The Curbsiders podcast

#414 Spooky Cakes: VKA vs DOACs in Frail Adults, RSV Vaccine, Cuff Size Matters, Bloating & Belching, AKI & Pip-Tazo

October 30, 2023 | By



Join us as we review recent practice-changing articles on VKAs vs DOACs in frail adults with atrial fibrillation, RSV vaccine for adults over 60, how much does blood pressure cuff size matter, cotton fever in people who inject drugs, new bloating and belching guidelines, and does pip-tazo cause more AKI than cefepime. Fill your brain hole with a delicious stack of hotcakes! Featuring Paul Williams (@PaulNWilliamz), Rahul Ganatra (@rbganatra), and Matt Watto (@doctorwatto).

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Show Segments

  • Intro, disclaimer
  • VKAs vs DOACs in frail adults with atrial fibrillation, 
  • RSV vaccine for adults over 60, 
  • how much does blood pressure cuff size matter?
  • cotton fever in people who inject drugs, 
  • new bloating and belching guidelines,
  • does pip-tazo cause more AKI than cefepime?
  • Outro

Spookycake #1: BP Cuff Size (Paul)

Ishigami J et al; Effects of cuff size on the accuracy of blood pressure readings: The Cuff (SZ) Randomized Crossover Trial.  JAMA Internal Medicine.  2023; 183(10): 1061-1068.

What was the research question? How does using a regular-sized blood pressure cuff (instead of an appropriately-sized cuff) affect accuracy of automated blood pressure readings?

Why is this study important? Prior studies have suggested that cuff size affects accuracy of BP measurement via auscultation, but current guidelines recommend use of automated oscillometric cuffs, and impact of cuff size on accuracy in these devices is unknown.

How was the study done? In this randomized crossover trial, subjects had their upper arm circumference measured, and then underwent 4 blood pressure measurements with different cuff sizes in random order (too large, too small, and appropriate twice). Proper measurement technique (as described in the 2017 AHA guidelines) was used. 

Who were the patients?  195 community-dwelling adults.  Mean age 54 years, with 66% female, 68% Black.  51% had a diagnosis of hypertension (49% on medications).  Mean BMI was 28.8 kg/m2.  

Top-line results: This was a positive trial: measurements with a poorly sized blood pressure cuff resulted in inaccurate readings that were clinically significant. Using a cuff that was too large led to underestimation of systolic BP by about 4 mm Hg, and using a cuff that was too small led to overestimation of systolic BP by as much as 20 mm Hg. 

Learning points & limitations: Thinking about applying these results to real-world practice, patients with greater BMI (and therefore larger arms) are likely at higher risk for overestimation of BP, since the degree of inaccuracy was greater at the extremes of cuff size mismatch. The bottom line here is that size does indeed matter, and even using automated cuffs does not insulate us from potential misdiagnosis of hypertension. 

Bottom Line/Spookycakes rating: Automatic blood pressure cuff size matters. Cuffs that are too small can falsely raise blood pressure. It should be common practice to verify correct BP cuff size to avoid over or undertreatment. We give this 5 of 5 spooky cakes.

Further reading:

Editorial: Lalika M, Juraschek SP, Brewer LC. There is no 1-size-fits-all to blood pressure measurement-cuff size matters. JAMA Intern Med. 2023;183(10):1069-1070.

Spookycake #2: RSV Vaccine (Watto)

Walsh EE, et al; RENOIR Clinical Trial Group. Efficacy and Safety of a Bivalent RSV Prefusion F Vaccine in Older Adults. N Engl J Med. 2023 Apr 20;388(16):1465-1477.

What was the research question? Does an RSV prefusion F vaccine protect against symptomatic RSV-associated lower respiratory tract infection and acute respiratory illness?

Why is this study important? In the US there are about 60-100,000 RSV-associated hospitalizations and 6-10,000 deaths each year in older adults (per the CDC). An RSV vaccine in the 1960s actually worsened RSV illness in children, and more recent RSV vaccines lacked immunogenicity. Older adults with underlying cardiopulmonary illness are at higher risk for severe RSV associated illness. 

How was the study done? This was a phase 3, randomized, placebo-controlled trial of 34,284 adults ≥60 years old randomized 1:1 to receive a single dose of RSVpreF vaccine or placebo. Participants kept a log of symptoms and self-collected nasal swabs if symptoms developed. Patient-reported adverse effects occurring within 7 days were also recorded.

Who were the patients? Most notably, immunocompromised patients were excluded. 

Top-line results: This was a positive trial: the RSVpreF vaccine prevented lower respiratory tract infection and acute respiratory illness with only mild side effects and rare serious adverse events. Vaccine efficacy was 67% for preventing infection with two or more symptoms and 86% for preventing infection with three or more symptoms. 

