his right lower cheek and a 1.2 × 1.0-cm pearly papule with overlying telangiectasias and a rolled border on his right lower lip. Aside from the lesions, the patient does not have any other medical problems, and he does not have any relevant social or family history.

A 70-year-old man presents for examination with a lesion on his left ear. He states that he has had this nonhealing lesion on his left ear for approximately 18 months. The lesion did not bother him until about 6 months ago, when it and the surrounding skin started to hurt. On examination, the patient has a large ulceration with overlying crust. The surrounding skin appears erythematous and inflamed. The lesion is tender on contact. Aside from the lesion, the patient does not have any other medical problems. In addition, the patient does not have any relevant social or family history.

www.ClinicalAdvisor.com • THE CLINICAL ADVISOR • NOVEMBER 2017 53

Dermatologic Look-Alikes CASE #1

Basal cell carcinoma

Basal cell carcinoma (BCC) is the most common form of cancer that occurs in white individuals, and its incidence continues to rise worldwide.1-3 The pathophysiology of BCC is not completely understood, but it is known that there are multiple genetic mutations that arise within the cells that lead to their clonal proliferation and tumor generation. Specific mutations in the hedgehog signaling pathway that lead to constituent pathway activation have been identified in both sporadic and familial cases of BCC.4 Additional loss of function mutations in PTCH1 and tumor suppressor genes such as p53 have been identified, all of which contribute to the cell’s ability to escape the normal regulatory pathways.4

Exposure to UV radiation appears to be the most widely recognized and strongest risk factor for basal cell carcinoma. Many risk factors for the development of BCC have been identified. However, exposure to ultraviolet (UV) radiation appears to be the most widely recognized and strongest risk factor.5 Increased duration and severity of UV exposure, as well as exposure in childhood and adolescence, contribute to the development of disease.5 In a study by Kricker and colleagues,6 it was found that intense, intermittent sun exposure was a greater risk to the future development of BCC than the same degree of continuous exposure. Family history of skin cancer, physical characteristics, including fair complexion, light hair and eye color, and various chemical exposures (eg, arsenic), are some of the additional risk factors that contribute to the development of BCC.2,7 Interplay between UV radiation exposure, genetic predisposition, inherent physical characteristics, and exposure to any risk factor all contribute to the likelihood of developing BCC. BCC presents commonly on the sun-exposed areas of the body; the majority of cases occur on the head and neck, followed by the trunk and extremities.4,8 There are many different clinicopathologic types of BCC; the predominant 3 types are nodular, superficial, and morpheaform.1-4,9 The

most common form of BCC is the nodular form, which typically presents clinically as a pearly papule or nodule with overlying telangiectasias and a rolled border, with occasional central crusting or ulceration.4 The superficial form of BCC presents as a scaly erythematous patch or plaque. Both the nodular and superficial forms can contain melanin, giving a brown, black, or blue hue to the lesions.4 The morpheaform type appears as an indurated, whitish, scar-like plaque with indistinct margins.4 The differential diagnosis of BCC varies based on its different forms. The differential diagnosis may include sebaceous hyperplasia, squamous cell carcinoma (SCC), trichoepithelioma, fibrous papules, and molluscum.10 In order to differentiate these various lesions from one another, a biopsy for histopathologic examination is helpful. Histologically, BCCs are a group of epithelial intradermal tumors whose cellular components resemble the undifferentiated basal cells of the epidermis and its appendages.8 Arrangement of cells into palisades at the tumor periphery is characteristic. Visible desmosomal intracellular structures are absent, and the tumor cells have a paucity of cytoplasm.8 Diagnosis of BCC is established histologically by the features described above, and can often be accomplished by a superficial shave biopsy due to the raised nature of the lesions.11 However, if the lesions are small enough and have clear, distinct borders, punch biopsies or excisional biopsies can be employed and can be both diagnostic and therapeutic if clear margins are achieved.11 Treatment of BCC varies based on the tumor’s size, morphology, and extent of growth. Because of the low metastatic potential of BCC, treatment focuses on local control rather than systemic therapy.4 After biopsy, once the diagnosis of BCC is confirmed, most lesions can be treated with either wide local excision or electrodessication and curettage. If a full thickness excisional biopsy produces clear margins, then no further treatment is required for BCC. An additional treatment option is 5-fluorouracil, applied topically or intralesionally.11,12 Recurrent cases of BCC, cases involving cosmetically sensitive areas (such as the face), those with indistinct margins, and lesions >2 cm should be referred for complete excision via Mohs micrographic surgery.11 Mohs micrographic surgery allows tissue sparing by taking smaller margins and checking them under the microscope while the patient waits. The patient in this vignette was diagnosed with 2 nodular BCCs after shave biopsies were performed. Because the lesions were on the patients face, the patient was referred to a Mohs surgeon for treatment.

