Rio Bravo qWeek

Episode 121: Genital Herpes.     
Wendy and Grace discuss the signs, symptoms, diagnosis, and management of genital herpes. 

Written by Jaspreet Johal, MS4, Ross University School of Medicine. Edits by Grace Yi, MS2, University of California Los Angeles; and Wendy Collins, MS3, Ross University School of Medicine. Comments by Hector Arreaza, MD.  December 1, 2022.

You are listening to Rio Bravo qWeek Podcast, your weekly dose of knowledge brought to you by the Rio Bravo Family Medicine Residency Program from Bakersfield, California, a UCLA-affiliated program sponsored by Clinica Sierra Vista, Let Us Be Your Healthcare Home. This podcast was created for educational purposes only. Visit your primary care provider for additional medical advice.

Definition & Epidemiology

Genital herpes is a common sexually transmitted infection caused by a virus called herpes simplex virus (HSV for short). There are two types of HSV. HSV type 1 commonly causes orolabial herpes (known as cold sores), and HSV type 2 typically causes genital herpes, which can present as painful blisters or ulcers in the genital regions. 

In recent years, an increasing number of genital herpes cases have been associated with HSV-1, especially in women. 

HSV infections are widespread among the global population and spread person to person through oral-to-oral contact or vaginal, anal, and oral sexual contact. Transmission can occur during periods of subclinical viral shedding, as in even when individuals are asymptomatic. In 2020, the seroprevalence of HSV-2 in the United States was approximately 13 percent among patients aged 15 to 49, with more women affected than men. Fifty to 80 percent of American adults have oral herpes (HSV-1), which causes cold sores or fever blisters in or around the mouth. 

HSV is a lifelong infection characterized by periodic reactivations that can be triggered by fatigue, stress, or illness, among other factors. Antiviral therapy can shorten symptom duration in primary infection and can also treat and prevent recurrences. 

Types of Infection

Genital HSV infection can be classified into three types: primary, nonprimary, and recurrent. 

• Primary – Primary infection refers to an infection in a patient without preexisting antibodies to either HSV-1 or HSV-2.
• Nonprimary infection, a patient has a first occurrence of a genital HSV lesion but already has pre-existing HSV antibodies that are different from the HSV type related to the genital lesion.
• Recurrent – Recurrent infection refers to the reactivation of genital HSV (so the patient already has pre-existing antibodies in the serum)

Clinical Features 

The incubation period for developing genital herpes after exposure ranges anywhere from 2 to 12 days.

Most patients with primary HSV infection are asymptomatic or mildly symptomatic. However, in more severe cases, individuals can present with painful genital ulcers, dysuria, fever, tender local inguinal lymphadenopathy, and headache. HSV infection also presents with characteristic 2-4mm wide skin lesions that are vesicular or ulcerated. The vesicles are often clustered and can be fluid-filled with underlying erythema. Sometimes vesicles might have a depression in the center (called “umbilicated” vesicles.” 

It’s important to note, though, that the clinical presentation can vary based on the type of infection (primary, nonprimary, or recurrent). As a general rule of thumb, the initial presentation of a non-primary genital infection tends to be milder (as in, fewer systemic symptoms and lesions) than that of a primary infection. Recurrent infections also tend to be less severe than primary or nonprimary infections. Also, around 50% of patients with symptomatic recurrent infections might experience prodromal symptoms in recurrent infections, like burning, pain, or pruritus, before lesions become visible.

Symptoms in patients with primary infections typically resolve after an average of 19 days, whereas symptoms in nonprimary or recurrent infections resolve within 10 days. Also, there are no clear differences in a clinical presentation based on whether the virus is caused by HSV-1 or HSV-2. However, infections due to HSV-2 are associated with a higher recurrence rate than infections due to HSV-1. 

Extragenital complications 

Genital HSV infection can cause extragenital manifestations that typically occur during the primary episode of HSV infection but can reappear with subsequent episodes. Complications include aseptic meningitis, urinary bladder retention, proctitis, and lumbosacral radiculitis. Other areas that can be affected outside of the genital area are fingers, eyes, and other skin areas.

Diagnosis.

A clinical diagnosis of genital herpes is usually initiated by the finding of vesicular or ulcerated genital lesions. The diagnosis can be confirmed with lab testing like viral culture, polymerase chain reaction (PCR), direct fluorescence antibody, and type-specific serologic testing. The most appropriate test for a patient depends on their clinical presentation. 

We might opt for PCR-based testing and cell culture if a patient has active lesions. Viral culture has typically been the gold standard method to isolate HSV, but HSV PCR assays are becoming increasingly popular as they have the best overall sensitivity and specificity. Cell cultures are most accurate in the early stages of the disease and have greater diagnostic yield with primary as opposed to recurrent genital herpes. 

Another method, type-specific serologic testing, tells us if a patient has type-specific antibodies to HSV, which develop in the first few weeks after infection and persist indefinitely. We might opt for this method if a patient has a history of genital lesions without a diagnostic workup or if the patient has an atypical presentation, in which case we may get type-specific serologic testing in addition to PCR. 

Management. 

All individuals experiencing a first episode of genital HSV should be treated with antiviral therapy, ideally as soon as a lesion appears. Most cases of genital HSV can be treated with oral drug therapy for 7 to 10 days, and as of 2021, the CDC recommends 3 different options for treatment: acyclovir, famciclovir, and valacyclovir. These drugs have been shown to decrease the duration of lesion healing time, duration of pain, and duration of viral shedding. For example, if the disease is disseminated or ocular, we may use IV acyclovir in complicated infections. 

It is important to note that treating the initial episode does not eliminate the latent virus. Patients are still at risk for recurrence and may require additional antiviral therapy. 

For recurrent infections, treatment options include episodic therapy and chronic suppressive therapy. 

Episodic therapy – involves patients starting therapy at the very first sign of prodromal symptoms (tingling, paresthesia, pruritus). Patients with infrequent recurrences or mild symptoms might opt for episodic therapy. 

• Wendy: Chronic suppressive therapy – involves daily antiviral therapy to decrease the risk of reactivation and recurrences. Suppressive therapy is helpful in patients with frequent recurrences or severe symptoms or at high risk for severe infections, such as those with HIV.

Screening

According to the US Preventive Services Task Force (USPSTF), routine screening for HSV-1 or HSV-2 is not recommended in asymptomatic adolescents and adults. The lack of specific treatment interventions for asymptomatic individuals, and the significant limitations of serologic testing, including low specificity and high false-positive rate, outweigh the potential benefits of screening. 

Prevention. 

Measures to prevent genital HSV infections include the use of barrier protection, patient education, and chronic suppressive therapy. 

• Barrier protection – The use of condoms is one of the best ways to prevent the spread of genital HSV infection and other sexually transmitted diseases. It reduces the risk of transmission while patients are asymptomatic but are in the viral shedding stage. Patients with active lesions or prodromal symptoms should abstain from sexual activity completely while having an active episode. 
• Patient Education – Counseling patients along with their sex partner(s) about safe sexual practices can decrease the incidence of HSV in our community and prevent the further spread of the disease. 
• Chronic suppressive therapy – can reduce recurrences and viral transmission.

Conclusion: Genital herpes is a sexually transmitted, worldwide infection that can be asymptomatic but often presents with painful vesicles that progress to ulcers in the genital area. Even though the course can be shortened, and the symptoms can be improved with medications, it is frequently recurrent. So, prevention is key to avoiding complications.

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Now we conclude episode number 121, “Genital herpes.” You listened to Grace and Wendy discuss the basics of genital herpes. They explained that episodic treatment of genital herpes with antivirals helps reduce the severity and duration of symptoms, while suppressive therapy prevents recurrences and transmission. Dr. Arreaza reminded us that screening asymptomatic adults and adolescents is not recommended by the USPSTF. HSV serology has a low sensitivity and specificity. PCR and viral culture are better diagnostic tools in most cases. And, as with all other STIs, promoting safe sex practices is key to the prevention of genital herpes.

We thank Hector Arreaza, Grace Yi, Wendy Collins, and Jaspreet Johal this week. Audio edition by Adrianne Silva.

Even without trying, you go to bed a little wiser every night. Thanks for listening to Rio Bravo qWeek Podcast. We want to hear from you. Send us an email at [email protected], or visit our website riobravofmrp.org/qweek. See you next week! 

_____________________

Links:

1. Albrecht, Mary A. Epidemiology, clinical manifestations, and diagnosis of genital herpes simplex virus infection, Up to Date, last updated: Dec 22, 2020. https://www.uptodate.com/contents/epidemiology-clinical-manifestations-and-diagnosis-of-genital-herpes-simplex-virus-infection.
2. Albrecht, Mary A. Treatment of genital herpes simplex infection, Up to Date, last updated: Jun 28, 2021. https://www.uptodate.com/contents/treatment-of-genital-herpes-simplex-virus-infection
3. James C, Harfouche M, Welton NJ, Turner KM, Abu-Raddad LJ, Gottlieb SL, Looker KJ. Herpes simplex virus: global infection prevalence and incidence estimates, 2016. Bull World Health Organ. 2020 May 1;98(5):315-329. doi: 10.2471/BLT.19.237149. Epub 2020 Mar 25. PMID: 32514197; PMCID: PMC7265941. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7265941/
4. Royalty-free music used for this episode: “Keeping Watch,” New Age Landscapes. Downloaded on October 13, 2022, from https://www.videvo.net/royalty-free-music-albums/new-age-landscapes/.

Even without trying, every night you go to bed a little wiser. Thanks for listening to Rio Bravo qWeek Podcast. We want to hear from you, send us an email at [email protected], or visit our website riobravofmrp.org/qweek. See you next week!

Episode 120: Immune Reconstitution Inflammatory Syndrome (IRIS) 

Abeda Faharti and Dr. Schlaerth present the definition, diagnosis, and treatment of IRIS. Moderated by Dr. Arreaza. 

Written by Abeda Farhati, MS4, Ross University School of Medicine. Editing and comments by Katherine Schlaerth, MD, and Hector Arreaza, MD.

You are listening to Rio Bravo qWeek Podcast, your weekly dose of knowledge brought to you by the Rio Bravo Family Medicine Residency Program from Bakersfield, California, a UCLA-affiliated program sponsored by Clinica Sierra Vista, Let Us Be Your Healthcare Home. This podcast was created for educational purposes only. Visit your primary care provider for additional medical advice.

Definition.

Have you heard of IRIS? No, not the color portion of our eyes. IRIS is short for Immune Reconstitution Inflammatory Syndrome. This condition occurs in immunocompromised patients with HIV/AIDS due to an overactive inflammatory response. In most cases, it occurs after initiating antiretroviral therapy (ART). To understand IRIS in HIV patients, we must first understand HIV.

HIV.
The Human Immunodeficiency Virus (HIV) infection was first reported in 1981. The virus attacks the immune system, destroying white blood cells called CD4+ T lymphocytes, which are part of our body's defense mechanism. These cells are also known as "helper T cells" and are responsible for destroying viruses, bacteria, and other germs that make us sick.