Learning points & Limitations: This study was an interim analysis and did not report on hard outcomes like hospitalization or death. The exclusion of immunocompromised adults is also a limitation, since this is a group at high priority for vaccination. The primary outcome was also changed after protocol registration, but the authors justify this change as occurring because not enough cases of severe RSV occurred to justify analysis. Also, this was a per-protocol analysis, rather than the more conservative intention-to-treat. 

Bottom line/Spookycakes rating:  I give this 3.5 of 5 spookycakes. RSV perfusion F vaccines lowered the risk of acute symptomatic RSV infection in relatively healthy adults ≥60 years old, but this study has severe limitations and rare, serious adverse events occurred (Guillain-Barre, Miller Fisher syndrome). I cannot strongly recommend vaccination until we know more and I will proceed with shared decision making based on patient risk factors and values. 

Further Reading:

Spookycake #3: FRAIL-AF (Rahul)

Joosten LPT, van Doorn S, van de Ven PM, et al. Safety of switching from a vitamin k antagonist to a non-vitamin k antagonist oral anticoagulant in frail older patients with atrial fibrillation: results of the frail-af randomized controlled trial. Circulation. Published online August 27, 2023

What was the research question? Should frail elderly patients on a VKA for AF be switched to a DOAC?

Why is this study important? The evidence is clear that DOACs are superior to warfarin in non-valvular AF in terms of efficacy, safety, and convenience (ROCKET-AF, ARISTOTLE, RE-LY). However, elderly patients and frail patients were excluded from those trials, so whether the 30-40% of such patients who remain on warfarin would benefit from switching is unknown. 

How was the study done? This was a pragmatic, multicenter, open-label superiority trial done at 7 sites in the Netherlands from 2018 to 2022, and funded by the Dutch government. 1,330 patients who were stable on a VKA (NOT warfarin: acenocoumarol or phenprocoumon) for non-valvular AF in an outpatient setting to either continue or switch to a DOAC (specific DOAC left to the discretion of treating clinicians). 

Who were the patients? Mean age was 83 years, just over one-third of patients were female, the mean Groningen Frailty Indicator score was 4, and comorbidities were common. Median CHADS2VASC = 4. Patients with GFR <30 or valvular AF were excluded. 

Top-line results: This was a positive trial, but for a bad outcome: switching was associated with MORE bleeding without better stroke risk reduction – so much so that the trial was stopped early for futility. At 1 year, the primary outcome of bleeding occurred in 9.4% of the VKA arm and 15.3% of the NOAC arm (HR 1.69; 95% CI: 1.23-2.32). The difference was driven by clinically relevant non-major bleeding (more gastrointestinal and urogenital bleeding); there were no differences in intracranial hemorrhage, thromboembolic events, or all-cause mortality. 

Learning points & Limitations: It is worth pointing out that there are a few sources of bias towards DOACs performing worse in this study. First, VKA management in the Netherlands is generally excellent, with the average time in the therapeutic range (TTR) for INR of 65 – 75% (in comparison, the US only achieves about 60%). Second, all patients in this study proved they could be successfully managed on a VKA at enrollment. Third, the most frequently used DOAC was rivaroxiban, which has been shown to have a higher bleeding risk than apixaban or edoxaban. Fourth, switching is not the same as starting de novo: a protocol amendment was required after it became clear that switching before the INR dropped below 1.3 led to excess bleeding. Fifth, in the DOAC arm, a median of 52 days elapsed between randomization and starting a DOAC. These results need replication in other settings but suggest that elderly patients who are doing well on a VKA for AF don’t need to be switched to a DOAC; it would still be reasonable to switch patients who are NOT doing well on a VKA. 

Bottom line/Spookycakes rating: 4 out of 5

Further reading:

Beinema M, Brouwers JRBJ, Schalekamp T, Wilffert B. Pharmacogenetic differences between warfarin, acenocoumarol and phenprocoumon. Thromb Haemost. 2008;100(6):1052-1057.

Patients’ time in therapeutic range on warfarin among US patients with atrial fibrillation: Results from ORBIT-AF registry. American Heart Journal. 2015;170(1):141-148.e1.

Hot take #1: Cotton Fever (Paul)

Xie et al. Cotton fever: Does the patient know best? 2014. J Gen Intern Med 31(4): 442-4.

Summary: This article describes a case of cotton fever, a benign self-limited febrile syndrome occurring in patients with injection drug use who filter their drug suspension through cotton balls.

This is obviously a diagnosis of exclusion. Symptoms begin 15-30 minutes following injection, and can include shortness of breath, chills, headache, myalgias, abdominal pain, and tachycardia.  There is usually acute onset fever and leukocytosis, with symptoms lasting between 6 hours and 2 days.  The pathophysiology is unclear, and may represent a pyrogenic response to products in cotton, some sort of immunologic response to cotton, or a response to endotoxin found in bacteria that colonize cotton.