54 THE CLINICAL ADVISOR • NOVEMBER 2017 • www.ClinicalAdvisor.com

CASE #2

Squamous cell carcinoma

Cutaneous squamous cell carcinoma (cSCC) is a locally invasive tumor that is second only to basal cell carcinoma as the most common form of skin cancer in white individuals; over 700,000 new cases are diagnosed each year in the United States.13-15 Although locally invasive, cSCC does have metastatic potential greater than that of BCC, giving it a slightly worse prognosis.15 The prevalence of SCC in men is twice that of women, and risk increases with increasing age, particularly in those over age 70 years.13 The development of cSCC is the result of multiple events that interact together to result in aberrant cell proliferation that escapes the cell cycle and ultimately results in cancer. Often, precursor lesions (actinic keratoses) arise before progressing to cSCC.14,16 Although the risk of transformation of actinic keratoses to invasive cSCC is low, the presence of precursor lesions signifies a greater risk for disease.14 There are many risk factors that contribute to the development of cSCC. Like BCC, exposure to UV radiation has

proven to be one of the strongest risk factors. However, cumulative UV radiation exposure appears to play more of a role in the development cSCC, whereas intense, intermittent UV radiation exposure is linked more to BCC.6,14 A study of the latitude in which individuals live and the incidence of cSCC found that the incidence doubles with each 8- to 10-degree decline in latitude, further emphasizing the relationship between UV exposure and cSCC.14 Sun exposure, phenotype, genotype, immune status, and chemical exposures all play a role in the development of cSCC. Some of these factors include fair complexion, light-colored hair, blue eyes, immunodeficiency, and exposure to substances such as arsenic or polycyclic aromatic hydrocarbons.2,7,14 The clinical presentation of cSCC can vary from scaly red patches, to hyperkeratotic papules, to nonhealing ulcers.13 The classic lesions are described as firm, skin-colored or pink papules or plaques that can be smooth or hyperkeratotic, and have the potential for ulceration.15 Some patients complain of pain at the area of the lesion. However, these lesions often go unnoticed due to the absence of pain.13 Although cSCC can present anywhere on the body, the lesions are often found in sun-exposed areas. The most common location of invasive SCC is the head and neck, followed by the trunk.16 cSCC can be described histologically as a proliferation of anastomosing nests, sheets, and strands of atypical

TABLE 1. Clinical characteristics of basal cell carcinoma and squamous cell carcinoma Classic dermatologic presentation Associations

Characteristic location Histology

Diagnosis Treatment

Basal cell carcinoma • Pearly papule or nodule with overlying telangiectasias and a rolled border • Occasional central crusting or ulceration (nodular type) • Related to UV exposure (especially intense, intermittent UV exposure) • More common in individuals with fair complexion, light hair, and light eyes Sun-exposed areas: head and neck > trunk and extremities • Arrangement of cells into palisades at the tumor periphery with central apoptotic cells • Absence of visible desmosomal intracellular structures • Paucity of cellular cytoplasm

Biopsy for histologic examination • Wide local excision with clear margins • Mohs micrographic surgery • Electrodessication and curettage

Squamous cell carcinoma • Firm, skin-colored or pink papules or plaques • Can be smooth or hyperkeratotic • Potential for ulceration • Related to UV Exposure (especially cumulative UV exposure) • More common in individuals with fair complexion, light hair, and light eyes Sun-exposed areas: head and neck > trunk and extremities • Proliferation of anastomosing nests, sheets, and strands of atypical keratinocytes originating in the epidermis and infiltrating into the dermis • Characteristic prominent intracellular bridges • Epithelial cells with a glassy eosinophilic cytoplasm and a large nucleus Biopsy for histologic examination Invasive cSCC: • Surgical excision (wide local or Mohs) with clear margins • ± adjuvant radiation therapy/chemotherapy if clear margins not obtained or if specific criteria are met SCC in situ: • Surgical excision • Electrodessication and curettage

Abbreviations: cSCC = cutaneous squamous cell carcinoma; SCC = squamous cell carcinoma; UV = ultraviolet.