When your CD4+ count is low, you are more likely to get serious infections from viruses, bacteria, and fungi, which usually do not cause problems in otherwise healthy individuals. These infections are called Opportunistic infections, and they can be deadly. To restore CD4+ T lymphocytes, HIV patients are started on ART to normalize their immune response to pathogens. As a result of these treatments, HIV patients' lives have been significantly improved and prolonged. 

[Comment by Dr. Arreaza: It is paradoxical, but some HIV patients are among the healthiest patients I have seen.]

Despite this, no treatment is guaranteed to be without side effects. Increases in CD4+ T lymphocytes trigger the immune system to respond to any persisting antigen, regardless of whether it is fragments or intact organisms. As a result, a hyperinflammatory response may occur.

Diagnosis.

There are no established criteria for diagnosing IRIS. It is generally accepted that IRIS requires the worsening of an existing infection or an unrecognized, preexisting infection in the context of improved immune function. 

For a diagnosis to be made, most, if not all of the following features must be present:

1. The presence of a low CD4 count (less than 100 cells) before initiating treatment with ART (Except IRIS secondary to preexisting TB infection can occur with CD4 counts >200 cells).
2. The presence of an inflammatory condition, especially after ART is initiated.
3. The absence of drug-resistant infection, bacterial superinfection, drug allergy, or other adverse drug reactions.
4. The absence of patient noncompliance or reduced drug levels due to drug-drug interactions or malabsorption.

Clinical Manifestations.

IRIS can be presented in patients in 2 ways:

1. Patient’s with a preexisting infectious disease that has NOT been treated, getting paradoxically worse after initiating treatment with ART ---this is known as “unmasking IRIS” OR
2. Patient’s with a preexisting infectious disease that has been previously diagnosed and treated but regained capacity after treatment with ART, causing it to mount an inflammatory response – this is known as “paradoxical IRIS.”

In summary: Unmasking IRIS and paradoxical IRIS.

Patients with IRIS have clinical features that vary widely. The presentations are strongly dependent on the type of preexisting opportunistic infection. For example, about 75% of patients with a mycobacterial or cryptococcal-related infection will develop a fever. In contrast, fever is rarely seen in cytomegalovirus (CMV) infections.

Risk & Prevention.
Researchers have found that lower CD4 cell counts or high HIV RNA levels at the time of anti-retroviral treatment initiation increase the risk of developing IRIS. One way to prevent IRIS development is to treat opportunistic infections prior to starting ART. Although this reduces the risk of IRIS development, it does not guarantee it.

Treatment.

In “unmasking IRIS,” patients can be treated with antibiotics, antivirals, or antifungals against the underlying infectious organism. In severe cases, steroids can also be used to suppress inflammation until the infection has been eradicated. Unfortunately, there is no treatment for paradoxical IRIS. Most patients who experience “paradoxical IRIS” reactions will get better spontaneously without additional therapy.

Incidence of IRIS.

The overall incidence of IRIS is unknown; however, studies have shown that anywhere from 25 to 30% of HIV patients who start antiretroviral treatment develop IRIS in the first six months. You may ask, which preexisting infections can lead to patients developing IRIS?

Pathogens associated with IRIS.

Different pathogens have been associated with the development of IRIS. The leading pathogens include:

• Mycobacterium tuberculosis
• Mycobacterium avium complex
• Cytomegalovirus
• Cryptococcus neoformans
• Pneumocystis jirovecii
• Herpes simplex virus
• Hepatitis B virus
• Human herpes virus 8 (associated with Kaposi sarcoma)

Non-HIV etiologies.

IRIS can also be seen in other immunocompromised conditions, such as:

1. Solid organ transplant recipients 
2. Postpartum period – 3 to 6 weeks after giving birth
3. Neutropenic patients – with an absolute neutrophil count of less than 500
4. Patients on Tumor Necrosis Factor Antagonists (TNF antagonists)- are used to treat chronic conditions such as ulcerative colitis, Crohn’s disease, or sarcoidosis.

In summary, Immune Reconstitution Inflammatory Syndrome (IRIS) is a hyper-inflammatory state seen after initiating ART in HIV patients whose improved immune system responds to previously acquired opportunistic infection, whether treated or not.

The treatment is directed to the unmasked specific opportunistic infection or support therapy if no active infection is found.

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Conclusion: Now we conclude episode number 121, “Immune Reconstitution Inflammatory Syndrome (IRIS).” This syndrome presents in about 30% of HIV patients when they start ART. A stronger immune system means a stronger immune reaction. So, keep in mind this diagnosis when your HIV patients get sicker when they are supposed to get better after starting ART. 

This week we thank Hector Arreaza, Abeda Farhati, and Katherine Schlaerth. Audio edition by Adrianne Silva.

Even without trying, every night you go to bed a little wiser. Thanks for listening to Rio Bravo qWeek Podcast. We want to hear from you, send us an email at [email protected], or visit our website riobravofmrp.org/qweek. See you next week! 

_____________________

Links:

1. “CD4 Lymphocyte Count: MedlinePlus Medical Test.” Medlineplus.gov, accessed on November 4, 2022.https://medlineplus.gov/lab-tests/cd4-lymphocyte-count/#:~:text=A%20CD4%20count%20is%20mostly,have%20trouble%20fighting%20off%20infections.
2. Sun HY, Singh N. Immune reconstitution inflammatory syndrome in non-HIV immunocompromised patients. Curr Opin Infect Dis. 2009 Aug;22(4):394-402. doi: 10.1097/QCO.0b013e32832d7aff. PMID: 19483618. https://pubmed.ncbi.nlm.nih.gov/19483618/
3. Thapa, Sushma, and Utsav Shrestha. “Immune Reconstitution Inflammatory Syndrome.” PubMed, StatPearls Publishing, 2022, www.ncbi.nlm.nih.gov/books/NBK567803/.
4. Wolfe, Cameron. Immune reconstitution inflammatory syndrome, UpToDate. ww.uptodate.com, https://www.uptodate.com/contents/immune-reconstitution-inflammatory-syndrome. Accessed November 14, 2022.
5. Royalty-free music used for this episode: “Keeping Watch,” New Age Landscapes. Downloaded on October 13, 2022, from https://www.videvo.net/royalty-free-music-albums/new-age-landscapes/.

Even without trying, every night you go to bed a little wiser. Thanks for listening to Rio Bravo qWeek Podcast. We want to hear from you, send us an email at [email protected], or visit our website riobravofmrp.org/qweek. See you next week!

Episode 119: Nurse Practitioner Week

Amy Arreaza is a family nurse practitioner who explains what this career is all about. She tells the history and the future of this profession.  

By Amy Arreaza, FNP. Comments by Hector Arreaza, MD.

Hector: When I moved to Utah from my home country, I went to a clinic to investigate why I was so fatigued. I wasn’t a practicing physician at that time. I got seen by a family physician who was very brief and somewhat cold. During my follow-up appointment, I was attended to by a very pleasant lady doctor. She made good eye contact, smiled, and explained the results in a simple and easy way. In summary, my second visit was very enjoyable. Later, I learned that this lady was a nurse practitioner. I had no idea what it meant, but after many positive interactions, I became a fan of nurse practitioners in general. Today, I want you to learn more about this profession, and I invited my favorite nurse practitioner in the whole world, my wife Amy. Welcome, Amy Arreaza.

Tell us who you are.

Amy: First of all, thank you for inviting me to your podcast to talk about this wonderful profession. And second, I must reciprocate in kind, you are my favorite family physician. So, as you said, I am a nurse practitioner, but more specifically, I am a family nurse practitioner, or FNP for short. I’ve been an FNP for 14 years and currently work in central CA in a federally qualified health center as a primary care provider for the medically vulnerable.  Caring for this patient population is where my passion truly lies. 

What is a Nurse Practitioner?

A nurse practitioner is an advanced practice registered nurse. This means they are RNs who have completed either a master's degree or a doctorate degree in nursing practice. With their extra education and training, they have similar job duties as a physician, and there is actually a lot of overlap in the roles of nurse practitioners and physicians. NPs' serve as primary care providers or as specialty care providers. They examine and assess patients’ needs, order and interpret labs and imaging tests, diagnose disease, and provide treatment, which includes prescribing medication. In the United States, the scope of practice of a nurse practitioner is regulated by state law. As of this year, NPs have full practice authority in 26 states, the District of Columbia, and 2 US territories. This means that NPs can work independently in those states without the supervision of a physician. In the remaining states, NPs need to have a collaborative agreement with a physician or work under the supervision of a physician. 

How was this career created?

Well, in the 1960s, Loretta Ford, a public health nurse in Colorado, recognized a deficit in health care in rural communities. She believed nurses could fill the healthcare gaps in rural America, and through the Western Interstate Commission for Higher Education in Nursing, she was given an opportunity to help develop a specialized clinical curriculum for community health nurses.  In 1965, Loretta Ford joined forces with Dr. Henry Silver, a pediatrician, to create the first pediatric nurse practitioner program at the University of Colorado.  So, 57 years ago, the NP profession was created to help alleviate the physician shortage at that time. And today, with a continued shortage of physicians, the NP profession has become essential in meeting primary care needs across the United States. 

Hector: There are 24 states that still do not offer full practice authority to NPs. Those states are more likely to have “geographic health care disparities, higher chronic disease burden, primary care shortages, higher costs of care and lower standings on national health rankings.”

Amy: That’s right, research shows that states with full practice authority for NPs' rank highest in the nation for best access to care, while 9 of the bottom 10 states ranked as the least healthy states in the US have not yet granted NPs full practice authority.

How do you become an NP?

The first step in becoming an NP is to become a registered nurse with either an Associate's Degree or Bachelor's Degree in Nursing Science. You can then enroll in an associate’s-to-master’s degree NP program or a bachelor's to master's  degree NP program.  At the minimum, you must complete a Master of Science in Nursing (or MSN) Degree. However, you may choose to advance your education with a Doctorate of Nursing Practice (or DNP) degree.  After graduation, NPs take a national certification exam to get certification from the specialty board that oversees their practice area. For example, I graduated from the University of Utah family nurse practitioner program and then took the national Family Nurse Practitioner Certification Exam from the American Nurses Credentialing Center. This makes me a board-certified FNP. 

How many kinds of NPs are there?

There are multiple kinds of NPs. I am a family nurse practitioner, meaning I can treat patients from infancy through their golden years to the end of life. Many FNPs work in family practice clinics; however, FNPs have a broad scope of practice which makes them very versatile, and they can work in different specialty care clinics as well. For example, as an FNP, besides working in family practice, I have worked in wound care and in urgent care. FNPs work in cardiology, pulmonology, dermatology, orthopedics, and various other specialty clinics. NP programs are generally patient-population focused, so besides the family nurse practitioner program, there are Adult, Emergency Care, Gerontology, Pediatric, Neonatal, Nurse Anesthetist, Nurse Midwife, Psychiatric, and Women’s Health nurse practitioner programs. 

How can IMG MDs become NPs?

I understand that it can be very difficult for an international medical graduate to be able to practice as an MD in the United States. If an IMG is interested in becoming an NP, I would recommend that they look for a university nursing program that offers an accelerated RN option for those who already hold a bachelor’s degree in another field, then find out if the program will accept their international bachelor’s degree. They will most likely need to validate their international degree before applying to the accelerated RN program. After graduating with a Bachelor of Science in Nursing degree, they could apply to a nurse practitioner program. Another option for IMGs is to look into physician assistant programs. 

