Rio Bravo qWeek

Episode 72: Depression in Adolescents.  

COVID-19 vaccine updates including booster shots and mix and match options. Depression in adolescents is discussed by Virginia Bustamante, Charizza Besmanos, and Hector Arreaza. 

Introduction: COVID Vaccines Update October 2021
Written by Hector Arreaza, MD. Participation: Lillian Petersen, RN, and Nathan Heathcoat, MS3.  

The FDA granted emergency use authorization for a booster shot with the Pfizer/BioNtech COVID-19 vaccine in September 2020.

On October 20, 2021, the FDA also granted emergency use authorization for a booster shot with the Moderna AND Johnson & Johnson (also known as Janssen or J&J) COVID-19 vaccines. 

Pfizer/BioNtech: Brand name Comirnaty®. It has full FDA approval for patients who are 18 years and older for the prevention of COVID-19. The rest of the indications of this vaccine are under the Emergency Use Authorization (EUA). It is authorized for 12 years and older. Total of two doses, 21 days apart. Authorized for 3rd dose in immunocompromised patients (on active cancer treatment, organ transplant recipients, taking immunosuppressive or high dose corticosteroids, have moderate to severe immunodeficiency). 3rd dose is given at least 1 month after the second dose. It is authorized for a single booster shot in special populations (older than 65 years of age OR 18-64 years of age at high risk of severe COVID-19 or with frequent occupational exposure). The booster shot must be given 6 months after the primary series is complete.

Moderna: No brand name yet. All uses are under emergency use authorization. It is authorized for 18 years and older for the prevention of COVID-19. Give a total of two doses, 4 weeks apart. A third dose is authorized to be given 1 month after the second dose. Patients who can receive a third dose include patients on active cancer treatment, organ transplant recipients, taking immunosuppressive or high dose corticosteroids, or have an immunodeficiency. It is authorized for a single booster shot 6 months after completing primary series. The booster shot of Moderna should be half dose. People who may receive a booster shot are those who are older than 65 years of age OR 18-64 years of age at high risk of severe COVID-19 or with frequent occupational exposure.

Johnson & Johnson (Janssen): No brand name yet. Authorized as a single dose vaccine. Authorized for a single booster shot 2 months after the first dose. 

Mix and Match Approval: The FDA authorized on October 20, 2021, heterologous booster dose for currently approved or authorized COVID-19 vaccines. You can give a booster shot with a different vaccine than the one you received primarily. For example, a patient who received J&J vaccine may receive a booster shot with Pfizer or Moderna 2 months later. Another example, a patient received primary series of Pfizer vaccine, may receive a booster shot with Moderna, Pfizer or J&J 6 months after completing primary series. Booster shots are authorized, again, for patients who are 65 years and older, 18-64 years of age at high-risk for severe COVID-19 or with frequent occupational exposure.

The vaccination of children 5-11 years old is still under discussion, more updates coming soon.

This is Rio Bravo qWeek, your weekly dose of knowledge brought to you by the Rio Bravo Family Medicine Residency Program from Bakersfield, California. Our program is affiliated with UCLA, and it’s sponsored by Clinica Sierra Vista, Let Us Be Your Healthcare Home. 

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Depression in Adolescents. 

By Virginia Bustamante, MS4; Charizza Besmanos, MS4; and Hector Arreaza, MD.  

Vicky: We will talk about adolescence and depression today. I was reading a piece on the Impact of COVID-19 Pandemic on Adolescent Mental Health on Psychiatry Advisor by Tori Rodriguez. She is a licensed professional counselor with a master’s in arts in counseling psychology. 

This article really got me thinking, how prevalent is depression in adolescents? Even before COVID-19. I read the article and I wasn't even aware of the numbers. So, I decided to do some research on the topic. 

Charizza: When you brought up the topic for discussion, I asked myself how much do I even know? I found that the CDC reported that “more than 1 in 3 high school students had experienced persistent feelings of sadness or hopelessness in 2019.” This was a 40% increase since 2009. 

It also said that, “in 2019 about 1 in 6 youth reported making a suicide plan in in the past year. That was a 44% increase since 2009.” 44% increase! That is almost unbelievable. Now I’m asking myself what is causing such a drastic increase.

Vicky: When I read Rodriguez’s piece it really got me thinking. What is or are there even known causes linked to this huge increase?

Charizza: Are adolescents more open to talk about mental illness? Or are there other factors affecting their mental illness? For example, increasing social media presence or other home/ social pressures. 

Vicky: Actually, that may be partially why. The U.S. News and World Report wrote a piece that highlighted the possible contributing factors that have led to this increase. They stated that data hasn’t really shown a conclusive answer but there are some common themes that have emerged. And I’d like to spend much of this podcast really going into those themes and discussing them. 

The U.S. News and World Report listed five common themes. Theme one, what they called “a modern-day diagnosis” - where they reference a John Hopkins Health Review which explained that adolescent depression is somewhat of a new diagnosis. 

Charizza: Up until about the 1980’s mental health professionals were reluctant to diagnose adolescents with a mood disorder. Because their brains were still developing, they thought it was not appropriate to diagnose someone so young with, for example depression. 

Vicky: Yes exactly, so the current thought is, that perhaps this change of thinking has played a part in the increasing numbers in the form of increased reporting and/or documentation. 

The second theme they listed was “hyper-connected & overstimulated.” This stems from how our world is today. Where electronic devices and social media are a big part of young people’s lives. The idea that they have a life in the real world and the virtual world. 

Charizza:  I read a study on Teens, Social Media and Technology, a Pew Research Center study, that more than 95% of teenagers have access to a smartphone and 45% of them described themselves as being online “almost constantly.”  

Vicky: To think, how does this affect the way they see themselves? For maybe a lot of us listening right now we’ve been on social media. That could be Facebook, Instagram, Tik-Tok, and going way back Myspace. We know that social media can be an amazing place to share our lives but can also be filled with a lot of criticism.

Arreaza: Have you heard of “FOMO”? It’s “Fear of Missing Out”. It’s a condition that can cause severe anxiety because others are having fun, or you missed a particular event, memorable experience, or an opportunity to connect with someone famous, or an online investment. People with FOMO need to stay always connected. 

Vicky: The Journal of Abnormal Psychology explained that the spike in depression and suicidal tendencies may be connected to social media among young people. They went on to describe how it's not uncommon for young people to measure their self-worth based on the likes. I've been there. Questioning myself whether to post or not post a picture based on whether it's “Instagram worthy”? Will it get enough likes to be posted? Rather than sharing moments of my life with friends and family as the platform was intended to. 

Charizza: It’s not something I’m proud of but I’ve gotten sucked into the fake reality of online. That's why I reduced my social media presence. 

Vicky: Was there a specific reason or situation that led to that?

Charizza: I just felt like that it was taking more energy than it was meant for. And honestly I’ve felt happier since not really using my Facebook anymore. 

Vicky: If that makes you happier, I support it. I mean I might consider it myself. 

Arreaza: Yes, a social media “fasting” may be beneficial for some people. 

Vicky: For the third theme, the article referred to what they called “uncertain times.”

Charizza: What does that even mean?

Vicky: Each generation is influenced and shaped, in a positive or negative way, by the events happening at that time in history. And sadly, today’s young people have grown up in a post-9-1-1 world, mass terrorist attacks, and shootings whether that be high schools, malls, and even churches. All these events mean that young people may know the fear of terrorism. A sense of security has been taken from them by these awful and cowardly attacks of others. 

Charizza: I had a friend who was afraid to go to the movies after the 2012 Aurora Colorado shooting. For a long time, every time she went, she couldn’t sit there and enjoy the movie. She kept turning around looking at the door every time it opened. Afraid something would happen. So, thinking of that and thinking that others may be going through similar and even more difficult times, I can completely understand this contributing depression among young people. 

Vicky: This fear and stress appears to be contributing to the increase in depression. The fourth theme was “not enough sleep.” The Nation Sleep Foundations recommends teens get 8.5 to 9.5 hours and instead teens get around 7 hours. When I am well rested, I perform my best. My energy, memory and overall mood is better. But with school, work, and everything else it’s hard sometimes to get the hours I need. I mean I don't know about you Charizza, but I can work on getting more sleep. 

Charizza: Sadly, I struggle with it too. But for adolescents where they're still developing and undergoing different physiological changes those hours are especially important. The Sleep Foundation stressed the importance of sleep for teens. 

They talk about how it helps with physical development - with all the changes they are undergoing, academic achievement - by promoting attention, improving memory (like you brought up), and definitely helps with emotional health. The website states that mental health disorders for example anxiety, depression, and even bipolar disorder have been linked to poor sleep. They even stated that sleep deprivation in teenagers can increase the risk for suicide.

Arreaza: A poor sleep also can lead to obesity in adolescents and adults. Something we should remember is also the timing of sleep for adolescents. The sleep pattern changes over the lifetime of people, and it’s not only in duration, but also the time they sleep. Normally, a teenager tends to go to bed late and wake up late. For this reason, high school schedules are being changed in California to start at 8:00 AM. 

Vicky: It sounds like improving sleep in adolescents can be a great way of preventing mental health disorders or even reducing their symptoms. The last and fifth theme discussed in The U.S. News and World Report as a possible contributing factor to the increase in adolescent depression is a “lack of community.” 

This goes back to the world we live in today. We live with this - what the article quotes as - “go-go mentality” and the community we would have previously built or created around us have gotten smaller. So as they quoted “our face-to-face connections” have decreased.

Charizza: Is there anything they suggest?

Vicky: The U.S. Preventive Services Task Force recommends primary caregivers screen adolescents 12-18 for depression. But this doesn't always happen. They suggested that identifying adolescent depression should NOT be something that only falls on the medical provider but something we should ALL be responsible for. We can do this by building healthy and trusting relationships with our young people. Hopefully also rebuild this sense of community. 

Today we highlighted some themes that are possibly related to the increase in adolescent depression. Those were: the idea of a modern-day diagnosis, second being hyper-connected & overstimulated, third the uncertain times we live in, fourth not enough sleep, and lastly the sense of a lack of community. 

Charizza: We hope you guys all really enjoyed listening. And remember if you are or know someone struggling with depression and/or suicide thoughts reach out to someone. Let someone know how you are doing. Tell a teacher, adult, someone.

Vicky: If you for whatever reason don't feel comfortable doing that or feel you may not have someone to reach out to and are in danger of hurting yourself or others please call 911. 

Charizza: There are also national suicide prevention hotlines. That is 1-800-SUICIDE and that’s 1-800-SUICIDE. There is also 1-800-273-TALK, again that's 1-800-273-TALK

Vicky: There is also the Mary K Shell Mental Health Center with a walk-in crisis center. They are located here in Bakersfield on College and Mt. Vernon. They are actually in the same parking lot as Kern Medical Center. Their number is 661- 868-8123.

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Conclusion: Now we conclude our episode number 72 “Depression in Adolescents.” Our adolescent patients are a special population, so special that you can even do a fellowship after finishing your residency. Our adolescents are under a lot of pressure, especially during this era of social media. Remember to screen for depression and start treatment right away with behavioral therapy and medications as needed or refer your depressed patients to a psychiatrist to start treatment promptly. Do not forget to assess risk of suicide and act fast to prevent suicide in your patients. Even without trying, every night you go to bed being a little wiser.

Thanks for listening to Rio Bravo qWeek. If you have any feedback about this podcast, contact us by email [email protected], or visit our website riobravofmrp.org/qweek. This podcast was created with educational purposes only. Visit your primary care physician for additional medical advice. This week we thank Hector Arreaza, Lillian Petersen, Nathan Heathcoat, Virginia Bustamante, and Charizza Besmanos. Audio edition: Suraj Amrutia. See you next week! 

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References:

Mental Health, Adolescent and School Health, Centers for Disease Control and Prevention, CDC.gov,  https://www.cdc.gov/healthyyouth/mental-health/index.htm, accessed on September 20, 2021. 

Lohmann, Rachel Cassada, What's Driving the Rise in Teen Depression?, US News, April 22, 2019. https://health.usnews.com/wellness/for-parents/articles/2019-04-22/teen-depression-is-on-the-rise. 

Anderson, Monica and Jingjing Jiang, Teens, Social Media and Technology 2018, Pew Research Center, May 31, 2018. https://www.pewresearch.org/internet/2018/05/31/teens-social-media-technology-2018/. 

Rodriguez, Tori, Impact of the COVID-19 Pandemic on Adolescent Mental Health, Psychiatry Advisor, April 30, 2021, https://www.psychiatryadvisor.com/home/topics/child-adolescent-psychiatry/adolescent-mental-health-issues-are-further-exacerbated-by-the-covid-19-pandemic/. 

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 71: Metabolic Syndrome. 

Dr Yomi defines metabolic syndrome and describes the basic principles of management. Nathan gives updates about aspirin use in primary prevention of cardiovascular disease.

Introduction: Aspirin Update.  
By Nathan Heathcoat, MS3, Ross University School of Medicine.  

Arreaza (comment): This week I was checking the list of the top 10 countries where we have the highest number of listeners, and I’m happy to see the Kingdom of Spain as the number 2 country with the most listeners. Out top 1 country is the United States, we also have listeners in Canada, Mexico, the Netherlands, Brazil, Ireland, Australia, South Africa, Mexico, and England. I send my greetings to you wherever you are. I hope you all enjoy today’s episode, from wherever you are, and please send us an email to [email protected] if you have any feedback. We would like to hear from you.

Hello, my name is Nathan Heathcoat I am a 3rd year medical student at Ross University School of Medicine. I will be giving a quick update on aspirin. 

Aspirin has been examined quite a bit by the USPSTF recently. In episode 68, Doctors Arreaza and Civelli discussed the continued recommendations for the use of aspirin for the prevention of preeclampsia in high-risk patients. 

Now as of October 12, 2021, The USPSTF has been working on draft changes on how we utilize aspirin for the prevention of cardiovascular disease (CVD) events.

