Shake off the February Doldrums with DIGEST 74

February 27, 2026 | By Nora Taranto

Welcome Back to The Curbsiders Digest!

In this issue we get into the drama around deprescribing , weight regain after weight-loss meds, and valacyclovir for Alzheimer’s
and so much more! Effortlessly absorb important medical news, with our twice monthly newsletter featuring easily digestible analysis of the latest practice-changing articles, and of course…bad puns. 

Yummy! 

If you or a friend are hungry for more, sign up here.

Menu 

Issue 74

02/27/2026

Appetizers (to whet your appetite) 

Palate Cleanser (aka the melon part of the meal) 

The Main Course

A Digestif or two

Appetizers

Brought to you hot off the stove, from a variety of specialties. Delivered in super tasty, bite-sized morsels.  

Beth “Garbs” Gasperlin MD, Laura Glick MD, Alyssa Mancini MD

• Weight Regain after Weight Loss? BMJ recently published a systematic review and meta-analysis looking at the rate of weight regain after cessation of weight management medications (WMMs) in adults with overweight or obesity. Thirty-seven studies with over 9,000 participants were included in the analysis. The average treatment duration was 39 weeks, and the average post-WMM follow up was 32 weeks. The average monthly rate of weight regain was 0.4 kg after cessation of any WMM, but up to 0.8 kg for the newer incretin mimetics (e.g. semaglutide, tirzepatide), with a projected return to baseline weight by 1.7 years for any WMM and 1.5 years for the newer incretin mimetics. Weight regain was faster after cessation of WMM than after cessation of behavioral weight management programs, with a predicted return to baseline weight of 3.9 years for the latter. Furthermore, all cardiometabolic markers (HbA1c, fasting glucose, blood pressure, cholesterol) were projected to return to baseline within 1.4 years of cessation of WMM. (AM)
• First-line Fidaxomicin to prevent C.Diff recurrence in immunocompromised hosts. Open Forum Infectious Diseases recently published the results of a retrospective cohort study that aimed to evaluate clinical outcomes after using fidaxomicin vs. vancomycin for first Clostridioides difficile infection (CDI) episode in immunocompromised hosts (ICHs). The study included 2362 ICHs with a first CDI episode – of whom, 47% had active solid tumors, 20% had hematologic malignancies or were HSCT recipients, 7% were solid organ transplant recipients, and 25% were on immunosuppressive medications. While treatment with fidaxomicin was not associated with a reduced risk of the composite outcome (recurrence within 8 weeks, 90-day mortality, and colectomy) compared to treatment with vancomycin, fidaxomicin use was associated with a significantly lower CDI recurrence rate compared to vancomycin (8% vs. 17%, p = 0.019).  Older age, prior antibiotics within 90 days, and hypoalbuminemia were associated with worse outcomes. CDI recurrence was also associated with worse long-term mortality. (AM)
• TTFields for Pancreatic Cancer. The U.S. Food and Drug Administration recently approved a wearable electrical medical device (Optune Pax) for patients with locally advanced unresectable pancreatic cancer. The device delivers tumor treating fields (TTFields), or alternating electrical field therapy, to the abdomen. This represents the first non-invasive, device-based approval in pancreatic cancer. Approval was based on the global, randomized, open-label phase 3 trial PANOVA-3, in which 571 patients with newly diagnosed, unresectable locally advanced pancreatic cancer were randomized to treatment with TTFields plus  gemcitabine/nab-paclitaxel (standard-of-care (SOC) chemotherapy) versus SOC chemotherapy alone. Patients randomized to the TTFields + chemotherapy arm experienced a significant improvement in overall survival compared to chemotherapy alone (16.2 vs. 14.2 months; HR 0.82, p=0.039), with minimal side effects. To use this device, adhesive patches are placed on the skin and connected to an electric field generator. The device is meant to be worn continuously, and based on PANOVA-3, used in combination with systemic therapy.  (LG) 
• Pads instead of Paps!? The pap smear is one of our most lifesaving interventions but unfortunately, up to 25% of eligible patients are not up-to-date on their cervical cancer screening.  A cross-sectional population study published in BMJ evaluated the diagnostic accuracy of a new, menstrual-blood based approach to cervical intraepithelial neoplasia (CIN) detection. Menstrual blood was collected using a ‘minipad’ –a prototype sampling strip of sterilized cotton that sticks to standard sanitary pads and that can collect and preserve DNA. The strip could then be mailed or hand-delivered to the study team within 3 months–with HPV DNA assessed from this sample. This method was compared to clinician-collected cervical samples for HPV DNA testing and cytology. Any patient with HPV detected or with abnormal cytology (ASCUS  or higher grade) was referred for colposcopy. Minipad testing had a comparable sensitivity and positive predictive value for CIN2/3+ detection compared to clinician-based testing. Specificity was slightly lower but the negative predictive value remained similar between groups, as did colposcopy referral rates after CIN2+ was detected. (BG) 
• Treating HSV and Alzheimer’s Progression – Multiple studies have highlighted a possible link between herpes simplex virus and Alzheimer’s disease (AD), so there has been hope that HSV treatment could potentially improve Alzheimer’s disease outcomes. Researchers just published an RCT in JAMA of 120 adults with probable AD or mild cognitive impairment with positive biomarkers for AD, who also had positive serologies for HSV-1 or HSV-2. Participants had early symptoms of dementia, with MMSE scores between 18-28.  Patients were assigned to 4 grams daily of valacyclovir or placebo. The primary outcome was the change in Alzheimer’s Disease Assessment Scale Cognitive Subscale score after 78 weeks, with changes in ADL completion ability and PET scan uptake as secondary outcomes. Patients assigned to valacyclovir actually demonstrated greater cognitive worsening than those treated with placebo. (BG) 