Current statistics about NPs': 

In 2020, there are about 210,00-270,000 practicing NPs in the United States. The number of nurse practitioners is expected to grow in the following years by about 52% between 202 and 2030, according to the U.S. Bureau of Labor Statistics. Currently, Americans make more than 1 billion visits to NPs'every year. The growth of NPs' is expected to address the current physician shortage.  

Thank you, Nurse Practitioners.

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Conclusion: Now we conclude episode number 119, “Nurse Practitioner Week.” Amy Arreaza, FNP, explained the basics about Nurse Practitioners and how they contribute to the health of our patients. This episode is a tribute to all the nurse practitioners who work shoulder to shoulder-as key members of the healthcare teams across the United States. We thank all of you and look forward to your continued support for healthier communities.

This week we thank Hector Arreaza and Amy Arreaza. Audio edition by Adrianne Silva.

Even without trying, you go to bed a little wiser every night. Thanks for listening to Rio Bravo qWeek Podcast. We want to hear from you. Send us an email at [email protected], or visit our website riobravofmrp.org/qweek. See you next week!

_____________________

References:

1. Royalty-free music used for this episode: Simon Pettersson – good vibes_ Fashionista, downloaded on October 1, 2022, from https://www.videvo.net

Even without trying, every night you go to bed a little wiser. Thanks for listening to Rio Bravo qWeek Podcast. We want to hear from you, send us an email at [email protected], or visit our website riobravofmrp.org/qweek. See you next week!

Dr. Malave explains the diagnosis and treatment of Wernicke’s encephalopathy. Editing and comments by Hector Arreaza.  

Written by Maria Fernanda Malave, edited by Hector Arreaza, MD.

You are listening to Rio Bravo qWeek Podcast, your weekly dose of knowledge brought to you by the Rio Bravo Family Medicine Residency Program from Bakersfield, California, a UCLA-affiliated program sponsored by Clinica Sierra Vista, Let Us Be Your Healthcare Home. This podcast was created for educational purposes only. Visit your primary care provider for additional medical advice.

Definition.

As a reminder for everyone, vitamin B1 and thiamine are the same substance with different names. Wernicke’s encephalopathy (WE) is a neurological syndrome secondary to severe, short-term B1 deficiency. In the past, but less frequently nowadays, it was more commonly associated with alcohol use disorder. However, today we know that any condition that decreases dietary intake and increases thiamine use, or its elimination, puts patients at risk of developing this encephalopathy. 

Causes:

Chronic alcoholism is the most important cause of WE. Around 70-80% of the causes are associated with chronic alcohol consumption. 

Non-alcoholic WE may be caused by 

• Decreased intake: Some types of WE may be caused by a psychiatric illness that decreases the dietary intake of B1, such as anorexia nervosa, schizophrenia, or dementia. Arreaza: Also, prolonged fasting or starvation.
• Lack of absorption of B1: Other causes might be related to malabsorptive syndromes, bariatric surgeries, or hyperemesis gravidarum
• Increased use of B1: Any disease that increases the use of B1 and, therefore, low levels of thiamine, such as cancer, thyrotoxicosis, and systemic illnesses like infections. High-carb diets are associated with high thiamine use. Also, patients who receive IV glucose w/o supplements are at risk of developing Wernicke’s encephalopathy.
• Increased elimination of B1: Other causes are related to increased elimination of B1, such as dialysis.
• Immunodeficiencies: Immunodeficiency syndromes and transplantation also cause WE.

Why is thiamine important?

Thiamine is one of the main cofactors in three key enzymes for energy metabolism: alpha-ketoglutarate dehydrogenase, pyruvate dehydrogenase, and transketolase. If we go back to biochemistry in med school, we can remember these enzymes play a significant role in the Krebs cycle and pentose phosphate pathways. Thiamine uses Mg+2 as a cofactor, so a magnesium deficiency can mimic WE.

Pathophysiology.

B1 deficiency causes lactic acid accumulation due to anaerobic glycolysis, leading to neuronal cytotoxic edema and vasogenic edema with petechial hemorrhages. MRI of the brain shows symmetrical hyperintensities, most commonly in the thalamus, mammillary bodies, cerebellum, and the periaqueductal area surrounding the third and fourth ventricles. The diagnosis of WE is made clinically, even though the MRI is a useful complementary tool to the clinical diagnosis. 

Diagnosis.

WE presentation has always been described as the classic triad of ophthalmoplegia (or nystagmus), encephalopathy (confusion or memory impairment), and gait ataxia. However, this presentation is present only in less than 20% of patients, and most of the patients present with a neurologic syndrome that includes 2 out of the classic triad plus nonspecific symptoms such as hallucinations, hypothermia, hypotension, indifference or inattentiveness, seizures, behavioral disturbances, and bilateral lower extremity weakness. 

In 1997, Caine et al. suggested that a diagnosis of WE can be made if 2 out of 4 of these criteria were present in a patient with ophthalmoplegia/nystagmus + ataxia + memory impairment or confusion and clinical evidence of malnutrition or from laboratory data. Thiamine levels can be normal in patients with WE, so thiamine level is not a requirement for diagnosis.

Almost 80% of WE cases are diagnosed on autopsy, which means this disease goes undiagnosed most of the time. The diagnosis is clinical, and MRI can assist in cases that are uncertain. 

Treatment.

Thiamine supplementation is inexpensive, accessible, and easy to administer, so if we have a patient with a suspicious neurologic syndrome that could be WE, B1 must be given as soon as possible. Treatment should not be delayed while waiting for MRI results, 

The treatment consists of IV thiamine 500mg TID for 2-3 days, followed by 250 IM or IV for additional 5 days, in combination with other B vitamins. Because GI absorption of thiamine is impaired in alcoholics and malnourished patients, oral administration is contraindicated during initial treatment for WE. Thiamine 100 mg PO should be continued after the completion of parenteral treatment and after discharge from the hospital until patients are no longer considered at risk. Magnesium and other vitamins are replaced as well, along with other nutritional deficits if present.

B1 blood levels or erythrocyte transketolase activity (which is a way to evaluate thiamine deficiency) are measured before and after thiamine pyrophosphate supplementation. A low transketolase and a more than 25 percent stimulation are positive for thiamine deficiency. This test is often not readily available, especially at the ED. High-quality liquid chromatography can also measure serum thiamine or TPP level in serum or whole blood.

For practical purposes, and given high undiagnosed rates and mortality, IV thiamine should be given to all patients with malnutrition admitted to the hospital or seen in clinic. 

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Conclusion: Now we conclude episode number 117 “Wernicke’s Encephalopathy.” Dr. Malave explained that a low thiamine level is not required for the diagnosis of Wernicke’s encephalopathy. Start supplementation if you have a high suspicion of thiamine deficiency, especially before giving IV glucose to a malnourished patient. We were reminded that GI absorption of thiamine is impaired in patients with chronic alcohol use, so make sure you give thiamine IV or IM. 

This week we thank Hector Arreaza and Maria Fernanda Malave. Audio edition by Adrianne Silva.

Even without trying, every night you go to bed a little wiser. Thanks for listening to Rio Bravo qWeek Podcast. We want to hear from you, send us an email at [email protected], or visit our website riobravofmrp.org/qweek. See you next week! 

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Links:

1. He Jingqi, Li Jinguang, Li Zhijun, Ren Honghong, Chen Xiaogang, Tang Jinsong. A Case Report of Wernicke's Encephalopathy Associated with Schizophrenia. Frontiers in Psychiatry. Vol 12. Year 2021. DOI=10.3389/fpsyt.2021.657649. https://www.frontiersin.org/articles/10.3389/fpsyt.2021.657649/full
2. Ota, Y., Capizzano, A.A., Moritani, T. et al. Comprehensive review of Wernicke encephalopathy: pathophysiology, clinical symptoms and imaging findings. Jpn J Radiol 38, 809–820 (2020). https://doi.org/10.1007/s11604-020-00989-3.
3. Yuen T So, MD, PhD, Wernicke encephalopathy, last updated: Feb 11, 2020, UpToDate. Retrieved October 25, 2022.https://www.uptodate.com/contents/wernicke-encephalopathy.
4. Patel S, Topiwala K, Hudson L. Wernicke's Encephalopathy. Cureus. 2018 Aug 22;10(8):e3187. doi: 10.7759/cureus.3187. PMID: 30364782; PMCID: PMC6199146. https://pubmed.ncbi.nlm.nih.gov/30364782/
5. Royalty-free music used for this episode: Simon Pettersson – good vibes_ Fashionista, downloaded on October 1, 2022, from https://www.videvo.net 

Even without trying, every night you go to bed a little wiser. Thanks for listening to Rio Bravo qWeek Podcast. We want to hear from you, send us an email at [email protected], or visit our website riobravofmrp.org/qweek. See you next week!

Adriana and Ikleel explain the new recommendation given by the USPSTF in October 2022 regarding screening for anxiety in children and adolescents 8-18 years old. Dr. Arreaza discusses the SCARED tool to screen for anxiety in pediatric patients. 

By Adriana Rodriguez, MS3, and Ikleel Moshref, MS3. Ross University School of Medicine. Moderated by Hector Arreaza, MD. 

You are listening to Rio Bravo qWeek Podcast, your weekly dose of knowledge brought to you by the Rio Bravo Family Medicine Residency Program from Bakersfield, California, a UCLA-affiliated program sponsored by Clinica Sierra Vista, Let Us Be Your Healthcare Home. This podcast was created for educational purposes only. Visit your primary care provider for additional medical advice.

Recommendation.

• The USPSTF recommends screening for anxiety in children and adolescents aged 8 to 18 years. Grade of recommendation: B (offer this service to your patients)
• The USPSTF concludes that the current evidence is insufficient to assess the balance of benefits and harms of screening for anxiety in children 7 years or younger. Grade of recommendation: I (insufficient evidence, unknown benefits vs. harms)

USPSTF concludes this new screening guideline for anxiety in this population has a moderate net benefit. For children 7 and younger, evidence is insufficient to determine screening tools accuracy and its effects, and benefit-to-risk balance. 

Anxiety. 

Anxiety disorder is characterized by excessive, persistent worry and or fear that is difficult to control, resulting in significant distress or impairment. Anxiety disorder manifests in psychological/emotional and physical/somatic symptoms. DSMV recognizes 7 types of anxiety disorders: GAD, social anxiety disorder, panic disorder, agoraphobia, specific phobias, separation anxiety disorder, and selective mutism. 

Comment: Anxiety is not your patient’s fault. In some cultures, anxiety is seen as a weakness. America seems to be a highly stressful society.

Epidemiology.

Anxiety disorder is a common mental health condition in the United States. According to the National Survey of Children’s Health in 2018-2019, 7.8% of people aged 3-17 yrs. old had an anxiety disorder that was current. In the adult population, past studies have shown ~3% past-year prevalence and ~5-12% lifetime prevalence of anxiety disorder in adults. 

Topic Importance.

