Clinical Advisor March/April 2022 Issue

A PEER-REVIEWED FORUM FOR NURSE PRACTITIONERS

CASE

Workup for Incidental Pituitary Adenoma in Primary Care Setting LEGAL ADVISOR

Gastric Band Infection and Later Stroke

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MARCH/APRIL 2022

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SCREENING IN PRIMARY CARE

A Perfect Storm: Rise in Eating Disorders Among Teens During COVID-19 Less than 6% of people with­ eating disorders are underweight.

FEATURE

Sudden, Bizarre Behavior Leads to Diagnosis of Novel Cause of Psychosis

DERMATOLOGIC LOOK-ALIKES

Growing Skin Lesion

Medical editor Kristin Della Volpe Assistant editor Jeanelle Jacobs Production editor Kim Daigneau Group creative director Jennifer Dvoretz Senior production manager Krassi Varbanov Account executive Michael Delaney, 551.206.5334 michael.delaney@haymarketmedia.com Publisher Kathleen Hiltz, 201.774.1078 kathleen.hiltz@haymarketmedia.com Vice president, content, medical communications Kathleen Walsh Tulley Chief commercial officer Jim Burke, RPh President, medical communications Michael Graziani Chairman & CEO, Haymarket Media, Inc. Lee Maniscalco All correspondence to: The Clinical Advisor 275 7th Avenue, 10th Floor, New York, NY 10001 For advertising sales, call 646.638.6085.

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FROM THE DIRECTOR PTSD From COVID-19 Have you heard the good news? The COVID-19 epidemic in the United States is over! On the stroke of midnight March 1, most states and local governments lifted their mask mandates, essentially declaring the pandemic under control. Or at least that is the message to consumers; health care professionals may be hearing a different message.

After 3 years of battling COVID-19, and close to 1 million deaths, the mental health toll of the pandemic is evident everywhere. As our cover story reports, children and adolescents are presenting with eating disorders in greater numbers and severity than prepandemic. “We are seeing eating disorder rise in rates that I have never seen in my whole career,” Jessica Peck, DNP, told The Clinical Advisor.

For at-risk youths, the COVID-19 pandemic caused major disruption in school, sports, social and leisure activities, as well as an increase in social media use. “We have seen patients who are coming in more malnourished and more entrenched in these eating disorder thoughts than I have ever seen before,” Christin Cwynar, DNP, said. Primary care clinicians can play a key role in early diagnosis and management of these youths.

This level of stress and anxiety is also reflected in the results of an online survey we conducted between January 7 and March 3, 2022, the results of which are published on page 20. “Pizza is not enough,” wrote one respondent. “Clinicians need to know that health care leaders hear their complaints and will respond to the need to be protected, prepared, supported, and cared for as they continue to” put themselves on the frontlines of this and future pandemics, wrote author Catherine R. Judd, MS, PA-C, CAQ-Psy. Another frightening example of the mental health effects of COVID-19 is a case report of a mother who tried to make her children drink bleach, thinking they were infected with parasites (see page 17). The patient was diagnosed with COVID-19 psychosis, which can occur both in the active phase of infection as well as up to 3 months after infection. The patient recovered after intense inpatient therapy and medication management.

These articles are just a reminder that although the pandemic may be “over,” its longer-term effects are just starting to be felt.

Nikki Kean, Director The Clinical Advisor www.ClinicalAdvisor.com • THE CLINICAL ADVISOR • MARCH/APRIL 2022 1

© JUANMONINO / GETTY IMAGES

Director Nikki Kean nikki.kean@haymarketmedia.com

CONTENTS MARCH/APRIL 2022

FEATURES 6

A Perfect Storm: Rise in Eating Disorders Among Teens During COVID-19 Eating disorders among adolescents have doubled since the beginning of the COVID-19 pandemic.

11

Workup for Incidental Pituitary Adenoma in Primary Care Setting Pituitary gland tumors are often found incidentally.

17

Sudden, Bizarre Behavior Leads to Diagnosis of Novel Cause of Psychosis A woman is evaluated after attempting to make her children drink bleach.

20

Pizza Is Not Enough: NPs, PAs Want to Be Heard, Protected, and Supported Results of The Clinical Advisor survey on mental wellness among health care workers.

11 Complete workup needed before referral.

20 Collateral damage from COVID-19.

DEPARTMENTS 1

From the Director PTSD From COVID-19

4

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

25

Dermatologic Look-Alikes Growing Skin Lesion

31

Legal Advisor Gastric Band Infection, Subarachnoid Hemorrhage, and Death

25 Scar emerging from removed cyst.

31 Delay in removing infected gastric band.

Follow us on Twitter @ClinicalAdvisor

MORE WAYS TO FIND US!

Like us on Facebook facebook.com/TheClinicalAdvisor Visit us on the web ClinicalAdvisor.com Download the app ClinicalAdvisor.com/App

www.ClinicalAdvisor.com

Newsline HOSPITALS THAT employ more inpatient NPs have improved patient outcomes, greater staff nurse satisfaction, and lower surgical mortality and cost of care, according to study findings published in Medical Care.

The researchers examined data collected between 2015 and 2016 from more than 1.4 million patients in 579 hospitals.The data were derived from the RN4CASTUS nurse surveys, Hospital Consumer Assessment of Healthcare Providers and Systems patient surveys, surgical patient discharge abstracts, Medicare Spending per Beneficiary reports, and the American Hospital Association annual survey.

The objective was to determine “for the first time in a nationally representative sample of hospitals and patients whether increased NP staffing in hospitals adds value after taking into account

investments hospitals have already made in RN staffing and preferential hiring of RNs with bachelor’s education,” said the study authors. Hospitals were grouped based on their NP to bed ratios (<1 NP/100 beds, n=132; 1–2.99 NPs/100 beds, n=279; 3+ NPs/100 beds, n=168).

Patients in hospitals with 3 or more NPs per 100 beds had lower 30-day mortality rates, fewer readmissions, and shorter length of stay than patients in hospitals with less than 1 NP per 100 beds. Both patients and nurses in hospitals with higher NP to bed ratios reported better quality of care and safety. Nurses also reported lower burnout rates, higher job satisfaction, and greater intentions of staying in their jobs.

“This is the first large study to document the significant added value of hospitals employing NPs in acute inpatient hospital care as well as having good RN

© TEMPURA / GETTY IMAGES

Higher Number of Inpatient NPs Improves Outcomes

Hospitals with higher NP to bed ratios reported better quality of care and safety.

staffing,” said the authors. “When we compared hospitals with the most and fewest NPs, we estimated that hospitals with more NPs had 21% fewer deaths after common surgical procedures and 5% lower Medicare costs per beneficiary.”

The findings “are relevant to policy debates taking place in many states regarding modernizing state practice acts governing NP scope of practice,” they added.

Intermittent Fasting Effective for Weight Loss in Adults With Obesity INTERMITTENT FASTING is associated with measurable weight loss and metabolic benefits in adults with overweight or obesity, researchers reported in JAMA Network Open.

The study authors selected 11 meta-analyses, which included 130 randomized clinical trials with a median sample size per trial of 38 participants and follow-up of 3 months. Among the types of intermittent fasting included in the studies were zero-calorie alternate-day fasting, modified alternate-day fasting, the 5:2 diet (fasting for 1 to 2 consecutive or nonconsecutive days per week), and time-restricted eating (fasting for 12 to 24 hours per day).

A total of 104 unique associations were identified, with varying levels of evidence. The associations primarily involved adults with overweight or obesity and showed beneficial outcomes

associated with intermittent fasting for BMI, body weight, fat mass, low-density lipoprotein cholesterol, total cholesterol, triglyceride level, fasting plasma glucose, fasting insulin, homeostatic model assessment for insulin resistance, and blood pressure. Intermittent fasting was also associated with reductions in fat-free mass.

Of the 7 associations supported with moderate- to highquality evidence, 6 were statistically significant. One significant association supported by high-quality evidence was that modified alternate-day fasting for 1 to 2 months was associated with lower BMI in healthy adults and adults with overweight, obesity, or nonalcoholic fatty liver disease vs regular diet (mean difference, −1.20; 95% CI, −1.44 to −0.96) in a meta-analysis.

www.ClinicalAdvisor.com • THE CLINICAL ADVISOR • MARCH/APRIL 2022 3

EXCLUSIVE TO THE WEB AT

ClinicalAdvisor.com

NEWS ClinicalAdvisor.com/News

CLINICAL CHALLENGE ClinicalAdvisor.com/Clinical-Challenge

Plant-Based Diet Reduces Risk for Severe COVID-19

Brady Pregerson, MD Cough, Fever, in Person Who Vapes A 16-year-old adolescent presents to the emergency department with a 3-day history of vomiting, tactile fevers, and a mild headache that went away 2 days earlier. The patient denies any abdominal or flank pain, dysuria, diarrhea, or other complaints.

When specifically questioned, she acknowledges a slight cough but has no shortness of breath or chest pain.

See the full case at: clinicaladvisor. com/case_march_april22

Studies suggest that adhering to a plantbased, healthy diet reduces the risk for chronic conditions such as diabetes and obesity, which in turn reduces the risk for severe COVID-19.

Black Women With Lupus at Increased Risk for Poor Perinatal Outcomes Black women with systemic lupus erythematosus (SLE) are at increased risk for adverse perinatal outcomes such as preterm and small-for-gestational-age infants compared with those without SLE.

Nonopioid Regimen Controls Postoperative Pain After Knee, Shoulder Surgery Multimodal nonopioid regimen of NSAIDs and muscle relaxants provides similar or better pain control than opioids after anterior cruciate ligament and rotator cuff surgeries.

Method Improves Risk Assessment for Lung Cancer Screening

TOP, MIDDLE IMAGES: © GETTY IMAGES

Risk assessment for lung cancer screening can be improved by combining a blood biomarker test and a risk prediction model.

THE WAITING ROOM

Official Blog of The Clinical Advisor ClinicalAdvisor.com/WaitingRoom Jim Anderson, MPAS, PA-C, DFAAPA COVID Fatigue: Is It Over Yet? Jim Anderson explores COVID19 fatigue and how it is all a bit numbing for medical providers who are trying to do their best to treat patients while clinging to trusted sources to help guide the way.

MY PRACTICE ClinicalAdvisor.com/MyPractice

Lumateperone Improves Depressive Symptoms Among Patients With Bipolar Disorder Investigators assessed the safety and efficacy of lumateperone for the treatment of bipolar I and II disorders in patients experiencing major depressive episodes.

4 THE CLINICAL ADVISOR • MARCH/APRIL 2022 • www.ClinicalAdvisor.com

Kristin Della Volpe AANP President’s Message to Frontline Clinicians Dr April Kapu addresses self-care and support systems among NPs and PAs during the COVID-19 pandemic.

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

Check out some of our latest cases below!

DERM DX

Pink Papule on Nose A 79-year-old man with a history of both basal cell carcinoma and squamous cell carcinoma presents with a slow-growing lesion on the nose that has been growing for 10 years. On examination, an 8-mm pink papule is present on the left nasal alar rim. A shave biopsy is collected. The histologic evaluation reveals a storiform pattern of fibrohistiocytic cells with intermixed cellular infiltrate, streaks of entrapped collagen, and epidermal hyperplasia.

CAN YOU DIAGNOSE THIS CASE?

• Dermatofibroma • Basal cell carcinoma

• Adnexal neoplasm • Mesanocytic nevi

● See the full case at ClinicalAdvisor.com/DermDx_march_april22

ORTHO DX

In partnership with

TheJopa.org

Journal of Orthopedics for Physician Assistants

Knee Pain Below Patella in Child An 11-year-old girl presents for evaluation of left knee pain for 2 months. The pain is located at the front of the knee just past the patella on the lower leg and is made worse with running and jumping.

She has tried ice and anti-inflammatory medications, which offered mild relief. On physical examination, the patient has knee effusion and tenderness to palpation over the tibial tubercle on the left knee.

WHAT IS THE NEXT BEST STEP IN TREATMENT?

• NSAIDs, rest, and quadriceps stretching • Physical therapy to include quadriceps strengthening and h ­ amstring stretching • Hinged knee brace locked in extension for 4 weeks • MRI of the knee ● See the full case at ClinicalAdvisor.com/OrthoDx_march_april22

www.ClinicalAdvisor.com • THE CLINICAL ADVISOR • MARCH/APRIL 2022 5

FEATURE: KRISTIN DELLA VOLPE

A Perfect Storm: Rise in Eating Disorders Among Teens During COVID-19 Eating disorders among adolescents have doubled since the start of the pandemic and patients are presenting with more severe symptoms.

