A PEER-REVIEWED FORUM FOR NURSE PRACTITIONERS | JULY/AUGUST 2022 | www.ClinicalAdvisor.com CASE A Case of Dyspnea and Cough in Young Man After Climb in Colorado LEGAL ADVISOR When Is Speech Free? FEATURE Anxiety and StartMushroomedDepressioninUSatofPandemic LOOK-ALIKESDERMATOLOGIC Lower Leg Ulcers WEIGHT MANAGEMENT Adults Without Diabetes Benefit From GLP-1 Agonists for Obesity GLP-1 receptors are found in the liver, pancreas, and digestive system.
Director Nikki nikki.kean@haymarketmedia.comKean 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, michael.delaney@haymarketmedia.com551.206.5334 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. For reprints/licensing requests, contact Customer Service at custserv@haymarketmedia.com. Persons appearing in photographs in “Newsline,” “The Legal Advisor,” and “Features” are not the actual individuals mentioned in the articles. They appear for illustrative purposes only. The Clinical Advisor® (USPS 017-546, ISSN 1524-7317), Volume 25, Number 4. Published 6 times a year, by Haymarket Media, Inc., 275 7th Avenue, 10th Floor, New York, NY 10001. For Advertising Sales & Editorial, call 646.638.6000 (M–F, 9am–5pm, ET). The Clinical Advisor is available on a paid subscription basis at the following annual rates: $75 USA, $85 Canada, $110 for all other foreign, in U.S. dollars, Single copy price: USA $20, Foreign $30. To order or update a paid subscription visit our website at www.ClinicalAdvisor.com or call Periodicals800.436.9269.postagerate paid at NewYork, NY, and additional mailing offices. Postmaster: Send changes of address to The Clinical Advisor, c/o Direct Medical Data, 10255 W. Higgins Rd., Suite 280, Rosemont, IL All60018.rightsreserved. Reproduction in whole or in part without permission is Copyrightprohibited.© 2022 www.ClinicalAdvisor.com • THE CLINICAL ADVISOR • JULY/AUGUST 2022 1 FROM THE DIRECTOR
In Los Angeles, California, the city named its first chief heat officer whose job is to coordinate a better response to extreme heat and develop sustainable cooling strategies, according to Kaiser Health News. To help people prepare for the next heat wave, the CDC has developed a Heat & Health Tracker that provides local heat and health information. Here is wishing everyone a wonderful summer, stay cool!
Heat is the leading weather-related killer in the United States, according to the Environmental Protection Agency. Extreme heat contributed to the deaths of 3644 people between 2019 and 2021, with Nevada reporting the highest rates of heat-related deaths in the nation. Exposure to extreme heat can cause muscle cramping, heat exhaustion (fatigue, headache, nausea, and vomiting), and heat stroke.
July 2021 was the hottest month ever recorded, according to the National Oceanic and Atmospheric Administration (NOAA). My daughter lives in Portland, Oregon. Last June, Portland experienced a “heat dome” that shattered records with temperatures reaching a high of 115 °F. The number of people who died during the heat-related events in Oregon reached 73. We are talking about the Pacific Northwest, where average summer temperatures typically top 80 °F with lows in the high 50s. For vulnerable people living in urban heat zones, getting relief from the heat may be challenging. Heat distribution is not always equitable. This can be especially true in neighborhoods with lower-income nonwhite residents, which experience significantly more extreme land surface temperatures than their wealthier, whiter counterparts, according to researchers.
Nikki Kean, Director The Clinical Advisor
Rising Temperatures Can Be Deadly
As we enter the dog days of summer, I dream of taking a cold dip in the Atlantic Ocean or swimming in a local pool to cool off. But for many Americans who have to work outside or do not have access to pools or air conditioning, rising temperatures can be deadly.
For young children, older adults, and people with chronic medical conditions, extreme temperatures can be particularly dangerous. Warmer temperatures also mean higher ozone levels, which can affect people with respiratory issues such as asthma, bronchitis, or emphysema.Theearthis getting hotter.
IMAGESGETTY/POLITOFRAN©
www.ClinicalAdvisor.com Follow us on @ClinicalAdvisorTwitterLikeusonFacebookfacebook.com/TheClinicalAdvisorVisitusonthewebClinicalAdvisor.comWAYSMORETOFINDUS! Download the ClinicalAdvisor.com/Appapp 23 Unknown rash in sexually active adult. 25 Hyperpigmented scaly patch. 6 Dyspnea following high-altitude hike. FEATURES6ACaseofDyspnea and Cough in Young Man After Climb in Colorado The patient develops cough and dyspnea while climbing Pike’s Peak in Colorado. 12 Anxiety and Depression Mushroomed in US at Start of Pandemic Anxiety disorders are the most common mental illness in the US and affect 40 million adults every year. 19 Adults Without Diabetes Benefit From GLP-1 Agonists for Obesity Review of the pathophysiology of obesity and the mechanism of action, efficacy, and safety of GLP-1 receptor agonists. DEPARTMENTS1FromtheDirector Rising Temperatures Can Be Deadly 4 Web Roundup A summary of our most recent opinion, news, and multimedia content from ClinicalAdvisor.com. 23 Dermatology Clinic Rash on Face, Trunk, and Extremities 25 Dermatologic Look-Alikes Lower Leg Ulcers 30 Legal Advisor When Is Speech Free? CONTENTSJULY/AUGUST2022 30 Beware of what you post on social media.
The Workweek Revolution: a Solution to the Health Care Exodus The author describes the evolution of the workweek and how shortening the expected hours for full-time work without decreasing compensation may increase the well-being of health care providers while maintaining current productivity.
Obesity in Adolescence Linked to Type 1 Diabetes Development in Adults Obesity in late adolescence is correlated with both adult-onset type 1 diabetes and type 2 diabetes.
IMAGESGETTY©IMAGES:BOTTOMMIDDLE,MD;PREGERSON,BRADY©IMAGE:TOP,
Sleep Disturbance Linked to Cognitive Performance in Schizophrenia Patients
Brady Pregerson, MD Bilateral Blurry Vision
Jonathan T. Baird, DMSc, PA-C-ATC
A man in his late 40s comes to the emergency department with a complaint of blurry vision that lasted for approximately 20 minutes before returning to normal. The loss of focused vision affected both eyes. Can you make the diagnosis? See the full case at: com/case_july_august22clinicaladvisor.
Preliminary results found strong associations between worse and more variable sleep and poorer cognitive performance in patients with schizophrenia. Food Allergies, But Not Asthma, Linked to Lower Risk for COVID-19
The Task Force recommends against the use of vitamin E or beta-carotene supplements for the prevention of heart disease, stroke, or cancer.
ClinicalAdvisor.com/Clinical-Challenge
ClinicalAdvisor.com/MyPracticePRACTICE
CLINICAL CHALLENGE 4 THE CLINICAL ADVISOR • JULY/AUGUST 2022 • www.ClinicalAdvisor.com
Kristin Della Volpe NP/PA Practice Patterns Leads to Less Resource Use in Emergency Departments Nurse practitioners (NPs) and PAs working independently in emergency departments used fewer resources and less low-value care than physicians, according to recent ndings.
ClinicalAdvisor.comEXCLUSIVE TO THE WEB AT MY
Eating Skyr Yogurt Alters Microbiome in Women With Obesity Daily long-term consumption of Skyr cultures containing Streptococcus thermophilus and Lactobacillus bulgaricus altered the microbiome in women with overweight and obesity.
foronUSPSTFClinicalAdvisor.com/NewsNEWSIssuesGuidelinesVitamin,SupplementsCVD,CancerPrevention
An NIH-sponsored study found that having a food allergy cuts a person’s risk of having COVID-19 by half, while people with asthma and allergic rhinitis are not at increased risk for infection.
extension • Splint the DIP joint in full flexion • Perform closed
WHAT IS THE BEST TREATMENT OPTION? • Resume range of motion to tolerance • Splint the
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A 64-year-old woman presents with right hand pain after a fall taken 2 days earlier. The patient notes that the distal interphalangeal (DIP) joint of the right ring finger took the brunt of the fall. She reports pain and swelling at the DIP joint but no deformity is noted and she is able to fully extend the joint. DIP full reduction full case DX Pigmented Lesion on Upper Arm 15-year-old adolescent presents for evaluation of acne, which is affecting his face and back. During the examination, the clinician notes a deeply pigmented macular lesion located on the patient’s left upper arm. According to the patient, the site had been present for several years and is asymptomatic. No other immediate fam members have a similar condition and the appearance is not of cosmetic concern to the patient.
Advisor Dx www.ClinicalAdvisor.com • THE CLINICAL ADVISOR • JULY/AUGUST 2022 5 In partnership with TheJopa.org Journal of Orthopedics for Physician Assistants 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! ORTHO DX Pain in DIP Joint of Ring Finger
ily
at clinicaladvisor.com/orthodx_july_august22 DERM
and percutaneous fixation ● See the
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CAN YOU DIAGNOSE THIS CASE? • Becker nevus • Congenital melanocytic nevus ● See the full case at clinicaladvisor.com/dermdx_july_august22 • Nevus spilus • Café au lait macule
A 27-year-old man presents to the emergency department with symptoms of dyspnea and cough for the past 3 days.
IMAGESGETTY/ROWELLGALEN© Case involves a 27-year-old hiker from Georgia.
Four days earlier, the patient (Mr M) and a friend arrived at Woodland Park, Colorado (elevation: 8400 ft) from their hometown of Atlanta, Georgia (elevation: 1050 ft). The patient states that their goal was to hike a 21-mile trail to the top of Pike’s Peak (elevation: 14,100 ft) in 2 days.
After
Upon arrival at the emergency department, Mr M reports chest tightness, drowsiness, and headache. He denies nausea, vomiting, abdominal pain, chest pain, edema, hemoptysis, or medical history of asthma. No signi cant family history of cardiac or respiratory conditions is noted. Mr M
The patient develops cough and dyspnea while climbing Pike’s Peak in Colorado, climbing 4000 feet to the elevation of 12,400 ft.
A Case of Dyspnea and Cough in Young Man Climb in Colorado
6 THE CLINICAL ADVISOR • JULY/AUGUST 2022 • www.ClinicalAdvisor.com Continues on page 8
FEATURE: DANILA TEPTSOV, PA-S; E. RACHEL FINK, MPA, PA-C
On the second day of their arrival at Woodland Park, they embarked on their hike covering 10 miles, climbing 4000 ft (elevation: 12,400 ft), before setting up camp for the night. During the rst evening, Mr M reported the onset of a nonproductive cough, mild headache, and shortness of breath when lying down to sleep.The following day, Mr M’s cough worsened and was associated with dyspnea during the ascent. He states that he had to take multiple breaks to catch his breath. Based on these symptoms, his friend decided to discontinue the hike and begin their descent. During the descent, Mr M began coughing up pink, frothy sputum and experienced dyspnea during rest. A park ranger was noti ed and Mr M was taken to the nearest hospital.
Physical Examination
TABLE 1. Vital Signs Height, in 70 Weight, lb 175 BMI 25.1 Blood pressure, mm Hg 132/85 Heart rate, bpm 115 Respiratory rate, per min23 Temperature 98.7 °F/37 °C Pulse oximetry, % 81 BMI, body mass index; bpm, beats per minute
PA-CMPA,FINK,RACHELE.ANDPA-S,TEPTSOV,DANILAOFCOURTESYIMAGE©
FIGURE . Ultrasonography of comet tail artifact.
PULMONOLOGY HEALTH: HAPE 8 THE CLINICAL ADVISOR • JULY/AUGUST 2022 • www.ClinicalAdvisor.com
lives a healthy lifestyle, is an avid hiker in the Appalachian Mountains of Georgia, is physically fit, and does not have a history of smoking cigarettes or use of any street drugs.