The previous guideline from 2016 gave aspirin use as CVD event prophylaxis a grade B (as in Bravo) recommendation in patients aged 50-59 who’s 10-year ASCVD risk was 10% or greater. Additionally, for those patients aged 60-69 with a 10-year risk of 10% or more, aspirin use is said to be an individual based approach and received a grade C recommendation. (1)

Now with these new draft recommendations, those patients aged 40-59, aspirin only adds marginal benefit. Its recommendation has been tentatively changed to grade C and its use should be an individual based approach. Most notably, for those patients aged 60-69, the USPSTF is suggesting that aspirin confers no net benefit for primary prevention of CVD, and they changed its recommendation to grade D as in delta. (2)

So going forward keep in mind that these practice guidelines are under draft review and the official recommendation should be finalized mid to late November 2021. 

This is Rio Bravo qWeek, your weekly dose of knowledge brought to you by the Rio Bravo Family Medicine Residency Program from Bakersfield, California. Our program is affiliated with UCLA, and it’s sponsored by Clinica Sierra Vista, Let Us Be Your Healthcare Home. 

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Metabolic Syndrome.    
By Timiiye Dawn Yomi, MD; and Hector Arreaza, MD.  

INTRODUCTION                                                                                                                                                            Obesity, especially abdominal obesity, is associated with an increase in insulin resistance which causes abnormal glucose and fatty acid utilization in peripheral muscles, among other consequences. 

Obesity can often result in type 2 diabetes. 

The hyperinsulinemia and hyperglycemia resulting from insulin resistance can result in vascular endothelial dysfunction, abnormal lipid profile, hypertension, and vascular inflammation and together, can increase the risk for developing ASCVD. 

A constellation of metabolic risk factors for type 2 diabetes and cardiovascular disease is what constitutes metabolic syndrome or insulin resistance syndrome.

What is a syndrome? It is a group of symptoms that are present together, or a condition characterized by a set of associated symptoms.

DEFINITION

The National cholesterol education program ATP III updated its definition of metabolic syndrome in 2005 and defined it as the presence of any 3 of the following 5 traits.

Abdominal obesity: waist circumference ≥ 102cm (40in) in men and 88 cm (35in) in females 

Serum triglycerides ≥150 mg/dl (1.7 mmol/L) or drug treatment for elevated triglycerides.

Serum high density lipoprotein (HDL) cholesterol < 40 mg/dl (1mmol/l) in males and < 50 mg/dl (1.3mmol/l) in females or drug treatment for low HDL cholesterol.

Blood pressure ≥ 130/85 mmHg or drug treatment for elevated blood pressure.

Fasting plasma glucose 100mg/dl or drug treatment for elevated blood glucose.

The International Diabetes Federation: 2009 – same criteria, except waist circumference has specific cut off points based on ethnicity and OGTT. 

Increased waist circumference with ethnic-specific cut off points (Look for table 2 in this handbook).

Serum triglycerides ≥150 mg/dl (1.7 mmol/L) or drug treatment for elevated triglycerides.

Serum high density lipoprotein cholesterol < 40 mg/dl (1mmol/l) in males and < 50 mg/dl (1.3mmol/l in Females or drug treatment for low HDL cholesterol.

Systolic blood pressure ≥ 130, diastolic blood pressure ≥85 or treatment for hypertension.

Fasting plasma glucose 100mg/dl (5.6 mmol/l) or previously diagnosed type 2 diabetes or oral glucose tolerance test which is recommended for patients with an elevated fasting plasma glucose.

As a side note, metabolic syndrome cannot be diagnosed in children <10 years but clinicians must be vigilant if waist circumference is ≥ 90th percentile for age

Risk factors

Weight is the most important risk factor: Increased body weight is a major risk factor in developing metabolic syndrome. In the National Health and Nutrition Examination Survey III, metabolic syndrome was present in 5 percent of those at normal weight, 22 percent of those with overweight, and 60 percent of those with obesity.

Other risk factors include age, race, postmenopausal status, smoking, low household incomes, high carbohydrate diet, no alcohol consumption, physical inactivity/poor cardiorespiratory fitness, soft drinks and sugar sweetened beverages, atypical antipsychotics– clozapine, and family history/genetics.

Clinical implication

A diagnosis of metabolic syndrome would help clinicians identify patients who are at increased risk for developing Type 2 DM and or CVD and as such helps to identify those needing aggressive lifestyle modification which focuses on weight loss and increased physical activity ultimately reducing the risk of developing Type 2 DM and CVD.  

It has become increasingly prevalent in our society. According to the 2001 Adults Treatment Panel III (ATP III) criteria, which evaluated about 8,800 adults in the US, who participated in the National Health and Nutrition Examination Survey (NHANES) from 1988-1994, 22% of participants met criteria for metabolic syndrome with an age dependent increase. 

Mexican Americans were found to have the highest age-adjusted prevalence of 31.9%, and prevalence was higher in females than males amongst the African and the Mexican Americans. 

Data from NHANES from1988 to 1994, 1999 to 2000 and from 2017 to 2018, revealed that obesity increased from 22.9 to 30.5 to 42.4 percent respectively in each studied period. The implication of this is an increase in the prevalence of metabolic syndrome and its attendant morbidities and mortality

The ASCVD score which assesses patient's 10-year risk for developing CVD, Framingham Risk Score and the Systematic Coronary Risk Score Evaluation Score are useful tools in targeting individuals needing medical intervention to help lower the blood pressure and cholesterol.

Management

In 2001, ATP 3 recommended two major therapeutic goals in patients with metabolic syndrome and these goals were reinforced by the National Institutes of Health (NIH) and American Heart Association (AHA) 

Treat underlying causes such as overweight/obesity and physical inactivity though aggressive lifestyle modification, weight lost and increase physical activity.

Treat CVD risk factors if they persist despite lifestyle modification.

Weight loss: This can be achieved through changes in eating habits (instead of “diet”), increased physical activity (instead of “exercise”), medications, behavioral therapy, or surgery. 

Examples of healthy eating to promote weight loss are the Mediterranean diet, the DASH diet, ketogenic diet, and intermittent fasting. If you would like to know more about the keto diet, listen to our episode 59, on The Keto diet. 

Exercise: The physical activity guidelines recommends that patients exercise daily minimum 30 minutes of moderate intensity exercise (150 minutes a week of brisk walking, for example) plus strengthening exercise twice a week. Exercise is important for health, even when it is not the best tool to lose weight.

Why are clinicians not diagnosing metabolic syndrome amongst patients?

The American Diabetes Association and the European Association for the Study of Diabetes published a joint statement raising questions about whether the components of metabolic syndrome, as defined above, warrant classification as a true "syndrome". Some arguments raised include:

Lack of clarity of definition

Multiple different phenotypes included within the syndrome

Not enough evidence for setting thresholds for the components of the syndrome.

Unclear pathogenesis.

Other risk factors for CVD that are not components of the syndrome, such as, inflammatory markers.

CVD risk associated with metabolic syndrome has not been shown to be greater than the sum of its individual components.

Whether patients will benefit from a diagnosis of metabolic syndrome with such uncertain characteristics remains a topic of debate. However, the consensus is to treat individual risk factors when present in patients with obesity and multiple risk factors, and to promote aggressive lifestyle modification with the focus on weight loss and increased physical activity.

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Conclusion: Now we conclude our episode number 71 “Metabolic Syndrome.” Think about metabolic syndrome in patients with enlarged abdomen, elevated glucose and triglycerides, low HDL, and high blood pressure. By identifying and treating these patients you may decrease mortality in your community. Even without trying, every night you go to bed being a little wiser.

Thanks for listening to Rio Bravo qWeek. If you have any feedback about this podcast, contact us by email [email protected], or visit our website riobravofmrp.org/qweek. This podcast was created with educational purposes only. Visit your primary care physician for additional medical advice. This week we thank Hector Arreaza, Timiiye Yomi, and Nathan Heathcoat. Audio edition: Suraj Amrutia. See you next week! 

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References:

Bibbins-Domingo, K. Aspirin Use for the Primary Prevention of Cardiovascular Disease and Colorectal Cancer: U.S. Preventive Services Task Force Recommendation Statement. Annals of Internal Medicine. 2016 Jun 16; 164(12): 836-845 https://doi.org/10.7326/M16-0577.

Guirguis-Blake, J. et al. Aspirin Use to Prevent Cardiovascular Disease and Colorectal Cancer: An Evidence Update for the U.S. Preventive Services Task Force. AHRQ Publication No. 21-05283-EF-1. 2021 Sep. Retrieved from https://www.uspreventiveservicestaskforce.org/uspstf/document/draft-evidence-review/aspirin-use-to-prevent-cardiovascular-disease-preventive-medication on October 12, 2021.

James BM. Metabolic syndrome (insulin resistance syndrome, syndrome X). In: Lisa K, ed. UpToDate. Waltham, Mass.: UpToDate, 2021. https://www.uptodate.com/contents/metabolic-syndrome-insulin-resistance-syndrome-or-syndrome. Accessed Aug 1, 2021.

The IDF consensus worldwide definition of the METABOLIC SYNDROME, International Diabetes Federation, published in 2006, last update July 29, 2020. PDF available for download: https://www.idf.org/e-library/consensus-statements/60-idfconsensus-worldwide-definitionof-the-metabolic-syndrome.html. 

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 70: HIV Prevention. 

Prevention is key in controlling HIV-AIDS. Listen to ways to prevent HIV, mainly by using condoms, PrEP and PEP.

Introduction: HIV and AIDS
By Robert Dunn, MS3.

Introduction: The Human Immunodeficiency Virus (HIV) is a retrovirus that is primarily transmitted via sex, needles or from mother to fetus. Once infected, the virus increases in its copies and decreases the individual’s CD4+ cell count, thus leading to an immunocompromised state known as Acquired Immune Deficiency Syndrome (AIDS). Once with AIDS, the patient is susceptible to opportunistic infections. 

Prevention from AIDS includes several options. Condoms for safe sex practices are the least invasive and most readily accessible option for all patients. Pre-exposure prophylaxis (PrEP) is also an option for men who have sex with men (MSM) and transgender women. If the patient is also exposed to HIV, post-exposure prophylaxis (PEP) may also be an option to prevent infection but must be administer ideally 1-2 hours after exposure but no later than 72 hours after. 

Today we will briefly discuss how to prevent HIV infection.

This is Rio Bravo qWeek, your weekly dose of knowledge brought to you by the Rio Bravo Family Medicine Residency Program from Bakersfield, California. Our program is affiliated with UCLA, and it’s sponsored by Clinica Sierra Vista, Let Us Be Your Healthcare Home.

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HIV Series IV: HIV Prevention. 
By Robert Dunn, MS3.
Participation by Huda Quanungo, MS3; Bahar Hamidi, MS3; and Hector Arreaza, MD.  

HIV Prevention
Introduction

The Human Immunodeficiency Virus (HIV) is a retrovirus that is primarily transmitted via sex, needles or from mother to fetus. Once infected, the virus increases in its copies and decreases the individual’s CD4+ cell count, thus leading to an immunocompromised state known as Acquired Immune Deficiency Syndrome (AIDS). Once with AIDS, the patient is susceptible to opportunistic infections. 

Prevention from AIDS includes several options. Condoms for safe sex practices are the least invasive and most readily accessible option for all patients. Pre-exposure prophylaxis (PrEP) is also an option for men who have sex with men (MSM) and transgender women. If the patient is also exposed to HIV, post-exposure prophylaxis (PEP) may also be an option to prevent infection, but it must be administered ideally 1-2 hours after exposure but no later than 72 hours after. We will concentrate in prevention during this episode. 

What is HIV?

The Human Immunodeficiency Virus (HIV) is a retrovirus. When the virus gains access to our body via cuts on the skin or mucosa:

The virus injects its 10kb sized RNA genome into our cells. 

The RNA is transcribed to DNA via viral reverse transcriptase and is incorporated into our cellular DNA genome. This causes our cells to become a virus producer. 

Viral proteins translated in the cell are transported to the edge of the cell and can bud off into new viruses without lysing the cell. 

Acute HIV symptoms. Some potential early symptoms of HIV can include fever, chills, rash, night sweats, muscle aches, sore throat, fatigue, lymphadenopathy, and mouth ulcers. The most common acute symptom is NO SYMPTOM. Many people do not feel sick with the acute infection of HIV. Some people can live years with HIV in “clinical latency” without knowing they are infected, but they can still be contagious during this time. 

As viral load (the amount of virus copies you have in your blood stream) increases, the CD4+ cells that contribute to our adaptive immunity continues to fall. That’s why the best test during this period is not going to be HIV antibody but you should test for antigens. Specifically, the 4th Generation HIV test, which tests for both antibody and p24 antigens.

Chronic symptoms. Once patients begin to present with opportunistic infections (i.e. Pneumocystis pneumonia – PCP), or have a CD4 count below 200, the patient is considered to have Acquired Immune Deficiency Syndrome (AIDS) and makes them susceptible to more serious infections. Without treatment, patients with AIDS typically survive about 3 years. 

Epidemiology of HIV

HIV incidence: In 2019, there were 34,800 new HIV infections in the United States. This is an 8% decline from 2015. Amongst age groups: 

Age 25-34 had the highest rate of incidence (30.1 per 100,000)

Age 35-44 had the second highest rate (16.5 per 100,000)

Age 45-54 remained stable

Age 13-24 had decreasing rates of incidence

Amongst ethnic groups: 

Black/African-American groups has the highest rate of incidence (42.1 per 100,000)

Hispanic/Latino had the second highest rate (21.7 per 100,000)

Person of multiple races had the third highest (18.4 per 100,000)

Amongst sex: 

Males had the highest rate of incidence (21 per 100,000)

Females had the lowest rate of incidence (4.5 per 100,000)

HIV Prevalence:

In 2019, 1.2 million people (Ages 13 and older) in the US have HIV and 13% of them do not even know it. In 2020, there were an estimated 1.5 million people worldwide that acquired a new HIV infection. This is a 30% decline since 2020. An estimated 66% are receiving some HIV care and 57% were virally suppressed. Mortality: In 2019, there were 15,815 deaths among adults and adolescents diagnosed with HIV in the US. 

Preventative Screening

The USPSTF gives a Grade A recommendation for HIV screening for: Pregnant people and everyone between 15-65 years of age. 

