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Episode 238 -- September 2025 -- Part 2 AFP: American Family Physician
In Episode 238 of the AFP Podcast, the hosts discuss key medical topics from the September 2025 issue, including lymphadenopathy evaluation, the effectiveness of galantamine for Alzheimer's, pare...
Episode 238 -- September 2025 -- Part 2 AFP: American Family Physician
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Speaker A
The AFP Podcast is brought to you by the American Academy of Family Physicians and by Mayo Clinic. Mayo Clinic proudly supports this AFP podcast. Mayo Clinic Family Medicine puts patients first by pursuing innovations that change lives and the future of care. Learn more about joining our team@jobs.mayoclinic.org FamilyMedicine.
Speaker B
Welcome to the American Family Physician podcast for part two of the September 2025 issue. I'm Jake.
Speaker C
I'm Puneet.
Speaker A
And I'm Justin.
Speaker B
And we are residents and faculty, mostly residents of the University of Arizona College of Medicine, Phoenix Family Medicine Residencies. Today on the podcast, we'll talk about lymphadenopathy, galantamine, parental agents for migraines, episwitch, prostate cancer screening test, vitamin B12 deficiency, and Fezalinitan for menopause.
Speaker C
The opinions expressed in the podcast are our own and do not represent the opinions of the American Academy of Family Physicians. The editor of American Family Physician or Banner Health do not use this podcast for medical advice. Instead, see your own family doctor for medical care.
Speaker B
We'Re on a Mission to Living the best From American Family Position On a Mission to Living the Best Strong American Family Position first up, we have a main topic, lymphadenopathy Evaluation and Differential Diagnosis, and it comes to us from the team out of Florida State University College of Medicine, Bay Care Family Medicine Residency Program in Winter Haven, Florida.
Speaker C
Lymphadenopathy is defined as lymph nodes with abnormal growth or character. The differential is quite extensive, ranging from serious conditions like lymphoma, autoimmune disorders, and HIV to more benign conditions such as transient infections or reactive processes.
Speaker A
So lymph nodes that have been enlarged or inflamed for less than two weeks and present without growth for more than a year are usually benign in both children and adults. But Hodgkin lymphoma and other indolent non Hodgkin lymphoma types can present as chronic lymphadenopathy without observable growth.
Speaker C
So when do we get concerned?
Speaker B
Notably, adults with hemoptysis, fever, or systemic symptoms such as night sweatshirt and weight loss should raise suspicion for malignancy or tuberculosis.
Speaker A
Plus, patients with lymphadenopathy due to autoimmune conditions may present with rash, arthralgias, myalgias, and other systemic or constitutional symptoms. Likewise, symptoms of fever, headache, along with recent exposure to animals, high risk sexual behaviors or travel to endemic areas should.
Speaker C
Raise concerns for infectious causes along with a thorough history. The physical exam should evaluate for location, size, texture, mobility and tenderness of the lymph nodes. Notably, lymph nodes that are larger than 2cm hard or attached to surrounding structures may indicate malignancy or granulomatous disease. In contrast, lymph nodes that are tender, fluctuant and not fixed are often associated with bacterial infections. Pain or tenderness on palpation is nonspecific and can be present in both benign and malignant causes.
Speaker A
So lymphadenopathy can also be generalized if it involves two or more non contiguous lymph node regions. Anatomically, drainage patterns for lymphatic fluids can help identify and localize infections. Generalized lymphadenopathy typically counts for 25% of all causes and often indicates an underlying systemic disease, but the most common causes are often self limited viral infections like Epstein Barr virus and medication use.
Speaker C
Additionally, systemic infections and autoimmune diseases such as hiv, rheumatoid arthritis and lupus can also result in generalized lymphadenopathy.
Speaker B
While a thorough history and examination can reveal the underlying cause, further evaluation is often needed with laboratory workup and imaging.
Speaker C
For generalized lymphadenopathy with unclear diagnosis and low concerns for malignancy, inflammatory, infectious and autoimmune workup is recommended and if diagnosis.
Speaker A
Is unclear but high risk symptoms are present, fine needle, core needle or excisional biopsy are appropriate. Also, if the lymph node is localized and persists for more than one month, biopsy is also appropriate.
Speaker B
Finally, imaging can provide further diagnostic clues with ultrasound being the first line modality in children less than 14 years of age. It is non invasive, radiation free and less expensive. Of course Connecticut imaging can be used in patients older than 14 and especially for evaluating the abdomen and pelvis. If concerned for malignancy in adults, CT or MRI with contrast is the preferred modality.