What is amazing about this paper is that the patient made the diagnosis at discharge, and the patient’s team did a literature search and agreed.

Bottom line: Know about cotton fever, but more importantly, be willing to learn from your patients and value their lived experiences.

Hot take #2: Bloating and Belching (Watto)

Moshiree B, Drossman D, Shaukat A. AGA Clinical Practice Update on Evaluation and Management of Belching, Abdominal Bloating, and Distention: Expert Review. Gastroenterology. 2023 Sep;165(3):791-800.e3.

Summary: Belching, abdominal bloating and/or distention are considered disorders of gut-brain interaction when frequent or severe enough to impair daily activities. 

Belching can be supragatric (voluntary) or gastric (involuntary). Supragastric belching is more frequent and does not occur with sleep or distraction. It can be treated with psychoeducation, CBT, diaphragmatic breathing (see YouTube), and central neuromodulators to decrease visceral hypersensitivity. Gastric belching is due to transient relaxation of the LES (TRLES) and is associated with GERD. Treatment includes PPI. Baclofen can be considered for TRLES. 

Abdominal bloating is the sensation of discomfort without visible abdominal distention, but both are treated similarly. They can occur in isolation without prominent pain symptoms (i.e. no IBS or dyspepsia). Assess for constipation, food allergy/intolerance (e.g. celiac, fructans), SIBO, gastroparesis or other motility disorders, visceral hypersensitivity and abdominopelvic dyssynergy (APD), which is paradoxical distention despite minimal abdominal gas. Target treatments at the underlying cause. Diaphragmatic breathing and central neuromodulators are recommended for visceral hypersensitivity and APD.

Bottom line: These conditions can be approached in primary care without fancy testing, especially when access to specialized care is limited.

Hot take #3: AKI, Cefepime, Pip-Tazo: the ACORN trial (Rahul)

Qian ET, Casey JD, Wright A, et al. Cefepime vs piperacillin-tazobactam in adults hospitalized with acute infection: the acorn randomized clinical trial. JAMA. Published online October 14, 2023.

Summary: The comparative safety of pip/tazo and cefepime with respect to AKI and neurological dysfunction is unknown. In this randomized open-label pragmatic superiority trial of adults with suspected infection presenting to the ED or ICU at Vanderbilt from 2021-2022,  

2,500 patients (mean age 58, ¾ also receiving vancomycin, 50% with sepsis, mostly intra-abdominal and pulmonary) were randomized 1:1 to cefepime or pip/tazo. At 14 days, after a median of 3 days of receipt of each antibiotic, there was no difference in severe AKI, death, or major adverse kidney outcomes; however, patients randomized to cefepime had slightly fewer days alive without coma or delirium (12.2 vs 11.9 days).

Bottom line: Pip/tazo, alone or in combination with vancomycin, is not associated with AKI, but is associated with less delirium and coma than cefepime. 

Really cool study done using automated alerts embedded in EMR – all the physician needed to decide was whether antipseudomonal Tx was needed, then patients were randomized and dosed. Probably should be practice-changing. 5/5. 


  1. Paul – and Back to the Water Below (album) by Royal Blood
  2. Rahul – The Three Body Problem (Book) by Liu Cixin
  3. Watto – The Thing (Film) 1982 version 


Listeners will review recent practice-changing articles and medical news.

Learning objectives

After listening to this episode listeners will…

  1. Evaluate the benefits of RSV vaccination for adults over 60 years old
  2. Discuss the safety of switching from vitamin K antagonist to DOAC in frail older adults
  3. Recognize the effect of “miscuffing” (incorrect cuff size) on blood pressure measurements


The Curbsiders report no relevant financial disclosures. 


Ganatra RB, Williams PN, Watto MF. “#414 Spooky Cakes: VKA vs DOACs in Frail Adults, RSV Vaccine, Cuff Size Matters, Bloating & Belching, AKI & Pip-Tazo”. The Curbsiders Internal Medicine Podcast. Final publishing date October 30, 2023.

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Episode Credits

Written and Hosted by: Rahul Ganatra MD, MPH; Paul Williams, MD, FACP, Matthew Watto MD, FACP
Cover Art: Matthew Watto MD, FACP
Reviewer: Sai Achi, MD
Technical Production: Pod Paste
Showrunners: Matthew Watto MD, FACP; Paul Williams MD, FACP

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The Curbsiders are partnering with VCU Health Continuing Education to offer FREE continuing education credits for physicians and other healthcare professionals. Visit and search for this episode to claim credit.

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