© GETTY IMAGES / MONTAGE BY VIVIAN CHANG

P

The pandemic was cited as a trigger among 40% of newlydiagnosed teens.

6 THE CLINICAL ADVISOR • MARCH/APRIL 2022 • www.ClinicalAdvisor.com

ediatric clinicians are sounding the alarm on the marked rise in eating disorders and symptom severity in children and adolescents during the COVID-19 pandemic. Eating disorders are the most deadly psychiatric condition in children, with 1 in 5 dying from suicide or medical complications related to the disorder.1,2 Experts have stressed that the need to take action is urgent.1,2 “We are seeing eating disorders rise in rates that I have never seen in my whole career,” said Jessica Peck, DNP, APRN, CPNP-PC, CNE, CNL, immediate past president of the National Association of Pediatric Nurse Practitioners (NAPNAP). As the COVID-19 pandemic surged, eating behaviors may have become an outlet for control among at-risk youth, said Dr Peck, who is also clinical professor at the Baylor University Louise Herrington School of Nursing in Dallas, Texas.

Eating disorders often have a protracted course and are difficult to treat, with only 31% of patients with anorexia nervosa recovering within 10 years.3 Early recognition and treatment of eating disorders is essential, Dr Peck said. But for children and teens, finding qualified mental health providers may be difficult.

Currently, only 10 child psychiatrists are available for every 100,000 pediatric patients.4 Nearly 3 million children and adolescents do not have access to a school-based mental health professional, such as a school psychologist, counselor, or

social worker.5 The Children’s Hospital Association has called the mental health crisis among children and teens a national emergency and has called on Congress to take immediate action to fund services to stem this escalating crisis.6 Given this dearth of specialty psychiatric care, “we need to get better at integrating mental health services into primary care,” Dr Peck said, adding that effective screening tools are available and allow for early intervention.

Why Are Rates Rising?

The COVID-19 pandemic led to a profound disruption in school, sports, work, as well as social and leisure activities among people of all ages. For at-risk youth, the mental and physical effects of these disruptions triggered or worsened disordered eating behaviors. Additionally, the pandemic led to increased social media use, which has been linked to worsening symptoms in individuals with eating disorders, and increased video interactions, which may increase self-criticism and negative appearance-related comparisons.7 Altered food accessibility, food insecurity, and limited access to health care during the pandemic may also have played roles in the rising rates.7 Together, these changes have created a perfect storm of stressors in this vulnerable patient population.

At a center for pediatric eating disorders, data showed that 40% of newly-diagnosed adolescents cited the pandemic as a trigger for their disorder.8 Data on new-onset anorexia nervosa or atypical anorexia nervosa from 6 pediatric tertiary-care ­hospitals in Canada showed an increase from a mean of 24.5 cases per month prepandemic to 40.6 cases per month in the first wave of the pandemic (P <.001).9 A near tripling of hospitalization rates in newly diagnosed children and adolescents was also found, and the severity of eating disorder symptoms was worse in those diagnosed during the COVID-19 pandemic than in those diagnosed prepandemic, with more rapid progression, greater weight loss, and more profound bradycardia found.9 Similar findings were reported at C.S. Mott Children’s Hospital in Ann Arbor, Michigan, which saw a more than 2-fold increase in hospital admissions among patients aged 10 to 23 years with eating disorders during the first 12 months of the COVID-19 pandemic: 125 vs 56 hospitalizations on average per year during the same time frame for the previous 3 years.7 The rate of hospitalizations for eating disorders were highest near the end of the study period, between 9 and 12 months after the pandemic started.7 At Cincinnati Children’s Hospital Medical Center, youth hospitalized after the pandemic started were over 8-times more likely to be readmitted within 30 days of discharge compared with patients hospitalized prepandemic (P =.002).10 “We have patients who are coming in more malnourished and more entrenched in these eating disorder thoughts than I

have ever seen before,” said Christina Cwynar, DNP, CPNP-PC, PMHNP-BC, during a NAPNAP TeamPeds Talks podcast.

“I have encountered some of the lowest BMIs, some of the youngest patients [9 and 10 years old], and some of the most significant behavioral issues that I have ever encountered,” said Dr Cwynar, who is a pediatric NP at C.S. Mott Children’s Hospital and assistant professor in the Primary Care Pediatric Nurse Practitioner Program at Rush University College of Nursing in Chicago.

With wait lists at many eating disorder clinics of 6 months to a year even before the pandemic, the greater demands posed by COVID-19 have led to even longer delays in treatment.This inability to seek timely treatment is at least partially responsible for the greater symptom severity observed in clinical practice, Dr Cwynar believes.

These numbers may represent a small percentage of the number of children and teens with eating disorders affected by the pandemic as the studies only show those people whose illness led to hospitalization.7 Eating Disorders Defy Stereotype

Although the stereotypical patient with an eating disorder is a White thin teenage girl, less than 6% of people with eating disorders are underweight.2,11 Binge eating disorder, which commonly leads to weight gain, is more common than anorexia nervosa and larger body size is a risk factor for developing eating disorders.2,11,12 However, people with eating disorders who are overweight are half as likely to be diagnosed with these conditions as those with smaller body sizes.2 “We are also seeing boys and teens of color with eating disorders, and people who are normal weight to overweight having binge eating disorder,” Dr Peck said. In boys and young men, disordered eating may focus on leanness, muscularity, and weight control.12 Adolescent athletes are also at risk.2,12 Data show that Black teenagers are 50% more likely to engage in binge eating and purging compared with White teenagers, but are significantly less likely to be asked by a clinician about eating disorder symptoms and 50% as likely to be diagnosed or treated for these disorders.2 Bulimia nervosa is more common among Hispanic persons than their non-Hispanic peers, and Asian American college students report higher rates of food restriction and higher rates of purging compared with their White peers.2 Teens in the LGBTQI community have significantly higher rates of unhealthy and disordered weight control behaviors than their cisgender peers.12 The risk may be particularly increased in transgender youth.12 Genetics, psychological factors, and social influences have all been linked to eating disorders and adolescents with low self-esteem or depressive symptoms are at especially high risk.7

www.ClinicalAdvisor.com • THE CLINICAL ADVISOR • MARCH/APRIL 2022 7

RISE IN EATING DISORDERS

Screening in Primary Care

The American Academy of Pediatrics (AAP) recommends screening for disordered eating and unhealthy weight-control behaviors annually at well visits and evaluating BMI, growth charts, menstrual status, and vital signs. Patient reports of dieting, body image dissatisfaction, weight-based stigma, or changes in eating or exercise may indicate the need for further exploration.12 “There are many misconceptions about eating disorders and what characteristics or behaviors are used when someone has an eating disorder,” said Amanda Dietz, MSN, FNP-C, CPN, who works at the Eating Disorder Center at Children’s Mercy Kansas City in affiliation with the Department of Pediatrics at the University of Missouri-Kansas City School of Medicine in Missouri. Weight loss noted on growth curves is an easy way to identify concerning behaviors and should prompt the provider to ask more questions, Dietz said.

The most widely used screening tools to identify anorexia nervosa and bulimia nervosa are the SCOFF questionnaire and Eating Disorder Screen for Primary Care (ESP), both of which are freely available (see Screening Tools for Primary Care).13,14 In patients with suspected eating disorders, primary care providers should initiate a comprehensive medical, psychological, and suicide risk assessment, as outlined in the AAP guidelines.

Normal laboratory results alone do not equal a medically stable patient and a holistic approach to assessment should be used, Dietz explained. In atypical anorexia nervosa, for example, patients meet all of the criteria for anorexia nervosa but their body weight remains within or above the expected range for age and height, which can lead to delayed diagnosis (Table 1).2,11,12 Screening Tools for Primary Care SCOFF QUESTIONNAIREa • Do you make yourself Sick because you feel uncomfortably full?

• Do you worry you have lost Control over how much you eat?

• Have you recently lost more than One stone (14 pounds) in a 3-month period?

• Do you believe yourself to be Fat when others say you are too thin?

• Would you say Food dominates your life?

EATING DISORDER SCREEN FOR PRIMARY CAREb • Are you satisfied with your eating patterns?

• Do you ever eat in secret?

• Does your weight affect the way you feel about yourself?

• Have any members of your family suffered with an eating disorder?

• Do you currently suffer with or have you ever suffered in the past with an eating disorder? a b

≥2 abnormal responses are considered a positive screen ≥3 abnormal responses are considered a positive screen

Clinicians may praise their patient for weight loss without being aware that the patient is at equal or greater risk for medical instability compared with their underweight counterparts.“Be cautious about encouraging rapid weight loss in some patient populations, especially pediatric patients,” Dietz said.

Patients who are being evaluated for eating disorders should undergo full psychosocial history that includes home environment, education level, activities, drugs/diet history, sexuality, and suicidality/depression (HEADSS) assessment.12 Equally important is the need to screen for common psychological comorbidities including mood and anxiety disorders, obsessive-compulsive disorder (OCD), attention-deficit hyperactivity disorder (ADHD), and alcohol and substance use disorders.1,2 The most commonly missed diagnosis in patients with disordered eating is ADHD.2 Treatment of Eating Disorders

Patients with mild nutritional, medical, and psychological dysfunction from eating disorders may be managed in the primary care setting in collaboration with mental health providers. Psychotherapy, such as cognitive-behavioral therapy, and nutritional repletion (replenishing the body with vitamin/ mineral supplementation and nutrients) are the cornerstones of treatment for eating disorders. Pharmacotherapy can be used as adjunctive therapy in select cases.12 The first step is to make sure the patient is medically stable and safe to continue treatment in the outpatient setting.

“Primary care providers often feel overwhelmed and underprepared to support patients during their eating disorder treatment,” Dietz noted. “Remembering that treatment is a team approach and that your role is to focus on the physical aspect of care can be helpful.”

“The refeeding process not only can be psychologically difficult, but also physically,” Dietz added. For restrictive disorders, clinicians “should focus on supporting the very real symptoms associated with malnutrition such as heartburn, fullness, bloating, and constipation. If these symptoms can be alleviated, it can make eating less distressing for the patient.” For example, the AAP recommends use of osmotic or bulk-forming laxatives over stimulant laxatives for patients with constipation.12 When counseling families, Dr Cwynar likens the fear of food in patients with restrictive eating disorders to being trapped in a room with a tiger. During treatment, patients have to overcome that fear every time they eat. Patients overtaken by an eating disorder cannot think rationally, she said.

She recommended giving parents ground rules including a meal plan handout (Table 2) and emphasized that “there is no negotiation with eating disorders.” All meals should have time limits so that “the individual is not spending all day attempting to eat food and to allow the body to learn to eat in normal patterns and digest normally again.” In addition to restrictive

8 THE CLINICAL ADVISOR • MARCH/APRIL 2022 • www.ClinicalAdvisor.com

eating disorders, meal plans are useful to break the binge/purge cycles in bulimia nervosa and binge-eating disorder. Dr Cwynar recommends an online video (https://www.youtube.com/ watch?v=2O9nZAWCkLc) to families on inspiring trust rather than using logic when relating to children with eating disorders.

“As these kids get more and more entrenched in their eating disorder, carbohydrates that were once okay to eat are now off-limits and become a fear food” but parents should not cater to these fears, Dr Cwynar said. This is not the time to adopt a gluten-free or dairy-free diet in children with no history of intolerance or transition to vegetarian or vegan diets, she said.

Dr Cwynar suggested time limits of 30 minutes for meals and 15 minutes for snacks “so that the individual is not spending all day attempting to eat food and to allow the body to learn to eat in normal patterns and digest normally again.” If children and teens do not comply with the plan, the eating disorder behavior has consequences such as seeing a doctor or not being able to see friends or play sports, Dr Cwynar said.

“Since we view eating disorders as a separate entity from the individual suffering from them, we talk about how eating disorders take things away from the child,” Dr Cwynar explained in an interview. “For example, because [some] eating disorders cause individuals to restrict food intake significantly leading to bradycardia, electrolyte imbalances, and other medical complications that place an individual at higher risk for seizures and death, individuals often miss out on things like planned activities with friends related to needing medical care or being unable to engage in sports or other hobbies that they like because it is too dangerous for them to engage in these activities at certain times during their disease and recovery process,” she said.