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Dermatologic Look-Alikes keratinocytes originating in the epidermis and infiltrating into the dermis. Characteristic squamous pearls can be seen. Prominent intracellular bridges are characteristic, and epithelial cells exhibit glassy eosinophilic cytoplasm and often a large nucleus.17 Morphologic features can vary based on the histologic subtype of the lesion, grades of differentiation, and depth and degree of invasion.17 The differential diagnosis for cSCC includes many lesions that mimic the appearance of cSCC. Variants of BCC, sebaceous carcinoma, and spindle cell melanoma all have features that can appear very similar to those of cSCC.15 In many cases, these tumors are hard to distinguish clinically from cSCC, and a biopsy must be performed for histopathologic examination. Inverted follicular keratosis can also mimic cSCC, and commonly presents as a scaly papule, nodule, or plaque. In contrast to cSCC, inverted follicular keratosis has a circumscribed border and a lack of significant cellular atypia.15 Keratoacanthomas are well-differentiated squamoproliferative tumors that some clinicians consider a variant of cSCC. Features that differentiate keratoacanthomas from cSCC include a limited pushing deep front, distinct tumorstromal interface, and lesional squamous cells with abundant cytoplasm centrally.15 These lesions usually lack the significant stromal desmoplasia and cellular atypia seen in cSCC.15 The diagnosis of cSCC is established histologically, and requires a biopsy sample from the lesion in question. The type of biopsy taken generally depends on the size of the lesion and may include a punch, shave, or excisional biopsy.17 Hematoxylin and eosin staining techniques are normally sufficient to make the diagnosis, but in the rare cases of an unclear diagnosis, immunohistochemical markers may be used.17 Treatment for cSCC varies depending on whether or not the disease is superficial or invasive. For individuals with SCC in situ, nonsurgical destructive treatment options including electrodessication and curettage may be used.16,17 Treatment of invasive cSCC is achieved via surgical excision. Wide local excision is considered first-line treatment and is the most effective means for achieving a cure in invasive cSCC, because it allows for detection of tumor-free margins.17 Recurrent cases of cSCC, cases involving cosmetically sensitive areas (such as the face), those with indistinct margins, and lesions >2 cm should be referred for complete excision via Mohs micrographic surgery. If tissue margins are not tumor free or if there is substantial perineural involvement, adjuvant radiation therapy should be considered.17 For patients with metastatic cSCC, chemotherapeutic agents can be used.17 The patient in this vignette was diagnosed with cSCC after a shave biopsy was performed. Due to the location on

the ear, the patient was referred to a Mohs surgeon who was able to clear the cSCC and reconstruct his left ear. n Joan Fernandez, BS, is a medical student at the Baylor College of Medicine, and Christopher Rizk, MD, is a dermatology resident at the Baylor College of Medicine in Houston. References 1. Lomas A, Leonardi-Bee J, Bath-Hextall F. A systematic review of worldwide incidence of nonmelanoma skin cancer. Br J Dermatol. 2012;166:1069-1080. 2. Verkouteren JAC, Ramdas KHR, Wakkee M, Nijsten, T. Epidemiology of basal cell carcinoma: scholarly review. Br J Dermatol. 2017;177:359-372. 3. Robinson JK, Rigel DS, Amonette RA.Trends in sun exposure knowledge, attitudes, and behaviors: 1986 to 1996. J Am Acad Dermatol. 1997;37(2 Pt 1):179-186. 4. Rubin AI, Chen EH, Ratner D. Basal cell carcinoma. N Engl J Med. 2005;535:2262-2269. 5. Gallagher RP, Hill GB, Bajdik CD, et al. Sunlight exposure, pigmentary factors, and risk of nonmelanocytic skin cancer. I. Basal cell carcinoma. Arch Dermatol. 1995;131:157-163. 6. Kricker A, Armstrong BK, English DR, Heenan PJ. Does intermittent sun exposure cause basal cell carcinoma? A case-control study in Western Australia. Int J Cancer. 1995;60:489-494. 7. Maloney ME. Arsenic in dermatology. Dermatol Surg. 1996 22:301-304. 8. Kerr JF, Searle J. A suggested explanation for the paradoxically slow growth rate of basal-cell carcinomas that contain numerous mitotic figures. J Pathol. 1972;107:41-44. 9. Sexton M, Jones DB, Maloney ME. Histologic pattern analysis of basal cell carcinoma: Study of a series of 1039 consecutive neoplasms. J Am Acad Dermatol. 1990;23(6 Pt 1):1118-1126. 10. Crowson AN. Basal cell carcinoma: biology, morphology and clinical implications. Mod Pathol. 2006;19(suppl 2):S127-S147. 11. Stulberg DL, Crandell B, Fawcett RS. Diagnosis and treatment of basal cell and squamous cell carcinomas. Am Fam Physician. 2004;70:1481-1488. 12. Miller BH, Shavin JS, Cognetta A, et al. Nonsurgical treatment of basal cell carcinomas with intralesional 5-fluorouracil/epinephrine injectable gel. J Am Acad Dermatol. 1997;36:72-77. 13. Davis J, Bordeaux J. Squamous cell carcinoma. JAMA Dermatol. 2013;149:1448. 14. Johnson TM, Rowe DE, Nelson BR, Swanson NA. Squamous cell carcinoma of the skin (excluding lip and oral mucosa). J Am Acad Dermatol. 1992;26(3 Pt 2):467-484. 15. Tan KB, Tan SH, Aw DC, et al. Simulators of squamous cell carcinoma of the skin: diagnostic challenges on small biopsies and clinicopathological correlation. J Skin Cancer. 2013; 2013:752864. doi: 10.1155/2013/752864. 16. Alam M, Ratner D. Cutaneous squamous-cell carcinoma. N Engl J Med. 2001;344:975-983. 17. Stratigos A, Garbe C, Lebbe C, et al. Diagnosis and treatment of invasive squamous cell carcinoma of the skin: European consensus-based interdisciplinary guideline. Eur J Cancer. 2015;51:1989-2007.