Speaker C
I would also get a chest X ray if you're concerned for inflammatory or infectious causes with the initial lab work, this can help identify mediastinal widening, hilar lymphadenopathy and calcifications in chronic cases.
Speaker B
And as far as treatment, a course of antibiotics can be considered in patients with symptoms suggestive of bacterial lymphadenitis. However, corticosteroids are avoided because they can mask histopathology findings of malignancy.
Speaker C
Well, the time is up on this educational piece.
Speaker A
Get it Dymus like where the immune cells go to get educated.
Speaker B
Oh boy. Next up we have a Cochrane for clinicians Galantamine for dementia and it comes to us from the team out of Penn State University College of Medicine in State College, Pennsylvania.
Speaker A
So the world of Alzheimer medications has expanded quite a bit over the last few years, but it's still pretty hard to get in with a specialist without waiting several months, let alone being able to afford these fancy new biologics like.
Speaker B
We talked about in part one of September.
Speaker C
Given that as primary care docs we still wield influence to make an impact on individuals with Alzheimer and mild cognitive impairment with our current established medications like galantamine.
Speaker B
So this Cochrane review asks the question, is galantamine effective for treating patients with mild to moderate Alzheimer's and mild cognitive impairment? And for mild to moderate Alzheimer 8 to 12 milligrams twice daily of galantamine slows decline in cognitive and behavioral function as well as functional disability and global function at six months compared with placebo.
Speaker A
And here's a nice number needed to treat for you just 10 to prevent one patient from experiencing cognitive decline over six months. The downside here though is that galantamine does lead to more all cause discontinuation of pharmacotherapy and more nausea, with numbers needed to harm of 18 and 8 respectively.
Speaker C
Then for people with mild cognitive impairment, Galantamine is responsible for more all cause discontinuation of pharmacotherapy, nausea and death compared with placebo. And that's a grade A recommendation. This is particularly a bummer since we actually have no approved drugs to treat mild cognitive impairment, further affirmed in this review that showed no difference in cognitive function or activities of daily living at 24 months in galantamine compared to placebo.
Speaker B
One upside here though is that the rate of progression from mild cognitive impairment to dementia was 26% lower in participants receiving galantamine compared with placebo at 24 months. But once again, compared with placebo, galantamine was responsible for more all cause discontinuation, nausea and even death with numbers needed to harm of 8, 5 and 250 respectively. Moving right along, we have a medicine by the numbers parenteral agents for mitigating migraine relapse, and it comes to us from Dr. Long out of the University of Virginia School of Medicine in Charlottesville and Dr. Gottlieb out of Rush University in Chicago.
Speaker A
Migraines are debilitating and tough to treat, meaning that if you're working in an acute care setting, you're bound to see patients presenting with this after their at home therapies have failed. And I sure know I have. In both a pediatric and adult acute care setting.
Speaker C
The American Headache Society and the Canadian Headache Society guidelines recommend a variety of parenteral agents for the treatment of an acute migraine episode, including non steroidal anti inflammatory drugs, metoclopramide, neuroleptics and triptans. Unfortunately, the risk of migraine persistence or relapse within 72 hours of this treatment is still significant.
Speaker B
So the authors identified a meta analysis that included 53 RCTs with over 6,000 adults and that received treatment for acute migraine headache in the emergency setting, with focus on the primary outcome of migraine relapse defined as recurrence or worsening after.
Speaker A
Discharge and included studies evaluated the effectiveness of two or more eligible parenteral agents, including quite a few different classes like antiemetics, NSAIDs, ergot agents, anticonvulsants, neuroleptics, opioids, magnesium sulfate, lidocaine or sedatives.
Speaker C
The meta analysis found that corticosteroids, lidocaine, ergot agents, neuroleptics, opioids and sedatives or hypnotics reduced the risk of migraine relapse and that corticosteroids, lidocaine and combination therapy reduced the risk of severe migraine relapse.
Speaker A
For example, when it came to overall migraine relapse they found an NNT of 11 for corticosteroids, 6 for lidocaine, 48 for ergot agents and 10 for neuroleptics, and when it came to severe migraine relapse, there was an NNT of nine for combination therapy.