Pharmacotherapy Fluoxetine is indicated for the treatment of bulimia nervosa in adult patients and other selective serotonin reuptake inhibitors (SSRIs) have also demonstrated efficacy in managing this subtype of eating disorders when used off-label.Although fluoxetine is not approved for bulimia nervosa in pediatric patients, it is approved for OCD in patients aged 7 years and older and major depressive disorder in children aged 8 years and older; thus, it is a reasonable option for pediatric patients in whom pharmacotherapy is being considered, according to AAP.12,15 In contrast, SSRIs have not demonstrated efficacy in the management of binge eating disorder or restrictive eating disorders, and are particularly not effective in acutely malnourished patients.12 For avoidant/ restrictive food intake disorder (ARFI), pharmacotherapy is targeted at treating comorbidities such as anxiety.12 Dr Cwynar noted that SSRIs are not a quick fix as they take weeks to become effective. Small doses of olanzapine, which has a faster onset (typically 15-20 minutes), used before meals may help with the anxiety and agitation symptoms. She

TABLE 1. Common Subtypes of Eating Disorders2,11,12 Anorexia nervosa

• Significant and persistent reduction in food intake leading to severe weight loss; distorted body image; and intense fear of gaining weight • More common in young women and girls

Bulimia nervosa

• Recurrent binge eating episodesa marked by feelings of lack of control followed by compensatory behavior such as purging (eg, vomiting, excessive use of laxatives, or diuretics), fasting, and/or excessive exercise • Occurs at least once a week

Binge eating disorder

• Recurrent binge eating episodesa marked by feelings of lack of control and guilt, disgust, or depression • Episodes are not followed by purging, excessive exercise, or fasting • Occurs at least once a week for 3 months • Patients are often overweight or obese

Avoidant/ restrictive food intake disorder (ARFID)

• Lack of interest in eating, avoidance of food based on sensory qualities, concern about unpleasant consequences of eating • Leads to significant weight loss or failure to meet expected growth or weight gain, marked nutritional deficiency, reliance on enteral feeding or nutritional supplements, significant interference with psychosocial functioning • Behavior cannot be explained by another medical or mental disorder

Other specified feeding or eating disorder

• Atypical anorexia nervosa: significant weight loss despite being within or above normal weight range • Bulimia nervosa of low frequency and or limited duration • Binge eating disorder of low frequency and or limited duration • Purging disorder: recurrent purging behavior without binge eating with the intent to control weight or body shape

Eating a larger quantity of food more rapidly than normal in a distinct time period (eg, 2 hours)

a

TABLE 2. Ground Rules for Parents of Children With Eating Disorders • Follow a clinician-provided meal plan consisting of 3 meals and 2 to 3 snacks per day • Have child eat at a kitchen table with someone present and a time limit on meals (eg, 30 minutes) and snacks (eg, 15 minutes) • Present fully-prepared meals at set times with no negotiations • All healthy fats and spreads should already be incorporated into the meal • A child who does not finish a meal can be provided with a meal supplement • For children who have tantrums or fights during meals, paper plates and plastic utensils may be used • Physical restraint with a bear hug may be needed to calm a tantruming child down • For children who binge, providing appropriate portions of typically binged foods during meals may help prevent cravings and future binges • Do not allow children who binge and purge to use the bathroom unsupervised for an hour after a meal • Limiting exercise and access to scales, mirrors, and social media may be necessary • Have an emergency action plan in case the child’s condition worsens

www.ClinicalAdvisor.com • THE CLINICAL ADVISOR • MARCH/APRIL 2022 9

RISE IN EATING DISORDERS

‘We are also seeing boys and teens of color with eating disorders, and people who are normal weight to overweight’ having binge disorders. has also used the antihistamine hydroxyzine hydrochloride to treat the physiologic response to anxiety in patients with eating disorders, and noted that aripiprazole can help break the cycle of rigid circular thoughts in some individuals with eating disorders.16

7. Otto AK, Jary JM, Sturza J, et al. Medical admissions among adolescents with eating disorders during the COVID-19 pandemic. Pediatrics. 2021;148(4): e2021052201.

8. Spettigue W, Obeid N, Erbach M, et al. The impact of COVID-19 on adolescents with eating disorders: a cohort study. J Eat Disord. 2021;9(1):65.

9. Agostino H, Burstein B, Moubayed D, et al. Trends in the incidence of new-

Emergency Plans Parents should be given emergency plans such as going to the emergency department if a child has not eaten in 24 hours or going to the doctor to check electrolytes. Patients with more severe symptoms or who do not improve with outpatient care should be referred promptly to day-treatment or inpatient programs as waitlists for these centers are long. Medical admission should be considered for patients with severe bradycardia (heart rate <50 beats per minute), hypotension (<90/45 mm Hg), and hypothermia as well as dehydration and electrolyte disturbance, according to the Society for Adolescent Health and Medicine.17

onset anorexia nervosa and atypical anorexia nervosa among youth during the COVID-19 pandemic in Canada. JAMA Netw Open. 2021;4(12):e2137395.

10. Matthews A, Kramer RA, Peterson CM, Mitan L. Higher admission and rapid readmission rates among medically hospitalized youth with anorexia nervosa/atypical anorexia nervosa during COVID-19. Eat Behav.

2021;43:101573.

11. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders. 5th ed. American Psychiatric Association; 2013.

12. Hornberger LL, Lane MA; Committee on Adolescence. Identification and management of eating disorders in children and adolescents. Pediatrics.

2021;147(1):e2020040279.

13. Morgan JF, Reid F, Lacey JH. The SCOFF questionnaire: assessment of a new screening tool for eating disorders. BMJ. 1999;319(7223):1467-1468.

Conclusion

14. Cotton MA, Ball C, Robinson P. Four simple questions can help screen for

Eating disorders are the most deadly mental health conditions in children and adolescents. The rising rates of eating disorders during the COVID-19 pandemic and the limited number of mental health specialists may lead to longer wait times. Primary care clinicians can play a key role in early diagnosis and management. ■

eating disorders. J Gen Intern Med. 2003;18(1):53-56.

15. Prozac. Prescribing information. Eli Lilly and Company; 2009.

16. Frank GK, Shott ME, Hagman JO, Schiel MA, DeGuzman MC, Rossi B. The partial dopamine D2 receptor agonist aripiprazole is associated with weight gain in adolescent anorexia nervosa. Int J Eat Disord. 2017;50(4):447-450.

17. Society for Adolescent Health and Medicine, Golden NH, Katzman DK, et al. Position Paper of the Society for Adolescent Health and Medicine: medical

Kristin Della Volpe is Medical Editor of The Clinical Advisor.

management of restrictive eating disorders in adolescents and young adults.

J Adolesc Health. 2015;56(1):121-125.

References 1. Balasundaram P, Santhanam P. Eating disorders. In: StatPearls. StatPearls Publishing; 2022 Jan-. Updated December 19, 2021. https://www.ncbi.nlm.nih. gov/books/NBK567717/ 2. National Association of Anorexia Nervosa and Associated Disorder. Eating disorder statistics. Accessed February 9, 2021. https://anad.org/eating-disorders-statistics/ 3. Eddy KT,Tabri N,Thomas JJ, Murray HB, et al. Recovery from anorexia nervosa and bulimia nervosa at 22-year follow-up. J Clin Psychiatry. 2017;78(2):184-189.

4. McBain RK, Kofner A, Stein BD, Cantor JH, Vogt WB, Yu H. Growth and distribution of child psychiatrists in the United States: 2007-2016. Pediatrics.

2019;144(6):e20191576.

5. The Education Trust. School Counselors Matter. Accessed February 17, 2022. https://www.schoolcounselor.org/getmedia/b079d17d-6265-4166a120-3b1f56077649/School-Counselors-Matter.pdf 6. Sound the Alarm for Kids. Sound the alarm for kids: we are in a national mental health emergency. Accessed February 17, 2021. https://www.

Case Study Library Check out all of our case studies in obesity, diabetes, and other important topics in primary care — along with our clinical challenges — by visiting us at: ClinicalAdvisor.com/Case-Study

soundthealarmforkids.org/a-national-emergency/#footnote-6

10 THE CLINICAL ADVISOR • MARCH/APRIL 2022 • www.ClinicalAdvisor.com

FEATURE: MELISSA WASILENKO, MSN, RN

Workup for Incidental Pituitary Adenoma in Primary Care Setting Pituitary gland tumors are often found incidentally on imaging studies or during workup for abnormal endocrine hormone levels.

© ISM / SOVEREIGN / MEDICALIMAGES.COM

Approximately 65% of pituitary adenomas are functioning tumors.

A

35-year-old woman is seen for evaluation of an incidental pituitary macroadenoma.

Her medical history is significant for hypertension, diabetes, hyperlipidemia, polycystic ovary syndrome, and obesity. She initially presented to the emergency department (ED) a week ago after an episode of right visual field changes that she described as waviness in her right eye and right hemibody sensory changes without motor deficits.While in the ED, she underwent a full workup for possible stroke, which was negative. Magnetic resonance imaging (MRI) of her brain without contrast revealed a 12-mm pituitary lesion; a repeat MRI with contrast was then ordered (Figure, page 12). No serum hormonal panel was available for review from ED records.

Upon further questioning of her medical history, the patient notes that a few years ago she was attempting to become pregnant and was evaluated by her gynecologist for amenorrhea.At that time, she reportedly completed an endocrine laboratory workup that showed a slightly elevated prolactin level between 30 and 40 ng/mL (normal level in nonpregnant women, <30 ng/mL).

Per the patient, the minimal elevation was not enough to concern the gynecologist and no MRI was ordered at that time. Her gynecologist recommended that she lose weight. Her menses returned to normal with weight loss. With a history of disrupted menstrual cycles, infertility, and patient-reported elevated prolactin level, there is high suspicion for endocrine disruption.

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© MELISSA WASILENKO, MSN, RN

ENDOCRINOLOGY

FIGURE 1. Magnetic resonance imaging of the case patient. Left image: sagittal view. Right image: coronal view with contrast.

A complete pituitary panel is ordered to examine the current hormone level considering the recent MRI findings. This revealed a prolactin of 33.7 ng/mL; all other hormone levels were within normal limits.

Because the patient reports multiple episodes of visual disturbances and the size of the pituitary adenoma on MRI, a neuroophthalmology referral is initiated for testing and to determine if the pituitary macroadenoma is causing mass effect and compressing the optic nerve.The neuro-ophthalmologist found she had no visual field defect from her adenoma on testing and believed that her visual disturbances were probably migraine in nature.

Discussion

Pituitary gland tumors are usually found incidentally on imaging studies obtained for other reasons or in workup of patients with abnormal endocrine hormone levels (both decreased and increased levels) or with symptoms of mass effect from the lesions.1 These tumors are typically benign in nature; cases with malignancy are extremely rare.1 The exact pathophysiology of pituitary adenomas remains unknown but is thought to be linked to heredity, hormonal influences, and genetic mutations.1 Pituitary tumors are commonly found in adults between the ages of 35 and 60 years.2,3 The estimated prevalence of pituitary adenomas varies widely by study and findings are typically based on autopsy and radiology data. Surveillance, Epidemiology, and End Results (SEER) Program data from 2004 to 2018 show an incidence rate of pituitary adenomas and pituitary incidentalomas of 4.28 ± 0.04 and 1.53 ± 0.02 per 100,000 population.4 Pituitary tumors have been found in 14.4% of unselected autopsy cases and 22.5% of radiology tests.1 The SEER data suggest that incidence rates are similar among women and men but are higher among women in early life

and higher among men in later life.5 Rates of prolactinomas (prolactin-secreting tumors) and corticotropinomas (adrenocorticotropic hormone-secreting tumors; Cushing disease) are higher in women than men.6 Earlier SEER data showed a significantly higher incidence of pituitary adenomas in Black individuals compared with other racial/ethnic groups; several factors may account for this discrepancy such as the higher stroke rate in this population, which leads to a greater likelihood for brain imaging that detects incident pituitary tumors.5 Incidental findings of pituitary adenoma may be found during workup related to hormonal dysfunction (amenorrhea, galactorrhea, fertility disorders, sexual dysfunction), noticeable vision change, new-onset headaches, or imaging performed for other diagnostic purposes.7 Pituitary Types

Pituitary tumor types are differentiated by location, size, and functional status. Pituitary tumors commonly arise from the anterior portion of the gland (adenohypophysis) and rarely from the posterior portion (neurohypophysis).2 Both adenohypophyseal and neurohypophyseal tumors are commonly benign and slow-growing.1 Malignant pituitary tumors account for less than 1% of pituitary lesions and are usually metastases from breast and lung cancers.3 Adenohypophyseal carcinoma is rare, with less than 140 reported cases.2 Pituitary tumors are categorized by the size1,2: • Microadenomas (<10 mm) • Macroadenomas (>10 mm to 40 mm) • Giant adenomas (>40 mm) Pituitary adenomas are further classified as functioning (hormone-secreting) or nonfunctioning (nonsecreting).1,6 If

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Continues on page 14

ENDOCRINOLOGY

the adenoma is functioning, hormone levels will be found in excess. If the levels are within normal limits, a nonfunctioning pituitary adenoma is suspected.