Anxiety disorders are the most common childhood-onset mental health condition. Childhood and adolescent anxiety disorder is associated with an increased likelihood of poor academic performance and co-occurring psychiatric conditions. It is also associated with future anxiety disorder, secondary depression, substance abuse, psychosocial functional impairment, chronic mental/somatic health conditions, and/or suicide. Screening anxiety disorder in youth may serve to improve potential prevent burdens in the future. 

Assessment of Risk. 

Although this new screening guideline is meant for children and adolescents aged 8-18 who have not been diagnosed with an anxiety disorder and without signs and symptoms, it is important to note what factors would increase their chances of developing any of the aforementioned anxiety disorders: 

• Genetic, personality, and environmental factors: biopsychological vulnerability, attachment difficulties, child maltreatment, adverse childhood experience 
• Demographic factors: poverty, low socioeconomic status
• Racial and ethnic factors: racial discrimination, historic trauma, structural racism
• Other factors: LGBTQ youth, older adolescents 12-17

Screening Tools.

Although there are many screening tests for anxiety, two are widely utilized in clinical practice for screening purposes: (1) SCARED (Screen for Child Anxiety Related Disorders), and (2) Social Phobia Inventory. These screening instruments are insufficient for the actual diagnosis of any particular anxiety disorder listed earlier; if positive, however, a confirmatory assessment and follow-up is required to establish diagnosis using DSM V criteria for any of the recognized anxiety disorders (GAD, social anxiety disorder, panic disorder, agoraphobia, specific phobias, separation anxiety disorder, and selective mutism).

SCARED (Screen for Children Anxiety Related Disorders): It is a 41-Item questionnaire, each question can be answered from 0-2 (0=not true or hardly true, 1=somewhat true or sometimes true, 2=very true or often true). A score greater than or equal to 25 is highly associated with anxiety disorder; panic disorder, significant somatic symptoms, generalized anxiety disorder, separation anxiety disorder, social anxiety disorder, and significant school avoidance. SCARED is available online (here). There is a child version and a parent version. The only difference between the two is the different pronouns, for example, question 17 is “My child worries about going to school” vs “I worry about going to school”. 

Although the USPSTF could not find optimal screening intervals, these screenings may be best used in older adolescents aged 12-17 yrs. old with risk factors for anxiety disorder. 

Other anxiety screening tools have been assessed by the USPSTF but were insufficient for the purposes of this guideline because they were too specific to a specific anxiety disorder (for example, the Social Phobia and Anxiety Inventory for Children), were for a particular set of disorders, or were too long to use for screening in a primary care setting. 

In studies found by the USPSTF, social anxiety disorder and GAD were the most common detected anxiety disorder in children and adolescents. 

Fun fact: What is the most common phobia in the US? Public speaking, AKA glossophobia.

Treatment. 

Anxiety disorders can be treated with medications, psychotherapy, a combination of both, or multidisciplinary care. Of the variety of psychotherapies available, cognitive behavioral therapy (CBT) is the most used. As for pharmacotherapy, US FDA has only approved duloxetine, an SNRI, for the treatment of GAD in children 7 yrs. and older. Off-label prescriptions of other drugs have been reported to treat anxiety in youth. 

Potential Harms.

False-positive screening results may lead to an unnecessary burden on the patient and family from avoidable referrals, monetary costs, anxiety, the stigma of illness, and adverse effects of pharmacotherapy (weight loss, cholesterol, etc.)

Bottom line: Anxiety is a treatable mental condition and detection in childhood is now recommended by the USPSTF. Screen if you have a way to treat (refer or treat yourself).

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Conclusion: Now we conclude episode number 117 “Anxiety Screening.” Adriana and Ikleel explained that screening for anxiety disorders in children between 8-18 is now a grade B recommendation by the United States Preventive Services Task Force. During this episode, you heard about “SCARED”, a useful screening tool to help in the diagnosis of anxiety disorders in children. Once diagnosed, anxiety is treated with psychotherapy, medications, or a combination of both. This week we thank Hector Arreaza, Adriana Rodriguez, and Ikleel Moshref. Audio edition by Adrianne Silva.

Even without trying, every night you go to bed a little wiser. Thanks for listening to Rio Bravo qWeek Podcast. We want to hear from you, send us an email at [email protected], or visit our website riobravofmrp.org/qweek. See you next week! 

_____________________

Links:

1. Final Recommendation Statement, Anxiety in Children and Adolescents: Screening, United States Preventive Services Task Force, https://www.uspreventiveservicestaskforce.org/uspstf/recommendation/screening-anxiety-children-adolescents#fullrecommendationstart, accessed on Oct 11, 2022. 
2. Screen for Child Anxiety Related Disorders (SCARED), available online, for example: Oregon Health & Science University: https://www.ohsu.edu/sites/default/files/2019-06/SCARED-form-Parent-and-Child-version.pdf
3. Bennett, Shannon, et al. Anxiety disorders in children and adolescents: assessment and diagnosis, UpToDate, last updated: Aug 19, 2022. https://www.uptodate.com/contents/anxiety-disorders-in-children-and-adolescents-assessment-and-diagnosis.
4. Baldwin, David, et al. Generalized anxiety disorder in adults: Epidemiology, pathogenesis, clinical manifestations, course, assessment, and diagnosis, UpToDate, last updated: Apr 18, 2022. https://www.uptodate.com/contents/generalized-anxiety-disorder-in-adults-epidemiology-pathogenesis-clinical-manifestations-course-assessment-and-diagnosis.
5. Craske, Michelle, et al. Generalized anxiety disorder in adults: Management, Up to Date, last updated Nov 12, 2021. https://www.uptodate.com/contents/generalized-anxiety-disorder-in-adults-management.
6. Royalty-free music used for this episode: Real Live by Gushito, downloaded on October 1, 2022, from https://www.videvo.net/. 

Even without trying, every night you go to bed a little wiser. Thanks for listening to Rio Bravo qWeek Podcast. We want to hear from you, send us an email at [email protected], or visit our website riobravofmrp.org/qweek. See you next week!

By Timiiye Yomi, MD. Editing and comments by Hector Arreaza, MD.

Dr. Yomi explains the benefits of breastfeeding for mother and baby. Three doctor listeners share their experiences with breastfeeding. 

You are listening to Rio Bravo qWeek Podcast, your weekly dose of knowledge brought to you by the Rio Bravo Family Medicine Residency Program from Bakersfield, California, a UCLA-affiliated program sponsored by Clinica Sierra Vista, Let Us Be Your Healthcare Home. This podcast was created for educational purposes only. Visit your primary care provider for additional medical advice.

Breastfeeding is the process by which a child is fed breast milk. It is an ancient practice that dates to pre-historic times. The American Academy of Pediatrics recommends breastfeeding as the sole source of nutrition for babies for about 6 months and can be continued for as long as both mother and baby desire it, while the World Health Organization recommends exclusive breastfeeding for the first 6 months of life and up to 2 years with appropriate complementary foods.

Human milk has many advantageous anti-infective and immunologic properties, making it the ideal nutritional source to optimize the infant's well-being. Of the over 130 million babies born every year in the world, only 42% of mothers breastfeed their newborn within the first hour of life, 38% practice exclusive breastfeeding, and over 50% breastfeed for up to 2 years. In this segment, we will be talking about the many benefits of breastfeeding to both children and mothers.

Benefits to the baby: 

• Breast milk has the right amount of nutrients and fluids needed for a baby’s growth and development.
• It is easier to digest than formula, and breastfed babies have less gas, fewer feeding problems, and less constipation.
• It contains antibodies that protect infants from illnesses like otitis media, gastroenteritis, and respiratory illnesses like asthma and allergies, especially in children breastfed beyond 6 months. 
• It reduces the risk of atopic dermatitis, NEC, Celiac Disease, Crohn’s Disease and ulcerative colitis, Late-onset sepsis in the preterm infant, and childhood leukemia.
• Reduces the risk of childhood obesity, HTN, and type 1 and 2 diabetes  
• Breastfed infants have a lower risk of sudden infant death syndrome (SIDS).
• Breastfed infants have been shown to have better cognitive development.

Benefits to the mother:

• Promotes weight loss and some degree of contraceptive for mothers
• Women who breastfeed longer have been shown to have lower rates of type 2 diabetes and high blood pressure, breast and ovarian cancer in premenopausal women, thyroid cancers, rheumatoid arthritis, and osteoporosis
• Reduces the risk of post-Partum depression
• Breastfeeding triggers the release of oxytocin that promotes uterine involution and may decrease the amount of postpartum hemorrhage.

Additional benefits:

• Promotes mother-infant bonding 
• Cheap and economical for families and society
• Convenient

In summary, breastfeeding delivers a lot of health, nutritional and emotional benefits to both children and mothers. When not contraindicated, we encourage mothers to engage in this practice as it presents babies with a healthy start in life.

The benefits of breastfeeding cannot be overstated. However, we recognize that some mothers have challenges breastfeeding. For those mothers, we say you are a great mother if you take good care of your baby, even if you cannot breastfeed him/her.

Testimonials:

Breastfeeding is highly recommended by healthcare professionals, and in most cases, it is a natural and smooth process. However, it is not always free of challenges. You will listen to testimonials about three different breastfeeding experiences. All these testimonials are anonymous and written by advanced-level healthcare providers. Their experiences fall on a spectrum ranging from positive and easy to negative and difficult.

Testimonial #1: My grandma told me so.

When I was pregnant with my first child, I was already keenly aware of the benefits of breastfeeding because by that time, I was established in my profession as a health care provider. I looked forward to breastfeeding my newborn. However, when my baby was born, I found that my breast anatomy made it extremely difficult for my baby to latch on. While it is possible for women to breastfeed with inverted nipples, for me and my baby, it did not work out. 

I felt like a failure as a new mother.  When my grandma came to visit me and my newborn, I told her how frustrated I was with my body.  She replied, “yah, sorry about that; you got those from me!” Yes, inverted nipples are a genetic trait, and 10-20% of women are born with inverted nipples. I had been feeling alone in my plight, but after talking with my grandma, I realized there were other women struggling just like me!  

Although I was very disappointed that I couldn’t breastfeed, I didn’t let that deter me from giving breast milk to my baby. Where there is a will, there is a way! I decided to bottle-feed my baby with my pumped breast milk. It was extra work and a bit time-consuming, but for me, the health benefits for both my baby and me were worth it. 

Thankfully, I am blessed with a supportive husband who took on the nighttime feedings while I pumped milk. I could only keep up this pumping routine for 3 months before my maternity leave ended. While I would have preferred my baby to receive breast milk for longer, I find peace in the saying, “something is better than nothing.” If only there had been wearable breast pumps back then, I’m sure I could have given my baby breast milk for much longer. Technology today is amazing!  

While I encourage all my patients to breastfeed, my personal experience has made me empathetic to the physical challenges and even heartache that women experience over breastfeeding. I always keep in mind that every woman and baby’s situation is unique, and I also give myself grace for what I initially felt was a shortcoming as a new mother.  

Testimonial 2: Fed is best.

I have been a breastfeeding advocate since medical school.Prior to the delivery of my first baby, I had my breast pump and bag ready. I had all the handouts about different breastfeeding techniques, positions, and all the available community resources.  I had the tablets and teas that would stimulate milk production. I was ready!