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LEGAL ADVISOR CASE

A patient commits murder

ANN W. LATNER, JD

Ms T was a family nurse practitioner (NP) working in a primary care practice. She saw her own patients and did her own prescribing. To be able to prescribe controlled substances, Ms T needed to have a consultation and referral plan with a consulting physician. Dr H, another physician in the practice, agreed to be Ms T’s consulting physician. The two clinicians worked well together, but as time went on Ms T consulted with the physician less often, and ultimately rarely, if ever. One of Ms T’s patients was Mr D, 32. The young man was married and had a new baby and a toddler, but he was stressed and exhausted. His marriage was struggling and he felt overwhelmed. He sought care from Ms T beginning in April for a variety of issues, including depression, anxiety, and other complaints. Ms T prescribed testosterone and pregnenolone for Mr D. The following month, she increased the dosage of both drugs. In July, Ms T diagnosed Mr D with attention-deficit/hyperactivity disorder and prescribed methylphenidate. In September, Ms T doubled the patient’s dosage. The patient was also taking diazepam, doxepin,

A nurse practitioner is sued by her patient’s children after their mother is murdered.

The lawsuit alleges clinician negligence in prescribing medications, which resulted in the patient killing his wife and leaving the children without a parent.

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and paroxetine, as well as the hair loss medication, finasteride. Ms T relied on her own judgment in prescribing and did not consult with Dr H when changing the dosage or ordering new medications for her patient. The clinician last saw Mr D in late December. He did not look well and confided in the clinician that his marriage was on the rocks and his wife had filed for separation. Ms T was sympathetic, but after the patient left her office she did not think about him until a few weeks later when she saw his picture on the news. Mr D had shot and killed his wife in the parking lot of a church as she was on her way into services with the children. He was arrested and eventually pled guilty to aggravated murder and was sentenced to 20 years to life in prison. During Mr D’s sentencing, he told the judge that he took full responsibility for his wife’s death. 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.

But he also claimed that he would not have murdered her had he not been on medications. Mr D’s two young children were taken in by their maternal grandmother, and a conservator was appointed to look after their legal and financial interests. Ms T, like everyone else in the community, was horrified by what had happened. But she did not understand that there could be a connection to her, until she was served with papers notifying her that she, and Dr H, were being sued by the minor children via the conservator. The lawsuit alleged that the clinicians were negligent in prescribing the medications to Mr D, and that this resulted in Mr D killing his wife and going to jail, leaving the children without a parent. The NP immediately sought counsel from a defense attorney, who reassured her, “We should be able to get this dismissed. You only owe a duty to your patient, not to a third-party.” Sure enough, the attorney made a motion to dismiss the case against Ms T based on the fact that “no patient–health care provider relationship existed” between the plaintiffs (the children) and the defendants (Ms T and Dr H). The lower court agreed, and the case was dismissed. Ms T’s relief was short-lived. The plaintiffs filed an appeal, claiming that the lower court had incorrectly concluded that defendants did not owe a duty of care to nonpatient plaintiffs. On appeal, the state’s supreme court agreed with the plaintiffs. Whether the prescriptions actually caused Mr D to act was not the issue, said the court. Rather, the question was whether a duty to nonpatients exists based on the act of prescribing. In its decision, the court wrote, “Healthcare providers perform a societal function of undoubted social utility. But they are not entitled to an elevated status in tort law that would categorically immunize them from liability when their negligent prescriptions cause physical injury to nonpatients. We uphold a duty of healthcare providers to nonpatients in the affirmative act of prescribing medication, and reverse the district court’s conclusion to the contrary.” After this decision, Ms T settled out of court with the plaintiffs. However, the physician, Dr H, was still a party to the lawsuit. The lawsuit claimed that Dr H was negligent as a consulting physician for not reaching out to Ms T to discuss her treatment decisions. The physician filed his own motion to dismiss. Regarding the physician’s responsibility, the court concluded that it was the NP’s duty, not the physician’s, to