Functioning Tumors Approximately 65% of all pituitary adenomas are functioning tumors.2 Functioning pituitary adenomas present in various ways depending on which hormone is involved and the level of hormone secretion. Prolactinomas are the most common type of functioning adenomas followed by growth hormone-secreting and adrenocorticotropic hormonesecreting pituitary tumors. Adenomas secreting thyrotropin and follicle-stimulating hormone are less commonly found.2 Clinical features of functional pituitary adenomas are outlined in Table 1.2,8 Nonfunctioning Tumors Approximately 20% to 30% of pituitary adenomas are nonfunctional.3 These tumors may go undiagnosed for years until the mass of the tumor starts to affect surrounding structures

and cause secondary symptoms such as compression of the optic chiasm resulting in vision impairment.

Nonfunctioning pituitary adenomas and prolactinomas (functioning) are the 2 most common types of pituitary adenomas.2,3 The consulting clinician must understand the difference in pathology of these 2 types of lesions, what diagnostic test to order, how to interpret the test results, and which specialty to refer the patient to based on the initial workup findings.

Initial Workup

Proper baseline workup should be initiated before referring patients with incidental pituitary adenoma to a specialist.The initial workup includes imaging, blood work to determine if the pituitary adenoma is causing hormonal dysfunction, and neuro-ophthalmology referral for visual field testing to determine if the optic nerve/chiasm is affected.

Imaging The most accurate diagnostic modality of pituitary gland pathology is MRI with and without contrast. The MRI

TABLE 1. Clinical Features and Laboratory Findings of Functioning Pituitary Adenomas2,8 Adenoma Type

Percentage of Functioning Pituitary Adenomas, %

Prolactin-secreting

Clinical Features

Laboratory Findings

48

• Amenorrhea • Erectile dysfunction • Loss of libido • Galactorrhea • Gynecomastia • Fertility issues

• Prolactin >150 ng/mL

Growth hormone-secreting

10

• Enlarged, protruding jaw • Enlarged frontal bones • Enlarged and swollen hands and feet • Metabolic disorders • Facial disfigurement • Musculoskeletal disabilities • Respiratory and cardiovascular dysfunction

• In acromegaly, GH >10 ng/mL • Elevated IGF-1

Adrenocorticotropic hormone-secreting

6

• Moon face appearance • Buffalo hump • Skin abnormalities: – Abdominal purple striae – Ecchymosis – Thinning of the skin • Proximal muscle weakness with distal strength intact

• Normal to elevated ACTH level • Hyperglycemia • Loss of diurnal variation in cortisol levels • Elevated 24-hour urine free cortisol

Thyrotropin-secreting

1

• Enlarged thyroid • Hypothyroidism • Headache • Loss of vision • Galactorrhea

• FT3 >14 pmol/L • Thyrotropin >3 mIU/L • Elevated alpha-GSU/thyrotropin molar ratio

ACTH, adrenocorticotropic hormone; FT3, tri-iodothyronine, free; GH, growth hormone; GSU, glycoprotein subunit; IGF-1, insulinlike growth factor 1

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should focus on the hypothalamic-pituitary area and include contrasted imaging to evaluate the soft tissue within the intracranial structure.9 The coronal and sagittal views are the best to display the pituitary gland width and height and identify abnormalities.9 The MRI provides a detailed evaluation of the pituitary gland related to adjacent structures within the skull, which helps to detect microalterations of the pituitary gland.10 If a pituitary adenoma is an incidental finding on another imaging modality (such as a computed tomography scan or MRI without contrast), an MRI with and without contrast that focuses on the pituitary gland should be obtained.

Pituitary Laboratory Panel A complete pituitary panel workup should be obtained including prolactin, thyrotropin, free thyroxine, cortisol (fasting), adrenocorticotropic hormone, insulinlike growth factor 1, growth hormone, follicle-stimulating hormone, luteinizing hormone, estradiol in women, and total testosterone in males.1 Tests should be completed in the morning while fasting for the most accurate results. For instance, normally cortisol levels drop during fasting unless there is an abnormality. Table 2 shows normal laboratory ranges for a complete pituitary panel.

Serum prolactin levels can slightly increase in response to changes in sleep, meals, and exercise; emotional distress; psychiatric medications; and oral estrogens. If the initial prolactin level is borderline high (21-40 ng/mL), the test should be repeated. Normal levels are higher in women than in men.

Microadenomas may cause slight elevations in prolactin level (ie, <200 ng/mL), while macroadenomas are likely to cause greater elevations (ie, >200 ng/mL).1 Patients with giant prolactinomas typically present with prolactin levels ranging from 1000 ng/mL to 100,000 ng/mL.11 Perimetry Pituitary adenomas may cause ophthalmologic manifestations ranging from impaired visual field to diplopia because of upward displacement of the optic chiasm. The optic chiasm is located above the pituitary gland and a pituitary tumor that grows superiorly can cause compression in this area.12 Optic chiasm compression from a pituitary adenoma commonly causes bitemporal hemianopsia.2 If the tumor volume is promptly reduced by surgical resection or medication (in the case of prolactinomas), initial vision changes resulting from compression may be reversible.12 Baseline and routine follow-up perimetry are important in patients with pituitary adenoma, as symptoms of optic chiasm compression may go unnoticed by patients as visual field deficits often develop gradually. Also, post-treatment perimetry assessments can be used to compare the initial testing to evaluate reversible visual field deficits. It is recommended that patients

TABLE 2. Normal Values for Pituitary Panela Pituitary Test

Normal Value

Thyrotropin

0.5-5.0 mIU/L

Thyroxine, free

0.7-1.9 ng/dL

Cortisol (fasting)

Adults 8 AM (7-9 AM) specimen: 4.0-22.0 µg/dL Adults 4 PM (3-5 PM) specimen: 3.0-17.0 µg/dL

Adrenocorticoid hormone

<54 ng/L

IGF-1

Age ng/mL 18-19.9 years . . . . . . . . . . . . . . . . . . . . 108-548 20-24.9 years . . . . . . . . . . . . . . . . . . . . . 83-456 25-29.9 years . . . . . . . . . . . . . . . . . . . . . 63-373 30-39.9 years . . . . . . . . . . . . . . . . . . . . . 53-331 40-49.9 years . . . . . . . . . . . . . . . . . . . . . 52-328 50-59.9 years . . . . . . . . . . . . . . . . . . . . . 50-317 60-69.9 years . . . . . . . . . . . . . . . . . . . . . 41-279 70-79.9 years . . . . . . . . . . . . . . . . . . . . . 34-245 ≥80 years . . . . . . . . . . . . . . . . . . . . . . . . 34-246 Z-Score (men): -2.0 to +2.0 SD Z-Score (women): -2.0 to +2.0 SD

Growth hormone

Adults: ≤7.1 ng/mL

Prolactin

Men: <25 ng/mL Women: • Nonpregnant: <30 ng/mL • Pregnant: 10-400 ng/mL

Follicle-stimulating hormone

Men: 1.6-8.0 mIU/mL Women: • Follicular phase: 2.5-10.2 mIU/mL • Mid-cycle peak: 3.1-17.7 mIU/mL • Luteal phase: 1.5-9.1 mIU/mL • Postmenopausal: 23.0-116.3 mIU/mL

Luteinizing hormone

Men: • Age 18-59: 1.5-9.3 mIU/mL • Age ≥60: 1.6-15.2 mIU/mL Women: • Follicular phase: 1.9-12.5 mIU/mL • Mid-cycle peak: 8.7-76.3 mIU/mL • Luteal phase: 0.5-16.9 mIU/mL • Postmenopausal: 10.0-54.7 mIU/mL

Estradiol

Men: ≤29 pg/mL Women: • Follicular stage: 39-375 pg/mL • Mid-cycle stage: 94-762 pg/mL • Luteal stage: 48-440 pg/mL • Postmenopausal: ≤10 pg/mL

Testosterone

Men: 250-827 ng/dL

IGF-1, insulinlike growth factor 1 a Values are from a single laboratory; values may vary per institution and/or laboratory.

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ENDOCRINOLOGY

with pituitary adenomas (both function and nonfunctiong) receive neuro-ophthalmologic evaluations twice a year to ensure no visual changes have occurred.12 Referral to a Specialist

Management of pituitary adenomas requires a multidisciplinary team of specialists including endocrinologists, neurosurgeons, and neuro-ophthalmologists. The type of adenoma governs which specialist patients with incidental adenoma should see first.

Patients with functioning pituitary adenomas should be referred to an endocrinologist before a neurosurgeon. The most prevalent functioning adenomas, prolactinoma, are initially treated with dopamine agonist medications.1,6 A patient with prolactinoma would only need to see a neurosurgeon if they have a macroadenoma that is not responsive or only partially responsive to dopamine agonists therapy or is causing vision deficits related to compression of the optic chiasm.2 Patients with nonfunctioning pituitary adenomas should first be referred to a neurosurgeon to discuss surgical options vs observation.The recommended treatment for patients with nonfunctioning adenomas and clinical features of mass effect (ie, visual deficits) is surgery.1,6 If the patient is asymptomatic with no signs of visual field deficits, the neurosurgery team may recommend continued surveillance with serial imaging and serial perimetry screenings.12 The patient in the case was found to have a nonfunctioning pituitary adenoma (prolactin was 33.7 ng/mL). Neuroophthalmology did not find any visual field defect upon initial assessment; the patient decided to continue observation with serial imaging (MRI) and serial neuro-ophthalmology

assessments. Serial imaging with brain MRI revealed slow progression of the pituitary macroadenoma (12 mm initially; 13 mm 6 months later; and 14 mm 1 year from initial MRI findings).

Although the patient still did not have any visual field defects per the neuro-ophthalmology reassessments, the documented growth on MRI over a short period of time was enough to make the patient more amenable to surgical resection. The patient underwent trans-sphenoidal resection of the pituitary lesion approximately 16 months after discovery of the tumor.

Conclusion

A thorough workup including laboratory testing, imaging, and vision field testing is the foundation of an effective referral process for pituitary adenomas and guides which specialist is consulted first. If patients are referred before initial workup is completed, delays in care, unnecessary specialty visits, and increased overall health care costs may occur. ■ Melissa Wasilenko, MSN, RN, is a registered nurse at Lyerly Neurosurgery in Jacksonville, Florida. She is currently pursuing a doctorate in nursing practice with a focus in family medicine at the University of North Florida in Jacksonville.

References 1. Russ S, Anastasopoulou C, Shafiq I. Pituitary adenoma. 2021 Jul 18. In: StatPearls. StatPearls Publishing; 2022 Jan–. Updated July 18, 2021.

2. Greenberg MS. Tumors of non-neural origin. In: Handbook of Neurosurgery, 9th ed. Thieme Medical Publishers: 2019;1655-1755 3. Yeung M, Tahir F. The pathology of the pituitary, parathyroids, thyroid and adrenal glands. Surgery. 2020;38(12):747-757.

4. Watanabe G, Choi SY, Adamson DC. Pituitary incidentalomas in the United States: a national database estimate. World Neurosurg. 2021:S1878-8750(21)01780-0.

POLL POSITION

5. McDowell BD, Wallace RB, Carnahan RM, Chrischilles EA, Lynch CF, Schlechte JA. Demographic differences in incidence for pituitary adenoma.

Pituitary. 2011;14(1):23-30.

Approximately what percentage of all pituitary adenomas are functioning tumors?

6. Molitch ME. Diagnosis and treatment of pituitary adenomas: a review. JAMA. 2017;317(5):516-524.

7.Yao S, Lin P,Vera M, et al. Hormone levels are related to functional compensation in prolactinomas: a resting-state fMRI study. J Neurol Sci. 2020;411:116720.