When I delivered my beautiful baby girl, she had trouble latching and it was very painful for me. All through that first night at the hospital, I requested the lactation coaches to come to the bedside to guide me, and they came by every shift. They even gave me all these extra syringes and tubes to feed my baby. We ended up feeding her with donor’s milk at the hospital. We even fed her via a syringe the first few nights. I was never able to get her to latch. I drank my water and my tea, I  took my tablets, and I was able to pump some milk,filling only 1/4 -1/2 of the bottle each time, only about 3-6 cc from each breast in a 20–30-minute session. My baby started to be fed with formula and my breast milk. I continued to pump during my lunch breaks when I returned to work. I did this until she turned 6 months old, then I stopped.

My second baby was able to latch a few times in the hospital. I felt so relieved that I would be a successful breastfeeder, but she started to get jaundiced because of inadequate intake. We decided to give her donor milk again. At home, I still could not breastfeed, but I was able to pump. I even bought the hands-free Willow pump, thinking I could pump while charting or seeing patients, but it was not for me. My baby alternated feedings between breast milk and formula. I stopped pumping at 3 months.

It was quite frustrating to not successfully latch and breastfeed. Somehow, I had this feeling as the song goes, “ I did my best, but I guess my best wasn’t good enough”. Thankfully, one of my pediatric colleagues put my mind at ease. She said, “fed is best.” Indeed, my baby girls have grown to be beautiful, healthy babies, and our bond is strong. Now I counsel with grace and consideration. My  mantra before was “breast is best”; now, it is “fed is best.”

Testimonial #3: A mother of seven.

I had seven babies, and each of them had different experiences with breastfeeding. I’d like to share with you how it went. 

• Breastfeeding my first baby was relatively easy. He was a cooperative, calm infant and caught on quickly to the process. 
• Baby number two was 6 weeks premature, so in the first week, he kept falling asleep, but as he got a bit older, things went well. 
• Baby number 3 was born with a cleft lip and alveolar ridge, and breastfeeding was necessary. The breast tissue filled up the cleft in his lip, so he was able to grow normally until big enough for reparative surgery. He did have a bit of nipple confusion when I had to return to work. Baby three actually continued some token breastfeeding for a couple of weeks when his newborn sister was co-nursing. Because the breast is a demand-organ, increased suckling increases milk productivity, so neither child was deprived of milk. 
• Baby four adapted well.
• Baby five was a somewhat slow learner but, with persistence, ultimately did well. 
• Baby six also was an eager learner, but when she was 9 months, decided that she had had enough of breastfeeding, so we stopped. 
• Baby seven adapted too well and breastfed for a couple of years. 

Several babies were breastfed during my pregnancies without issues. In my opinion, the first week is when you must teach a baby how to breastfeed, and it is generally the most difficult. If you can tough it through that first week, things become a lot easier. Babies have their own personalities and their own way of learning, so whereas one baby will prove a natural at the task, another may require a bit more patience. 

Breastfeeding and working can be challenging, but I was able to continue breastfeeding and return to work. It took determination and the reversal of day and night feeds. I didn’t get much sleep at first, but the babies stayed so much healthier due to the immune benefits of breastfeeding, which meant less time off work with a sick child!

If you have a “special needs” baby, and this includes premies and children with orofacial problems, breastfeeding prevents nutritional issues. Breastfeeding provided me with a special feeling of tranquility and peace, that’s why it may reduce the risk of postpartum depression. Also, the luxury of being able to feed anytime, anywhere, was very helpful for me!

All seven of our kids have advanced degrees, and several have their doctorates. I would like to think that breast milk played a role in their academic success. I think breastfed babies are smarter! 

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Conclusion: Now we conclude episode number 116, “Benefits of breastfeeding.” We hope your knowledge about breastfeeding was enriched by Dr. Yomi’s presentation and that the testimonials gave you a broader perspective on the breastfeeding experience. 

This week we thank Hector Arreaza, Timiiye Yomi, Chelsea Dunn, Carmen Ruby, Anna Stewart, and three anonymous doctor mothers. Audio edition by Adrianne Silva.

Even without trying, every night, you go to bed a little wiser. Thanks for listening to Rio Bravo qWeek Podcast. We want to hear from you. Send us an email at [email protected], or visit our website riobravofmrp.org/qweek. See you next week! 

_____________________

Links: 

1. Madore LS, Fisher DJ. The Role of Breast Milk in Infectious Disease. Clin Perinatol. 2021 Jun;48(2):359-378. doi: 10.1016/j.clp.2021.03.008. PMID: 34030819. https://pubmed.ncbi.nlm.nih.gov/34030819/
2. American Academy of Pediatrics. (2021). Benefits of breastfeeding, Patient Care. Retrieved from https://www.aap.org/en/patient-care/breastfeeding/breastfeeding-overview/
3. Westerfield KL, Koenig K, Oh R. Breastfeeding: Common Questions and Answers. Am Fam Physician. 2018 Sep 15;98(6):368-373. PMID: 30215910. https://www.aafp.org/pubs/afp/issues/2018/0915/p368.html
4. Royalty-free music used for this episode: Gushito, Latin Pandora by Videvo, downloaded on May 06, 2022, from https://www.videvo.net

Even without trying, every night you go to bed a little wiser. Thanks for listening to Rio Bravo qWeek Podcast. We want to hear from you, send us an email at [email protected], or visit our website riobravofmrp.org/qweek. See you next week!

Discussion about the diagnosis of erectile dysfunction with Andrew, Adriana, and Dr. Arreaza. Causes, labs, and physical exam is briefly discussed. Written by Andrew Kim, MSIV, Western University of Health Sciences, College of Osteopathic Medicine of the Pacific. Comments by Adriana Rodriguez, MS3, Ross University School of Medicine; and Hector Arreaza, MD.

September 22, 2022.

You are listening to Rio Bravo qWeek Podcast, your weekly dose of knowledge brought to you by the Rio Bravo Family Medicine Residency Program from Bakersfield, California, a UCLA-affiliated program sponsored by Clinica Sierra Vista, Let Us Be Your Healthcare Home. This podcast was created for educational purposes only. Visit your primary care provider for additional medical advice.

In episode 39 o erectile dysfunction, Dr. Ihejirika gave us an overview, but today we will be more detailed about the diagnosis of ED. 

Definition.

The American Urological Association (AUA) published an erectile dysfunction guideline in May 2018, which is available online at no cost. Based on that guideline, erectile dysfunction can be defined as “the consistent or recurrent inability to attain and/or maintain penile erection sufficient for sexual satisfaction, including satisfactory sexual performance.” Comment: This guideline provides 25 principles for diagnosing and treating ED. 

Diagnosis.

Getting a good history is important when diagnosing erectile dysfunction. The patient should be asked about the onset of symptoms, severity, how much it hinders his sexual performance, whether the patient can get and maintain an erection, psychological factors, social factors, and presence of morning erections. 

One can use different questionnaires: the five-question International Index of Erectile Function (IIEF-5) or a single-question self-assessment. 

Single-question self-assessment:

Impotence means not being able to get and keep an erection that is rigid enough for satisfactory sexual activity. How would you describe yourself?

1. Not impotent: always able to get and keep an erection good enough for sexual intercourse.
2. Minimally impotent: usually able to get and keep an erection good enough for sexual intercourse.
3. Moderately impotent: sometimes able to get and keep an erection good enough for sexual intercourse.
4. Completely impotent: never able to get and keep an erection good enough for sexual intercourse.

Comment: Basically, the single-question self-assessment is a self-diagnosis of erectile dysfunction; the patient is giving you the severity of his condition. This questionnaire seems to be very subjective. 

International Index of Erectile Function (IIEF-5):

IIEF-5 asks five questions, and the patient answers on a scale of 1 to 5 (1 is the worst, 5 is the best)

1. How do you rate your confidence that you could get and keep an erection?
2. When you had erections with sexual stimulation, how often were your erections hard enough for penetration?
3. During sexual intercourse, how often were you able to maintain your erection after you had penetrated your partner?
4. During sexual intercourse, how difficult was it to maintain your erection to completion of intercourse?
5. When you attempted sexual intercourse, how often was it satisfactory for you?

Diagnosis can be made based on the total score. 1 to 7: severe ED, 8 to 11: moderate ED, 12 to 16: mild-moderate ED, 17 to 21: mild ED, and 22 to 25: no ED.

This is a self-reported questionnaire, and the score should be interpreted in a clinical context. Answers will likely be biased if, for example, the questionnaire is asked by a female medical assistant.

Causes of ED:

It is important to assess for medical conditions, psychological conditions, and medications because ED can be caused by vascular, neurological, psychological, and hormonal problems. 

• Cardiovascular: Some common conditions related to ED are cardiovascular disease (PAD, CAD) and HTN.
• Endocrine: DM, HLD, obesity, testosterone deficiency (hypogonadism), hyperprolactinemia, thyroid disorder, metabolic syndrome.
• Neurologic: Neurologic conditions (multiple sclerosis, stroke, spine injury), trauma, and venous leakage.
• Lifestyle causes: sedentary lifestyle, tobacco use.
• Psychological: Performance anxiety, relationship issues, anxiety, depression, and stress are common psychological causes.
• Medications and substances: Alcohol, illicit drugs, and nicotine are important causes of ED, but some medications also cause or worsen ED: opiates, diuretics (spironolactone), antifungals (azoles), anticonvulsants, antidepressants (SSRIs), antihistamines, H2 blocker (cimetidine) antihypertensives, nasal decongestants, and antipsychotics. Remember to ask about over-the-counter medications and supplements.

Physical exam: Measure blood pressure, BMI, and a complete exam, especially a genital exam. 

A comprehensive genitourinary exam should include the inspection of the testicles (atrophy, varicocele, signs of hypogonadism). The penis should be inspected and palpated (look for scar tissue and Peyronie’s plaques) and assessment of penile stretch/flaccid length (it is done by stretching the penis. An elastic penis is a healthy penis). Dr. Winter’s expert opinion: consider a prostate exam in older patients presenting with ED.

Labs: Following physical examination, some lab tests can be ordered to further evaluate possible causes of ED. 

-A1C and glucose levels can be ordered to look for diabetes. 

-Lipid panel for hyperlipidemia.

-TSH should be checked for thyroid function and to rule out hypothyroidism. 

-Testosterone deficiency can be assessed by measuring morning serum total testosterone level, which is defined as total testosterone < 300 with signs and symptoms. 

-Prolactin (perform pituitary MRI in any degree of hyperprolactinemia. In patients taking medications that cause hyperprolactinemia, get MRI if prolactin is above 100) 

Why is it important to diagnose ED?

ED can be linked to organic causes.

- Glucose: ED is linked to increased fasting serum glucose levels (diabetes). People with PMH of DM are 3 times more likely to develop ED. The longer the patient had diabetes, the stronger association with ED. Fasting glucose levels are associated with the highest risk of ED. The probability of having undiagnosed DM is 1/50 in the age group 40 to 59 without ED but increases to 1/10 for those with ED.