Speaker B
Some important notes here. There was significant heterogeneity across studies including differences in dosing, administration route, migraine duration and baseline severity. Most studies also had high or unclear risk of bias. Multiple studies were pharmaceutical industry sponsored and many of the studies didn't specify whether patients received additional medications for symptom relief.
Speaker C
The harms of these treatments were also.
Speaker A
Not addressed because of all these caveats. The Medicine by the Numbers team gives these parenteral treatments and specifically lidocaine and corticosteroids for migraine a color recommendation of yellow meaning unclear benefits and calls for further studies with less heterogeneity. We'll be back after this message. The AFP Podcast is sponsored by the American Academy of Family Physicians and by the journal fpm. FPM Journal provides you with simple yet powerful solutions to your everyday practice challenges. Available in print and online subscription information is available@aafp.org fpm.
Speaker B
We have a diagnostic test epi switch prostate cancer screening test and it comes to us from Doctors Parton, Martin and Newberry.
Speaker C
The US Preventive Services Task Force recommends shared decision making for PSA based prostate cancer screening in men aged 55 to 69 years and recommends against PSA based screening in men 70 years and older.
Speaker A
However, potential harms of the PSA include false positive results as well as over diagnosis and treatment harms.
Speaker B
So in steps the EPI Switch Prostate Screening Exam to try and help the.
Speaker C
EPI switch prostate screening or for short, the PSE test combines PSA measurement with polymerase chain reaction evaluation of five DNA regulatory markers associated with high risk prostate cancer, including markers like DAP, K1, MMP1 and Microrna 98.
Speaker A
The test produces a binary result of high likelihood or low likelihood for prostate cancer. Important to note here, the PSC is a newer test not approved by the fda.
Speaker B
All right, so how accurate is it?
Speaker C
Unfortunately, there are no randomized controlled trials evaluating patient oriented outcomes for the pse. The best available data is from a retrospective case control study that used 109 whole blood samples from men aged 50 to 69 years to analyze the accuracy of combining PSA levels with PSE DNA regulatory markers compared with PSA levels alone.
Speaker A
I must say I'm pretty apprehensive if our best available data is a retrospective case control study, but anywho of the 109 samples, 88 were negative for cancer and 21 had confirmed prostate cancer, 13 of which were moderately aggressive disease and eight were less aggressive disease. The prevalence of prostate cancer in this mixed cohort was 34%, which is comparable to a hospital referral population with suspected prostate cancer. However, screening cohorts typically have a much lower prostate cancer prevalence of 3 to 4%.
Speaker C
In this study, PSE with continuous PSA measurement was the most accurate with a sensitivity of 86% and specificity of 97%. This is compared to the continuous PSA alone which had a sensitivity of 66% and a specificity of 41%. Put another way, the PSE with continuous PSA had a positive likelihood ratio of over 28 and a negative likelihood ratio of 0.14 compared with the PSA alone, which had a likelihood ratio of 1.12 and a negative likelihood ratio of 0.83.
Speaker A
So there seems to be a real benefit in accuracy here. However, the PSC may cause patient distress by identifying clinically insignificant prostate cancers. As a screening test, the PSC predicts presence but doesn't provide info on the stage or grade of cancer.
Speaker C
Yeah, and cost is another big downside as well. Whereas a PSA is often covered by Medicare, the PSC is around $950 and there are no published reimbursement data, so patients may be responsible for the entire cost.
Speaker B
All right, Justin, bottom line it for us.
Speaker A
Okay, so current evidence for the PSC is limited to a single case control study with a small sample size. No prospective screening trials have evaluated its effect on patient oriented outcomes such as disease specific mortality rates. And it's expensive. The PSC should not be used at this time for prostate cancer screening in primary care.
Speaker B
We have another main topic, vitamin B12 deficiency. Common questions and answers, and it comes to us from Drs. Patel and McGurrick from the Ohio State University.
Speaker A
All right, team, it's time to talk about the one thing that probably single handedly funds med spas across the country by convincing people it will, quote, boost their energy levels. That's right.
Speaker B
So true.
Speaker A
Yeah, that's right. It's B12 time.
Speaker C
In part because of social media use and its use in med spas. Along with these new peptides that are coming out, my patients are coming in with questions about vitamin B12 now more than ever before. So this article has plenty of information to equip us with all the right answers backed by loads of evidence.
Speaker B
Okay, so first question, who is at risk? Patients we should be on the lookout for include those who have a disease that causes chronic GI inflammation like Crohn or celiac, who have received bariatric surgery, who eat a vegan diet, suffer from alcohol use disorder, take certain medications like metformin or PPIs, or even just pregnancy or older age.