■ 25%

8. Beck-Peccoz P, Persani L, Lania A.Thyrotropin-secreting pituitary adenoma. In: 25.23%

Feingold KR, Anawalt B, Boyce A, et al, eds Endotext. MDText.com, Inc.; 2019.

■ 45% ■ 50%

4.5%

58.56%

11.71% ■ 65%

9. Yadav P, Singhal S, Chauhan S, Harit S. MRI evaluation of size and shape of normal pituitary gland: age and sex related changes. J Clin Diagnostic Research.

2017;11(12):1-4.

10. Varrassi M, Cobianchi Bellisari F, Bruno F, et al. High-resolution magnetic resonance imaging at 3T of pituitary gland: advantages and pitfalls. Gland Surg.

2019;8(Suppl 3):S208-S215.

For more polls, visit ClinicalAdvisor.com/Polls.

11. Shimon I. Giant prolactinomas. Neuroendocrinology. 2019;109(1):51-56.

12. Vié AL, Raverot G. Modern neuro-ophthalmological evaluation of patients with pituitary disorders. Best Pract Res Clin Endocrinol Metab. 2019;33(2):101279.

16 THE CLINICAL ADVISOR • MARCH/APRIL 2022 • www.ClinicalAdvisor.com

Conference Roundup American Academy of Allergy, Asthma & Immunology (AAAAI) 2022 Annual Meeting February 25 to 28, 2022 Phoenix, Arizona

© TOP, BOTTOM: GETTY IMAGES

GUT MICROBIOTA, DIET, AND ALLERGIC ASTHMA PHENOTYPES IN CHILDREN Metabolic dysfunction/gut microbiota associated with atopy and asthma in children are related to the consumption of processed food, according to study findings presented at the AAAAI 2022 Annual Meeting.The study also identified specific diet-microbe interactions that potentially contribute to disease severity.

Researchers sought to determine whether gut microbes and their by-products interact with dietary exposures and influence allergy and asthma phenotypes.The trial included 345 children who were classified into 6 respiratory phenotypes

Specific diet-microbe interactions may contribute to asthma severity in children.

based on lung function, wheeze, and atopic disease trajectories. The researchers then assessed these children for features of the gut microbiome (utilizing 16S ribosomal ribonucleic acid [rRNA] and shotgun metagenomic sequencing) and diet (using the Block Food Frequency Questionnaire).

Researchers found 4 gut microbiota structures that were significantly associated with respiratory phenotype (P =.04), socioeconomic status (P =.04), site (P =.005), and a range of measurements of atopy (all P <.04). In children with allergic asthma and low lung function, a bacterial network dominated by Prevotella showed significantly reduced abundance.

Dietary exposures were also associated with respiratory phenotypes (analysis of variance P =.03). Children less likely to have severe asthma were those with a low abundance of gut networks of Christenellaceae, Methanobacteriales, and Clostridia and whose diets were rich in whole foods (interaction P =.03).

“Our data indicate that the gut microbiota remains associated to phenotypes of atopic asthma in later childhood and also [identify] specific diet-microbe interactions that may modulate or contribute to disease severity,” the researchers concluded.

REAL WORLD STUDY EVALUATES ORAL PEANUT IMMUNOTHERAPY Children who underwent real-world peanut oral immunotherapy (P-OIT) at a large tertiary referral academic center tolerated the treatment well, but older

children required more dose reductions when being desensitized to high-dose maintenance therapy, according to research presented at the AAAAI 2022 Annual Meeting.

Investigators conducted a real-world, retrospective review of patients who underwent P-OIT at an academic tertiary referral center between 2018 and 2020. All participants were sensitized to low-dose (ie, 300-500 mg) or highdose (ie, 1500-2000 mg) daily peanut protein (PP). Measures of effectiveness included the following: (1) proportion of patients who attained maintenance; and (2) tolerance of a 6000-mg PP challenge following 12 months of high-dose maintenance. All patients were stratified into 2 groups based on age: a younger group of children 72 months of age and younger (preschool-aged) and an older group of children (older than 72 months of age).

A total of 85 patients underwent P-OIT, with 45 in the younger group and 40 in the older group. Overall, 17 patients discontinued the study prior to maintenance therapy and 11 withdrew because of adverse reactions. A maintenance dose was achieved in 80.0% (68 of 85) of the participants, and 69.4% (59 of 85) of patients achieved high-dose maintenance regardless of age (younger group: 68.9% [31 of 45] vs older group: 72.5% [28 of 40]).

Six patients in the younger group receiving high-dose maintenance therapy Continues on page A12

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were reduced to low-dose maintenance therapy because of adverse reactions and/ or taste aversion; 1 patient in the older group discontinued maintenance therapy.

Of the 52 participants who remained on high-dose maintenance, 43 were eligible for the 12-month 6000-mg PP challenge, with 93.9% (31 of 33) of them tolerating the challenge without any adverse reactions. No significant differences were reported between the 2 age group cohorts for either of the effectiveness measures.

The researchers concluded that children who continued high-dose maintenance for at least 12 months were desensitized to high levels of PP exposure, which is consistent with the results of other clinical trials and real-world studies of P-OIT.

SUBOPTIMAL TREATMENT ADHERENCE LINKED TO ESCALATION TO BIOLOGICS In patients with uncontrolled asthma, the need for escalation to biologics may often be attributable to suboptimal treatment adherence rather than lack of efficacy, according to findings presented at the AAAAI 2022 Annual Meeting.

Up to 59% of patients prescribed highdose inhaled corticosteroid/long-acting beta-agonist combination therapy fail to achieve control, according to recent studies. Researchers sought to investigate whether suboptimal adherence to the prescribed treatment instead of the lack of efficacy was the reason for poor control.

This retrospective analysis included data from the IQVIA Real World Claims US Database and ambulatory electronic medical records claims between January 2016 and June 2020 for 506 patients (69% female) aged 12 years and older with diagnosed asthma who had been escalated to biologics. All patients had been enrolled for 12 months before being escalated to their first biologic treatment.

The researchers examined adherence to oral corticosteroids (OCS) and other controller medication classes for the 12 months prior to the first escalation, with adherence defined as the ratio of the days the patient was supplied with controller medications to the total 12-month duration (adherence = proportion days covered [PDC]). Suboptimal adherence was defined as PDC less than 80%.

The investigators discovered that 63% of the patients had suboptimal adherence to controller medication (66% of patients had 1 or more claims for OCS) in the 12 months before being escalated to biologics (mean PDC: 59.3%).

“This analysis suggests that many patients with uncontrolled asthma are escalated to biologics despite suboptimal maintenance therapy adherence. For some, adherence may have been insufficient to assess the need for biologics,” the researchers concluded.

IMMUNOCOMPROMISED LACK IMMUNOGENICITY AFTER COVID VACCINES Individuals on active immunosuppression did not demonstrate a positive antibody

Patients on immunosuppressive therapy have lower response rates to COVID-19 vaccines.

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response to RNA-based COVID-19 vaccines, supporting the continued need for these patients to be closely monitored and vigilant in protecting themselves from exposure to COVID-19, according to findings reported at the AAAAI 2022 Annual Meeting.

This quality improvement project assessed antibody production in response to an RNA-based COVID-19 vaccine in immunocompromised individuals.

The goal was to determine the level of active immunity among these individuals to improve decision-making regarding medical management.

A retrospective chart review was conducted between January and August 2021 involving 18 participants who were immunocompromised and had no history of infection with COVID-19.

Among these participants, 7 had common variable immunodeficiency (CVID), 4 had specific antibody deficiency (SAD), and 7 were receiving immunosuppression for several reasons, including having undergone a solid organ transplant or having an autoimmune disease.

All 18 individuals had received either the Moderna (56% of participants) or Pfizer BioNTech (44% of participants) COVID-19 vaccine. All study participants had been assessed for postvaccination immunoglobulin (Ig)G antibodies against the SARS-CoV-2 spike protein at least 2 weeks after they had received their second vaccination.

Overall, 33.3% of participants exhibited positive antibodies. Among individuals with SAD, 75% had positive antibodies detected; in contrast, positive antibodies were detected in only 42.9% of participants with CVID. Notably, none of the patients who were receiving active immunosuppression exhibited a positive antibody response.

The findings support the continued need for close monitoring of immunocompromised participants who have been vaccinated against COVID-19. ■

© MARKO GEBER / GETTY IMAGES

Conference Roundup

M. LENAHAN, DNP, MSN, FNP-BC; DEEDRA HARRINGTON, DNP, MSN, APRN, ACNP-BC; FEATURE: CHRISTY FRANCES STUEBEN, DNP, RN, CHSE

Sudden, Bizarre Behavior Leads to Diagnosis of Novel Cause of Psychosis A woman is evaluated after attempting to make her children drink bleach to “clean the parasites out of their bodies.”

© DONKEYWORX / GETTY IMAGES

A

Neuropsychiatric symptoms are not uncommon after viral infections.

39-year-old woman presents to the emergency department via a protective order after attempting to make her children drink bleach because she believed they were infected with parasites. The protective order was initiated by her husband and stated the patient had been acting “out of the ordinary” for the past 2 weeks, but this is the first time any potentially harmful behavior had occurred.

On initial presentation, the patient is calm, alert, and oriented to person, place, and time.

She is unaware of why she is being evaluated in the emergency department. She has a flat affect.

The patient denies suicidal or homicidal ideation, but does admit that she attempted to make her children drink bleach to “clean the parasites out of their bodies.” The patient denies use of prescription or illicit drugs. She also denies use of alcohol and tobacco. The patient states she has not experienced any recent stressors and currently works as a paralegal for a local attorney.

Diagnostic tests for psychiatric evaluation and medical clearance are ordered and include the following: complete blood cell count (CBC), basic metabolic profile (BMP), liver function tests (LFT), acetylsalicylic acid (ASA) level, acetaminophen level, urine toxicology, ethanol alcohol (ETOH) level, urine pregnancy test (UPT), thyrotropin level, electrocardiogram (ECG), and brain computed tomography (CT) without contrast.1,2 Laboratory results are all within normal range and urine pregnancy test is negative. The

www.ClinicalAdvisor.com • THE CLINICAL ADVISOR • MARCH/APRIL 2022 17

PSYCHIATRIC DISORDERS

COVID-19 psychosis can occur in both the active stage of the infection (0-13 days) and postinfection (14-90 days) phase in otherwise healthy people. urine toxicology is negative. The ECG reveals normal sinus rhythm with no ST-segment abnormalities. The CT scan of her head was read by the radiologist as “normal.”

potential causes contributing to COVID-19 psychosis include social isolation and utilization of glucorticoids.1,4 Diagnosis

Significant Medical/Psychiatric History

The patient has no significant medical or psychiatric history.

Her last menstrual cycle was 2 weeks ago and normal per patient report. The patient does admit to being diagnosed with COVID-19 approximately 3 weeks ago, but she reports only having mild symptoms, which included headache and nonproductive cough for 3 days.

The patient’s family history is negative for any psychiatric disorders or hospitalizations. The patient’s mother has type 2 diabetes and her father has hypertension.

Physical Examination

The patient is a well-appearing woman with no signs of physical distress. Admission vital signs are as follows: blood pressure 118/68 mm Hg, heart rate 78 beats per minute, respiratory rate 18 breaths per minute, and oxygen saturation 99% on room air. Physical examination is benign and neurologic examination reveals no deficits.

The patient is diagnosed with post-COVID-19 psychosis with delusional disorder and admitted to a local psychiatric inpatient unit for treatment and observation. She is started on 1-mg risperidone daily and increased to 2 mg daily after 3 days. After 7 days of inpatient care and pharmacotherapy with risperidone, the patient no longer believes she needed to “clean the parasites” out of her children’s bodies and she is discharged with close outpatient follow-up and continuation of 2-mg risperidone daily.