- Testosterone and obesity: Low serum testosterone levels can contribute to the link between metabolic syndrome and ED. In men with obesity, the adipose tissue enzyme aromatase is more prevalent and can convert testosterone into estradiol to cause hypogonadism. Furthermore, adipocytes can cause inflammation and recruit inflammatory cytokines, leading to impaired endothelial function and ED. 

- Cardiovascular disease: ED and CVD have some common risk factors: older age, HTN, dyslipidemia, smoking, obesity, and DM. ED is related to an increased risk of CVD, CAD, and stroke. Usually, it is thought that ED arises two to five years prior to CAD. If a patient develops signs and symptoms of ED before CAD, the patient can be counseled and educated to make lifestyle modifications to prevent CAD.

Furthermore, men with ED are more likely to experience angina, MI, stroke, TIA, CHF, and cardiac arrhythmias when compared to their counterparts without ED. A study from 2003 suggested that patients with ED have a 75% increased risk of developing peripheral vascular disease. Studies suggest ED can predict silent CAD, and one study concluded that the incidence of CAD in men below 40 years of age with ED was seven times higher than that of the control population without ED. It is important to diagnose ED because it can be used as a marker for assessing cardiovascular risk.

ED can be linked to many causes, and we as clinicians should be able to identify those causes to prescribe a more specific treatment. Not all ED will respond to “the blue pill”. We will talk about treatment in another episode. 

Conclusion: Now we conclude episode number 115, “Erectile Dysfunction Diagnosis.” Male sexual health sometimes can be taboo, and patients may not fully disclose personal issues like erectile dysfunction. Andrew and Adrianna explained that an open discussion about erectile dysfunction can help you diagnose underlying conditions, including cardiovascular disease. Dr. Arreaza reminded us that the diagnosis of erectile dysfunction should prompt a deeper investigation in most cases before you attribute it to psychological factors. 

This week we thank Hector Arreaza, Andrew Kim, Adriana Rodriguez, and Fiona Axelsson. Audio edition by Adrianne Silva. 

Even without trying, every night you go to bed a little wiser. Thanks for listening to Rio Bravo qWeek Podcast. We want to hear from you, send us an email at [email protected], or visit our website riobravofmrp.org/qweek. See you next week! 

___________________________________________________

References:

1. Burnett AL, Nehra A, Breau RH, et al. Erectile Dysfunction: AUA Guideline. Journal of Urology. 2018;200(3):633-641. doi:10.1016/j.juro.2018.05.004. https://www.auajournals.org/doi/epdf/10.1016/j.juro.2018.05.004.
2. Rew KT, Heidelbaugh JJ. Erectile Dysfunction. American Family Physician. 2016;94(10):820-827. Accessed September 19, 2022. https://www.aafp.org/pubs/afp/issues/2016/1115/p820.html.
3. Khera M. Evaluation of male sexual dysfunction. UpToDate. www.uptodate.com. Last updated: April 28, 2020. Accessed September 19, 2022. https://www.uptodate.com/contents/evaluation-of-male-sexual-dysfunction.
4. Abrams H, Winter A, Williams PN, Watto MF. “#317 Erectile Dysfunction”. The Curbsiders Internal Medicine Podcast. https://thecurbsiders.com/episode-list. January 24, 2022.
5. Royalty-free music used for this episode: Gushito, Burn Flow. by Videvo, downloaded on May 06, 2022, from https://www.videvo.net/royalty-free-music-track/good-vibes-alt-mix/1017292/

Even without trying, every night you go to bed a little wiser. Thanks for listening to Rio Bravo qWeek Podcast. We want to hear from you, send us an email at [email protected], or visit our website riobravofmrp.org/qweek. See you next week!

Yvette presents updates from ADA on diabetes care regarding SGLT-2 inhibitors, GLP-1 receptor agonists, and finerenone. Written by Yvette Singh, MSIV, American University of the Caribbean. Comments and text edition by Hector Arreaza, MD. 

You are listening to Rio Bravo qWeek Podcast, your weekly dose of knowledge brought to you by the Rio Bravo Family Medicine Residency Program from Bakersfield, California, a UCLA-affiliated program sponsored by Clinica Sierra Vista, Let Us Be Your Healthcare Home. This podcast was created for educational purposes only. Visit your primary care provider for additional medical advice.

The American Diabetes Association (ADA) released revisions in May 2022; specifically regarding sodium-glucose cotransporter-2 (SGLT-2) inhibitors, glucagon-like peptide-1 receptor agonists (GLP-1 RA), and finerenone for cardiovascular and renal comorbidities. 

What are SGLT2 inhibitors and GLP-1 receptor agonists?

SGLT2 inhibitor class of oral antidiabetic drugs, including empagliflozin, canagliflozin, dapagliflozin, and more. They increase the excretion of glucose and sodium in the urine by inhibiting SGLT2 in the kidney, thus lowering blood glucose levels. In other words, it has a glucoretic effect. 

GLP-1 receptor agonists are a class of non-insulin drugs, including exenatide, liraglutide, semaglutide, and more. They mimic the intestinal hormone incretin and bind to its receptor, which slows the rate at which foods leave the stomach, controls appetite, and regulates insulin and glucagon secretion.

What is the NEW use of SGLT-2 Inhibitors and GLP-1 RA in treatment?

Traditional glucocentric approaches recommend initial medications such as metformin for most adults with type 2 diabetes, leaving SGLT-2 inhibitors and GLP-1 receptor agonists as alternative options mainly for patients with high risk for atherosclerotic cardiovascular disease in whom additional glucose lowering was needed after metformin treatment. 

Current guidelines now recommend these agents (SGLT-2 inhibitors and GLP-1 RA) for any T2DM patient with current or high-risk for ASCVD, chronic kidney disease (CKD), or heart failure (HF). This guideline stands regardless of the need for additional glucose lowering and/or metformin use. This has now changed through trials, demonstrating that cardiovascular disease and chronic kidney disease benefits independent of a medication’s glucose-lowering potential.

HbA1c has long been used to guide clinical decision-making about type 2 diabetes. However, systematic reviews have revealed minimal benefits in the normalization of HbA1c.

Moreover, the cardiovascular and kidney protection of SGLT-2 inhibitors and GLP-1 receptor agonists are unrelated to their impact on HbA1c. Double-blinded randomized clinical trials showed that SGLT-2 inhibitors reduced the risk of cardiovascular death and hospitalization for heart failure in patients with or without diabetes. Therefore, cardiovascular and kidney risk, rather than HbA1c, constitutes a possible indication for the two medication classes. 

If patients with ASCVD remain above goal A1C despite the addition of an SGLT-2 inhibitor or GLP-1 RA, then adding the agent the patient is not currently on out of the two is recommended before dipeptidyl peptidase-4 aka (DPP-4) inhibitors, basal insulin, or sulfonylureas because the combined use of an SGLT-2 inhibitor and GLP-1 RA can produce an additive risk reduction for cardiovascular and renal adverse events.

What is Finerenone, and how does it help with diabetes? 

Finerenone (Kerendia®) selectively blocks sodium reabsorption and overactivation of mineralocorticoid receptors within epithelial and non-epithelial tissues. This, in turn, reduces fibrosis and inflammation of both the kidneys and blood vasculature.

Finerenone use for patients with advanced CKD, i.e., moderately elevated albuminuria, eGFR of 25- 60 mL/min, and diabetic retinopathy, is encouraged for nephroprotection. However, Patients with less-advanced CKD, i.e., stages 1-2, do not receive any benefit. Regardless of the severity of CKD, SGLT-2 inhibitors remain first-line therapy.

Although Finerenone improves cardiovascular outcomes and reduces CKD progression for patients, it is still unknown if there are any additive cardioprotective effects if used with SGLT2 inhibitors and/or GLP-1 receptor agonists.

Some Closing Pearls: 

The use of SGLT2 inhibitors in patients with eGFR > 25 decreased from 30 previously.

If the A1c goal is not being met, combination therapy of insulin with a GLP receptor agonist can be considered, as this combination treatment has been shown to increase the efficacy and duration of insulin.

Overall, this new change could be very beneficial if accepted internationally. Though understandably, there could be some limitations to this guideline given the availability and cost of these medications, as well as their contraindication of use in specific populations such as pregnancy, ages >65 with concurrent risk factors for hypoglycemia or dehydration, and those with history of acute pancreatitis. 

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Conclusion: Now we conclude our episode number 114 “Diabetes care update.” Yvette explained that the ADA now recommends the use of SGLT2 inhibitors and GLP-1 agonists in any patient with type 2 diabetes with current or at high risk for cardiovascular disease, chronic kidney disease, or heart failure. Primary care physicians should become familiar with the dosing, cautions, side effects, and contraindications of these meds. Also, a newer medication for CKD in diabetes was mentioned: Finerenone. Diabetes treatment continues to evolve, and we hope this information is useful for you. 

This week we thank Hector Arreaza, Yvette Singh, and Fiona Axelsson. Audio edition by Adrianne Silva.

Even without trying, every night you go to bed a little wiser. Thanks for listening to Rio Bravo qWeek Podcast. We want to hear from you, send us an email at [email protected], or visit our website riobravofmrp.org/qweek. See you next week! 

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1. Lacanlale, Jana K et al. “Notable Revisions in Diabetes Treatment According to ADA Guidelines.” Pharmacy Times, 26 Mar. 2021, https://www.pharmacytimes.com/view/notable-revisions-in-diabetes-treatment-according-to-ada-guidelines.
2. Li, Sheyu, et al. “SGLT-2 inhibitors or GLP-1 receptor agonists for adults with type 2 diabetes: a clinical practice guideline.” British Medical Journal 2021; 373:n1091. doi:10.1136/BMJ.n1091
3. Royalty-free music used for this episode: BUrn Flow by Gushito, downloaded on September 22, 2022, from https://www.videvo.net/royalty-free-music-track/burn-flow/1008877/

Even without trying, every night you go to bed a little wiser. Thanks for listening to Rio Bravo qWeek Podcast. We want to hear from you, send us an email at [email protected], or visit our website riobravofmrp.org/qweek. See you next week!

Episode 112: Statins in Primary Care

Dr. Tiwana explains the use of statins for the primary prevention of cardiovascular disease.

Written by Ripandeep Tiwana, MD (Post-Doctoral Research Fellow at Cedar Sinai Medical Center – Heart Institute). Edition of text and comments by Hector Arreaza, MD.

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You are listening to Rio Bravo qWeek Podcast, your weekly dose of knowledge brought to you by the Rio Bravo Family Medicine Residency Program from Bakersfield, California, a UCLA-affiliated program sponsored by Clinica Sierra Vista, Let Us Be Your Healthcare Home. This podcast was created for educational purposes only. Visit your primary care provider for additional medical advice.

Definition.

Statins commonly referred to as lipid-lowering medications, are important in primary care as they serve multiple long-term benefits than just lipid lowering alone. They are HMG-CoA reductase inhibitors. As a refresher, this is the rate-controlling enzyme of the metabolic pathway that produces cholesterol. This enzyme is more active at night, so statins are recommended to be taken at bedtime instead of during the day. Statins are most effective at lowering LDL cholesterol. However, they also help lower triglycerides and raise HDL cholesterol.