Major risk factors for HAPE include higher or greater changes in altitude, rapid ascent rate, and individual susceptibility;
High-altitude pulmonary edema is defined as noncardiogenic pulmonary edema caused by exaggerated hypoxic pulmonary vasoconstriction, high pulmonary artery pressure, and increased capillary pressure in individuals exposed to altitudes above 8200 ft.1 Environmental conditions at elevations above 8200 ft include lower oxygen concentrations, lower barometric air pressure, and lower temperatures. Hypobaric hypoxia causes the body to go through maladaptive responses, which can result in impairment of gas exchange from abnormal accumulation of plasma and reticulocytes in alveoli because of breakdown of pulmonary blood-gas barriers.2 Impairment of gas exchange can be fatal if no interventions are performed during initial symptomHigh-altitudeonset. pulmonary edema can occur in 2 distinct forms. The first form occurs in people who live at low altitudes and ascend rapidly to altitudes greater than 8200 ft. The second form, also known as re-entry HAPE, occurs in people who live at high altitudes and return home after a period of being at a lower altitude.3 The onset of HAPE usually presents within 2 to 4 days of ascent at an elevation above 8200 ft and rarely occurs after more than 4 to 5 days at the same altitude because of remodeling and adaptation.4
Upon physical examination, the patient is alert and oriented to person, place, time, and situation. He appears to be in mild respiratory distress with signs of dyspnea while sitting with his arms leaning on his legs to assist in breathing.The patient also has a productive-sounding cough. Cyanosis is present around his lips and throughout his oral mucosa.The patient is tachypneic and tachycardic and has decreased oxygen saturation (Table 1). Upon auscultation of the posterior lung fields, inspiratory crackles and bronchial breath sounds are heard bilaterally. No other abnormalities are noted on his physical examination.
Diagnostic Workup/Diagnosis
Based on the patient’s history and presentation, the emergency department physician suspects high-altitude pulmonary edema (HAPE) and wants to confirm the diagnosis by ruling out other possible differentials through laboratory tests and imaging studies. Given the patient’s condition, he is quickly started on high-flow supplemental oxygen therapy via facemask. Complete blood cell count and metabolic panel findings indicate a mild elevation of white blood cells (11,000/µL). A respiratory pathogen panel was negative for common viral and bacterial causes such as pneumonia, influenza, and SARSCoV-2. Electrocardiography findings are normal, ruling out any associated cardiac complications. Bedside ultrasonography of the lung parenchyma reveals comet tail artifact, also known as lung rockets. This type of artifact is the ultrasonography equivalent of Kerley B lines indicating interstitial edema (Figure). Chest radiography reveals patchy opacities and alveolar infiltrates bilaterally.
High-Altitude Pulmonary Edema
Signs and Symptoms
Pharmacotherapy should not be regarded as a substitute for descent or supplemental oxygen and should only be used when the nonpharmacologic approaches are not feasible or available.11 Staying at the same altitude, receiving supplemental
Physical examination reveals tachycardia, tachypnea, cyanosis, and elevated body temperature that generally does not exceed 38.5 °C.4 Auscultation of the lung fields reveals discrete initial rales located over the middle lung fields.3 Furthermore, crackles may be unilateral or bilateral, but initially are auscultated in the right middle lobe and are heard first in the right axilla.9 Oxygen saturation is often 10% less than expected for altitude and the patient will often appear better than expected given their level of hypoxemia and oxygen saturation value.8
2.
Heavy exertion Prior history of HAPE
A suitable alternative to descent is supplemental oxygen delivery by nasal cannula or face mask at flow rates sufficient enough to achieve an oxygen saturation greater than 90%.10
TABLE Risk Factors for HAPE
Cold temperatures Pre-existing respiratory infection
www.ClinicalAdvisor.com • THE CLINICAL ADVISOR • JULY/AUGUST 2022 9 the effects of these risk factors are cumulative (Table 2). 2
High-altitude pulmonary edema presents within 2 to 4 days of ascent to a high altitude and it is rarely observed at altitudes below 8200 ft or after 1 week of acclimatization to the exposed altitude.3 High-altitude pulmonary edema symptoms have an insidious onset and include nonproductive cough, decreased exercise tolerance, chest pain, and exertional dyspnea.8 As HAPE progresses, the cough and dyspnea worsen and orthopnea develops.2 In advanced HAPE progression, individuals can experience dyspnea at rest, severe exertional dyspnea, and the cough may become productive of bloodtinged, frothy sputum.8
Additionally, patients who have access to oxygen, whether in a hospital or high-altitude medical clinic, can be treated with oxygen at the current elevation without needing to descend to a lower elevation.10 When descent and supplemental oxygen administration are not feasible, simulated descent with the use of a portable hyperbaric chamber should be used at 2 to 4 pounds per square inch for several hours as a temporary measure until real descent can be achieved.4
Higher altitudes achieved Rapid ascent rates Male sex HAPE, high-altitude pulmonary edema
It is vital to minimize exertion on descent because exertion may increase hypoxemia from metabolic demands that can further increase pulmonary artery pressure and exacerbate edema formation.10
Treatment Depending on the resources that are available at a medical facility, nonpharmacologic or pharmacologic interventions may be used. In the nonpharmacologic approach, immediate improvement of oxygenation either by supplemental oxygen, hyperbaric treatment, or rapid descent is the treatment of choice.3 Further studies have found that descent is the mainstay of treatment and individuals should try to passively descend at least 3280 ft or until symptom resolution.8
Furthermore, individuals with cardiopulmonary circulation abnormalities that may lead to pulmonary hypertension, such as mitral stenosis, primary pulmonary hypertension, unilateral absence of pulmonary artery, and patent foramen ovale, may be at an increased risk for HAPE at moderate and even low altitudes.5 Genetics can also play a role in susceptibility to developing HAPE. The genes associated with the occurrence of HAPE include polymorphisms in renin-angiotensin-aldosterone system (RAAS) pathway genes, more specifically with the angiotensin conversion enzyme (ACE), nitric oxide (NO) pathway genes (ie, NOS3), endothelin-1, and pulmonary surfactant proteins A1 and A2.6 Hypoxia-inducible factors (HIF), also known as the master regulators of oxygen homeostasis, are key transcription factors consisting of 1α (or 2α) and 1β subunits that form active transcriptional complexes under hypoxic conditions to stimulate expression of target genes.7 Hypoxia-inducible factors are involved in the release of vascular endothelial growth factor (VEGF) in the brain, erythropoiesis, and other pulmonary and cardiac functions at high altitudes.7 EPAS1 is a gene that codes for transcriptional regulator HIF-2α and is involved in decreasing inflammatory and vasoconstrictive responses to hypoxia, which allowed for the adaptation of people from Tibet and the Andes to live at high altitudes.5,7 Genetic predisposition determines how different groups of individuals will be affected and be able to adapt to high-altitude stress by a mechanism of minute ventilation.8Theincidence of HAPE among individuals at 14,763 ft is 0.6% to 6% and at 18,044 ft is 2% to 15%, with a faster ascent resulting in a higher incidence.8 In addition, those with a prior history of HAPE have a recurrence rate as high as 60% and should be managed accordingly.8
14. Wimalasena Y, Windsor J, Edsell M. Using ultrasound lung comets in the diagnosis of high altitude pulmonary edema: fact or fiction? Wilderness Environ Med. 2013;24(2):159-164.
References 1. Bärtsch P, Swenson ER. Acute high-altitude illnesses. N Engl J Med. 2013 2.13;368(24):2294-302.LuksAM,SwensonER, Bärtsch P. Acute high-altitude sickness. Eur Respir Rev. 3.2017;26(143):160096.ParalikarSJ.Highaltitude pulmonary edema—clinical features, patho physiology, prevention and treatment. Indian J Occup Environ Med. 2012;16(2): 4.59-62.Korzeniewski K, Nitsch-Osuch A, Guzek A, Juszczak, D. High altitude pulmonary edema in mountain climbers. Respir Physiol Neurobiol. 2015;209: 5.33-38.Basnyat B, Tabin G. Altitude illness. In: Loscalzo J, Fauci As, Kasper DL, Hauser SL, Longo DL, Jameson JL, eds. Harrison’s Principles of Internal Medicine, 21st ed. McGraw Hill; 2022;462. 6. Luo Y, Zou Y, Gao Y. Gene polymorphisms and high-altitude pulmonary edema susceptibility: a 2011 update. Respiration. 2012;84(2):155-162.
13. Bliss A, Mahajan S, Boehm K M. Systematic review of the effects of phosphodiesterase-5 inhibitors and dexamethasone on high altitude pulmonary edema (HAPE). Spartan Med Res J. 2019;3(3):7111.
The diagnosis of HAPE is based on results of a thorough history and physical examination.14 This case demonstrates the importance of recognizing the initial signs and symptoms of HAPE. If symptoms are recognized early, HAPE is an easily and completely reversible condition. Not only is it imperative for providers to accurately identify early signs of HAPE, but also it is important to educate patients traveling to high-altitude environments about the effects of hypoxic conditions. Simple interventions, such as having information readily available at trailheads warning of the condition and how to avoid it with acclimatization techniques, could better inform the public and decrease the incidence of HAPE. It is vital for hikers to recognize initial symptoms of HAPE so they can pursue treatment without developing long-term consequences.
PULMONOLOGY HEALTH: HAPE 10 THE CLINICAL ADVISOR • JULY/AUGUST 2022 • www.ClinicalAdvisor.com
10. Luks AM, Auerbach PS, Freer L, et al. Wilderness Medical Society practice guidelines for the prevention and treatment of acute altitude illness: 2014 update. Wilderness Environ Med. 2019;30(4S):S3-S18.
12. Leshem E, Caine Y, Rosenberg E, Maaravi Y, Hermesh H, Schwartz E. Tadalafil and acetazolamide versus acetazolamide for the prevention of severe high-altitude illness. J Travel Med. 2012;19(5):308-310.
■ Danila Teptsov, PA-S, is currently a PA student at Augusta University in Georgia. E. Rachel Fink, MPA, PA-C, is an assistant professor at the Augusta University Physician Assistant Program.
11. Pennardt A. High-altitude pulmonary edema: diagnosis, prevention, and treatment. Curr Sports Med Rep. 2013;12(2):115-119.
focuses on reduction of pulmonary artery pressure through the use of vasodilators, such as the calcium channel blocker nifedipine, which can reduce systolic pulmonary artery pressure by 50%.11 In hikers who develop HAPE at 14,957 ft elevation, taking extended-release nifedipine 20 mg every 6 hours leads to “a persistent relief of symptoms, improvement of gas exchange, and radiographic clearance of pulmonary edema over an observational period of 34 hours.”3 If nifedipine is unavailable, phosphodiesterase inhibitors such as tadalafil or sildenafil may help decrease pulmonary artery and capillary pressure. 8 In one study, tadalafil was found to be effective in reducing the incidence of HAPE in susceptible adults, those with a previous history of HAPE, and those exposed to hypoxic high-altitude environments.12
Prognosis High-altitude pulmonary edema is the more severe end of the high-altitude illness spectrum and it is the leading cause of death from altitude illness.13 If HAPE is left untreated, it can progress to dyspnea at rest and cyanosis. In a report by Jensen et al, the mortality rate from untreated HAPE is as high as 50%; when treated, the mortality rate is up to 11%.8 However, HAPE is completely and easily reversible if recognized early and treated properly.3 Individuals treated for HAPE may consider resuming ascent at an appropriate rate once they are asymptomatic, no longer require oxygen or vasodilator therapy, and have an increased exercise tolerance compared with symptom onset.8,9 Conclusion
HAPE presents within 2 to 4 days of ascent at an elevation above 8200 ft and rarely occurs after more than 4 to 5 days at the same altitude. low flow oxygen for 24 to 48 hours to maintain an arterial saturation above 90%, and bed rest can lead to relief of symptoms within hours and complete clinical recovery within several Pharmacotherapydays.4
7. Woods P, Alcock J. High-altitude pulmonary edema. Evol Med Public Health. 8.2021;9(1):118-119.JacobD,JensenJD, Vincent AL. High altitude pulmonary edema. In: StatPearls [Internet]. StatPearls Publishing; May 1, 2022. 9. Zafren K, Thurman RJ, Jones ID. High-altitude pulmonary edema. In: Koop KJ, Stack LB, Storrow AB, Thurman J. The Atlas of Emergency Medicine, 5th ed. McCraw Hill; 2021;16-01:548.