Discussion

COVID-19 psychosis can occur in both the active (0-13 days) and postinfection (14-90 days) phases of COVID-19.1-4 Patients with no previous diagnosis of a psychiatric disorder have a greater probability of being diagnosed with their first psychiatric disorder 14 to 90 days after being diagnosed with COVID-19.3 It is theorized that microvascular injury secondary to a cytokine-mediated inflammatory response to COVID-19 infection is responsible for new-onset or relapse of neuropsychiatric symptoms.2-4 Neuropsychiatric symptoms have been affiliated with several types of respiratory viruses such as reports of schizophrenia, depression, encephalitis, and acute psychosis with specific strains of influenza and other severe acute respiratory syndromes (SARS) caused by different strains of coronavirus.3,4 Other

COVID-19 psychosis, whether during the acute or postinfection phase, can present with a multitude of neuropsychiatric symptoms such as anxiety, agitation, confusion, delusions, disorganized thinking, visual and auditory hallucinations, insomnia, suicidal or homicidal ideation, and paranoia.2,4 Diagnosis of COVID-19 psychosis can be made when a patient with no history of psychiatric disorder presents with new-onset neuropsychiatric symptoms or when a patient with a well-controlled psychiatric disorder presents with a psychotic relapse; all patients much have recently been diagnosed (14-90 days) with or currently have COVID-19 infection and have no other explanation for the presenting symptoms.1-4 Laboratory Studies COVID-19 PCR testing should be performed if there is no recent history of a positive COVID-19 test.4 Routine laboratory tests for psychiatric clearance, such as CBC, BMP, LFT, ASA level, acetaminophen level, ETOH level, urine Recommended Diagnostic/Laboratory Tests for COVID-19 Psychosis1,4,5 COVID-19 PCR testing

Urine toxicology

Complete blood cell count

Urine pregnancy test (in women)

Basic metabolic profile

Thyrotropin level

Liver function tests

C-reactive protein level

Acetylsalicylic acid level

CT of the head

Acetaminophen level

MRI of the brain

ETOH level

Lumbar puncture

CT, computed tomography; ETOH, ethanol alcohol; MRI, magnetic resonance imaging; PCR, polymerase chain reaction

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Duration of treatment for COVID-19 psychosis ranges from days to months and is determined based on resolution of symptoms. toxicology, UPT, and thyrotropin levels, should be conducted to rule out other potential causes of psychosis.5 Thyrotropin level assessment is extremely important because a thyrotoxic patient may present with new-onset psychosis.5 C-Reactive Protein C-reactive protein (CPR) is made by the liver as a result of inflammation that occurs in an immune response.4 While not measured in the case presentation above, CRP is typically elevated in patients presenting with COVID-19 psychosis.

Computed Tomography Regardless of COVID-19 status, patients undergoing psychiatric evaluation with altered mental status, trauma, immunodeficiency, or focal neurologic findings should undergo a CT scan of the head to rule out organic brain disorders as an underlying cause of psychosis.5 Even in patients with a normal CT of the head, central nervous system pathology cannot be ruled out.4 Magnetic Resonance Imaging Magnetic resonance imaging (MRI) of the brain is more sensitive than CT and can better detect white matter and inflammatory changes.4 Lumbar Puncture Presence of cytokines in cerebrospinal fluid (CSF) may indicate immune activation. Further evaluation for presence of COVID-19 RNA in CSF could indicate viral invasion of the central nervous system.2,6

Discussion/Follow-Up

Duration of treatment for COVID-19 psychosis ranges from days to months and is determined based on resolution of neuropsychiatric symptoms and patient’s return to baseline.

Once acute psychosis has resolved, close outpatient follow-up is recommended. Discontinuation of antipsychotics should be performed at the discretion of the provider. Of note, some cases may only require a few days of pharmacotherapy while others may require pharmacotherapy indefinitely.6 ■ Christy L. McDonald Lenahan, DNP, FNP-BC, ENP-C, CNE, is an advanced practice registered nurse in family and emergency medicine who works for an emergency medicine and hospitalist staffing agency.

She is also an associate professor at the University of Louisiana at Lafayette and teaches in the masters and doctoral programs.

Deedra Harrington, DNP, MSN, APRN, ACNP-BC, is associate professor at the College of Nurse and Allied Health Professions, University of Louisiana at Lafayette. Dr Harrington is an advanced practice registered nurse-acute care who works with an inpatient cardiology intensivist group in Louisiana.

Frances Stueben, DNP, RN, CHSE, is an assistant professor and simulation program coordinator at the University of Louisiana at Lafayette.

She teaches in the graduate and undergraduate nursing programs.

The authors have published an 8-part series on complications in patients with COVID-19.To read the first article in the series, please go to: clinicaladvisor.com/cardiovascular-covid series_march_april22 References

Management and Treatment

1. Al-Bussaidi S, Huseini S, Al-Shehhi R, Zishan AA, Moghadas M,

Treatment for COVID-19 psychosis is dependent on presenting symptoms and may include supportive care, pharmacotherapy, and management of any underlying complications from COVID-19 infection. Case severity can range from mild, with symptoms such as insomnia and agitation, to severe, with symptoms such as delusions and hallucinations.

If patients are at risk of harming themselves or others, inpatient hospitalization is appropriate until they can be stabilized.

In the case of acute psychosis, antipsychotics such as risperidone, quetiapine, olanzapine, or aripiprazole are appropriate.1,4,6 For patients experiencing panic attacks, agitation, or anxiety, benzodiazepines such as lorazepam are appropriate.2,4,6 Other medications may include antidepressants and mood stabilizers depending on symptomology.6

Al-Adawi S. COVID-19 induced new-onset psychosis: a case report from Oman. Oman Med J. 2021;36(5):e303.

2. Losee S, Hanson H. COVID-19 delirium with psychosis: a case report.

S D Med. 2020;78(8):346-349.

3. Desai S, Sheikh B, Belzie L. New-onset psychosis following COVID-19 infection. Cureus. 2021;3(9):e17904.

4. Ferrando SJ, Klepacz L, Lynch S, et al. COVID-19 psychosis: a potential new neuropsychiatric condition triggered by novel coronavirus infection and the inflammatory response. Pychosomatics. 2020;61(5):551-555.

5. D’Orazio JL. Medical clearance of psychiatric patients: pearls & pitfalls. emDOCs. Updated May 28, 2015. Accessed January 29, 2022. http://www. emdocs.net/medical-clearance-of-psychiatric-patients-pearls-pitfalls/ 6. Smith CM, Gilbert EB, Riordan PA, et al. COVID-19-associated pyschosis: a systematic review of case reports. Gen Hosp Pyschiatry. 2021;73:84-100.

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FEATURE: CATHERINE R. JUDD, MS, PA-C, CAQ-Psy, DFAAPA

Pizza Is Not Enough: NPs, PAs Want to Be Heard, Protected, and Supported The vast majority of NPs and PAs report symptoms of moral injury such as anxiety, PTSD, and suicidality in The Clinical Advisor’s online survey.

© GETTY IMAGES. MONTAGE BY VIVIAN CHANG

Over 970,000 COVID-19 deaths have been reported in the United States.

A

nother grim milestone has been reached during the COVID-19 pandemic; close to 1 million deaths from COVID-19 were reported in the United States, more than in any other country in the world.1 We do not have to look far for evidence of collateral damage suffered by the frontline health care workforce from the COVID-19 pandemic.These providers come with resilience, commitment, and acceptance that the conditions they work under will be challenging. However, the COVID-19 pandemic has been unprecedented in the toll it has taken on the health care workforce.

Moral distress and moral injury in frontline health care providers are similar to that experienced by combat veterans. In the case of the pandemic, critical care providers who were found to be at higher risk for symptoms of moral injury were younger in age, spent less time in practice, and had higher levels of anxiety and depression as well as burnout.2 This level of stress and anxiety is also reflected in the results of an online survey conducted by The Clinical Advisor between January 7 and March 3, 2022. The survey accompanied my article COVID-19 and Moral Injury: a Mental Health Pandemic for Frontline Health Care Workers.3 A total of 478 nurse practitioners (NPs) and PAs responded to the survey.

The first question asked about symptoms of COVID-19-related moral injury; 90% of Continues on page 22

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MENTAL HEALTH TOLL OF COVID-19

respondents acknowledged they have experienced symptoms such as insomnia, depression, anxiety, panic attacks, posttraumatic stress disorder (PTSD), and suicidal thoughts (Question 1).

Respondents who reported these symptoms were then asked if they had sought professional help from a mental health professional. Sixty-five percent (n=297) said no and 35% (n=161) said yes. (Question 2).When asked,“Has mental wellness and the emotional wellbeing of you and your colleagues been a priority of your employer,” 81% of respondents said “no” (Question 3).

The immediate challenge going forward is to identify what strategies and interventions need to be put in place to provide a safety net and salvage a critically injured health care workforce.

The potential loss is already present as clinicians are choosing to leave the health care profession. Many of those who can are deciding to retire. Others are pursuing other clinical care settings outside of critical care.

Recognition in this area must include the need for targeted therapeutic interventions and support for those experiencing

QUESTION 1. Have you experienced any of the following symptoms during the COVID-19 pandemic: insomnia, depression, anxiety, panic attacks, PTSD, or suicidal thoughts?

90.31% (n=424)

10% (n=47)

QUESTION 2. If yes, have you sought professional help from a mental health professional?

35% (n=161)

65% (n=247)

QUESTION 3. Has mental wellness and the emotional wellbeing of you and your colleagues been a priority of your employer?

17% (n=81)

KEY: ■ Yes

81% (n=378)

■ No

moral injury to prevent functional impairment as a result of depression, anxiety, and PTSD. What Do Health Care Workers Want?

Shanafelt et al conducted a study of the expectations and needs of health care workers (physicians, nurses, advanced practice clinicians, residents, and fellows) during the first week of the pandemic at one hospital in New York City.4 The authors identified the following 5 requests of their employer: hear me, protect me, prepare me, support me, and care for me.

These “asks” have not changed over the course of the epidemic. For example, when The Clinical Advisor readers were asked to provide comments to the survey, some respondents cited work from home, availability of wellness coaches, online zoom peer-support meetings, and counseling as morale boosters. Others expressed frustration at being asked to work longer hours for less pay in unsafe environments.

Hear Me In the study by Shanafelt et al, “hear me” was one of the top requests respondents had of their organizations.Their ask was to have input and feedback and be assured their voices were being heard and they were being included in the decisionmaking process addressing the challenges of the pandemic.4 Respondents to The Clinical Advisor survey also noted: • “Superficial things [have been offered] like having counseling and listening sessions but no real change. Less staff and same expectations for metrics as prepandemic when staffing was always lean. Now we work with half the staff for double the patient visits per day.”

• “They have tried and clearly want to support us, but I don’t think they really know what to do.”

Protect Me Many health care workers also lacked access to sufficient personal protective equipment (PPE) and testing. If they did become ill, many health care workers who responded to the survey and in the study by Shanafelt et al questioned whether they could ask for and be given the needed time off with understanding and support and without judgment. Changing policies and lack of communication left some to wonder about support from leadership.4 A survey respondent wrote: “Employers push us to see more patients each day because of COVID-19 to help keep [the patients] out of the emergency departments.They push [us to work] more with fewer staff members and then send messages to take care of our mental health, but they don’t support this in actions.”

Prepare Me Most health care providers on the frontline have never experienced anything like the overwhelming challenges they faced

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with COVID-19 patients.These included changing protocols, shortages of PPE and supplies, feelings of powerlessness and hopelessness, inability to provide the standard of care to their patients, and overwhelming numbers of patients dying alone, separated from their families.

Their “ask” was for management and leadership to provide them with training and resources, to give them permission to ask for help, and for leadership to communicate honestly and with transparency.4 Support Me The expression that the pandemic is a marathon and not a sprint has been repeated many times. Self-care is frequently overlooked. However, when frontline health care workers ask for support they are also asking for recognition of their own physical, mental, and emotional limitations; they ask for time off, the need for “rest” in order to reset. Frontline health care providers face not only demands at work but the challenge of meeting personal and family needs.

Their “ask” is for leadership to make a difference by recognizing their limitations and supporting them as they seek help professionally and personally. For some, the reluctance to seek help from mental health professionals may be related to determination to be self-reliant or fear of judgment or stigma. The survey results showed 90% of respondents were experiencing stress-related symptoms but only 35% reported seeking help from a mental health professional.

“There is the acknowledgment of the huge emotional burden and burnout. There are people we can reach out to if we need help. But being understaffed and having wages locked has caused me to seriously consider retiring early,” noted one respondent.

School Nurses Affected

One respondent to the survey said: “School nurses are being forced to tell families to send kids to school when they know it is not a safe environment. To tell kids to return on day 5 when they know children test positive on day 8, to not be able to keep up with contact tracing because numbers are too high. Not ‘frontline’ but severely impacted.”

Another wrote: “We have been expected to work past our contracted hours, weekends, holiday breaks. We have been expected to let parents and staff members verbally assault us over policies that have been in place by local, state, and federal health agencies. No one cares if there will be plenty of nurses to care for them or their loved ones until there is not.”