Statins are not limited to just patients with hyperlipidemia. They reduce illness and mortality in those who have diabetes, have a history of cardiovascular disease (including heart attack, stroke, peripheral arterial disease), or are simply at high risk for cardiovascular disease. Statins are used for primary and secondary prevention.

Types of statins.

How do we determine which statin our patients need?

First, we need to know that not all statins are created equal. They vary by intensity and potency thus, and they are categorized as either low, moderate, or high intensity.

Several statins are available for use in the United States. They include Atorvastatin (Lipitor), Fluvastatin (Lescol XL), Lovastatin (Altoprev), Pitavastatin (Livalo, Zypitamag), Pravastatin (Pravachol), Rosuvastatin (Crestor, Ezallor), Simvastatin (Zocor)

Commonly used in clinics: Simvastatin, Atorvastatin, and Rosuvastatin.

Statin Dosing and ACC/AHA Classification of Intensity

                                  Low-intensity                                   Moderate-intensity                                     High-intensity

Atorvastatin              NA 1                                                          10 to 20 mg                                                   40 to 80 mg

Fluvastatin                20 to 40 mg                                          40 mg 2×/day; XL 80 mg                                NA

Lovastatin                 20 mg                                                       40 mg                                                                         NA

Pitavastatin               1 mg                                                          2 to 4 mg                                                                   NA

Rosuvastatin             NA                                                            5 to 10 mg                                                          20 to 40 mg

Simvastatin                10 mg                                                      20 to 40 mg                                                             NA

Of note, atorvastatin and rosuvastatin are only for moderate or high-intensity use, and do not use simvastatin 80 mg.

Identifying patients at risk.

How do we determine who needs statin therapy?

Once we become familiar with the different statins, we must figure out which intensity is advised for our patient. Recommendations for statin therapy are based on guidelines from The U.S. Preventive Services Task Force (USPSTF), American Diabetes Association (ADA), and the American College of Cardiology/American Heart Association (ACC/AHA) which recommend utilizing the ASCVD risk calculator in those patients who do not already have established cardiovascular disease.

ASCVD stands for atherosclerotic cardiovascular disease, defined as coronary heart disease, cerebrovascular disease, or peripheral arterial disease presumed to be of atherosclerotic origin. ASCVD remains a leading cause of morbidity and mortality in the United States, especially in individuals with diabetes.

The ASCVD risk score determines a patient’s 10-year risk of cardiovascular complications, such as a myocardial infarction or stroke. This risk estimate considers age, sex, race, cholesterol levels, use of blood pressure medication, diabetic status, and smoking status. Regarding age, this calculator only applies to the age range of 40-79 as there is insufficient data to predict risk outside this age group.

There are several online and mobile applications available to calculate this score. Once calculated it gives a recommendation for which intensity statin to use. However, as this is a recommendation, it is essential to use your own clinical judgment to decide what is best for your individual patient. Please refer to the above table as a reference for which statin and dose you may consider using.

Keeping the above calculator in mind, additional statin guidelines are recommended by the ACC:

• Patients ages 20-75 years and LDL-C ≥190 mg/dl use high-intensity statin without risk assessment. (You do not need the calculator.)
• People with type 2 diabetes and aged 40-75 years use moderate-intensity statins, and risk estimate to consider high-intensity statins. (It means moderate for all diabetics older than 40, high for some.)
• Age >75 years, clinical assessment, and risk discussion.
•  Age 40-75 years and LDL-C ≥70 mg/dl and <190 mg/dl without diabetes, use the risk estimator that best fits the patient to decide the intensity of statin.
  •  Risk 5% to <7.5% (borderline risk). Risk discussion: if risk-enhancing factors are present, discuss moderate-intensity statin and consider coronary calcium score in select cases.
  • Risk ≥7.5-20% (intermediate risk). Risk discussion: use moderate-intensity statins and increase to high-intensity with risk enhancers.
  • Risk ≥20% (high risk). Risk discussion to initiate high-intensity statin to reduce LDL-C by ≥50%.

Combining the ASCVD score with the coronary artery calcium score can help you better stratify at-risk patients.

USPSTF Update, August 22, 2022:

Grade B - Adults 40-75 years with >=1 cardiovascular risk factor (dyslipidemia, diabetes, hypertension, or smoking) and an estimated 10-year ASCVD risk > 10%. Grade B recommendation: prescribe a statin for the primary prevention of CVD.

Grade C – 40-75 years with >= 1 cardiovascular risk factor AND estimated 10-year ASCVD risk 7.5-10%. Grade C recommendation: selectively offer a statin for the primary prevention of CVD. The likelihood of benefit is smaller in this group than in persons with a 10-year risk of 10% or greater.

Grade I - The USPSTF found insufficient evidence to recommend for or against initiating a statin for the primary prevention of CVD events and mortality in adults 76 years or older.

The USPSTF is also very clear regarding the intensity of statin therapy. They explained that there is limited data directly comparing the effects of different statin intensities on health outcomes. Most of the trials they reviewed used moderate-intensity statin therapy. They conclude that moderate-intensity statin therapy seems reasonable for most persons' primary prevention of CVD.

The USPSTF has a broader recommendation, whereas the ACC guidelines are more detailed and individualized and provide guidance on the recommended intensity of statin therapy.

Labs needed.

Establish baseline labs for serum creatinine, LFTs, and CK only if there is a myopathy risk. Routine monitoring of LFTs, serum creatinine, and CK is unnecessary; only check if clinically indicated.

A lipid panel should be checked in 6-8 weeks, and the patient should monitor themselves for any side effects, including myalgias. If LDL-C reduction is adequate (≥30% reduction with intermediate statins and 50% with high-intensity statins), regular interval monitoring of risk factors and compliance with statin therapy is necessary to sustain long-term benefit.

Side effects and contraindications.

Some common side effects include URI-like symptoms, headache, UTI, and diarrhea. Some patients are very hesitant to take any medications. Warning about side effects may decrease compliance. Major  contraindications for statin therapy include active liver disease, muscle disorders, pregnancy, and breastfeeding.

Special considerations.

Chronic kidney disease: The preferred statins for CKD with severe renal impairment are atorvastatin and fluvastatin because they do not require dose adjustment. Pravastatin would be a second choice.

Chronic liver disease: Statins are contraindicated in patients with decompensated cirrhosis or acute liver failure. Abstinence from alcohol is critical in patients with chronic liver disease who are taking statins. Pravastatin and rosuvastatin are the preferred agents. Check lipid levels to determine if LDL-C reduction is accomplished with no changes in aminotransferases. You may consider stopping, increasing dose, or changing statin as you discuss the risks vs. benefits with your patient.

Conclusion: Simply put, if a patient has an LDL of greater than 190, is a diabetic, has an established history of cardiovascular disease, or is at risk for it, then the patient should ideally be taking a statin unless there is a contraindication, allergy, or other special circumstance that limits him/her from doing so. If you have patients that apply to any of the above scenarios and are not already on a statin, determine their risk, and consider starting them on a statin “stat” to reduce morbidity and mortality. On the other hand, be mindful of overprescribing. Do not prescribe statins to patients who do not meet the above criteria.

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Now we conclude our episode number 113, “Statins in Primary Care.” Statins are powerful medications for the prevention of cardiovascular disease. Do not forget to recommend non-pharmacologic measures such as healthy eating and physical activity, but let’s also consider adding a statin to patients who are at moderate to high risk for cardiovascular disease.

This week we thank Hector Arreaza and Ripandeep Tiwana. Audio by Adrianne Silva.

Even without trying, every night, you go to bed a little wiser. Thanks for listening to Rio Bravo qWeek Podcast. We want to hear from you; send us an email at [email protected], or visit our website riobravofmrp.org/qweek. See you next week!

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References:

1. Statins, U.S. Food & Drug Administration, 2014, December 16, fda.gov, https://www.fda.gov/drugs/information-drug-class/statins, accessed September 14, 2022.

2. Chou R, Cantor A, Dana T, et al. Statin Use for the Primary Prevention of Cardiovascular Disease in Adults: A Systematic Review for the U.S. Preventive Services Task Force [Internet]. Rockville (MD): Agency for Healthcare Research and Quality (US); 2022 Aug. (Evidence Synthesis, No. 219.) Available from: https://www.ncbi.nlm.nih.gov/books/NBK583661/

3. 2019 ACC/AHA Guideline on the Primary Prevention of Cardiovascular Disease: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. J Am Coll Cardiol 2019; March 17. https://www.acc.org/latest-in-cardiology/ten-points-to-remember/2019/03/07/16/00/2019-acc-aha-guideline-on-primary-prevention-gl-prevention.

4. ASCVD Risk Estimator Plus, published by the American College of Cardiology, https://tools.acc.org/ascvd-risk-estimator-plus/#!/calculate/estimate/, accessed September 14, 2022.

5. Statin Use for the Primary Prevention of Cardiovascular Disease in Adults: Preventive Medication, U.S. Preventive Services Task Force, Final Recommendation Statement, 2022, August 23. https://uspreventiveservicestaskforce.org/uspstf/recommendation/statin-use-in-adults-preventive-medication

6.  Videvo. “Distinction.” Https://Www.videvo.net/Royalty-Free-Music-Track/Distinction/227882/, Https://Www.videvo.net/, https://www.videvo.net/royalty-free-music-track/distinction/227882/. Accessed 26 Sept. 2022.

Even without trying, every night you go to bed a little wiser. Thanks for listening to Rio Bravo qWeek Podcast. We want to hear from you, send us an email at [email protected], or visit our website riobravofmrp.org/qweek. See you next week!

Introduction: False positive RPR. 
By Hector Arreaza, MD. Read by Alinor Mezinord, MS III, Ross University School of Medicine.  

Today we will talk about syphilis. Significant research has been done to determine the origin of this ancient infection. Some experts support that syphilis originated in the New World (the Americas) because the first cases in Europe were reported after the Christopher Columbus crew returned from their expeditions. On the other hand, some people defend the idea of the origin of syphilis in the Old World. 

Whatever its origin, syphilis is still affecting thousands of people worldwide. According to the World Health Organization, “syphilis in pregnancy is the second leading cause of stillbirth globally and also results in prematurity, low birth weight, neonatal death, and infections in newborns.”[1] The cases in the US are not as high as in other countries, but certain areas have cases higher than the national or state average. Such is the case in Kern County. Our incidence of syphilis is higher than the national average.

That’s why it is important to screen for this disease. RPR is the most common test to screen for syphilis; however, it may not be completely accurate. RPR is a non-treponemal test that can cause false positive results. On December 20, 2021, the CDC released a letter announcing an FDA alert regarding a high RPR false positive rate when done with Bio-Rad Laboratories BioPlex 2200 Syphilis Total & RPR kit. You may not know which kit was used for the test, but you need to know what to do with a positive RPR. Some conditions associated with false positive RPR include COVID-19 vaccines, tuberculosis, endocarditis, rickettsial disease, recent immunizations (smallpox), and pregnancy. 

In case of RPR positive, you need to confirm syphilis with a treponemal test, which will be more reliable regardless of the possibility of a false positive RPR. We still need to screen because syphilis continues to increase in our nation. I hope you enjoy this episode.