DNP, PMHNP, ANP
IMAGESGETTY/MCQUEENCATHERINE©
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12 THE CLINICAL ADVISOR • JULY/AUGUST 2022 • www.ClinicalAdvisor.com
Anxiety and MushroomedDepressioninUSatStartofPandemic COOK-PERRY, Anxiety disorders affect 40 million adults in the US.
Rates of anxiety and depression among US adults were 4 times higher between April 2020 and August 2021 compared with rates in 2019.
he COVID-19 pandemic brought to light the growing mental health crisis in America, which has a ected patients of all ages. Before 2020, mental health disorders were among the leading causes of the global health-related burden, with depressive and anxiety disorders the most disabling.1 The ongoing pandemic has exacerbated many determinants of poor mental health. As a result, rates of anxiety and depression among US adults were 4 times higher between April 2020 and August 2021 compared with rates in 2019 (Figure).2,3 Men, Asian Americans, young adults, and parents with children in the home had the greatest increases in rates of anxiety and depression, according to the Centers for Disease Control and Prevention.3 The COVID pandemic further highlighted the need to monitor children’s mental health as well. The 2020 National Survey of Children’s Health (NSCH) examined 5-year trends in children’s well-being, including potential e ects of the COVID-19 pandemic. Between 2016 and 2020, signi cant increases in the rates of children diagnosed with anxiety (from 7.1% to 9.2%) and depression (3.1% to 4.0%) were found along with decreases in daily physical activity (24.2% to 19.8%) and in caregiver mental health (69.8% to 66.3%; trend P < .001 for all comparisons).4 Primary care settings often serve as the only point of contact for individuals experiencing mental health problems. Primary care providers play a crucial role in the management of these patients.
FEATURE: JENNIFER ALLAIN, DNP, MSN, APRN, FNP-C; SHIRLEY GRIFFEY, DNP, PMHNP; CHRISTY
Panic attacks tend to occur and escalate rapidly, peaking after 10 minutes (however, a panic attack may last for hours)
The Generalized Anxiety Disorder 7-item Scale (GAD-7) is a free self-administered questionnaire that can be used to support diagnosis and as a severity measure for GAD. The tool can be introduced to patients by saying “Please complete this form so I can get a bit more information on the nature of your worries. It won’t take very long, there are only 7 questions, and it will help 2020-August 2021
•
FIGURE
•
•
Anxiety disorders in children and adolescents often co-occur with other disorders such as depression, eating disorders, and attention-deficit/hyperactivity disorder (ADHD).4,5 Identifying anxiety disorders at an early age may be important because childhood onset of some psychiatric disorders has been linked to a worse prognosis compared with adult onset.6 In older adults, generalized anxiety disorder (GAD) is the most commonly diagnosed anxiety disorder.5,7 Anxiety disorders in this older population are frequently associated with traumatic events such as a fall (or fear of a fall), safety, or onset of illness. When symptoms of anxiety become pervasive, are consistent with the Diagnostic and Statistical Manual of Mental Disorders (DSM) criteria, and affect the patient’s ability to function, the presumed diagnosis is an anxiety disorder (Table 1).5,7,8
disorderPanic
•
Diagnosing Anxiety in Adults Anxiety disorders can negatively impact a patient’s quality of life and disrupt important activities of daily living. Screening questions to ask in primary care include the following8:
disorderanxietySocial
• The fear of negative judgment from others in ≥1 social situations or of public embarrassment
• Attacks may be expected (response to a typically feared object) or unexpected (occurs for no apparent reason)
• Please tell me a bit more about the difficulties your anxiety is causing for you in terms of how you are functioning in your daily life at work and at home
• Includes a range of feelings such as stage fright, fear of intimacy, and anxiety around humiliation and rejection
•
• Often occurs with MDD
www.ClinicalAdvisor.com • THE CLINICAL ADVISOR • JULY/AUGUST 2022 13
•
• People with this disorder are not always able to identify the cause of their anxiety and find it difficult to control their worry
• Hallmark sign: fear of being scrutinized
disorderanxietyGeneralized
• Onset is typically around age 13 years
MDD, major depressive disorder
TABLE 1. Common Types of Anxiety Disorders Treated in Primary Care5,7,8
• Can cause people to avoid public situations and human contact to the point that everyday living is rendered extremely difficult
Equally common among men and women
The most common anxiety disorder
Chronic disorder involving excessive, long-lasting anxiety and worries about nonspecific life events, objects, and situations that occur more days than not for at least 6 months, about several different events/activities
.
Percentage of US adults reporting symptoms of anxiety, January to December 2019 (monthly average) and April 2020 to August 2021 (submonthly average)2,3
• Over the past 2 weeks, how often have you been bothered by either feeling nervous, anxious, or on edge?
• Includes recurrent or unexpected brief and sudden attacks of intense terror and apprehension
Anxiety disorders are the most common mental illness in the US and affect 40 million adults (or 19.1% of the population) every year.5 Anxiety disorders are highly treatable, yet only 36.9% of those diagnosed with these disorders receive treatment.5 Lack of access to mental health providers and limited insurance coverage prevent patients from obtaining proper treatment.1,2,5
•
• ≥1 attack has been followed by ≥1 month of persistent concern about additional attacks or their consequences and/or a significant maladaptive change in behavior related to attacks
• Women are twice as likely as men to be affected
Fear, anxiety, or avoidance is persistent and lasts for ≥6 months
People with anxiety disorders are 3 to 5 times more likely to go to the doctor and 6 times more likely to be hospitalized for psychiatric disorders than those without anxiety disorders.5 Anxiety develops from a complex set of risk factors, including genetics, brain chemistry, personality, and life events.5 Depression is a common comorbidity in patients with anxiety with approximately 50% of those diagnosed with depression also diagnosed with an anxiety disorder.5 Anxiety disorders affect 31.9% of children between the ages of 13 and 18 years.4 Children with untreated anxiety are at higher risk of performing poorly in school, missing important social experiences, and engaging in substance abuse (often as self-medication).4,5
Hallmark signs: shaking, sweating, palpitations, fear of dying, confusion, dizziness, nausea, and breathing difficulties
• Hallmark signs: excessive, persistent, out-of-control worry about various domains
403530252015105%Anxiety,ofRates Jan 2019-Dec 2019 April
The Truth About Anxiety
• Have you been unable to stop or control your worrying?
• Many of these patients will wait 10 years or more before seeking help
Physical symptoms include restlessness, fatigue, difficulty concentrating, irritability, muscle tension, and sleep disturbance
• Avoid
disorder • Addiction/abuse is
• Often
Many symptoms of anxiety (heart palpitations, increase in blood pressure, shaking, tremors) are caused by sympathetic overactivity
Chronic obstructive pulmonary diseasePheochromocytoma heart failure embolism or Adults Primary such as venlafaxine and duloxetine, are indicated the of anxiety as they are safer and more often within for no more than 1 month when used for GAD, panic disorder, and social anxiety possible and withdrawal symptoms may occur if stopped suddenly; important to taper off when discontinuing clonazepam, lorazepam (preferred in the elderly), and diazepam dopamine D2 receptor blocking action Does not produce antipsychotic or extrapyramidal side effects prescribed with an antidepressant little potential for producing tolerance or physical dependence; no abuse liability Slow onset of action; not suitable for an acute episode of anxiety is commonly used to treat GAD; this agent does not produce significant sedation or cognitive impairment use in patients with renal or hepatic impairment is used for short-term treatment of anxiety and tension symptoms as well as to treat allergic reactions Acts quickly by rapidly absorbing into the stomach; begins working as soon as 15-30 minutes after administration
Propranolol and other nonselective beta-blockers can help with these symptoms Do not affect psychological symptoms such as worry, tension, and fear but are valuable in acutely stressful situations (examinations, public speaking)
• Buspirone
• Have
Most common side effect is sleepiness; this agent is also commonly used to treat insomnia
1 hour • Typically prescribed
Azapirones • Weak
TABLE Disease States Associated With Anxiety9 arrhythmia
•
•
β-blockers •
Cardiac
Care10-12 Antidepressants • Antidepressants are typically first-line treatment for anxiety, particularly SSRIs • SSRIs take 6-8 weeks to be fully effective • SSRIs are not addictive • Examples include paroxetine, sertraline, fluoxetine, and escitalopram • Some serotonin and norepinephrine reuptake inhibitors (SNRIs),
•
2.
in
The median age of onset of anxiety disorders in children is approximately 11 years and onset typically occurs during a specific developmental phase such as specific phobias in the school-age years; social anxiety in the early adolescent years; and GAD, panic, and agoraphobia in the later adolescent/ young adult years.13 While no universal recommendation for screening for anxiety disorders in children and adolescents exists, free screening tools such as the GAD-7 and the Screen
Pneumonia Encephalitis Porphyria Hyperadrenalism Pulmonary
use • Safe for short-term use with antidepressants • Examples include alprazolam,
for anxiety Benzodiazepines • Have largely replaced barbiturates in
GAD, generalized anxiety disorder; SSRIs, selective serotonin reuptake inhibitors
effective • Work quickly,
•
MENTAL HEALTH AND COVID-19 14 THE CLINICAL ADVISOR • JULY/AUGUST 2022 • www.ClinicalAdvisor.com me to work out how best to help you.” In addition to assessing a person’s symptoms and associated functional impairment, consider how the following factors may affect the development, course, and severity of the person’s presenting problem7,8: • History of any mental health problem • History of a chronic physical problem • Any past use of, and response to, treatments • Quality of interpersonal relationships • Living conditions and social isolation • Family history of mental illness • History of domestic violence or sexual abuse
treatment
antihistamineSedative • Hydroxyzine
Neoplasms
Anxiety Disorders in Children and Adolescents
Hyper-
•
•
hypothyroidism Vestibular dysfunction Hyperventilation Vitamin B12 deficiency TABLE 3. Medications Used to Treat Anxiety Disorders Among
Continues on page 16
Congestive
The rates of underdiagnosis and misdiagnosis of GAD and panic disorder in primary care are high, with symptoms often ascribed to physical causes.8,9 Careful evaluation of an anxious patient will help to determine if the cause of the anxiety is organic or psychological (Table 2).9-11 Clinical guidelines for pharmacologic treatment of anxiety in adults recommend a selective serotonin reuptake inhibitor (SSRI), such as paroxetine and escitalopram, as first-line treatment (Table 3).12 Current treatment guidelines discourage the use of benzodiazepines (except as a short-term measure during crises) and antipsychotics for the treatment of anxiety disorders in primary care.12
8.clinical-case-scenarios-pdf-version-pdf-181726381https://www.nice.org.uk/guidance/cg123/resources/AmericanPsychiatricAssociation. Diagnostic and Statistical Manual of Mental Disorders. 5th ed. American Psychiatric Association; 2013.