All pregnant people at any point of their pregnancy, including those who present in labor or delivery and have an unknown status of HIV.

The USPSTF only recommends a one-time screening and shows no benefit of repeat screening thereafter. Women may also be screened for subsequent pregnancies

Also screen all Adolescents and adults ages 15-65. 

An effective approach is routine opt-out HIV screening. This approach includes HIV screening as part of the standard preventive tests. This approach removes the stigma associated with HIV testing, it promotes earlier diagnosis and treatment, reduces risk of transmission, and it is cost-effective.

The determination for repeated screening of individuals should take into account the following risk factors: 

-Men who have sex with men (MSM)

-Individuals who live in areas with high prevalence of HIV

Including attending to tuberculosis clinics, stay in a correctional facility, or homelessness

-Injection drug use

-Transactional/commercial sex work

-1 or more new sexual partners 

-History of previous STIs

Annual screening for HIV is reasonable, however, clinicians may want to screen patients every 3-6 months if they have an increased risk of HIV. 

Condoms

A simple and very effective method in HIV prevention is the use of condoms for safe sex practices. In 2009, the American College of Physicians (ACP) and the HIV medicine Association called for the wider availability of condoms and education to minimize HIV transmission. 

A meta-analysis of 12 HIV studies amongst heterosexual couples demonstrated the use of condoms in all penetrative sex acts reduced the risk of HIV transmission 7.4 times in comparison to those who never used condoms. Other studies show a 90-95% effectiveness in HIV prevention when “consistently” using condoms. 

A Cochrane review shoed that the use of a male latex condom in all acts of penetrative vaginal sex reduced HIV incidence by 80%. Overall, condoms are effective in HIV prevention.

Pre-Exposure Prophylaxis (PrEP)

Truvada and Descovy:

Another option for prevention amongst HIV negative individuals is the use of Pre-Exposure Prophylaxis (PrEP). It is an anti-retroviral pill that is taken daily to maintain a steady-state level of the medication in the blood stream. The medication specifically a combination of 2 antiretroviral medications – Tenofovir and Emtricitabine. Both medications are nucleoside reverse transcriptase inhibitors (NRTIs) that work by blocking the viral reverse transcriptase from HIV and prevent the enzyme from copying the RNA genome into DNA. Therefore, it stops viral replications. 

There are 2 formulations of PrEP: Truvada and Descovy. Truvada’s primary side effects are renal and bone toxicity with long-term use. Descovy’s primary side effects are mild weight gain and dyslipidemia. Truvada is the most commonly prescribed PrEP because it has the most data since it has been around the longest. 

However, extra consideration should be taken for: 

Adolescents should weigh at least 35 kg before being prescribed PrEP

Descovy may be preferred for adolescents by the prescribing physician as it is not associated with reduction in bone density, as Truvada is. 

Estimated GFR between 30 – 60

Truvada is associated with acute and chronic kidney disease whereas Descovy is safe for patients with a GFR greater than 30

Patients with osteoporosis

Truvada is associated with bone toxicity, whereas Descovy is not.

It is important to note that PrEP has only been studied in men or people who were assigned men at birth. So, its efficacy in vaginal sex and with vaginal fluids cannot be generalized at this time. 

Future of PrEP: In May 2020, the HIV Prevention Trials Network (HPTN) 083 randomized trial demonstrated the potential of an injectable PrEP. Carbotegravir, is an integrase inhibitor, which prevents the HIV integrase from incorporating the HIV genome into the cellular genome. This study demonstrated its efficacy as PrEP in comparison to Truvada with few new infections (13 versus 39, respectively). Carbotegravir would be given via injection once every 8 weeks. 

In September 2021, the pharmaceutical company Moderna will begin 2 human clinical trials for an HIV vaccine that use mRNA technology. Previous studies conducted with non-mRNA vaccines demonstrated that B cells can be stimulated to create antibodies against HIV. Since HIV becomes integrated in the cellular genome within 72 hours of transmission, a high level of antibodies must be produced and present in the body to offer an adequate level of immunity. 

Post-Exposure Prophylaxis (PEP)

If an individual is exposed to blood or bodily fluids with high risk of HIV via percutaneous, mucus membrane or nonintact skin route, post-exposure prophylaxis (PEP) may be an option. 

PEP is indicated when the HIV status of the exposure source is unknown and are awaiting test results, or if the exposure source is HIV positive. Therapy should be started within 1 or 2 hours of exposure and it is not effective after 72 hours of initial exposure. The recommended duration of therapy is 4 weeks but no evidence has been shown for an optimal duration. 

Occupational exposure. There are 2 regimens for PEP: 

Truvada with Dolutegravir 

Truvada  with Raltegravir

Both Doltegravir and Raltegravir are integrase inhibitors which block the integration of the viral genome into the cellular DNA. The regiments are chosen based on efficacy, side effects, patient convenience, and completion rates. Dolutegravir is chosen because it is given once daily. While Raltegravir is taken twice daily, most experience with PEP has been with Raltegravir. Other risk with Raltegravir are potential skeletal muscle toxicity and systemic-cutaneous reactions resembling Steven-Johnson syndrome. 

One final word about prevention of vertical transmission is making sure pregnant women are treated during pregnancy and if the baby is delivered from a patient whose viral load is “detectable”, the baby needs to be treated, but we’ll let that topic for another time to discuss. 

Joke: What do you call the patient zero of HIV? First Aids.

HIV incidence is decreasing thanks to many prevention measures taken globally, and we discussed screening, condoms, PrEP and PEP as part of this prevention efforts. Stay tuned for more relevant medical information in our next episode. 

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Now we conclude our episode number 70 “HIV Prevention.” Robert, Huda and Bahar explained some ways to prevent HIV, mainly by screening those at risk, using condoms, PrEP (pre-exposure prophylaxis) and PEP (post-exposure prophylaxis). Let’s also remember that having a monogamous relationship and avoiding high risk sexual behaviors confer significant protection against HIV. Even without trying, every night you go to bed being a little wiser.

Thanks for listening to Rio Bravo qWeek. If you have any feedback about this podcast, contact us by email [email protected], or visit our website riobravofmrp.org/qweek. This podcast was created with educational purposes only. Visit your primary care physician for additional medical advice. This week we thank Hector Arreaza, Robert Dunn, Huda Quanungo, and Bahar Hamidi. Audio edition: Suraj Amrutia. See you next week! 

References:

About HIV. Center for Disease Control and Prevention, CDC.gov, June 1, 2021. https://www.cdc.gov/hiv/basics/whatishiv.html . Accessed September 21, 2021.

Simon V, Ho DD, Abdool Karim Q. HIV/AIDS epidemiology, pathogenesis, prevention, and treatment. Lancet. 2006 Aug 5;368(9534):489-504. doi: 10.1016/S0140-6736(06)69157-5. PMID: 16890836; PMCID: PMC2913538. [https://pubmed.ncbi.nlm.nih.gov/16890836/]  

US Statistics. HIV.gov, June 2, 2021. https://www.hiv.gov/hiv-basics/overview/data-and-trends/statistics . Accessed September 21, 2021. 

The global HIV/AIDS Epidemic. HIV.gov, June 25, 2021. https://www.hiv.gov/hiv-basics/overview/data-and-trends/global-statistics. Accessed September 21, 2021. 

Human Immunodeficiency Virus (HIV) Infection: Screening. U.S. Preventative Services Task Force, June 11, 2019. https://www.uspreventiveservicestaskforce.org/uspstf/recommendation/human-immunodeficiency-virus-hiv-infection-screening. Accessed September 21, 2021. 

Holmes KK, Levine R, Weaver M. Effectiveness of condoms in preventing sexually transmitted infections. Bull World Health Organ. 2004 Jun;82(6):454-61. PMID: 15356939; PMCID: PMC2622864. [https://pubmed.ncbi.nlm.nih.gov/15356939/]

Weller S, Davis K. Condom effectiveness in reducing heterosexual HIV transmission. Cochrane Database Syst Rev. 2002;(1):CD003255. doi: 10.1002/14651858.CD003255. PMID: 11869658. [https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD003255/full]

Mayer, Kenneth H, MD, and Douglas Krakower, MD. Administration of pre-exposure prophylaxis against HIV infection. UpToDate, June 24, 2020. Accessed September 21, 2021. [https://www.uptodate.com/contents/administration-of-pre-exposure-prophylaxis-against-hiv-infection?search=8)%09Administration%20of%20pre-exposure%20prophylaxis%20against%20HIV%20infection&source=search_result&selectedTitle=1~150&usage_type=default&display_rank=1]

Zachary, Kimon C, MD. Management of health care personnel exposed to HIV. UpToDate, June 07, 2019. Accessed September 21, 2021. [https://www.uptodate.com/contents/management-of-health-care-personnel-exposed-to-hiv?search=9)%09Management%20of%20health%20care%20personnel%20exposed%20to%20HIV&source=search_result&selectedTitle=1~150&usage_type=default&display_rank=1]

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 69: Asymptomatic Bacteriuria. 

When do you screen for and treat asymptomatic bacteriuria? Find out what the IDSA recommends during this episode. PARTNER studies demonstrated that HIV transmission is minimal with condom-less sex if viral load is undetectable.

Introduction: Urine.  

Urine is a straw-colored, pale yellow, or colorless liquid, which is a by-product of metabolism. It is normally sterile when excreted under normal conditions, but it can also have bacteria even in the absence of infection. When you have bacteriuria with no symptoms, it is called asymptomatic bacteriuria or ASB. Today you will hear Dr Covenas, Dr Civelli and Dr Lundquist discussing when to screen and treat asymptomatic bacteriuria.

This is Rio Bravo qWeek, your weekly dose of knowledge brought to you by the Rio Bravo Family Medicine Residency Program from Bakersfield, California. Our program is affiliated with UCLA, and it’s sponsored by Clinica Sierra Vista, Let Us Be Your Healthcare Home. [Music continues and fades…]

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Asymptomatic bacteriuria (update by the IDSA)
Written by Hector Arreaza, MD. 
Participation by Cecilia Covenas, MD; Valeri Civelli, MD; and Ariana Lundquist, MD.

Case: 19-year-old female who came to clinic to review lab results with you. She is coming from another clinic and brings her results on paper. Routine labs were done 1 week ago. Her complete blood count is normal, TSH (thyroid stimulating hormone) is normal, hemoglobin A1C of 5.3, and a urine culture showing >100,000 CFU of E. coli. Patient denies dysuria, polyuria, or any urinary symptoms. She has a negative pregnancy test in clinic today. What are you going to do with this significant bacteriuria?

This is an Asymptomatic Bacteriuria (ASB). The first question you may ask is “why did she get a urine culture in the first place?” The Infectious Disease Society of America (IDSA) published in its journal “Clinical Infectious Disease” an update in the management of ASB. It is a 28-page long document with answers to 14 questions regarding ASB screening and management in different patient populations.

Recommended ASB screening and treatment: IDSA concluded that the only two groups of patients who benefit from screening and treatment of asymptomatic bacteriuria are: Pregnant women and patients who undergo traumatic urologic interventions that result in mucosal bleeding.

Pregnant women: Recommend one urine culture at one of the initial visits early in pregnancy. There is insufficient evidence to recommend for or against repeat screening during the pregnancy for a woman with an initial negative screening culture or following treatment of an initial episode of ASB. Treatment: IDSA suggests 4–7 days of antimicrobial treatment rather than a shorter duration, the optimal duration of treatment will vary depending on the antimicrobial given; the shortest effective course should be used.

Patients who will undergo endoscopic urologic procedures associated with mucosal trauma: Screening for ASB and treating prior to surgery is RECOMMENDED. The goal is to avoid serious post-operative complication of sepsis. IDSA suggests a urine culture prior to the procedure and targeted antimicrobial therapy prescribed rather than empiric therapy. If bacteriuria is detected, a short course (1 or 2 doses) rather than more prolonged antimicrobial therapy is recommended, and antibiotic should be initiated 30–60 minutes before the procedure.

Against ASB screening and treatment: IDSA suggests no screening for or treating ASB in these patients:

Pediatric patients

Healthy nonpregnant women

Community-dwelling persons who are functionally impaired

Older persons residing in long-term care facilities

Patients with diabetes

Patients who had a renal transplant over 1 month ago (insufficient evidence for less than 1 month ago)

Patients with nonrenal solid organ transplant

Individuals with impaired voiding following spinal cord injury (consider atypical symptoms of UTI when deciding treatment vs nontreatment of bacteriuria in these patients)

Short-term indwelling urethral catheter (<30 days)

Patients with long-term indwelling catheters (>30 days)

Patients undergoing elective nonurologic surgery

Patients planning to undergo surgery for an artificial urine sphincter or penile prosthesis implantation (these patients should receive standard preop antibiotics before surgery)

Patients living with implanted urologic devices

Insufficient evidence to recommend for or against ASB screening and treatment: Evidence is insufficient to recommend ASB screening and treatment in patients with high-risk neutropenia (absolute neutrophil count <100 cells/mm3, >7 days duration after chemotherapy). These patients should be treated with prophylactic antibiotics and start antibiotics promptly in there is fever. For low-risk neutropenic patients (neutrophils >100, <7 days, clinically stable) ASB risk is not greater than in patients with normal neutrophil count. In patients with indwelling catheters, IDSA makes no recommendation for or against screening and treating ASB at the time of catheter removal.

Special populations: In older patients with cognitive impairment with bacteriuria and confusion WITHOUT urinary symptoms or other signs of infection, such as fever or hemodynamic instability: Look for causes of altered mental status other than UTI, have close monitoring of symptoms, antibiotics are NOT recommended as a first line treatment unless you have signs or symptoms of infection.

If a patient with these characteristics (older, cognitively impaired, nonlocalizing symptoms) experienced a fall, the recommendation is the same: assess for other causes and observation rather than antimicrobial treatment of bacteriuria. 

The reason behind this recommendation is avoiding adverse outcomes of antibiotic therapy (C. diff, increased antibiotic resistance, or adverse drug effects). 

Sepsis: For patients with BACTERIURIA, fever, and other systemic signs potentially consistent with sepsis and without a localizing source, broad-spectrum antimicrobial therapy directed against urinary and nonurinary sources should be initiated. 

