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The Curbsiders Digest!

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 40

Appetizers (to whet your appetite) 
Palate Cleanser (aka the melon part of the meal) 
The Main Course
A Digestif or two 


Jennifer Desalvo MD; Laura Glick MD; Hannah Smith MD 


  • Working more hours–worse for residents and patients? A recent study published in BMJ Medicine found that residents who worked more weekly hours or extended duration shifts (≥24 hours) were more prone to errors affecting patients and themselves. This nationwide prospective cohort study surveyed 4,826 U.S. resident-physicians (PGY-2 or beyond) monthly over eight years about work hours and patient/resident safety outcomes.  Working over 48 hours per week was associated with an increased risk of medical errors, preventable adverse events, and fatal preventable adverse events as well as safety events affecting residents–including near-crashes, occupational exposures, percutaneous injuries and attentional failures (P<0.001).  These risks increased even further for those working 60-70 hours weekly or more, and for those working any extended shifts (>24 hours) in a month. (LG) 

  • A new bacterial treatment for Clostridioides difficile infection (CDI)?  The latest innovation in treating the hard-to-treat C.Diff, VE303 is a novel biotherapeutic consisting of 8 commensal strains of Clostridia given orally once daily for 14 days.  In this phase 2, double-blind, placebo-controlled trial just published in JAMA, high-dose VE303, low-dose, and placebo capsules were administered to 79 adults with CDI and ≥1 prior CDI in the past 6 months or at high risk of recurrence.  CDI rates at 8 weeks of treatment were 13.8% for high-dose VE303, 37.0% for low-dose VE303, and 45.5% for placebo (P = .006, high-dose VE303 vs placebo). VE303 was well-tolerated, with less than half of recipients reporting a treatment-related gastrointestinal adverse effect.  Stay tuned for the phase 3 trial! (JD) 

  • Not quite time to add routine skin checks to the annual physical. According to the US Preventive Services Task Force (USPSTF) systematic review published in JAMA, there remains insufficient evidence to recommend a visual skin examination to screen asymptomatic adolescents and adults for skin cancer without a history of premalignant or malignant skin lesions. The USPSTF found limited and inconsistent data to support the benefits or harms of universal skin screening exams for early detection and treatment of skin cancer, without sufficient data to support a mortality benefit.  This is, in part, because studies have not historically included an adequate diversity of skin types and colors.  There is a need for better skin color inclusion in future studies in order to adequately reflect the US population and determine overall benefits and harms of screening skin examination. (JD) 

  • Should patients with type 2 diabetes mellitus (T2DM) avoid NSAIDs? A recent study published in JACC evaluated the risk of heart failure, and its association with Non-Steroidal Anti-Inflammatory Drug (NSAID) use, in > 300,000 Danish patients with T2DM.  In this case-crossover design, patients were considered exposed to NSAIDs if a prescription was claimed within 28 days before a first-time heart failure hospitalization.  NSAID use in patients with T2DM was associated with an increased risk of first-time heart failure (HF) hospitalization, especially in patients ≥80 years, those with elevated hemoglobin A1c levels on ≤1 anti-diabetic medications, and those without prior NSAID use. (JD) 

  • Does the sex of blood donors affect mortality outcomes in transfusion recipients? In a recent double-blind, randomized, multicenter study published in NEJM, researchers in Canada randomized over 8000 patients already set to receive blood transfusion to units of blood from either male or female donors. There were no differences in mortality between those who received male and female donor blood over a mean follow-up of 11.2 months.  Previous theories and observational studies had suggested potential differences in mortality based on theorized sex-related differences in red-cell deformability, oxygen-carrying capacity, susceptibility to lysis, immunomodulatory activity, and induction of vasculopathy. (HS) 

Palate Cleanser 

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


The Urine Tells The Story  


There’s a whole history to “reading urine,” as we learn in Katherine Harvey’s riveting essay, “Troubled Waters”--an exploration of uroscopy in medieval times, just published in The Public Domain Review. The practice of examining urine in medical practice dates back to the Babylonians and was such an important component of medicine that many medieval illustrations featured physicians peering closely at flasks of urine.  Texts such as The Dome of Uryne were widely used to assist in uroscopic interpretation, from diagnosis of disease and imbalance of the humors to assistance with fertility.  It took practice, and education, to learn how to read the color, the smell, the texture and layering of the urine–for the urine could tell a story that the experienced physician could interpret.  Read the article, and see excerpts from these medieval uroscopic texts and illustrations, here