Low-intensity psychological interventions for anxiety disorders include psychoeducation groups and individual guided self-help with written or electronic materials of appropriate reading age.12 High-intensity treatment recommendations include 12 to 15 weekly sessions of cognitive behavioral therapy (CBT) delivered by trained and competent practitioners.12 Adult CBT usually combines several di erent interventions such as psychoeducation, worry exposure, applied relaxation, problem-solving, cognitive restructuring, and interpersonal psychotherapy.12 The AACAP recommends that CBT be o ered to patients 6 to 18 years old with social anxiety, GAD, separation anxiety, speci c phobia, or panic disorder.13 Cognitive behavioral therapy in children is aimed at both the child and parents with a focus on learning positive self-talk, coping skills training, and thought challenging.13
9. Chen JP, Reich L, Chung H. Anxiety disorders. West J Med 2002;176(4):249-253.
References 1. COVID-19 Mental Disorders Collaborators. Global prevalence and burden of depressive and anxiety disorders in 204 countries and territories in 2020 due to the COVID-19 pandemic. Lancet. 2021;398(10312):1700-1712.
2.Terlizzi EP, Schiller, JS. Estimates of mental health symptomatology, by month of interview: United States, 2019. National Center for Health Statistics. March 2021. Accessed June 18, 2022. www.cdc.gov/nchs/data/nhis/mental-health-monthly-508.pdf
What percentage of children between the ages of 13 and 18 years have anxiety disorders? ■ 25.1% ■ 31.9% ■ 39.2% ■ 42.6% For more polls, visit ClinicalAdvisor.com/Polls POLL POSITION 23.08% 19.23% 21.15% 36.54%
12. National Institute for Health and Care Excellence. Generalized anxiety disorder and panic disorder in adults: management. Updated June 2020. Accessed June 27, 2022. https://www.nice.org.uk/guidance/cg113
Conclusion Given the marked increase in anxiety rates among both adults and children during the COVID-19 pandemic, primary care clinicians should ask patients about anxiety symptoms and use simple screening tools such as the GAD-7 at regular visits. ■ Jennifer Allain, DNP, MSN, APRN, FNP-C, is the NP program coordinator and master teacher of mental health psychiatric nursing at The LHC Group, Myers School of Nursing of the University of Louisiana at Lafayette College of Nursing and Health Sciences. Shirley Gri ey, DNP, PMHNP, is a psychiatric nurse practitioner at Baton Rouge General Medical Center and an instructor at Southeastern Louisiana University School of Nursing. Christy Cook-Perry, DNP, PMHNP, ANP, is assistant professor at Southeastern Louisiana University College of Nursing and Health Sciences.
5. Facts and statistics. Anxiety and Depression Association of America. June 18, 2022. Accessed June 21, 2022. https://adaa.org/understanding-anxiety/facts-statistics
Nonpharmacologic Recommendations
for Child Anxiety Related Disorders are readily available. Treatment guidelines for children are similar to those for adults.
4. Lebrun-Harris LA, Ghandour RM, Kogan MD, Warren MD. Five-year trends in US children’s health and well-being, 2016-2020. JAMA Pediatr. 2022 Mar 14:e220056.
MENTAL HEALTH AND COVID-19 16 THE CLINICAL ADVISOR • JULY/AUGUST 2022 • www.ClinicalAdvisor.com
6. Scheeringa MS, Burns LC. Generalized anxiety disorder in very young children: rst case reports on stability and developmental considerations. Case Rep Psychiatry. 2018;2018:7093178.
13. Walter HJ, Bukstein OG, Abright AR, et al. Clinical practice guideline for the assessment and treatment of children and adolescents with anxiety disorders. J Am Acad Child Adolesc Psychiatry. 2020;59(10):1107-1124.
The American Academy of Child and Adolescent Psychiatry (AACAP) recommends that SSRIs be o ered to patients 6 to 18 years old with social anxiety, GAD, separation anxiety, or panic disorder.13 All SSRIs have a boxed warning for suicidal thinking and behavior through age 24 years with the rate for suicidal ideation across all antidepressant classes reported to be 1% compared with 0.2% for placebo.13 The US Food and Drug Administration recommends close monitoring of children for suicidality, especially during the rst months of treatment.11,12
7. National Institute for Health and Clinical Excellence. Common mental health problems. Clinical case scenarios for primary care. May 2012. Accessed May 27, 2022.
10. Stahl MS. Stahl’s Essential Psychopharmacology. 4th ed. Cambridge University Press; 2011. 11. Stahl MS. Stahl’s Essential Psychopharmacology: Prescriber’s Guide. 6th ed. Cambridge University Press; 2017.
3. National Center for Health Statistics. Household pulse survey — anxiety and depression. Centers for Disease Control and Prevention. Accessed June 21, 2022. www.cdc.gov/nchs/covid19/pulse/mental-health.htm
IMAGESGETTY©IMAGES:BOTTOMTOP, www.ClinicalAdvisor.com • THE CLINICAL ADVISOR • JULY/AUGUST 2022 17
Conference Roundup
The researchers studied the benefits of administration of CAGE-AID and SBIRT (screening, brief intervention, and referral to treatment) over a 10-week
Antibiotic use for suspected UTIs is common and often inappropriate in older adults. Florida
A workflow protocol for urine testing for these patients resulted in appropriate treatment based on laboratory results rather than just taking an often inappropriate educated guess. Hospitalization in this population results in another myriad of problems and this easy to implement framework decreases the chance that hospitalization will be the treatment outcome,” Dr Koslap-Petraco said.
2022 AANP National Conference American Association of Nurse Practitioners June 21 to 26, 2022, Orlando,
Half of all patients enrolled in the Senior Services Homebound Program received the intervention. Calls from patients and caregivers were managed by a nurse care coordinator who triaged symptom-based calls. The nurse would then report findings to a nurse practitioner or PA.The researchers compared infection rates among 15 enrolled patients with those among nonenrolled homebound patients. Among the patients enrolled in the protocol, 73% were women, 53% lived in assisted living facilities, and 53% were between 80 to 90 years of age.
“This clinically significant project offers a standardized method for addressing this condition in an evidence-based paradigm.
The implementation of a standardized workflow for the diagnosis and management of urinary tract infections (UTIs) in patients using home health care did not increase emergency department visits or hospitalization rates, according to the results of a pilot “Antimicrobialstudy.usefor suspected UTI among older adults is very common and often inappropriate,” said the study authors. Homebound older adults are at higher risk for infection and UTI diagnosis can be challenging. “This often results in high antibiotic use, which can lead to multidrug-resistant infections, drug interactions, and medication-related adverse effects,” noted the authors. Delay in administering empiric antibiotics raises the risk for sepsis in older patients.
CAGE-AID HELPS IDENTIFY PATIENTS WITH SUD FOR RECOVERY
The total number of UTIs in the protocol group was 23 compared with 20 in the control group; the number of UTI-related hospitalizations was lower in the protocol group than in the control group (2 vs 6).
WORKFLOW PROTOCOL IMPROVES UTI CARE IN OLDER ADULTS
The workflow protocol was easy for nurses to implement, according to the authors. Patients who were triaged for urinary testing were more likely to receive testing following implementation of the protocol; those with symptoms not appropriate for empiric treatment were provided with supportive care instructions and revisited 2 days later, the authors concluded.
The use of the CAGE-AID screening tool in an emergency department (ED) was linked to increased referral to an addiction recovery coach for treatment of alcohol and drug use disorders, the authors of a poster reported. Approximately 1 in 4 ED patients screen positive for risky alcohol and/or drug use. However, previous attempts to integrate screening for alcohol and drug use into ED nurses’ workflow have had mixed results.
The lack of a clinical standard for diagnosis and management of UTIs in homebound older adults led the team to embark on a quality improvement project. This included the development of a standardized workflow protocol for the initial diagnosis and management of urinary symptoms.
LIFESTYLE MODIFICATIONS
• Exercise • Elimination of dietary triggers Dizziness Handicap Inventory (DHI) and Headache Disability Inventory (HDI) were used to calculate results.
• Mealtime regularity
Over the 10-week control period, 15.7% of 209 patients were referred to an addiction recovery coach. According to lead author Julie M. Daly, DNP, MSN, APN,“recovery coaches serve as personal guides and mentors to people seeking or already in long-term recovery.” They connect patients to resources, develop wellness plans, monitor progress with recovery, and provide encouragement. They complement counseling, 12-step recovery programs, and other recovery supportDuringsystems.theintervention period, the percentage of patients referred to an addiction recovery coach rose to 33% and included 77 patients. “It was noted that 59% of patients with a documented positive CAGE-AID screening were also documented as having agreed to and received a referral to ARC,” noted Dr Daly.
A nurse practitioner (NP)-led, mindfulnessbased intervention for underserved elementary students led to improvements in emotional regulation and behavior, explained Cara C. Young, PhD, RN, FNP-C, FAANP, FAAN.
period compared with standard of care during the preceding 10 weeks.
All patients who presented to Jefferson Health older than 18 years and did not qualify for emergency or mental health services were assessed for social history by a licensed provider (physician, nurse practitioner, or PA). All patients who answered yes to either question about history of alcohol or drug use were administered CAGE-AID by the ED physician.
The study was designed to investigate the effects of the standardized mindfulness-based intervention A Still Quiet Place when used in at-risk, predominantly Hispanic (75%) elementary school students in fourth and fifth grades (N=16) before they transitioned from elementary to middle school. The mindfulness sessions were conducted after school hours. The A Still Quiet Place program is an 8-week mindfulness-based stress reduction program designed for therapists, teachers, and other professionals to use with children and adolescents. A majority of the students (88%) completed the intervention. Outcomes were based on parent reports.
Dizziness scores improved by a mean of 14 points overall and 39.2% of patients experienced an 18-point or greater decrease in DHI score postintervention. Headache scores also decreased by a mean of 14 points with 17.9% of the group experiencing a 29-point or greater decrease in HDI score.
MINDFULNESS IMPROVES MOOD AND BEHAVIOR IN UNDERSERVED STUDENTS
ALLEVIATE VESTIBULAR MIGRAINE SYMPTOMS
The sleep intervention appeared to be linked to the greatest improvement in symptoms, according to the researchers.
■
• Restful sleep
A majority of parents reported improvement in their child’s mood, attitude, and behavior (ie, sibling and family interactions) at home. Parents said they appreciated the movement and stillness practices, take-home materials, and after-school timing. Parents also suggested the need for improved feedback loops, additional parent-involved group sessions, and the ability to track mindfulness homework. School staff reported “excitement of the children in their participation” in the mindfulness training and noted logistical challenges with implementation, Dr Young said.
A majority of parents reported improvement in their child’s mood, attitude, and behavior.
Vestibular migraine is a common cause of vertigo and can significantly impact quality of life. Interventions to treat vestibular migraine include lifestyle modifications as well as prophylactic and rescue medications.While lifestyle modifications can improve symptoms of other forms of migraine, these strategies have yet to be studied in vestibular migraine.
The current study was comprised of 28 patients with vestibular migraine as defined by ICHD-3 criteria. All participants agreed to be treated without pharmacological intervention. Participant were asked to adhere to the following lifestyle modifications for 60 days:
The benefits of an NP-school partnership during mindfulness training in this population include the potential for increased identification of at-risk students in need of health care services and for the NP to act as an advocate and liaison to ensure that additional services are provided to students in need, Dr Young said.
Those who answered yes to 1 or more of the CAGE-AID questions were encouraged by the provider to accept a referral to an addiction recovery coach.
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Adults Without Diabetes Benefit From GLP-1 Agonists for Obesity FEATURE: DARLENE M. SANDERS, DMSc, MPAS, PA-C www.ClinicalAdvisor.com • THE CLINICAL ADVISOR • JULY/AUGUST 2022 19
The agents were approved based on clinical studies supporting the use of these GLP-1 agonists as targeted antiobesity therapies.2,3
CHANGVIVIANBYMONTAGE/IMAGESGETTYIMAGES:©
New increaseandreducetreatmentsappetitefoodintakeandsatiety.