As for our non-pregnant 19-yo female patient with significant bacteriuria and no urinary symptoms, the answer is do not treat.

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HIV Series Part III: PARTNER 1 and PARTNER 2

Hello everyone! Welcome back to the introduction to HIV series with the Rio Bravo qWeek Podcast. Today we will focus on the PARTNER-1 and PARTNER-2 studies. Let’s review these studies together. 

The PARTNER-1 and PARTNER-2 studies were important in providing evidence-based support for the claim undetectable equals untransmissible, or U=U. SO in this podcast, we can break down what these studies are. 

Previous studies

In 2011, the HIV Prevention Trials Network (HPTN) 052 study team conducted a clinical trial demonstrating a 96% reduction in HIV transmission amongst heterosexual couples when one partner is HIV positive and the other is HIV negative. However, in this study and other, there was still consistent condom use and PrEP use and no data concerning anal sex. 

PARTNER 1 study

The PARTNER 1 (Partners of People on ART – A New Evaluation of the Risks) study was the first observational study to assess the risk of HIV transmission between couples, including both heterosexual and homosexual couples, without condoms, and including anal sex. It was conducted from September 2010 to May 2014, enrolled 1166 couples, and reported 22,000 condomless sex acts amongst men who have sex with men (MSM) and 36,000 condomless sex acts amongst heterosexual couples. The HIV positive partner had to maintain their viral load below 200 copies/mL and the HIV negative patient was not to use condoms or be on pre-exposure prophylaxis (PrEP) in order to be eligible for the study. The results showed that there were no documented cases of within-couple HIV transmission, with a 95% confidence limit.

Some limitations to the study include that there were 11 patients who were HIV negative that contracted HIV during the study time. However, none of the HIV genotypes were phylogenetically linked to the HIV positive partner. Furthermore 8 of these patients endorsed that they were engaging in sex with people other than their partner. Another limitation was that this was an observational study, so all the parameters of the study are self-reported. And the study was conducted for 4 years, so a longer study would need to be conducted to give a stronger estimate of risk. 

PARTNER 2 study

In the PARTNER 2 study, the observational study was focused on only homosexual men (MSM), enrolled some patients from PARTNER 1 study, and therefore included data from September 2010 to April 2018. Once again, the study collected data about their sexual behavior, required the HIV positive partner to maintain a viral load below 200 copies/mL, and required condomless sex and no use of PrEP or post-exposure prophylaxis (PEP) to be eligible for the study. This study enrolled 972 gay couples, contributing to 1596 couple years (years they have been together) and documented 77000 condomless sex acts. The findings once again demonstrated no HIV transmission within couples.

A limitation to this study is that 15 patients did contract HIV, however, none of the new infections could be phylogenetically linked to their partner from the study. Furthermore, it is important to note that 37% of the couples were in open relationships, 24% of the HIV negative partners contracted at least one STI and 27% of the HIV positive patients contracted at least one STI. 

Significance

The significance of this study demonstrates the effectiveness of HAART therapy in not only treating a patient with HIV, but also demonstrates that “undetectable” levels of HIV viral loads does mean it is untransmissible. The common campaign symbol “U=U” (undetectable = untransmissible) is often used to promote this concept. And these studies finally give us evidence-based data to demonstrate U=U. Hopefully with more education, the prejudice surrounding people living with HIV can be removed. 

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Conclusion: Now we conclude our episode number 69 “Asymptomatic Bacteriuria.” When do you screen for and treat asymptomatic bacteriuria? The answer is, in pregnant women and in patients who will undergo traumatic urology procedures. Robert also explained in his HIV series that the PARTNER 1 and PARTNER 2 studies showed no transmission of HIV to a seronegative partner when the seropositive partner has undetectable viral load, even without use of condoms. Even without trying, every night you go to bed being a little wiser.

Thanks for listening to Rio Bravo qWeek. If you have any feedback about this podcast, contact us by email [email protected], or visit our website riobravofmrp.org/qweek. This podcast was created with educational purposes only. Visit your primary care physician for additional medical advice. This week we thank Hector Arreaza, Cecilia Covenas, Valerie Civelli, Arianna Lundquist, and Robert Dunn. Audio edition: Suraj Amrutia. See you next week! 

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References:

Nicolle LE, Gupta K, Bradley SF, Colgan R, DeMuri GP, Drekonja D, Eckert LO, Geerlings SE, Köves B, Hooton TM, Juthani-Mehta M, Knight SL, Saint S, Schaeffer AJ, Trautner B, Wullt B, Siemieniuk R. Clinical Practice Guideline for the Management of Asymptomatic Bacteriuria: 2019 Update by the Infectious Diseases Society of America. Clin Infect Dis. 2019 May 2;68(10):e83-e110. doi: 10.1093/cid/ciy1121. PMID: 30895288. [https://pubmed.ncbi.nlm.nih.gov/30895288/]  

Cohen MS, Chen YQ, McCauley M, Gamble T, Hosseinipour MC, Kumarasamy N, Hakim JG, Kumwenda J, Grinsztejn B, Pilotto JH, Godbole SV, Mehendale S, Chariyalertsak S, Santos BR, Mayer KH, Hoffman IF, Eshleman SH, Piwowar-Manning E, Wang L, Makhema J, Mills LA, de Bruyn G, Sanne I, Eron J, Gallant J, Havlir D, Swindells S, Ribaudo H, Elharrar V, Burns D, Taha TE, Nielsen-Saines K, Celentano D, Essex M, Fleming TR; HPTN 052 Study Team. Prevention of HIV-1 infection with early antiretroviral therapy. N Engl J Med. 2011 Aug 11;365(6):493-505. doi: 10.1056/NEJMoa1105243. Epub 2011 Jul 18. PMID: 21767103; PMCID: PMC3200068. [https://www.nejm.org/doi/full/10.1056/nejmoa1105243] 

Rodger AJ, Cambiano V, Bruun T, et al. Sexual Activity Without Condoms and Risk of HIV Transmission in Serodifferent Couples When the HIV-Positive Partner Is Using Suppressive Antiretroviral Therapy. JAMA. 2016;316(2):171–181. doi:10.1001/jama.2016.5148. [https://jamanetwork.com/journals/jama/fullarticle/2533066] 

Rodger AJ, Cambiano V, Bruun T, Vernazza P, Collins S, Degen O, et al. Risk of HIV transmission through condomless sex in serodifferent gay couples with the HIV-positive partner taking suppressive antiretroviral therapy (PARTNER): final results of a multicentre, prospective, observational study. The Lancet. 2019; 393(10189): 2428-2438. Doi: 10.1016/S0140-6736(19)30418-0. [https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(19)30418-0/fulltext]

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 68: Prevention - Aspirin, STIs, and Diabetes. 

Updates on aspirin use for preeclampsia prevention, updated STIs screening guidelines, and new age to start screening for diabetes.  

Introduction:  COVID-19 Booster Shots.  

Every week there is a lot of information to cover about COVID-19. I’m sure you are aware of some of this information, but here you have it again for historical purposes. 

Pfizer and BioNtech announced on September 20, 2021, that their COVID-19 vaccine is protective in pediatric patients between 5 and 11 years of age. 

Let’s remember that this vaccine is being used for patients older than 12, but so far none of the vaccines have been authorized for younger patients. A submission to FDA has been sent, but no approval has been given yet.

Recently, we mentioned to you that a booster shot for the mRNA COVID-19 vaccines were likely to be authorized by the FDA around September 20. Indeed, an authorization for a booster was given on September 22, 2021. This authorization was given to the Pfizer/BioNtech vaccine only, and it can be given at least 6 months after the completion of the primary series.

The patients who are authorized to receive the booster shot are: Patients who are 65 years of age and older; patients between 18 and 64 years of age at high risk of severe COVID-19; and individuals 18 through 64 years of age with frequent occupational exposure to COVID-19.

The Moderna vaccine has not been authorized for a booster shot.

Let’s remember that both Pfizer and Moderna have been authorized for a third dose in patients who are immunocompromised. The third dose can be given 4 weeks after completing he initial 2 doses of these vaccines. Patient who may receive a third dose are those who are receiving active cancer treatment, recipients of an organ transplant, or have a moderate or severe immunodeficiency. 

Stay tuned for more updates in the future.

This is Rio Bravo qWeek, your weekly dose of knowledge brought to you by the Rio Bravo Family Medicine Residency Program from Bakersfield, California. Our program is affiliated with UCLA, and it’s sponsored by Clinica Sierra Vista, Let Us Be Your Healthcare Home. 

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Prevention - Aspirin, STIs and Diabetes
By Hector Arreaza, MD, and Valerie Civelli, MD

The USPSTF has been very active lately. They have released several recommendations in the last few months. 

Aspirin and preeclampsia: On September 28, 2021, the USPSTF released their recommendation about the use of aspirin to prevent preeclampsia in pregnant persons at high risk. This recommendation is consistent with the previous recommendation given in 2014. New evidence has reinforced that aspirin is effective at reducing risk of perinatal mortality when used properly.

The recommendation states: “The USPSTF recommends the use of low-dose aspirin (81 mg/day) as preventive medication after 12 weeks of gestation in persons who are at high risk for preeclampsia.” This is a grade B recommendation. A grade B recommendation means the net benefit of this preventive intervention is moderate to substantial.

Who is at risk for preeclampsia? You can classify the risk as High, Moderate, and Low.

High: Preeclampsia during previous pregnancies (especially if you had an adverse outcome), multifetal gestation, chronic hypertension, type 1 or 2 diabetes before pregnancy, kidney disease, autoimmune disease, or a combination of multiple moderate-risk factors. Recommend aspirin if a woman has 1 or more of those high-risk factors. 

Moderate: Nulliparity, obesity, history of preeclampsia in mother or sister, black persons, low income, age 35 years or older, personal history factors (e.g. low birth weight or small for gestational age, previous adverse pregnancy outcome, >10-year pregnancy interval, and in vitro conception. Recommend aspirin if patient has 2 or more of these moderate risk factors. You may recommend aspirin even to women with 1 of these risk factors. 

Low: Do not recommend aspirin to pregnant women who have low risk for preeclampsia. A patient is considered low risk if she had a previous uncomplicated term delivery and has none of the risk factors mentioned above.

As a side note, given the current movement for diversity, equality and inclusion, the article also states that “black persons have higher rates of preeclampsia and are at increased risk for serious complications due to various societal and health inequities,” not due to biological propensities.

When do you stop aspirin in pregnancy?

The decision to continue aspirin in the presence of obstetric bleeding (or bleeding risk) should be considered on a case-by-case basis. You can decide to stop at 36 weeks or continue until delivery based on your clinical judgement or local protocol.

Bottom-line: Recommend low-dose aspirin to pregnant women who are at increased risk for preeclampsia after 12 weeks of gestation.

Chlamydia and gonorrhea screening: On September 14, 2021, the USPSTF recommended screening women younger than 24 years old who are sexually active for BOTH chlamydia and gonorrhea infection. Also, screen all women 25 years and older who are at increased risk.

Increased risk means: a previous or coexisting STI, history of incarceration, and any kind of sexual intercourse out of a mutually monogamous relationship (new partner, more than one partner, partner who has sex with other partners, partner with an STI, history of exchanging sex for money or drugs). 

The screening for GC/Chlamydia in women is a grade B recommendation.

In this recommendation, the term “women” refers to persons born with female genitalia and does not apply to persons who identify as women but have male genitalia. 

This recommendation also includes pregnant persons and adolescents.

The evidence is insufficient (Grade I) to assess the balance and benefits and harms of screening for chlamydia and gonorrhea in asymptomatic men. Remember, a grade I recommendation is not a recommendation for or against a preventive intervention. To make it easy to remember “I stands for I don’t know, more research is needed”.

Recommendations about the age to start screening or the frequency of screening is not given explicitly, but the population with the highest incidence is women between 15-24 years old. Use your clinical judgement to determine when to start and how often.

Prediabetes and diabetes screening: On August 24, 2021, the USPSTF updated their recommendation for prediabetes and diabetes screening.

The recommendations states: “The USPSTF recommends screening for prediabetes and type 2 diabetes in adults aged 35 to 70 years who have overweight or obesity (BMI above 25). Clinicians should offer or refer patients with prediabetes to effective preventive interventions. This is a Grade B recommendation.

The age to start screening is now 35 years old (instead of the previous recommended age of 40). This is an update from the recommendation given in 2015.

We should consider screening at a younger age in:

Persons from groups with high incidence and prevalence. These groups are American Indian/Alaska Native, Asian American, Black, Hispanic/Latino, or Native Hawaiian/Pacific Islander persons. 

Persons with family history of diabetes, history of gestational diabetes, or a history of polycystic ovarian syndrome.

Screen Asian Americans with a BMI of 23 or greater after age 35.

How to screen for prediabetes and diabetes? You have three options: 

Fasting glucose (normal below 100, prediabetes below 125, diabetes above 126)

Hemoglobin A1C (normal Below 5.6, prediabetes below 6.4%, diabetes above 6.5%). Do not use point of care A1C for screening, use a venous sample instead.

Oral glucose tolerance test in the morning (fasting); measure glucose 2 hours after ingesting 75 g of oral glucose (normal below 140, prediabetes below 200, diabetes above 200). The diagnosis of prediabetes or type 2 diabetes should be confirmed with repeat testing before starting intervention.

Random glucose above 200 is highly suggestive of diabetes. 

     The diagnosis of diabetes should be confirmed before starting interventions.

Summary: Aspirin for preeclampsia prevention, screen for gonorrhea and chlamydia all women younger than 24, and screen for diabetes everyone older than 35 with overweight or obesity.

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HIV Series Part II: HIV Transmissibility
By Robert Dunn, MS3, Ross University School of Medicine.

People infected with HIV are often thought to be contagious even by touch; though the reality is transmission is primarily transmitted via sexual contact, bodily fluids, from mother to baby during pregnancy, shared needles, or accidental needle sticks in the medical workplace. And when it comes to sex, it is common that a person is afraid to engage in any sexual contact with a HIV positive person, even though the patient may have their infection controlled with medicine.