– Nora Taranto MD


The Main Course

Alyssa Mancini MD 


The Main Course

Doxycycline: the PEP in our step for STI prevention


Rates of bacterial sexually-transmitted infections (STIs) are rising in the U.S., according to the CDC, and cisgender men who have sex with men (MSM) and transgender women have been disproportionately affected by this increase.  Moreover, antimicrobial-resistant gonorrhea is on the rise, with about half of gonorrhea infections in 2021 demonstrating resistance to at least one antibiotic.  As a response to these worrisome trends, the search for STI prophylaxis has begun.  So far, doxycycline appears to be a frontrunner – it’s effective against chlamydia and syphilis, it’s not currently used for gonorrhea treatment (thus conferring a lower risk of resistance), it has a good drug safety profile, and it’s affordable.  Several early studies have evaluated doxycycline post-exposure prophylaxis (doxy-PEP) for the prevention of bacterial STIs, including a 2015 pilot study of 30 MSM living with HIV in whom doxy-PEP substantially reduced bacterial STIs rates.  A substudy of the ARNS IPERGAY trial in 2018 then found a 47% reduction in STI incidence with doxy-PEP in MSM taking pre-exposure prophylaxis (PrEP) for HIV prevention.  Now, DoxyPEP is evaluating the efficacy, safety, and effect on antimicrobial resistance of doxycycline for STI prevention in a larger, randomized cohort of MSM and transgender women taking HIV PrEP or living with HIV.


Breaking it Down


DoxyPEP was an open-label, randomized study including 501 MSM and transgender women who were taking HIV PrEP (PrEP cohort) or living with HIV infection (persons living with HIV infection [PLWH] cohort), had a history of condomless anal or oral sex with a man in the past year, and had gonorrhea, chlamydia, or syphilis in the past year.  Participants were randomly assigned in a 2:1 ratio to take 200 mg doxycycline within 72 hours after condomless sex (doxy-PEP group) or receive standard care without doxycycline (standard-care group).  In the doxy-PEP groups, 86% of participants reported taking doxy-PEP consistently within 72h after condomless sex, and 71% reported never missing doxy-PEP after condomless sex.  


In both the PrEP and PLLWH cohorts, an STI was diagnosed in 10-11% of quarterly visits in the doxy-PEP groups and 30-31% in the standard-care groups, with absolute differences of -21.2%  and -18.7%, respectively, and relative risks (RR) of infection of 0.34 and 0.38 with doxy-PEP compared to standard-care.  Each individual STI rate was also decreased in Doxy-PEP.  The number needed to treat (NNT) to prevent a quarter with an incident STI was 4.7 in the PrEP cohort and 5.3 in the PLWH cohort.  There were no serious adverse events attributed to doxycycline.  Researchers did observe higher tetracycline resistance rates in gonorrhea isolates in the doxy-PEP groups (though available culture data was limited).  Ultimately, the trial ended early because both the PrEP and PLWH cohorts crossed the stopping boundary for effectiveness, and the data and safety monitoring board therefore recommended that all participants be offered doxy-PEP.


The Takeaways


In DoxyPEP, doxycycline taken within 72 hours after condomless sex decreased incident gonorrhea, chlamydia, and early syphilis by two thirds among MSM and transgender women who had had a bacterial STI in the previous year.  Limitations of the study include challenges in accurately measuring adherence to doxy-PEP in retrospect and limited availability of gonorrhea resistance data. These results may also have limited generalizability, including to transgender women (< 5% of the study population) and other high risk populations not assessed in the study (and in fact, there is preliminary randomized data presented at CROI 2023 suggesting that, among cisgender women taking PrEP in Kenya, Doxy-PEP may, for unclear reasons, not reduce STI rates).  But overall, this study further confirms that doxy-PEP is an effective STI prevention intervention for MSM with risk factors for STI infection, regardless of HIV status–adding another tool to our sexual health toolbox. 


Read the Paper Here





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

Consolidate your learning with a Quiz

This week on Curbsiders: Episode #392, Live! Opioid and Xylazine Withdrawal, takes us deep into the world of “Tranq”--a new drug, with similarities to clonidine and other alpha 2 agonists, that was taken from the world of animal sedatives and can cause profound sedation and withdrawal–with overdoses that are not responsive to Narcan. Learn more from expert Dr. Joseph D’Orazio in this fabulous episode.  

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The Curbsiders Digest
Issue 40

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


Hannah Smith, Alyssa Mancini, Laura Glick, Jennifer Desalvo, and Nora Taranto report no disclosures. 

Kate Grant reports no disclosure

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