The prevalence of obesity among adults in the US has been increasing and has reached 41.9%, with the highest rates found among non-Hispanic Black adults (49.9%) followed by Hispanic adults (45.6%), according to data from the 2017-2020 Obesity is associated with an increased risk of developing diabetes, heart disease, stroke, and some types of cancer and reduced quality of life.
Prevalence of Obesity
besity was first recognized by the American Medical Association as a chronic disease requiring medical interventions in 2013.1 Although medications promoting weight loss have been available since the 1930s, few remain on the market because of side effects, including cardiotoxicity, psychiatric disturbances, and dependency.2,3 The US Food and Drug Administration (FDA) has approved 6 agents for the long-term management of obesity: liraglutide, lorcaserin, naltrexone/bupropion, orlistat, phentermine/topiramate, and semaglutide.2 This review will focus on the 2 most recently approved antiobesity medications — liraglutide and semaglutide. These agents are glucagonlike peptide-1 (GLP-1) receptor agonists, which were first approved for the treatment of type 2 diabetes. The new indications include weight loss in adults with obesity (body mass index [BMI] ≥30) without diabetes and adults with a BMI of 27 or greater and 1 weight-related comorbidity (hypertension, type 2 diabetes, or dyslipidemia).2
Glucagon-like peptide-1 receptor agonists improve glycemic control by enhancing insulin secretion from the beta-pancreatic cells and inhibiting glucagon release from the alpha-pancreatic cells.9,10 Additionally, the agonists slow gastric emptying, increase satiety, and reduce appetite, resulting in weight reduction.9,10
GLP-1 Receptor Agonists Approved for Obesity Liraglutide (Victoza) and semaglutide (Ozempic) are longacting GLP-1 receptor agonists made by the same manufacturer (Novo Nordisk) and currently approved for the treatment of type 2 diabetes.3 Both medications also are approved as adjuncts to a reduced-calorie diet and increased exercise for chronic weight management at different doses than those used for diabetes treatment and under the brand names Saxenda and Wegovy, respectively.3,11,12
Semaglutide manufacturing problems have also limited the supply of this agent; this issue is expected to be resolved later this year. (Kolata G. The doctor prescribed an obesity drug. Her insurer called it ‘vanity.’ New York Times. May 31, 2022).
Lack of Insurance Coverage for Antiobesity Medications
WEIGHT MANAGEMENT: GLP-1 RECEPTOR AGONISTS 20 THE CLINICAL ADVISOR • JULY/AUGUST 2022 • www.ClinicalAdvisor.com
Many health insurance companies do not cover the cost of GLP-1 receptor agonists when used for weight loss or other antiobesity medications. Patients may be counseled that coupons and patient assistance programs may assist in getting access to these GLP-1 receptor agonists in the near future.
Pathophysiology of Obesity
Incretin Effects on Organs
Role of Incretin Hormones in Metabolism
Endogenous GLP-1 has a half-life of less than 2 minutes because it is rapidly degraded by dipeptidyl peptidase IV (DPP4).9 Glucagon-like peptide-1 receptor agonists are identified as short- or long-acting agents.10 Short-acting receptor agonists circulate for a few hours, followed by periods of GLP-1 inactivity.10 Long-acting receptor agonists produce a long-lasting drug concentration with little fluctuation in drug levels.10 Short-acting GLP-1 receptor agonists lower glucose levels by slowing gastric emptying, while long-acting GLP-1 receptor agonists lower glucose levels by slowing gastric emptying, increasing insulin production, and inhibiting glucagon.10 Both liraglutide and semaglutide are long-acting agents; no short-acting agents are currently approved for weight loss.10-12
The incretin effect is a 2- to 3-fold increase in insulin stimulation after oral glucose consumption, which leads to GIP and GLP-1 secretion. National Health and Nutrition Examination Survey.4,5 Obesity is associated with an increased risk of developing diabetes, heart disease, stroke, and some types of cancer.4 Obesity is also associated with poorer mental health outcomes and reduced quality of life.6
The latest antiobesity agents target GLP-1 receptors, which are concentrated within the pancreas, GI system, central nervous system, heart, lungs, kidneys, blood vessels, and peripheral nervous system.1 Incretin hormones are GI peptides secreted following food intake and an elevation of blood glucose level.1 The focus on incretin hormones as an obesity treatment evolved after observing the incretin effect.1 This effect describes the 2- to 3-fold increased insulin stimulation from the pancreas following oral glucose consumption as compared with intravenous infusion.1 Ingestion of oral glucose leads to the secretion of glucose-dependent insulinotropic polypeptide (GIP) and GLP-1 from specialized cells in the gut.1 K-cells produce GIP in the duodenum and upper jejunum, and L-cells produce GLP-1 in the lower GI system.1 The combined effect of GIP and GLP-1 secretion in healthy adults results in increased insulin secretion and delayed gastric emptying.1 In people with type 2 diabetes, however, this incretin effect is decreased or nonexistent.1
Glucagon-like peptide-1 uptake in the hypothalamus reduces appetite and food intake and increases satiety.7-10 Alpha cells of the pancreas produce glucagon and beta cells of the pancreas secrete insulin.8 Both cell types have GIP and GLP-1 receptors on their membranes.1 The presence of GLP-1 delays gastric emptying and acid secretion while slowing transit through the gut.8 Uptake of GLP-1 in the liver decreases gluconeogenesis, increases glycogen storage, and decreases lipogenesis.8-10 Mechanism of Action of GLP-1 Receptor Agonists
While weight gain is commonly thought to be caused by an imbalance of calorie intake to calorie expenditure, the risk of developing obesity also is associated with environmental and genetic factors.2 Data from the genome project have identified more than 140 genetic chromosomal regions related to obesity.7 Weight gain also is related to use of certain medications such as antidepressants and corticosteroids as well as certain illnesses, including Cushing disease and hypothyroidism.6 Research into the role of the gastrointestinal (GI) system has found that an altered microbiome also appears to play a role in the development of obesity.2
Liraglutide
In June 2021, the FDA approved semaglutide for chronic weight management in adults with obesity and overweight.12 With a starting dose of 0.25 mg, the once-weekly subcutaneous injection should be increased in 4-week intervals to 2.4 mg.12 Semaglutide has an extended half-life of approximately 1 week, making it suitable for once-weekly administration.9,12,14
Obesity Pillars. 2022. Published online April 15, 2022. 3. O’Neil PM, Birkenfeld AL, McGowan B, et al. Efficacy and safety of semaglutide compared with liraglutide and placebo for weight loss in patients with
Few patients stopped GLP-1 receptor agonists because of drug-related adverse events, and those that did cited GI-related events.
www.ClinicalAdvisor.com • THE CLINICAL ADVISOR • JULY/AUGUST 2022 21
The initial dose is 0.6 mg once daily for 1 week to be increased weekly to a target dose of 3 mg once daily.11 Liraglutide is long-acting and administered by daily subcutaneous injections and has a half-life of 12.6 to 14.3 hours.3 Semaglutide
Statementinvestigational2.ama-recognizes-obesity-as-a-disease.htmlhttps://www.nytimes.com/2013/06/19/business/BaysHB,FitchA,ChristensenS,BurridgeK,TondtJ.Antiobesitymedicationsandagents:anObesityMedicineAssociation(OMA)ClinicalPractice(CPS)2022.
The weight loss observed with semaglutide is greater than that reported for other approved antiobesity drugs: orlistat (6%), lorcaserin (6%), phentermine-topiramate (8%-10%), and naltrexone-bupropion (5%).3 Most established guidelines define meaningful weight loss as 5% to 10% of initial weight at which point an improvement in cardiovascular risk factors is Once-weeklyobserved.2 administration may improve patient compliance and quality of life over once-daily dosing as has been demonstrated in the management of type 2 diabetes with GLP-1 receptor agonists as well as administration of medications for other chronic diseases.15,16 Conclusion Glucagon-like peptide-1 receptor agonists access specific brain areas important for appetite regulation, resulting in weight loss.17 These mechanisms may help explain how treatment with GLP-1 agonists leads to reduced appetite and food cravings and better control of eating.3,17 Evidence supports both GLP-1 agonists liraglutide and semaglutide as effective agents for weight loss in patients with obesity without diabetes, with semaglutide data providing a more significant weight loss in clinical trials. Although GLP-1 agonists have side effects, the weight loss benefits may outway their risks.
References
Safety Profiles and Side/Adverse Effects
The most common side effects of GLP-1 agonists reported in clinical trials for weight management were nausea, diarrhea, vomiting, constipation, abdominal pain, headache, fatigue, dyspepsia, dizziness, abdominal distension/pain, injection site reactions (liraglutide), increased lipase (liraglutide), pyrexia (liraglutide), eructation (semaglutide), flatulence (semaglutide), hypoglycemia in patients with type 2 diabetes, gastroenteritis, and gastroesophageal reflux disease (semaglutide).11,12 Most adverse events reported were mild (69%) and severe adverse events were rare.3 Few patients stopped the medications because of drug-related adverse events, and those that did cited GI-related events.3,11,12 The discontinuations occurred during escalating doses of semaglutide rather than after reaching the final dose.3 Both acute pancreatitis and acute gallbladder disease have been observed in patients treated with GLP-1 receptor agonists, including semaglutide and liraglutide.3,11,12 Reports of cholelithiasis and cholecystitis increased across the semaglutide dosing range (2%-7%).3 An increased risk of developing upper respiratory infections has been reported with the use of GLP-1 receptor agonists.14 The increased risk is listed as an adverse reaction in some package inserts of this class but is not a contraindication to use and is not listed as a warning or precaution.14 Efficacy of Liraglutide and Semaglutide O’Neil and colleagues compared liraglutide with semaglutide in adults without diabetes and with a BMI of 30 or greater (mean BMI, 39.3).The authors, who disclosed that the study was funded by the drug’s manufacturer, reported that liraglutide 3.0 daily was associated with an estimated mean weight loss of 7.8% at week 52, while semaglutide 0.2 mg, 0.3 mg, and 0.4 mg resulted in an 11.6%, 11.2%, and 13.8% weight reduction. Estimated mean weight loss was 2.3% for the placebo group.3
In 2015, the FDA approved liraglutide (3 mg) as the first GLP-1 receptor agonist for chronic weight management in adults with obesity and overweight.11 In December 2020, the FDA approved an updated label for use of liraglutide in the treatment of obesity in adolescents (12-17 years).13
Darlene M. Sanders, DMSc, MPAS, PA-C, is a family practice PA in rural Disclosure:Montana.DrSanders has no relevant financial disclosures.
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1. Pollack A. AMA recognizes obesity as a disease. New York Times June 18, 2013. Accessed June 1, 2022.
16. Iglay K, Cao X, Mavros P, Joshi K, Yu S, Tunceli K. Systematic literature review and meta-analysis of medication adherence with once-weekly versus oncedaily therapy. Clin Ther. 2015;37(8):1813-21.e1.
the editor
17. Blundell J, Finlayson G, Axelsen M, Flint A, Gibbons C, Kvist T, Hjerpsted JB. Effects of once-weekly semaglutide on appetite, energy intake, control of eating, food preference and body weight in subjects with obesity. Diabetes Obes Metab. 2017;19(9):1242-1251. to at
11. Saxenda® (liraglutide). Prescribing information. Novo Nordisk; 2021. Accessed June 2, 2022. https://www.novo-pi.com/saxenda.pdf
WEIGHT MANAGEMENT: GLP-1 RECEPTOR AGONISTS 22 THE CLINICAL ADVISOR • JULY/AUGUST 2022 • www.ClinicalAdvisor.com obesity: a randomised, double-blind, placebo and active controlled, doseranging, phase 2 trial. Lancet. 2018;392(10148):637-649. 4. Adult obesity facts. Centers for Disease Control and Prevention. Updated May 17, 2022. Accessed May 31, 2022. https://www.cdc.gov/obesity/data/adult.html
13. Novo/Nordisk. FDA approves Saxenda® for the treatment of obesity in adolescents aged 12-17. Press release. December 2, 2020.