Per the CDC, the most common ways of contracting HIV are through sex without protection, shared needles, and perinatal transmission from mother to child.

Sexual transmission:

With anal sex, the receptive partner, or bottom, is at higher risk of contracting HIV because the rectal mucosa is thin, more prone to micro-abrasions and create an opportunity to contract HIV. The insertive partner, or top is also at risk of infection via the opening of the urethra, the foreskin of an uncircumcised penis, or any cuts, scratches or open sores on the penis. 

With vaginal sex, the woman can be infected via the mucus membranes that line the vagina and cervix. And the man can become infected from the vaginal fluid or blood that may carry HIV. 

Needlesticks:

Sharing needles is high risk for contracting HIV. If one person has HIV and uses a needle, the blood of that person is carried on the needle and can inject the virus directly into anyone else who uses that needle. This can occur if people are sharing injected drugs, medications, or even in a needle stick accident that may occur when treating patients in the hospital with HIV. 

Vertical transmission:

Perinatal transmission occurs when the mother infected with HIV passes the infection to her newborn. It is now recommended to test every pregnant woman for HIV and treat as needed. This can occur while the fetus is in the womb or upon delivery. It is recommended that the mother be placed on HIV medication immediately to reduce the risk of infecting the baby. 

These are ways how HIV is NOT transmitted: kissing on the cheeks, hugging, holding hands, sharing silverware, talking to someone, mosquitos, or sharing toilet.

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Now we conclude our episode number 68 “Prevention – Aspirin, STIs, and Diabetes.” Dr Arreaza and Dr Civelli explained the most recent updates by the USPSTF regarding use of aspirin to prevent preeclampsia, screening for gonorrhea and chlamydia in women, and screening for diabetes in patients older than 35. Robert continued with his HIV series and explained how HIV is mostly transmitted, a good reminder for all of us that the most common way of transmission continues to be sexual transmission. Even without trying, every night you go to bed being a little wiser.

Thanks for listening to Rio Bravo qWeek. If you have any feedback about this podcast, contact us by email [email protected], or visit our website riobravofmrp.org/qweek. This podcast was created with educational purposes only. Visit your primary care physician for additional medical advice. This week we thank Hector Arreaza, Hasaney Sin, Valerie Civelli and Robert Dunn. Audio edition: Suraj Amrutia. See you next week! 

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References:

Erman, Michael, Pfizer/BioNTech say data show COVID-19 vaccine safe and protective in kids, Reuters, reuters.com, September 20, 2021. https://www.reuters.com/business/healthcare-pharmaceuticals/pfizerbiontech-say-data-show-covid-19-vaccine-safe-protective-kids-2021-09-20/, accessed on September 29, 2021.

Aspirin Use to Prevent Preeclampsia and Related Morbidity and Mortality: Preventive Medication, United States Preventive Services Taskforce, September 28, 2021, https://www.uspreventiveservicestaskforce.org/uspstf/recommendation/low-dose-aspirin-use-for-the-prevention-of-morbidity-and-mortality-from-preeclampsia-preventive-medication.

Chlamydia and Gonorrhea: Screening, United States Preventive Services Taskforce, September 14, 2021, https://www.uspreventiveservicestaskforce.org/uspstf/recommendation/chlamydia-and-gonorrhea-screening.

Prediabetes and Type 2 Diabetes: Screening, United States Preventive Services Taskforce, August 24, 2021, https://www.uspreventiveservicestaskforce.org/uspstf/recommendation/screening-for-prediabetes-and-type-2-diabetes

Ways HIV can be Transmitted. CDC, April 21, 2021. https://www.cdc.gov/hiv/basics/hiv-transmission/ways-people-get-hiv.html. Accessed on September 21, 2021.

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 67: Covid, Food, and HIV.  

Medical students discuss the relationship between high cholesterol and COVID-19, the effect of food order in postprandial glucose and insulin, and HIV history. Moderated by Hector Arreaza, MD.  

During this episode you will listen to three medical students discussing some topics that they found interesting during their family medicine rotation. All the credit goes to them because they read these topics and provided a very good summary. I hope you enjoy it.

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High Cholesterol and COVID-19
By Milan Hinesman, MS3, Ross University School of Medicine

Given the current state of the world, there’s been a lot more attention to COVID-19 presentation, risks, and treatment. One study conducted by Dr. Kun Zhang and collaborators shows that there may be a relationship between higher total cholesterol levels and ApoB levels to increased risk of COVID-19 infection[1]. Dr. Zhang used a mendelian randomization from the UK Biobank data to test for lipid effects on COVID susceptibility and severity. 

The study performed analysis of data from the host genetics initiative consisting of more than 14,000 cases and more than one million controls showing a potential positive causal effect between high total cholesterol and ApoB and COVID susceptibility. 

A mendelian randomization is a process of taking genes which functions are already known and measuring their response to exposure to a disease in observational studies[2]. In short, high cholesterol and high ApoB are linked to COVID-19 infection.

This is Rio Bravo qWeek, your weekly dose of knowledge brought to you by the Rio Bravo Family Medicine Residency Program from Bakersfield, California. Our program is affiliated with UCLA, and it’s sponsored by Clinica Sierra Vista, Let Us Be Your Healthcare Home. 

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Impact of food order on glucose after meals.   
By Yvette Singh, MS3, American University of the Caribbean

In the management of diabetes, health care providers usually assess glycemic control with fasting plasma glucose and pre-prandial glucose measurements, as well as by measuring Hemoglobin A1c. 

Therapeutic goals for Hemoglobin A1c and pre-prandial glucose levels have been established based on the results of controlled clinical trials. Unfortunately, many patients with diabetes fail to achieve their glycemic goals. Elevated glucose after eating may be the cause of poor glycemic control leading to vascular complications. 

Postprandial hyperglycemia is one of the earliest abnormalities of glucose homeostasis associated with type 2 diabetes. This is one of the important therapeutic targets for glycemic control. Current studies show that the amount and timing of carbs in the diet primarily influence blood glucose levels. Other studies also show that eating whey protein before meals, as well as changing the macronutrients in meals, reduces postprandial glucose levels; however, these studies did not have patients with type 2 diabetes. 

The main author of this study was Alpana P. Shukla and many other collaborators. The title is Food Order Has a Significant Impact on Postprandial Glucose and Insulin Levels, published by the American Diabetes Association on Diabetes Care in July 2015.

This study was performed to analyze the order of food consumption with vegetables, protein and carbohydrates and its effects on postprandial glucose in overweight/obese patients with type 2 diabetes being treated with metformin. Subjects were studied for 1 week. They were given a meal with the same number of calories, after fasting for 12 hours: 55g protein, 68g carbs, and 16g fat. They were asked to eat carbs first, then to eat vegetables and protein fifteen minutes later. This order was reversed during the second week. Their postprandial glucose and insulin levels were measured at 30/60/120 mins after meals. 

The statistical studies showed an average post prandial glucose decrease by more than 25% when protein was consumed first. As well as the average post prandial insulin levels decreased by more than 40%. 

These results demonstrated that the timing of carbs during a meal has a significant impact on glucose and insulin levels comparable to some pharmacological agents. Reduced insulin excretion with this meal pattern may also improve insulin sensitivity. This may help patients with type 2 diabetes control their HbA1c, and possibly help reverse early diabetes. 

Educating patients about this approach is not controlling how much they are eating or restricting their diet so patients will likely comply with this recommendation. Eat your protein first!

The potential problems of this study are that it was a small sample size (11 patients), limited food types, and insulin was measured only up to 120 minutes after meals. Further studies are needed to demonstrate the full effectiveness of this recommendation.

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HIV Series Part I: HIV History
By Robert Dunn, MS3, Ross University School of Medicine 

This is an HIV series for the Rio Bravo qWeek Podcast. The following episodes will include some of the history of HIV, transmissibility, the PARTNER-1 and PARTNER-2 studies, and will finalize with a full episode on HIV prevention. Today we are starting with HIV history.

Prejudice against those with HIV stems from the history surrounding the virus. Between 1981-1983, cases of rare infections like Pneumocystis carinii pneumonia (PCP) and aggressive cancers like Kaposi Sarcoma were appearing predominantly amongst gay men and injection drug users.  Even children were presenting with AIDS creating misconceptions of how the disease was transmitted by touch. By 1982, this syndrome was referred to as the Gay-Related Immunodeficiency (GRID), which we now know as AIDS. 

Some History of HIV

The start of the Human Immunodeficiency Virus (HIV) was thought to have started in the Democratic Republic of Congo in 1920 when the virus crossed species to humans and gave its ability to infect humans[4]. 

In 1981, five young gay men in Los Angeles, California, presented with a rare lung infection called Pneumocystis carinii pneumonia (PCP). Two other groups of men also presented with a rare and aggressive cancer called Kaposi Sarcoma, in New York and California. By December of the same year, the first case of PCP was found in an injection drug user. And by the end of the year, there were 270 reported cases of this severe immunodeficiency and about 121 of them had already died from it, almost 50%. 

In 1982, due to the prevalence of these rare diseases being present among gay men, the syndrome was called the Gay-Related Immune Deficiency (GRID). The CDC later officially called the disease the Acquired Immune Deficiency Syndrome (AIDS). The term “gay cancer” was used in Venezuela before AIDS was known.

In 1983, the disease was found in both women and children. In May 1983, in a joint conference between the Pasteur Institute in France and the National Cancer Institute, they announced that LAV and HTLV-III were the same virus and the cause of AIDS.

In 1985, Ryan White, a teenager with hemophilia was banned from school when he was diagnosed with HIV after he received contaminated blood products. Ryan later died at 18 years old due to AIDS-related illnesses. At the same time, the FDA licensed the first commercial blood test to detect HIV. A foundation was later created to provide primary care and medications for low-income HIV patients.

In 1987, the first antiretroviral drug, Zidovudine (AZT) was approved by the FDA to treat for HIV. 

In 1991, the famous basketball player Magic Johnson announced he tested positive for HIV and retired immediately. After his retirement he planned to educate young people about the virus which helped dispel stereotypes. Also in 1991, the famous singer of Queen announced he had AIDS and died the next day.

In 1993, the movie Philadelphia with Tom Hanks promoted further discussion about HIV and AIDS. 

In June 1995, the first protease inhibitor was approved by the Food and Drug Administration (FDA), which started the era for Highly Active Antiretroviral Therapy (HAART). This brought down the rate of AIDS-related deaths and hospitalizations by 60-80%. 

Of special note, in 1986, the FDA passed the policy to ban all men who had sex with men (MSM) from 1977 onward, from donating blood or plasma to avoid the risk of transmitting HIV or Hepatitis A. This policy was amended in December 2015, when the revised policy said any MSM within the last 12 months, would need to wait at least 1 year before donating blood. In light of the COVID-19 pandemic, the FDA amended it its policy once more to decrease the wait time to 3 months form the last time the man had sex with another man.

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Conclusion: Now we conclude our episode number 67 “Covid, Food, and HIV.” Kudos to Milan, Yvette and Robert, they presented relevant information for our practice of medicine. They taught us that high cholesterol is a risk for COVID-19 infection; Also, when you eat proteins first, your glucose and insulin after meals are lower than when you eat carbs first; and you will be hearing from Robert for a couple episodes regarding HIV. Today he gave us a little piece of HIV history. Even without trying, every night you go to bed being a little wiser.

Thanks for listening to Rio Bravo qWeek. If you have any feedback about this podcast, contact us by email [email protected], or visit our website riobravofmrp.org/qweek. This podcast was created with educational purposes only. Visit your primary care physician for additional medical advice. This week we thank Hector Arreaza, Milan Hinesman, Yvette Singh, and Robert Dunn. Audio edition: Suraj Amrutia. See you next week! 

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References:

Zhang, K. Dong, S. Guo, et. al., Causal Associations Between Blood Lipids and COVID-19 Risk: A Two-Sample Mendelian Randomization Study. Arteriosclerosis, Thrombosis, and Vascular Biology, originally published on September 9, 2021. https://doi.org/10.1161/ATVBAHA.121.316324.

What is Mendelian Randomization and How Can it be Used as a Tool for Medicine and Public Health? Opportunities and Challenges, Webinar announcement given by Professor George Davey Smith on November 27, 2018. Centers for Disease Control and Prevention, https://www.cdc.gov/genomics/events/precision_med_pop.htm

Alpana P. Shukla, Radu G. Iliescu, Catherine E. Thomas and Louis J. Aronne, Food Order Has a Significant Impact on Postprandial Glucose and Insulin Levels, Diabetes Care 2015 Jul; 38(7): e98-e99. https://doi.org/10.2337/dc15-0429.

History of HIV and AIDS Overview. Avert, October 10, 2019. https://www.avert.org/professionals/history-hiv-aids/overview. Accessed on September 21, 2021.

Shaw, Maggie. FDA’s Revised Blood Donation Guidance for Gay Men Still Courts Controversy. AJMC, April 3, 2020. https://ajmc.com/view/fdas-revised-blood-donation-guidance-for-gay-men-still-courts-controvery. Accessed on September 21, 2021. 

BAYER, R. (2015), Science, Politics, and the End of the Lifelong Gay Blood Donor Ban. Milbank Quarterly, 93: 230-233. https://doi.org/10.1111/1468-0009.12114.

Ways HIV can be Transmitted. Centers for Disease Control and Prevention, April 21, 2021. https://www.cdc.gov/hiv/basics/hiv-transmission/ways-people-get-hiv.html. Accessed on September 21, 2021.

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 66: Meth Abuse. 

By Ikenna Nwosu, MD, and Hector Arreaza, MD.  

Discussion about screening, epidemiology, clinical presentation, diagnosis, and treatment of meth abuse. Association between intranasal corticosteroids and lower risk of COVID-19 complications is mentioned.

Introduction: Intranasal corticosteroids associated with better outcomes in COVID-19
By Bahar Hamidi, MS3, American University of the Caribbean 

When I first heard of the news of a pandemic occurring, I never thought it would last more than a couple weeks. Of course, as a medical student the first thing I wanted to know was what bug is causing all this commotion in the news. When I discovered “Coronavirus” my first reaction was a chuckle and blurting out “no way.” Why did I respond this way you may ask? As a student when we studied that coronavirus would cause nothing more than a regular cold, thus a mere pesky virus causing a whole pandemic seemed odd to me at the time. Little did I know almost two years later we are still talking about it! 