Finally, there is empowerment in an expression of recognition and gratitude that honors frontline clinicians’ commitment to the work they do and compassion for those they take care of. Messages of gratitude are carried forth by the media and the public. Frontline providers also need to hear that same gratitude expressed with empathy and sincerity by management and leadership.6 “Pizza is not enough,” wrote one respondent. Clinicians need to know those same leaders hear them and will respond to their need to be heard, protected, prepared, supported, and cared for as they continue to put themselves on the frontlines during the COVID-19 pandemic.4 ■ Catherine R. Judd, MS, PA-C, CAQ-Psy, DFAAPA, is an assistant clinical professor in the Department of Physician Assistant Studies at the School of Health Professions,The University of Texas Southwestern Medical Center, Dallas,Texas.

References 1. Coronavirus Resource Center. COVID-19 data in motion. Johns Hopkins

Care for Me Early on in the pandemic, nurses and frontline health care providers were hailed as heroes. As the pandemic has entered its third year, they do not feel like heroes.They cope with the moral distress of not being able to provide the care they want to for patients and families and the conflict between what they want to do and can do.5 For many clinicians, what is needed is an expression of gratitude, recognition of their commitment to go “above and beyond.” Humanness, support, and empathy is needed from leadership at a very personal level for the sacrifices they have made. A need to not be taken for granted.6 “Some programs have been provided but all online resources, nothing to support leaders on the frontline of health care,” said one survey respondent. Another wrote:“They try to give us breaks and incentives, however, there are just too few workers and too much work with little compensation.”

University of Medicine. Accessed March 2, 2022. https://coronavirus.jhu.edu/ 2. Mantri S, Lawson JM, Wang Z, Koenig HG. Prevalence and predictors of moral injury symptoms in health care professionals. J Nerv Ment Dis. 2021;209(3):174-180.

3. Judd CR. COVID-19 and moral injury: a mental health pandemic for frontline health care workers. The Clinical Advisor. Accessed March 2, 2022. https://www.clinicaladvisor.com/home/topics/psychiatry-information-center/ covid-19-moral-injury-mental-health-pandemic-health-care-workers/ 4. Shanafelt T, Ripp J, Trockel M. Understanding and addressing sources of anxiety among health care professionals during the COVID-19 pandemic.

JAMA. 2020;323(21):2133-2134.

5. Hossain F, Clatty A. Self-care strategies in response to nurses’ moral injury during COVID-19 pandemic. Nurs Ethics. 2021;28(1):23-32.

6. Horan KM, Dimino K. Supporting novice nurses during the COVID-19 pandemic. Am J Nurs. 2020;120(12):11.

7. Singer T. Klimecki OM. Empathy and compassion. Curr Biol. 2014;24(18): R875-878.

www.ClinicalAdvisor.com • THE CLINICAL ADVISOR • MARCH/APRIL 2022 23

Dermatologic Look-Alikes Growing Skin Lesion TIFFANY TRAN, BS;TARA L. BRAUN, MD

CASE #1

CASE #2

A 33-year-old woman presents to the dermatology clinic with a 2-year history of an enlarging mass on her left foot. The patient reports that the mass was initially painless but has become increasingly painful over the last year. The patient has no medical history of similar lesions and does not remember any trauma to the area.

She is in good general health, has never had surgery, and does not take any medication. Her family history is also negative for similar lesions. Findings from the physical examination revealed a firm, hyperpigmented, shiny, multilobulated tumor on the left proximal dorsal foot measuring 3.0 x 2.5 cm.

A 40-year-old man presents to the dermatology clinic for evaluation of a skin lesion on his upper back. The patients notes that he had a cyst surgically removed from that spot about a year ago. At the site of the excision, a resultant scar has grown over the past year. The patient notes that the lesion is itchy and sometimes painful. He has not tried any medications on the scar to manage the puritis. The patient’s brother has a history of similar lesions that have appeared after skin trauma. Physical examination of the left upper back reveals a firm, shiny, hyperpigmented tumor that has extended beyond the area of the original scar.

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Dermatologic Look-Alikes CASE #1

Dermatofibrosarcoma Protuberans

Dermatofibrosarcoma protuberans (DFSP) is an uncommon low-grade sarcoma of the skin and soft tissue.1 The fibrohistiocytic tumor is derived from connective tissue cells called fibroblasts located in the dermis.2 Though slow-growing with low metastatic potential, DFSP is locally aggressive and tends to recur following surgical treatment.2 Given its indolent clinical course, diagnosis of DFSP is frequently delayed.

In the late 1800s, DFSP was recognized as a keloid sarcoma given its resemblance to keloids.3 In the early 1900s, the tumor was described as a progressive recurrent dermatofibroma by French dermatologist Ferdinand-Jean Darier (1856-1938).3 Shorty afterward in 1925, German dermatologist Erich Hoffmann (1868-1959) coined the modern term dermatofibrosarcoma protuberans to describe the protuberant sarcomatous tumor.3 Comprising less than 0.1% of all malignancies, DFSP is relatively rare.4,5 Based on the Surveillance, Epidemiology, and End Results (SEER) program, the annual incidence of DFSP in the US population is estimated to be 4.1 to 4.2 cases per million people.4,5 The majority of cases occur among middleaged adults, though cases have been reported across all age groups including children and older adults.4,5 The SEER-based epidemiologic studies also identified an increased incidence among Black individuals (6.5-7.1 per million) compared with White persons (3.6-3.9 per million).4,5 Men and women are affected at roughly the same ratio with some evidence of a slightly increased incidence among women.4,5 The cause of DFSP is unknown.A history of trauma or injury to the affected skin may be a predisposing factor.1 Factors associated with worse survival outcomes include increased age at diagnosis, male sex, Black race, and atypical anatomic locations such as the extremities and the head.5 Previous reports have suggested accelerated tumor growth during pregnancy.6 Biopsy specimens of DFSP appear to express low levels of hormone receptors such as progesterone receptors that may facilitate the rapid tumor enlargement observed in pregnant patients.6 In addition, multiple DFSPs have been reported in patients with immunodeficiency disorders, such as adenosine deaminase-deficient severe combined immunodeficiency in children.2 Although risk factors for DFSP remain obscure, multiple studies have identified a genetic basis for the tumorigenesis

of DFSP. In the 1990s, scientists identified the reciprocal translocation t(17;22)(q22;q13) in a significant majority of DFPS specimens.7,8 This unique cytogenetic abnormality was found to result in the formation of a COL1A1-PDGFβ fusion gene transcript. The resultant constitutive expression of the platelet-derived growth factor β (PDGFβ) protein is believed to drive the long-term self-propagation of DFSP cells.8 These discoveries eventually paved the way for the current use of targeted therapy against the PDGFβ receptor in the treatment of DFSP.8,9 This condition occurs most frequently on the trunk followed by the proximal extremities (including the shoulders and the pelvic region) and the head/neck region.1,4,5 The clinical and pathologic course of DFSP is divided broadly into 2 stages: plaque and nodular. In the plaque stage, an early nonprotuberant lesion with subcutaneous thickening may be observed.2,10 The lesion is usually asymptomatic and may be reddish-brown, reddish-blue, or skin-colored.2

Although risk factors for DFSP remain obscure, multiple studies have identified a genetic basis for the tumorigenesis of DFSP. On histopathologic analysis, spindle cells are loosely scattered in the upper dermis and CD34-positive on immunostaining.2 Over a span of months or years, the lesion enlarges into a cluster of indurated nodules or protuberances.2 Microscopically, spindle cells in the nodular stage are arranged in a storiform pattern, forming uniform short fascicles that infiltrate the subcutaneous tissue.2 If left untreated, tumor cells may invade more deeply and cause significant cosmetic disfigurement.2 Dermatofibrosarcoma protuberans may be difficult to clinically diagnose because it resembles many benign skin growths.

Depending on the stage of the tumor (plaque or nodular) at the time of clinical presentation, the differential diagnosis for DFSP may include keloid, dermatofibroma, dermatomyofibroma, peripheral nerve sheath tumor (eg, neurofibroma, schwannoma), intradermal spindle cell/pleomorphic lipoma, and desmoplastic melanoma.2,10 To facilitate specific pathologic diagnosis, a generous biopsy (punch or excisional) should be performed to collect sufficient tissue for histopathologic evaluation.2 In immunohistochemistry studies, spindle cells in DFPS typically are strongly and diffusely positive for the marker CD34 and negative for other immunostains such as factor XIIIa, S-100, and α-smooth muscle actin.2,8,11 For difficult cases, molecular studies using fluorescence in situ

26 THE CLINICAL ADVISOR • MARCH/APRIL 2022 • www.ClinicalAdvisor.com

hybridization (FISH) and reverse transcriptase–polymerase chain reaction (RT-PCR) are especially valuable in detecting specific tumor-associated chromosomal translocations and fusion gene transcripts.2 Once the diagnosis is confirmed, the initial treatment of DFSP is mainly surgical.1,10 Mohs micrographic surgery (MMS) is generally preferred over wide local excision in most cases because of the higher cure rate and lower recurrence rate associated with MMS.1,2 For patients with unresectable, recurrent, or metastatic DFSP, the oral chemotherapy agent imatinib mesylate has demonstrated long-term antitumor activity in DFSP characterized by the COL1A1-PDGFβ fusion gene.12 As an FDA-approved and well-tolerated treatment for DFSP in adults, this small molecule inhibitor functions by inhibiting PDGFβ receptors.12 Overall, the 5-year survival rate for DFSP is highly favorable (>99%).4,5 To promote early detection of local recurrence, follow-up examinations are recommended every 6 months for the first 5 years following diagnosis and every year thereafter.10 In addition to clinical examinations, imaging examinations with local ultrasound, magnetic resonance imaging (MRI), and/or computed tomography (CT), may be performed in patients with a history of disease recurrence.10 A punch biopsy taken from the lesion of the patient in this case was consistent with DFSP. Given the size and location of this lesion, she was referred for excision with surgical oncology with subsequent tissue reconstruction with plastic surgery.

CASE #2

Keloids

Keloids are benign fibroproliferative scars with a thick, bulky, and irregular appearance.13 Though generally harmless, keloids may cause cosmetic disfigurement and induce symptoms of pain and pruritus in affected patients, drastically affecting quality of life.14 The earliest known historical records of keloidal scarring can be found in the Edwin Smith Papyrus, an ancient Egyptian medical text dating back to roughly 1700 BC.13,15 The surgical treatise described clusters of firm nodular swellings on the breast and recognized an association between these swellings and a history of trauma to the affected skin.15 In 1806, French dermatologist Jean-Louis Marc Alibert (1768-1837) referred to these raised growths as

cancroïdes because of their tumor-like appearance.15 To avoid associations between these benign growths and cancer,Alibert later coined the term chéloïde or keloïde derived from the Greek word for crab claws.15 This name reflects the claw-like extensions of keloids beyond the margins of the original wound and into the surrounding skin.15 Keloids occur commonly in African and Asian populations, though limited epidemiologic data is available for specific populations.16 Estimates of the prevalence of keloids in African populations range from 6% to 16%.16 In one prospective study, keloidal scarring was more commonly observed in Black women (7.1%) and Asian women (5.2%) compared with White women (0.5%) following cesarean delivery.17

Keloids that arise within existing scar tissue represent an exuberant response to injury of the skin.