5. Stierman B, MPH, Afful J, et al. National Health and Nutrition Examination Survey 2017-march 2020 pre-pandemic data files-development of files and prevalence estimates for selected health outcomes. National Health Statistics Reports Number. 2021;158. 6. Obesity basics. Centers for Disease Control and Prevention. Updated April 7, 2022. Accessed May 31, 2022. https://www.cdc.gov/obesity/basics/ 7.index.htmlFallT,Mendelson M, Speliotes EK. Recent advances in human genetics and epigenetics of adiposity: pathway to precision medicine? Gastroenterology 8.2017;152(7):1695-1706.NauckMA,MeierJJ.Incretin hormones: Their role in health and disease. Diabetes Obes Metab. 2018;20 Suppl 1:5-21.
12. Wegovy™ (semaglutide). Prescribing information. Novo Nordisk; 2021. Accessed June 2, 2022. https://www.novo-pi.com/wegovy.pdf
editor@ClinicalAdvisor.com
Become a Peer Reviewer for The Clinical Advisor is seeking highly qualified peer reviewers to review our manuscript submissions. All of our feature articles, case studies, and clinical challenges undergo medical peer review. Each review is double-blinded to ensure confidentiality. If you are interested, please provide a list of the subject areas in which you have expertise, and submit your resume/curriculum vitae
9. Tilinca M, Tiuca R, Burlacu A, Varga A. A 2021 update on the use of liraglutide in the modern treatment of ‘Diabesity’: A narrative review. Medicina (Kaunas). 2021;57(7):669. 10. Brown E, Cuthbertson DJ, Wilding JP. Newer GLP-1 receptor agonists and obesity-diabetes. Peptides. 2018;100:61-67.
weekly14.us.com/content/nncorp/us/en_us/media/news-archive/news-details.html?id=39225https://www.novonordisk-WildingJPH,BatterhamRL,CalannaS,etal;STEP1StudyGroup.Once-semaglutideinadultswithoverweightorobesity. N Engl J Med. 15.2021;384(11):989-1002.PolonskyWH,Arora R, Faurby M, Fernandes J, Liebl A. Higher rates of persistence and adherence in patients with type 2 diabetes initiating once-weekly vs daily injectable glucagon-like peptide-1 receptor agonists in US clinical practice (STAY Study). Diabetes Ther. 2022;13(1):175-187.
Rash on Face, Trunk, and Extremities
DIAGNOSIS
Dermatology Clinic CASE www.ClinicalAdvisor.com • THE CLINICAL ADVISOR • JULY/AUGUST 2022 • 23
Syphilis is an infection from the bacterium Treponema pal lidum that spreads through sexual transmission or vertically from mother to baby. The only known host of T pallidum is humans, affecting 16% to 30% of individuals who have had sexual contact with an infected person within the last 30 days.1 The bacterium can inoculate intact mucous membranes or microabrasions leading to anogenital ulcer and then spread to the regional lymph nodes and blood to other parts of the body.2
A 60-year-old Black woman presents with a 30-day history of a nonitchy rash.The rash is located on her face, trunk, and extremities. She reports that she has tried topical steroids on the rash, which did not help. The patient has no other medical conditions and takes no medications. She notes that she had unprotected sex with a new partner about 4 months prior to presentation. On physical examination, the patient has many scattered erythematous scaly papules on her face, abdomen, back, and upper and lower extremi ties including the palms and soles.
Syphilis has been broken down into 3 distinct stages. Primary syphilis presents as a single chancre at the site of inoculation. A chancre appears approximately 3 weeks after exposure with an incubation period of 10 to 90 days. As the disease progresses, it spreads to other tissues and manifests as secondary syphilis around 3 months after initial infection. Secondary syphilis presents as a disseminated mucocutaneous rash and maculopapular lesions in 50% to 70% of patients. In about 10% of patients, secondary lesions are accompanied by condylomata lata, highly infectious lesions favoring warm and moist areas of the body.1,2 After healing of clinical lesions, patients enter the latency stage, which is characterized by positive serologic tests in the absence of symptoms. Approximately 70% of untreated individuals will remain in latency for the rest of their lives.4 Clinical manifestations of tertiary syphilis may appear 20 to 40 years after initial infection and include gummas (localized bone destruction), cardiovascular syphilis (aortic insufficiency or aneurysm), and neurosyphilis.1,2 Syphilis affected 129,813 individuals in 2019, which repre sents a 74% increase from 2015. Of the 30,644 cases in 2017, 88% occurred in men with 58% of overall cases occurring in men who have sex with men.5 Syphilis rates have increased among women every year since 2003 and in every age group. From 2012 to 2016, the rates of congenital syphilis increased by 86.9%, from 8.4 cases in 2012 to 15.7 cases per 100,000 live births in 2016.6 The clinical presentation of an anogenital chancre is typically indurated and painless and is accompanied by enlarged regional lymph nodes. However, atypical presentations may occur as soft, multiple, or painful lesions, and lesions may occur in other Secondary Syphilis
SARAH FRISKE, BBA;TARA L. BRAUN, MD
Throughout the centuries, sexually transmitted diseases (STDs) were seen as a single disease. However, Ricord helped differentiate syphilis from gonorrhea in an 1831 study. The discovery of the etiologic agent of syphilis around 1905 by Schaudinn and Hoffman further helped identify syphilis as its own separate disease. The use of dark-field microscopy and serologic testing were introduced in the early 1900s.3
5
The most sensitive and specific test for diagnosis of primary syphilis is dark-field microscopy of fluid from the chancre.
The most sensitive and specific test for diagnosis of primary syphilis is dark-field microscopy of fluid from the chancre. Antibodies to cardiolipin are present in about 80% of patients with clinical symptoms of primary syphilis. Antibodies to T palladium are detected via microhemagglutination T pallidum (MHA-TP) and fluorescent treponemal-antibody absorption (FTA-ABS) assays.These assays are positive in approximately 90% of patients with symptoms of primary syphilis and remain positive for life; therefore, dark-field microscopy is required to differentiate between primary syphilis and an earlier infection. Secondary syphilis is diagnosed via dark-field microscopic examination of serous exudates from lesions of skin and mucous membranes (except those of the oral cavity) and via antibody serologic tests.4
The diverse histologic and clinical presentations of secondary syphilis have led to the nickname the great masquerader. As a result, there are many conditions to consider in the differential diagnosis of syphilis such as alopecia areata, bullous pemphigoid, cutaneous lymphoid hyperplasia, granuloma annulare, histiocytoma, mycosis fungoides, pemphigus vulgaris, pityriasis lichenoides et varioliformis acuta (PLEVA), eczematous dermatoses, sarcoidosis, vasculitis, leprosy, lichen planus, and lupus erythematosus.7 Differential diagnosis of a truncal rash should include acute HIV infection, viral exanthems, pityriasis rosea, drug eruption, and psoriasis. In addition, clinicians should eliminate erythema multiforme; hand, foot, and mouth disease; and Rocky Mountain spotted fever for a palmoplantar rash.
8. Flamm A, Parikh K, Xie Q, Kwon EJ, Elston DM. Histologic features of secondary syphilis: a multicenter retrospective review. J Am Acad Dermatol. 9.2015;73(6):1025-1030.HoEL,LukehartSA.Syphilis: using modern approaches to understand an old disease. J Clin Invest. 2011;121(12):4584-4592.
■ Sarah K. Friske, BBA, is a medical student at Baylor College of Medicine in Houston,Texas;Tara L. Braun, MD, is a resident physician at Baylor College of Medicine.
The histopathologic features of secondary syphilis demonstrate extensive variability. The epidermis may be normal, psoriasiform, ulcerated, or necrotic. Dilated blood vessels and vascular proliferation may also be present.4,7,8
References
1. Lafond RE, Lukehart SA. Biological basis for syphilis. Clin Microbiol Rev. 2.2006;19(1):29-49.GohBT.Syphilis in adults. Sex Transm Infect. 2005;81(6):448-452.
4. Stary G, Stary A. Sexually transmitted infections. In: Bolognia J, ed. Dermatology. Elsevier Limited; 2018:1447-1469.
3. Tampa M, Sarbu I, Matei C, Benea V, Georgescu SR. Brief history of syphilis. J Med Life. 2014;7(1):4-10.
In secondary syphilis, a generalized rash, generalized lymphadenopathy, and condylomata lata are common clinical findings. Systemic symptoms include sore throat, muscle aches, malaise, low-grade fever, and weight loss. The rash of secondary syphilis consists of scaly, nonpruritic, macules or papules that vary from pink to violaceous to red-brown in color. The exanthema is distributed on the trunk and extremities with the palms and soles involved in 40% to 80% of cases.2,4,5 Less common presentations of secondary syphilis include patchy alopecia, split papules at the oral commissure, granulomatous nodules and plaques, uveitis, retinitis, and hepatosplenomegaly.2,4
Dermatology Clinic 24 THE CLINICAL ADVISOR • JULY/AUGUST 2023 • www.ClinicalAdvisor.com
7. Carlson JA, Dabiri G, Cribier B, Sell S. The immunopathobiology of syphilis: the manifestations and course of syphilis are determined by the level of delayed-type hypersensitivity. Am J Dermatopathol. 2011;33(5):433-460.
5. Forrestel AK, Kovarik CL, Katz KA. Sexually acquired syphilis: laboratory diagnosis, management, and prevention. J Am Acad Dermatol. 2020;82(1):17-28.
sites such as the lip or fingers. The primary chancre may not be recognized by the patient.2,4 Heterosexual men experience syphilis most commonly on the penis, homosexual men are more likely to experience syphilis on the rectum and anal canal, and women develop syphilis typically on the labia or cervix.1
6. Rowe CR, Newberry SM, Jnah AJ. Congenital syphilis: a discussion of epidemiology, diagnosis, management, and nurses’ role in early identification and treatment. Adv Neonatal Care. 2018;18(6):438-445.
Treatment guidelines recommend penicillin as the drug of choice for syphilis.1,2 For early syphilis, an intramuscular (IM) dose of benzathine penicillin 2.4 million units is recommened.2,4 An alternative treatment for individuals allergic to penicillin includes oral doxycycline, tetracycline, ceftriaxone, or azithromycin.2 However, a rise in the prevalence of macrolide-resistant T pallidum has occurred as a result of increased usage of azithromycin.1,9 Patients with early syphilis who are pregnant require 2 doses of weekly IM benzathine penicillin 2.4 million units. Patients with concurrent HIV infections are at higher risk for neurologic involvement and treatment failure. There is no evidence for alteration of treatment regimens to prevent these outcomes.2,4 The patient in this case had a positive rapid plasma reagin for syphilis; a punch biopsy of her rash further confirmed a diagnosis of secondary syphilis. She was treated with 1 dose of intramuscular benzathine penicillin 2.4 million units.
Lower Leg Ulcers
A 72-year-old man presents to the dermatology clinic with a 6-month history of swelling of the lower extremities with associated painful ulcers. The ulcers are currently being managed with gentle wound care by another health care provider. His medical history includes obesity, diabetes mellitus, and hypertension. The patient reports drinking approximately 1 alcoholic drink per month and does not smoke. On physical examination, the clinician notes bilateral pitting edema of the lower extremities and ulcerations on the lateral ankle and foot with yellow exudate and red granulation tissue at the base.