“Don’t touch your face before washing your hands.” These are the words that run through my mind anywhere I am nowadays. Why? Well, SARS-CoV-2 spike (S) protein is why. This protein engages ACE2 (angiotensin-converting enzyme 2) as the entry receptor. This virus’s receptor is found to be highly expressed in our nasal mucosa. How much of this ACE2 we have interestingly can correlate with your age; lower in children compared with adults. Other things that can affect a person’s susceptibility is the level of eosinophils in your body. High absolute eosinophil count showed to have a lower hospitalization risk in a group of individuals with asthma and COVID, but we must keep in mind that the study can be confounded by the use of inhaled corticosteroids (iCS). This was taken into account during a study.

The study was done by Ronald Strauss and collaborators, it’s titled, Intranasal Corticosteroids Are Associated with Better Outcomes in Coronavirus Disease 2019, and it was published on The Journal of Allergy and Clinical Immunology: In Practice, September 2021.

So how may inhaled corticosteroids prevent significant illness from COVID? The answer is lower expression of ACE2 and its cellular serine protease TMPRSS2. Theoretically, it makes sense because the less entry gates the virus has the less sick someone may possibly get. Therefore, the study hypothesizes that by suppressing receptor expression, intranasal corticosteroid use is protective against complicated outcomes like hospitalizations, admission to ICU and mortality.

Interestingly in addition, two types of corticosteroids [ciclesonide (Alvesco®) and mometasone (Asmanex® for asthma and Nasonex for allergic rhinitis)] were discovered to suppress replication of coronavirus. This overall study has pertinent findings for the treatment of this everlasting pandemic and proves there is yet much left to discover and continue to research.

This is Rio Bravo qWeek, your weekly dose of knowledge brought to you by the Rio Bravo Family Medicine Residency Program from Bakersfield, California. Our program is affiliated with UCLA, and it’s sponsored by Clinica Sierra Vista, Let Us Be Your Healthcare Home. 

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Meth Abuse. 
By Ikenna Nwosu, MD, and Hector Arreaza, MD

Introduction

Drug use is a growing problem with serious consequences to individuals, families, and whole nations. Today we will discuss one of the most common drugs abused by our patients: Methamphetamine.

Definition   

Methamphetamine (street name chalk, crank, crystal, glass, ice, meth) is a stimulant commonly abused in many parts of the United States. It is a psychostimulant that causes the release and blocks the reuptake of monoamine neurotransmitters, including dopamine, norepinephrine, and serotonin. Methamphetamine is most often smoked or snorted and is less commonly injected or ingested orally. 

Arreaza: Phentermine (appetite suppressant) is not meth. Phentermine is less potent because it acts mostly on norepinephrine, very little on dopamine, and minimally on serotonin. 

Epidemiology  

Amphetamine-type stimulants, which include methamphetamine, are the fastest rising drug of abuse worldwide. An estimated 2.1% of the United States population have been reported to have tried methamphetamine at some time in their lives with its rate of use found to be similar among men and women. Data indicates that methamphetamine is a significant public health problem. Mortality has increased by about 40 percent from 2015 to 2016 and drug overdose deaths involving methamphetamine have tripled since 2011.

Arreaza: The mortality is high but also the morbidity. I can imagine how costly it is for health systems to take care of the complications of meth use, from dental work to cardiovascular disease, i.e., heart failure. It is a serious problem in Bakersfield, California. As an interesting fact, meth is the most common drug identified in urine drug screenings, then follows marijuana, cocaine, heroin, and fentanyl.

Clinical manifestations  

When someone uses meth, they have increased energy and alertness, pupillary dilation, tachycardia, euphoria, decreased need for sleep, grinding teeth, dry mouth, loss of appetite, and other symptoms of sympathetic nervous system activation. 

Repeated use causes weight loss, dental decay, chronic adverse mood, and cognitive changes, including irritability, aggression, panic, suspiciousness, and/or paranoia, hallucinations, and memory impairment. 

Chronic use also can exacerbate depression and anxiety, and those changes can interfere tremendously in patient care. The risk of suicide is also higher.

It can also cause complications in other systems:

-Cardiovascular (cardiomyopathy, myocardial infarction, and stroke)

-Skin (abscesses, aged appearance, and skin lesions)

-Neurologic (confusion, memory loss, slowed learning)

-Oral (dental decay or “meth mouth”)

Acute intoxication

Complications of severe acute intoxication: hypovolemia, metabolic acidosis, hyperthermia, disseminated intravascular coagulation (DIC), rhabdomyolysis, tachydysrhythmia, hypertension, and seizures. 

Methamphetamine as a psychostimulant, has a half-life of 12 hours, so its effects last longer than those of cocaine. It is metabolized by the liver through the cytochrome P2D6 system. After the acute intoxication you can see the opposite: sedation, slurred speech, hypersomnia. 

Screening  

No specific guidelines regarding screening for methamphetamine use are available. 

In 2008, The U.S. Preventive Services Task Force concluded that evidence available at that time was insufficient to assess the balance of benefits and harms of screening adolescents, adults, and pregnant women for illicit drug use. 

This guideline was updated in June 2020. The USPSTF now gives a grade of recommendation “B” to screening for unhealthy drug use. How do you screen? By asking questions about unhealthy drug use in all adults older than 18 years old. This recommendation does not include testing biological specimens. Screening should be implemented when diagnosis, effective treatment and care can be offered at your clinic or you can refer to other providers for treatment.

The American Academy of Pediatrics, the American Medical Association's Guidelines for Adolescent Preventive Services, and the Bright Futures initiative endorse screening adolescents for illicit substance use.

On the other hand, the USPSTF concluded in June 2020 that the current evidence is insufficient to recommend screening for unhealthy drug use in adolescents. So, it gives a grade of recommendation “I”. Remember, “I” does not mean “Do not screen”, “I” means “Insufficient or I don’t know”.

The American College of Obstetricians and Gynecologists recommends direct questioning of all patients about their use of drugs as part of periodic assessments. Screening for methamphetamine use by history should be considered for pregnant women, teenagers and young adults, persons with criminal histories, men who have sex with men, and persons in high-risk ethnic groups.

Diagnostic testing with informed consent can be useful in patients with stimulant-associated symptoms and signs, but this is not screening, this is a diagnostic test.

Diagnosis  

DSM-5 criteria — A problematic pattern of methamphetamine use leading to clinically significant impairment or distress, as manifested by two or more of the following within a 12-month period:

• Methamphetamine is often taken in larger amounts or over a longer period than was intended (patient wants more and more meth)

• There is a persistent desire or unsuccessful efforts to cut down or control methamphetamine use (patients want to quit but they can’t)

• A great deal of time is spent in activities necessary to obtain methamphetamine, use methamphetamine, or recover from its effects (patient spends a long time using meth and recovering)

• Craving, or a strong desire or urge to use methamphetamine (patient crave)

• Recurrent methamphetamine use resulting in a failure to fulfill major role obligations at work, school, or home

• Continued methamphetamine use despite having persistent or recurrent social problems caused or exacerbated by the effects of methamphetamine

• Important social, occupational, or recreational activities are given up or reduced because of methamphetamine use

• Recurrent methamphetamine use in situations in which it is physically hazardous

• Continued methamphetamine use despite knowledge of having a persistent or recurrent physical or psychological problem that is likely to have been caused or exacerbated by methamphetamine

Subtypes of severity of methamphetamine use disorder 

●Mild: Two to three symptoms

●Moderate: Four to five symptoms

●Severe: Six or more symptoms

Urine drug test

Methamphetamine can be detected in urine for approximately 48 hours after use. It can be detected in meconium in newborns,indicating maternal use in the second half of pregnancy. Pseudoephedrine can cause a false positive test result for amphetamines.The amphetamine portion of the "tox screen" is susceptible to both false positive and false negative results and must be interpreted in clinical context. 

Drugs of abuse, such as benzphetamine and bupropion (a synthetic cathinone), may give positive results. Medications such as selegiline and nonprescription nasal inhalers (decongestants) containing the active ingredient l-methamphetamine (l-desoxyephedrine) may yield positive results for amphetamine.

Phentermine can give a false positive result in Utox for meth or MDMA (ecstasy). If a patient states he/she is taking phentermine, you can order a confirmatory test, which will then show that it was phentermine and not amphetamine or methamphetamine. If you are taking phentermine for weight loss, you should stop taking it a week before the drug test.

Treatment of acute intoxication

The treatment of acute methamphetamine intoxication is largely supportive. 

-Activated charcoal (after oral ingestion) when there are severe symptoms of intoxication and absorption needs to be reduced

-Benzodiazepines may be indicated for seizures or agitation

-Antipsychotics may be needed for paranoia or psychosis. 

-Cooling measures may be required if there is hyperthermia. 

-If elevated blood pressure is dangerously high, it should be lowered, but there are no data regarding blood pressure goals or which medications to use. 

-Abuse of multiple substances is possible. Patients may have used a combination of marijuana, alcohol, and cocaine, for example.

You should also consider testing for several STIs in meth users since high risk sexual behaviors are possible.

Treatment of abuse

Outpatient behavioral therapies are the standard treatment for methamphetamine abuse and dependence. Inpatient treatment may be needed in some cases. 

-Cognitive behavior therapy and contingency management programs are successful in treating cocaine addiction and may be effective in treating methamphetamine addiction as well. 

-Contingency programs consists of rewarding patients who provide a drug-free urine sample.

-The Matrix Model is an individualized outpatient regimen that has been used successfully to treat patients who abuse stimulants. It is based on cognitive principles, incorporating individual, group, and family therapies, as well as drug testing and a 12-step program. 

Medications to treat meth abuse

There are no medications approved by the U.S. Food and Drug Administration to treat methamphetamine dependence.

Some studies on this topic include:

-A Cochrane review showed that fluoxetine (Prozac, 40 mg per day) may have modest benefit in reducing cravings for a short time but does not reduce use of meth, and that imipramine (Tofranil) may improve adherence to therapy in methamphetamine users. 

-One small RCT showing that bupropion (Wellbutrin) decreased subjective methamphetamine-induced effects and craving in a laboratory setting. 

-A randomized controlled trial enrolled 60 men who have sex with men; participants had methamphetamine use disorder and were actively using the drug. All the men received weekly counseling plus mirtazapine (Remeron), 30 mg per day, or placebo. Men in the mirtazapine group had decreased methamphetamine use and sexual risk, despite low adherence.

In Episode 47, Kafiya Arte mentioned the Accelerated Development of Additive Treatment for Methamphetamine Disorder (ADAPT-2), which assessed the efficacy of combined bupropion and naltrexone for the treatment of meth use disorder. 403 participants were enrolled. The efficacy of extended-release injectable naltrexone (380 mg every 3 weeks) combined with once-daily oral extended-release bupropion (450 mg) was evaluated, as compared to placebo.  Results: 13.6% response rate in the naltrexone-bupropion group and only 2.5% response with placebo. The response rate among participants that received naltrexone and bupropion was low, but it was higher than those who received placebo. 

Withdrawal

-Stimulant withdrawal is less dangerous than withdrawal from alcohol, opioids, or sedatives, but seizures are possible.

-Stimulant withdrawal symptoms include depression, somnolence, anxiety, irritability, inability to concentrate, psychomotor slowing, increased appetite, and paranoia. 

-There are no known effective treatments. 

-Methamphetamine withdrawal is associated with more severe and prolonged depression than is cocaine withdrawal, so patients with withdrawal should be monitored closely for suicidal ideation.

How is methamphetamine made?

Most methamphetamine used in the United States comes from small illegal laboratories in Mexico and within the US. It is unexpensive, potent, and highly pure. Pseudoephedrine is a common component used in the production of meth, along with many other dangerous ingredients. These chemicals can cause deadly lab explosions and house fires and they may remain in the air of the houses used as laboratories.  

Can you get high if you breath second-hand methamphetamine smoke?

Researchers have not proven that people who inhale secondhand methamphetamine smoke get high or have other health consequences but breathing these fumes can cause a positive urine test for methamphetamine. More research is needed in this field.

Methamphetamine use is a big problem. Prevention of use is key in fighting this devastating addiction. In patients who are addicted, treatment includes behavioral health strategies. No medications have been approved for treatment of dependence, but we hope new research finds an effective medication to treat it.

Conclusion: Now we conclude our episode number 66 “Meth Abuse.” This topic is very extensive, but Dr Nwosu presented a good summary. Meth will continue to be a significant problem as long as we do not find a cure for this devastating addiction. Remember to screen your patients for drug use by asking direct and simple questions, then offer the addiction services available in your area. Even without trying, every night you go to bed being a little wiser.

Thanks for listening to Rio Bravo qWeek. If you have any feedback about this podcast, contact us by email [email protected], or visit our website riobravofmrp.org/qweek. This podcast was created with educational purposes only. Visit your primary care physician for additional medical advice. This week we thank Hector Arreaza, Ikenna Nwosu, and Bahar Hamidi. Audio edition: Suraj Amrutia. See you next week!

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 References: 

Ronald Strauss, Nesreen Jawhari, Amy H. Attaway, Bo Hu, Lara Jehi, Alex Milinovich, Victor E. Ortega, Joe G. Zein, Intranasal Corticosteroids Are Associated with Better Outcomes in Coronavirus Disease 2019, The Journal of Allergy and Clinical Immunology: In Practice, September 2021, ISSN 2213-2198, https://doi.org/10.1016/j.jaip.2021.08.007.

