The Curbsiders podcast

#437 Clinical Pearls ACP #IM2024

April 29, 2024 | By

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We cover angina, COPD-asthma overlap, home oxygen, colon cancer screening, cancer survivorship, tobacco cessation, e-cigarettes, step counts for health,  new drugs, the RSV vaccine, addiction medicine, interstitial lung disease, APOL1-mediated kidney disease, testosterone therapy, antimicrobial resistance, office-based allergy testing and more! The Curbsiders review highlights, clinical pearls, and practice-changing updates from the American College of Physician Internal Medicine Meeting #IM2024! 

No CME for this episode due to rapid turnaround, but claim CME for most episodes at  curbsiders.vcuhealth.org!

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Show Segments

  • Intro
  • ACP Pearls
  • Outro

ACP Recap: Part 1 Show Notes 

Clinical Pearls: Cardiology and Pulmonary Medicine w/ Dr.  Megan Scrodin, Dr. Michael Cullen

Dr. Cullen highlighted that the term ‘atypical angina’ is no longer recommended, and instead, cardiac, possible cardiac, and noncardiac chest pain is preferred (ACC/AHA 2022).  Chest pain relief with nitroglycerin is not predictive of the chest pain being due to ischemia, and suggested we do not consider that in our evaluation.  He cited a study which showed that nitro relieves chest pain in 35% of patients with ACS and 41% of patients without (Hendrikson 2003).

Dr. Scrodin highlighted the importance of the asthma-COPD overlap.  She suggested fractional exhaled nitric oxide testing which is a non-invasive measure of eosinophilic inflammation and is a good positive predictive value for diagnosing asthma, allergic rhinitis, and non-asthmatic eosinophilic bronchitis (with the caveat that normal levels do not rule out asthma; and smoking with  inhaled corticosteroids are associated with lower FeNO).  Patients should be optimized with high dose ICS (with LABA/LAMA) before other advanced therapies (in contrast to treating COPD alone where LABA/LAMA would be appropriate) (GINA 2023). 

Dr. Scrodin also emphasized that in patients with advanced COPD who have exertional hypoxia but no resting hypoxia, exertional home oxygen does not improve quality of life or functional capacity (NEJM 2016). 

News You Can Use: Current Clinical Guidelines in Colorectal Cancer Screening w/ Dr. Amir Qaseem, Dr. Wanda Nicholson, Dr. Timothy Wilt

The ACP 2023 CRC screening guidelines state that “clinicians should consider not screening asymptomatic average risk between the ages of 45-49 years old.  Clinicians should discuss the uncertainty around benefits and harms of screening in this population.” Incidence is low in this age group and thus benefit is small, even though there was a 15% increase in colorectal cancer rates in those age 45-49 from 2016-2021, the absolute rates are still low (only from 29→33 per 100,000, only a 4/100,000 increase.) Of note, these guidelines are different from the USPSTF guidelines for Colon Cancer screening.  

Multiple Small Feedings of the Mind: General Internal Medicine, Oncology, Infectious Disease/Immunology  w/ Dr. Rachel Brook, Dr. Stephanie Faubion, Dr. Narjust Florez, Dr. F. Lee

Models predict cancer survivors will make up a larger share of patients in coming decades (Bluethmann 2016).  Dr. Florez pointed out that anyone with cancer currently living is a survivor, and that we will be treating more and more survivors (both on treatment and who have completed treatment) in coming years.  

We need to be aware, therefore, of toxicities from treatments that these patients may be currently on or have received in the past, especially toxicities from checkpoint inhibitors, which can cause long-term inflammatory side effects and can occur at any point after treatment (including years out).   Skin toxicity (ie: rash) tends to come first (Martins 2019), followed by colitis (ie: significant, liquidy diarrhea), and then the endocrinopathies–including the thyroid (either hypo or hyperthyroid) and other adrenal/endocrine problems.  Check out this graphic by Weber et al (2015) and the paper by Martins et al. (2019) for the whole range of possible inflammatory symptoms from checkpoint inhibitors, including which may be permanent.  A reminder that many side effects need to be treated promptly (often with high dose steroids or hormone replacement) and are also not reversible

Dr. Florez also notes that other lifestyle recommendations,  other cancer surveillance and screening, often get forgotten in patients who are cancer survivors or on long-term treatment., so remember to do your smoking cessation, get the colonoscopy, for them too! 