Look-Alikes CASE #2CASE #1 www.ClinicalAdvisor.com • THE CLINICAL ADVISOR • JULY/AUGUST 2022 25
Dermatologic
BRIANA FERNANDEZ; SIDRA DEEN; CARLY DUNN, MD; TARA L. BRAUN, MD
A 63-year-old man presents to the dermatology clinic with a 3-month history of a nonhealing ulcer on his right lower leg.The patient notes that the ulcer has been getting bigger and is painful (including when touched by socks or pants). He has no other similar lesions on his body. He has a history of diabetes mellitus, hyperlipidemia, and 30 years of smoking. On physical examination, a hyperpigmented scaly patch is found above the right lateral malleolus with several small areas of shallow ulceration.The area is tender to palpation. His lower legs have no hair and his feet are cool to the touch.
An ankle-brachial index (ABI) measurement is one of the most common methods for confirming PAD, with a value below 0.9 signifying PAD and values below 0.5 indicating advanced arterial damage that may be unlikely to heal. 1
Arterial Ulcers
Arterial ulcers comprise a quarter of leg ulcers and are most commonly caused by atherosclerosis and thrombosis.1 Atherosclerosis results in lower extremity peripheral arterial occlusive disease (PAOD), a subset of peripheral arterial disease (PAD), which occurs in 30% to 40% of patients older than 60 years.2 Advanced PAOD can lead to the formation of arterial ulcers and may be asymptomatic before the loss of tissue, making the condition difficult to detect.2 Other forms of ischemia and impaired arterial flow such as thrombosis or trauma also can produce arterial ulcers.3 Occlusion of arterial blood can occur in capillaries, arterioles, and large arteries.3 Risk factors for PAD and arterial ulcers include hyperviscosity, hypercoagulability, cerebrovascular disease, coronary artery disease, hyperlipidemia or dyslipidemia, hyperhomocysteinemia, diabetes mellitus, smoking, renal failure or insufficiency, hypertension, associated vasculitis, family history of arterial disease, sedentary lifestyle, and advanced age.1-3 Smoking is one of the most important factors in the progression of peripheral atherosclerosis to arterial ulcer.2 Increased number of pack years are associated with an increased risk for vascular graft occlusions, amputations, and mortality. Diabetes mellitus is another major contributing factor that can triple or quadruple the risk for PAOD. Reduced psychosocial status as seen in patients with alcohol abuse, malnutrition, poor hygiene, and mental illness is an additional risk factor.2
A review of systems of patients with PAOD may reveal leg pain on exertion, fatigue or numbness in the legs when walking, decreased walking, and numbness and/or nighttime pain in the feet.2 Symptoms of intermittent claudication may go unnoticed if the patient does not have an active lifestyle.1
Signs of PAOD include cool, shiny, dry, or dark purple skin; dry or wet soft crusty tissue; mummified or blackened toes; thickened toenails; and hair loss which commonly occurs around the leg and/or ankle.2 If untreated, these sites could develop arterial ulcers.2
Arterial ulcers are commonly found on the distal leg, especially around the lateral malleoli, pretibial and lateral leg, toes, dorsum of the feet, and bony protuberances.1,3 These lesions vary in depth and are typically painful even if they are not large. Ischemic arterial ulcers are small and round and often have smooth, demarcated borders with a “punched-out” appearance. The base of the ulcer is usually pale but may present with wet or dry gangrene. No granulation tissue and typically no or minimal exudate are found. Local hair loss, atrophy, slow capillary refill, decreased or absent peripheral pulses, decreased temperature, and pallor may be seen around the ulcer.1,3 Ischemia of the affected leg can be noted by induced pallor when the limb is raised to greater than 30 degrees.3 Pain increases when the leg is raised and mild improvement may be observed when the leg is lowered into a dependent position.1
Dermatologic
Diseases that mimic arterial ulcers include hypertensive ulcers, eosinophilic vasculitis, pyoderma gangrenosum, calciphylaxis, spider bites, scleroderma, venous ulcers, and trauma.3
Arterial ulcers can be improved through surgery to revascularize the leg and restore blood flow and/or skin grafts to cover the ulceration.4,7 If bone or tendon becomes exposed, Treatments for arterial ulcers include pain control, debridement, occlusive dressings, and ways to increase circulation.
Look-Alikes
CASE #1 26 THE CLINICAL ADVISOR • JULY/AUGUST 2022 • www.ClinicalAdvisor.com
The primary treatments for arterial ulcers include pain control, conservative debridement, occlusive dressings, and measures to increase circulation.3 Compression and aggressive debridement could lead to further necrosis and should be avoided.1,3 Evidence suggests that spinal cord stimulation may reduce pain.4 To care for an ulcer bed, it is important to assess and treat the etiology and contributing factors, such as hypertension, diabetes, nutrition, smoking, and use of immunosuppressive drugs.3-4 If an ulcer becomes moist, it should be treated with foam dressings, alginates, hydrocolloids, and negative wound pressure therapy to prevent infections.4 Ulcers that are new or accompanied by increased odor, erythema, edema, exudate, temperature, or size may signify an infection and systemic antibiotics should be given if a combination of any 3 of the prior signs is noted.1
Arterial calcification can manifest as an ABI greater than 1.2.1 Doppler waveform changes and toe-brachial-pressure-index can also help confirm PAD diagnosis.4,5 Histopathologic examination of arterial ulcers most commonly shows epidermal thinning, progressive necrosis of the epidermis, dermal sclerosis, and thrombi in dermal blood vessels; but this evaluation is not necessary for diagnosis.6
The patient in this case was diagnosed clinically with arterial ulcer and referred to vascular surgery for additional management.
Clinically, venous ulcers typically affect the gaiter area of the legs, defined as the area between the mid-calf and ankle.13 The most common location is the medial malleolus.16 The wound normally appears as a shallow, well-defined ulcer with an irregular shape and a base of fibrin and granulation tissue.13,14 It is associated with moderate to heavy exudate, leg hyperpigmentation, edema, dull pain, and lipodermatosclerosis.14,16
When a biopsy is performed, tissue should be obtained from both the wound edge and the ulcer base. Histology of the epidermis shows spongiosis, marked epidermal hyperplasia, and abrupt transition from normal epidermis to ulceration (termed “step sign”).6 Dermal changes include the presence of diffuse edema, granulation tissue, collagen-bundle degeneration, fibrin, and hemosiderin-laden macrophages.6
frequently in women compared with men with an average age of onset between 70 and 79 years.9 In normal conditions, contraction of lower extremity muscles and working intraluminal valves promote the forward flow of blood within veins. In venous insufficiency, reflux and/or obstruction in the superficial, perforator, or deep veins of the legs occurs, which leads to poor venous return to the heart. This increase in blood in the venous system results in venous hypertension, which if chronic can manifest as edema, pain, varicose veins, stasis dermatitis, ulcerations, and other cutaneous changes.12,13 At the cellular level, mast cells, leukocytes, matrix metalloproteinase inhibitors, prostacyclins, and myofibroblasts create a proinflammatory microenvironment with eventual remodeling of vessel walls.13 Chronic inflammation combined with blood pooling in the lower limbs favors thrombus formation, fibrosis, and destruction of intraluminal valves.When all of these factors are present they impair proper healing and result in ulcer formation within chronic wounds.
The following are risk factors for venous insufficiency and the subsequent development of venous ulcers: advanced age, female sex, obesity, immobility, congenitally absent or incompetent valves, and history of either deep vein thrombosis or phlebitis.10,14
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Risk factors for venous ulcers include advanced age, obesity, immobility, and history of deep vein thrombosis.
Approximately 60% to 80% of all lower extremity ulcers are caused by venous insufficiency.9,10 These ulcers can last for several years, especially with inadequate treatment, and have a high rate of recurrence. Chronic venous ulcers have been linked to pain, disability, depression, social isolation, and decreased quality of life.11 Venous ulcers also have significant financial implications as they account for approximately 2% to 3% of total health care expenditure in developed countries.11
It is estimated that between 1.5 and 3.0 in 1000 people have active leg ulcers.12 Although the prevalence and incidence of lower extremity ulcers with venous causes continue to be contested, 1 study found that the incidence of venous ulcers ranged from 0.5 to 1.0 cases per 1000 people between 2010 and 2014.9 The incidence of venous ulcers increases with age to approximately 20 in 1000 people older than 80 years.12 With baby boomers reaching older age, an estimated 10% of the population is expected to develop a chronic wound and 1% of the population will develop a venous leg ulcer at least once in their lifetime.9 Venous ulcers occur 3 times more CASE #2 Venous Ulcers free or pedicled flaps should be considered.7 Extensive arterial ulcers can be revascularized with a 1-stage multiple arterial reconstruction with an omental free flap if standard free flaps cannot be used.7 If the wound cannot be revascularized, the limb may need to be amputated or treated with prostaglandin E1 derivatives.1,4 Transcutaneous oxygen pressure (TcPO2) measurement can help identify the severity of ischemia and the appropriate level of amputation if necessary.1 In patients with end-stage renal disease or heel gangrene, amputation may be considered before surgical revascularization or skin flaps because of surgical risks and the decreased likelihood of successful perfusion.4 Hyperbaric oxygen therapy should be considered as adjuvant therapy in hypoxic ulcers responsive to oxygen if revascularization is unsuccessful, especially in patients with diabetes.1,4 Findings from a case study by Carbinatto et al showed promise for a triple-therapy approach of low-level laser therapy, photodynamic therapy, and cellulose membranes.8
A cross-sectional study that enrolled 854 men and 1580 women found that age, family history of venous disease, and ligamentous laxity were the strongest risk factors for venous disease.15 In addition, prior lower limb injury in women and smoking in men were found to be correlated with severe disease.15
28 THE CLINICAL ADVISOR • JULY/AUGUST 2022 • www.ClinicalAdvisor.com Dermatologic Look-Alikes TABLE. Arterial Ulcers vs Venous Ulcers Arterial Ulcers1-8 Venous Ulcers6,9-16 Dermatologic presentation • Small and round with smooth, demarcated borders and a “punched-out” appearance • Base of the ulcer is usually pale, may be gangrenous • No granulation tissue and typically no or minimal exudate are found • May have local hair loss, atrophy, slow capillary refill, decreased or absent peripheral pulses, decreased temperature, and pallor • Shallow, exudative, well-defined ulcer with an irregular shape and a base of fibrin and granulation tissue • Associated with lipodermatosclerosis, skin hyperpigmentation, and edema Characteristic location • Distal leg, especially around the lateral malleoli • Pretibial and lateral leg • Dorsum of feet, toes, and bony protuberances • Gaiter area • Medial > lateral malleolus Epidemiology • ~25% of leg ulcers • Advanced POAD, which can lead to formation of arterial ulcers, occurs in 30%-40% of patients older than 60 years • 0.5%-1.0% of the population • 3 times more common in women compared with men Potential risk factors • Advanced age >60 years • Associated vasculitis • Cerebrovascular disease • Coronary artery disease • Diabetes mellitus • Family history of arterial disease • Hypercoagulability • Hyperlipidemia or dyslipidemia • Hyperhomocysteinemia • Hypertension • Hyperviscosity • Renal failure or insufficiency • Sedentary lifestyle • Smoking • Advanced age >65 years • Congenitally absent or incompetent valves • Family history of venous disease • Female sex • History of either deep vein thrombosis or phlebitis • Obesity Etiology • Atherosclerosis • Other forms of ischemia and impaired arterial flow, such as thrombosis or trauma • Venous hypertension Histology • Epidermis: thinning and progressive necrosis • Dermis: sclerosis and thrombi in blood vessels • Epidermis: spongiosis, marked epidermal hyperplasia, and “step sign” • Dermis: diffuse edema, granulation tissue, collagen-bundle degeneration, fibrin, and hemosiderin-laden macrophages Diagnosis • History and physical examination • Arterial-brachial pressure index, toe-brachial pressure index, Doppler waveform changes • History and physical examination • Venous duplex ultrasonography and arterial-brachial pressure index may provide additional assistance Treatment • Conservative debridement • Occlusive dressings • Pain control • Revascularization • Treat etiology and underlying contributing factors • Antibiotics, if needed • Compression therapy • Debridement • Dressing • Pentoxifylline PAOD, peripheral arterial occlusive disease
2. Hopf HW, Ueno C, Aslam R, et al. Guidelines for the prevention of lower extremity arterial ulcers. Wound Repair Regen. 2008;16(2):175-188.