Winslow BT, Voorhees KI, Pehl KA. Methamphetamine abuse. Am Fam Physician. 2007 Oct 15;76(8):1169-74. PMID: 17990840. https://www.aafp.org/afp/2007/1015/p1169.html

Klega AE, Keehbauch JT. Stimulant and Designer Drug Use: Primary Care Management. Am Fam Physician. 2018 Jul 15;98(2):85-92. PMID: 30215997. https://www.aafp.org/afp/2018/0715/p85.html

Paulus, Martin, Methamphetamine use disorder: Epidemiology, clinical manifestations, course, assessment, and diagnosis, Up ToDate, last updated: July 20, 2021. https://www.uptodate.com/contents/methamphetamine-use-disorder-epidemiology-clinical-manifestations-course-assessment-and-diagnosis?search=methamphetamine%20use%20disorder&source=search_result&selectedTitle=2~128&usage_type=default&display_rank=2

Boyer, Edward W and Steven A Seifert, et. al, Methamphetamine: Acute intoxication, Up To Date, last updated: December 24, 2019. https://www.uptodate.com/contents/methamphetamine-acute-intoxication?search=Methamphetamine:%20Acute%20intoxication&source=search_result&selectedTitle=1~150&usage_type=default&display_rank=1

Methamphetamine, Drug Facts, National Institute on Drug Abuse (NIDA), accessed on July 28. 2021. https://www.drugabuse.gov/publications/drugfacts/methamphetamine.

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 65: Delta Variant.    

Harendra and Dr Arreaza present current evidence regarding the delta variant of SARS-CoV-2 (COVID-19), effectiveness of vaccines, and more.  

Introduction: Booster shots for the COVID-19 vaccine.  
The Department of Health and Human Services (HHS) announced in a statement dated August 18, 2021, that “a booster shot will be needed to maximize vaccine-induced protection and prolong its durability.”

This fall people may start getting their booster shots of mRNA vaccines (i.e. Pfizer and Moderna) as long as 8 months have passed since their second dose of the vaccine. The estimated date to start giving booster shots is the week of September 20, 2021.

It is anticipated that patients who received the J&J vaccine will also need a booster shot, but more data is needed to make it official. So, stay tuned for updates.

This is Rio Bravo qWeek, your weekly dose of knowledge brought to you by the Rio Bravo Family Medicine Residency Program from Bakersfield, California. Our program is affiliated with UCLA, and it’s sponsored by Clinica Sierra Vista, Let Us Be Your Healthcare Home.

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Delta Variant – The Science 

By Harendra Ipalawatte, MS4, and Hector Arreaza, MD.

A growing concern and much of the recent talk about COVID 19 has been revolving around the emerging delta variant as well as other noted virus around the world different from the alpha strain. Much like the influenza virus and swine flu, SARS-CoV-2 seems to be changing and adapting in its current form.

On July 27, 2021, the CDC recommended to urgently increase COVID-19 vaccination and reinforced the need to wear a mask in public indoor places in areas of high risk for transmission, even for fully vaccinated people. 

Concerns about Delta

CDC issued this new guidance due to several concerning developments and newly emerging data signals.

There is a reversal in the downward trajectory of cases. CDC has seen a rapid and alarming rise in the COVID case and hospitalization rates around the country. In late June 2021, the 7-day moving average of reported cases was around 12,000. In contrast, on July 27, the 7-day moving average of cases reached over 60,000. This case rate looked more like the rate of cases we had seen before the vaccine was widely available.

New data shows the delta variant is more infectious even in vaccinated individuals. Data was taken from CDC and unpublished surveillance data that will be posted soon. Delta causes more infections and spreads faster than early forms of SARS-CoV-2. Delta has shown to be more than 2x as contagious as previous variants.

The delta variant might cause more severe illness than previous strains in unvaccinated persons. In two different studies from Canada and Scotland, patients infected with the delta variant were more likely to be hospitalized than patients infected with alpha or the original virus strains.

Delta is currently the predominant strain of the virus in the United States. 

Unvaccinated people are considered the greatest concern 

Breakthrough infections (i.e., infections in patients who are fully vaccinated) happen less often than infections in unvaccinated people, all symptomatic patients infected with the delta variant can transmit it to others. 

CDC is studying the data on whether fully vaccinated people with asymptomatic breakthrough infections can transmit the infection. However, the greatest risk of transmission is among unvaccinated people who are much more likely to contract and transmit the virus.

Fully vaccinated people with delta breakthrough infections can spread the virus to others. However, vaccinated people appear to be infectious for a shorter period. 

Previous variants typically produced less viral load in the body of infected fully vaccinated people, but the delta variant produces the same high amount of viral load in both unvaccinated and fully vaccinated people. 

Effectivity of vaccines against delta

In one recent study, infection rates in India were analyzed which showed the BNT162b2 (Pfizer-BioNtech) and ChAdOx1 nCoV-19 (Oxford-AstraZeneca) vaccines were effective against the delta variant. Data on all symptomatic sequenced cases of Covid-19 in England were used to estimate the proportion of cases with either variant according to the patients’ vaccination status. The effectiveness after one dose of vaccine (BNT162b2 or ChAdOx1 nCoV-19) was notably lower among persons with the delta variant than among those with the alpha variant. The results were similar for both vaccines. 

With the Pfizer vaccine, the effectiveness of two doses was 93.7% among persons with the alpha variant and 88.0% among those with the delta variant. 

With the ChAdOx1 nCoV-19 vaccine, the effectiveness of two doses was 74.5% among persons with the alpha variant and 67.0% among those with the delta variant.

Only modest differences in vaccine effectiveness were noted with the delta variant as compared with the alpha variant after the receipt of two vaccine doses. Absolute differences in vaccine effectiveness were more marked after the receipt of the first dose. This finding would support efforts to maximize vaccination with two doses among vulnerable populations. (study was funded by Public Health England)

Vaccines available in the US

Vaccines in the US are highly effective, including against the delta variant – Pfifzer especially showing to be 88% effective after two doses.

Vaccines reduce a person’s risk of contracting COVID-19, including the delta variant. The COVID-19 vaccines authorized in the United States are highly effective at preventing severe disease and death, including against the delta variant. They are not 100% effective, and some fully vaccinated people will become infected (called a breakthrough infection) and experience illness. For such people, the vaccine still provides them strong protection against serious illness and death.

Given what we know about the Delta variant, vaccine effectiveness, and current vaccine coverage, layered prevention strategies, such as wearing masks and social distancing, are needed to reduce the transmission of this variant

Conclusion

Vaccines are playing a crucial role in limiting spread of the virus and minimizing severe disease. Although vaccines are highly effective, they are not perfect and there will be vaccine breakthrough infections. 

Millions of Americans are vaccinated, and that number is growing. This means that even though the risk of breakthrough infections is low, there will be thousands of fully vaccinated people who might become infected and able to infect others, especially with the surging spread of the delta variant.

Low vaccination coverage in many communities is driving the current rapid and large surge in cases associated with the Delta variant, which also increases the chances that even more concerning variants could emerge.

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Now we conclude our episode number 65 “Delta variant.” Harendra did a great job by presenting the most current evidence about this newer strain of SARS-CoV-2. Vaccinated people are not 100% protected against the delta variant but are more likely to get a mild disease and spread the virus for a shorter period. Vaccinations continue to be the best weapon we have against this destructive pandemic. Even without trying, every night you go to bed being a little wiser.

Thanks for listening to Rio Bravo qWeek. If you have any feedback about this podcast, contact us by email [email protected], or visit our website riobravofmrp.org/qweek. This podcast was created with educational purposes only. Visit your primary care physician for additional medical advice. This week we thank Hector Arreaza and Harendra Ipalawatte. Audio edition: Suraj Amrutia. See you next week! 

_____________________

References:

Delta Variant: What We Know About the Science. Centers for Disease Control and Prevention, updated on August 26, 2021. https://www.cdc.gov/coronavirus/2019-ncov/variants/delta-variant.html.

Lopez Bernal J, Andrews N, Gower C, Gallagher E, Simmons R, Thelwall S, Stowe J, Tessier E, Groves N, Dabrera G, Myers R, Campbell CNJ, Amirthalingam G, Edmunds M, Zambon M, Brown KE, Hopkins S, Chand M, Ramsay M. Effectiveness of Covid-19 Vaccines against the B.1.617.2 (Delta) Variant. N Engl J Med. 2021 Aug 12;385(7):585-594. doi: 10.1056/NEJMoa2108891. Epub 2021 Jul 21. PMID: 34289274; PMCID: PMC8314739. https://pubmed.ncbi.nlm.nih.gov/34289274/

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 64: H. pylori. 

Dr Lorenzo explains testing, diagnosis, and treatments for H. pylori, a bacterium that can cause peptic ulcer disease and other complications.

By Anabell Lorenzo, MD, and Hector Arreaza, MD.  

This is Rio Bravo qWeek, your weekly dose of knowledge brought to you by the Rio Bravo Family Medicine Residency Program from Bakersfield, California. Our program is affiliated with UCLA, and it’s sponsored by Clinica Sierra Vista, Let Us Be Your Healthcare Home.

Today we are going to discuss a topic that may be very basic for many of our listeners, but it is important to check our knowledge foundation to keep building on it. Helicobacter pylori was discovered in 1982 by Barry Marshall and Robin Warren from Australia. They received the Nobel prize in 2005 for their discovery of “the bacterium Helicobacter pylori and its role in gastritis and peptic ulcer disease”.

1. What is H. pylori?

It’s a gram-negative bacteria found in the stomach causing infection and GI symptoms such as dyspepsia. It is a chronic infection and it’s usually acquired in childhood. Incidence and prevalence of H. pylori infection are generally higher in people born outside of North America than among people born here. About 50% of humans are infected by H. pylori in the world. The infection can be life-long and cause no symptoms. The infection can cause peptic ulcers too.

2. When do you test for H. pylori and treat it?

Test these patients for H. pylori: 

-All patients with active peptic ulcer disease (PUD).

-Patients with history of PUD (unless previous cure of H. pylori infection has been documented).

-Patients diagnosed with low-grade gastric mucosa-associated lymphoid tissue (MALT) lymphoma.

-Patients with a history of endoscopic resection of early gastric cancer (EGC).

In a few words, test patients with PUD and stomach malignancies. 

Controversial indications include:

- Consider non-endoscopic test (stool or breath) in patients with unexplained dyspepsia who are younger than 60 years old without red flags.

- Patients with typical symptoms of gastroesophageal reflux disease (GERD) who do not have a history of PUD do not need to be tested for H. pylori infection. However, for those who are tested and found to be infected, treatment should be offered, but to the patient that the effects of treatment of H. pylori on GERD symptoms are unpredictable. This means that eradication of H. pylori may or may not affect GERD symptoms. 

-Patients taking long-term, low-dose aspirin (to reduce the risk of ulcer bleeding)

-Prior to initiation of chronic treatment with NSAIDs

-Patients with unexplained iron deficiency anemia despite an appropriate evaluation 

3. What are the testing options for H. pylori?

-In patients is having an EGD, they can be tested with gastric biopsy histology and biopsy urease (best options). Endoscopy biopsy is the best diagnostic test for H. pylori.

-In patients who do not require EGD, NONINVASIVE TESTING like STOOL ANTIGEN ASSAY and UREA BREATH TEST are a great option

-Before performing the test, it is important to stop PPIs (proton pump inhibitors) for 2-4 weeks and Bismuth/antibiotics use within 4 weeks to avoid false negative results. 

4. What ar ethe recommended first-line treatments for H. pylori?

Triple therapy: Clarithromycin triple therapy is the recommended option. This treatment includes PPI, clarithromycin, and amoxicillin OR metronidazole for 14 days. This is the recommended in areas where clarithromycin resistance is less than 15%, and in patients with no exposure to macrolides. The two antibiotics and PPI twice a day are given for 2 weeks, and the PPI is continued once daily for one month. PPI may be omeprazole, pantoprazole, or others.

Quadruple therapy: Bismuth quadruple therapy consisting of a PPI, bismuth, tetracycline, and a nitro imidazole for 10–14 days is another treatment option. Bismuth quadruple therapy is particularly attractive in patients with any previous macrolide exposure or who are allergic to penicillin.

5. Should we test for H. pylori eradication?

Confirmation of eradication should be performed in all patients treated for H. pylori because of increasing antibiotic resistance. There is not a lot of information about antibiotic resistance in the US. The test should be done 4 weeks after completing treatment.

6. What is refractory H. pylori infection? 

Refractory H. pylori infection is defined by a persistent positive H. pylori test (no serologic), at least 4 weeks after 1 or more full course(s) of a recommended first-line therapy, and when the patient has been off any medications, such as proton-pump inhibitors (PPIs), that may impact the test sensitivity.

Refractory H. pylori infection should be differentiated from recurrent infection. A recurrent infection happens when a no serologic test was negative after treatment, then becomes positive again.

7. What tests can be done to evaluate H. pylori antibiotic resistance?

We can test for resistance with culture or molecular testing, but these tests are currently not widely available in US.

8. What are the option for salvage therapy after failure of treatment? 

In patients with persistent H. pylori infection, try to avoid antibiotics that have been previously taken by the patient. Bismuth quadruple therapy or levofloxacin salvage regimens are the preferred treatment options if a patient received a first-line treatment containing clarithromycin. 

Regimens that contain clarithromycin or levofloxacin are the preferred treatment options if a patient received bismuth quadruple therapy. 

Rifabutin triple regimen consisting of a PPI, amoxicillin, and rifabutin for 10 days is a suggested salvage regimen.

Conclusion:

H. pylori is an infection that can be asymptomatic, but it needs to be eradicated if symptoms are present. Detection of H. pylori is fairly easy, but we may need to perform an EGD if patient has red flags. Antibiotics and PPIs are the first line of treatment. Test of cure is recommended for all patients.

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Now we conclude our episode number 64 “H. pylori.” Dr Lorenzo explained when and how to test patients for H. pylori. She explained that patients with GERD symptoms to not need to be tested for H. pylori, but if they are tested and have positive results, then we should eradicate H. pylori. Remember to stop PPIs 2-4 weeks before non-endoscopic tests for H. pylori. Even without trying, every night you go to bed being a little wiser.

Thanks for listening to Rio Bravo qWeek. If you have any feedback about this podcast, contact us by email [email protected], or visit our website riobravofmrp.org/qweek. This podcast was created with educational purposes only. Visit your primary care physician for additional medical advice. This week we thank Hector Arreaza and Anabell Lorenzo. Audio edition: Suraj Amrutia. See you next week! 