consult with the physician about the prescriptions that she was writing, and the court dismissed the case against Dr H. Legal background

After this case was decided, the legislature in the state where this case took place enacted the “Nonpatient Cause of Action,” recognizing a legal relationship between a healthcare provider and nonpatients in negligence claims. There is no

The court stated that the issue was whether a duty to nonpatients exists based on the act of prescribing. need to establish a clinician–patient relationship to bring a negligence claim against a healthcare provider. The language of the statute requires that to establish a malpractice action against a healthcare provider, a nonpatient plaintiff must show: • That the nonpatient plaintiff suffered an injury; • That the injury was proximately caused by an act or omission of the healthcare provider; and, • That the healthcare provider’s act or omission was conduct that manifests a knowing and reckless indifference toward, and a disregard of, the injury suffered by the non-patient plaintiff. Protecting yourself

This case never got to the causation part, so it is hard to tell whether Ms T’s prescribing was a contributing factor to Mr D’s actions. However, a few things can be learned from this. It is essential to always keep up-to-date concerning medications and controlled substances and the interactions and possible adverse reactions that may occur. It also is important to review your nurse practice act and rules and requirements for consultation, particularly with controlled substances. Remember, the onus is on you to seek advice from your consulting physician. When in doubt about a prescription, or a course of treatment, speak to your consulting physician. Ms T might have protected herself and her patient and his family, if she had consulted with Dr H before writing new prescriptions and increasing dosages for her patient. n Ms Latner, a former criminal defense attorney, is a freelance medical writer in Port Washington, N.Y.

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ALTERNATIVE MEDS UPDATE

What you should know about the herbs and supplements patients use By Sherril Sego, FNP-C, DNP Ms. Sego is an independent consultant in Kansas City, Mo.

Copper

In light of increasing regulation and concern regarding the use of opioid pain medications, patients are searching for alternative pain management methods. As healthcare providers, we must be aware of these methods and their safety and efficacy to advise patients properly. One popular ancient remedy is copper. The medicinal use of copper dates to nearly 2000 BC and has been noted in the writings of several ancient cultures.1 More recently, American folk medicine purports the use of copper, especially in the form of jewelry and bracelets, to mitigate the pain and swelling of osteoarthritis.

Background Considering that arthritis affects an estimated 30 million people in the United States alone, with an annual economic burden exceeding $128 billion, safe and effective methods of treatment would be tremendously beneficial.2 Expand the etiology of pain to include all sources, and conservative estimates of the number of people with chronic pain suggest that more than 100 million people in the United States deal with this malady on a daily basis.3 The resulting economic costs are calculated into the billions of dollars annually in lost work time and productivity and medical care costs. Copper is a metal with an atomic number of 29 on the Periodic Chart of the Elements.4 It is considered a trace element that, even though metallic, is essential to human life. It is a key part of many metabolic processes. Copper deficiency can contribute to conditions such as osteoporosis, impaired neurologic development, and overall immune dysfunction.5 The discussion about the safety and efficacy of copper in

the form of bracelets and jewelry is much the same as for other alternative therapies. The “Does it work” question is often answered by testimonials and folklore rather than by scientific study. However, our first question should be “Is it safe.” If the answer to that is affirmative, then we are able to concentrate on what our patient wants and feels is effective. Based on available research, copper would appear to be one of those treatments.