Tobacco Dependence: Promoting Health Behavior Change and Smoking Cessation w/ Dr. Hasmeena Kathuria

We have options for treating tobacco cessation in patients who have psychiatric history (throwback to EAGLES trial: Anthenelli 2016). The EAGLES trial, a large-scale randomized, placebo-controlled study, evaluated the neuropsychiatric safety and cessation efficacy of varenicline, bupropion, and nicotine patches in smokers with and without psychiatric disorders. It found no significant increase in moderate or severe neuropsychiatric adverse events for varenicline or bupropion compared to the nicotine patch or placebo. Varenicline was the most effective in helping smokers quit, followed by bupropion and the nicotine patch, both of which were more effective than placebo. TL;DR – varenicline and bupropion are safe from a neuropsychiatric standpoint and effective for smoking cessation. 

Recent studies like Auer 2024 have shown that e-cigarettes can provide higher rates of tobacco abstinence vs just counseling plus optional Nicotine Replacement Therapy (NRT).  However, fewer participants in the e-cigarette group abstained from all nicotine sources compared to the control. It is possible we are just replacing one addiction with another. For many people who are now dependent on vape and e-cigarettes, we now have some better evidence on how to treat that.

Varenicline and counseling for vaping cessation was looked at in Caponnetto 2023. This randomized, double-blind, placebo-controlled trial evaluated the efficacy and safety of varenicline, combined with counseling, for vaping cessation among exclusive daily electronic cigarette users. Varenicline significantly increased the continuous abstinence rate compared to placebo during both the treatment phase (weeks 4-12) and the follow-up phase (weeks 4-24), demonstrating its potential as an effective aid for vaping cessation. In addition, evidence for NRT and counseling was seen in Palmer 2023. This study found that adults are motivated to quit vaping due to health concerns, dependence, stigma, and cost, with NRT showing promise in facilitating cessation, particularly among mono users, who reported a 33.3% abstinence rate at the end of treatment.

Consult Talk w/ Dr. Geno Merli and Dr. Howard Weitz

What is the evidence for encouraging patients to walk 10,000 steps per day? Apparently, Leonardo da Vinci was credited with envisioning the first pedometer (Bassett 2017). The craze for 10,000 steps started with the Tokyo Olympic Games in 1964. After the Olympics, there was a physical fitness rage in Japan and the Yamasa Company created the manpo-kei (aka 10,000 steps meter) as the slogan just sounded good (source provided in the talk).  Saint-Maurice 2020 showed a higher daily step count was significantly linked to reduced all-cause mortality, with participants taking 8,000 steps per day having about half the mortality risk of those taking 4,000 steps per day. 

In this very recent Journal of the American College of Cardiology study by Stens 2023, they found that as few as 2,517 steps per day can be associated with an 8% reduction in all-cause mortality, while 2,735 steps per day achieve an 11% reduction in cardiovascular disease (CVD) risk. The study found that the optimal daily step count for maximizing health benefits to be 8,763 steps for a 60% reduction in all-cause mortality and 7,126 steps for a 51% reduction in CVD risk. Both the number of steps and their intensity (measured in steps per minute) independently contributed to lowering the risks of mortality and CVD. However, exceeding 10,000 steps per day did not provide significant additional health benefits, indicating a plateau effect at higher step counts.

New Meds to Know in Primary Care w/ Dr. Gerald (Gerry) Smetana

Vonoprazan for refractory GERD: Persistent reflux symptoms in patients taking proton pump inhibitors (PPIs) are common, and GERD is the most common GI symptom encountered in primary care. Vonoprazan is a member of a new class of antireflux medications called PCABs (potassium competitive acid blockers) that is more rapidly absorbed, has a longer half-life, and is more potent than PPIs. In a large RCT, vonoprazan was more effective than lansoprazole for severe erosive esophagitis, but had similar efficacy for uncomplicated GERD. Drawbacks include more frequent diarrhea among patients receiving vonoprazan, potential for reduced absorption of drugs that need a low pH, and high cost ($650 per month). It is also currently only approved for 6 months of use. Consider use for patients with severe erosive esophagitis who have failed standard therapy with PPIs.

