Digest 60: A Delicious December Digest

December 20, 2024 | By Nora Taranto

Welcome Back to The Curbsiders Digest!

In this issue, we discuss new HPV screening recommendations, cfDNA and cancer risk in pregnancy, antibiotic duration for bacteremia, 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. 

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Issue 60

12/20/2024

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. 
-Jennifer DeSalvo MD; Laura Glick MD

• Cutting down on antibiotics for patients with bacteremia? In BALANCE, a multicenter, noninferiority trial just published in NEJM, over 3,600 patients with bloodstream infections (including ICU and hospital ward patients) were randomized to receive 7 or 14 days of antibiotics.  There was no significant difference in the primary outcome of mortality at 90 days, occurring in 14.5% in 7-day arm vs. 16.1% in 14-day arm, with a -1.6% absolute difference between groups (95% CI -4.0 to 0.8)–within the prespecified noninferiority margin of 4%.  Secondary outcomes were similar between groups, including in-hospital mortality, ICU mortality, length of stay, hospital-free days at 28 days, and antibiotic-free days at 28 days. Limitations include the potential for nonadherence and exclusion of certain patients (e.g. those with severe immunocompromise, Staph Aureus bacteremia, or single cultures with possible contaminants). (LG)
• GLP-1s in Alcohol Use Disorder (AUD)? In a cohort study published in JAMA Psychiatry, researchers used a within-individual design to study the effect of GLP-1 agonists on risk of hospitalization in patients with AUD. Over 220,000 patients (ages 16-64) diagnosed with AUD from 2006 – 2021 were followed for a median of 8.8 years. Semaglutide and liraglutide (but not other GLP-1 agonist) use was associated with a significant decrease in alcohol use-related hospitalizations (adjusted HR 0.64 / 95% CI 0.50-0.83 for semaglutide; and 0.72 / 0.57-0.92 for liraglutide). GLP1-agonist use was also associated with a significant decrease in substance use disorder (SUD)-related hospitalizations and somatic hospitalizations. Medications approved for AUD (including disulfiram, acamprosate, and naltrexone) were associated with only a modest decrease in AUD-related hospitalizations. The use of GLP-1 agonists was not associated with a significant change in risk of a suicide attempt. (LG)
• Urea–A salty solution. The American Journal of Kidney Diseases recently published a systematic review and meta-analysis on the safety and efficacy of urea therapy to treat hyponatremia due to syndrome of inappropriate antidiuretic hormone (SIADH) secretion. This review included 16 observational studies evaluating 518 patients with SIADH treated with urea given orally or via nasogastric tube. Urea therapy significantly increased serum sodium in patients with SIADH (mean difference in sodium 9 mEq/L, 95% CI 7.6-10.5, p<0.01), with greater increases occurring in patients with severe compared to moderate or mild hyponatremia. Notably, urea therapy was comparable to current standard-of-care treatments including fluid restriction and vaptans, and significantly better than placebo. Given that urea is safe, effective in mild to severe disease, low-cost, and well-tolerated, it may be a useful alternative therapy. (JD)
• Perioperative Aspirin in Patients with Stents: To Continue or Not?  A multicenter, open-label, randomized controlled trial (ASSURE-DES) just published in JACC randomized nearly 1,000 patients who had a drug-eluting stent (DES) placed >1 year prior and were undergoing elective noncardiac surgery to either continue aspirin monotherapy or discontinue all antiplatelet agents five days before surgery. Patients resumed antiplatelet agents within 48 hours post-surgery, unless contraindicated. The primary outcome (a composite of all-cause mortality, myocardial infarction, stent thrombosis, or stroke between 5-30 days after noncardiac surgery) occurred at similar rates, in 3 (0.6%) patients in the aspirin group and 4 (0.9%) in the no-antiplatelet group (95% CI 1.3 to 0.9; p>0.99).  Minor bleeding occurred more frequently with aspirin (14.9% vs 10.1%; p=0.027), but there were similar rates of major bleeding in the two groups. An editorial review highlights study limitations (a low event rate, study design, and type of surgeries) and current practice guidelines to continue aspirin therapy in the perioperative period, unless contraindicated. (JD)
• Unveiling occult maternal cancers using prenatal cell-free DNA (cfDNA). Prenatal cfDNA screening is a test that can be used to non-invasively look for fetal chromosome/genetic abnormalities. NEJM just published a multi-center cohort study of 107 pregnant/postpartum patients with unusual prenatal cell-free DNA (cfDNA) results or results that were non-reportable (i.e. unable to assess fetal aneuploidy status), without signs or symptoms of cancer.  These individuals underwent rapid whole-body MRI, laboratory tests, and genome-wide cfDNA sequencing for cancer screening. The presence of cancer (the primary outcome) was identified on screening in 52 (48.6%) patients. The sensitivity and specificity of whole-body MRI in detecting occult cancer were 98% and 88.5%, while physical exam and laboratory tests had limited use. Full sequencing demonstrated copy-number gains and losses across ≥3 chromosomes in 49 participants, with cancer detected in 47 of 49.  While cfDNA is offered as part of routine prenatal care to screen for fetal aneuploidy, there are a variety of products available for this assessment (with varying cost and coverage), with the possibility of false positives and no specific guidelines yet about how to handle these abnormal test results. (JD)

Palate Cleanser

The melon part. To get rid of the taste of those pesky apps.  And to fill your brain with some fun facts.