Science Few human clinical trials evaluating the safety and efficacy of copper for pain are found in the current literature, and most existing trials fail to show efficacy against a placebo control. With that said, the proposed mechanism of action of copper for pain is based on a theory known as trapped electricity.6 This somewhat controversial concept is based on the known electrical impulses involved in all neuromuscular function. An insult that results in the perception of pain

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causes the production of abnormal or aberrant electrical impulses from the nervous system. These impulses are received and perceived by the central nervous system as pain.7 The theory of trapped electricity purports that pain involves an excessive or hyperproduction of electrical activity that is in excess of that which our bodies can normally disperse, resulting in retained, or trapped, electrical activity. This energy, much like a pinball, continues to bounce back and forth in the system, perpetuating the pain sensation. Copper, usually in the form of jewelry or impregnated fabric, with its positive ionic charge, is theorized to neutralize this trapped electricity by submicron transdermal absorption. In possibly the only actual randomized, placebo-controlled human study with copper bracelets, 45 individuals with diagnosed osteoarthritis were enrolled into the trial.8 Participants wore a blinded rotation of magnetic, copper, and demagnetized metal wrist bracelets. Each bracelet was worn for 4 weeks, with participants evaluated during each phase by the standardized arthritis symptom scales of the WOMAC-A, B, and C. Even though results were statistically significant among the bracelets (favoring the copper bracelet), the overall outcome did not reach significance compared with placebo.

Safety, how supplied, dose, cost

Summary

Copper bracelets are theorized to neutralize trapped electricity.

Oral copper supplements are not recommended unless extensive metabolic testing shows a true copper deficiency.

Despite generations of believers, there is no scientific evidence of any efficacy of copper for the treatment of arthritic pain. There is, however, often a significant placebo effect of the treatment because of the long history in folklore and there is no real safety risk. In contrast, oral supplementation that is unmonitored or in excess of recommended amounts can be potentially lethal. Supplementation should not be recommended unless extensive metabolic testing shows a true copper deficiency. n References 1. Dollwet HHA, Sorenson JRJ. Historic uses of copper compounds in medicine. In: Trace Elements in Medicine. 2nd ed. Totowa, NJ: Humana Press; 2001:80-87. 2. Centers for Disease Control and Prevention. Arthritis. https://search.cdc.gov/search?query=arthritis&utf8=%E2%9C% 93&affiliate=cdc-main. Updated 2017. Accessed October 6, 2017. 3. Gaskin DJ, Richard P. The economic costs of pain in the United States. J Pain. 2012;13:715-724. 4. Meija J, Coplen TB, Berglund M, et al. Atomic weight of the elements 2013 (IUPAC Technical Report). Pure Appl Chem. 2016;88:265-291. 5. Stern BR, Solioz M, Krewski D, et al. Copper and human health: biochemistry, genetics, and strategies for modeling dose-response relationships. J Toxicol Environ Health B Crit Rev. 2007;10:157-222. 6. Grace H. Copper for pain: the theory of trapped electricity. Intractable Pain J. https://thepainjournal.wordpress. com/2011/04/23/copper-for-pain-the-theory-of-trappedelectricity/. 2011. Accessed October 6, 2017. 7. DeSantana JM, Walsh DM, Vance C, Rakel BA, Sluka KA. Effectiveness of transcutaneous electrical nerve stimulation for treatment of hyperalgesia and pain. Curr Rheumatol Rep. 2008;10:492-499. 8. Richmond SJ, Brown SR, Campion PD, et al. Therapeutic effects of magnetic and copper bracelets in osteoarthritis: a randomised placebo-controlled crossover trial. Complement Ther Med. 2009;17:249-256. 9. Bush AI,Tanzi RE.Therapeutics for Alzheimer’s disease based on the metal hypothesis. Neurotherapeutics. 2008;5:421-432. 10. Institute of Medicine (US) Panel on Micronutrients. Dietary reference intakes for vitamin A, vitamin K, arsenic, boron, chromium, copper, iodine, iron, manganese, molybdenum, nickel, silicon, vanadium, and zinc. Washington (DC): National Academies Press (US); 2001.

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The safety of external copper is only a problem in individuals who exhibit an allergic response to contact with jewelry or clothing items. However, using oral supplements to augment nutritional copper can lead to serious conditions as a result of copper accumulation in tissues. Excess tissue concentration of copper has been implicated in Alzheimer dementia and is a known consequence of the genetic condition Wilson disease.9 More minor side effects include nausea and vomiting. Copper in minute doses can be found in many over-the-counter supplements as well as in a variety of foods. Normal diets do not typically create a toxic level of copper, and supplemental copper in doses greater than 1 mg/day are not recommended.10 Cost of supplements is negligible and copper bracelets can be purchased for less than $10.