Fezolinetant for menopausal hot flashes: Menopausal hot flashes can interfere with sleep and quality of life. Hormone replacement therapy (HRT) is the most effective treatment, but it carries risks (breast cancer, coronary disease, stroke, pulmonary embolism, and others) that many women may rightly want to avoid. Gabapentin and SSRIs are alternatives, but these are less effective. Fezolinetant is a neurokinin 3 (NK3) receptor antagonist that modulates neuronal transmission in the part of the brain that controls temperature regulation and sweating. In two small RCTs (SKYLIGHT-1 and SKYLIGHT-2), fezolinetant reduced the frequency and severity of menopausal hot flashes better than placebo. Headache and transaminase elevations occurred more commonly than with placebo, and currently FDA recommends women undergo frequent monitoring of liver tests. Based on these data, fezolinetant currently has a level I recommendation for use from the North American Menopause Society.

RSV vaccines to prevent lower respiratory tract illness: The burden of RSV on elderly and immunocompromised patients in the United States is similar to influenza, infecting 4-10% of older adults annually. Lower respiratory tract disease occurs in up to 1/3 of elderly patients, who experience an increased risk of hospitalization after age 60 (and especially after age 80). Currently there are two vaccines available in the US: one from GSK (an adjuvanted pre-fusion F protein vaccine) and one from Pfizer (a bivalent pre-fusion F protein vaccine without an adjuvant). Both the GSK and Pfizer vaccines have been shown in large RCTs (here and here) to reduce the risk for lower respiratory tract disease; however, the absolute risk reductions for both were low, ranging from 0.3% – 0.5%. Minor adverse events were very common, and a small number of patients who received these vaccines developed severe neuroinflammatory complications (Guillain-Barre syndrome and acute disseminated encephalomyelitis). Neither trial was powered to detect an impact on hospitalization or mortality, and patients with relevant comorbidities were excluded. Currently CDC recommends engaging in shared decision-making for adults over 60 who are interested in the vaccine. Note that an mRNA vaccine for RSV that is hoped will have a better side effect profile is currently in development by Moderna; stay tuned for clinical trial results and post-marketing surveillance data.

Gepirone for treatment of major depression: Although SSRIs are effective for many patients with depression, side effects limit their use. Gepirone is a recently-approved 5-HT1A partial agonist similar to buspirone that earned FDA approval in 2023. Despite its interesting backstory (it was previously rejected by the FDA 3 times), it may have a place in the armamentarium for depression because of its favorable side effect profile. In a small RCT, dizziness and nausea were more common with gepirone than placebo, however, patients on-treatment reported no increase in weight gain, fatigue, or sexual side effects. Overall, the adverse effect profile is closer to that of bupropion than the SSRIs. For this reason, gepirone may ultimately find a role in the treatment of sexual dysfunction, with or without depression. 

What’s New in Addiction Medicine w/ Dr. Charles Reznikoff 

The vasoactive properties of cannabis (coronary vasoconstriction, peripheral vasodilation, endothelial inflammation and possible thrombogenesis) may confer an increased risk of adverse cardiovascular outcomes. This is particularly important given the high prevalence of cannabis use among aging baby boomers. In particular, cannabis use disorder has been shown to increase risk of perioperative MACE, and other studies have linked cannabis use to motor vehicle accidents, falls, and drug-drug interactions. Dr. Reznikoff encouraged the audience to maintain a high index of suspicion for cardiovascular disease when evaluating patients who regularly use cannabis for symptoms that may reflect ischemia and to avoid diagnostic anchoring on cannabis hyperemesis syndrome.  