Palate Cleanser

Imagine grand rounds with background music and fewer slides sans the crisp white coat – enter “The Pitt,” a television series that takes place in a Pittsburgh emergency department.  In a recent write-up for The Atlantic, Sophie Gilbert describes the show as “a visceral study of moral injury in the modern attending,” where every episode is an hour of a shift for a crusty, middle-aged attending and his chronically overstretched team of residents, medical students, nurses, and ancillary staff.  The healthcare system attempts to compensate for the missing safety nets for patients, with hospital employees caring for an infant abandoned in the bathroom, an unhoused man with a smoldering soft tissue infection, and an uninsured patient in diabetic ketoacidosis who disappears from the hospital prematurely for fear of incurring additional medical debt. The series also demonstrates the risk-taking behavior and fallibility of healthcare providers despite their interactions with frequent catastrophes – the main attending rides a motorcycle without a helmet for his last shift before a three month cross country motorcycle ride, while a charge nurse smokes and (spoiler!) a resident is caught stealing prescription drugs from patients prompting him to enter and participate in rehab. The show ultimately reflects the failures of society to take care of its own – in a riveting and classic, medical procedural form. Check out Gilbert’s take on “The Pitt” here, and the television series on HBO Max!

– Jennifer DeSalvo MD 

The Main Course

Alexander Chaitoff MD, MPH

Better health through less medication

Most adults have at least one chronic disease, and clinicians spend much of their time counseling patients on why adding another medication will improve their health. However, there is a growing movement to “deprescribe” medications among older adults, who are at particularly high risk of experiencing serious side effects.  The term “deprescribing” has many definitions in the academic literature, but at its core, ”deprescribing” refers to proactively stopping medications because the risk-to-benefit ratio no longer favors continued treatment.  In recent years, studies on deprescribing have taken off. In 2025, >550 articles were published on the topic.  Research networks have grown to explore the central premise that, at least for some older adults, less is more. But a core question remains: does deprescribing actually improve outcomes?

Fewer medications for better living…through behavioral science

In a recent issue of JAMA, Lauffenberger et al. sought to explore whether electronic health record (EHR)-integrated behavioral “nudges” could effectively drive the deprescribing of potentially inappropriate medications (PIMs), especially benzodiazepines, Z-drugs, and anticholinergics. Chronic use of these medications has been associated with an increased risk of hospitalization and falls. 