Speaker A
Okay, how does it present? This is a huge spectrum. Some patients will have fatigue, anemia, paresthesias or brain fog. And when a deficiency has been around for a while, it can progress to impaired gait, pancytopenia, cognitive impairment or psychosis. Patients can also be completely asymptomatic, though.
Speaker C
So who should be screened or tested for the deficiency to start? Population screening is not recommended given the low incidence of deficiency. So testing should only be offered to those with at least one risk factor and one clinical feature of B12 deficiency. Testing can also be considered when there's just one clinical feature without risk factors, but a high suspicion for the deficiency as well.
Speaker B
The American Diabetes association tells us to consider periodic screening for those on metformin long term. And the American Gastroenterological association recommends screening in patients with ileal resection or Crohn with extensive ileal disease.
Speaker A
Alright, here's what we all came for. What does the testing algorithm look like? You start with a total serum B12 level. Obviously, for levels greater than 350, you can rule out deficiency, and then for levels less than 180. Deficiency can be formally diagnosed in between 180 and 350, though you should order a methylmalonic acid level and when that's low or normal, you can rule out B12 deficiency. When it's elevated, deficiency can be diagnosed. These levels are helpful in those borderline cases since B12 is a cofactor in a reaction that converts methylmalonic acid.
Speaker C
And once diagnosed, additional testing, when the cause is unclear, is centered around atrophic gastritis. So we should obtain an H. Pylori test as well as levels of anti intrinsic factor antibodies and antiparietal cell antibodies, with the former being more specific and the latter more sensitive. For autoimmune gastritis, definitive diagnosis does require a biopsy, which is important given the risk of gastric cancers.
Speaker B
And how about treatment? Right, the big question oral or intramuscular B12? Well, both effectively increase B12 levels, so the choice is yours. You could consider intramuscular for severely symptomatic patients to increase the levels more quickly.
Speaker A
To bring us home. Let's talk about elevated B12 levels. Is there any significance there? So persistently elevated levels, which is greater than 1,000 on at least two tests, are associated with increased risk of solid tumors, hematologic malignancy, chronic liver and kidney disease, cardiovascular mortality, and autoimmune disease. Anyone with elevated levels should be screened with labs for hematologic liver and kidney diseases.
Speaker B
All right, we're going to wrap things up with a poem. Fezalinitant for Menopause symptoms, and it comes to us from Dr. Alan Shaughnessy.
Speaker C
The investigators enrolled 453 participants with moderate to severe vasomotor symptoms associated with menopause. Participants had to be considered unsuitable for hormone therapy because either they preferred not to receive hormones or had a strong contraindication like a history of breast cancer, uterine cancer, active liver disease or thromboembolic disease, or had a weaker contraindication like metabolic syndrome or had previously discontinued hormone treatment.
Speaker A
The patients were randomized using concealed allocation to receive placebo or phezilenitant once daily in a double blind manner.
Speaker C
After six months of treatment, the primary outcome of patient rated frequency of vasomotor symptoms decreased from an average of 10.6 events per day to 2.61 events per day compared with 4.67 events in the placebo group.
Speaker A
While subjective, the global impression of change in vasomotor symptoms was much better or moderately better in 78.6% of participants who received treatment compared with 52.3% who received placebo, and we have a number needed to treat here of 3.8.
Speaker C
Similarly, patient rated sleep scores were much better or moderately better in 61% of treated patients, compared with 40.5% of the control patients with the number needed to treat of 4.9. There were also similar rates of adverse events in both groups.
Speaker A
You know, it sounds like Vasilena can't be touched by hot flashes.
Speaker B
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Speaker C
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Speaker A
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Speaker C
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Speaker B
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Speaker A
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Speaker B
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Speaker A
This podcast is brought to you by the residents and faculty of the University of Arizona College of Medicine, Phoenix Family Medicine Residency Programs. We'll talk to you soon for the.
Speaker B
Next edition of the American Family Physician Podcast.
Topics Covered
AFP Podcast
American Academy of Family Physicians
Mayo Clinic Family Medicine
lymphadenopathy
Alzheimer medications
galantamine
migraine treatment
prostate cancer screening
vitamin B12 deficiency
autoimmune diseases
Cochrane review
diagnostic tests
chronic GI inflammation
mild cognitive impairment
acute migraine episode
healthcare innovations