Keloids that arise within existing scar tissue represent an exuberant response to injury of the skin. Possible predisposing injuries include incisions, lacerations, abrasions, insect bites, burns, tattoos, piercings, and needle sticks.13 In a genetically susceptible individual, such injuries may result in the abnormal proliferation of fibroblasts in the connective tissue.14 Compared with normal skin fibroblasts, keloidal fibroblasts demonstrate increased expression of receptors for growth factors such as transforming growth factor-β (TGF-β) and connective tissue growth factor (CTGF).13 These growth factors are believed to contribute to the excessive production of stromal components and scar tissue.13 The pathogenesis of keloids may thus be conceived as failure to regulate the wound healing process.13 On histopathologic analysis, keloids contain type I and type III collagen bundles (called keloidal collagen) in a disarray.13 This compares with hypertrophic scars that primarily contain type III collagen organized parallel to the surface of the skin.13 Known risk factors for the development of keloids include darker pigmented skin, genetic susceptibility, and a family history of keloidal scars or folliculitis keloidalis.16 The results of a cross-sectional study discovered that Black persons with albinism were equally affected by keloids as their darker skin counterparts; both were higher than the general population.16 This suggests that genetic susceptibility may play a more important role in the pathogenesis of keloids than the degree of pigmentation in the skin.16 Keloids also tend to occur at anatomic sites with high physical tension such as the anterior chest, shoulder, deltoid, jaw, and ear lobe.14 Mechanical factors,

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Dermatologic Look-Alikes TABLE. Dermatofibrosarcoma Protuberans vs Keloid DFSP1-12

Keloid13-19

Dermatologic presentation

• Expanding indurated plaque with or without firm nodules • Red-brown, red-blue, or skin-colored • Asymptomatic

• Thick raised lesion at the site of a previous wound, firm to palpation • Pink, purple, brown • Symptomatic, painful, pruritic

Characteristic location

• Trunk • Upper extremity • Lower extremity • Head/neck

• Chest • Shoulder • Jaw • Ear lobe

Associations

• Previous trauma or injury • Pregnancy • Immunodeficiency disorders

• Black or brown skin • African or Asian descent • Family history of keloids

Etiology

• Reciprocal t(17;22)(q22;q13) translocation resulting in the COL1A1-PDGFβ fusion gene transcript • Overexpression of PDGFβ

• Aberrant wound healing in response to injury of skin • Excessive proliferation of fibroblasts • Overproduction of type I and type III collagen

Histology

• Plaque stage: elongated spindle cells arranged as long fascicles parallel to surface of skin • Nodular stage: bland spindle cells arranged as uniform short fascicles in a storiform pattern, infiltration into subcutaneous tissue

• Thick collagen bundles in disarray

Diagnosis

• Positive for CD34 (immunostaining) • Presence of t(17;22)(q22;q13) (FISH or RT-PCR)

• Scar tissue extending beyond margins of original wound (clinical presentation)

Treatment

• If resectable: surgical removal with Mohs micrographic surgery (preferred) or wide local excision • If unresectable, recurrent, or metastatic: chemotherapy with imatinib mesylate

• Intralesional corticosteroid injections • Topical silicone sheeting • Compression therapy • Surgical excision • Radiation therapy • Intralesional 5-fluorouracil injections • Cryotherapy • Laser therapy

CD, cluster of differentiation; DFSP, dermatofibrosarcoma protuberans; FISH, fluorescence in situ hybridization; RT-PCR, reverse transcriptase-polymerase chain reaction

such as intense or repetitive skin stretching at the edges of the keloid scar, may induce changes in biologic signaling pathways involved in wound healing.14 On clinical examination, keloids appear as protuberant scars originating from an existing wound but extending well beyond its borders.13 The well-circumscribed lesion may be many times larger in size than that of the original wound, and its color may appear pink, purple, or brown.13 Keloids are also frequently symptomatic, and patients may complain of pain and pruritus.These symptoms could be explained by abnormalities in small nerve fiber function caused by nerve compression by keloidal collagen.18 Other hypotheses involve the presence of mast cells within keloidal tissue that release active substances such as histamine, generating painful or pruritic sensations.18

The differential diagnosis for a keloid includes hypertrophic scar, dermatofibroma, dermatofibrosarcoma protuberans (DFSP), or cutaneous sarcoidosis. Unlike a hypertrophic scar or dermatofibroma, keloids classically extend beyond the margins of the original wound; an important distinguishing factor. If the clinical presentation becomes concerning for DFSP or cutaneous sarcoidosis, a biopsy specimen may be obtained and evaluated microscopically for uniform spindle cell fascicles or noncaseating epithelioid cell granulomas, respectively.

Although keloids represent benign growths, spontaneous regression is rare.13 Patients may pursue treatment for cosmetic purposes or symptomatic relief, though treatment of keloids may be difficult given the risk for recurrence. To attenuate the scarring process, common nonsurgical treatments

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include intralesional corticosteroid injections, topical silicone gel sheeting, and compression therapy.13 Invasive treatments involve surgical excision of the keloid, but these procedures may unsatisfactorily lead to a new or even larger keloid.13 To decrease the risk for recurrence, surgical procedures may be combined with adjuvant therapy such as irradiation and/or administration of corticosteroids.13 Additional therapeutic options for keloids include intralesional 5-fluorouracil injections, cryotherapy, and laser therapy.13,19 The patient outlined in this case was diagnosed with a keloid based on clinical history and examination. He is being managed with intralesional steroids to help with symptoms of pain and itching and to soften the lesion. He was counseled on avoiding future injury to the skin including elective surgical procedures, piercings, and tattoos. ■

10. Saiag P, Grob JJ, Lebbe C, et al. Diagnosis and treatment of dermatofibrosarcoma protuberans. European consensus-based interdisciplinary guideline.

Eur J Cancer. 2015;51(17):2604-2608.

11. Aiba S, Tabata N, Ishii H, Ootani H, Tagami H. Dermatofibrosarcoma protuberans is a unique fibrohistiocytic tumour expressing CD34. Br J Dermatol. 1992;127(2):79-84.

12. Rutkowski P, Klimczak A, Ługowska I, et al. Long-term results of treatment of advanced dermatofibrosarcoma protuberans (DFSP) with imatinib mesylate — the impact of fibrosarcomatous transformation.

Eur J Surg Oncol. 2017;43(6):1134-1141.

13. Mari W, Alsabri SG, Tabal N, Younes S, Sherif A, Simman R. Novel insights on understanding of keloid scar: article review. J Am Coll Clin Wound Spec.

2016;7(1-3):1-7.

14. Tsai CH, Ogawa R. Keloid research: current status and future directions.

Scars Burn Heal. 2019;5:2059513119868659.

15. Limandjaja GC, Niessen FB, Scheper RJ, Gibbs S.The keloid disorder: hetero-

Tiffany Tran, BS, is a medical student at Baylor College of Medicine in Houston,Texas;Tara L. Braun, MD, is a resident in the department of dermatology at Baylor College of Medicine.

geneity, histopathology, mechanisms and models. Front Cell Dev Biol. 2020;8:360.

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www.ClinicalAdvisor.com • THE CLINICAL ADVISOR • MARCH/APRIL 2022 29

LEGAL ADVISOR CASE

© PIXELSEFFECT / GETTY IMAGES

Gastric Band Infection and Later Stroke Delay in removal of gastric band leads to infection, subarachnoid hemorrhage, and death.

ANN W. LATNER, JD

Dr P is a bariatric surgeon who specializes in the treatment of obesity. He maintained privileges at a local health system (the hospital) and rented office space in one of its buildings. As part of the rental agreement, the hospital assigned a nurse practitioner (NP), Ms M, to assist Dr P in his office. Ms M’s duties as an NP included evaluating new and postoperative patients and covering Dr P’s patients admitted to the hospital when he was not available.

Dr P performed laparoscopic gastric band placement on Mrs F, a 40-year-old woman with obesity.

In addition to placing the adjustable gastric band, the surgeon placed an access port under the patient’s abdominal skin. Over the years, Mrs F routinely followed up with the physician for adjustment of the gastric band tightness.

Nine years after the gastric band was installed, Mrs F went to see Dr P with complaints of severe pain near the port site. Dr P ordered a computed tomography (CT) scan. The scan results revealed a hiatal hernia and inflammation. Seven weeks later, the patient returned to the office and saw Ms M, the NP. At this appointment, the patient

The bariatric surgeon, infectious disease specialist, NP, and hospital that employed the NP are sued for wrongful death.

said that the pain at the port site had resolved.

Ms M tightened the patient’s gastric band by inserting more saline into the port.

The next day the patient returned to the office complaining that the band was too tight. When Ms M attempted to aspirate fluid from the port, purulent liquid came into the syringe. Concerned about a possible infection, Ms M sent a sample of the fluid to the laboratory to be cultured, prescribed antibiotics to Mrs F, and recommended that the patient follow up with Dr P. Ms M discussed the case and her findings with Dr P, and the physician ordered additional laboratory studies.

A week later, Mrs F went to the hospital with abdominal pain, fever, and chills.The wound was aspirated and cultured at the hospital. Dr P was called in to examine Mrs F; he noted an enlarging left sided abdominal mass in the vicinity of the patient’s port. He surgically removed the infected Cases presented are based on actual occurrences.

Names of participants and details have been changed.

Cases are informational only; no specific legal advice is intended. Persons pictured are not the actual individuals mentioned in the article.

www.ClinicalAdvisor.com • THE CLINICAL ADVISOR • MARCH/APRIL 2022 31

LEGAL ADVISOR subcutaneous gastric port and drained the abdominal wall abscess.The patient was discharged home.

The patient was seen 2- and 4-weeks postoperatively by Ms M, who evaluated the patient’s wound and repacked it.

On those dates, the NP noted that the wound was clean and seemed to be healing. On the third postoperative visit, Ms M noted a strong fishy odor at the site of the wound. She took a culture and sent it to the hospital for analysis; the laboratory results indicated the presence of pseudomonas and staphylococcus bacteria.

Fourteen days later, the patient was admitted to the hospital for an abdominal abscess and discharged 5 days later. The last time Ms M examined Mrs F was 3 weeks later when she checked the patient’s incision and noted a small amount of drainage. She spoke to the patient about the possibility of having the gastric band removed and recommended that she follow up with Dr P if there was no improvement.

The NP’s attorney argued that the ultimate decision to remove the port and gastric band was made by the physician.

Two days later, Mrs F was admitted to the hospital with abdominal pain. Dr P performed surgery to remove the gastric band. After approximately 2 weeks of treatment in the hospital, an infectious disease expert determined that the infection had resolved and Mrs F was discharged. Three days later she was brought to the hospital by ambulance for evaluation of symptoms of right-sided weakness and droop, and she was diagnosed with intracranial and subarachnoid hemorrhage.

The patient spent the next 18 months in nursing homes and extended care centers until she died at age 50.

After her death, her husband sued numerous parties including the bariatric surgeon, infectious disease specialist, NP, and hospital that employed the NP. Ms M.The hospital and Ms M filed a motion for summary judgment, asking the court to dismiss them from the case.

and fulfilled her duties and responsibilities as an NP to Dr P. The expert said that Dr P, not Ms M, was ultimately responsible for all aspects of surgical care and follow-up treatment including the timing and removal of all devices related to the gastric band. The expert said that Ms M met the standard of care with respect to her communications with Dr P, and that none of the injuries suffered by Mrs F, including her death, were caused by any negligence on the part of Ms M. In opposition, the plaintiff introduced an affidavit from a board-certified surgeon. The surgeon said that Dr P should have realized that the entire gastric band, not just the port, needed to be removed based on the patient’s condition and the fact that she made several visits to the office for treatment of her wound. According to the plaintiff ’s expert, Ms M cannot avoid responsibility for her failures simply because she is an NP and not a medical doctor. The assessment and recommendation for band removal was well within the bounds of what a bariatric surgery NP is authorized to perform. Dr P relied on Ms M to assist in the diagnosis of gastric band infections, recognize the need for surgery, and recommend surgery to remove the band, noted the expert. With the exception of performing the actual surgery, Ms M was responsible for appropriately assessing and diagnosing the patient’s condition and recommending immediate band removal.

In its decision, the court said that “the practice of a registered nurse practitioner includes the diagnosis of illness and physical condition and the performance of therapeutic and corrective measures in collaboration with a licensed physician qualified to collaborate in the specialty involved.” The court said that Dr P and Ms M worked as a team, and Ms M saw Dr P’s patients on her own and planned and ordered necessary treatment without needing Dr P’s authorization or supervision.

Although surgical removal of the gastric band is not within the scope of Ms M’s responsibilities, she had a duty to determine if the gastric band was infected, recognize the need for surgical removal, and recommend surgical removal, said the court. The court concluded that there is sufficient evidence from which a reasonable person might conclude that Ms M’s conduct was a substantial factor in causing injury to the patient.

The court refused to dismiss the case against Ms M and the hospital.The case has been remanded for trial.

Legal Background

To support the motion to dismiss the case, the hospital and Ms M noted that Dr P had testified that although Ms M could make recommendations as to whether a band or port needed removal, the ultimate decision was made exclusively by the physician. The defense also introduced an affidavit from an expert surgeon. According to the expert, Ms M acted in accordance with accepted standards of good medical practice

Protecting Yourself

With increased responsibilities comes increased risks, which makes it all the more important to advocate for patients and not simply rely on a supervisor’s judgment. ■ Ann W. Latner, JD, a former criminal defense attorney, is a freelance medical writer in Port Washington, New York.

32 THE CLINICAL ADVISOR • MARCH/APRIL 2022 • www.ClinicalAdvisor.com