To study this, investigators employed a cluster-randomized trial in which primary care physicians (PCPs) who had prescribed a potentially high-risk medication to at least one older adult were randomized to one of three arms: 1) a precommitment intervention, 2) a boostering intervention, and 3) usual care. The precommitment intervention involved a sequential strategy that first prompted a clinician to commit to a “soft” action with a patient—e.g. discussing medication risks with the patient. They were then prompted to consider the “hard” action of actual deprescribing at subsequent visits. Meanwhile, boostering was a reinforcement strategy that provided clinicians an initial notification to deprescribe during a patient encounter, followed by repeated automated reminders sent during subsequent visits and to their electronic inboxes to ensure the goal remained top-of-mind.  PCPs received these notifications for encounters with patients > 65 years who had been prescribed significant quantities of benzodiazepine or other sedative hypnotics or >2 strongly anticholinergic medications over the past 180 days. If a patient was on multiple of these high-risk medications, the PCP received notifications about each medication in accordance with their experimental arm. Notably, clinicians were not blinded to their experimental arm.

Among the 1146 patients (mean age 73.6 years) followed for a mean ~290 days, those seeing PCPs in the precommitment and boostering group were 40% and 26% more likely to experience a deprescribing event compared with patients experiencing usual care. Despite the secondary outcomes (e.g. cumulative lorazepam milligram equivalents, cumulative pill quantities) showing no significant differences between usual care and the intervention arms, this trial was considered positive on the basis of the primary result.

Another EHR alert coming to you?

So, should your local EHR hurry up and integrate deprescribing alerts? Maybe, but maybe not. Let’s be clear that these findings are impressive. Absolute differences in deprescribing were between 6.5% and 10.4%—that means a Number Needed To Treat (NNT) of around 14 and 10, respectively. But we need to ask – is a deprescribing event the outcome that matters most? Let’s consider an analogous prescribing example: the NNT with a statin. The NNT with a high-intensity statin to lower LDL cholesterol is about ~1 – almost everybody will respond to treatment. But the NNT with a statin to prevent a clinically relevant outcome – a.k.a. a fatal heart attack– is ~84, which is probably one of several outcomes we care more about.

And while these electronic nudges led to deprescribing events, there was no evidence presented in the trial to suggest that clinical outcomes we might care most about (e.g., serious adverse events) were different between experimental arms. This adds to a long literature – from EMPOWER to Shed-MEDS to OPTICA to many more – that shows there are a number of effective strategies for getting patients off potential inappropriate medications, but no clear evidence of better clinical outcomes for patients.

Furthermore, other work has shown that many older adults using PIMs also have poorly controlled chronic diseases, like hypertension, that would need to be treated with more medications. This further complicates the idea of using nudges to promote deprescribing. You can only nudge about so many things during a visit, so how do you decide when to nudge about deprescribing versus adding treatments for chronic diseases, especially when we have more evidence about the ability of treatments to improve outcomes?  

Lastly, it also remains unclear whether or not patients consistently want to be on fewer medications.  Even the general patient preference to be on fewer medications turns out to be nuanced. In the abstract, it is true that patients want to take fewer medications. However, when the offer is made concrete and involves stopping specific medications, many patients report reservations. Furthermore, patients are generally much more comfortable staying on an old medication than starting a new one. 

Ultimately, patients on medications with minimal benefit and only potential for harm should, of course, be taken off those medications. But most medications labeled as potentially inappropriate or high-risk in the literature may still offer potential benefits to some patients. The behavioral science principles tested above performed well, and it’s reasonable to suggest they be incorporated into EHR alerts. But whether or not such EHR alerts should be deployed more widely to encourage deprescribing–and for which medications this approach makes the most sense–ought to be the subject of much future research.

Read the trial results HERE!

Digestifs

Before you go….
we’ve got a few nibbles!

Consolidate your learning with a Quiz!  

This week on The Curbsiders: On Episode 515 this week, expert Dr. Anand Vaidya covers Primary Aldosteronism without any salt, giving us exactly the pearls we need to treat this often-challenging-to-diagnose disease. 

Comments for the Chef

We want to hear from you!

Please share your feedback and ideas in this Survey!

Thanks so much for joining us this week.

Until next time, keep that brain hole digesting! 

The Curbsiders Digest

Issue 74
Editor in Chief: Nora Taranto MD
Banner: Kate Grant  MBChB, DipGUMed

Jennifer DeSalvo,  Joshua Gilman,  Laura Glick, Alyssa Mancini, and Nora Taranto report no disclosures.

Kate Grant reports no disclosures.  

Alex chaitoff reports consultancy for Alosa Health.

PATREON is LIVE!

Join the Inner Circle