You are listening to Rio Bravo qWeek Podcast, your weekly dose of knowledge brought to you by the Rio Bravo Family Medicine Residency Program from Bakersfield, California, a UCLA-affiliated program sponsored by Clinica Sierra Vista, Let Us Be Your Healthcare Home. This podcast was created for educational purposes only. Visit your primary care provider for additional medical advice.

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Latent Syphilis. 
By Carol Avila, MD. Comments by Hector Arreaza, MD.

Dr. Avila: I had the amazing opportunity to do inpatient pediatrics during my first rotation at a local hospital, and I often treated patients with neonatal syphilis. I was curious to know what is happening in this area (Bakersfield) that made syphilis (seems to me) a very frequent diagnosis of admission in peds, especially because newborns are impacted by a preventable disease.

Epidemiology:

The latest update available on the CDC website is the 2020 Surveillance Report of Nationally Notifiable STDs which showed:

-In 2020, the national rate of syphilis was about 40 per 100,000 population (all stages).

-The rate of national congenital syphilis was about 57 cases per 100,000 live births.

-During that year, California was ranked #7 for primary and secondary syphilis (P&S), with a 19.5 per 100,000 population. Nevada was the number #1 state.

Local data:

In 2018 data, the Kern County Public Health Services Department reported:

-A total of 1,520 cases of syphilis (all stages) were diagnosed during that year, about 4 cases/day. It is important to mention that there was a spike in the number of cases of syphilis by 86% compared to the prior year, 2017.

-In 2020, 250 cases of congenital syphilis per 100,000 live births were reported in Kern County. Significantly higher than the national average (mentioned above, 40 cases per 100,000 residents). 

-For primary and secondary syphilis, Kern County was 62% higher than the state average, with almost 35 per 100,000 population, and was ranked #6 in the state of California. 

-San Francisco was ranked #1.

-Bottomline: The rate of syphilis and congenital syphilis in Kern County is higher than the state and national average.

Definition:

Syphilis is a systemic bacterial infection caused by the gram-negative spirochete Treponema pallidum.

Transmission:

Syphilis is well known as a sexually transmitted disease; however, while many cases happen due to sexual activity, there are a few other ways that syphilis can also be spread.

-It can be transmitted during pregnancy, resulting in congenital syphilis.

-Also, passing on syphilis via blood transfusions was very common but is now rare thanks to blood supply screening.

-Syphilis transmission is also possible through an organ donor, which nowadays is very rare.

-Before healthcare providers were wearing gloves as a standard precaution, it was common for syphilis lesions to appear on their fingers and noses.

-It can also be transmitted through close and repetitive contact with mucosal or skin lesions of people with active syphilis.

Classification:

-Syphilis is divided into stages based on clinical findings. Primary, secondary, and tertiary.

-The latent phase occurs between secondary and tertiary. 

-Patients pass through secondary syphilis and may not realize it.

-The most contagious stages are primary and secondary, and syphilis could still be contagious in the early latent phase.

-Easy classification: Early (primary, secondary, early latent); Late (tertiary and late latent); Neurosyphilis (which occurs any time).

Primary syphilis:

-It usually happens 3 weeks after the initial contact with the spirochete, but it can also be seen after 90 days. The bacteria will destroy the local tissue when we see the syphilitic chancre, a painless, well-demarcated lesion with firm, indurated margins. It might go unnoticed; without treatment, the bacteria will spread to the bloodstream, and the infection will progress to the secondary stage.

Secondary syphilis:

-In the secondary stage, the patient can have a wide variety of signs and symptoms. General constitutional symptoms are common; however, it is characterized by a body-wide rash, prominent in palms and soles. This rash can be macular, papular, or pustular; patients can also develop patches in oral mucosa and tongue, as well as wart-like sores called condylomata lata.

Tertiary syphilis:

-In the pre-antibiotic era, 15 to 30 years after the initial infection, patients could develop any of the three forms of tertiary syphilis. 

-Cardiovascular syphilis involves the ascending thoracic aorta. Patients may present with aortic

aneurysm or left heart failure. 

-Gummatous syphilis is uncommon, but it is especially important in patients coinfected with HIV. Gummas can appear in the skin, bones, or internal organs. 

-Central Nervous System syphilis presents with general paresis, tabes dorsalis, meningitis, hearing and vision loss, and dementia.

Latent syphilis:

-It occurs when the patient has positive serology for T. pallidum, but the patient is asymptomatic. 

-Latent syphilis can also be divided into early latent (when the primary infection occurred within the previous 12 months); and late latent syphilis (when the primary stage happened more than 12 months ago.)

-Differentiating early and late latent syphilis is vital because the treatment will differ.

Congenital syphilis:

-The infection occurs during pregnancy.

-It can cause miscarriage, stillbirth, or birth defects like nasal cartilage destruction, and frontal

bossing, among others.

Screening and Diagnostic Testing:

-The USPSTF recommends screening asymptomatic, nonpregnant adults and adolescents at increased risk for syphilis infection (Grade A).

-The USPSTF recommends early screening for syphilis infection in all pregnant women. as early as possible when they first present to care. 

-Repeat screening: The CDC and joint guidelines from the American Academy of Pediatrics (AAP) and the ACOG endorse repeat screening, especially for women at risk, early in the third trimester (at about 28 weeks of gestation) and again at delivery.

-High-risk patients include men who have sex with men (MSM) and men and women living with HIV. 

-Also, people with a history of incarceration, a history of commercial sex work, certain racial/ethnic groups (African Americans and Hispanics), and being a male younger than 29 years.

How to screen: 

-Initial screening should be done with a nontreponemal test (RPR or VDRL); if positive, a treponemal test (TP-PA or FTA-ABS) would be the next step. 

-Nontreponemal tests can be positive in patients with preexisting conditions, e.g., collagen vascular diseases, pregnancy, malignancy, tuberculosis, etc.

-The USPSTF also refers to the reverse sequence screening algorithm, where we perform a treponemal test first in those patients that could be missed after a nontreponemal test, for example, people who are homeless, also in nontraditional and nonclinical settings. 

-A treponemal test will be followed by a nontreponemal test, however, there is no evidence of the accuracy of this screening algorithm, so it is an open field for researchers.

-Remember that most patients will have positive antibodies for life, irrespective of treatment or disease stage.

Treatment:

-One word: Penicillin is the treatment of choice.

-Additionally, every patient diagnosed with primary and secondary syphilis should be tested for HIV and other sexually transmitted diseases at the time of diagnosis.

Primary, secondary, and early latent syphilis: Benzathine penicillin G, 2.4-million-unit IM, in a single dose.

-Children/Infant age > 1 month of age: Benzathine PCN G, 50,000 units/kg body weight IM up to 2.4 million-unit in a single dose. 

-Children > 1 month with P&S syphilis should be evaluated for sexual abuse.

Arreaza:

-Pregnancy: Treatment is still penicillin G, if there is a penicillin allergy, desensitization should be done in a controlled setting.

-In non-pregnant with PCN allergy- alternatives are doxycycline 100 mg BID x14 days or Ceftriaxone 1 G daily IM or IV for 10-14 days.

-For P&S syphilis: clinical and serological evaluation should be done at 6 to 12 months after treatment.

Late latent syphilis and tertiary: Benzathine penicillin G, 7.2-million-unit total, administered as 2.4 million units IM each week x3 doses. (2.4 x3 = 7.2). A good strategy is to assume all latent syphilis are late latent. 

-Follow up with a quantitative nontreponemal serologic test at 6, 12, and 24 months, and compare this

titer with the initial titer at the time of diagnosis.

-Special recommendation: Check RPR titer the same day you give the first dose of penicillin.

Neurosyphilis: 

-CSF examination is recommended if neurologic findings are present.

-If neurosyphilis is confirmed, it will require aqueous penicillin G, 3-4 million units IV every 4 hours for 10-14 days. Alternative ceftriaxone 2 G IV daily x14 days. Get guidance from an ID specialist. We will continue talking about syphilis in another episode, which was an excellent introduction.

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Conclusion: Now we conclude episode number 112, “Syphilis Basics.” Dr. Avila raised our awareness of syphilis in our community and the importance of screening all adolescents and adults at risk of infection, and especially ALL pregnant persons, during their first prenatal visit or as early as possible. Timely treatment with penicillin is important to prevent late complications of syphilis and especially to prevent the devastating consequences of congenital syphilis. This week we thank Hector Arreaza, Carol Avila, and Alinor Mezinord. Audio edition by Adrianne Silva.

Even without trying, every night, you go to bed a little wiser. Thanks for listening to Rio Bravo qWeek Podcast. We want to hear from you; send us an email at [email protected], or visit our website riobravofmrp.org/qweek. See you next week!

References:

1. Data on syphilis, The Global Health Observatory, World Health Organization, who.int, https://www.who.int/data/gho/data/themes/topics/topic-details/GHO/data-on-syphilis,  accessed September 14, 2022.

2. Center for Disease Control and Prevention. (2022, April 11). National Overview of STD.  https://www.cdc.gov/std/statistics/2020/overview.htm#CongenitalSyphilis.

3. STDs in Kern County, Kern County Public Health Services Department, STDS in Kern County 2018, https://kernpublichealth.com/wp-content/uploads/STDs-in-Kern-County-2018-slide-set-comparison.pdf, downloaded on Sep 12, 2022.

4. Center for Disease Control and Prevention. (2022, April 4). Reported Cases and Rates of Reported Cases by State, Ranked by Rates, United States, 2020. https://www.cdc.gov/std/statistics/2020/tables/13.htm

5. Morgen, Sam, Reported cases of STDs in Kern County dropped in 2020, but decrease could be misleading, The Bakersfield Californian, Apr 17, 2022, bakersfield.com, https://www.bakersfield.com/news/reported-cases-of-stds-in-kern-county-dropped-in-2020-but-decrease-could-be-misleading/article_6e7d8d36-bd18-11ec-a98f-7f247bc2517e.html.

6. U.S. Preventive Services Task Force. (2016, June 7). Syphilis Infection in Nonpregnant Adults and Adolescents: Screening. https://www.uspreventiveservicestaskforce.org/uspstf/recommendation/syphilis-infection-in-nonpregnant-adults-and-adolescents.

7. Center For Disease Control And Prevention. (2022, July 21). Sexually Transmitted Infections Treatment Guidelines. https://www.cdc.gov/std/treatment-guidelines/syphilis.htm.

8. Calonge N; U.S. Preventive Services Task Force. Screening for syphilis infection: recommendation statement. Ann Fam Med. 2004 Jul-Aug;2(4):362-5. doi: 10.1370/afm.215. Erratum in: Ann Fam Med. 2004 Sep-Oct;2(5):517. PMID: 15335137; PMCID: PMC1466700. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1466700/.

9. Royalty-free music used for this episode: Good Vibes Alt Mix by Videvo, downloaded on May 06, 2022 from https://www.videvo.net/royalty-free-music-track/good-vibes-alt-mix/1017292/

Even without trying, every night you go to bed a little wiser. Thanks for listening to Rio Bravo qWeek Podcast. We want to hear from you, send us an email at [email protected], or visit our website riobravofmrp.org/qweek. See you next week!