Curious about the future of artificial intelligence (AI) in medicine?  This perspective article by Dr. Manesh Patel explores a framework for AI integration into clinical practice. This will require the creation of AI tools based on specific clinical indications and use, safety and efficacy studies followed by prospective trials evaluating outcomes and monitoring data, and guideline recommendations based on risk-benefit analysis of available evidence. This framework emphasizes the need for a “refocusing of AI technology development toward a closer alignment with the health goals that clinicians and patients understand are required to ensure widespread adoption and maximal impact to improve human health.” Check out the article to learn more about “Translating AI for the clinician!”

– Jennifer DeSalvo MD

The Main Course

Alyssa Mancini MD

An Update to Cervical Cancer Screening Recommendations
Earlier in December, the United States Preventive Services Task Force (USPSTF) released a draft recommendation statement on screening for cervical cancer. For the most part, the draft recommendation is consistent with the 2018 recommendations, except for two significant changes likely to be included in the final recommendations– Human Papillomavirus (HPV) primary screening every 5 years is now the preferred screening strategy for those aged 30-65 years, and patient-collected HPV screening is now included as an option.

HPV Testing and Recommendations–A Little Background
HPV is a common virus spread through close skin-to-skin contact, in particular by sexual transmission. While most infections with HPV will go away on their own, some will last longer and over time can cause cancer (including cervical cancer), with certain strains of HPV (e.g. HPV16, 18, 31, 33, 42) carrying a higher risk of cancer than others. Cervical cancer screening has evolved substantially, building on the standard historical approach of Pap smears to look at abnormal cytology around the cervix with new tests to look for evidence of the HPV itself (aka HPV testing). This HPV testing can either be done in combination with Pap/cytology (a.k.a. co-testing) or by itself (primary HPV testing or screening).

Society guidelines have been evolving to incorporate HPV testing over the last decade or so. The American Cancer Society has recommended primary HPV testing every 5 years as the preferred screening strategy in those aged 25 to 65 years since 2020. The American College of Obstetricians and Gynecologists (ACOG) and the American Academy of Family Physicians (AAFP) endorsed the 2018 USPSTF guidelines on cervical cancer screening, which had recommended any of the following options for women aged 30-65: cytology every 3 years, HPV testing alone every 5 years, or co-testing every 5 years. The USPSTF’s 2024 updated draft recommendations now emphasize primary HPV screening every 5 years in this age cohort as the recommended screening strategy, with alternative options including cervical cytology every 3 years or co-testing every 5 years. In these new recommendations, HPV primary screening can be either “clinician- or patient-collected.”

What’s the Data on Self-Collection?
The USPSTF did a deep dive into patient self-collection of HPV specimens, particularly the agreement and test accuracy of self-collected HPV screening specimens compared with clinician-collected specimens to detect precancer. The pooled sensitivity of self-collected samples to detect CIN2+ (cervical intraepithelial neoplasia (CIN) 2 or worse) was 0.86 (95% CI 0.78-0.93) and the pooled specificity was 0.81 (95% CI 0.71-0.91). Agreement between self-collected vaginal and clinician-collected cervical samples was high, similar proportions screened positive, and the relative accuracy of self-collected vaginal samples to detect CIN2+ compared with clinician-collected samples was high. Furthermore, offering self-collected vaginal HPV tests increased cervical cancer screening rates in 40/42 participation trials, especially among traditionally under-screened groups.  

These draft recommendations reflect new testing approvals by the FDA and concerted efforts by the National Cancer Institute (NCI) to improve access to cervical cancer screening. In May 2024, the FDA approved two HPV tests for self-collection (for now, only in the in-clinic setting)–the result of efforts by the NCI’s “Last Mile” Initiative to improve cervical cancer screening uptake, with the SHIP trial currently evaluating multiple self-collection assays for HPV detection.  

What about HPV Vaccination?
Of course, evidence is also emerging that HPV vaccination lowers the risk of precancer and cervical cancer among those who are directly vaccinated and in populations with high coverage of HPV vaccination (thank you, herd immunity!). HPV vaccination is currently recommended by the CDC for all individuals around age 11-12 (with catch-up vaccination recommended for all those age 26 and under, and consideration to vaccination for those likely to benefit between 27 and 45).  Vaccine uptake may, over decades, reduce the benefits of cervical cancer screening in these populations. The USPSTF’s decision modeling analyses found potential reductions in the lifetime benefit of screening in vaccinated vs unvaccinated women. Given the increasing rates of vaccination among younger persons, the draft recommendations suggest that screening may eventually be able to start at later ages or occur less frequently–or focus on HPV screening. But for now, there is not sufficient evidence for the USPSTF to make specific recommendations by vaccination status.

Read The USPSTF Draft Recommendations Here!

Digestifs

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

Consolidate your learning with a Quiz!  

This week on The Curbsiders: We have a reboot this week, with Episode #429, Anxiety 2.0 with Dr. Jessi Gold. Packed with tips on which med to start, how to start them, and nonpharmacologic therapy options, Dr. Gold covers a ton of ground in this high-yield episode.

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Until next time, keep that brain hole digesting! 

The Curbsiders Digest

Issue 60

Editor in Chief: Nora Taranto MD

Banner: Kate Grant  MBChB, DipGUMed

Disclosures:
.Jennifer DeSalvo,  Laura Glick, Alyssa Mancini, and Nora Taranto report no disclosures.

Kate Grant reports no disclosures.  

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