_____________________

References:

William D. Chey, Grigorios I. Leontiadis, Colin W. Howden, and Steven F. Moss. ACG Clinical Guideline: Treatment of Helicobacter pylori Infection. Am J Gastroenterol 2017; 112:212–238. https://pubmed.ncbi.nlm.nih.gov/28071659/

Shailja C. Shah, Prasad G. Iyer, and Steven F. Moss. AGA Clinical Practice Update on the Management of Refractory Helicobacter pylori Infection: Expert Review. Gastroenterology 2021;160:1831–1841. https://pubmed.ncbi.nlm.nih.gov/33524402/

J. Thomas Lamont. Treatment regimens for Helicobacter pylori in adults. Up to date, last updated on May, 20, 2021. https://www.uptodate.com/contents/treatment-regimens-for-helicobacter-pylori-in-adults?search=h%20pylori%20treatment&source=search_result&selectedTitle=1~150&usage_type=default&display_rank=1. 

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 63: Tumor Markers Basics. 

George and Harendra discuss with Dr Arreaza the role of tumor markers in the diagnosis and monitoring of different types of cancer.  

Introduction: Recent News about COVID-19
Written by Hector Arreaza, MD. Participation: George Karaghossian, MS3, and Harendra Ipalawatte, MS3.

Before we talk about our topic today, there are three news worth sharing about COVID-19.

First, we are all aware of the increased number of patients affected by COVID-19 and increased mortality. Most of the patients who are severely ill or those who require admission are unvaccinated. The cases of breakthrough infections (infections in patients who are fully vaccinated) continues to be rare.

Second, CDC has officially recommended COVID-19 vaccination in pregnant women (August 11, 2021)[1].  All people 12 years of age and older is recommended to get vaccinated against COVID-19, including pregnant women. There were 2,500 women who received the mRNA vaccine against COVID-19, and there was not an increased risk for miscarriage. Vaccinated pregnant women (or persons) had a miscarriage rate of 13% (similar to the miscarriage average in general population, which is 11-16%).

Third, FDA gave an emergency use authorization for a third dose of mRNA vaccines (Pfizer and Moderna) for certain immunocompromised patients (August 12, 2021)[2]. The third dose of the vaccine (it has to be the same vaccine you received) has to be given at least 28 days apart from your last dose. Patients who may receive a third dose include: Patients who are undergoing active treatment for solid tumor and hematologic malignancies, recipients of solid-organ transplant and taking immunosuppressive therapy, moderate or severe primary immunodeficiency (e.g. DiGeorge syndrome, Wiskott-Aldrich syndrome), patients with advanced or untreated HIV infection, patient who are taking high-dose corticosteroids (i.e. >20 mg prednisone or equivalent per day) and other immunosuppressive medications. If in doubt, consult our oncologists and rheumatologists.

Let’s switch gear and introduce the topic for today. Given the high mortality and morbidity of cancer, in general, early detection of cancer is one of the most important goals in primary care. Today George and I will discuss the usefulness, pitfalls and will mention some of the most common tumor makers.

This is Rio Bravo qWeek, your weekly dose of knowledge brought to you by the Rio Bravo Family Medicine Residency Program from Bakersfield, California. Our program is affiliated with UCLA, and it’s sponsored by Clinica Sierra Vista, Let Us Be Your Healthcare Home. 

Tumor Markers Basics. 
By George Karaghossian, MS3, Ross University School of Medicine; Harendra Ipalawatte, MS3, Ross University School of Medicine; and Hector Arreaza, MD.  

Introduction:
Do you remember how we came up with the idea for this topic? We had a patient with an intraabdominal malignancy which appeared to be from the GI tract vs an adnexal mass. We order tumor markers to assist in the diagnosis of the origin of this malignancy. 

Definition: Tumor markers are usually proteins or other substances that are produced by cancer cells or non-cancerous cells. Circulating biomarkers and tissue biomarkers are the two types of tumor markers we utilize to track the course of the tumor’s growth. Circulating tumor markers are found in bodily fluids such as blood, urine, and stool. Tissue markers are typically found on the actual cancer cells. These markers can help in the assessment of certain cancers. The downside of tumor markers is that they are not always reliable, and they may not be detected in the early stages of cancer[2]. 

Characteristics of a good screening test: A good screening test must be capable of detecting a high proportion of disease when patients are asymptomatic, tests should be safe, not excessively expensive, lead to improved health outcomes, be widely available, and interventions after a positive test should also be available.

Can tumor markers be used for cancer screening?
Tumor markers should not be used as a primary tool for cancer screening because they lack sensitivity and specificity. The most definitive tool for diagnosis of cancer therefore is biopsy, thus tumor markers cannot be used to diagnose cancer.

Tumor markers can be done in blood, in urine, and in tissue (biopsy). An example of tumor markers in biopsies are estrogen receptor (ER) and progesterone receptor (PR).

What are tumor markers good for?

Tumor markers may be good indicators of response to cancer therapy. When cancer patients are undergoing therapy for treatment of their cancer, we usually track tumor markers to see if there is downward trend over the course of therapy indicating that the therapy is working. 

Tumor markers are also a good tool to monitor early relapse of certain malignancies. After treatment, tumor markers may be measured to see if the cancer is returning after treatment. Some tumor markers also assist in deciding which treatment is best. For example, the example I mentioned before ER and PR are tumor markers that can be used to pick the best treatment for certain breast tumors.

Pitfalls of tumor markers. 

A benign disease can raise some tumor marker levels. Some people without cancer can have high levels of a tumor marker. Tumor marker levels can change over time, and levels may be undetectable until cancer gets worse. 

Common tumor markers:

PSA (Prostate specific antigen): Elevated in prostate cancer, BPH, DRE (recently showed to be questionable for screening). PSA is one of the most controversial tumor markers when it comes to screening for prostate cancer. Although PSA has been shown to be elevated prostate cancers, it has also been shown to be increased in BPH, prostatitis, digital rectal exams as well as post ejaculation. This tumor marker remains controversial in screening because there is an uncertainty about the outcome of localizing such prostate cancers. According to the American Urological Association they suggest that patients should be given an abundant amount of education about PSA, and they should ultimately decide if they would like this marker to be used as a tool for screening for their prostate cancer. 

PSA was widely used in the past for prostate cancer screening. It was like the “savior” for men who wanted to avoid digital rectal exam. Well, several years later, PSA increased the number of biopsies and even mortality related to prostate cancer diagnostic tests. The IsoPSA may be a better tool, but it is not ready for prime time yet (listen to episode 60). If you find a PSA higher than 4, refer to urology.

ALP (alkaline phosphatase): Elevated in metastasis to bone and liver and Paget’s disease of the bone. In Paget’s disease, you will not be able to use ALP to tell if the patient has bone cancer or just the progression of the disease, but an incidental elevated ALP can prompt you to investigate and come to a diagnosis of Paget’s disease after an extensive work up. 

ALP is also elevated in many other conditions, for example, obstruction of the biliary tree.

AFP (alpha feto-protein): Elevated in hepatocellular carcinoma, yolk sac tumor, neural tube defects, ataxia telangiectasia, mixed germ cell tumors.

Beta-hCG (beta human chorionic gonadotropin): Elevated in hydatidiform mole, testicular cancer, mixed germ cell tumors.

After treatment of a molar pregnancy, the patient has regular measurements of hCG until it is undetectable. A rise in hCG may prompt additional treatment or work up because there is an increased risk of choriocarcinoma.

CA 19-9 - pancreatic adenocarcinoma.
CA 19-9: When we think of this tumor marker our minds tend to think about the possibility of pancreatic adenocarcinoma. However, this tumor marker is also associated with other malignancies such as biliary tract cancers and esophageal cancer as well. CA 19-9 has less than 1% PPV, but in the case where pancreatic cancer is already diagnosed, screening with CA 19-9 has a positive predictive value of 97%. Also, there is an 80% and 90% sensitivity and specificity respectively for pancreatic cancer, when already diagnosed.

CA 125: Elevated in ovarian carcinoma, and malignant ascites. This tumor marker is often associated with epithelial ovarian cancers, often increased when malignancy is present. CA 125 levels are elevated in 85% of women with malignant type ovarian cancer. However, this marker is insensitive to early stages of ovarian cancer and are not very useful. CA 125 has not shown an increase in survival for women with ovarian malignancies.

CEA (Carcinoembryonic antigen): Commonly elevated in colon or pancreatic cancers. Less commonly elevated in gastric cancers, breast cancers, medullary thyroid carcinoma, irritable bowel disease, non-small cell lung carcinoma, increased in smokers.[4]

CEA is a tumor marker that is overexpressed in adenocarcinomas especially when it comes to colorectal cancers. When we see elevated CEA values, we tend to think colorectal cancer is imminent however, this is one of the tumor markers that are ultimately one of the most nonspecific. CEA is also elevated in cigarette smoking, PUD, IBD, pancreatitis and medullary thyroid cancers. The American Society of clinical oncology recommends that we monitor CEA levels every two to three months for at least two years with patients for surgical candidates with stage II/III colorectal cancers. 

Calcitonin: Elevated in medullary thyroid carcinoma, MEN2A/2B. 
Some doctors may be tempted to measure calcitonin before initiating a GLP-1 receptor agonist medication, these meds are very popular now for diabetes treatment and obesity. Calcitonin measurement is not recommended before starting treatment. Medullary thyroid carcinoma was demonstrated in mice who received GLP-1 RA, not in humans. MEN2 (multiple endocrine neoplasia type 2) and personal and family history of medullary thyroid cancer are contraindications to GLP-1 RA (exenatide, dulaglutide, semaglutide, those meds that end in -tide). 

As a reminder, all MEN2 presents with pheochromocytoma and medullary thyroid carcinoma. MEN2A, additionally presents with parathyroid hyperplasia, and MEN2B presents with mucocutaneous neuromas, GI symptoms and muscular hypotonia (marfanoid habitus). 

Chromogranin A: Elevated in neuroendocrine tumors (insulinoma, glucagonoma, VIPoma) carcinoid tumor, small cell lung cancer.

LDH (lactate dehydrogenase): Elevation indicates tumor invasiveness. This is widely used test for many non-malignant conditions as well, for example hemolytic anemias.

CYFRA 21-2: Elevated in lung cancer (non-small cell type), squamous cell lung carcinoma (68% sensitivity, 94% specificity).[3]

SMRP (serum soluble mesothelin related peptide): Elevated in mesothelioma.

NSE (neuron specific enolase): Elevated in small cell lung cancer, carcinoid, neuroblastoma, also released 2/2 brain injuries.

Monoclonal immunoglobulins: Elevated in multiple myeloma, Waldenstrom macroglobulinemia.

S-100: Elevated in malignant melanoma.

B2 microglobulin: Elevated in multiple myeloma, CLL.

Final remarks.
George: The biggest challenge we face with these biomarkers is the inconsistency of the results which may be influenced by our collection methods and sample storage[4].  The science community has come a long way over the years in assessing these markers and using them to the best of their abilities, however it remains a subject matter that must be further assessed to make sure our research and data does not result in false and misleading outcomes.

Arreaza: For now, use tumor markers with responsibility. Discuss with patients the consequences of elevated tumor markers, as you may end up with more questions than answers. But, we have to be fair and also highlight the role of tumor markers in monitoring response to treatment and cancer recurrence. Also, they may be useful (especially the tissue specific markers in identification of cancers and in the decision on treatments).

Conclusion: Now we conclude our episode number 63 “Tumor Markers.” Some of the most common markers were discussed. We hope this information will help you decide when to use tumor makers to evaluate your patients. Remembering which conditions cause elevation for each tumor marker is challenging, but with practice and time, you can master the most common ones. Even without trying, every night you go to bed being a little wiser.

Comirnaty®: I want to make sure you know about this. The FDA finally gave official approval to the Pfizer BioNTech COVID-19 vaccine on August 23, 2021. This vaccine now has a brand name: Comirnaty®. It is approved for persons older than 16 years old, however, it continues to be available for children between 12-15 years old. Safety monitoring will continue but so far, this vaccine has a strong evidence of being effective and safe.

Thanks for listening to Rio Bravo qWeek. If you have any feedback about this podcast, contact us by email [email protected], or visit our website riobravofmrp.org/qweek. This podcast was created with educational purposes only. Visit your primary care physician for additional medical advice. This week we thank Hector Arreaza, Harendra Ipalawatte, and George Karaghossian. Audio edition: Suraj Amrutia. See you next week! 

_____________________

References:

New CDC Data: COVID-19 Vaccination Safe for Pregnant People, CDC Online Newsroom, August 11, 2021. https://www.cdc.gov/media/releases/2021/s0811-vaccine-safe-pregnant.html.

Talking with Patients Who Are Immunocompromised about an additional dose of an mRNA COVID-19 vaccine, Centers for Disease Control and Prevention, https://www.cdc.gov/vaccines/covid-19/clinical-considerations/immunocompromised-patients.html.

Perkins GL, Slater ED, Sanders GK, Prichard JG. Serum tumor markers. Am Fam Physician. 2003 Sep 15;68(6):1075-82. PMID: 14524394. https://www.aafp.org/afp/2003/0915/p1075.html

Nagpal M, Singh S, Singh P, Chauhan P, Zaidi MA. Tumor markers: A diagnostic tool. Natl J Maxillofac Surg. 2016;7(1):17-20. doi:10.4103/0975-5950.196135 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5242068/

Wieskopf Bram, et al, CYFRA 21-1 as a biological marker of non-small cell lung cancer. Chest Journal, Clinical Investigations, vol 108, issue 1, P163-169, July 01, 1995, DOI:https://doi.org/10.1378/chest.108.1.163. https://journal.chestnet.org/article/S0012-3692(16)38611-1/fulltext#relatedArticles.

Schrohl, Anne-Sofie, et al. Tumor Markers, from laboratory to clinical utility. Molecular and Cellular Proteomics. Journal of Oncological Studies, vol 2, issue 6, P378-387. June 01, 2003. https://www.mcponline.org/article/S1535-9476(20)34451-0/fulltext.

Tumor Markers in Common Use. National Cancer Institute. National Institutes of Health. https://www.cancer.gov/about-cancer/diagnosis-staging/diagnosis/tumor-markers-list.

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!