Interstitial Lung Disease: Evaluation and Management w/ Dr. Kevin Wilson

Dr. Wilson reminds us to consider interstitial lung disease (ILD) in patients with unexplained chronic cough, chronic dyspnea, or ground glass opacities seen on imaging that are not better explained by other causes. And of course, ILD is an umbrella classification, and acute presentation of ILD can be due to hypersensitivity pneumonitis, connective tissue disease-related ILD, drug-induced ILD, cryptogenic organizing pneumonia, acute eosinophilic pneumonia, and acute interstitial pneumonia.  Check out our full-episode on ILD from 2020 for more background on this topic. 

There is ongoing debate as to whether someone with acute presentation of suspected ILD should undergo empiric therapy or invasive diagnostic testing to confirm diagnosis.  Invasive diagnostic options include bronchoalveolar lavage, transbronchial forceps biopsy, transbronchial cryobiopsy,  and surgical biopsy.  Cryobiopsy seems to have a higher diagnostic yield than forceps biopsy (Chami et al 2021), but may not be as widely available. 

In any case, treatment is largely with prednisone, but this should be avoided if this is thought to be scleroderma-related lung disease, as it might precipitate renal crisis (Raghu et al 2024).  Antifibrotics are usually not started early in the disease course, as many types of ILD do not typically progress to fibrosis (Raghu et al 2024).

As the number of CT scans we do increases, we are also finding more findings suggestive of interstitial lung disease in patients without symptoms, and these are deemed “interstitial lung abnormalities.”  These findings are associated with advanced age, tobacco use, and chronic obstructive pulmonary disease.  Dr. Wilson suggests CT follow up at 3, 6, and 12 months, and the Fleischner Society recommends repeat testing in 3-12 months, including pulmonary function testing, and then 12-24 months unless symptoms change (Hatabu et al 2021).

Update in Nephrology w/ Dr. Michael J. Ross

APOL1-mediated kidney disease: Apolipoprotein L1 (encoded by APOL1) is a protein that protects against African sleeping sickness, caused by Trypanosoma brucei. Unfortunately, APOL1 gain-of-function variants also increase the risk of kidney failure (progressive, proteinuric nephropathy). Dr. Ross notes that some patients formerly classified as hypertensive CKD might be re-classified as APOL1 mediated disease. Now, a new drug, inaxaplin, has shown early promise in proteinuric kidney disease in persons with two APOL1 variants by reducing proteinuria in an open-label phase 2a clinical study (Egbuna 2023). 

Cystatin-C: Creatinine measurements are insensitive to small changes in GFR and creatinine is affected by many non-kidney factors. Cystatin C is more sensitive to small changes in GFR, more predictive of future clinical events, and less affected by non-kidney factors. Combined formulas using both creatinine and cystatin C are most accurate for predicting GFR. (Chen 2022). Dr. Ross recommends checking cystatin C in adults over 65 years old with GFR 45-59 to identify those at high risk.  

Testosterone Therapy w/ Dr. Bradley Anawalt

Dr. Anawalt thinks of hypogonadism as a continuum. Testosterone therapy is more likely to benefit those with severe hypogonadism than those with mild-moderate hypogonadism or eugonadism. 

Testosterone therapy can be given as IM injections or via gel. Weekly injections, which tend to be the cheapest formulation, cause a supraphysiologic peak before levels taper off between doses. But, don’t be fooled. The testosterone level from gel therapies varies widely even when measured over time in the same patient due to factors that affect muscle blood flow or time for absorption like exercise, swimming, or showering. Testosterone levels should be checked between 7 to 10 am, preferably fasting and lab reference ranges are based on healthy young men. 

Don’t miss Klinefelter syndrome! It may affect up to 1 in 500-600 men so the average primary care panel may have 2-3 cases. Patients are tall with gynecomastia, small testes (measure with an orchidometer), and might complain of fertility issues. Labs would show high FSH more so than LH, and low serum testosterone. Karyotype analysis can confirm the diagnosis (Anawalt UpToDate accessed April 22, 2024). 