Treatment of venous ulcers consists of compression therapy and direct wound management.13,14 Compression therapy is the standard of care for initial and long-term management of venous ulcers in patients without concomitant arterial disease. Leg elevation and exercise may also be beneficial in increasing venous flow and decreasing edema. Direct wound management consists of debridement, dressings, and medications. Treatment with pentoxifylline, a hemorrheologic agent that improves microcirculation and oxygenation, has been found to improve healing with or without compression therapy.13,14 Antibiotics are indicated when there is evidence of a superimposed infection. When suspected, tissue cultures are needed to guide antimicrobial therapy. Despite adequate treatment, only 20% of venous ulcers heal in less than 3 months.9
Venous ulcers are diagnosed clinically, but noninvasive venous imaging with duplex ultrasonography demonstrating reflux and/or obstruction in the veins can confirm the diagnosis.9,14 Arterial pulse examination and ABI can also help differentiate venous ulcers from other diagnoses. Further evaluation with biopsy is warranted if the ulcer is not responsive to treatment or if there is suspicion of an alternate diagnosis.
The patient in this case was diagnosed with venous ulcer confirmed via biopsy of the edge of the ulcer. He is being managed with wound care and compression therapy. ■ Briana Fernandez and Sidra Deen are medical students at Baylor College of Medicine in Houston,Texas; Carly Dunn, MD, and Tara L. Braun, MD, are resident physicians at Baylor College of Medicine.
10. Probst S, Weller CD, Bobbink P, et al. Prevalence and incidence of venous leg ulcers — a protocol for a systematic review. Syst Rev. 2021;10(1):148.
15. Criqui MH, Denenberg JO, Bergan J, Langer RD, Fronek A. Risk factors for chronic venous disease: the San Diego Population Study. J Vasc Surg. 16.2007;46(2):331-337.AbbadeLP,Lastória S, Rollo Hde A. Venous ulcer: clinical characteristics and risk factors. Int J Dermatol. 2011;50(4):405-411. Sign up for our daily Clinical Advisor newsletter to get more features, cases, meeting coverage, and news. Want More? To sign up, go to registrationClinicalAdvisor.com/
7. Horch RE, Horbach T, Lang W. The nutrient omentum free flap: revascularization with vein bypasses and greater omentum flap in severe arterial ulcers. J Vasc Surg. 2007;45(4):837-840.
3. Hess CT. Arterial ulcer checklist. Adv Skin Wound Care. 2010;23(9):432.
5. Kavros SJ, Coronado R. Diagnostic and therapeutic ultrasound on venous and arterial ulcers: a focused review. Adv Skin Wound Care. 2018;31(2):55-65.
1. Abbade LPF, Frade MAC, Pegas JRP, et al. Consensus on the diagnosis and management of chronic leg ulcers - Brazilian Society of Dermatology. An Bras Dermatol. 2020;95 Suppl 1(Suppl 1):1-18.
9. Berenguer Pérez M, López-Casanova P, Sarabia Lavín R, González de la Torre H, Verdú-Soriano J. Epidemiology of venous leg ulcers in primary health care: Incidence and prevalence in a health centre — a time series study (2010-2014). Int Wound J. 2019;16(1):256-265.
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8. Carbinatto FM, de Aquino AE Jr, Coelho VHM, Bagnato VS. Photonic technology for the treatments of venous and arterial ulcers: case report. Photodiagnosis Photodyn Ther. 2018;22:39-41.
Although venous ulcers are the most common type of lower extremity ulceration, the differential diagnosis should include arterial ulcer, neuropathic ulcer, pressure ulcer, pyoderma gangrenosum, and malignancy.14 Arterial ulcers are typically caused by atherosclerosis and can be differentiated from venous ulcers with the ABI. Neuropathic ulcers are often a result of diabetes mellitus and are associated with peripheral neuropathy and foot deformities. Pressure ulcers are seen in dependent areas in patients with limited mobility. Pyoderma gangrenosum and malignancy should be suspected when the ulcer is not responding to standard treatment.14
11. Finlayson K, Wu ML, Edwards HE. Identifying risk factors and protective factors for venous leg ulcer recurrence using a theoretical approach: a longitudinal study. Int J Nurs Stud. 2015;52(6):1042-1051.
12. Nelson EA, Adderley U. Venous leg ulcers. BMJ Clin Evid. 2016;2016:1902.
References
In: StatPearls. StatPearls Publishing; 2022 Apr 14. 14. Bonkemeyer Millan S, Gan R, Townsend PE. Venous ulcers: diagnosis and treatment. Am Fam Physician. 2019;100(5):298-305.
13. Robles-Tenorio A, Lev-Tov H, Ocampo-Candiani J. Venous leg ulcer.
4. Federman DG, Ladiiznski B, Dardik A, et al. Wound Healing Society 2014 update on guidelines for arterial ulcers. Wound Repair Regen. 2016;24(1):127-135.
6. Misciali C, Dika E, Baraldi C, et al. Vascular leg ulcers: histopathologic study of 293 patients. Am J Dermatopathol. 2014;36(12):977-983.
“Do not be afraid to be yourself, but do so respectfully,” read the policy. “This includes the obvious (no ethnic slurs, personal insults, obscenity, etc.) but also proper consideration of privacy and of topics that may be considered objectionable or inflammatory — such as politics and religion…” Ms M had a personal Facebook account. Her profile prominently stated her current job title at the medical center and also listed her former position as a nurse. In late May 2020, the death of George Floyd, a Black man who was killed by a police officer while being taken into custody, spurred national public demonstrations, calls for police reform, public mourning, and a focus on the Black Lives Matter movement. In the midst of this, Ms M participated in a Facebook discussion about the Black Lives Matter movement. Among the things she wrote in her The
CASE LEGAL ADVISORCasespresentedarebasedonactualoccurrences.Namesofparticipantsanddetailshavebeenchanged.Casesareinformationalonly;nospecificlegaladviceisintended.Personspicturedarenottheactualindividualsmentionedinthearticle. IMAGESGETTY/PRODUCTIONSSDI©
at-willterminatingemployerprivatepreventsAmendmentthedecidecourtappellatehadtowhetherFirstafromanemployee.
BY ANN W. LATNER, JD Ms M began working as a nurse at a medical center in 2005 as an at-will employee. During the course of her career, she was promoted several times and eventually assumed the position of corporate director of customer service. Ms M’s employer had a written social media policy that covered its employees’ professional and personal social media platforms. The policy explained that employees were personally responsible for the content they posted on social media and that it reflected on the employer. “Employee use of social media activities, inside or outside the workplace, has the potential to affect employee job performance, the performance of others, [the medical center’s] brand and/or reputation and the [medical center’s] business interests,” noted the policy. The policy advised employees to be aware of their association with their employer, and if they publicly identify as being employed by the medical center, they should ensure their profile and related content is consistent with how they wish to present themselves to colleagues and clients.
The policy went on to note that the center’s physicians, staff, patients, and vendors reflect a diverse set of customs, values, and points of view.
Can an employer fire a worker for posting racially insensitive comments on social media accounts? When Is Speech Free? 30 THE CLINICAL ADVISOR • JULY/AUGUST 2022 • www.ClinicalAdvisor.com
Legal Background
In her appeal, Ms M argued that her right to speak her mind outweighed her employer’s right to promote an inclusive, nondivisive environment for its patients and employees.
One exception is that at-will employees cannot be disciplined or fired under circumstances that violate public policy. So, for example, a nurse who raised a red flag about patient health and safety could not be fired for doing so because that would be a violation of public policy. In Ms M’s case, however, the court held that voicing personal political opinions that have no particular value in furthering a public purpose do not qualify for the public policy exception.
The appeals court disagreed, stating that Ms M’s interest in publicly posting her remarks was minimal. The court wrote in its decision that the judges had balanced Ms M’s “slight interest in publicly making her position on the Black Lives Matter movement known” against her employer’s “strong interest in protecting and fostering the diverse set of customs, values, and points of view of its physicians, staff, volunteers, and patients.” Under the circumstances of the case, the employer did not violate the clear mandate of public policy when it terminated Ms M, the court held. Protecting Yourself You may think that your social media account is private, but it is not. Increasingly, human resources professionals are looking at the social media accounts of candidates and rejecting those who post things that are outside of the culture of the company. If your employer has a social media policy, familiarize yourself with it. Consider not including your employment information in your social media profile at all if you think you may be posting something contrary to the values of your employer.
LEGAL ADVISOR post was that she found the phrase “Black Lives Matter” to be racist. “Yes, I find it racist,” she posted. “Yes, it bothers me. ‘Black lives matter’ causes segregation. Have you ever heard of ‘white lives’ matter or ‘Jewish lives’ matter? No. Equal opportunity.” Another commenter wrote that “Black Lives Matter is bringing attention to the plight of Black folks in America. That they’re dying.” Ms M’s response was, “they are not dying… they are killing themselves.”
An administrator at the medical center discovered Ms M’s Facebook posts and a vice president called Ms M to discuss the remarks. During the discussion, Ms M acknowledged the posts and discussed some of the content.The VP told her that “it was bad,” and she was suspended that same day, pending an investigation. Five days later, senior administration met with Ms M. After she revealed that she was recording the conversation, the meeting ended and she was fired. She was told her firing was because of repeated instances of poor management judgment — a failure to uphold the medical center’s values.”
Ann W. Latner, JD, a former criminal defense attorney, is a freelance medical writer in Port Washington, New York.
■
The appeals court agreed and affirmed the trial court’s holding that the First Amendment does not apply in this case. The appeals court then noted that as an at-will employee, Ms M’s employment could be terminated at any time, for any reason or no reason at all. “Without a union collective bargaining agreement or an employment contract, Ms M could be fired at will.
Ms M’s Facebook profile prominently stated her current job title and listed her former position as a nurse.
Keep in mind that unless you are working for a government employer or agency, there is no protection of free speech; as noted in this case, private employers do not have that obligation unless you qualify for the public policy exception. If you are not part of a union or covered under an employment contract, note that as an at-will employee you can be terminated at any time for any or no reason.
Later Ms M wrote that she supported “all” lives and that as a nurse they all matter and she did not discriminate, but she added that she did not “condone the rioting that had occurred in response to this specific Black man’s death.”
32 THE CLINICAL ADVISOR • JULY/AUGUST 2022 • www.ClinicalAdvisor.com
The trial court dismissed Ms M’s case because there is no cause of action for free speech against a private employer. The protection of free speech only applies to restrictions imposed by governmental officials or agencies. So, if Ms M were working for a state hospital, her constitutional right would be protected and she would have a valid argument if she were fired for her speech. An employee of a private company, however, has no such protection, regardless of how large the employer is.
Ms M hired an attorney who filed a 1-count complaint against her former employer, alleging that her termination was punishment for exercising her rights protected by the free speech amendment. Her employer filed a motion to dismiss the case, which was granted by the trial court.