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Is Less More?

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Published November 5, 2023

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Good morning and happy fall! Is your city home to a pro sports team—with a large stadium or arena? Having this totem of hometown pride may be an assault on your city’s public health, suggests a recent article (shared by Debbie Downer). US cities that acquired a new pro team between 1962 and 2016 saw a swelling of influenza cases and related mortality relative to their pre–pro-team numbers. A new MLB, NFL, NBA, or NHL team could drive influenza mortality up 4% to 24%. The concern peaks when a pro hockey team skates into town: (1) the junction of a packed indoor arena, (2) the heart of influenza season, and (3) predominantly cold-weather cities seemingly emboldens the virus.

No word yet on virus transmission rate hikes likely to occur when Travis Kelce’s Chiefs plus a swarm of Swifties descend on your city.

Is Less More in Celiac Disease Diagnostic Testing?

GI GIST

Authors of a research paper on diagnosing celiac disease have a suggestion for clinicians: Trust the diagnostic reliability of serum testing, and consider forgoing biopsy. Your patients would love nothing more than skipping this invasive procedure, but is this a reasonable approach?

Serum testing vs biopsy

In a prospective cohort study, investigators gathered 436 adults with symptoms of celiac disease and without IgA deficiency and tested them via serum anti-tissue transglutaminase IgA (tTG-IgA) and then duodenal biopsy (the gold standard). How did serum testing stack up?

348 true positives, 66 true negatives, 15 false positives, 7 false negatives
Positive predictive value (PPV) of 95.9%, negative predictive value of 90.4%
When tTG-IgA was >10 times the upper limit of normal, PPV jumped to 97.5%

From this, the authors conclude that “a serology-based celiac disease diagnosis without biopsy is possible in adults with reliable suspicion of celiac disease.”

Yeah, but …

Skeptics using Lloyd Christmas logic (“so you're telling me there’s a chance”) argue that a 97.5% PPV still isn’t 100%, and the stakes are too high (a dietary overhaul) to get it wrong.

Key takeaway

tTG-IgA testing is “highly likely” to detect celiac disease in many patients, but highly likely may not be good enough. For this reason, the American Gastroenterological Association recommends biopsy as the diagnostic standard “for now.” But if “for now” changes to “not anymore” on the strength of subsequent findings, patients could win big. Until then, some experts suggest serum testing, a trial gluten-free diet, and then biopsy as a reasonable approach to establishing the diagnosis of celiac disease.

Can Erectile Dysfunction Meds Shrink Risk of Alzheimer's Disease?

NEURO NEWS

In the seesaw world of scientific research, phosphodiesterase-5 inhibitors (PDE5is) sildenafil (Viagra) and tadalafil (Cialis) have teetered between showing protection against Alzheimer disease and related dementias (ADRD) and not. Now fresh research thrusts these erectile dysfunction (ED) drugs back into the spotlight and aims to reconcile this growing debate.

Will they? Won’t they?

To determine if PDE5is protect against ADRD, researchers conducted a massive case-control study of patients ≥65 years with at least one chronic indication for PDE5i (eg, ED, benign prostatic hyperplasia [BPH], or pulmonary hypertension [pHTN]). They identified patients with ADRD and found that these patients had significantly lower odds of taking PDE5i than did control patients without ADRD. This held true across each condition: ED (64.2%), BPH (55.7%), and pHTN (54.0%). Findings were similar between both drugs and both sexes.

Study authors noted a slew of limitations, starting with reliance on aggregate data, but conclude that a significant link exists between PDE5i use and ADRD risk reduction. Hypotheses for the benefit include greater cerebral blood flow, neuroprotection, and increased neurogenesis.

Key takeaways

If future prospective studies bear out these retrospective-study findings, ED drugs could potentially reinvent themselves as treatment for ADRD. Mounting evidence, including another recent retrospective study showing a 60% relative risk reduction in AD with sildenafil use, reinforces the above conclusions. And in more good news, a third retrospective study in 2023 quantified PDE5i users as having a 39% lower relative risk of cardiovascular disease and a 25% lower relative risk of premature mortality. But what goes up must come down: A 2023 case report and systematic review points to possible (albeit rare) severe retinal vascular accidents with sildenafil use.

FDA Approves …

Study Examines Metformin’s Role in Gestational Diabetes

DIABETES DIGEST

Healthcare societies can’t seem to agree on whether metformin is an appropriate initial treatment for gestational diabetes mellitus (GDM). The ADA and the ACOG say, “Not typically”; the Society for Maternal-Fetal Medicine says, “It depends,” and the National Institute for Health and Care Excellence says, “Yes.” Researchers embarked on a new study in hopes of sparking consensus—if the House can elect a Speaker, anything is possible.

A mixed bag

A double-blind, placebo-controlled trial set in Ireland assessed the effects of metformin initiation at the time of GDM diagnosis. Investigators randomly assigned >500 moms—er, mums—to-be who were diagnosed with GDM to either metformin or placebo, plus usual care. The primary outcome, a combo of insulin initiation or elevated fasting glucose at gestation weeks 32 or 38, did not significantly differ between the two groups. But a conscious uncoupling of that composite outcome favored the metformin group—patients saw a 25% lower relative risk of requiring insulin.

The metformin group distinguished itself in secondary outcomes, reporting longer time to insulin initiation, greater glycemic control, and less gestational weight gain. But this group also saw a nonsignificant increase in small-for-gestational-age neonates (but without health issues).

Key takeaways

This trial failed to establish the statistical superiority of early metformin over a placebo in the primary outcome. Although it wasn’t the mic-drop study investigators hoped for, the research did unveil several secondary outcomes that demonstrated potential, prompting further investigation into metformin in early GDM. The use of an oral medication would not only provide relief to pregnant women looking to avoid insulin injections in an already taxing stage of life but could also offer a lifeline to those in low-income regions with likely limited insulin availability and storage options. Per lead author Fidelma Dunne, PhD, “If you have a medication that in the majority of women is safe and effective it may actually help a lot of women.” More to come.

Interested in more healthcare news? Here are some other articles we don’t want you to miss:

Morning Report is written by:

Alissa Scott, author
Aylin Madore, MD, MEd, editor
Margaret Oliverio, MD, editor
Emily Ruge, Author, editor

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