Antimicrobial Resistance in Inpatient Medicine: How to Treat the Toughest Bugs, w/ Dr. Paul Pottinger

Dr. Pottinger talked about both community-associated and hospital-associated MRSA, describing the skin and soft tissue infections more typically representing community-associated MRSA and those more invasive infections typically concerning for hospital-associated MRSA–but notes that today, the strains that we actually see in the hospital mostly came into the hospital with your patient and are community-associated strains. 

What about the MRSA Nasal Swab? It’s a really good test, with a very high negative predictive value (NPV) in the upper 90s (Parente 2018) and is therefore extremely helpful in decision-making about peeling off MRSA coverage for both community acquired and hospital-acquired pneumonia.  Of course, a reminder that the test does not have a 100% NPV, and therefore the MRSA nasal swab should not supersede clinical judgment or very high-level suspicion for a MRSA pneumonia based on imaging, acuity of illness, or prior data suggesting prior MRSA infections. 

Another pearl from Dr. Pottinger came regarding antibiotic susceptibility testing, and testing for doxycycline susceptibility. Tests typically report tetracycline susceptibility on antibiograms, not doxycycline susceptibility, because it’s easier for the lab to run tetracycline testing than doxycycline. 

If you have a tetracycline susceptible strain, you can use doxycycline (tetra susceptible = doxy susceptible). If however you see a report of tetracycline resistance, ask the lab to measure doxycycline susceptibility, as about half of the strains that are tetracycline resistant will actually end up being doxycycline (or minocycline) susceptible. 

Lastly, he linked to a quick clinical decision support tool called PALERGY to help clinicians decide about next steps for antibiosis in the setting of a reported penicillin allergy.  

Office-Based Allergy Testing for the Primary Care Physician w/ Dr. John Kelso 

Serum Specific IgE Testing: This testing can help identify specific allergies, but Dr. Kelso recommends against sending large panels that can pick up false positives (or information that you don’t know what to do with) to substances in the environment or food, and instead recommends sending specific serum IgE based on that patient’s clinical history.  Don’t send total IgE levels because the total IgE level is not predictive of atopy and allergic reactions. 

Delabeling Penicillin Allergies: Not everyone needs to be referred to allergy for desensitization. If patients had a non-serious reaction or little memory of it and no recurrences (no hospitalization/systemic signs or symptoms, don’t remember the reaction, didn’t have a bad skin reaction or SJS/TEN, didn’t have hives immediately after taking a medication), you can consider proceeding with in-office amoxicillin challenge without referring to allergy (Instructions: give oral 250 mg once, observe in office for 1 hour, then can go with return precautions, and instructions to call if rash develops). Obviously, if the history is anaphylaxis or urticaria shortly after a first dose, those patients should go to an allergy clinic for penicillin skin testing.  


Links

  1. Annals Consult Guys
  2. PALERGY

Goal

Listeners will develop recap the top pearls from ACP #IM2024. 

Learning objectives

After listening to this episode listeners will…  

  1. Feel generally warm and happy inside.
  2. Feel like they attended ACP #IM2024.
  3. Fall deeper in love with Dr. Paul Nelson Williams, #AmericasPCP

Disclosures

The Curbsiders report no relevant financial disclosures. 

Citation

Heublein M, Taranto N, Chiu C, Ganatra R, Garbitelli B, Williams PN, Watto MF. “#437 Clinical Pearls ACP #IM2024”. The Curbsiders Internal Medicine Podcast. thecurbsiders.com/category/curbsiders-podcast April 29, 2024.

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Episode Credits

Producers: Matthew Watto MD, FACP; Paul Williams MD, FACP, Molly Heublein MD, Nora Taranto MD, Chris Chiu MD, Rahul Ganatra MD MPH, Beth Garbitelli MD
Show Notes: Matthew Watto MD, FACP; Paul Williams MD, FACP, Molly Heublein MD, Nora Taranto MD, Chris Chiu MD, Rahul Ganatra MD MPH, Beth Garbitelli MD
Hosts: Matthew Watto MD, FACP; Paul Williams MD, FACP
Reviewer:Matthew Watto MD FACP
Showrunners: Matthew Watto MD, FACP; Paul Williams MD, FACP
Technical Production: PodPaste

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